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Sample records for hemoglobin zinc protoporphyrin

  1. Monte Carlo simulation of zinc protoporphyrin fluorescence in the retina

    NASA Astrophysics Data System (ADS)

    Chen, Xiaoyan; Lane, Stephen

    2010-02-01

    We have used Monte Carlo simulation of autofluorescence in the retina to determine that noninvasive detection of nutritional iron deficiency is possible. Nutritional iron deficiency (which leads to iron deficiency anemia) affects more than 2 billion people worldwide, and there is an urgent need for a simple, noninvasive diagnostic test. Zinc protoporphyrin (ZPP) is a fluorescent compound that accumulates in red blood cells and is used as a biomarker for nutritional iron deficiency. We developed a computational model of the eye, using parameters that were identified either by literature search, or by direct experimental measurement to test the possibility of detecting ZPP non-invasively in retina. By incorporating fluorescence into Steven Jacques' original code for multi-layered tissue, we performed Monte Carlo simulation of fluorescence in the retina and determined that if the beam is not focused on a blood vessel in a neural retina layer or if part of light is hitting the vessel, ZPP fluorescence will be 10-200 times higher than background lipofuscin fluorescence coming from the retinal pigment epithelium (RPE) layer directly below. In addition we found that if the light can be focused entirely onto a blood vessel in the neural retina layer, the fluorescence signal comes only from ZPP. The fluorescence from layers below in this second situation does not contribute to the signal. Therefore, the possibility that a device could potentially be built and detect ZPP fluorescence in retina looks very promising.

  2. Blood lead and zinc protoporphyrin levels in donkeys and mules near a secondary lead smelter in Jamaica, 1987-88

    SciTech Connect

    Ostrowski, S.R.; Gunter, E.W.; Matte, T.D. )

    1990-02-01

    During the course of an investigation into community lead poisoning near a secondary lead smelter in Jamaica, blood lead and zinc protoporphyrin levels were measured in 8 exposed and 6 (3 Jamaican, 3 US) unexposed donkeys and mules. The blood lead levels of 6 animals in the contaminated area ranged from 7.5 to 33 micrograms/dl (mean = 17.6 micrograms/dl), compared to 1.8 and 2.4 in unexposed Jamaican animals. More striking was the difference in zinc protoporphyrin levels; all 8 exposed donkeys and mules had values between 900 and 1890 micrograms/dl, compared with a range of 34-46 micrograms/dl for 3 Jamaican control donkeys. These findings suggest that zinc protoporphyrin may be a useful method of screening for subclinical lead toxicity in equines.

  3. Formation of zinc protoporphyrin IX in Parma-like ham without nitrate or nitrite.

    PubMed

    Wakamatsu, Jun-ichi; Uemura, Juichi; Odagiri, Hiroko; Okui, Jun; Hayashi, Nobutaka; Hioki, Shoji; Nishimura, Takanori; Hattori, Akihito

    2009-04-01

    Zinc protoporphyrin IX (ZPP) is a characteristic red pigment in meat products that are manufactured without the addition of a curing agent such as nitrate or nitrite. To examine the effects of impurities such as mineral components in sea salt on the formation of ZPP, we manufactured Parmatype dry-cured hams that were salted with refined salt or sea salt and examined the involvement of oxidation-reduction potential (ORP) in the formation of ZPP. The content of ZPP was increased drastically after 40 weeks. Microscopic observation showed strong fluorescence caused by ZPP muscle fiber after 40 weeks. Conversely, heme content varied considerably during processing. ORP increased during processing. However, there was no obvious difference between ham salted with refined salt and that salted with sea salt. Therefore, it was concluded that impurities in sea salt were not involved in the formation of ZPP.

  4. Zinc protoporphyrin IX enhances chemotherapeutic response of hepatoma cells to cisplatin

    PubMed Central

    Liu, Yang-Sui; Li, Huan-Song; Qi, Dun-Feng; Zhang, Jun; Jiang, Xin-Chun; Shi, Kui; Zhang, Xiao-Jun; Zhang, Xin-Hui

    2014-01-01

    AIM: To investigate the effect of zinc protoporphyrin IX on the response of hepatoma cells to cisplatin and the possible mechanism involved. METHODS: Cytotoxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was determined by a flow cytometric assay. Western blotting was used to measure protein expression. Heme oxygenase (HO)-1 activity was measured by determining the level of bilirubin generated in isolated microsomes. Reactive oxygen species (ROS) production was monitored by flow cytometry. Caspase-3 activity was measured with a colorimetric assay kit. Mice were inoculated with 1 × 107 tumor cells subcutaneously into the right flanks. All mice were sacrificed 6 wk after the first treatment and tumors were weighed and measured. RESULTS: Overexpression of HO-1 in HepG2 cell line was associated with increased chemoresistance to cis-diaminedichloroplatinum (cisplatin; CDDP) compared to other cell lines in vitro. Inhibition of HO-1 expression or activity by zinc protoporphyrin IX (ZnPP IX) markedly augmented CDDP-mediated cytotoxicity towards all liver cancer cell lines in vitro and in vivo. In contrast, induction of HO-1 with hemin increased resistance of tumor cells to CDDP-mediated cytotoxicity in vitro and in vivo. Furthermore, cells treated with ZnPP IX plus CDDP exhibited marked production of intracellular ROS and caspase-3 activity, which paralleled the incidence of cell apoptosis, whereas hemin decreased cellular ROS and caspase-3 activity induced by CDDP. CONCLUSION: ZnPP IX increases cellular sensitivity and susceptibility of liver cancer cell lines to CDDP and this may represent a mechanism of increasing ROS. PMID:25024611

  5. Tracking Blood Lead and Zinc Protoporphyrin Levels in Andean Adults Working in a Lead Contaminated Environment

    PubMed Central

    Ortega, Fernando; Counter, S. Allen; Buchanan, Leo H.; Parra, Angelica Maria Coronel; Collaguaso, Maria Angela; Jacobs, Anthony B.

    2014-01-01

    The purpose of this study was to investigate current blood lead (PbB) and zinc protoporphyrin (ZPP) levels in adults presently living in environmentally Pb-contaminated Andean communities, and to compare the findings with the PbB and ZPP levels of Pb-exposed adult cohorts from the same study area tested between 1996 and 2007. Blood samples from 39 adults were measured for PbB and ZPP concentrations. The current mean PbB level (22.7 μg/dl) was significantly lower than the mean (37.9 μg/dl) of the initial 1996 cohort. PbB levels for the 1997, 1998, 2003, and 2006 cohorts were also significantly lower than the levels for the 1996 group. Elevated ZPP/heme ratios of 103.3, 128.4 and 134.2 μmol/mol were not significantly different for the 2006, 2007 and 2012 groups, indicating chronic Pb exposure. While ZPP levels of Andean Ecuadorian Pb-glazing workers have remained elevated, PbB levels declined. Pb exposure of the workers need to be continually monitored. PMID:24274152

  6. Elevation of zinc protoporphyrin levels in lead workers with iron- sufficient microcytosis.

    SciTech Connect

    Ronin, D.; Strehl, F.; Human Resources

    1998-05-01

    Zinc protoporphyrin (ZPP) measurement is a required test under the Occupational Safety and Health Administration's lead standard. However, there is no mention of the influence of hemoglobinopathy on the ZPP test value. We undertook a retrospective laboratory review of 382 employees at the Argonne National Laboratory who had been subjects in a lead surveillance program since 1982. A total of 321 samples were analyzed, after female subjects and samples with abnormally high bilirubin levels were excluded. A group with low mean red blood cell volume (MCV; less than 80.0 fL) was compared with a group with normal MCV (greater or equal to 80.0 fL). A statistically significant difference was noted in ZPP (P < 0.007) and total bilirubin (P< 0.0003) values of two groups. There was no statistically significant difference noted in age, lead levels, or iron levels between the two groups. Abnormally high ZPP levels may occur in individuals with hemoglobinopathies. Only a minor part of this elevation could be explained by the higher bilirubin levels.

  7. Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria

    SciTech Connect

    Sandberg, S.; Brun, A.

    1982-09-01

    The photohemolysis of normal erythrocytes incubated with protoporphyrin is reduced in the presence of albumin. When globin is added to normal erythrocytes loaded with protoporphyrin, protoporphyrin is bound to globin. During irradiation protoporphyrin moves from globin to the erythrocyte membrane and photohemolysis is initiated. Erythrocytes in patients with erythropoietic protoporphyria contain large amounts of protoporphyrin bound to hemoglobin. Upon irradiation of these cells in the absence of albumin, 40% of protoporphyrin and 80% of hemoglobin is released after 240 kJ/m2. The released protoporphyrin is hemoglobin bound. In contrast, when albumin is present only 8% of hemoglobin is released whereas protoporphyrin is released to 76%. The released protoporphyrin is albumin bound. A hypothesis for the release of erythrocyte protoporphyrin in erythropoietic protoporphyria without simultaneous hemolysis is proposed. Upon irradiation protoporphyrin photodamages its binding sites on hemoglobin, moves through the plasma membrane, and is bound to albumin in plasma.

  8. Hierarchical coassembly of DNA–triptycene hybrid molecular building blocks and zinc protoporphyrin IX

    PubMed Central

    Kumari, Rina; Singh, Sumit; Monisha, Mohan; Bhowmick, Sourav; Roy, Anindya

    2016-01-01

    Summary Herein, we describe the successful construction of composite DNA nanostructures by the self-assembly of complementary symmetrical 2,6,14-triptycenetripropiolic acid (TPA)–DNA building blocks and zinc protoporphyrin IX (Zn PpIX). DNA–organic molecule scaffolds for the composite DNA nanostructure were constructed through covalent conjugation of TPA with 5′-C12-amine-terminated modified single strand DNA (ssDNA) and its complementary strand. The repeated covalent conjugation of TPA with DNA was confirmed by using denaturing polyacrylamide gel electrophoresis (PAGE), reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). The biologically relevant photosensitizer Zn PpIX was used to direct the hybridization-mediated self-assembly of DNA–TPA molecular building blocks as well as a model guest molecule within the DNA–TPA supramolecular self-assembly. The formation of fiber-like composite DNA nanostructures was observed. Native PAGE, circular dichroism (CD) and atomic force microscopy (AFM) have been utilized for analyzing the formation of DNA nanofibers after the coassembly. Computational methods were applied to discern the theoretical dimension of the DNA–TPA molecular building block of the nanofibers. A notable change in photocatalytic efficiency of Zn PpIX was observed when it was inside the TPA–DNA scaffold. The significant increase in ROS generation by Zn PpIX when trapped in this biocompatible DNA–TPA hybrid nanofiber may be an effective tool to explore photodynamic therapy (PDT) applications as well as photocatalytic reactions. PMID:27335759

  9. Hemin and Zinc Protoporphyrin IX Affect Granisetron Constipating Effects In Vitro and In Vivo

    PubMed Central

    Zigrino, Addolorata; Leo, Valentina; Renna, Giuseppe; Montagnani, Monica

    2013-01-01

    Granisetron is a 5-HT3 receptors antagonist used in the management of emesis associated with anticancer chemotherapy. It affects intestinal motility with constipating effect. Since the pathway heme oxygenase/carbon monoxide (HO/CO) is involved in gastrointestinal motility, we evaluated the possible interplay between granisetron and agents affecting HO/CO pathways such as zinc protoporphyrin IX (ZnPPIX), an HO inhibitor, or hemin, an HO-1 inducer. ZnPPIX (10 µM) or hemin (10 µM), but not granisetron (0.1, 0.3, 1 µM), affected spontaneous basal activity recorded in rat duodenal strips, in noncholinergic nonadrenergic conditions. Granisetron restored spontaneous basal activity after ZnPPIX, but not after hemin. ZnPPIX decreased and hemin increased the inhibition of activity after electrical field stimulation (EFS), but they did not affect the contraction that follows the relaxation induced by EFS called off contraction. Granisetron did not alter the response to EFS per se but abolished both ZnPPIX and hemin effect when coadministered. In vivo study showed constipating effect of granisetron (25, 50, 75 µg/kg/sc) but no effect of either ZnPPIX (50 µg/kg/i.p.) or hemin (50 µM/kg/i.p.). When coadministered, granisetron effect was abolished by ZnPPIX and increased by hemin. Specimens from rats treated in vivo with hemin (50 µM/kg/i.p.) showed increased HO-1 protein levels. In conclusion, granisetron seems to interact with agents affecting HO/CO pathway both in vitro and in vivo. PMID:23864955

  10. Declining Blood Lead and Zinc Protoporphyrin levels in Ecuadorian Andean Children

    PubMed Central

    Ortega, Fernando; Counter, S. Allen; Buchanan, Leo H.; Coronel Parra, Angelica M.; Collaguaso, Maria Angela; Jacobs, Anthony B.; Rifai, Nader; Hoover, Patricia Nolan

    2013-01-01

    Objectives To investigate current lead (Pb) exposure in children living in Andean Ecuadorian communities. Blood Pb (PbB) and zinc protoporphyrin (ZPP) levels were used respectively as biomarkers of acute and chronic Pb poisoning. The current PbB-ZPP levels were compared with previous pediatric PbB-ZPP levels recorded over years in the study area. Design and Methods Samples of whole blood were collected from 22 Andean children of Quechua and Mestizo backgrounds and measured for PbB concentrations by graphite furnace atomic absorption spectroscopy. ZPP/heme ratio and ZPP whole blood (ZPP WB) levels were measured with a hematofluorometer. Results The mean PbB level for children in the current study group was 14.5 μg/dL, which was significantly lower than the mean PbB level of 41.1 μg/dL found in the same study area in the 1996–2000 test period, and lower than the 22.2 μg/dL mean level found in the 2003–2007 period. The current mean ZPP/heme ratio was 102.1 μmol/mol, and the mean ZPP WB level was 46.3 μg/dL, both lower than values previously found in children in the study area. Conclusion While the current pediatric PbB-ZPP levels in the study area remain elevated in some children, the overall levels indicate a decline relative to levels observed in the same Pb-contaminated area in the period between 1996 and 2007. The elevated ZPP levels suggest a history of chronic Pb exposure, and potential iron deficiency in some children. The overall reduction in PbB-ZPP levels suggests a positive outcome of a Pb-exposure education and prevention program, and the therapeutic intervention of succimer chelation therapy. PMID:23684775

  11. Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip

    PubMed Central

    Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M.; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M.

    2016-01-01

    Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure. PMID:26883939

  12. Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip.

    PubMed

    Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M

    2016-02-17

    Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure.

  13. Interrelationships of blood lead, zinc protoporphyrin and hemoglobin in tests from one lead battery plant

    SciTech Connect

    Bernhardt, J.H.

    1983-01-01

    A period prevalence study examining concurrent PbB, ZPP and Hgb test values from 236 employees of one lead-acid battery manufacturing plant over a six month period was conducted. Fifty-six job categories in the plant were grouped on the basis of proximity and/or similarity of lead exposure. Diagrams of plant layout, the process flow chart, work order, department numbers and biological and environmental data from earlier plant surveys were used in dividing the jobs into five exposure index groups. Length of service with the company was calculated to provide an indication of the duration of occupational exposure to lead. Length of service in the exposure index group was calculated to provide information regarding the duration of exposure as measured by the type of job. Recommendations were made that: 1) a single set of tests not be evaluated in isolation but considered as part of the overall pattern of an individual's laboratory data; 2) ZPP be required by OSHA for periodic monitoring; 3) use of both the PbB and ZPP tests is necessary for biological monitoring at PbB levels less than or equal to 55 ..mu..g/dL; and 4) a PbB value of 40 ..mu..g/dL is a good level to use in determining who will have more frequent biological monitoring for the purpose of OSHA compliance.

  14. Polymeric micelles of zinc protoporphyrin for tumor targeted delivery based on EPR effect and singlet oxygen generation.

    PubMed

    Iyer, Arun K; Greish, Khaled; Seki, Takahiro; Okazaki, Shoko; Fang, Jun; Takeshita, Keizo; Maeda, Hiroshi

    2007-01-01

    Polymeric micelles of zinc protoporphyrin (ZnPP) with water soluble biocompatible and amphiphilic polymer, polyethylene glycol (PEG) demonstrated unique characteristics to target tumor tissues selectively based on the enhanced permeability and retention (EPR) effect. The micellar macromolecular drug of ZnPP (SMA-ZnPP and PEG-ZnPP) previously showed notable anticancer activity as a consequence of selective tumor targeting ability and its potent HO-1 inhibitory potential, resulting in suppressed biliverdin/bilirubin production in tumors thereby leading to oxystress induced tumor cell killing. Furthermore, recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light, laser, or xenon light source, which could augment its oxystress induced cell killing abilities. In the present paper, we report the synergistic effects of light induced photosensitizing capabilities and HO-1 inhibitory potentials of these unique micelles when tested in vitro and in vivo on tumor models under localized, mild illumination conditions using a tungsten-xenon light source. The results indicate that these water soluble polymeric micelles of ZnPP portend to be promising candidates for targeted chemotherapy as well as photodynamic therapy against superficial tumors as well as solid tumors located at light penetrable depths.

  15. X-ray absorption and photoemission spectroscopy of zinc protoporphyrin adsorbed on rutile TiO{sub 2}(110) prepared by in situ electrospray deposition

    SciTech Connect

    Rienzo, Anna; Mayor, Louise C.; Magnano, Graziano; Satterley, Christopher J.; O'Shea, James N.; Ataman, Evren; Schnadt, Joachim; Schulte, Karina

    2010-02-28

    Zinc-protoporphyrin, adsorbed on the rutile TiO{sub 2}(110) surface, has been studied using photoemission spectroscopy and near-edge absorption fine structure spectroscopy to deduce the nature of the molecule-surface bonding and the chemical environment of the central metal atom. To overcome the difficulties associated with sublimation of the porphyrin molecules, samples were prepared in situ using ultrahigh vacuum electrospray deposition, a technique which facilitates the deposition of nonvolatile and fragile molecules. Monolayers of Zn protoporphyrin are found to bond to the surface via the oxygen atoms of the deprotonated carboxyl groups. The molecules initially lie largely parallel to the surface, reorienting to an upright geometry as the coverage is increased up to a monolayer. For those molecules directly chemisorbed to the surface, the interaction is sufficiently strong to pull the central metal atom out of the molecule.

  16. Zinc Protoporphyrin Suppresses β-Catenin Protein Expression in Human Cancer Cells: The Potential Involvement of Lysosome-Mediated Degradation

    PubMed Central

    Wang, Shuai; Hannafon, Bethany N.; Lind, Stuart E.; Ding, Wei-Qun

    2015-01-01

    Zinc protoporphyrin (ZnPP) has been found to have anticancer activity both in vitro and in vivo. We have recently demonstrated that ZnPP diminishes β-catenin protein expression in cancer cells. The present study examined the cellular mechanisms that mediate ZnPP’s suppression of β-catenin expression. We demonstrate that ZnPP induces a rapid degradation of the β-catenin protein in cancer cells, which is accompanied by a significant inhibition of proteasome activity, suggesting that proteasome degradation does not directly account for the suppression. The possibility that ZnPP induces β-catenin exportation was rejected by the observation that there was no detectable β-catenin protein in the conditioned medium after ZnPP treatment of cancer cells. Further experimentation demonstrated that ZnPP induces lysosome membrane permeabilization, which was reversed by pretreatment with a protein transportation inhibitor cocktail containing Brefeldin A (BFA) and Monensin. More significantly, pretreatment of cancer cells with BFA and Monensin attenuated the ZnPP-induced suppression of β-catenin expression in a concentration- and time-dependent manner, indicating that the lysosome protein degradation pathway is likely involved in the ZnPP-induced suppression of β-catenin expression. Whether there is cross-talk between the ubiquitin-proteasome system and the lysosome pathway that may account for ZnPP-induced β-catenin protein degradation is currently unknown. These findings provide a novel mechanism of ZnPP’s anticancer action and reveal a potential new strategy for targeting the β-catenin Wnt signaling pathway for cancer therapy. PMID:26000787

  17. Triplet state magnetic resonance and fluorescence spectroscopy of metal-substituted hemoglobins.

    PubMed Central

    Polm, M W; Schaafsma, T J

    1997-01-01

    Fluorescence detected magnetic resonance (FDMR) spectra detected at 596 nm of zinc-substituted hemoglobins at 4.2 K show a split D-E transition, which is not observed for zinc protoporphyrins ligated by methylimidazole in glasses. Incorporation of the zinc heme into the globin pocket is also accompanied by a blue shift of the fluorescence of 20 nm at 4.2 K. FDMR spectra recorded at 576 nm do not show the D-E splitting. The D-E splitting and the huge blue shift are not observed for the magnesium-substituted hemoglobins. Fluorescence measurements at 4.2 K and 77 K, and EPR measurements at 110 K, were carried out to obtain information about the ligation states of the zinc and magnesium protoporphyrins in glasses and in hemoglobin. The results are explained by considering ligation effects and distortion of the porphyrin plane. Images FIGURE 12 PMID:8994622

  18. Zinc protoporphyrin inhibition of lipopolysaccharide-, lipoteichoic acid-, and peptidoglycan-induced nitric oxide production through stimulating iNOS protein ubiquitination

    SciTech Connect

    Chow, J.-M.; Lin, H.-Y.; Shen, S.-C.; Wu, M.-S.; Lin, C.-W.; Chiu, W.-T.; Lin, C.-H. Chen, Y.-C.

    2009-06-15

    In the present study, zinc protoporphyrin (ZnPP), but not ferric protoporphyrin (FePP), tin protoporphyrin (SnPP), or zinc chloride (ZnCl{sub 2}), at the doses of 0.5, 1, and 2 {mu}M, dose-dependently inhibited lipopolysaccharide- (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN)-induced inducible nitric oxide (iNOS) and nitric oxide (NO) production with an increase in heme oxygenase 1 (HO-1) protein in RAW264.7 macrophages in a serum-free condition. NO inhibition and HO-1 induction by ZnPP were blocked by the separate addition of fetal bovine serum (FBS) and bovine serum albumin (BSA). A decrease in the iNOS/NO ratio and an increase in HO-1 protein by ZnPP were identified in three different conditions including ZnPP pretreatment, ZnPP co-treatment, and ZnPP post-treatment with LPS and LTA. Activation of c-Jun N-terminal kinases (JNKs) and extracellular regulated kinases (ERKs) were detected in LPS-, LTA-, and PGN-treated RAW264.7 cells, and iNOS/NO production was blocked by adding the JNK inhibitor, SP600125, but not the ERK inhibitor, PD98059. However, ZnPP addition potentiated ERK and JNK protein phosphorylation stimulated by LPS, LTA, and PGN. Increases in total protein ubiquitination and ubiquitinated iNOS proteins were detected in ZnPP-treated macrophages elicited by LPS according to Western and immunoprecipitation/Western blotting assays, respectively. The decrease in LPS-induced iNOS protein by ZnPP was reversed by adding the proteasome inhibitors MG132 and lactacystin. The reduction in HO-1 protein induced by ZnPP via transfection of HO-1 small interfering RNA did not affect the inhibitory effect of ZnPP against LPS-induced iNOS/NO production and protein ubiquitination induced by ZnPP in macrophages. Data of the present study provide the first evidence to support ZnPP effectively inhibiting inflammatory iNOS/NO production through activation of protein ubiquitination in a HO-1-independent manner in macrophages.

  19. Combined use of zinc protoporphyrin (ZPP), mean corpuscular volume and haemoglobin measurements for classifying microcytic RBC disorders in children and young adults.

    PubMed

    Hershko, C; Konijn, A M; Link, G; Moreb, J; Grauer, F; Weissenberg, E

    1985-01-01

    The diagnostic potential of the combined use of zinc-protoporphyrin (ZPP), mean corpuscular volume (MCV) and haemoglobin measurements for discriminating between iron deficiency anaemia, beta-thalassaemia minor and lead poisoning has been studied. Lead poisoning could be identified by ZPP greater than 50 micrograms/dl in the presence of normal MCV or ZPP greater than 150 micrograms/dl in the presence of microcytosis (MCV less than 80 fl) with a sensitivity of 97% and specificity 94%. Beta-thalassaemia minor was identified by the coexistence of microcytosis and ZPP less than 50 micrograms/dl with a sensitivity of 91% and specificity 79%. Iron deficiency anaemia defined by the combination of microcytosis and ZPP ranging from 50 to 150 micrograms/dl was identified with a sensitivity of 95%, but the specificity was only 51%, with many of the patients overlapping with thalassaemia minor. This problem did not exist in iron-deficiency anaemia with haemoglobin less than 10 g/dl as at that range no patients with uncomplicated thalassaemia minor have been encountered. A great advantage of the combined use of ZPP, MCV and haemoglobin for the initial screening of microcytic anaemia is its ease of performance and low cost. However, this information should only be regarded as presumptive evidence of disease, requiring subsequent confirmation by appropriate direct measurements such as transferrin saturation, serum ferritin, haemoglobin electrophoresis, or blood lead determinations.

  20. Phenylhydrazine-mediated induction of haem oxygenase activity in rat liver and kidney and development of hyperbilirubinaemia. Inhibition by zinc-protoporphyrin.

    PubMed Central

    Maines, M D; Veltman, J C

    1984-01-01

    Phenylhydrazine was found to be a potent inducer of microsomal haem oxygenase activity in rat liver and kidney, but not in spleen. The phenylhydrazine-mediated increase in haem oxygenase activity was time-dependent. Maximum activity was attained 12h after treatment in the liver, and 24h after treatment in the kidney. The increases in the activity of haem oxygenase in the liver and the kidney could be inhibited by cycloheximide. Furthermore, the increases could not be elicited by the treatment of microsomal preparations in vitro with phenylhydrazine. In consonance with the increased haem oxygenase activity, a marked increase (16-fold) was observed in the serum total bilirubin concentration in phenylhydrazine-treated rats. The mechanism of haem degradation promoted by phenylhydrazine in vivo appears to differ from that in vitro; only in the former case is bilirubin formed as the end-product of haem degradation. When rats were given zinc-protoporphyrin (40 mumol/kg) 12h before and after phenylhydrazine treatment, the phenylhydrazine-mediated increases in haem oxygenase activity in the liver and the kidney were effectively blocked. Treatment of rats in vivo with the metalloporphyrin also inhibited the activity of splenic haem oxygenase, and promoted a major decrease in the serum bilirubin levels. In phenylhydrazine-treated animals, the microsomal content of cytochrome P-450 was significantly decreased in the absence of a decrease in the microsomal haem concentration. The decrease in cytochrome P-450 content was accompanied by an increased absorption in the 420nm region of the reduced CO-difference spectrum, suggesting the conversion of the cytochrome to an inactive form. The marked depletion of cellular glutathione levels suggests that this conversion may be related to the action of active intermediates and free radicals formed in the course of the interaction of phenylhydrazine with the haem moiety of cytochrome P-450. PMID:6546515

  1. Effect of different chemical bonds in pegylation of zinc protoporphyrin that affects drug release, intracellular uptake, and therapeutic effect in the tumor.

    PubMed

    Tsukigawa, Kenji; Nakamura, Hideaki; Fang, Jun; Otagiri, Masaki; Maeda, Hiroshi

    2015-01-01

    Pegylated zinc protoporphyrin (PEG-ZnPP) is a water-soluble inhibitor of heme oxygenase-1. In this study, we prepared two types of PEG-ZnPP conjugates with different chemical bonds between PEG and ZnPP, i.e., ester bonds and ether bonds, where both conjugates also contain amide bonds. Cleavability of these bonds in vitro and in vivo, especially cancer tissue, and upon intracellular uptake, was investigated in parallel with biological activities of the conjugates. Each conjugate showed different cleavability by plasma esterases and tumor proteases, as revealed by HPLC analyses. PEG-ZnPP with ester bond (esPEG-ZnPP) was more sensitive than PEG-ZnPP with ether bond (etPEG-ZnPP) for cleavage of PEG chains. etPEG-ZnPP showed no cleavage of PEG chains and had lower intracellular uptake and antitumor activity than did esPEG-ZnPP. The degradation of esPEG-ZnPP appeared to be facilitated by both serine and cysteine proteases in tumor tissues, whereas it was significantly slower in normal organs except the liver. Depegylated products such as free ZnPP had higher intracellular uptake than did intact PEG-ZnPP. We also studied hydrolytic cleavage by blood plasma of different animal species; mouse plasma showed the fastest cleavage whereas human plasma showed the slowest. These results suggest that ester-linked conjugates manifest more efficient cleavage of PEG, and greater yield of the active principle from the conjugates in tumor tissues than in normal tissues. More efficient intracellular uptake and thus an improved therapeutic effect with ester-linked conjugates are thus anticipated with fain stability, particularly in human blood.

  2. [Food security, growth and vitamin A, hemoglobin and zinc levels of preschool children in the northeast of Brazil].

    PubMed

    Pedraza, Dixis Figueroa; Queiroz, Daiane de; Paiva, Adriana de Azevedo; Cunha, Maria Auxiliadora Lins da; Lima, Zilka Nanes

    2014-02-01

    This study sought to examine the association between the food (in)security and nutritional status of preschool children attended in daycare centers. Food security was assessed using the Brazilian Food Insecurity Scale. The nutritional status was evaluated using the weight/height, weight/age, height/age, hemoglobin, serum retinol and serum zinc status. The prevalence of stunting (6.2%), overweight (3.1%), underweight (2.1%), vitamin A deficiency (24.4%), anemia (15.5%), and zinc deficiency (15%) was established. Food insecurity was found in 64.4% of the families, predominantly in its mild form (32.6%). This study concludes that food insecurity as measured by the EBIA was not associated with Z-score growth or with vitamin A, hemoglobin and zinc biochemical concentrations.

  3. Sulfide binding is mediated by zinc ions discovered in the crystal structure of a hydrothermal vent tubeworm hemoglobin.

    PubMed

    Flores, Jason F; Fisher, Charles R; Carney, Susan L; Green, Brian N; Freytag, John K; Schaeffer, Stephen W; Royer, William E

    2005-02-22

    Key to the remarkable ability of vestimentiferan tubeworms to thrive in the harsh conditions of hydrothermal vents are hemoglobins that permit the sequestration and delivery of hydrogen sulfide and oxygen to chemoautotrophic bacteria. Here, we demonstrate that zinc ions, not free cysteine residues, bind sulfide in vestimentiferan hemoglobins. The crystal structure of the C1 hemoglobin from the hydrothermal vent tubeworm Riftia pachyptila has been determined to 3.15 A and revealed the unexpected presence of 12 tightly bound Zn(2+) ions near the threefold axes of this D(3) symmetric hollow sphere. Chelation experiments on R. pachyptila whole-coelomic fluid and purified hemoglobins reveal a role for Zn(2+) ions in sulfide binding. Free cysteine residues, previously proposed as sulfide-binding sites in vestimentiferan hemoglobins, are found buried in surprisingly hydrophobic pockets below the surface of the R. pachyptila C1 molecule, suggesting that access of these residues to environmental sulfide is restricted. Attempts to reduce the sulfide-binding capacities of R. pachyptila hemoglobins by addition of a thiol inhibitor were also unsuccessful. These findings challenge the currently accepted paradigm of annelid hemoglobin evolution and adaptation to reducing environments. PMID:15710902

  4. Toxic effects of zinc from trout farm sediments on ATP, protein, and hemoglobin concentrations of Limnodrilus hoffmeisteri.

    PubMed

    Martinez-Tabche, L; Gutiérrez Cabrera, I; Gómez Oliván, L; Galar Martinez, M; Germán Faz, C

    2000-04-14

    Zinc (Zn) is a nutritionally essential metal, and deficiency results in severe health consequences to aquatic organisms. In this study toxicity data for Limnodrilus hoffmeisteri produced by Zn in systems using three natural sediments (trout farms: El Oyamel, El Truchón, and El Potrero) are presented. Hemoglobin, adenosine triphosphate (ATP), and protein concentrations were measured in L. hoffmeisteri exposed to spiked sediments, as indicators of exposure. Physicochemical characteristics of water and sediments were also considered. Zn concentrations were measured in water and sediment. El Oyamel, El Truchón, and El Potrero pond sediments did not have similar physicochemical characteristics. Zn concentrations of water obtained from the rustic ponds were near 0.4575 mg/L; however, this metal was always found to be higher in the sediments (0.0271-0.9754 mg/kg). The bioassay with worms demonstrated that pond sediments from El Oyamel, El Potrero, and El Truchón produced toxicity since ATP and protein concentrations were low compared to controls (organisms without metal). All spiked sediments had a significant reduction effect on ATP, protein, and hemoglobin concentrations. This investigation clearly shows that sediments of El Truchón, El Oyamel, and El Potrero possess toxicity potential. These results suggest the usefulness of these bioassays to evaluate the toxicity of sediments polluted with heavy metals. PMID:10777248

  5. A label-free fluorescence assay for thrombin based on aptamer exonuclease protection and exonuclease III-assisted recycling amplification-responsive cascade zinc(II)-protoporphyrin IX/G-quadruplex supramolecular fluorescent labels.

    PubMed

    Lv, Yanqin; Xue, Qingwang; Gu, Xiaohong; Zhang, Shuqiu; Liu, Jifeng

    2014-05-21

    A simple, label-free and sensitive fluorescence protein assay has been developed on the basis of aptamer exonuclease protection and exonuclease III (Exo III)-assisted recycling amplification-responsive cascade ZnPPIX/G-quadruplex supramolecular fluorescent labels. In the sensing system, a special aptamer probe containing the aptamer sequence at the 3'-terminus and the DNAzyme sequence at the 5'-terminus was applied, which has the capacity to recognize a protein target with high affinity and specificity. Exonuclease I (Exo I) can efficiently catalyze the degradation of free single stranded DNA probes in the 3' to 5' direction. In the presence of the target protein, the strong binding between the target protein and its aptamer can protect aptamer probes from degradation. Subsequently, the protected aptamer probes act as catalysators to trigger hybridization with the hairpin DNA probe that contains a partially "caged" G-quadruplex sequence. Upon interaction with the protected aptamer probes, the hairpin opens to yield the active G-quadruplex structure. In the presence of exonuclease III (Exo III), Exo III-assisted recycling amplification occurs generating numerous G-quadruplex supramolecular structures. The zinc(ii)-protoporphyrin IX (ZnPPIX) fluorophore binds to the G-quadruplexes and this results in the enhanced fluorescence of the fluorophore. The resulting fluorescence of the ZnPPIX/G-quadruplex provides the readout signal for the sensing event. Thrombin is used as the model analyte in the current proof-of-concept. The developed method was demonstrated to have very high sensitivity for the detection of proteins with a limit of detection of 0.2 pM without using washes or separations. In addition, this new method for protein detection is simple and inherits all the advantages of aptamers. The mechanism, moreover, may be generalized and used for other forms of protein analysis.

  6. Protoporphyrin formation in Rhizobium japonicum.

    PubMed Central

    Keithly, J H; Nadler, K D

    1983-01-01

    The obligately aerobic soybean root nodule bacterium Rhizobium japonicum produces large amounts of heme (iron protoporphyrin) only under low oxygen tensions, such as exist in the symbiotic root nodule. Aerobically incubated suspensions of both laboratory-cultured and symbiotic bacteria (bacteroids) metabolize delta-aminolevulinic acid to uroporphyrin, coproporphyrin, and protoporphyrin. Under anaerobic conditions, suspensions of laboratory-cultured bacteria form greatly reduced amounts of protoporphyrin from delta-aminolevulinic acid, whereas protoporphyrin formation by bacteroid suspensions is unaffected by anaerobiosis, suggesting that bacteroids form protoporphyrin under anaerobic conditions more readily than do free-living bacteria. Oxygen is the major terminal electron acceptor for coproporphyrinogen oxidation in cell-free extracts of both bacteroids and free-living bacteria. In the absence of oxygen, ATP, NADP, Mg2+, and L-methionine are required for protoporphyrin formation in vitro. In the presence of these supplements, coproporphyrinogenase activity under anaerobic conditions is 5 to 10% of that observed under aerobic conditions. Two mechanisms for coproporphyrinogen oxidation exist in R. japonicum: an oxygen-dependent process and an anaerobic oxidation in which electrons are transferred to NADP. The significance of these findings with regard to heme biosynthesis in the microaerophilic soybean root nodule is discussed. PMID:6841317

  7. A multimicronutrient-fortified seasoning powder enhances the hemoglobin, zinc, and iodine status of primary school children in North East Thailand: a randomized controlled trial of efficacy.

    PubMed

    Winichagoon, Pattanee; McKenzie, Joanne E; Chavasit, Visith; Pongcharoen, Tippawan; Gowachirapant, Sueppong; Boonpraderm, Atitada; Manger, Mari S; Bailey, Karl B; Wasantwisut, Emorn; Gibson, Rosalind S

    2006-06-01

    Anemia and co-existing deficiencies of zinc, iron, iodine, and vitamin A occur among children in many developing countries including NE Thailand, probably contributing to impairments in growth, immune competence, and cognition. Sustainable strategies are urgently required to combat these deficiencies. We assessed the efficacy of a micronutrient-fortified seasoning powder served with a school lunch on reducing anemia and improving the micronutrient status of rural NE Thai children. Children (n = 569) aged 5.5-13.4y from 10 schools were randomly assigned to receive a seasoning powder either unfortified or fortified with zinc (5 mg), iron (5 mg), vitamin A (270 microg), and iodine (50 microg) (per serving) and incorporated into a school lunch prepared centrally and delivered 5 d/wk for 31 wk. Teachers monitored school lunch consumption. Baseline and final micronutrient status, hemoglobinopathies, and infection or inflammation were assessed from blood and urine samples. For the primary outcome, anemia (based on hemoglobin), no intervention effect was apparent (odds ratio: 1.02 95% CI: 0.69, 1.51) after adjustment for design strata. The odds of zinc (based on serum zinc) and urinary iodine deficiency in the fortified group were 0.63 (0.42, 0.94) and 0.52 (0.38, 0.71) times those in the unfortified group, respectively. Fortification had no effect on serum retinol (0.61: 0.25,1.51), ferritin (1.12: 0.43, 2.96), or mean red cell volume (1.16: 0.82, 1.64). Therefore, a micronutrient-fortified seasoning powder is a promising vehicle for improving zinc, iodine, and hemoglobin status, and its potential for incorporation into lunch programs in day care centers and schools in NE Thailand warrants investigation. PMID:16702330

  8. [Erythrocyte protoporphyrin during recovery from malnutrition in rats].

    PubMed

    Haydée Langini, S; Río de Gómez del Río, M E; Pita Martín de Portela, M L

    1999-09-01

    Interrelationships between Erythrocyte Protoporphyrin (EP), dietary Iron/Protein ratio (Fe/Prot) and Fe liver content (Feh) were studied during nutritional recovery in an experimental model: weanling female Wistar rats (To) were depleted with a protein-free diet (LP), losing 20% of their initial body weight. Then they were recovered until 45 days of age (T45) with diets containing: casein: 20 g/100 g; Fe (ammonium Fe citrate) (ppm.): 0, 75 or 100 (groups A1, A2 and A3, respectively). Hematocrit, Hemoglobin (Hb) (g/dL). Erythrocyte Protoporphyrin (EP) (microgram/dL Red Blood Cells) and Feh (microgram) were determined at To, LP and T45. Results were compared with control rats (C) fed with 20% of casein and Fe, 50 ppm. EP: a) decreased in C from To to T45 (99 +/- 24; 36 +/- 9; p < 0.01); b) increased in A1 and A2 at T45 (123 +/- 21; 93 +/- 29, respectively, p < 0.01) while A3 did not show significant difference (45 +/- 7) regarding to C: c) correlated inversely with Feh. According to the inverse correlation between EP and Fe/Prot (r = -0.99), we found that 92 ppm was an adequate Fe amount to prevent EP increase. These results confirm that during recovery from undernutrition EP depends on iron liver content, being an adequate indicator of iron nutritional status; therefore, EP would be useful as a predictor of the optimum Fe/Prot ratio for nutritional recovery.

  9. Zinc

    MedlinePlus

    ... ulcers and promoting weight gain in people with eating disorders such as anorexia nervosa. Some people use zinc ... is abnormal): 25-100 mg zinc. For the eating disorder anorexia nervosa: 100 mg of zinc gluconate daily. ...

  10. Zinc.

    PubMed

    Barceloux, D G

    1999-01-01

    The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound healing. Zinc is a relatively common metal with an average concentration of 50 mg/kg soil and a range of 10-300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recommended daily allowance for adults is 15 mg zinc. The ingestion of 1-2 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and interstitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent. PMID:10382562

  11. Hemoglobin (image)

    MedlinePlus

    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 ...

  12. Hydrogen peroxide biosensor based on hemoglobin immobilized at graphene, flower-like zinc oxide, and gold nanoparticles nanocomposite modified glassy carbon electrode.

    PubMed

    Xie, Lingling; Xu, Yuandong; Cao, Xiaoyu

    2013-07-01

    In this work, a highly sensitive hydrogen peroxide (H2O2) biosensor based on immobilization of hemoglobin (Hb) at Au nanoparticles (AuNPs)/flower-like zinc oxide/graphene (AuNPs/ZnO/Gr) composite modified glassy carbon electrode (GCE) was constructed, where ZnO and Au nanoparticles were modified through layer-by-layer onto Gr/GCE. Flower-like ZnO nanoparticles could be easily prepared by adding ethanol to the precursor solution having higher concentration of hydroxide ions. The Hb/AuNPs/ZnO/Gr composite film showed a pair of well-defined, quasi-reversible redox peaks with a formal potential (E(0)) of -0.367 V, characteristic features of heme redox couple of Hb. The electron transfer rate constant (k(s)) of immobilized Hb was 1.3 s(-1). The developed biosensor showed a very fast response (<2 s) toward H2O2 with good sensitivity, wide linear range, and low detection limit of 0.8 μM. The fabricated biosensor showed interesting features, including high selectivity, acceptable stability, good reproducibility, and repeatability along with excellent conductivity, facile electron mobility of Gr, and good biocompatibility of ZnO and AuNPs. The fabrication method of this biosensor was simple and effective for determination of H2O2 in real samples with quick response, good sensitivity, high selectivity, and acceptable recovery.

  13. A simple and efficient method for hemoglobin removal from mammalian tissue cytosol by zinc sulfate and its application to the study of lipoxygenase.

    PubMed

    Hover, C G; Kulkarni, A P

    2000-02-01

    A simple and efficient method is described to remove hemoglobin (Hb) from human term placental cytosol to study dioxygenase and co-oxidase activities of lipoxygenase. In the untreated samples, 70%-80% of the linoleic acid-dependent dioxygenase and co-oxidase activities were found to be associated with the pseudo-lipoxygenase activity of Hb. Zinc sulfate (0.5 mM) precipitated >97% of the Hb present in the cytosol. The dioxygenase activity of the ZnSO4 treated cytosol exhibited a Vmax value of 313 nmoles linoleic acid hydroperoxide formed/min/mg protein and a K(M) of 1.4 mM for linoleic acid. The ZnSO4 treated cytosol displayed co-oxidase activity toward benzidine, dimethoxybenzidine, guaiacol, pyrogallol, tetramethylbenzidine and tetramethyl-p-phenylenediamine. Nordihydroguaiaretic acid, 5,8,11-eicosatriynoic acid, butylated hydroxyanisole, butylated hydroxytoluene and gossypol caused concentration dependent inhibition of dioxygenase and co-oxidase activities. These results suggest ZnSO4 precipitation of Hb from cytosol does not alter the functional characteristics of the human term placental lipoxygenase.

  14. Zinc

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zinc was recognized as an essential trace metal for humans during the studies of Iranian adolescent dwarfs in the early 1960s. Zinc metal existing as Zn2+ is a strong electron acceptor in biological systems without risks of oxidant damage to cells. Zn2+ functions in the structure of proteins and is ...

  15. Altered Concentrations of Copper, Zinc, and Iron are Associated With Increased Levels of Glycated Hemoglobin in Patients With Type 2 Diabetes Mellitus and Their First-Degree Relatives

    PubMed Central

    Atari-Hajipirloo, Somayeh; Valizadeh, Neda; Khadem-Ansari, Mohammad-Hassan; Rasmi, Yousef; Kheradmand, Fatemeh

    2016-01-01

    Background The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. Objectives The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated. Patients and Methods We studied 46 subjects with T2DM, 46 FDR, and 50 control subjects matched for age and sex. Serum concentrations of Cu, Zn, and Fe were measured by colorimetric kit. Fasting blood glucose (FBG) and HbA1c were assayed using the standard kit. Results An imbalance in the levels of the studied metals was observed in both patients with T2DM and FDR. We found significantly decreased levels of Zn and higher levels of Cu and Fe in the patients with T2DM and FDR when compared with the control subjects (P < 0.05). HbA1c levels were positively correlated with Cu and Fe and inversely correlated with Zn in the patients with T2DM and FDR (P < 0.05). Conclusions The patients with T2DM and FDR had altered contents of Cu, Zn, and Fe that might be a predisposing factor to the development of diabetes in future or vice versa the result of diabetes development. Impaired metabolism of these elements may contribute to the augmented risk of developing type 2 diabetes mellitus later in the life of their first-degree relatives. PMID:27761143

  16. Zinc

    MedlinePlus

    ... deficiency also causes hair loss, diarrhea, eye and skin sores and loss of appetite. Weight loss, problems ... pneumonia and other infections. Zinc also helps the skin stay healthy. Some people who have skin ulcers ...

  17. Hemoglobin substitutes.

    PubMed

    Anbari, Kevin K; Garino, Jonathan P; Mackenzie, Colin F

    2004-10-01

    Orthopaedic patients frequently require blood transfusions to treat peri-operative anemia. Research in the area of hemoglobin substitutes has been of great interest since it holds the promise of reducing the reliance on allogeneic blood transfusions. The three categories of hemoglobin substitutes are (1) cell-free, extracellular hemoglobin preparations made from human or bovine hemoglobin (hemoglobin-based oxygen carriers or HBOCs); (2) fluorine-substituted linear or cyclic carbon chains with a high oxygen-carrying capacity (perfluorocarbons); and (3) liposome-encapsulated hemoglobin. Of the three, HBOCs have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile. This has been demonstrated in vascular, cardiothoracic, and orthopaedic patients. HBOC-201, which is a preparation of cell-free bovine hemoglobin, has been approved for clinical use in South Africa. These products may well become an important tool for physicians treating peri-operative anemia in orthopaedic patients.

  18. Hemoglobin electrophoresis

    MedlinePlus

    ... sickle cell anemia. Other, less common, abnormal Hb molecules cause other types of anemia . ... adults, these are normal percentages of different hemoglobin molecules: Hb A: 95% to 98% Hb A2: 2% ...

  19. Hemoglobin derivatives

    MedlinePlus

    ... in red blood cells that moves oxygen and carbon dioxide between the lungs and body tissues. This article ... attached to carbon monoxide instead of oxygen or carbon dioxide. High amounts of this type of abnormal hemoglobin ...

  20. Hemoglobin uptake by Paracoccidioides spp. is receptor-mediated.

    PubMed

    Bailão, Elisa Flávia Luiz Cardoso; Parente, Juliana Alves; Pigosso, Laurine Lacerda; de Castro, Kelly Pacheco; Fonseca, Fernanda Lopes; Silva-Bailão, Mirelle Garcia; Báo, Sônia Nair; Bailão, Alexandre Melo; Rodrigues, Marcio L; Hernandez, Orville; McEwen, Juan G; Soares, Célia Maria de Almeida

    2014-05-01

    Iron is essential for the proliferation of fungal pathogens during infection. The availability of iron is limited due to its association with host proteins. Fungal pathogens have evolved different mechanisms to acquire iron from host; however, little is known regarding how Paracoccidioides species incorporate and metabolize this ion. In this work, host iron sources that are used by Paracoccidioides spp. were investigated. Robust fungal growth in the presence of the iron-containing molecules hemin and hemoglobin was observed. Paracoccidioides spp. present hemolytic activity and have the ability to internalize a protoporphyrin ring. Using real-time PCR and nanoUPLC-MSE proteomic approaches, fungal growth in the presence of hemoglobin was shown to result in the positive regulation of transcripts that encode putative hemoglobin receptors, in addition to the induction of proteins that are required for amino acid metabolism and vacuolar protein degradation. In fact, one hemoglobin receptor ortholog, Rbt5, was identified as a surface GPI-anchored protein that recognized hemin, protoporphyrin and hemoglobin in vitro. Antisense RNA technology and Agrobacterium tumefaciens-mediated transformation were used to generate mitotically stable Pbrbt5 mutants. The knockdown strain had a lower survival inside macrophages and in mouse spleen when compared with the parental strain, which suggested that Rbt5 could act as a virulence factor. In summary, our data indicate that Paracoccidioides spp. can use hemoglobin as an iron source most likely through receptor-mediated pathways that might be relevant for pathogenic mechanisms. PMID:24831516

  1. Hemoglobin Uptake by Paracoccidioides spp. Is Receptor-Mediated

    PubMed Central

    Bailão, Elisa Flávia Luiz Cardoso; Parente, Juliana Alves; Pigosso, Laurine Lacerda; de Castro, Kelly Pacheco; Fonseca, Fernanda Lopes; Silva-Bailão, Mirelle Garcia; Báo, Sônia Nair; Bailão, Alexandre Melo; Rodrigues, Marcio L.; Hernandez, Orville; McEwen, Juan G.; Soares, Célia Maria de Almeida

    2014-01-01

    Iron is essential for the proliferation of fungal pathogens during infection. The availability of iron is limited due to its association with host proteins. Fungal pathogens have evolved different mechanisms to acquire iron from host; however, little is known regarding how Paracoccidioides species incorporate and metabolize this ion. In this work, host iron sources that are used by Paracoccidioides spp. were investigated. Robust fungal growth in the presence of the iron-containing molecules hemin and hemoglobin was observed. Paracoccidioides spp. present hemolytic activity and have the ability to internalize a protoporphyrin ring. Using real-time PCR and nanoUPLC-MSE proteomic approaches, fungal growth in the presence of hemoglobin was shown to result in the positive regulation of transcripts that encode putative hemoglobin receptors, in addition to the induction of proteins that are required for amino acid metabolism and vacuolar protein degradation. In fact, one hemoglobin receptor ortholog, Rbt5, was identified as a surface GPI-anchored protein that recognized hemin, protoporphyrin and hemoglobin in vitro. Antisense RNA technology and Agrobacterium tumefaciens-mediated transformation were used to generate mitotically stable Pbrbt5 mutants. The knockdown strain had a lower survival inside macrophages and in mouse spleen when compared with the parental strain, which suggested that Rbt5 could act as a virulence factor. In summary, our data indicate that Paracoccidioides spp. can use hemoglobin as an iron source most likely through receptor-mediated pathways that might be relevant for pathogenic mechanisms. PMID:24831516

  2. Zinc and cadmium interference with four commonly performed diagnostic tests for lead intoxication

    SciTech Connect

    D'Alleinne, C.P.

    1984-01-01

    Increases in erythrocytic delta-aminolevulinic acid dehydratase(delta-ALAD) activity, erythrocytic zinc protoporphyrin (ZPP) concentration, urinary delta-aminolevulinic acid (delta-ALA-U) concentration, and blood lead (Pb-B) concentration are indicative of lead intoxication and are the basis for determining exposure to lead. The influence of oral or parenteral zinc and cadmium on the toxicity of oral lead was investigated in Hartley guinea pigs. Compared to the administration of lead alone, the concomitant oral administration of lead and zinc resulted in reduced Pb-B and delta-ALA-U concentrations. Similarly, the concomitant administration of lead and cadmium resulted in decreased packed cell volume (PCV) and hemoglobin (Hb) concentrations, and increased ZPP concentration in blood. Delta-ALAD activity was maximally inhibited in all groups which received lead. Consequently, no significant data concerning the effects of cadmium or zinc on delta-ALAD activity was obtained. This data indicates that delta-ALA-U analysis is an inappropriate test to determine intoxication which may have been caused by simultaneous oral exposure to lead and zinc, and that simultaneous exposure apparently decreases the absorption of lead. These observations seriously question the validity of using only delta-ALA-U or Pb-B as a screening test for lead intoxication.

  3. Serum free hemoglobin test

    MedlinePlus

    Blood hemoglobin; Serum hemoglobin ... Hemoglobin (Hb) is the main component of red blood cells. It is a protein that carries oxygen. ... people may contain up to 5 mg/dL hemoglobin. Normal value ranges may vary slightly among different ...

  4. Hemoglobin C disease

    MedlinePlus

    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 ...

  5. On the fate of extracellular hemoglobin and heme in brain.

    PubMed

    Lara, Flavio A; Kahn, Suzana A; da Fonseca, Anna Cc; Bahia, Carlomagno P; Pinho, João Pc; Graca-Souza, Aurélio V; Houzel, Jean C; de Oliveira, Pedro L; Moura-Neto, Vivaldo; Oliveira, Marcus F

    2009-06-01

    Intracerebral hemorrhage (ICH) is a major cause of disability in adults worldwide. The pathophysiology of this syndrome is complex, involving both inflammatory and redox components triggered by the extravasation of blood into the cerebral parenchyma. Hemoglobin, heme, and iron released therein seem be important in the brain damage observed in ICH. However, there is a lack of information concerning hemoglobin traffic and metabolism in brain cells. Here, we investigated the fate of hemoglobin and heme in cultured neurons and astrocytes, as well as in the cortex of adult rats. Hemoglobin was made traceable by conjugation to Alexa 488, whereas a fluorescent heme analogue (tin-protoporphyrin IX) was prepared to allow heme tracking. Using fluorescence microscopy we observed that neurons were more efficient in uptake hemoglobin and heme than astrocytes. Exposure of cortical neurons to hemoglobin or heme resulted in an oxidative stress condition. Viability assays showed that neurons were more susceptible to both hemoglobin and heme toxicity than astrocytes. Together, these results show that neurons, rather than astrocytes, preferentially take up hemoglobin-derived products, indicating that these cells are actively involved in the ICH-associated brain damage.

  6. Two-photon excited fluorescence emission from hemoglobin

    NASA Astrophysics Data System (ADS)

    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.

  7. Methods of producing protoporphyrin IX and bacterial mutants therefor

    DOEpatents

    Zhou, Jizhong; Qiu, Dongru; He, Zhili; Xie, Ming

    2016-03-01

    The presently disclosed inventive concepts are directed in certain embodiments to a method of producing protoporphyrin IX by (1) cultivating a strain of Shewanella bacteria in a culture medium under conditions suitable for growth thereof, and (2) recovering the protoporphyrin IX from the culture medium. The strain of Shewanella bacteria comprises at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX. In certain embodiments of the method, the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or of shew_1140. In other embodiments, the presently disclosed inventive concepts are directed to mutant strains of Shewanella bacteria having at least one mutant hemH gene which is incapable of normal expression, thereby causing an accumulation of protoporphyrin IX during cultivation of the bacteria. In certain embodiments the strain of Shewanella bacteria is a strain of S. loihica, and more specifically may be S. loihica PV-4. In certain embodiments, the mutant hemH gene of the strain of Shewanella bacteria may be a mutant of shew_2229 and/or shew_1140.

  8. Interaction of Human Serum Albumin with Metal Protoporphyrins

    NASA Astrophysics Data System (ADS)

    Hu, Jie; Brancaleon, Lorenzo

    2015-03-01

    Fluorescence spectroscopy is widely used in biotechnology, nanotechnology, and molecular biophysics, since it can provide information on a wide range of molecular processes, e.g. the interactions of solvent molecules with fluorophores, conformational changes, and binding interactions etc. In this study, we present the photophysical properties of the interaction of human serum albumin (HSA) with a series of metal compound of Protoporphyrin IX (PPIX), including ZnPPIX, FePPIX, MgPPIX, MnPPIX and SnPPIX respectively, as well as the free base PPIX. Binding constants were retrieved independently using the Benesi-Hildebrand analysis of the porphyrin emission or absorption spectra and the fluorescence quenching (i.e. Stern-Volmer analysis) and reveal that the two methods yield a difference of approximately one order or magnitude between the two. Fluorescence lifetimes was used to probe whether binding of the porphyrin changes the conformation of the protein or if the interaction places the porphyrin at a location that can prompt resonance energy transfer with the lone Tryptophan residue. In recent years it has been discovered that HSA provides a specific binding site for metal-chelated protoporphyrins in subdomain IA. This has opened a novel field of study over the importance of this site for biomedical applications but it has also created the potential for a series of biotechnological applications of the HSA/protoporphyrin complexes. Our study provides a preliminary investigation of the interaction with metal-chelated protoporphyrins that had not been previously investigated.

  9. Biomarkers of metals exposure in fish from lead-zinc mining areas of Southeastern Missouri, USA

    USGS Publications Warehouse

    Schmitt, C.J.; Whyte, J.J.; Roberts, A.P.; Annis, M.L.; May, T.W.; Tillitt, D.E.

    2007-01-01

    The potential effects of proposed lead-zinc mining in an ecologically sensitive area were assessed by studying a nearby mining district that has been exploited for about 30 y under contemporary environmental regulations and with modern technology. Blood and liver samples representing fish of three species (largescale stoneroller, Campostoma oligolepis, n=91; longear sunfish, Lepomis megalotis, n=105; and northern hog sucker, Hypentelium nigricans, n=20) from 16 sites representing a range of conditions relative to mining activities were collected. Samples were analyzed for metals (also reported in a companion paper) and for biomarkers of metals exposure [erythrocyte ??-aminolevulinic acid dehydratase (ALA-D) activity; concentrations of zinc protoporphyrin (ZPP), iron, and hemoglobin (Hb) in blood; and hepatic metallothionein (MT) gene expression and lipid peroxidation]. Blood lead concentrations were significantly higher and ALA-D activity significantly lower in all species at sites nearest to active lead-zinc mines and in a stream contaminated by historical mining than at reference or downstream sites. ALA-D activity was also negatively correlated with blood lead concentrations in all three species but not with other metals. Iron and Hb concentrations were positively correlated in all three species, but were not correlated with any other metals in blood or liver in any species. MT gene expression was positively correlated with liver zinc concentrations, but neither MT nor lipid peroxidase differences among fish grouped according to lead concentrations were statistically significant. ZPP was not detected by hematofluorometry in most fish, but fish with detectable ZPP were from sites affected by mining. Collectively, these results confirm that metals are released to streams from active lead-zinc mining sites and are accumulated by fish. ?? 2007 Elsevier Inc. All rights reserved.

  10. [Prevalence of deficiency and dietary intake of iron, zinc and copper in Chilean childbearing age women].

    PubMed

    Mujica-Coopman, María F; Borja, Angélica; Pizarro, Fernando; Olivares, Manuel

    2014-03-01

    The aim of the present study was to evaluate anemia, the biochemical status and dietary adequacy of iron (Fe), zinc (Zn) and copper (Cu), in Chilean childbearing age women. We studied a convenience sample of 86 women aged 18 to 48 years from Santiago, Chile. We determined anemia and the micronutrient status through hemoglobin (Hb) mean corpuscular volume, transferrin saturation, zinc protoporphyrin, serum ferritin (SF), serum Zn and Cu. Dietary adequacy was estimated using a food frequency questionnaire. Of all women, 4.7% had Fe deficiency (ID) anemia, 21 % ID without anemia, 26 % depleted Fe stores and 48.3% normal Fe status. Obese women had higher SF (p<0.01) compared with those classified as having normal BMI. Also, showed higher Hb (p<0.05) concentrations compared with overweight and normal weight women. Partidipants showed 3.5 % and 2.3 % of Zn and Cu deficiency, respectively. Also, 95 %, 94 % and 99 % had adequate intake of Fe, Zn and Cu respectively, according to EAR cut points. There were no significant differences in micronutrients intake across different nutritional status. There was a low prevalence of anemia, Fe, Zn and Cu deficiency. A high percentage of women reached micronutrient adequacy. However, 47% of women had ID without anemia and Fe depleted stores.

  11. Combined iron and folic acid supplementation with or without zinc reduces time to walking unassisted among Zanzibari infants 5- to 11-mo old.

    PubMed

    Olney, Deanna K; Pollitt, Ernesto; Kariger, Patricia K; Khalfan, Sabra S; Ali, Nadra S; Tielsch, James M; Sazawal, Sunil; Black, Robert; Allen, Lindsay H; Stoltzfus, Rebecca J

    2006-09-01

    Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron+folic acid (FeFA) (12.5 mg Fe + 50 mug folic acid), zinc (Zn) (10 mg), and iron+folic acid+zinc (FeFA+Zn) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba, Zanzibar. The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5-11 mo at the start of supplementation. Treatment effects on changes in hemoglobin (Hb) and zinc protoporphyrin (ZPP) and height-for-age (HAZ) and weight-for-age (WAZ) Z scores were evaluated using linear regression. Attained motor milestone was recorded every 2 wk for 1 y. Hb, ZPP, HAZ, and WAZ were measured at baseline and after 6 mo of treatment. FeFA with or without Zn reduced the time it took for children to walk assisted. Children who received any iron walked unassisted sooner than those who received no iron [median difference approximately 15 d, P = 0.035, risk ratio (RR) = 1.28, 95% CI = 1.02, 1.61] and this effect was stronger in those who had iron deficiency anemia (IDA) at baseline (median difference was approximately 30 d; P = 0.002; RR = 1.68; 95% CI = 1.21, 2.32). FeFA alone and Zn alone improved Hb and ZPP compared with placebo. There were no significant treatment effects on changes in HAZ or WAZ. The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin, but were not mediated through improvements in growth.

  12. The Hemoglobin E Thalassemias

    PubMed Central

    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

  13. Spectral hole burning study of protoporphyrin IX substituted myoglobin.

    PubMed Central

    Zollfrank, J; Friedrich, J; Parak, F

    1992-01-01

    Protoporphyrin IX substituted myoglobin reveals excellent hole burning properties. We investigated the frequency shift of persistent spectral holes under isotropic pressure conditions in a range from 0 to 2.4 MPa. In this range, the protein behaves like an elastic solid. The shift of the holes under pressure shows a remarkable frequency dependence from which the compressibility of the protein can be determined. The compressibility, in turn, allows for an estimation of the equilibrium volume fluctuations. Within the frame of the model used to interpret the pressure data, it is possible to determine the absorption frequency of the isolated chromophore and the associated solvent shift in the protein environment. PMID:1504243

  14. Interaction of Fe-protoporphyrin IX and heme analogues with purified recombinant heme oxygenase-2, the constitutive isozyme of the brain and testes.

    PubMed

    Rublevskaya, I; Maines, M D

    1994-10-21

    Heme oxygenase-2 (HO-2) is the predominant form of heme oxygenase in the brain and testes. The enzyme is not readily amenable to isolation from mammalian tissues and has not been characterized for its kinetic properties and interaction with metalloporphyrins. Presently a rat HO-2 cDNA (Rotenberg, M.O., and Maines, M. D. (1990) J. Biol. Chem. 265, 7501-7506) was used to generate a construct with a neutral hydrophobicity profile at its COOH terminus for expression of nearly full-length HO-2 protein in Escherichia coli. The procedures used for HO-1 were of no utility in purification of HO-2. A multistep protocol developed for isolation of HO-2 resulted in a homogeneous protein with a specific activity up to 6,500 nmol of bilirubin/mg/h. Based on SDS-polyacrylamide gel electrophoresis and Western blot analyses, the protein had an apparent molecular mass of approximately 34 kDa. HO-2 binds Fe-protoporphyrin (heme) at near molar unity to give a complex with the absorption maximum at 403 nm. The Soret band has a blue shift to 430 nm when heme iron is reduced, with distinct alpha and beta bands at 485 and 550 nm, respectively. The Soret band of the CO complex of ferrous heme.HO-2 is at 420 nm, and alpha and beta bands are at 540 and 572 nm, respectively. The apparent Km for Fe-protoporphyrin is 0.33 microM, with a Vmax of 0.45 nmol of bilirubin/mg/h. Zn-protoporphyrin is a strong mixed inhibitor of enzyme activity, whereas Co-protoporphyrin is a poor competitive inhibitor of activity. When HO-2 was preincubated (10 min at 4 degrees C) with Fe-protoporphyrin, the cobalt complex did not inhibit enzyme activity, whereas the Zn-protoporphyrin effectively inhibited activity. Calorimetric measurements suggest that HO-2/heme interaction involves one type of association producing a single heat absorption peak upon melting of the complex and that the unfolding is not reversible. The association increases the enthalpy of HO-2 (130 kcal/mol versus 184 kcal/mol) and increases the

  15. Processed complementary food does not improve growth or hemoglobin status of rural tanzanian infants from 6-12 months of age in Kilosa district, Tanzania.

    PubMed

    Mamiro, Peter S; Kolsteren, Patrick W; van Camp, John H; Roberfroid, Dominique A; Tatala, Simon; Opsomer, Anne S

    2004-05-01

    A double-blind, randomized, placebo-controlled trial was conducted from March 2001 to March 2002 involving 309 infants who received either a processed complementary food (CF) or an unprocessed placebo from 6 to 12 mo of age. The groups were comparable in baseline characteristics. The study took place in Kilosa district, Tanzania. The processed CF contained germinated, autoclaved, and dried finger millet (65.2%), kidney beans (19.1%), roasted-peanuts (8%), and mango purée (7.7%). The same blend, but not processed, served as the placebo. Processing increased iron solubility and energy density without affecting viscosity. Mean length for age, weight for age, hemoglobin, and zinc protoporphyrin at 6 and 12 mo did not differ between the 2 groups. The results show that the processed food did not differ from the unprocessed placebo in improving growth, hemoglobin, and iron status of infants when given under the study conditions. The control group consumed equal amounts of macronutrients, and the higher energy density in this study did not seem to have any benefits. In our study, there was a very intensive follow-up; at every encounter with mothers, giving the required amounts and adding extra lipids was strongly reinforced. Under those conditions, a well-balanced complementary food with additional lipids can meet the energy needs of young children. The reduction in phytates by 34% and improvement in iron solubility to 19% due to processing might not have been enough to compensate for the rather low iron content of the complementary food. PMID:15113950

  16. Reductive Precipitation of Metals Photosensitized by Tin Protoporphyrin

    SciTech Connect

    ABDELOUAS,A.; GONG,W.L.; SHELNUTT,JOHN A.

    2000-01-18

    For the first time, we show that redox-sensitive metals, which are highly soluble in the oxidized state can be reduced and precipitated from aqueous solution using tin protoporphyrin and light in the presence of an electron donor. Hg{sup 2+} and Cu{sup 2+} were reduced to the metallic state, and Ub{sup 6+} precipitated as oxide with very low volubility, suggesting that removal of these metals via reductive photoreduction and precipitation may be an innovative way for wastewater treatment. Ag{sup 2+} and Au{sup 2+} were reduced to the metallic state and precipitated as nanoparticles. Finally, using tin porphyrins and light for a variety of purposes involving reactions that require a low redox potential may be a good step toward energy conservation and environmentally benign processing.

  17. Protoporphyrin IX binding and transport by recombinant mouse PBR.

    PubMed

    Wendler, Gregor; Lindemann, Peter; Lacapère, Jean-Jacques; Papadopoulos, Vassilios

    2003-11-28

    The mitochondrial 18kDa peripheral-type benzodiazepine receptor (PBR), a high affinity cholesterol binding protein, has been shown to interact with protoporphyrin IX (PPIX) and this interaction was assumed to be involved in the regulation of heme biosynthesis and porphyrin-based photodynamic therapy in cancer. In order to test this hypothesis recombinant mouse PBR was expressed in Escherichia coli. The recombinant gene product showed in E. coli protoplasts specific affinity for PPIX binding. PPIX could displace PK 11195 binding. Moreover, induced PBR protein expression in E. coli protoplasts caused an uptake of PPIX that could be completely inhibited by cholesterol and to a lesser extent inhibited by PK 11195 and Ro5-4864. These results suggest that PBR, in addition to its role in cholesterol and coproporphyrinogen III transport, is also directing the mitochondrial PPIX import, a function that can be ascribed to the 18kDa PBR protein alone.

  18. Photodynamic action of protoporphyrin IX derivatives on Trichophyton rubrum*

    PubMed Central

    Ramos, Rogério Rodrigo; Kozusny-Andreani, Dora Inês; Fernandes, Adjaci Uchôa; Baptista, Mauricio da Silva

    2016-01-01

    BACKGROUND Dermatophytes are filamentous keratinophilic fungi. Trichophyton rubrum is a prevalent infectious agent in tineas and other skin diseases. Drug therapy is considered to be limited in the treatment of such infections, mainly due to low accessibility of the drug to the tissue attacked and development of antifungal resistance in these microorganisms. In this context, Photodynamic Therapy is presented as an alternative. OBJECTIVE Evaluate, in vitro, the photodynamic activity of four derivatives of Protoporphyrin IX by irradiation with LED 400 nm in T. rubrum. METHOD Assays were subjected to irradiation by twelve cycles of ten minutes at five minute intervals. RESULT Photodynamic action appeared as effective with total elimination of UFCs from the second irradiation cycle. CONCLUSION Studies show that the photodynamic activity on Trichophyton rubrum relates to a suitable embodiment of the photosensitizer, which can be maximized by functionalization of peripheral groups of the porphyrinic ring. PMID:27192510

  19. Latex carrier for improving protoporphyrin IX for photodynamic therapy.

    PubMed

    Bui, Brian; Liu, Li; Chen, Wei

    2016-06-01

    Attachment of Protoporphyrin IX (PPIX) to poly (styrene-co-4-vinylpyridine) (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions. After using an oil-in-water heated emulsion polymerization technique to synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing self-reactions between the carboxyl groups and the porphyrin core. Refraining the two parts from interacting while attached to the nanobeads prevented PPIX from aggregating, which then increased water solubility, enhanced luminescence and singlet oxygen production. Attachment also improved cell uptake and cell destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve aspects of photodynamic therapy for the treatment of cancer. PMID:27020668

  20. Phylogeny of Echinoderm Hemoglobins

    PubMed Central

    Christensen, Ana B.; Herman, Joseph L.; Elphick, Maurice R.; Kober, Kord M.; Janies, Daniel; Linchangco, Gregorio; Semmens, Dean C.; Bailly, Xavier; Vinogradov, Serge N.; Hoogewijs, David

    2015-01-01

    Background 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. Results 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. Conclusion 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

  1. THE RENAL HANDLING OF HEMOGLOBIN

    PubMed Central

    Bunn, H. Franklin; Esham, William T.; Bull, Robert W.

    1969-01-01

    The glomerular filtration of hemoglobin (α2β2) was studied under conditions in which its dissociation into αβ dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of 59Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose. PMID:5778789

  2. Rice (Oryza) hemoglobins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Temperature modulation of bovine hemoglobins.

    PubMed

    Condò, S G; el-Sherbini, S; Giardina, B

    1991-06-28

    The functional properties of hemoglobin from Egyptian water buffalo have been characterized as a function of pH, temperature and chloride concentration. Alongside overall similarities shared with ox and Arctic ruminant hemoglobins, hemoglobin from buffalo shows significant differences with respect to the effect of temperature. The results obtained may suggest that the limited effect of temperature on oxygen binding recently reported for ox hemoglobin could be regarded as an interesting case of a reminiscence of a past glacial age.

  4. Differential effects of protoporphyrin and uroporphyrin on murine mast cells

    SciTech Connect

    Lim, H.W.; Gigli, I.; Wasserman, S.I.

    1987-03-01

    To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with (/sup 3/H)serotonin and (/sup 14/C)arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators ,f 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence of URO (50-5000 ng/ml) resulted in less than 5% net release. (3H)Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.

  5. Levels of cadmium, lead and zinc protoporphyrin absorption in different risk groups.

    PubMed

    Aurelio, L M; Pilar, D L; Fulgencio, G G; Adoración, P B; Enrique, G C; Alicia, H M; Aurelio, L M

    1993-12-01

    We studied groups of workers, of pregnant women and of neonates exposed and unexposed to cadmium and lead at their place of work or in the environment. A total of 118 exposed and 28 unexposed workers were studied, together with 90 exposed and 100 unexposed pregnant women and neonates. Concentrations of cadmium and lead in the blood were determined by atomic absorption spectrophotometry. There were significant differences in cadmium concentrations between workers and neonates, and significant differences in lead concentrations between workers and pregnant women. We believe these differences are due mainly to high levels of pollution in the area studied.

  6. Hemoglobin interacting proteins and implications of spectrin hemoglobin interaction.

    PubMed

    Basu, Avik; Chakrabarti, Abhijit

    2015-10-14

    In this report we have analyzed interacting partners of hemoglobin inside erythrocyte and sought possible implications of hemoglobin-spectrin interaction. Our list of identified cytosolic hemoglobin interacting proteins includes redox regulators like peroxiredoxin-2, Cu-Zn superoxide dismutase, catalase, aldehyde dehydrogenase-1, flavin reductase and chaperones like HSP70, α-hemoglobin stabilizing protein. Others include metabolic enzymes like carbonic anhydrase-1, selenium binding protein-1, purine nucleoside phosphorylase and nucleoside diphosphate kinase. Additionally, various membrane proteins like α and β spectrin, ankyrin, band3, protein4.1, actin and glyceraldehyde 3 phosphate dehydrogenase have been shown to interact with hemoglobin. Our result indicates that major membrane skeleton protein spectrin, that also has a chaperone like activity, helps to fold the unstable alpha-globin chains in vitro. Taken together our results could provide insight into a protein network evolved around hemoglobin molecule inside erythrocyte that may add a new perspective in understanding the hemoglobin function and homeostasis.

  7. Antimicrobial properties of hemoglobin.

    PubMed

    Sheshadri, Preethi; Abraham, Jayanthi

    2012-12-01

    Hemoglobin consists of a heme containing component and a globin unit. It exists as a tetramer with 2 α subunits and 2 β subunits in adults and with 2 α subunits and 2 γ chains in infants. On proteolytic cleavage, hemoglobin breaks down to produce many biologically active compounds, among which are hemocidins, those which exhibit antimicrobial property. The generation of these peptides does not depend on the blood group, Rhesus factor, age and sex of the healthy donors. The microbicidal activity has been observed against a variety of gram positive and Gram-negative bacteria, and against filamentous fungi, yeast and even certain parasites. The discovery of hemocidins opens a new field for research into the details of the peptides acting as second line of defence in boosting the innate immune system of the organisms.

  8. Combined iron sucrose and protoporphyrin treatment protects against ischemic and toxin-mediated acute renal failure.

    PubMed

    Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

    2016-07-01

    Tissue preconditioning, whereby various short-term stressors initiate organ resistance to subsequent injury, is well recognized. However, clinical preconditioning of the kidney for protection against acute kidney injury (AKI) has not been established. Here we tested whether a pro-oxidant agent, iron sucrose, combined with a protoporphyrin (Sn protoporphyrin), can induce preconditioning and protect against acute renal failure. Mice were pretreated with iron sucrose, protoporphyrin, cyanocobalamin, iron sucrose and protoporphyrin, or iron sucrose and cyanocobalamin. Eighteen hours later, ischemic, maleate, or glycerol models of AKI were induced, and its severity was assessed the following day (blood urea nitrogen, plasma creatinine concentrations; post-ischemic histology). Agent impact on cytoprotective gene expression (heme oxygenase 1, hepcidin, haptoglobin, hemopexin, α1-antitrypsin, α1-microglobulin, IL-10) was assessed as renal mRNA and protein levels. AKI-associated myocardial injury was gauged by plasma troponin I levels. Combination agent administration upregulated multiple cytoprotective genes and, unlike single agent administration, conferred marked protection against each tested model of acute renal failure. Heme oxygenase was shown to be a marked contributor to this cytoprotective effect. Preconditioning also blunted AKI-induced cardiac troponin release. Thus, iron sucrose and protoporphyrin administration can upregulate diverse cytoprotective genes and protect against acute renal failure. Associated cardiac protection implies potential relevance to both AKI and its associated adverse downstream effects. PMID:27165818

  9. Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria.

    PubMed Central

    Bloomer, J R; Brenner, D A; Mahoney, M J

    1977-01-01

    The activity of heme synthetase, which catalyzes the chelation of ferrous iron to protoporphyrin to form heme, is deficient in sonicates of skin fibroblasts cultured from patients with protoporphyria. During culture in Eagle's medium supplemented with fetal calf serum, these cells do not accumulate protoporphyrin, however. This may be due to a minimal requirement for heme synthesis, since glycine is incorporated into heme at a low rate which is similar to that in normal fibroblasts. In addition, the activity of delta-aminolevulinic acid (ALA) synthetase, the first and rate-limiting enzyme of heme biosynthesis which catalyzes the formation of ALA from glycine, is normal in lysates of the fibroblasts. Cultured fibroblasts were therefore incubated with ALA in order to bypass the rate-limiting step of heme biosynthesis. In the presence of 25 muM iron, protoporphyrin was detected in protoporphyria cell lines when the concentration of ALA in the medium reached 50 muM, but not in normal lines. As the concentration of ALA was increased above 50 muM, all lines accumulated protoporphyrin. However, the amount was 2-3 times more in cultured fibroblasts from patients with protoporphyria, reflecting their deficiency of heme synthetase activity. When iron was not added to the medium, protoporphyrin accumulated to a similar degree in normal and protoporphyria fibroblasts; this was significantly more than that in the presence of iron. These studies indicate that excessive protoporphyrin accumulation in protoporphyria, which is due principally to deficient heme synthetase activity, may be modified by the rate of ALA formation in heme-producing tissues, and by the availability of iron. PMID:915001

  10. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  11. Syntheses of protoporphyrin-IX derivatives bearing extended propionate side-chains.

    PubMed

    Holmes, Robert T; Lu, Jianming; Mwakwari, Celinah; Smith, Kevin M

    2009-05-29

    In order to investigate the relationship between depth within membranes of singlet oxygen generation and effectiveness of photodynamic therapy of tumors, analogs of protoporphyrin-IX 1 bearing five 4 and seven 5 carbon atoms (in place of the 3-carbon atom chain in 1) were synthesized from monopyrrole precursors.

  12. Syntheses of protoporphyrin-IX derivatives bearing extended propionate side-chains.

    PubMed

    Holmes, Robert T; Lu, Jianming; Mwakwari, Celinah; Smith, Kevin M

    2009-05-29

    In order to investigate the relationship between depth within membranes of singlet oxygen generation and effectiveness of photodynamic therapy of tumors, analogs of protoporphyrin-IX 1 bearing five 4 and seven 5 carbon atoms (in place of the 3-carbon atom chain in 1) were synthesized from monopyrrole precursors. PMID:20161404

  13. Zinc Enzymes.

    ERIC Educational Resources Information Center

    Bertini, I.; And Others

    1985-01-01

    Discusses the role of zinc in various enzymes concerned with hydration, hydrolysis, and redox reactions. The binding of zinc to protein residues, properties of noncatalytic zinc(II) and catalytic zinc, and the reactions catalyzed by zinc are among the topics considered. (JN)

  14. The magnesium-protoporphyrin IX (oxidative) cyclase system. Studies on the mechanism and specificity of the reaction sequence.

    PubMed

    Walker, C J; Mansfield, K E; Rezzano, I N; Hanamoto, C M; Smith, K M; Castelfranco, P A

    1988-10-15

    Mg-protoporphyrin IX monomethyl ester cyclase activity was assayed in isolated developing cucumber (Cucumis sativus L. var. Beit Alpha) chloroplasts [Chereskin, Wong & Castelfranco (1982) Plant Physiol. 70, 987-993]. The presence of both 6- and 7-methyl esterase activities was detected, which permitted the use of diester porphyrins in a substrate-specificity study. It was found that: (1) the 6-methyl acrylate derivative of Mg-protoporphyrin monomethyl ester was inactive as a substrate for cyclization; (2) only one of the two enantiomers of 6-beta-hydroxy-Mg-protoporphyrin dimethyl ester had detectable activity as a substrate for the cyclase; (3) the 2-vinyl-4-ethyl-6-beta-oxopropionate derivatives of Mg-protoporphyrin mono- or di-methyl ester were approx. 4 times more active as substrates for cyclization than the corresponding divinyl forms; (4) at the level of Mg-protoporphyrin there was no difference in cyclase activity between the 4-vinyl and 4-ethyl substrates; (5) reduction of the side chain of Mg-protoporphyrin in the 2-position from a vinyl to an ethyl resulted in a partial loss of cyclase activity. This work suggests that the original scheme for cyclization proposed by Granick [(1950) Harvey Lect. 44, 220-245] should now be modified by the omission of the 6-methyl acrylate derivative of Mg-protoporphyrin monomethyl ester and the introduction of stereo-specificity at the level of the hydroxylated intermediate.

  15. Zinc poisoning

    MedlinePlus

    ... other materials to make industrial items such as paint, dyes, and more. These combination substances can be ... Compounds used to make paint, rubber, dyes, wood preservatives, and ... Zinc chloride Zinc oxide (relatively nonharmful) Zinc ...

  16. Subunit dissociation in fish hemoglobins.

    PubMed

    Edelstein, S J; McEwen, B; Gibson, Q H

    1976-12-10

    The tetramer-dimer dissociation equilibria (K 4,2) of several fish hemoglobins have been examined by sedimentation velocity measurements with a scanner-computer system for the ultracentrifuge and by flash photolysis measurements using rapid kinetic methods. Samples studied in detail included hemoglobins from a marine teleost, Brevoortia tyrannus (common name, menhaden); a fresh water teleost, Cyprinus carpio, (common name, carp); and an elasmobranch Prionace glauca (common name, blue shark). For all three species in the CO form at pH 7, in 0.1 M phosphate buffer, sedimentation coefficients of 4.3 S (typical of tetrameric hemoglobin) are observed in the micromolar concentration range. In contrast, mammalian hemoglobins dissociate appreciably to dimers under these conditions. The inability to detect dissociation in three fish hemoglobins at the lowest concentrations examined indicates that K 4,2 must have a value of 10(-8) M or less. In flash photolysis experiments on very dilute solutions in long path length cells, two kinetic components were detected with their proportions varying as expected for an equilibrium between tetramers (the slower component) and dimers (the faster component); values of K 4,2 for the three fish hemoglobins in the range 10(-9) to 10(-8) M were calculated from these data. Thus, the values of K 4,2 for liganded forms of the fish hemoglobins appear to be midway between the value for liganded human hemoglobin (K 4,2 approximately 10(-6) M) and unliganded human hemoglobin (K 4,2 approximately 10(-12) M). This conclusion is supported by measurements on solutions containing guanidine hydrochloride to enhance the degree of dissociation. All three fish hemoglobins are appreciably dissociated at guanidine concentrations of about 0.8 M, which is roughly midway between the guanidine concentrations needed to cause comparable dissociation of liganded human hemoglobin (about 0.4 M) and unliganded human hemoglobin (about 1.6 M). Kinetic measurements on

  17. Effect of daily supplementation with iron and zinc on iron status of childbearing age women.

    PubMed

    Mujica-Coopman, María F; Borja, Angélica; Pizarro, Fernando; Olivares, Manuel

    2015-05-01

    The objective was to determine the effect of daily supplementation with 30 mg of iron (Fe) plus 30 mg of zinc (Zn) for 3 months on Fe status of women of childbearing age. This was a randomized double-blind, placebo-controlled trial. Eighty-one women (18-45 years) were randomly assigned to receive either a daily single dose of 30 mg of Fe (group 1; n = 28) and 30 mg of Fe plus 30 mg of Zn (group 2; n = 26) or placebo (n = 27) for 3 months. Hemoglobin (Hb), mean corpuscular volume, serum Fe, total iron-binding capacity, transferrin saturation, erythrocyte Zn protoporphyrin, serum ferritin (SF), serum transferrin receptor (TfR), total body Fe, serum Zn, and high-sensitivity C-reactive protein were measured at baseline and at the end of the study. At baseline, 3.7, 28.4, and 3.7 % of women had iron-deficiency anemia (IDA), Fe deficiency without anemia, and depleted Fe stores, respectively. No significant differences on Fe status were found between groups before supplementation. After supplementation, group 2 showed a significant increase of Hb and total body Fe and a significant decrease of TfR compared with placebo (p < 0.05). Moreover, serum Zn increased significantly in group 2 compared with group 1 (p < 0.01) and placebo (p < 0.01). In conclusion, daily supplementation with 30 mg of Fe plus 30 mg of Zn for 3 months improved significantly the Fe and Zn status of women, compared with those who received placebo. The positive effect of Fe supplementation on Fe status is enhanced by combined Zn supplementation.

  18. Hemoglobin variants in Cyprus.

    PubMed

    Kyrri, Andreani R; Felekis, Xenia; Kalogerou, Eleni; Wild, Barbara J; Kythreotis, Loukas; Phylactides, Marios; Kleanthous, Marina

    2009-01-01

    Cyprus, located at the eastern end of the Mediterranean region, has been a place of eastern and western civilizations, and the presence of various hemoglobin (Hb) variants can be considered a testimony to past colonizations of the island. In this study, we report the structural Hb variants identified in the Cypriot population (Greek Cypriots, Maronites, Armenians, and Latinos) during the thalassemia screening of 248,000 subjects carried out at the Thalassaemia Centre, Nicosia, Cyprus, over a period of 26 years. A sample population of 65,668 people was used to determine the frequency and localization of several of the variants identified in Cyprus. The localization of some of the variants in regions where the presence of foreign people was most prevalent provides important clues to the origin of the variants. Twelve structural variants have been identified by DNA sequencing, nine concerning the beta-globin gene and three concerning the alpha-globin gene. The most common beta-globin variants identified were Hb S (0.2%), Hb D-Punjab (0.02%), and Hb Lepore-Washington-Boston (Hb Lepore-WB) (0.03%); the most common alpha-globin variant was Hb Setif (0.1%). The presence of some of these variants is likely to be directly linked to the history of Cyprus, as archeological monuments have been found throughout the island which signify the presence for many years of the Greeks, Syrians, Persians, Arabs, Byzantines, Franks, Venetians, and Turks. PMID:19373583

  19. Oxygen transport by hemoglobin.

    PubMed

    Mairbäurl, Heimo; Weber, Roy E

    2012-04-01

    Hemoglobin (Hb) constitutes a vital link between ambient O2 availability and aerobic metabolism by transporting oxygen (O2) from the respiratory surfaces of the lungs or gills to the O2-consuming tissues. The amount of O2 available to tissues depends on the blood-perfusion rate, as well as the arterio-venous difference in blood O2 contents, which is determined by the respective loading and unloading O2 tensions and Hb-O2-affinity. Short-term adjustments in tissue oxygen delivery in response to decreased O2 supply or increased O2 demand (under exercise, hypoxia at high altitude, cardiovascular disease, and ischemia) are mediated by metabolically induced changes in the red cell levels of allosteric effectors such as protons (H(+)), carbon dioxide (CO2), organic phosphates, and chloride (Cl(-)) that modulate Hb-O2 affinity. The long-term, genetically coded adaptations in oxygen transport encountered in animals that permanently are subjected to low environmental O2 tensions commonly result from changes in the molecular structure of Hb, notably amino acid exchanges that alter Hb's intrinsic O2 affinity or its sensitivity to allosteric effectors. Structure-function studies of animal Hbs and human Hb mutants illustrate the different strategies for adjusting Hb-O2 affinity and optimizing tissue oxygen supply.

  20. Nonlinear photoacoustic spectroscopy of hemoglobin

    SciTech Connect

    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.

  1. More Refined Experiments with Hemoglobin.

    ERIC Educational Resources Information Center

    Morin, Phillippe

    1985-01-01

    Discusses materials needed, procedures used, and typical results obtained for experiments designed to make a numerical stepwise study of the oxygenation of hemoglobin, myoglobin, and other oxygen carriers. (JN)

  2. Facile heme vinyl posttranslational modification in a hemoglobin.

    PubMed

    Preimesberger, Matthew R; Wenke, Belinda B; Gilevicius, Lukas; Pond, Matthew P; Lecomte, Juliette T J

    2013-05-21

    Iron-protoporphyrin IX, or b heme, is utilized as such by a large number of proteins and enzymes. In some cases, notably the c-type cytochromes, this group undergoes a posttranslational covalent attachment to the polypeptide chain, which adjusts the physicochemical properties of the holoprotein. The hemoglobin from the cyanobacterium Synechocystis sp. PCC 6803 (GlbN), contrary to the archetypical hemoglobin, modifies its b heme covalently. The posttranslational modification links His117, a residue that does not coordinate the iron, to the porphyrin 2-vinyl substituent and forms a hybrid b/c heme. The reaction is an electrophilic addition that occurs spontaneously in the ferrous state of the protein. This apparently facile type of heme modification has been observed in only two cyanobacterial GlbNs. To explore the determinants of the reaction, we examined the behavior of Synechocystis GlbN variants containing a histidine at position 79, which is buried against the porphyrin 4-vinyl substituent. We found that L79H/H117A GlbN bound the heme weakly but nevertheless formed a cross-link between His79 Nε2 and the heme 4-Cα. In addition to this linkage, the single variant L79H GlbN also formed the native His117-2-Cα bond yielding an unprecedented bis-alkylated protein adduct. The ability to engineer the doubly modified protein indicates that the histidine-heme modification in GlbN is robust and could be engineered in different local environments. The rarity of the histidine linkage in natural proteins, despite the ease of reaction, is proposed to stem from multiple sources of negative selection. PMID:23607716

  3. Rice ( Oryza) hemoglobins

    PubMed Central

    Arredondo-Peter, Raúl; Moran, Jose F.; Sarath, Gautam

    2014-01-01

    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 single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit a very high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs. PMID:25653837

  4. Rice ( Oryza) hemoglobins.

    PubMed

    Arredondo-Peter, Raúl; Moran, Jose F; Sarath, Gautam

    2014-01-01

    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 single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit a very high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs.

  5. Soluble diamagnetic model for malaria pigment: coordination chemistry of gallium(III)protoporphyrin-IX.

    PubMed

    Bohle, D Scott; Dodd, Erin L; Pinter, Tyler B J; Stillman, Martin J

    2012-10-15

    The facile axial ligand exchange properties of gallium(III) protoporphyrin IX in methanol solution were utilized to explore self-association interactions by NMR techniques. Structural changes were observed, as well as competitive behavior with the ligands acetate and fluoride, which differed from that seen with the synthetic analogue gallium(III) octaethylporphyrin which lacks acid groups in its side-chains and has less solution heterogeneity as indicated by absorption and MCD spectroscopies. The propionic acid side chains of protoporphyrin IX are implicated in all such interactions of PPIX, and both dynamic metal-propionic interactions and the formation of propionate-bridged dimers are observed. Fluoride coordination provides an unusual example of slow ligand exchange, and this allows for the identification of a fluoride bridged dimer in solution. An improved synthesis of the chloride and hydroxide complexes of gallium(III) protoporphyrin IX is reported. An insoluble gallium analogue of hematin anhydride is described. In general, the interactions between solvent and the metal are found to confer very high solubility, making [Ga(PPIX)](+) a useful model for ferric heme species.

  6. Structure of cobalt protoporphyrin chloride and its dimer, observation and DFT modeling.

    PubMed

    de la Lande, Aurélien; Ha-Thi, Minh-Huong; Chen, Shufeng; Soep, Benoît; Shafizadeh, Niloufar

    2016-06-22

    In this article we present a joint study by time-of-flight mass spectroscopy and density functional theory of cobalt protoporphyrin dimer complexes. The main novelty of the experimental part is to reveal the formation of porphyrin dimers that eventually include a chlorine atom. Density functional theory calculations have been performed to shed light on the structural and electronic properties of monomers and dimers that may be formed experimentally. Various geometries of the monomers are analyzed in the two lowest spin states. The electronic structures are examined by means of population analysis relying on the iterative Hirshfeld scheme and the topological analyses of the electron localization function. It is shown that the cobalt ligand bond is purely ionic in the triplet states but shows a noticeable covalent character in the singlet state. Ionization potential of Co-protoporphyrin and binding energies of the chlorine ligand are also reported. Concerning the dimers, several association patterns are investigated for the chlorinated and non-chlorinated complexes. It is found that the structures of the most stable complexes involve four hydrogen bonds between the carboxylic acid moieties of the protoporphyrins. However other association modes are likely to be possible in the experiments. PMID:27270590

  7. Electrocatalytic Nitrate Reduction by a Cobalt Protoporphyrin Immobilized on a Pyrolytic Graphite Electrode.

    PubMed

    Shen, Jing; Birdja, Yuvraj Y; Koper, Marc T M

    2015-08-01

    A series of simple molecular catalysts, i.e., Co(III), Fe(II), Ni(II), Cu(II), and Rh(II) protoporphyrins (metal-PP), directly adsorbed on pyrolytic graphite have been utilized for catalyzing the electrochemical reduction of nitrate. These catalysts are studied by combining cyclic voltammetry with online electrochemical mass spectrometry (OLEMS) to monitor volatile products and online ion chromatography (IC) to detect ionic products in the aqueous electrolyte solution. Among all investigated porphyrins, the Co-based protoporphyrin shows the highest selectivity toward hydroxylamine (NH2OH), which made it the catalyst of primary interest in the article. The reactivity and selectivity of the immobilized Co-protoporphyrin depend significantly on pH, with more acidic conditions leading to higher reactivity and higher selectivity toward hydroxylamine over ammonia. Potential controlled electrolysis results show that the potential also greatly influences the selectivity: at pH 1, hydroxylamine is the main product around -0.5 V with approximately 100% selectivity, while hydroxylamine and ammonia are both formed at a more negative potential, -0.75 V. The mechanism of the reaction is discussed, invoking of the possibility of two pathways for hydroxylamine/ammonia formation: a sequential pathway in which hydroxylamine is produced as an intermediate, with ammonia subsequently formed through the reduction of NH2OH/NH3OH(+), and a parallel pathway in which the formation of hydroxylamine and ammonia is derived from a common intermediate. PMID:26154347

  8. Effects of low oral lead and cadmium exposure and zinc status of heme metabolites in weanling rats.

    PubMed

    Panemangalore, M; Bebe, F N

    1996-01-01

    The effects of moderate zinc deficiency and low oral lead and cadmium exposure on metabolites of porphyrin synthesis were investigated in weanling rats. Groups of weanling Sprague-Dawley rats (6/group) were fed diets containing either zinc (Zn) deficient (Zn D), pair-fed (Zn PF), Zn high (Zn H) or control (Zn C) and given sodium (10 micrograms/mL as NaCl), lead (20 micrograms/mL as Pb acetate) or cadmium (5 micrograms/mL as CdCl2) in drinking water for 4 weeks. Porphyrins in tissues were analyzed by HPLC. Feeding of zinc deficient diets decreased food intake and body weight of rats; plasma and erythrocyte zinc levels were 60 and 27% less than the control group, respectively. Kidney was the target organ for lead and cadmium accumulation. The concentration of lead in tissues were about: kidney = 98 micrograms/g; liver = 74 micrograms/g; whole blood = 22 micrograms/mL. Porphyrin intermediates detected in tissues were: heptaporphyrin, pentaporphyrin, coproporphyrin and protoporphyrin. The Zn D diet increased protoporphyrin concentrations in the liver by nearly 100% (P < or = 0.05), but exposure to Pb or Cd decreased protoporphyrin to levels found in the Zn C group. Erythrocyte protoporphyrin concentrations were evaluated by 21% in Zn D rats; other metabolites were unchanged. In the kidney coproporphyrin was slightly higher in ZN D + Pb group. Low oral Cd exposure had no effect on porphyrin metabolites in all tissues. These results suggest that Zn deficiency triggers the accumulation of protoporphyrin in the liver and to some extent in the erythrocytes, and enhances renal coproporphyrin accretion in low lead exposed rats.

  9. Iron and zinc supplementation improved iron and zinc status, but not physical growth, of apparently healthy, breast-fed infants in rural communities of northeast Thailand.

    PubMed

    Wasantwisut, Emorn; Winichagoon, Pattanee; Chitchumroonchokchai, Chureeporn; Yamborisut, Uruwan; Boonpraderm, Atitada; Pongcharoen, Tippawan; Sranacharoenpong, Kitti; Russameesopaphorn, Wanphen

    2006-09-01

    Iron deficiency is prevalent in children and infants worldwide. Zinc deficiency may be prevalent, but data are lacking. Both iron and zinc deficiency negatively affect growth and psychomotor development. Combined iron and zinc supplementation might be beneficial, but the potential interactions need to be verified. In a randomized, placebo-controlled trial using 2 x 2 factorial design, 609 Thai infants aged 4-6 mo were supplemented daily with 10 mg of iron and/or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth. Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined. Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined. Baseline iron deficiency was very low, and iron deficiency anemia was almost nil. After supplementation, prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc. Serum zinc was higher in infants receiving zinc (16.7 +/- 5.2 micromol/L), iron and zinc (12.1 +/- 3.8 micromol/L) or iron alone (11.5 +/- 2.5 micromol/L) than in the placebo group (9.8 +/- 1.9 micromol/L). Iron and zinc interacted to affect iron and zinc status, but not hemoglobin. Iron supplementation had a small but significant effect on ponderal growth, whereas zinc supplementation did not. To conclude, in Thai infants, iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. Overall, for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone.

  10. Reactions of arsine with hemoglobin

    SciTech Connect

    Hatlelid, K.M.; Brailsford, C.; Carter, D.E.

    1996-02-09

    The mechanism of arsine (AsH{sub 3}) induced hemolysis was studied in vitro using isolated red blood cells (RBCs) from the rat or dog. AsH{sub 3}-induced hemolysis of dog red blood cells was completely blocked by carbon monoxide (CO) preincubation and was reduced by pure oxygen (O{sub 2}) compared to incubations in air. Since CO and O{sub 2} bind to heme and also reduced hemolysis, these results suggested a reaction between AsH{sub 3} and hemoglobin in the hemeligand binding pocket or with the heme iron. Further, sodium nitrite induction of methemoglobin (metHb) to 85% and 34% of total Hb in otherwise intact RBCs resulted in 56% and 16% decreases in hemolysis, respectively, after incubation for 4 h. This provided additional evidence for the involvement of hemoglobin in the AsH{sub 3}-induced hemolysis mechanism. Reactions between AsH{sub 3} and hemoglobin were studied in solutions of purified dog hemoglobin. Spectrophotometric studies of the reaction of AsH{sub 3} with various purified hemoglobin species revealed that AsH{sub 3} reacted with HbO{sub 2} to produce metHb and, eventually, degraded Hb characterized by gross precipitation of the protein. AsH{sub 3} did not alter the spectrum of deoxyHb and did not cause degradation of metHb in oxygen, but bound to and reduced metHb in the absence of oxygen. These data indicate that a reaction of AsH{sub 3} with oxygenated hemoglobin, HbO{sub 2}, may lead to hemolysis, but there are reactions between AsH{sub 3} and metHb that may not be directly involved in the hemolytic process. 17 refs., 6 figs.

  11. [Homozygous hemoglobin-E (Hb-EE) disease].

    PubMed

    Amendola, G; Danise, P; Di Palma, A; Franzese, M; Avino, D; D'Arco, A M

    2004-01-01

    The Authors report on a 16 year-old girl, of Cambodian descent, who was admitted to the hospital for hematuria. She showed a mild microcytic, hypochromic anemia with a normal iron balance; clinical examination was normal with neither pallor nor icterus nor splenomegaly; electrophoresis of hemoglobin yielded no hemoglobin A, a sligtly increased amount of HbF and a single band with a mobility similar to that of HbA2; the patient showed no evidence of overt increased hemolysis. With the DNA technology a final diagnosis of homozygous hemoglobin E was made. Hemoglobin E is the most common Hb variant among Southeast Asian populations. The Authors discuss on the benign nature of Hb-EE disease, pointing out that the presence of a single HbE gene in combination with that for beta-thalassemia leads generally to a disorder often comparable in severity to that of homozygous beta-thalassemia. With the recent migration of a high number of people from the countries, where HbE is extremely frequent, to the Western world (including Italy), this thalassemia syndrome is now a global health problem; therefore its knowledge is an important diagnostic challenge to all the experts involved in the care of thalassemic patients.

  12. The efficacy of protoporphyrin as a predictive biomarker for lead exposure in canvasback ducks: effect of sample storage time

    USGS Publications Warehouse

    Franson, J.C.; Hohman, W.L.; Moore, J.L.; Smith, M.R.

    1996-01-01

    We used 363 blood samples collected from wild canvasback ducks (Aythya valisineria) at Catahoula Lake, Louisiana, U.S.A. to evaluate the effect of sample storage time on the efficacy of erythrocytic protoporphyrin as an indicator of lead exposure. The protoporphyrin concentration of each sample was determined by hematofluorometry within 5 min of blood collection and after refrigeration at 4 °C for 24 and 48 h. All samples were analyzed for lead by atomic absorption spectrophotometry. Based on a blood lead concentration of ≥0.2 ppm wet weight as positive evidence for lead exposure, the protoporphyrin technique resulted in overall error rates of 29%, 20%, and 19% and false negative error rates of 47%, 29% and 25% when hematofluorometric determinations were made on blood at 5 min, 24 h, and 48 h, respectively. False positive error rates were less than 10% for all three measurement times. The accuracy of the 24-h erythrocytic protoporphyrin classification of blood samples as positive or negative for lead exposure was significantly greater than the 5-min classification, but no improvement in accuracy was gained when samples were tested at 48 h. The false negative errors were probably due, at least in part, to the lag time between lead exposure and the increase of blood protoporphyrin concentrations. False negatives resulted in an underestimation of the true number of canvasbacks exposed to lead, indicating that hematofluorometry provides a conservative estimate of lead exposure.

  13. The electrochemical preparation of FAD/ZnO with hemoglobin film-modified electrodes and their electroanalytical properties.

    PubMed

    Lin, Kuo-Chiang; Chen, Shen-Ming

    2006-03-15

    Flavin adenine dinucleotide (FAD)-modified zinc oxide self-assembly films were prepared using repeated cyclic voltammetry. The electrochemical reaction of the hemoglobin with the FAD/ZnO self-assembly film-modified electrodes and their electrocatalytic properties were investigated. This paper describes the successful loading of the electrochemically active molecules of hemoglobin and FAD along with ZnO by electrochemical method. In addition to the cyclic voltammetry, an electrochemical quartz crystal microbalance was used to study the growth mechanism and the properties of the films. The FAD/zinc oxide films exhibited a single redox couple, which corresponded to the FAD redox couple. The electrocatalytic properties of the O2, H2O2, trichloroacetic acid and SO(3)2- were studied by the FAD/zinc oxide films in the absence or in the presence of hemoglobin. The electrocatalytic reduction current had been developed from the cathodic peak of the FAD/zinc oxide redox couple. The electrocatalytic process involved an interaction of hemoglobin and FAD/GC film-modified electrode to increase the electrocatalytic reduction current. The electrocatalytic reduction of O2 using the FAD/zinc oxide films was investigated by cyclic voltammetry and rotating ring-disk electrode methods.

  14. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  15. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  16. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  17. THE PREPARATION OF COMPLETELY COAGULATED HEMOGLOBIN

    PubMed Central

    Anson, M. L.; Mirsky, A. E.

    1929-01-01

    As a preliminary to the study of the reversal of the coagulation of hemoglobin several methods are described for the preparation of completely denatured and coagulated hemoglobin and the evidence is given that hemoglobin is a typical coagulable protein. PMID:19872511

  18. Mechanism of the antihypoxic action of zinc compounds

    SciTech Connect

    Uryupov, O.Y.; Sumina, E.N.

    1985-10-01

    This paper studies the mechanism of the protective action of zinc compound in acute carbon monoxide poisoning. The survival rate of animals receiving a preliminary injection of bis (1-vinylimidazole) zinc sulfate before exposure to hypobaric and mormobaric hypoxia was 60% respectively compared with 10 and 15% in the control groups. During CO poisoning the rise of the HbCO level in the blood of mice receiving prophylactic zinc complex was delayed. It is suggested that the antihypoxic effect of the zinc ion is connected with changes in the functional properties of the hemoglobin molecule.

  19. The influence of merocyanine 540 and protoporphyrin on physicochemical properties of the erythrocyte membrane.

    PubMed

    Lagerberg, J W; Williams, M; Moor, A C; Brand, A; van der Zee, J; Dubbelman, T M; VanSteveninck, J

    1996-01-31

    The interaction of the red cell membrane with merocyanine 540 or protoporphyrin led to four phenomena, most probably interrelated. (i) The morphology changed from the normal discoid to an echinocytic form. This morphological change persisted when followed over a period of 24 h. (ii) Simultaneously, cell deformability was decreased, as revealed by viscosity measurements and a cell-filtration technique. (iii) Both drugs caused swelling of the erythrocytes in isotonic medium, due to a very-short-term increased permeability of the membrane, also for larger molecules such as lactose. The pathway of this temporary leak seems to be unrelated to the Na+/K+ -ATPase, the K+/Cl- and the Na+/K+/Cl- cotransport systems, the Ca2+-activated Gardos pathway, the oxidation/deformation-activated leak pathway and the so-called residual transport route. Despite the morphological changes, K+-leakage induced by mechanical stress was not increased. (iv) During osmotic swelling, the critical hemolytic volume was found to be increased in the presence of either merocyanine 540 or protoporphyrin. The increase critical volume protected erythrocytes against osmotic hemolysis. PMID:8593283

  20. Electrocatalytic reduction of carbon dioxide to carbon monoxide and methane at an immobilized cobalt protoporphyrin

    PubMed Central

    Shen, Jing; Kortlever, Ruud; Kas, Recep; Birdja, Yuvraj Y.; Diaz-Morales, Oscar; Kwon, Youngkook; Ledezma-Yanez, Isis; Schouten, Klaas Jan P.; Mul, Guido; Koper, Marc T. M.

    2015-01-01

    The electrochemical conversion of carbon dioxide and water into useful products is a major challenge in facilitating a closed carbon cycle. Here we report a cobalt protoporphyrin immobilized on a pyrolytic graphite electrode that reduces carbon dioxide in an aqueous acidic solution at relatively low overpotential (0.5 V), with an efficiency and selectivity comparable to the best porphyrin-based electrocatalyst in the literature. While carbon monoxide is the main reduction product, we also observe methane as by-product. The results of our detailed pH-dependent studies are explained consistently by a mechanism in which carbon dioxide is activated by the cobalt protoporphyrin through the stabilization of a radical intermediate, which acts as Brønsted base. The basic character of this intermediate explains how the carbon dioxide reduction circumvents a concerted proton–electron transfer mechanism, in contrast to hydrogen evolution. Our results and their mechanistic interpretations suggest strategies for designing improved catalysts. PMID:26324108

  1. Protoporphyrin IX nanoparticle carrier: preparation, optical properties, and singlet oxygen generation.

    PubMed

    Rossi, Liane M; Silva, Paulo R; Vono, Lucas L R; Fernandes, Adjaci U; Tada, Dayane B; Baptista, Maurício S

    2008-11-01

    The present study is focused on developing a nanoparticle carrier for the photosensitizer protoporphyrin IX for use in photodynamic therapy. The entrapment of protoporphyrin IX (Pp IX) in silica spheres was achieved by modification of Pp IX molecules with an organosilane reagent. The immobilized drug preserved its optical properties and the capacity to generate singlet oxygen, which was detected by a direct method from its characteristic phosphorescence decay curve at near-infrared and by a chemical method using 1,3-diphenylisobenzofuran to trap singlet oxygen. The lifetime of singlet oxygen when a suspension of Pp IX-loaded particles in acetonitrile was excited at 532 nm was determined as 52 micros, which is in good agreement with the value determined for methylene blue in acetonitrile solution under the same conditions. The Pp IX-loaded silica particles have an efficiency of singlet oxygen generation (eta Delta) higher than the quantum yield of free porphyrins. This high efficiency of singlet oxygen generation was attributed to changes on the monomer-dimer equilibrium after photosentisizer immobilization. PMID:18834155

  2. Diaminoacid derivatives of protoporphyrine used as photosensitizers in photodynamic method of tumor diagnosis and treatment

    NASA Astrophysics Data System (ADS)

    Graczyk, Alfreda; Kwasny, Miroslaw; Ye, Shu; Milosz, Ewa; Kowalska, Agnieszka; Podhajska, Anna

    2003-10-01

    Observation and selective destruction of biological tissues, due to use of photochemical reaction sensitised with photosensitive dyes, are applied in modern method of tumor diagnosis and treatment as well as destruction of atheromatous plaques and restenosis prevention. This method, called photodynamic method (PDT), has been developed for recent 30 years in USA, Canada, Japan, and China and in majority of European countries. It has many advantages that distinguish it from among other currently used diagnostic and therapeutic methods. Both, the applied photosensitizers and photodynamic effect influence on active biological compounds present in an organism, mainly on enzymatic proteins, hormones, and particular elements of immunological system. The PDT method can be used not only for in situ tumor treatment but also for the treatment in metastasis state. It was thought previously that direct activity of cytotoxic radicals and singlet oxygen causes tissues necrosis. At present, additional investigations are performed on destruction mechanisms, i.e., occlusion of blood vessels and lymphatic vessels and PDT influence on immunological system revealing in cytokines release. In Poland, the technology of new class of photosensitizer - diaminoacid derivatives of protoporphyrin PP(AA)2Arg2 as well as the basic half-product - hemis of very high purity has been developed and activities for their industrial production have been performed. In vitro investigations on quantum luminescence yield and singlet oxygen quantum yield of the obtained preparations were made. These compounds do not show toxic properties and they are neither mutagenic nor teratogenic. Three aminoacid protoporphyrine derivatives were chosen for industrial scale production, i.e., PP(Ala)2Arg2, PP(Ser)2Arg2, PP(Plu)2Arg2 that were efficient for the largest number of tumors investigated on cell lines. A preparation being the mixture of these derivatives is called Sensyphyrine. In the first stage of Sensyphyrine

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

    PubMed

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

    2016-10-01

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

  4. Egg-Citing! Isolation of Protoporphyrin IX from Brown Eggshells and Its Detection by Optical Spectroscopy and Chemiluminescence

    ERIC Educational Resources Information Center

    Dean, Michelle L.; Miller, Tyson A.; Bruckner, Christian

    2011-01-01

    A simple and cost-effective laboratory experiment is described that extracts protoporphyrin IX from brown eggshells. The porphyrin is characterized by UV-vis and fluorescence spectroscopy. A chemiluminescence reaction (peroxyoxalate ester fragmentation) is performed that emits light in the UV region. When the porphyrin extract is added as a fluor…

  5. Hemoglobin

    MedlinePlus

    ... the anemia is severe Some conditions affect RBC production in the bone marrow and may cause an ... there is a problem with red blood cell production and/or lifespan, but it cannot determine the ...

  6. Hemoglobin

    MedlinePlus

    ... disease ) Failure of the right side of the heart ( cor pulmonale ) Severe chronic obstructive pulmonary disease (COPD) Scarring or thickening of the lungs ( pulmonary fibrosis ) and other severe lung disorders Other reasons for ...

  7. Prolactin-stimulated mitogenesis in the Nb2 rat lymphoma cell: Lack of protoporphyrin IX effects

    SciTech Connect

    Gerrish, K.E.; Putnam, C.W.; Laird, H.E. II )

    1990-01-01

    Pharmacological characterization of the Nb2 cell peripheral-type benzodiazepine receptor (PBR) was determined using selected 1,4-benzodiazepines, PK 11195, and protoporphyrin IX (PPIX) to compete for specific ({sup 3}H) Ro5-4864 binding. These data suggest that PPIX possesses an affinity for the Nb2 cell PBR. We have previously reported that the peripheral benzodiazepine ligands, Ro5-4864 and PK 11195, modulate prolactin-stimulated mitogenesis in the Nb2 cell. In contrast, PPIX, a putative endogenous ligand for the PBR had no effect on prolactin-stimulated mitogenesis in the Nb2 cell over the concentration range from 10{sup {minus}15} M to 10{sup {minus}6} M. Taken together these data show that PPIX has an affinity for the Nb2 cell PBR but does not modulate prolactin-stimulated mitogenesis at concentrations which should bind to the Nb2 cell PBR.

  8. New developments in fluorescence detection of ALA-induced protoporphyrin IX for cancer localization

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Betz, Christian; Bise, Karl; Brand, P.; Gamarra, Fernando; Haeussinger, Karl; Hillemanns, Peter; Huber, Rudolf M.; Knuechel, Ruth; Kriegmair, M.; Leunig, Andreas; Pichler, J.; Rick, Kai; Schulz, H.; Stanzel, F.; Stocker, Susanne; Wagner, Simon; Weigandt, H.

    1997-12-01

    After the very promising clinical results for the detection of bladder cancer in urology, preclinical and clinical studies on aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) are preformed in various disciplines now. This paper provides a brief overview of the progress on 5-ALA assisted fluorescence diagnosis in urology, pulmonology, neurosurgery, gynecology and ENT performed in collaboration with the Laser Research Laboratory at the Department of Urology of the Ludwig-Maximilians-University in Munich. Five-ALA can be applied either topically or systemically to induce an intracellular accumulation of fluorescing PPIX. With appropriate dosage of 5-ALA, malignant tissue can be stained selectively, and irradiation with violet light excites a bright red fluorescence of the tumor. Optical properties of the tissue tend to hamper the precise identification and demarcation of suspect areas in fluorescence images. Multicolor remission and fluorescence imaging, therefore, seems to be indispensable for a reliable tumor localization.

  9. [Fluorescence spectroscopic study of interaction between Fe-protoporphyrin in myoglobin and Cu(II) ions].

    PubMed

    Feng, Yu-ying; Yang, Hui; Gu, Xiao-tian; Jiang, Hui-jun; Lu, Tian-hong

    2003-06-01

    In this paper, the interaction between Cu(II) ions and Fe-protoporphyrin in horse-heart myoglobin (FePP-Mb) was studied. As a result, some of the Fe(II) ions in FePP-Mb were found to be replaced by Cu(II) ions forming CuPP-Mb, by adding Cu(II) ions into the myoglobin solution. The interaction became stronger when adding more Cu(II) ions into the myoglobin solution. By studying the metal ions' interaction with myoglobin proteins as macromolecules and discussing the interaction mechanism, this work provides a theoretical basis for the further study of hazardous metal ions' interaction with the human body and its mechanism. The fluorescence spectroscopic method used in this study has higher sensitivity than the ordinary UV and CD methods.

  10. Setting the optimal erythrocyte protoporphyrin screening decision threshold for lead poisoning: a decision analytic approach

    SciTech Connect

    DeBaun, M.R.; Sox, H.C. Jr. )

    1991-07-01

    Erythrocyte protoporphyrin (EP) was introduced in the 1970s as an inexpensive screening test for lead poisoning. As greater knowledge of lead poisoning has accumulated, the recommended EP level at which further evaluation for lead poisoning should be initiated has been lowered from greater than or equal to 50 micrograms/dL to greater than or equal to 35 micrograms/dL. The purpose of this study was to evaluate the utility of this EP threshold. A receiver operator characteristic curve was constructed to assess the relationship between the true-positive rate and false-positive rate of EP at various decision thresholds. The receiver operator characteristic curve was constructed with data from the second National Health and Nutrition Examination Survey from 1976 to 1980, which included 2673 children 6 years of age or younger who had both blood lead and EP level determinations. Decision analysis was then used to determine the optimal EP decision threshold for detecting a blood lead level greater than or equal to 25 micrograms/dL. The receiver operator characteristic curve demonstrated that EP is a poor predictor of a blood lead level greater than or equal to 25 micrograms/dL. At the currently recommended EP decision threshold of 35 micrograms/dL, the true-positive rates and false-positive rates of EP are 0.23 and 0.04, respectively. As a result of the inadequate performance of EP screening for lead poisoning, when the prevalence of lead poisoning is greater than 8%, there is no EP decision threshold that optimizes the relationship between the cost of screening normal children and the benefit of detecting lead-poisoned children. Erythrocyte protoporphyrin measurement is not sufficiently sensitive to be recommended uniformly as a screening test for lead poisoning.

  11. The decomposition of protoporphyrin IX by ultrasound is dependent on the generation of hydroxyl radicals.

    PubMed

    Xu, Haobo; Sun, Xin; Yao, Jianting; Zhang, Jian; Zhang, Yun; Chen, Haibo; Dan, Juhua; Tian, Zhen; Tian, Ye

    2015-11-01

    The ultrasound activation of certain drugs, such as porphyrins, could cause synergistic cytotoxic effects on cells. Both sonomechanical and sonochemical effects occur and the latter play a critical role because antioxidant agents could exert significant protective effects against the cytotoxicity. To investigate the reactive oxygen species involved in the sonochemical effects, aqueous protoporphyrin IX (PpIX) solutions were characterized under ultrasound sonication in this study. Inertial cavitation was indirectly evaluated using terephthalic acid dosimetry. The fluorescence intensity of the PpIX was measured using a fluorescence spectrophotometer. The effects of PpIX concentration, ultrasound parameters and free radical scavengers on the PpIX activation by ultrasound were investigated. Our results showed that the increase in PpIX decomposition was significantly correlated with cavitation activities (R=0.9874, p<0.05), and the decomposing effect increases with ultrasound intensity (0.6-1.5 W/cm(2)), initial PpIX concentration (1-5 μM), duty cycle (10-100%) and the sonication duration (2-10 min). The fluorescence and absorption spectra of PpIX showed a decrease in the peak intensity without spectral shifts or new peak build-up after sonication. The PpIX decomposition was significantly inhibited by hydroxyl radical scavengers, histidine, mannitol, acetone, methanol and ethanol, but the decomposition was not inhibited by sodium azide, catalase or superoxide dismutase. These results suggest that the decomposition of protoporphyrin IX by ultrasound is dependent on the generation of hydroxyl radicals, which sheds some light on the sonochemical effects of the interaction between ultrasound and porphyrins.

  12. Hemoglobin variant (hemoglobin Aalborg) mimicking interstitial pulmonary disease.

    PubMed

    Panou, Vasiliki; Jensen, Peter-Diedrich Mathias; Pedersen, Jan Freddy; Thomsen, Lars Pilegaard; Weinreich, Ulla Møller

    2014-01-01

    Hemoglobin Aalborg is a moderately unstable hemoglobin variant with no affiliation to serious hematological abnormality or major clinical symptoms under normal circumstances. Our index person was a healthy woman of 58, not previously diagnosed with hemoglobinopathy Aalborg, who developed acute respiratory failure after a routine cholecystectomy. Initially she was suspected of idiopathic interstitial lung disease, yet a series of tests uncovered various abnormal physiological parameters and set the diagnosis of hemoglobinopathy Aalborg. This led us to examine a group of the index person's relatives known with hemoglobinopathy Aalborg in order to study whether the same physiological abnormalities would be reencountered. They were all subjected to spirometry and body plethysmography, six-minute walking test, pulse oximetry, and arterial blood gas samples before and after the walking test. The entire study population presented the same physiological anomalies: reduction in diffusion capacity, and abnormalities in P(a)O2 and p50 values; the latter could not be presented by the arterial blood gas analyzer; furthermore there was concordance between pulse oximetry and arterial blood gas samples regarding saturation. These data suggest that, based upon the above mentioned anomalies in physiological parameters, the diagnosis of hemoglobinopathy Aalborg should be considered.

  13. Hemoglobin Variant (Hemoglobin Aalborg) Mimicking Interstitial Pulmonary Disease

    PubMed Central

    Panou, Vasiliki; Jensen, Peter-Diedrich Mathias; Pedersen, Jan Freddy; Thomsen, Lars Pilegaard; Weinreich, Ulla Møller

    2014-01-01

    Hemoglobin Aalborg is a moderately unstable hemoglobin variant with no affiliation to serious hematological abnormality or major clinical symptoms under normal circumstances. Our index person was a healthy woman of 58, not previously diagnosed with hemoglobinopathy Aalborg, who developed acute respiratory failure after a routine cholecystectomy. Initially she was suspected of idiopathic interstitial lung disease, yet a series of tests uncovered various abnormal physiological parameters and set the diagnosis of hemoglobinopathy Aalborg. This led us to examine a group of the index person's relatives known with hemoglobinopathy Aalborg in order to study whether the same physiological abnormalities would be reencountered. They were all subjected to spirometry and body plethysmography, six-minute walking test, pulse oximetry, and arterial blood gas samples before and after the walking test. The entire study population presented the same physiological anomalies: reduction in diffusion capacity, and abnormalities in PaO2 and p50 values; the latter could not be presented by the arterial blood gas analyzer; furthermore there was concordance between pulse oximetry and arterial blood gas samples regarding saturation. These data suggest that, based upon the above mentioned anomalies in physiological parameters, the diagnosis of hemoglobinopathy Aalborg should be considered. PMID:25400945

  14. Determination Of Ph Including Hemoglobin Correction

    DOEpatents

    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.

  15. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    PubMed Central

    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

  16. Hemoglobin variants: biochemical properties and clinical correlates.

    PubMed

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

    2013-03-01

    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.

  17. Accumulation of protoporphyrin IX from delta-aminolevulinic acid in bovine skin fibroblasts with hereditary erythropoietic protoporphyria. A gene-dosage effect

    PubMed Central

    1981-01-01

    Bovine skin fibroblasts accumulated protoporphyrin IX when incubated in culture with the porphyrin-heme precursor, delta-aminolevulinic acid (ALA). Fibroblasts from cattle homozygous for erythropoietic protoporphyria (EPP) and with the clinical symptoms of the disease accumulated approximately sixfold greater amounts of protoporphyrin IX than cells from normal control animals. Cells from obligatory heterozygous animals, which are clinically normal, accumulated an intermediate level of protoporphyrin IX. When these cells were incubated with ALA and CaMg EDTA, all types of cells accumulated approximately the same amount of protoporphyrin IX (approximately 500 nmol/mg protein), suggesting that ferrochelatase activity was equally low after inhibition by treatment with CaMg EDTA in all cells. Thus the ratio of protoporphyrin IX accumulation from ALA in cultures treated with CaMg EDTA compared with controls treated with ALA alone was greatest in normal cells, least in EPP cells, and intermediate in the heterozygote cells. These findings suggest that the amount of protoporphyrin IX accumulation from ALA reflects the extent of deficiency of ferrochelatase and is proportional to the dosage of abnormal EPP gene in cultured fibroblasts. Similarly, stimulation of porphyrin accumulation by CaMg EDTA reflects diminished ferrochelatase activity in these cells. Thus, the results of this study demonstrate the usefulness of estimating protoporphyrin IX formation from ALA for the detection of an EPP gene defect in cultured bovine skin fibroblasts. PMID:6788885

  18. Hemoglobin Labeled by Radioactive Lysine

    DOE R&D Accomplishments Database

    Bale, W. F.; Yuile, C. L.; DeLaVergne, L.; Miller, L. L.; Whipple, G. H.

    1949-12-08

    This paper reports on the utilization of tagged epsilon carbon of DL-lysine by a dog both anemic and hypoproteinemic due to repeated bleeding plus a diet low in protein. The experiment extended over period of 234 days, a time sufficient to indicate an erythrocyte life span of at least 115 days based upon the rate of replacement of labeled red cell proteins. The proteins of broken down red cells seem not to be used with any great preference for the synthesis of new hemoglobin.

  19. Hemoglobin potentiates central nervous system damage.

    PubMed Central

    Sadrzadeh, S M; Anderson, D K; Panter, S S; Hallaway, P E; Eaton, J W

    1987-01-01

    Iron and iron compounds--including mammalian hemoglobins--catalyze hydroxyl radical production and lipid peroxidation. To determine whether hemoglobin-mediated lipid peroxidation might be important in hemorrhagic injuries to the central nervous system (CNS), we studied the effects of purified hemoglobin on CNS homogenates and injected hemoglobin into the spinal cords of anesthetized cats. Hemoglobin markedly inhibits Na/K ATPase activity in CNS homogenates and spinal cords of living cats. Hemoglobin also catalyzes substantial peroxidation of CNS lipids. Importantly, the potent iron chelator, desferrioxamine, blocks these adverse effects of hemoglobin, both in vitro and in vivo. Because desferrioxamine is not known to interact with heme iron, these results indicate that free iron, derived from hemoglobin, is the proximate toxic species. Overall, our data suggest that hemoglobin, released from red cells after trauma, can promote tissue injury through iron-dependent mechanisms. Suppression of this damage by desferrioxamine suggests a rational therapeutic approach to management of trauma-induced CNS injury. Images PMID:3027133

  20. Net charge and oxygen affinity of human hemoglobin are independent of hemoglobin concentration

    PubMed Central

    1978-01-01

    The dependence of net charge and oxygen affinity of human hemoglobin upon hemoglobin concentration was reinvestigated. In contrast to earlier reports from various laboratories, both functional properties of hemoglobin were found to be independent of hemoglobin concentration. Two findings indicate a concentration-independent net charge of carbonmonoxy hemoglobin at pH 6.6: (A) The pH value of a given carbonmonoty hemoglobin solution remains constant at 6.6 when the hemoglobin concentration is raised from 10 to 40 g/dl, indicating that there is no change in protonation of titratable groups of hemoglobin: (b) the net charge of carbonmonoxy hemoglobin as estimated from the Donnan distribution of 22Na+ shows no dependence on hemoglobin concentration in this concentration range. The oxygen affinity of human hemoglobin was determined from measurements of oxygen concentrations in equilibrated samples using a Lex-O2-Con apparatus (Lexington Instruments, Waltham, Mass.). P50 averaged 11.4 mm Hg at 37 degrees C, pH = 7.2, and ionic strength approximately 0.15. Neither P50 nor Hill's n showed any variation with hemoglobin concentrations increasing from 10 to 40 g/dl. PMID:32221

  1. Zinc deficiency in molybdenum poisoned cattle

    SciTech Connect

    Parada, R.

    1981-02-01

    Clinical signs ascribable to zinc deficiency were noted in a group of Friesian cows industrially poisoned with molybdenum. Zinc, copper, and molybdenum were determined in blood serum and black hair, and in the contaminated alfalfa pasture the group grazed on. Hematological parameters, and serum calcium and alkaline phosphatase activity, were also determined. Pooled samples of alfalfa from 2 uncontaminated pastures, and of blood, serum and black hair of clinically normal Friesian cattle grazing on these were used as controls. A mixed contamination of the polluted pasture with molybdenum and copper was found, both metals being inversely correlated with he distance to the polluting chimney. Zinc concentrations were normal and not significantly correlated with the distance to the chimney very high molybdenum was found in serum and hair of the poisoned animals; copper was normal in serum and hair. Low calcium and Alkaline phosphatase activity were found in serum, both variables being significantly correlated with serum zinc. Reduced red blood cell number, packed cell volumes and hemoglobin concentrations were also found, but no significant correlation of these parameters with any of the trace metals in serum or hair was found. Signs ascribed to zinc deficiency were consistent with the reduction of zinc in serum and hair and decreased alkaline phosphatase activity in serum. A zinc deficiency conditioned by a simultaneous increased intake of molybdenum and copper is proposed.

  2. Spectrophotometric Properties of Hemoglobin: Classroom Applications.

    ERIC Educational Resources Information Center

    Frary, Roger

    1997-01-01

    Discusses simple and safe techniques that can be used in the educational laboratory to study hemoglobin. Discusses the spectral properties of hemoglobin, spectral-absorbence curves of oxyhemoglobin and carboxyhemoglobin, tracking the conversion of oxyhemoglobin to methemoglobin, and changing from the oxyhemoglobin to deoxyhemoglobin conformation.…

  3. Blood glycated hemoglobin evaluation in sick dogs.

    PubMed Central

    Marca, M C; Loste, A; Unzueta, A; Pérez, M

    2000-01-01

    Blood glycated hemoglobin concentration reflects long-term serum glucose levels in dogs. In this study, the effects of several diseases on blood glycated hemoglobin levels have been evaluated. For this study, blood samples were drawn from 93 unhealthy dogs. The animals were distributed into 10 groups according to pathological process (group 1, digestive problems; group 2, leishmaniasis; group 3, anemia; group 4, dermatological disorders; group 5, urinary problems; group 6, cardiorespiratory problems; group 7, diabetes mellitus; group 8, insulinoma; group 9, general diseases; group 10, control group). Blood glucose and glycated hemoglobin concentrations and hemoglobin and hematocrit values were analyzed in all the animals. In diabetic dogs, a strong increase in blood glycated hemoglobin was observed when compared with the other groups (P < 0.01). In contrast, dogs with insulinoma showed a decrease in blood glycated hemoglobin, though significant differences were not reported in all cases. No change in blood glycated hemoglobin concentrations were reported in dogs affected by other diseases. So, we can suppose that only the chronic alterations in glucose metabolism (chronic hyper- or hypoglycemia) can induce significant changes on the blood glycated hemoglobin concentrations in dogs. PMID:10805256

  4. Determination of Human Hemoglobin Derivatives.

    PubMed

    Attia, Atef M M; Ibrahim, Fatma A A; Abd El-Latif, Noha A; Aziz, Samir W; Abdelmottaleb Moussa, Sherif A; Elalfy, Mohsen S

    2015-01-01

    The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4-1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The method is highly sensitive, accurate and reproducible.

  5. Monoclonal antibodies specific for sickle cell hemoglobin

    SciTech Connect

    Jensen, R.H.; Vanderlaan, M.; Grabske, R.J.; Branscomb, E.W.; Bigbee, W.L.; Stanker, L.H.

    1985-01-01

    Two mouse hybridoma cell lines were isolated which produce monoclonal antibodies that bind hemoglobin S. The mice were immunized with peptide-protein conjugates to stimulate a response to the amino terminal peptide of the beta chain of hemoglobin S, where the single amino acid difference between A and S occurs. Immunocharacterization of the antibodies shows that they bind specifically to the immunogen peptide and to hemoglobin S. The specificity for S is high enough that one AS cell in a mixture with a million AA cells is labeled by antibody, and such cells can be analyzed by flow cytometry. Immunoblotting of electrophoretic gels allows definitive identification of hemoglobin S as compared with other hemoglobins with similar electrophoretic mobility. 12 references, 4 figures.

  6. The Biochemistry of Vitreoscilla hemoglobin

    PubMed Central

    Stark, Benjamin C.; Dikshit, Kanak L.; Pagilla, Krishna R.

    2012-01-01

    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. PMID:24688662

  7. Determination of aminolevulinic-acid-induced protoporphyrin IX in mice skin

    NASA Astrophysics Data System (ADS)

    Stolik, S.; Tomás, S. A.; Ramón-Gallegos, E.; Cruz-Orea, A.; Sánchez-Sinencio, F.

    2003-01-01

    The kinetics of Protoporphyrin IX (PpIX) production in mice skin was studied by photoacoustic spectroscopy. PpIX was induced in mice by intraperitoneal administration of δ-aminolevulinic acid (δ-ALA) in doses of 10, 20, and 30 mg/kg. Mice were sacrificed at specific times within an 8 h interval following δ-ALA administration, and their abdominal skin was excised for the optical measurements. The PpIX content was determined from the photoacoustic amplitude at 410 nm, where PpIX presents its Soret band. For each dose, maximum PpIX was observed at two points. The first maximum occurred at around 15-45 min, depending on the ALA dose, and the second one took place approximately 2 h after δ-ALA administration. These peaks are associated with PpIX production in blood vessels and tissue, respectively. Fluorescence measurements of the PpIX content in plasma extracted intracardiacally confirmed the previous statement. Finally, phase resolved photoacoustic spectroscopy was applied to evaluate the mean depth at which PpIX is generated within the mice skin. This evaluation confirms that the ALA-induced porphyrins in skin are rather produced in the epidermis than in the dermis.

  8. Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy

    PubMed Central

    Rollakanti, Kishore R.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

    2014-01-01

    Photodynamic therapy (PDT) is a treatment modality that uses a specific photosensitizing agent, molecular oxygen, and light of a particular wavelength to kill cells targeted by the therapy. Topically administered aminolevulinic acid (ALA) is widely used to effectively treat cancerous and precancerous skin lesions, resulting in targeted tissue damage and little to no scarring. The targeting aspect of the treatment arises from the fact that ALA is preferentially converted into protoporphyrin IX (PpIX) in neoplastic cells. To monitor the amount of PpIX in tissues, techniques have been developed to measure PpIX-specific fluorescence, which provides information useful for monitoring the abundance and location of the photosensitizer before and during the illumination phase of PDT. This review summarizes the current state of these fluorescence detection techniques. Non-invasive devices are available for point measurements, or for wide-field optical imaging, to enable monitoring of PpIX in superficial tissues. To gain access to information at greater tissue depths, multi-modal techniques are being developed which combine fluorescent measurements with ultrasound or optical coherence tomography, or with microscopic techniques such as confocal or multiphoton approaches. The tools available at present, and newer devices under development, offer the promise of better enabling clinicians to inform and guide PDT treatment planning, thereby optimizing therapeutic outcomes for patients. PMID:25599015

  9. Iron(III) protoporphyrin IX complexes of the antimalarial Cinchona alkaloids quinine and quinidine.

    PubMed

    de Villiers, Katherine A; Gildenhuys, Johandie; le Roex, Tanya

    2012-04-20

    The antimalarial properties of the Cinchona alkaloids quinine and quinidine have been known for decades. Surprisingly, 9-epiquinine and 9-epiquinidine are almost inactive. A lack of definitive structural information has precluded a clear understanding of the relationship between molecular structure and biological activity. In the current study, we have determined by single crystal X-ray diffraction the structures of the complexes formed between quinine and quinidine and iron(III) protoporphyrin IX (Fe(III)PPIX). Coordination of the alkaloid to the Fe(III) center is a key feature of both complexes, and further stability is provided by an intramolecular hydrogen bond formed between a propionate side chain of Fe(III)PPIX and the protonated quinuclidine nitrogen atom of either alkaloid. These interactions are believed to be responsible for inhibiting the incorporation of Fe(III)PPIX into crystalline hemozoin during its in vivo detoxification. It is also possible to rationalize the greater activity of quinidine compared to that of quinine.

  10. Flourescence analysis of ALA-induced Protoporphyrin IX in psoriatic plaque

    NASA Astrophysics Data System (ADS)

    Stringer, Mark R.; Robinson, Dominic J.; Collins, P.

    1996-01-01

    The success reported for the treatment of superficial skin carcinomas by photodynamic therapy (PDT), following topical application of 5-aminolaevulinic acid (ALA), has therapeutic implications for the treatment of other skin disorders. This presentation describes the accumulation of the photosensitizing agent protoporphyrin IX (PpIX) in areas of psoriatic plaque, by monitoring the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present the results from 15 patients, with a total of 42 plaques. These results show that PpIX fluorescence increases in intensity within the 6 hour period following application of ALA, which implies there is a potential for PDT. The emission is localized to the area of ALA application and the effect of occlusion appears insignificant. Also, the rate of increase, and maximum intensity of fluorescence emission, is not directly related to the applied quantity of ALA. The variability of the fluorescence intensity is as great between plaques at different sites on the same patient as between different patients. We also present measurements of the depletion in intensity of fluorescence emission during PDT treatment, using white light, at an irradiance of 25 mW cm-2, that is a consequence of the molecular photo-oxidation of PpIX. The use of fluorescence measurements in predicting the therapeutic effect of treating plaque psoriasis by ALA-PDT is discussed.

  11. Temporal fluctuations in the SERRS spectra of single iron protoporphyrin IX molecule

    NASA Astrophysics Data System (ADS)

    Bizzarri, Anna Rita; Cannistraro, Salvatore

    2003-05-01

    Surface enhanced resonance Raman spectra of Fe-protoporphyrin IX, adsorbed on silver colloidal nanoparticles immobilized onto a polymer-coated glass slide have been investigated at very low concentrations. The spectra exhibit drastic temporal fluctuations on a time scale of seconds in both line frequency and intensity; such a trend suggesting that the single molecule limit is approached. Sequences of spectra have been analyzed in terms of an underlying continuum and of Raman peaks superimposed on this continuum. A statistical analysis of the spectrum intensity has allowed us to put into evidence that main contribution to the intensity fluctuations arises from the continuum. In addition, a high correlation between the total integrated intensity and the intensity detected at different Raman peaks has been revealed. Furthermore, the ratio between the intensity detected in correspondence of different FePP vibrational modes shows a temporal variability likely reflecting the intrinsic dynamics of the molecule. All these findings have been ascribed to a desorption-adsorption mechanism of the molecules at the silver surface.

  12. Modelling topical photodynamic therapy treatment including the continuous production of Protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Campbell, C. L.; Brown, C. T. A.; Wood, K.; Moseley, H.

    2016-11-01

    Most existing theoretical models of photodynamic therapy (PDT) assume a uniform initial distribution of the photosensitive molecule, Protoporphyrin IX (PpIX). This is an adequate assumption when the prodrug is systematically administered; however for topical PDT this is no longer a valid assumption. Topical application and subsequent diffusion of the prodrug results in an inhomogeneous distribution of PpIX, especially after short incubation times, prior to light illumination. In this work a theoretical simulation of PDT where the PpIX distribution depends on the incubation time and the treatment modality is described. Three steps of the PpIX production are considered. The first is the distribution of the topically applied prodrug, the second in the conversion from the prodrug to PpIX and the third is the light distribution which affects the PpIX distribution through photobleaching. The light distribution is modelled using a Monte Carlo radiation transfer model and indicates treatment depths of around 2 mm during daylight PDT and approximately 3 mm during conventional PDT. The results suggest that treatment depths are not only limited by the light penetration but also by the PpIX distribution.

  13. Imaging protoporphyrin IX fluorescence with a time-domain FMT/microCT system

    NASA Astrophysics Data System (ADS)

    Leblond, Frederic; Kepshire, Dax; O'Hara, Julia A.; Dehghani, Hamid; Srinivasan, Subha; Mincu, N.; Hutchins, M.; Khayat, M.; Pogue, B. W.

    2009-02-01

    Fluorescence molecular tomography (FMT) has the potential to become a powerful quantitative research tool for pre-clinical applications such as evaluating the efficacy of experimental drugs. In this paper, we show how a time-domain FMT/microCT instrument can in principle be used to monitor volumetric fluorescence intensity over time for low fluorophore concentration levels. The experimental results we present relate to Protoporphyrin IX which has a quantum efficiency as much as two orders of magnitude lower compared to more conventional extrinsic dyes used for molecular imaging (e.g., Alexa Fluor dyes, Cyanine dyes). Our results highlight the high sensitivity of the single photon counting technology on which the optical system we have built is based. In conjunction with this system we have developed a diffuse optical fluorescence reconstruction technique that is robust and shown here to perform adequately even in cases when the contribution of noise to the data is important. Related to this, we show that the regularization scheme we have developed is reliable even for low fluorophore concentration values and that no adjustment of the regularization parameter needs to be made for different levels of noise. This generic reconstruction approach insures that images reconstructed from data sets acquired at different times and for different fluorescence levels can be compared on an equal footing.

  14. Sonodynamic therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX.

    PubMed

    Su, Xiaomin; Wang, Xiaobing; Zhang, Kun; Yang, Shuang; Liu, Quanhong; Leung, Albert W; Xu, Chuanshan; Wang, Pan

    2016-04-01

    Sonodynamic therapy (SDT) is expected to be a novel therapeutic strategy for tumor. The protoporphyrin IX disodium salt (PpIX), a photosensitizer, can be activated by ultrasound. The present study aims to investigate apoptosis of HL-60 cells induced by PpIX-mediated SDT. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was adopted to examine cell toxicity. Apoptosis was detected using Annexin V-PE/7-amino-actinomycin D (7-AAD) double staining. Detection of apoptotic bodies was examined by Hoechst33342 (HO) staining. Western blotting was used to analyze the protein of caspase-3 and poly ADP-ribose polymerase (PARP). Intracellular reactive oxygen species (ROS) was detected by a flow cytometer after exposures. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound were significantly boosted. In addition, as determined by Annexin V-PE/7-AAD staining, SDT significantly induced HL-60 cell apoptosis, the obvious nuclear condensation was also found with HO staining at 4 hours post-SDT treatment. Furthermore, Western blotting showed visible enhancement of caspase-3 and PARP cleavage in this process. Besides, intracellular ROS production was significantly enhanced after SDT. Our findings demonstrate that PpIX-mediated SDT could induce apoptosis on HL-60 cells, suggesting that apoptosis is an important mechanism of cell death induced by PpIX-mediated SDT. PMID:26891272

  15. Improved in vitro and in vivo cutaneous delivery of protoporphyrin IX from PLGA-based nanoparticles.

    PubMed

    da Silva, Carolina L; Del Ciampo, José O; Rossetti, Fábia C; Bentley, Maria V L B; Pierre, Maria B R

    2013-01-01

    We report the development of D, L lactic co-glycolic acid) (PLGA)-based nanoparticles (NPs) for topical delivery of protoporphyrin IX (PpIX), a photosensitizer (PS), in treatments like photodynamic therapy (PDT) of skin cancers. PpIX-NPs were obtained in ~75.0% yield, encapsulation efficiency of 67.7%, drug content of 50.3 μg mg(-1), average diameter of 290 nm maintained up to 30 days and a zeta potential of 32.3 mV. Sustained in vitro release of PpIX through artificial membranes following Higuchi kinetics was kept up to 10 days. In vitro retentions of PpIX both in stratum corneum (SC) and epidermis + dermis ([EP + D]) were higher from NPs (23.0 and 10.0 times, respectively) compared to control solutions at all times. Quantification of PpIX by extraction, after in vivo skin application of NPs-PpIX on hairless mice, showed higher retention of the PS both in SC and in [EP + D] (3.0 and 2.0 times, respectively) compared to control solutions. Taken together, the results indicate that NPs are suitable for PpIX encapsulation showing minimal permeation through the skin and a localized effect, characteristics of a potential and promising delivery system for PDT-associated treatments of skin cancers, photodiagnosis and their off-label uses.

  16. Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug-Resistant Acinetobacter baumannii Isolates

    PubMed Central

    Chang, David; Garcia, Rebecca A.; Akers, Kevin S.; Mende, Katrin; Murray, Clinton K.; Wenke, Joseph C.; Sanchez, Carlos J.

    2016-01-01

    Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO3)3 was moderately effective at reducing planktonic bacteria (64 to 128 µM) with little activity against biofilms (≥512 µM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 µM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 µM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. PMID:26999163

  17. Protoporphyrin (PPIX) efflux by the MacAB-TolC pump in Escherichia coli.

    PubMed

    Turlin, Evelyne; Heuck, Gesine; Simões Brandão, Maria Inês; Szili, Noémie; Mellin, J R; Lange, Norbert; Wandersman, Cécile

    2014-12-01

    In most organisms, heme biosynthesis is strictly controlled so as to avoid heme and heme precursor accumulation, which is toxic. Escherichia coli regulates heme biosynthesis by a feedback loop involving heme-induced proteolytic cleavage of HemA, glutamyl-tRNA reductase, which is the first enzyme in the heme biosynthetic pathway. We show here that heme homeostasis can be disrupted by overproduction of YfeX, a cytoplasmic protein that captures iron from heme that we named deferrochelatase. We also show that it is disrupted by iron chelation, which reduces the intracellular iron concentration necessary for loading iron into protoporphyrin IX (PPIX, the immediate heme precursor). In both cases, we established that there is an increased PPIX concentration and we demonstrate that this compound is expelled by the MacAB-TolC pump, an efflux pump involved in E. coli and Salmonella for macrolide efflux. The E. coli macAB and tolC mutants accumulate PPIX and are sensitive to photo-inactivation. The MacAB-TolC pump is required for Salmonella typhimurium survival in macrophages. We propose that PPIX is an endogenous substrate of the MacAB-TolC pump in E. coli and S. typhimurium and that this compound is produced inside bacteria when natural heme homeostasis is disrupted by iron shortage, as happens when bacteria invade the mammalian host. PMID:25257218

  18. Mg-Protoporphyrin IX Signals Enhance Plant’s Tolerance to Cold Stress

    PubMed Central

    Zhang, Zhong-Wei; Wu, Zi-Li; Feng, Ling-Yang; Dong, Li-Hua; Song, An-Jun; Yuan, Ming; Chen, Yang-Er; Zeng, Jian; Chen, Guang-Deng; Yuan, Shu

    2016-01-01

    The relationship between Mg-protoporphyrin IX (Mg-Proto IX) signals and plant’s tolerance to cold stress is investigated. Arabidopsis seedlings grown for 3 weeks were pretreated with 2 mM glutamate (Glu) and 2 mM MgCl2 for 48 h at room temperature to induce Mg-Proto IX accumulation. Then cold stress was performed at 4°C for additional 72 h. Glu + MgCl2 pre-treatments alleviated the subsequent cold stress significantly by rising the leaf temperature through inducing Mg-Proto IX signals. The protective role of Glu + MgCl2 treatment was greatly compromised in the mutants of Mg-Proto IX synthesis, Mg-Proto IX signaling, and cyanide-resistant respiration. And the enhancement of cold-responsive gene expression was greatly compromised in the mutants of Mg-Proto IX synthesis, Mg-Proto IX signaling and ABA signaling, but not in the mutant of cyanide-resistant respiration. Cold stress promoted cyanide-resistant respiration and leaf total respiration exponentially, which could be further induced by the Glu + MgCl2 treatment. Mg-Proto IX signals also activate antioxidant enzymes and increase non-enzymatic antioxidants [glutathione but not ascorbic acid (AsA)] to maintain redox equilibrium during the cold stress. PMID:27803706

  19. Structure-function relations of human hemoglobins

    PubMed Central

    2006-01-01

    In 1949 Pauling and his associates showed that sickle cell hemoglobin (HbS) belonged to an abnormal molecular species. In 1958 Ingram, who used a two-dimensional system of electrophoresis and chromatography to break down the hemoglobin molecule into a mixture of smaller peptides, defined the molecular defect in HbS by showing that it differed from normal adult hemoglobin by only a single peptide. Since then, more than 200 variant and abnormal hemoglobins have been described. Furthermore, the construction of an atomic model of the hemoglobin molecule based on a high-resolution x-ray analysis by Dr. Max Perutz at Cambridge has permitted the study of the stereochemical part played by the amino acid residues, which were replaced, deleted, or added to in each of the hemoglobin variants. Some of the variants have been associated with clinical conditions. The demonstration of a molecular basis for a disease was a significant turning point in medicine. A new engineered hemoglobin derived from crocodile blood, with markedly reduced oxygen affinity and increased oxygen delivery to the tissues, points the way for future advances in medicine. PMID:17252042

  20. Oxygen Measurements in Liposome Encapsulated Hemoglobin

    NASA Astrophysics Data System (ADS)

    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. Hemoglobin-based red blood cell substitutes.

    PubMed

    Chang, Thomas Ming Swi

    2004-09-01

    Polyhemoglobin is already well into the final stages of clinical trials in humans with one approved for routine clinical use in South Africa. Conjugated hemoglobin is also in ongoing clinical trials. Meanwhile, recombinant Hb has been modified to modulate the effects of nitric oxide. Other systems contain antioxidant enzymes for those clinical applications that may have potential problems related to ischemia-reperfusion injuries. Other developments are based on hemoglobin-lipid vesicles and also the use of nanotechnology and biodegradable copolymers to prepare nanodimension artificial red blood cells containing hemoglobin and complex enzyme systems.

  2. Associations between dietary iron and zinc intakes, and between biochemical iron and zinc status in women.

    PubMed

    Lim, Karen; Booth, Alison; Szymlek-Gay, Ewa A; Gibson, Rosalind S; Bailey, Karl B; Irving, David; Nowson, Caryl; Riddell, Lynn

    2015-04-20

    Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18-50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12-38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort.

  3. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... the person's average blood sugar levels over that time. Why It's Done Doctors use the hemoglobin A1c test to determine if your child's diabetes management plan needs to be adjusted. Typically the test ...

  4. Nanobiotechnology for hemoglobin-based blood substitutes.

    PubMed

    Chang, T M S

    2009-04-01

    Nanobiotechnology is the assembling of biological molecules into nanodimension complexes. This has been used for the preparation of polyhemoglobin formed by the assembling of hemoglobin molecules into a soluble nanodimension complex. New generations of this approach include the nanobiotechnological assembly of hemoglobin, catalase, and superoxide dismutase into a soluble nanodimension complex. This acts as an oxygen carrier and an antioxidant for those conditions with potential for ischemiareperfusion injuries. Another recent novel approach is the assembling of hemoglobin and fibrinogen into a soluble nanodimension polyhemoglobin-fibrinogen complex that acts as an oxygen carrier with platelet-like activity. This is potentially useful in cases of extensive blood loss requiring massive replacement using blood substitutes, resulting in the need for the replacement of platelets and clotting factors. A further step is the preparation of nanodimension artificial red blood cells that contain hemoglobin and all the enzymes present in red blood cells.

  5. Zinc phosphide

    Integrated Risk Information System (IRIS)

    Zinc phoshide ; CASRN 1314 - 84 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  6. Zinc cyanide

    Integrated Risk Information System (IRIS)

    Zinc cyanide ; CASRN 557 - 21 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effe

  7. Hemoglobins, programmed cell death and somatic embryogenesis.

    PubMed

    Hill, Robert D; Huang, Shuanglong; Stasolla, Claudio

    2013-10-01

    Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival.

  8. Cloned Hemoglobin Genes Enhance Growth Of Cells

    NASA Technical Reports Server (NTRS)

    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.

  9. Evolution of ruminant hemoglobins. Thermodynamic divergence of ox and buffalo hemoglobins.

    PubMed

    Giardina, B; Arevalo, F; Clementi, M E; Ferrara, L; Di Luccia, A; Lendaro, E; Bellelli, A; Condò, S G

    1992-03-01

    The ligand-binding properties of hemoglobins from two homozygote phenotypes (AA and BB) of water buffalo (Bubalus bubalis) have been characterized by equilibrium and kinetic techniques. In the case of the BB phenotype, the two constituent hemoglobins have been purified and separately analysed. Buffalo hemoglobins display the reduced sensitivity to organic phosphates characteristic of ruminant hemoglobins, their physiological effector probably being the chloride ion. In contrast to the other known hemoglobins from ruminants, all the hemoglobins from the water buffalo display a significant temperature sensitivity, the delta H for oxygen binding in the presence of physiological effectors approaching that of human hemoglobin (delta H = -30.5 kJ/mol O2). This discrepancy with the other ruminant hemoglobins (e.g. ox, delta H = -10.4 kJ/mol O2), whose primary structure is very similar to that of buffalo, hemoglobins might be correlated to the different habitat and phylogenetic history of the two subfamilies (Bos and Bubalus) of Bovidae.

  10. Enteral and parenteral feeding influences mortality after hemoglobin-E. coli peritonitis in normal rats.

    PubMed

    Kudsk, K A; Stone, J M; Carpenter, G; Sheldon, G F

    1983-07-01

    Enteral feeding with 25% dextrose-4.25% Freamine II (TPN) improves the survival of malnourished animals to normal levels after hemoglobin-E. coli adjuvant peritonitis, whereas intravenous feeding does not. To determine whether intravenous feeding maintained a high survival rate in previously well-nourished animals, 81 rats received TPN via gastrostomy or intravenous infusion for 12 days. They were then fasted for 24 hours and given a septic challenge. Gastrostomy-fed animals survived the challenge significantly better than intravenously fed animals. Enteral feeding appears to be important in producing a high survival rate after hemoglobin-E. coli adjuvant peritonitis.

  11. Dual control mechanism for heme oxygenase: tin(IV)-protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver.

    PubMed Central

    Sardana, M K; Kappas, A

    1987-01-01

    Tin(IV)-protoporphyrin (Sn-protoporphyrin) potently inhibits heme degradation to bile pigments in vitro and in vivo, a property that confers upon this synthetic compound the ability to suppress a variety of experimentally induced and naturally occurring forms of jaundice in animals and humans. Utilizing rat liver heme oxygenase purified to homogeneity together with appropriate immunoquantitation techniques, we have demonstrated that Sn-protoporphyrin possesses the additional property of potently inducing the synthesis of heme oxygenase protein in liver cells while, concurrently, completely inhibiting the activity of the newly formed enzyme. Substitution of tin for the central iron atom of heme thus leads to the formation of a synthetic heme analogue that regulates heme oxygenase by a dual mechanism, which involves competitive inhibition of the enzyme for the natural substrate heme and simultaneous enhancement of new enzyme synthesis. Cobaltic(III)-protoporphyrin (Co-protoporphyrin) also inhibits heme oxygenase activity in vitro, but unlike Sn-protoporphyrin it greatly enhances the activity of the enzyme in the whole animal. Co-protoporphyrin also acts as an in vivo inhibitor of heme oxygenase; however, its inducing effect on heme oxygenase synthesis is so pronounced as to prevail in vivo over its inhibitory effect on the enzyme. These studies show that certain synthetic heme analogues possess the ability to simultaneously inhibit as well as induce the enzyme heme oxygenase in liver. The net balance between these two actions, as reflected in the rate of heme oxidation activity in the whole animal, appears to be influenced by the nature of the central metal atom of the synthetic metalloporphyrin. Images PMID:3470805

  12. Hemoglobin parameters from diffuse reflectance data

    PubMed Central

    Mourant, Judith R.; Marina, Oana C.; Hebert, Tiffany M.; Kaur, Gurpreet; Smith, Harriet O.

    2014-01-01

    Abstract. Tissue vasculature is altered when cancer develops. Consequently, noninvasive methods of monitoring blood vessel size, density, and oxygenation would be valuable. Simple spectroscopy employing fiber optic probes to measure backscattering can potentially determine hemoglobin parameters. However, heterogeneity of blood distribution, the dependence of the tissue-volume-sampled on scattering and absorption, and the potential compression of tissue all hinder the accurate determination of hemoglobin parameters. We address each of these issues. A simple derivation of a correction factor for the absorption coefficient, μa, is presented. This correction factor depends not only on the vessel size, as others have shown, but also on the density of blood vessels. Monte Carlo simulations were used to determine the dependence of an effective pathlength of light through tissue which is parameterized as a ninth-order polynomial function of μa. The hemoglobin bands of backscattering spectra of cervical tissue are fit using these expressions to obtain effective blood vessel size and density, tissue hemoglobin concentration, and oxygenation. Hemoglobin concentration and vessel density were found to depend on the pressure applied during in vivo acquisition of the spectra. It is also shown that determined vessel size depends on the blood hemoglobin concentration used. PMID:24671524

  13. Subunit dissociations in natural and recombinant hemoglobins.

    PubMed

    Manning, L R; Jenkins, W T; Hess, J R; Vandegriff, K; Winslow, R M; Manning, J M

    1996-04-01

    A precise and rapid procedure employing gel filtration on Superose-12 to measure the tetramer-dimer dissociation constants of some natural and recombinant hemoglobins in the oxy conformation is described. Natural sickle hemoglobin was chosen to verify the validity of the results by comparing the values with those reported using an independent method not based on gel filtration. Recombinant sickle hemoglobin, as well as a sickle double mutant with a substitution at the Val-6(beta) receptor site, had approximately the same dissociation constant as natural sickle hemoglobin. Of the two recombinant hemoglobins with amino acid replacements in the alpha 1 beta 2 subunit interface, one was found to be extensively dissociated and the other completely dissociated. In addition, the absence of an effect of the allosteric regulators DPG and IHP on the dissociation constant was demonstrated. Thus, a tetramer dissociation constant can now be determined readily and used together with other criteria for characterization of hemoglobins and their interaction with small regulatory molecules. PMID:8845768

  14. AMINO ACIDS AND HEMOGLOBIN PRODUCTION IN ANEMIA

    PubMed Central

    Whipple, G. H.; Robscheit-Robbins, F. S.

    1940-01-01

    Certain individual amino acids when given to standard anemic dogs cause an increase in new hemoglobin production. Occasional negative experiments are recorded. Glycine, glutamic acid, aspartic acid, cystine, histidine, phenylalanine, and proline when given in 1 gm. doses daily for 2 weeks, increase hemoglobin output on the average 23 to 25 gm. above the control level. This reaction amounts to 25 to 30 per cent of the new hemoglobin produced by the feeding of 300 gm. liver daily for 2 weeks—a standard liver test. Alanine, valine, isoleucine, and arginine in the same dosage increase the hemoglobin output on the average 13 to 17 gm. per 2 weeks over the control level. Leucine, methionine, lysine, tryptophane, and tyrosine fall in a middle group with hemoglobin output of about 20 gm. Isovaleric acid, β-hydroxybutyric acid, glutaric acid, and asparagine have shown positive effects and the butyrate is unusually potent for hemoglobin production (Table 2). The isomeric and dl-synthetic forms of the amino acids are as effectively utilized in this reaction as are the natural forms. PMID:19870982

  15. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  16. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  17. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  18. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  19. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  20. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  1. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  2. Protoporphyrin IX-β-cyclodextrin bimodal conjugate: nanosized drug transporter and potent phototoxin.

    PubMed

    Aggelidou, Chrysie; Theodossiou, Theodossis A; Yannakopoulou, Konstantina

    2013-01-01

    Topical or systemic administration of 5-aminolevulinic acid (ALA) and its esters results in increased production and accumulation of protoporphyrin IX (PpIX) in cancerous lesions allowing effective application of photodynamic therapy (PDT). The large concentrations of exogenous ALA practically required to bypass the negative feedback control exerted by heme on enzymatic ALA synthesis and the strong dimerization propensity of ALA are shortcomings of the otherwise attractive PpIX biosynthesis. To circumvent these limitations and possibly enhance the phototoxicity of PpIX by adjuvant chemotherapy, covalent bonding of PpIX with a drug carrier, β-cyclodextrin (βCD) was implemented. The resulting PpIX + βCD product had both carboxylic termini of PpIX connected to the CD. PpIX + βCD was water soluble, was found to preferentially localize in mitochondria rather than in lysosomes both in MCF7 and DU145 cell lines while its phototoxiciy was comparable to that of PpIX. Moreover, PpIX + βCD effectively solubilized the breast cancer drug tamoxifen metabolite N-desmethyltamoxifen (NDMTAM) in water. The PpIX + βCD/NDMTAM complex was readily internalized by both cell lines employed. Furthermore, the multimodal action of PpIX + βCD was demonstrated in MCF7 cells: while it retains the phototoxic profile of PpIX and its fluorescence for imaging purposes, PpIX + βCD can efficiently transport tamoxifen citrate intracellularly and confer cell death through a synergy of photo- and chemotoxicity. PMID:23819797

  3. Fluorescence imaging and spectroscopy of ALA-induced protoporphyrin IX preferentially accumulated in tumor tissue

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert G.; Baumgartner, Reinhold; Beyer, Wolfgang; Knuechel, Ruth; Koerner, T. O.; Kriegmair, M.; Rick, Kai; Steinbach, Pia; Hofstetter, Alfons G.

    1995-12-01

    In a clinical pilot study performed on 104 patients suffering from bladder cancer it could be shown that intravesical instillation of a solution of 5-aminolevulinic acid (5-ALA) induces a tumorselective accumulation of Protoporphyrin IX (PPIX). Malignant lesions could be detected with a sensitivity of 97% and a specificity of 67%. The Kr+-laser as excitation light source could successfully be replaced by a filtered short arc Xe-lamp. Its emission wavelength band (375 nm - 440 nm) leads to an efficiency of 58% for PPIX- excitation compared to the laser. Two-hundred-sixty mW of output power at the distal end of a slightly modified cystoscope could be obtained. This is sufficient for recording fluorescence images with a target integrating color CCD-camera. Red fluorescence and blue remitted light are displayed simultaneously. Standard white light observation is possible with the same instrumentation. Pharmacokinetic measurements were performed on 18 patients after different routes of 5-ALA application (oral, inhalation and intravesical instillation). PPIX-fluorescence measurements were made on the skin and on the blood plasma. Pharmacokinetic of 5-ALA could be performed on blood plasma. Endoscopical florescence spectroscopy showed the high fluorescence contrast between tumor and normal tissue with a mean value of 10.7. Forthcoming clinical multicenter studies require an objective measure of the fluorescence intensity. Monte Carlo computer simulations showed that artifacts due to observation geometry and varying absorption can largely be reduced by ratioing fluorescence (red channel of camera) to remission (blue channel). Real time image ratioing provides false color images with a reliable fluorescence information.

  4. Measurement and modelling of protoporphyrin IX photo-oxidation during superficial PDT

    NASA Astrophysics Data System (ADS)

    Robinson, Dominic J.; Stringer, Mark R.; Crum, William R.; Collins, P.

    1996-12-01

    The oxidation of photosensitizers during photodynamic therapy (PDT) has important implications for their therapeutic and diagnostic potential. The reduction in sensitizer concentration during illumination progressively reduces the effectiveness of therapy and, ultimately, limits the destruction of the host tissue. In the course of our studies of the effects of PDT upon superficial skin disorders, following topical application of 5- aminolaevulinic acid (ALA), we routinely record the surface fluorescence emission of protoporphyrin IX (PpIX) before, during, and after therapy, in order to monitor the sensitizer photo-oxidation. It is important, therefore, to establish that measurements made in this way are representative of the variation in sensitizer concentration throughout the illuminated volume. We have developed a time- dependent Monte-Carlo model to simulate PpIX photo-oxidation during either low intensity laser (488 nm) or white light irradiation of plaque psoriasis. We have assessed the effect of differences in the optical properties of tissue at sites on different patients prior to treatment, and the effect of these variations on the surface fluorescence signal detected during treatment, at sites within the same plaque. The results show that the PpIX fluorescence intensity recorded from plaque psoriasis is an accurate indicator of the relative concentration of the sensitizer and can be used as a direct comparison between different sites and different patients. Also, the reduction in fluorescence emission during PDT is an effective measure of the depletion in sensitizer concentration throughout the illuminated volume. These results illustrate that the light dose required to achieve significant PpIX photo-oxidation is significantly lower than that often adopted for the treatment of superficial skin conditions.

  5. Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes

    PubMed Central

    Arivett, Brock A.; Fiester, Steven E.; Ohneck, Emily J.; Penwell, William F.; Kaufman, Cynthia M.; Relich, Ryan F.

    2015-01-01

    A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606T and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606T and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606T or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media. PMID:26416873

  6. Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes.

    PubMed

    Arivett, Brock A; Fiester, Steven E; Ohneck, Emily J; Penwell, William F; Kaufman, Cynthia M; Relich, Ryan F; Actis, Luis A

    2015-12-01

    A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606(T) and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606(T) and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606(T) or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media.

  7. An intraoperative spectroscopic imaging system for quantification of Protoporphyrin IX during glioma surgery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Angulo-Rodríguez, Leticia M.; Laurence, Audrey; Jermyn, Michael; Sheehy, Guillaume; Sibai, Mira; Petrecca, Kevin; Roberts, David W.; Paulsen, Keith D.; Wilson, Brian C.; Leblond, Frédéric

    2016-03-01

    Cancer tissue often remains after brain tumor resection due to the inability to detect the full extent of cancer during surgery, particularly near tumor boundaries. Commercial systems are available for intra-operative real-time aminolevulenic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence imaging. These are standard white-light neurosurgical microscopes adapted with optical components for fluorescence excitation and detection. However, these instruments lack sensitivity and specificity, which limits the ability to detect low levels of PpIX and distinguish it from tissue auto-fluorescence. Current systems also cannot provide repeatable and un-biased quantitative fluorophore concentration values because of the unknown and highly variable light attenuation by tissue. We present a highly sensitive spectroscopic fluorescence imaging system that is seamlessly integrated onto a neurosurgical microscope. Hardware and software were developed to achieve through-microscope spatially-modulated illumination for 3D profilometry and to use this information to extract tissue optical properties to correct for the effects of tissue light attenuation. This gives pixel-by-pixel quantified fluorescence values and improves detection of low PpIX concentrations. This is achieved using a high-sensitivity Electron Multiplying Charge Coupled Device (EMCCD) with a Liquid Crystal Tunable Filter (LCTF) whereby spectral bands are acquired sequentially; and a snapshot camera system with simultaneous acquisition of all bands is used for profilometry and optical property recovery. Sensitivity and specificity to PpIX is demonstrated using brain tissue phantoms and intraoperative human data acquired in an on-going clinical study using PpIX fluorescence to guide glioma resection.

  8. The renal handling of hemoglobin. I. Glomerular filtration.

    PubMed

    Bunn, H F; Esham, W T; Bull, R W

    1969-05-01

    The glomerular filtration of hemoglobin (alpha(2)beta(2)) was studied under conditions in which its dissociation into alphabeta dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of (59)Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose.

  9. Anion Bohr effect of human hemoglobin.

    PubMed

    Bucci, E; Fronticelli, C

    1985-01-15

    The pH dependence of oxygen affinity of hemoglobin (Bohr effect) is due to ligand-linked pK shifts of ionizable groups. Attempt to identify these groups has produced controversial data and interpretations. In a further attempt to clarify the situation, we noticed that hemoglobin alkylated in its liganded form lost the Bohr effect while hemoglobin alkylated in its unliganded form showed the presence of a practically unmodified Bohr effect. In spite of this difference, analyses of the extent of alkylation of the two compounds failed to identify the presence of specific preferential alkylations. In particular, the alpha 1 valines and beta 146 histidines appeared to be alkylated to the same extent in the two proteins. Focusing our attention on the effect of the anions on the functional properties of hemoglobin, we measured the Bohr effect of untreated hemoglobin in buffers made with HEPES [N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid], MES [2-(N-morpholino)ethanesulfonic acid], and MOPS [3-(N-morpholino)propanesulfonic acid], which being zwitterions do not need addition of chlorides or other anions for reaching the desired pH. The shape acquired by the Bohr effect curves, either as pH dependence of oxygen affinity or as pH dependence of protons exchanged with the solution, was irreconcilable with that of the Bohr effect curves in usual buffers. This indicated the relevance of solvent components in determining the functional properties of hemoglobin. A new thermodynamic model is proposed for the Bohr effect that includes the interaction of hemoglobin with solvent components. The classic proton Bohr effect is a special case of the new theory.

  10. Metals content of Glossoscolex paulistus extracellular hemoglobin: Its peroxidase activity and the importance of these ions in the protein stability.

    PubMed

    Caruso, Celia S; Biazin, Ezer; Carvalho, Francisco A O; Tabak, Marcel; Bachega, José F R

    2016-08-01

    In this work we investigate the presence of divalent cations bound to the Glossoscolex paulistus (HbGp) hemoglobin and their effect over the protein stability and the peroxidase (POD) activity. Atomic absorption studies show that the HbGp iron content is consistent with the presence of 144 ions per protein. Moreover, using iron as a reference, the content of calcium was estimated as 30±4 ions per protein, independently of the EDTA pre-treatment or not prior to the acidic treatment performed in the protein digestion. The zinc content was 14±2 ions in the absence of EDTA pre-treatment, and 3±1 ions per protein in the presence of EDTA pre-treatment, implying the presence of one zinc ion per protomer (1/12 of the whole molecule). Finally, the copper concentration is negligible. Different from the vertebrate hemoglobins, where the effectors are usually organic anions, the hexagonal bilayer hemoglobins have as effectors inorganic cations that increase the oxygen affinity and stabilize the structure. Previous studies have suggested that the presence of divalent cations, such as copper and zinc, is related to the different types of antioxidant enzymatic activities as the superoxide dismutase (SOD) activity shown by giant hemoglobin from Lumbricus terrestris (HbLt). Recently, studies on HbGp crystal structure have confirmed the presence of Zn(2+) and Ca(2+) binding sites. The Ca(2+) sites are similar as observed in the HbLt crystal structure. Otherwise, the Zn(2+) sites have no relation with those observed in Cu/Zn SODs. Our peroxidase assays with guaiacol confirm the POD activity and the effect of the zinc ions for HbGp. Our present results on HbGp metal content and their stability effects is the first step to understand the role of these cations in HbGp function in the future. PMID:27221949

  11. Properties of Hemoglobin Solutions in Red Cells

    PubMed Central

    Gary-Bobo, C. M.; Solomon, A. K.

    1968-01-01

    The present studies are concerned with a detailed examination of the apparent anomalous osmotic behavior of human red cells. Red cell water has been shown to behave simultaneously as solvent water for nonelectrolytes and nonsolvent water, in part, for electrolytes. The nonsolvent properties are based upon assumptions inherent in the conventional van't Hoff equation. However, calculations according to the van't Hoff equation give osmotic volumes considerably in excess of total cell water when the pH is lowered beyond the isoelectric point for hemoglobin; hence the van't Hoff equation is inapplicable for the measurement of the solvent properties of the red cell. Furthermore, in vitro measurements of osmotic and other properties of 3.7 millimolal solutions of hemoglobin have failed to reveal the presence of any salt exclusion. A new hypothesis has been developed from thermodynamic principles alone, which predicts that, at constant pH, the net charge on the hemoglobin molecule decreases with increased hemoglobin concentration. The existence of such cooperative interaction may be inferred from the effect of pH on the changes in hemoglobin net charge as the spacing between the molecules decreases. The resultant movement of counterions across the cell membrane causes the apparent anomalous osmotic behavior. Quantitative agreement has been found between the anion shift predicted by the equation and that observed in response to osmotic gradients. The proposed mechanism appears to be operative in a variety of tissues and could provide an electrical transducer for osmotic signals. PMID:5688085

  12. Classification of the Disorders of Hemoglobin

    PubMed Central

    Forget, Bernard G.; Bunn, H. Franklin

    2013-01-01

    Over the years, study of the disorders of hemoglobin has served as a paradigm for gaining insights into the cellular and molecular biology, as well as the pathophysiology, of inherited genetic disorders. To date, more than 1000 disorders of hemoglobin synthesis and/or structure have been identified and characterized. Study of these disorders has established the principle of how a mutant genotype can alter the function of the encoded protein, which in turn can lead to a distinct clinical phenotype. Genotype/phenotype correlations have provided important understanding of pathophysiological mechanisms of disease. Before presenting a brief overview of these disorders, we provide a summary of the structure and function of hemoglobin, along with the mechanism of assembly of its subunits, as background for the rationale and basis of the different categories of disorders in the classification. PMID:23378597

  13. Cobalt protoporphyrin induces differentiation of monocytic THP-1 cells through regulation of cytoplasmic Ref-1-related NADPH oxidase activity.

    PubMed

    Song, Ju Dong; Lee, Sang Kwon; Park, Si Eun; Kim, Kang Mi; Kim, Koanhoi; Park, Yeong Min; Park, Young Chul

    2011-11-01

    Cobalt protoporphyrin (CoPP) is a potent and effective metalloporphyrin inducer of heme oxygenase-1 (HO-1) activity in many tissues. Here, we report that CoPP induces differentiation of monocytic THP-1 cells into macrophage-like cells. CoPP induced a marked growth inhibition with a slight reduction in viability, and increased adhesion and spreading of THP-1 cells. However, other protoporphyrins did not. CoPP also resulted in expression of CD11b, MMP9, MSR1, CD14 and ICAM-1, which are differentiation markers for macrophages. Interestingly, we observed a decrease of cytoplasmic redox factor-1 (Ref-1) levels in the process of CoPP-induced differentiation of THP-1 cells. In addition, knockdown of Ref-1 by siRNA enhanced cell adhesion induced by CoPP. Furthermore, an inhibitor of NADPH oxidase, diphenyleneiodonium (DPI), completely abolished CoPP-induced adhesion of Ref-1-deficient cells using an siRNA. A cytosolic factor for NADPH oxidase activity, p47phox, was significantly increased in THP-1 cells by CoPP treatment. Κnockdown of Ref-1 increased CoPP-induced p47phox expression in THP-1 cells. Taken together, these results suggest that CoPP induces differentiation of monocytic THP-1 cells, and that the CoPP-induced differentiation is associated with cytoplasmic Ref-1-related NADPH oxidase activity.

  14. [Structural-functional organization of the cells of Brc-1 mutant Chlamydomonas reinhardtii, supplying protoporphyrin IX in the dark].

    PubMed

    Ladygin, V G; Chekunova, E M; Semenova, G A; Kosobriukhov, A A

    2014-01-01

    The structural-functional characteristics of the cells of wild type CC-124 and Brc-1 mutant of the unicellular green algae Chlamydomonas reinhardtii while growing in the dark and light were studied. It has been shown that the cells of the wild type in heterotrophic and mixotrophic growth conditions had a well developed structure and high functional activity due to the ability of the cells to synthesize chlorophyll both in the light and in the dark. The cells of Brc-1 mutant lost their ability to synthesize chlorophyll in the dark and the cells' color was orange due to brc-1 mutation in the nuclear gene LTS3 that regulated the activity of Mg-chelatase enzyme. In the dark the mutant cells accumulated protoporphyrin IX and had a weakly developed structure with low functional activity. It has been ascertained that due to high content of protoporphyrin IX even a short-term exposure of the cells of Brc-1 mutant to the light was accompanied by very strong destructive changes in all the membranes in a cell: plasmalemma, chloroplast, mitochondrion, shells of the nucleus and vacuoles. The reasons of these significant damages of the membrane components and O2-gas exchange in the cells of Brc-1 mutant are discussed.

  15. Characterization of Polyethylene Glycol Modified Hemoglobins

    NASA Astrophysics Data System (ADS)

    Salazar, Gil; Barr, James; Morgan, Wayne; Ma, Li

    2011-03-01

    Polyethylene glycol modified hemoglobins (PEGHbs) was characterized by liquid chromatography and fluorescence methods. We prepared four samples of two different molecular weight PEG, 5KDa and 20KDa, modified bovine and human hemoglobin. We studied the oxygen affinities, stabilities, and peroxidase activities of PEGHbs. We have related oxygen affinities with different degrees of modifications. The data showed that the modification on the beta subunits was less stable than that of the alpha subunits on the human Hb based samples especially. We also compared peroxidase activities among different modified PEGHbs.

  16. Asymptomatic child heterozygous for hemoglobin S and hemoglobin Pôrto Alegre.

    PubMed

    Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

    2011-03-01

    Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser → Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation.

  17. Asymptomatic Child Heterozygous for Hemoglobin S and Hemoglobin Pôrto Alegre

    PubMed Central

    Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

    2013-01-01

    Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser→Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation. PMID:21225927

  18. Unrecognized hemoglobin SE disease as microcytosis

    PubMed Central

    Cooper, Barry; Guileyardo, Joseph; Mora, Adan

    2016-01-01

    Hemoglobin SE disease was first described during the 1950s as a relatively benign microcytosis, but increasing prevalence has revealed a predisposition towards vasoocclusive sickling. Recognition of SE hemoglobinopathies’ potential complications is crucial so medical measures can be utilized to avoid multiorgan injury. PMID:27365881

  19. Metastable Polymerization of Sickle Hemoglobin in Droplets

    PubMed Central

    Aprelev, Alexey; Weng, Weijun; Zakharov, Mikhail; Rotter, Maria; Yosmanovich, Donna; Kwong, Suzanna; Briehl, Robin W.; Ferrone, Frank A.

    2007-01-01

    Sickle cell disease arises from a genetic mutation of one amino acid in each of the two hemoglobin β chains, leading to the polymerization of hemoglobin in the red cell upon deoxygenation, and is characterized by vascular crises and tissue damage due to the obstruction of small vessels by sickled cells. It has been an untested assumption that, in red cells that sickle, the growing polymer mass would consume monomers until the thermodynamically well-described monomer solubility was reached. By photolyzing droplets of sickle hemoglobin suspended in oil we find that polymerization does not exhaust the available store of monomers, but stops prematurely, leaving the solutions in a supersaturated, metastable state typically 20% above solubility at 37°C, though the particular values depend on the details of the experiment. We propose that polymer growth stops because the growing ends reach the droplet edge, whereas new polymer formation is thwarted by long nucleation times, since the hemoglobin concentration is lowered by depletion of monomers into the polymers that have formed. This finding suggests a new aspect to the pathophysiology of sickle cell disease, namely, that cells deoxygenated in the microcirculation are not merely undeformable, but will actively wedge themselves tightly against the walls of the microvasculature by a ratchet-like mechanism driven by the supersaturated solution. PMID:17493634

  20. Circular dichroism and conformation of fish hemoglobins.

    PubMed

    Greenwood, C; Gibson, Q H

    1983-04-10

    The circular dichroism spectrum of fully liganded CO hemoglobin from the Atlantic bluefin tuna (Tunnus thynnus) shows a pH- and temperature-dependent feature at 416 nm. It is half-developed at pH 5.9 and 20 degrees C and its change with temperature corresponds to a heat of 34 kcal/mol (tetramer) for the transition. Correlation with studies on function (Morris, R. J., and Gibson, Q. H. (1982) J. Biol. Chem. 257, 4869-4874) shows that the dichroism feature changes at about 1 pH unit below the R-T transition. There is a close correlation between the 416 nm band and changes in circular dichroism at 287 nm. The new 416 nm band is seen in several fish hemoglobins, but not with human hemoglobin. With hemoglobin from Brevoortia tyrannus, which has been sufficiently studied to permit the comparison, there is a smaller gap between the change in dichroism spectrum and the functional R-T transition. So far, no change in function has been associated with the appearance of the 416 nm circular dichroism band. PMID:6833248

  1. Hemoglobin: A Nitric-Oxide Dioxygenase

    PubMed Central

    Gardner, Paul R.

    2012-01-01

    Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry. PMID:24278729

  2. Trematode hemoglobins show exceptionally high oxygen affinity.

    PubMed

    Kiger, L; Rashid, A K; Griffon, N; Haque, M; Moens, L; Gibson, Q H; Poyart, C; Marden, M C

    1998-08-01

    Ligand binding studies were made with hemoglobin (Hb) isolated from trematode species Gastrothylax crumenifer (Gc), Paramphistomum epiclitum (Pe), Explanatum explanatum (Ee), parasitic worms of water buffalo Bubalus bubalis, and Isoparorchis hypselobagri (Ih) parasitic in the catfish Wallago attu. The kinetics of oxygen and carbon monoxide binding show very fast association rates. Whereas oxygen can be displaced on a millisecond time scale from human Hb at 25 degrees C, the dissociation of oxygen from trematode Hb may require a few seconds to over 20 s (for Hb Pe). Carbon monoxide dissociation is faster, however, than for other monomeric hemoglobins or myoglobins. Trematode hemoglobins also show a reduced rate of autoxidation; the oxy form is not readily oxidized by potassium ferricyanide, indicating that only the deoxy form reacts rapidly with this oxidizing agent. Unlike most vertebrate Hbs, the trematodes have a tyrosine residue at position E7 instead of the usual distal histidine. As for Hb Ascaris, which also displays a high oxygen affinity, the trematodes have a tyrosine in position B10; two H-bonds to the oxygen molecule are thought to be responsible for the very high oxygen affinity. The trematode hemoglobins display a combination of high association rates and very low dissociation rates, resulting in some of the highest oxygen affinities ever observed.

  3. Zinc and zinc transporters in prostate carcinogenesis

    PubMed Central

    Kolenko, Vladimir; Teper, Ervin; Kutikov, Alexander; Uzzo, Robert

    2013-01-01

    The healthy human prostate accumulates the highest level of zinc of any soft tissue in the body. This unique property is retained in BPH, but is lost in prostatic malignancy, which implicates changes in zinc and its transporters in carcinogenesis. Indeed, zinc concentrations diminish early in the course of prostate carcinogenesis, preceding histopathological changes, and continue to decline during progression toward castration-resistant disease. Numerous studies suggest that increased zinc intake might protect against progression of prostatic malignancy. Despite increased dietary intake, zinc accumulation might be limited by the diminished expression of zinc uptake transporters, resulting in decreased intratumoural zinc levels. This finding can explain the conflicting results of various epidemiological studies evaluating the role of zinc supplementation on primary and secondary prostate cancer prevention. Overall, more research into the mechanisms of zinc homeostasis are needed to fully understand its impact on prostate carcinogenesis. Only then can the potential of zinc and zinc transport proteins be harnessed in the diagnosis and treatment of men with prostate cancer. PMID:23478540

  4. Zinc improves antioxidative enzymes in red blood cells and hematology in lithium-treated rats.

    PubMed

    Malhotra, Anshoo; Dhawan, Devinder K

    2008-01-01

    The present study was designed to evaluate the protective role of zinc in attenuating the adverse effects induced by lithium in blood of female Wistar rats. Female Wistar rats received lithium in the form of lithium carbonate in diet at a dose level of 1.1 g/kg diet, zinc alone in the form of zinc sulfate in drinking water at a dose level of 227 mg/L drinking water, or lithium plus zinc treatments in the combined group for a total duration of 2 months. Effects of the treatments were studied on antioxidant defense system, various hematologic parameters, and percentage of (65)Zn-specific activity. Lithium treatment resulted in a significant increase in lipid peroxidation levels but caused a significant decrease in reduced glutathione levels and the activities of catalase, glutathione S-transferase, and superoxide dismutase. Lithium treatment also caused a significant decrease in the activities of aminolevulinic acid dehydratase and Na(+) K(+) adenosine triphosphatase. However, it resulted in a significant increase in total leukocyte counts, neutrophils, and lymphocyte counts as well as zinc protoporphyrin levels, whereas a significant decrease in counts of monocytes, eosinophils, and percentage specific activity of (65)Zn in blood and its various fractions was noticed. Furthermore, lithium treatment caused a significant decrease in serum zinc levels. However, zinc supplementation to lithium-treated rats effectively raised the reduced glutathione levels and also normalized lipid peroxidation and the activities of antioxidative enzymes, which included catalase, glutathione S-transferase, and superoxide dismutase. Moreover, zinc supplementation could raise the activities of the enzymes aminolevulinic acid dehydratase and Na(+) K(+) adenosine triphosphatase as well as the percentage uptake values of (65)Zn in blood and its fractions. The study suggests that zinc, as a nutritional supplement, has the potential in attenuating most of the adverse effects induced by lithium

  5. Production of zinc pellets

    DOEpatents

    Cooper, John F.

    1996-01-01

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries.

  6. Production of zinc pellets

    DOEpatents

    Cooper, J.F.

    1996-11-26

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries. 6 figs.

  7. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  8. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  9. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  10. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  11. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  12. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  13. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    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... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  14. Bioimaging techniques for subcellular localization of plant hemoglobins and measurement of hemoglobin-dependent nitric oxide scavenging in planta.

    PubMed

    Hebelstrup, Kim H; Østergaard-Jensen, Erik; Hill, Robert D

    2008-01-01

    Plant hemoglobins are ubiquitous in all plant families. They are expressed at low levels in specific tissues. Several studies have established that plant hemoglobins are scavengers of nitric oxide (NO) and that varying the endogenous level of hemoglobin in plant cells negatively modulates bioactivity of NO generated under hypoxic conditions or during cellular signaling. Earlier methods for determination of hemoglobin-dependent scavenging in planta were based on measuring activity in whole plants or organs. Plant hemoglobins do not contain specific organelle localization signals; however, earlier reports on plant hemoglobin have demonstrated either cytosolic or nuclear localization, depending on the method or cell type investigated. We have developed two bioimaging techniques: one for visualization of hemoglobin-catalyzed scavenging of NO in specific cells and another for visualization of subcellular localization of green fluorescent protein-tagged plant hemoglobins in transformed Arabidopsis thaliana plants.

  15. Blood lead: Its effect on trace element levels and iron structure in hemoglobin

    NASA Astrophysics Data System (ADS)

    Jin, C.; Li, Y.; Li, Y. L.; Zou, Y.; Zhang, G. L.; Normura, M.; Zhu, G. Y.

    2008-08-01

    Lead is a ubiquitous environmental pollutant that induce a broad range of physiological and biochemical dysfunctions. The purpose of this study was to investigate its effects on trace elements and the iron structure in hemoglobin. Blood samples were collected from rats that had been exposed to lead. The concentration of trace elements in whole blood and blood plasma was determined by ICP-MS and the results indicate that lead exists mainly in the red blood cells and only about 1-3% in the blood plasma. Following lead exposure, the concentrations of zinc and iron in blood decrease, as does the hemoglobin level. This indicates that the heme biosynthetic pathway is inhibited by lead toxicity and that lead poisoning-associated anemia occurs. The selenium concentration also decreases after lead exposure, which may lead to an increased rate of free radical production. The effect of lead in the blood on iron structure in hemoglobin was determined by EXAFS. After lead exposure, the Fe-O bond length increases by about 0.07 Å and the Fe-Np bond length slightly increases, but the Fe-N ɛ bond length remains unchanged. This indicates that the blood content of Hb increases, but that the content of HbO 2 decreases.

  16. Distribution of protoporphyrin IX in Bowen's disease and basal cell carcinomas treated with topical 5-aminolaevulinic acid

    NASA Astrophysics Data System (ADS)

    Roberts, David J.; Stables, G. I.; Ash, D. V.; Brown, Stanley B.

    1995-03-01

    We have used ultra-low light level fluorescence microscopy to examine the suggestion that the relatively poor response of human basal cell carcinomas (BCC) to topical 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) arises from limited drug penetration into the lesion. The distribution of ALA-induced protoporphyrin IX (PpIX) in human BCC and Bowen's disease was examined and, in almost all cases, was found to be most intense in those regions of tumor immediately adjacent to the dermis. This distribution was independent of tumor type, and did not appear to be affected by tumor depth in the skin. It is suggested that ALA penetration may not limit the efficacy of ALA-PDT in the treatment of BCC. Failure of superficial ALA-based PDT in basal cell carcinoma may, instead, be related to the histological structure of this type of lesion.

  17. Identification of the chlE gene encoding oxygen-independent Mg-protoporphyrin IX monomethyl ester cyclase in cyanobacteria.

    PubMed

    Yamanashi, Kaori; Minamizaki, Kei; Fujita, Yuichi

    2015-08-01

    The fifth ring (E-ring) of chlorophyll (Chl) a is produced by Mg-protoporphyrin IX monomethyl ester (MPE) cyclase. There are two evolutionarily unrelated MPE cyclases: oxygen-independent (BchE) and oxygen-dependent (ChlA/AcsF) MPE cyclases. Although ChlA is the sole MPE cyclase in Synechocystis PCC 6803, it is yet unclear whether BchE exists in cyanobacteria. A BLAST search suggests that only few cyanobacteria possess bchE. Here, we report that two bchE candidate genes from Cyanothece strains PCC 7425 and PCC 7822 restore the photosynthetic growth and bacteriochlorophyll production in a bchE-lacking mutant of Rhodobacter capsulatus. We termed these cyanobacterial bchE orthologs "chlE."

  18. Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

    NASA Astrophysics Data System (ADS)

    Rollakanti, Kishore Reddy

    Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

  19. Dietary phytate, zinc and hidden zinc deficiency.

    PubMed

    Sandstead, Harold H; Freeland-Graves, Jeanne H

    2014-10-01

    Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency.

  20. Proton NMR study of the interaction of tin(IV) protoporphyrin IX monomers and dimers with apomyoglobin

    SciTech Connect

    Deeb, R.S.; Peyton, D.H. )

    1992-01-21

    Events during the reconstitution of apomyoglobin to form the holoprotein were probed by porphyrin-metal substitution. Thus interactions between tin(IV) protoporphyrin IX (SnPP) and equine apomyoglobin (apoEqMb), and between tin(IV) protoporphyrin IX dimers ((SnPP){sub 2}) and apoEqMb, were observed by {sup 1}H NMR and optical absorbance spectroscopic techniques. The chief advantages of using SnPP are that products and intermediates can easily be related to SnPP{center dot}EqMb which has been studied and that at least one step during reconstitution is slowed considerably as compared to heme. Reactions of apoEqMb with SnPP and (SnPP){sub 2} produce different intermediates, although the final product, SnPP{center dot}EqMb, is the same for each. An intermediate observed for reaction of SnPP with apoEqMb at pH 10 is in exchange with free SnPP, with the observed rate constant k{sub off} {approximately} 1 s{sup {minus}1}. meso-Proton resonances were assigned for this intermediate by correlation to SnPP resonances via chemical exchange. The intermediate observed for reaction of (SnPP){sub 2} with apoEqMb at pH 7.5 is heterogeneous. The reaction of either SnPP or (SnPP){sub 2} with apoEqMb at neutral pH produces another species which may be the alternate porphyrin-insertion isomer arising from a 180{degree} rotation about the {alpha},{gamma}-meso axis of the porphyrin. Although optical absorbance spectroscopy of the Soret region shows evidence for each reaction, only in combination with {sup 1}H NMR are the various processes assigned.

  1. Effect of the period of resting in elite judo athletes: hematological indices and copper/ zinc-dependent antioxidant capacity.

    PubMed

    Koury, Josely C; de Oliveira, Cyntia F; Portella, Emilson S; Oliveira, Astrogildo V; Donangelo, Carmen M

    2005-12-01

    The purpose of this study was to evaluate the effect of the resting period on hematological and copper-zinc-dependent antioxidant indices in Brazilian elite judo athletes (n = 7). Venous blood samples were collected after 24-h and 5-d periods of resting following a competition, with an interval of 30 d between collections. Two months prior to and during the study, each athlete received an individualized adequate diet. Body composition was determined at both study periods. The following were analyzed: in whole blood, hemoglobin, hematocrit, red cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width, and white cell count; in plasma, zinc, copper, iron, ceruloplasmin, and total iron-binding capacity; in erythrocytes, metallothionein, copper/zinc superoxide dismutase, and osmotic fragility. Dietary intake and body composition did not affect the biochemical measurements. A significant reduction in ceruloplasmin and superoxide dismutase activity was found after 5 d compared to 24 h of resting. A significant correlation between erythrocyte metallothionein and red cell distribution width was observed after 24 h of resting (r = -0.83, p = 0.02), whereas positive correlations of metallothionein with hemoglobin, red cell count, and mean corpuscular hemoglobin concentration were observed after 5 d of resting (r >/= 0.76, p zinc-dependent antioxidant system in elite judo athletes. PMID:16286676

  2. Zinc and vegetarian diets.

    PubMed

    Saunders, Angela V; Craig, Winston J; Baines, Surinder K

    2013-08-19

    Well planned vegetarian diets can provide adequate amounts of zinc from plant sources. Vegetarians appear to adapt to lower zinc intakes by increased absorption and retention of zinc. Good sources of zinc for vegetarians include whole grains, tofu, tempeh, legumes, nuts and seeds, fortified breakfast cereals and dairy products. The inhibitory effects of phytate on absorption of zinc can be minimised by modern food-processing methods such as soaking, heating, sprouting, fermenting and leavening. Absorption of zinc can be improved by using yeast-based breads and sourdough breads, sprouts, and presoaked legumes. Studies show vegetarians have similar serum zinc concentrations to, and no greater risk of zinc deficiency than, non-vegetarians (despite differences in zinc intake).

  3. Transient neonatal zinc deficiency.

    PubMed

    Krieger, I; Alpern, B E; Cunnane, S C

    1986-06-01

    We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA. PMID:3717070

  4. Universal metastability of sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Weng, Weijun

    Sickle hemoglobin (HbS) is a natural mutation of the normal hemoglobin (HbA) found in the red blood cells of human body. Polymerization of HbS occurs when the concentration of deoxyHbS exceeds a well-defined solubility, which is the underlying cause of the Sickle Cell Disease. It has long been assumed that thermodynamic equilibrium is reached when polymerization comes to an end. However, in this thesis we demonstrate that in confined volume as well as in bulk solution, HbS polymerization terminates prematurely, leaving the solution in a metastable state. A newly developed Reservoir method as well as modulated excitation method were adopted for the study. This discovery of universal metastability gives us new insights into understanding the mechanism of sickle cell disease.

  5. Zinc: the neglected nutrient.

    PubMed

    Shambaugh, G E

    1989-03-01

    Zinc was first recognized as essential for animals at the University of Illinois School of Agriculture in 1916, when it was found that zinc-deficient baby pigs were runty, developed dermatitis on their legs, and were sterile. Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit 26 years ago when he measured serum and hair zinc levels in young male Egyptian dwarfs who had failed to mature and were small in stature. By simply adding zinc to their regular diet, they grew in height and became sexually mature. It is now recognized that dwarfism in males is frequent around the Mediterranean, where wheat is the staple of life and has been grown for 4,000 years on the same soil, thereby resulting in the depletion of zinc. Professor Robert Henkin first suggested that zinc deficiency might cause hearing-nerve impairment. Assay of the soft tissues of the cochlea and vestibule revealed a zinc level higher than that of any other part of the body. Previously, the eye was considered to have the highest level of zinc of any organ. To diagnose zinc deficiency clinically, we use serum zinc assays made at the Mayo Clinic Trace Element Laboratory. With zinc supplementation in patients who are marginally zinc deficient, there has been improvement in tinnitus and sensorineural hearing loss in about one-third of elderly adults. We believe zinc deficiency is one causation of presbycusis; by recognizing and correcting it, a progressive hearing loss can be arrested.

  6. Zinc: the neglected nutrient.

    PubMed

    Shambaugh, G E

    1989-03-01

    Zinc was first recognized as essential for animals at the University of Illinois School of Agriculture in 1916, when it was found that zinc-deficient baby pigs were runty, developed dermatitis on their legs, and were sterile. Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit 26 years ago when he measured serum and hair zinc levels in young male Egyptian dwarfs who had failed to mature and were small in stature. By simply adding zinc to their regular diet, they grew in height and became sexually mature. It is now recognized that dwarfism in males is frequent around the Mediterranean, where wheat is the staple of life and has been grown for 4,000 years on the same soil, thereby resulting in the depletion of zinc. Professor Robert Henkin first suggested that zinc deficiency might cause hearing-nerve impairment. Assay of the soft tissues of the cochlea and vestibule revealed a zinc level higher than that of any other part of the body. Previously, the eye was considered to have the highest level of zinc of any organ. To diagnose zinc deficiency clinically, we use serum zinc assays made at the Mayo Clinic Trace Element Laboratory. With zinc supplementation in patients who are marginally zinc deficient, there has been improvement in tinnitus and sensorineural hearing loss in about one-third of elderly adults. We believe zinc deficiency is one causation of presbycusis; by recognizing and correcting it, a progressive hearing loss can be arrested. PMID:2786676

  7. Serum ferritin levels in hemoglobin H disease.

    PubMed

    Galanello, R; Melis, M A; Paglietti, E; Cornacchia, G; de Virgiliis, S; Cao, A

    1983-01-01

    This study shows that hemoglobin H disease patients aged between 0.5 and 44 years, usually (27 out of 30) have normal serum ferritin levels according to age. This reconfirms that in this disease there are usually normal iron stores. However, in a few patients (3 out of 30) increased levels were found. This may be due to inappropriate iron medication, transfusions or associated idiopathic hereditary hemocromatosis gene.

  8. Free heme and sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Uzunova, Veselina V.

    This work investigates further the mechanism of one of the most interesting of the protein self-assembly systems---the polymerization of sickle hemoglobin and the role of free heme in it. Polymerization of sickle hemoglobin is the primary event in the pathology of a chronic hemolytic condition called sickle cell anemia with complex pathogenesis, unexplained variability and symptomatic treatment. Auto-oxidation develops in hemoglobin solutions exposed to room temperature and causes release of ferriheme. The composition of such solutions is investigated by mass spectrometry. Heme dimers whose amount corresponds to the initial amounts of heme released from the protein are followed. Differences in the dimer peak height are established for hemoglobin variants A, S and C and depending on the exposure duration. The effects of free heme on polymerization kinetics are studied. Growth rates and two characteristic parameters of nucleation are measured for stored Hb S. After dialysis of polymerizing solutions, no spherulites are detected at moderately high supersaturation and prolonged exposure times. The addition of 0.16-0.26 mM amounts of heme to dialyzed solutions leads to restoration of polymerization. The measured kinetic parameters have higher values compared to the ones before dialysis. The amount of heme in non-dialyzed aged solution is characterized using spectrophotometry. Three methods are used: difference in absorbance of dialyzed and non-dialyzed solutions, characteristic absorbance of heme-albumin complex and absorbance of non-dialyzed solutions with added potassium cyanide. The various approaches suggest the presence of 0.12 to 0.18 mM of free ferriheme in such solutions. Open questions are whether the same amounts of free heme are present in vivo and whether the same mechanism operates intracellulary. If the answer to those questions is positive, then removal of free heme from erythrocytes can influence their readiness to sickle.

  9. Imidazolidinone adducts of peptides and hemoglobin

    SciTech Connect

    San George, R.C.; Hoberman, H.D.

    1986-05-01

    Acetaldehyde reacts selectively with the terminal amino groups of the ..cap alpha.. and ..beta.. chains of hemoglobin to form stable adducts, the structures of which, based on /sup 13/C NMR studies, are proposed to be diastereomeric 2-methyl imidazolidin-4-ones. In this scheme, acetaldelhyde forms a reversible Schiff base with the ..cap alpha..-amino groups of the polypeptide chains which cyclize with the amide nitrogen of the first peptide bond to form the stable imidazolidinone adducts. In support of this mechanism, the authors found that in following the reaction of the peptide val-gly-gly with (1,2-/sup 13/C) acetaldehyde, /sup 13/C NMR resonances attributed to a Schiff base (delta = 170 ppm) were observed which slowly disappeared prior to appearance of resonances from a pair of stable adducts (delta = 70 and 71 ppm) believed to be the diastereomeric imidazolidinones. Schiff base formation appeared to limit the overall rate. Tetraglycine reacted in a similar manner but with a resonance from a single stable adduct observed representing the enantiomeric imidazolidinone adducts of this peptide. Peptides with proline in position 2 should be incapable of forming imidazolidinones, and the authors found that ala-pro-gly did in fact fail to form a stable adduct with acetaldehyde. The 2-methyl imidazolidin-4-one adducts of hemoglobin may be useful in determining the contribution of the amino terminal groups to the structure and functional properties of hemoglobins.

  10. High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes.

    PubMed

    Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Rubio, Julio; Gonzales-Castañeda, Cynthia

    2011-12-01

    Chronic mountain sickness (CMS), a lack of adaptation to altitude characterized by excessive erythrocytosis (EE), is a health problem associated with life at high altitude. The erythropoietic process is regulated by both erythropoietin and testosterone. Zinc (Zn) is known to be related with testosterone and hemoglobin levels; meanwhile, nitric oxide was also associated with adaptation to high altitude. The aim of this study was to determine the relationship of hemoglobin and CMS score with serum levels of zinc, total testosterone (TT), calculated free testosterone (cFT), bioavailable testosterone (BAT), hemoglobin, and nitric oxide in men at high altitude with or without EE. Men residing in Lima (150 m) and Cerro de Pasco (4,340 m), Peru, were divided into three groups: (1) low altitude, (2) high altitude without EE (hemoglobin < 21 g/dl), and (3) high altitude with EE (hemoglobin ≥ 21 g/dl). Adjusted multivariable regression models showed that serum testosterone (total or free) and Zn levels were independently correlated with increased hemoglobin levels. Similarly, hemoglobin was positively related with signs/symptoms of CMS; however, both increased the serum Zn and the nitric oxide levels correlated with reduced risk for signs/symptoms of CMS. In conclusion, higher serum testosterone levels and Zn levels were associated with EE, and low scores of signs/symptoms of CMS were associated with higher Zn and nitric oxide levels.

  11. Hemoglobin concentration in men with type 2 diabetes mellitus.

    PubMed

    Harusato, Ichiko; Fukui, Michiaki; Tanaka, Muhei; Shiraishi, Emi; Senmaru, Takafumi; Sakabe, Kazumi; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

    2010-06-01

    Anemia is a common but often overlooked complication of diabetes. We investigated the relationship between hemoglobin concentration and various factors as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Hemoglobin concentration was measured in 319 men with type 2 diabetes mellitus. We evaluated the relationship between hemoglobin concentration and various factors including age, body mass index, and glycemic control, as well as between hemoglobin concentration and pulse wave velocity or ankle-brachial index (n = 209) and between hemoglobin concentration and carotid intima-media thickness or plaque score (n = 125). Mean hemoglobin concentration was 14.2 +/- 0.80 g/dL. Body mass index (r = 0.340, P < .0001) and estimated glomerular filtration rate (r = 0.219, P = .0011) were positively associated with hemoglobin concentration, whereas age (r = -0.388, P < .0001), glycated albumin (r = -0.148, P = .0121), serum creatinine concentration (r = -0.206, P = .0019), and log (urinary albumin excretion) (r = -0.188, P = .0010) were negatively associated with hemoglobin concentration. Multiple regression analysis identified age (beta = -0.222, P = .0019), body mass index (beta = 0.145, P = .0432), systolic blood pressure (beta = 0.214, P = .0015), total cholesterol concentration (beta = 0.170, P = .0077), and serum creatinine concentration (beta = -0.181, P = .0045) as independent determinants of hemoglobin concentration. No significant association was observed between hemoglobin concentration and serum erythropoietin concentration (r = -0.079, P = .2980). Negative correlations were found between hemoglobin concentration and pulse wave velocity (r = -0.289, P < .0001) and between hemoglobin concentration and plaque score (r = -0.275, P = .0024). In conclusion, hemoglobin concentration was associated with various factors; and decreased hemoglobin concentration was associated with subclinical markers of atherosclerosis in men with type 2

  12. Measurements of plasma zinc

    PubMed Central

    Davies, I. J. T.; Musa, M.; Dormandy, T. L.

    1968-01-01

    Zinc is an essential trace element. Previous methods of measuring zinc in clinical material have been difficult and reported findings must be treated with caution. Using atomic absorption spectroscopy it has been established that plasma zinc is one of the most uniform biochemical characteristics of normal adult blood. Sex and age differences in adult life are insignificant. Increased metabolic activity, on the other hand, induces a marked, immediate fall in plasma zinc level. The possible implications of this are discussed. Zinc levels in patients with diabetes mellitus, cardiovascular disease, and anaemia due to acute blood loss have been within normal limits. Plasma zinc is low in certain types of liver disease. PMID:5303355

  13. Is zinc a neuromodulator?

    PubMed

    Kay, Alan R; Tóth, Katalin

    2008-01-01

    The vesicles of certain glutamatergic terminals in the mammalian forebrain are replete with ionic zinc. It is believed that during synaptic transmission zinc is released, binds to receptors on the pre- or postsynaptic membranes, and hence acts as a neuromodulator. Although exogenous zinc modulates a wide variety of channels, whether synaptic zinc transits across the synaptic cleft and alters the response of channels has been difficult to establish. We will review the evidence for zinc as a neuromodulator and propose diagnostic criteria for establishing whether it is indeed one. Moreover, we will delineate alternative ways in which zinc might act at synapses.

  14. Responses of Siberian ferrets to secondary zinc phosphide poisoning

    USGS Publications Warehouse

    Hill, E.F.; Carpenter, J.W.

    1982-01-01

    The hazard of operational-type applications of zinc phosphide (Zn3P2) on a species closely related to the black-footed ferret (Mustela nigripes), was evaluated by feeding 16 Siberian ferrets (M. eversmanni) rats that had been killed by consumption of 2% zinc phosphide treated bait or by an oral dose of 40, 80, or 160 mg of Zn3P2. All ferrets accepted rats and a single emesis by each of 3 ferrets was the only evidence of acute intoxication. All ferrets learned to avoid eating gastrointestinal tracts of the rats. Subacute zinc phosphide toxicity in the ferrets was indicated by significant decreases (18-48%) in hemoglobin, increases of 35-91 % in serum iron, and elevated levels of serum globulin, cholesterol, and triglycerides. Hemoglobin/iron, urea nitrogen/creatinine, and albumin/globulin ratios also were altered by the treatments. This study demonstrated that Siberian ferrets, or other species with a sensitive emetic reflex, are afforded a degree of protection from acute zinc phosphide poisoning due to its emetic action. The importance of toxicity associated with possible respiratory, liver, and kidney damage indicated by altered blood chemistries is not known.

  15. Evaluation of Gallium as a Tracer of Exogenous Hemoglobin-Haptoglobin Complexes for Targeted Drug Delivery Applications

    NASA Astrophysics Data System (ADS)

    Xu, Shengsheng; Kaltashov, Igor A.

    2016-09-01

    Haptoglobin (Hp) is a plasma glycoprotein that generates significant interest in the drug delivery community because of its potential for delivery of antiretroviral medicines with high selectivity to macrophages and monocytes, the latent reservoirs of human immunodeficiency virus. As is the case with other therapies that exploit transport networks for targeted drug delivery, the success of the design and optimization of Hp-based therapies will critically depend on the ability to accurately localize and quantitate Hp-drug conjugates on the varying and unpredictable background of endogenous proteins having identical structure. In this work, we introduce a new strategy for detecting and quantitating exogenous Hp and Hp-based drugs with high sensitivity in complex biological samples using gallium as a tracer of this protein and inductively coupled plasma mass spectrometry (ICP MS) as a method of detection. Metal label is introduced by reconstituting hemoglobin (Hb) with gallium(III)-protoporphyrin IX followed by its complexation with Hp. Formation of the Hp/Hb assembly and its stability are evaluated with native electrospray ionization mass spectrometry. Both stable isotopes of Ga give rise to an abundant signal in ICP MS of a human plasma sample spiked with the metal-labeled Hp/Hb complex. The metal label signal exceeds the spectral interferences' contributions by more than an order of magnitude even with the concentration of the exogenous protein below 10 nM, the level that is more than adequate for the planned pharmacokinetic studies of Hp-based therapeutics.

  16. Studies of hemoglobin denaturation and Heinz body formation in the unstable hemoglobins.

    PubMed

    Winterbourn, C C; Carrell, R W

    1974-09-01

    The sequential changes that occur during the precipitation on mild heating of the unstable hemoglobins, Hb Christchurch, Hb Sydney, Hb Köln, and Hb A, were examined with particular attention to the possibility of an accompanying oxidative process. Hb Christchurch, Hb Sydney, and Hb A precipitated with equal amounts of alpha- and beta-chains and full heme complement. Hb Köln, however, was one-half hemedepleted and showed a slight excess of precipitated beta-chains. In all cases the spectrum of the precipitated material was typical of a hemichrome. There was no evidence that sulfhydryl oxidation contributed to the precipitation process. Reduced glutathione was unable to protect the hemoglobin against precipitation, and mixed disulfide formation between the precipitating hemoglobin and glutathione was insignificant, even in the presence of excess glutathione. No blockade of beta93 cysteines could be demonstrated in the unstable hemoglobins. Precipitation of oxyhemoglobin and carboxyhemoglobin in all cases gave nonspecific oxidation of approximately two of the six hemoglobin sulfhydryl groups to give intra- and intermolecular disulfide bonds. Single alpha- and beta-chains, plus polymers of up to five or six chains linked by disulfide bridges, were demonstrated by polyacrylamide gel electrophoresis. This disulfide oxidation was not observed with deoxy- or methemoglobin and did not appear to influence the rate of precipitation. These findings fit the theoretical prediction that autoxidation of oxy- and carboxyhemoglobin is accompanied by formation of a free radical, with the reactions of this free radical being confined intramolecularly.Together, these results are in keeping with predictions based on the known structural abnormalities of the unstable hemoglobins, all of which result in greater molecular flexibility. Our findings support the conclusion that the usual precipitating event is altered bonding at the heme to give the formation of hemichromes. There is no

  17. Zinc oxide overdose

    MedlinePlus

    Zinc oxide is an ingredient in many products. Some of these are certain creams and ointments used ... prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone eats one of ...

  18. Bacitracin zinc overdose

    MedlinePlus

    ... Small amounts of bacitracin zinc are dissolved in petroleum jelly to create antibiotic ointments. Bacitracin zinc overdose ... is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation ...

  19. Possibilities of Using Fetal Hemoglobin as a Platform for Producing Hemoglobin-Based Oxygen Carriers (HBOCs).

    PubMed

    Ratanasopa, Khuanpiroon; Cedervall, Tommy; Bülow, Leif

    2016-01-01

    The expression levels of fetal hemoglobin (HbF) in bacterial recombinant systems are higher compared with normal adult hemoglobin (HbA). However, heme disorientation in globins are often observed in recombinant production processes, both for HbA and HbF, although the degree of heme oriental disorder is much lower for HbF. In addition, the heme disorientation can be converted to a normal conformation by an oxidation-reduction process. A chromatographic cleaning process involving a strong anion exchanger can be utilized to remove such unstable and nondesirable forms of Hb.

  20. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  1. Mini-hemoglobins from nemertean worms.

    PubMed

    Vandergon, Thomas L; Riggs, Austen F

    2008-01-01

    Hemoglobins (Hbs) found in members of the phylum Nemertea are smaller than any other known Hb molecules. These mini-Hbs have been of great interest because of their unique three-dimensional structure and their stable ligand-binding properties. Also of interest is the expression of mini-Hb in neural tissue, body wall muscle tissue, and red blood cells. This chapter outlines methods that may be used to isolate and purify functional mini-Hbs from all three tissue types in nemertean worms.

  2. Neutral changes during divergent evolution of hemoglobins

    NASA Technical Reports Server (NTRS)

    Jukes, T. H.

    1978-01-01

    A comparison of the mRNAs for rabbit and human beta-hemoglobins shows that synonymous changes in codons have accumulated three times as rapidly as nucleotide replacements that produced changes in amino acids. This agrees with predictions based on the so-called neutral theory. In addition, seven codon changes that appear to be single-base changes (according to maximum parsimony) are actually two-base changes. This indicates that the construction of primordial sequences is of limited significance when based on inferences that assume minimum base changes for amino acid replacements.

  3. Zinc oxyfluoride transparent conductor

    SciTech Connect

    Gordon, R.G.

    1991-02-05

    Transparent, electrically conductive and infrared-reflective films of zinc oxyfluoride are produced by chemical vapor deposition from vapor mixtures of zinc, oxygen and fluorine-containing compounds. The substitution of fluorine for some of the oxygen in zinc oxide results in dramatic increases in the electrical conductivity. For example, diethyl zinc, ethyl alcohol and hexafluoropropene vapors are reacted over a glass surface at 400 C to form a visibly transparent, electrically conductive, infrared reflective and ultraviolet absorptive film of zinc oxyfluoride. Such films are useful in liquid crystal display devices, solar cells, electrochromic absorbers and reflectors, energy-conserving heat mirrors, and antistatic coatings. 8 figures.

  4. Zinc oxyfluoride transparent conductor

    DOEpatents

    Gordon, Roy G.

    1991-02-05

    Transparent, electrically conductive and infrared-reflective films of zinc oxyfluoride are produced by chemical vapor deposition from vapor mixtures of zinc, oxygen and fluorine-containing compounds. The substitution of fluorine for some of the oxygen in zinc oxide results in dramatic increases in the electrical conductivity. For example, diethyl zinc, ethyl alcohol and hexafluoropropene vapors are reacted over a glass surface at 400.degree. C. to form a visibly transparent, electrically conductive, infrared reflective and ultraviolet absorptive film of zinc oxyfluoride. Such films are useful in liquid crystal display devices, solar cells, electrochromic absorbers and reflectors, energy-conserving heat mirrors, and antistatic coatings.

  5. The High Prevalence of Anemia in Cambodian Children and Women Cannot Be Satisfactorily Explained by Nutritional Deficiencies or Hemoglobin Disorders

    PubMed Central

    Wieringa, Frank Tammo; Dahl, Miriam; Chamnan, Chhoun; Poirot, Etienne; Kuong, Khov; Sophonneary, Prak; Sinuon, Muth; Greuffeille, Valerie; Hong, Rathavuth; Berger, Jacques; Dijkhuizen, Marjoleine Amma; Laillou, Arnaud

    2016-01-01

    Background: Anemia is highly prevalent in Cambodian women and children, but data on causes of anemia are scarce. We performed a national micronutrient survey in children and women that was linked to the Cambodian Demographic Health Survey 2014 (CDHS-2014) to assess the prevalence of micronutrient deficiency, hemoglobin disorders and intestinal parasite infection. Methods: One-sixth of households from the CDHS-2014 were selected for a follow-up visit for the micronutrient survey. Households were visited from two weeks to two months after the CDHS-2014 visit. Data on micronutrient status were available for 1512 subjects (792 children and 720 women). Results: Anemia was found in 43% of the women and 53% of the children. Hemoglobin disorders affected >50% of the population, with Hemoglobin-E the most prevalent disorder. Deficiencies of iron (ferritin < 15 g/L), vitamin A (retinol-binding-protein (RBP) < 0.70 mol/L) or vitamin B12 (<150 pmol/L) were not prevalent in the women (<5% for all), whereas 17.8% of the women had low concentrations of folic acid (<10 nmol/L). In the children, the prevalence of iron, vitamin A, vitamin B12 or folic acid deficiency was <10%. Zinc deficiency, hookworm infection and hemoglobinopathy were significantly associated with anemia in children, whereas in the women none of the factors was significantly associated with anemia. Iron deficiency anemia (IDA) was more prevalent in children <2 years, but in older children and women, the prevalence of IDA was <5%. The most prevalent, preventable causes of anemia were hookworm infection and zinc and folic acid deficiency. Over 40% of the anemia was not caused by nutritional factors. Conclusion: The very high prevalence of anemia in Cambodian women and children cannot be explained solely by micronutrient deficiencies and hemoglobin disorders. Micronutrient interventions to improve anemia prevalence are likely to have limited impact in the Cambodian setting. The focus of current interventions to

  6. Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Isolation of an NN-bridged benzyne-protoporphyrin IX adduct.

    PubMed

    Ortiz de Montellano, P R; Mathews, J M

    1981-06-01

    Destruction of hepatic cytochrome P-450 during catalytic processing of 1-amino-benzotriazole is accompanied by an equal loss of microsomal haem but not by loss of cytochrome b5, or stimulation of lipid peroxidation. An abnormal porphyrin, tentatively identified as an NN-bridged benzyne-protoporphyrin IX adduct, appears to be formed by the addition of catalytically generated benzyne to prosthetic haem.

  7. Polymeric nanoparticles for hemoglobin-based oxygen carriers.

    PubMed

    Piras, Anna Maria; Dessy, Alberto; Chiellini, Federica; Chiellini, Emo; Farina, Claudio; Ramelli, Massimiliano; Della Valle, Elena

    2008-10-01

    This article reports on the current status of the research on blood substitutes with particular attention on hemoglobin-based oxygen carriers (HBOCs). Insights on the physiological role of hemoglobin are reported in the view of the development of both acellular and cellular hemoglobin-based oxygen carriers. Attention is then focused on biocompatible polymeric materials that find application as matrices for cellular based HBOCs and on the strategies employed to avoid methemoglobin formation. Results are reported regarding the use of bioerodible polymeric matrices based on hemiesters of alternating copolymer (maleic anhydride-co-butyl vinyl ether) for the preparation of hemoglobin loaded nanoparticles.

  8. WAXS studies of the structural diversity of hemoglobin in solution.

    SciTech Connect

    Makowski, L.; Bardhan, J.; Gore, D.; Lal, J.; Mandava, S.; Park, S.; Rodi, D. J.; Ho, N. T.; Ho, C.; Fischetti, R. F.

    2011-01-01

    Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobin structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structure.

  9. Characterization of the hemoglobin of the backswimmer Anisops deanei (Hemiptera).

    PubMed

    Wawrowski, Agnes; Matthews, Philip G D; Gleixner, Eva; Kiger, Laurent; Marden, Michael C; Hankeln, Thomas; Burmester, Thorsten

    2012-09-01

    While O(2)-binding hemoglobin-like proteins are present in many insects, prominent amounts of hemoglobin have only been found in a few species. Backswimmers of the genera Anisops and Buenoa (Notonectidae) have high concentrations of hemoglobin in the large tracheal cells of the abdomen. Oxygen from the hemoglobin is delivered to a gas bubble and controls the buoyant density, which enables the bugs to maintain their position without swimming and to remain stationary in the mid-water zone where they hunt for prey. We have obtained the cDNA sequences of three Anisops deanei hemoglobin chains by RT-PCR and RACE techniques. The deduced amino acid sequences show an unusual insertion of a single amino acid in the conserved helix E, but this does not affect protein stability or ligand binding kinetics. Recombinant A. deanei hemoglobin has an oxygen affinity of P(50) = 2.4 kPa (18 torr) and reveals the presence of a dimeric fraction or two different conformations. The absorption spectra demonstrate that the Anisops hemoglobin is a typical pentacoordinate globin. Phylogenetic analyses show that the backswimmer hemoglobins evolved within Heteroptera and most likely originated from an intracellular hemoglobin with divergent function. PMID:22575160

  10. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  11. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  12. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  13. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  14. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  15. [Zinc and gastrointestinal disorders].

    PubMed

    Higashimura, Yasuki; Takagi, Tomohisa; Naito, Yuji

    2016-07-01

    Zinc, an essential trace element, affects immune responses, skin metabolism, hormone composition, and some sensory function, so that the deficiency presents various symptoms such as immunodeficiency and taste obstacle. Further, the zinc deficiency also considers as a risk of various diseases. Recent reports demonstrated that -20% of the Japanese population was marginally zinc deficiency, and over 25% of the global population is at high risk of zinc deficiency. In gastrointestinal disorders, zinc plays an important role in the healing of mucosal and epithelial damage. In fact, polaprezinc, a chelate compound of zinc and L-carnosine, has been used for the treatment of gastric ulcer and gastritis. We describe here the therapeutic effect of zinc on gastrointestinal disorders. PMID:27455800

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

    PubMed

    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.

  17. LCAA, a Novel Factor Required for Magnesium Protoporphyrin Monomethylester Cyclase Accumulation and Feedback Control of Aminolevulinic Acid Biosynthesis in Tobacco1[W][OA

    PubMed Central

    Albus, Christin Anne; Salinas, Annabel; Czarnecki, Olaf; Kahlau, Sabine; Rothbart, Maxi; Thiele, Wolfram; Lein, Wolfgang; Bock, Ralph; Grimm, Bernhard; Schöttler, Mark Aurel

    2012-01-01

    Low Chlorophyll Accumulation A (LCAA) antisense plants were obtained from a screen for genes whose partial down-regulation results in a strong chlorophyll deficiency in tobacco (Nicotiana tabacum). The LCAA mutants are affected in a plastid-localized protein of unknown function, which is conserved in cyanobacteria and all photosynthetic eukaryotes. They suffer from drastically reduced light-harvesting complex (LHC) contents, while the accumulation of all other photosynthetic complexes per leaf area is less affected. As the disturbed accumulation of LHC proteins could be either attributable to a defect in LHC biogenesis itself or to a bottleneck in chlorophyll biosynthesis, chlorophyll synthesis rates and chlorophyll synthesis intermediates were measured. LCAA antisense plants accumulate magnesium (Mg) protoporphyrin monomethylester and contain reduced protochlorophyllide levels and a reduced content of CHL27, a subunit of the Mg protoporphyrin monomethylester cyclase. Bimolecular fluorescence complementation assays confirm a direct interaction between LCAA and CHL27. 5-Aminolevulinic acid synthesis rates are increased and correlate with an increased content of glutamyl-transfer RNA reductase. We suggest that LCAA encodes an additional subunit of the Mg protoporphyrin monomethylester cyclase, is required for the stability of CHL27, and contributes to feedback-control of 5-aminolevulinic acid biosynthesis, the rate-limiting step of chlorophyll biosynthesis. PMID:23085838

  18. Alkaline Bohr effect of human hemoglobin Ao.

    PubMed

    Di Cera, E; Doyle, M L; Gill, S J

    1988-04-01

    Differential oxygen binding measurements obtained over the pH range 6.95 to 9.10 at 25 degrees C have allowed a detailed description of the alkaline Bohr effect of human hemoglobin Ao. Phenomenological analysis of the data in terms of the Adair equation shows that: (1) the oxygen binding curves are asymmetrical with the population of the triply oxygenated species being negligible throughout the pH range studied: (2) the shape of the oxygen binding curve is affected by pH, especially at low saturation; and (3) the maximum O2-proton linkage is -0.52 mole of proton per mole of oxygen at pH 7.4. A possible molecular mechanism of the Bohr effect is proposed within the framework of an allosteric model which accounts for the low population of triply oxygenated hemoglobin species. At least three Bohr groups are necessary for a quantitative description of the alkaline Bohr effect. Two of these groups titrate in the range of the His146 beta and Vall alpha residues, which have long been identified as the main alkaline Bohr groups, and altogether contribute 84% of the alkaline Bohr effect at physiological pH. A third ionizable group, linked to oxygenation presumably at the beta chains, is implicated and is titrated in a pH range characteristic of a surface histidyl residue.

  19. Hemoglobin alpha in the blood vessel wall

    PubMed Central

    Butcher, Joshua T.; Johnson, Tyler; Beers, Jody; Columbus, Linda; Isakson, Brant E

    2014-01-01

    Hemoglobin has been studied and well haracterized in red blood cells for over one hundred years. However, new work has indicated that the hemoglobin alpha subunit (Hbα) is also found within the blood vessel wall, where it appears to localize at the myoendothelial junction (MEJ) and plays a role in regulating nitric oxide (NO) signaling between endothelium and smooth muscle. This discovery has created a new paradigm for control of endothelial nitric oxide synthase activity, nitric oxide diffusion, and ultimately, control of vascular tone and blood pressure. This review will discuss the current knowledge of hemoglobin’s properties as a gas exchange molecule in the blood stream, and extrapolate the properties of Hbα biology to the MEJ signaling domain. Specifically, we propose that Hbα is present at the MEJ to regulate NO release and diffusion in a restricted physical space, which would have powerful implications for the regulation of blood flow in peripheral resistance arteries. PMID:24832680

  20. Rare hemoglobin variants in Tunisian population.

    PubMed

    Zorai, A; Moumni, I; Mosbahi, I; Douzi, K; Chaouachi, D; Guemira, F; Abbes, S

    2015-04-01

    During the last 30 years, many studies concerning hemoglobinopathies were realized among Tunisians. More than twenty different thalassemic alleles were detected on the β-globin gene, and less are affecting the α-globin genes. Unusual hemoglobin (Hb) variants other than Hb S, Hb C, and Hb O-arab, which are the most frequent variants in Tunisia, were also detected. Eight Tunisian subjects were studied at phenotypic and molecular levels. Hematological indices and hemoglobin (Hb) pattern were performed by alkaline electrophoresis and isoelectric focusing (IEF),and the Hb fractions were quantitated by cation exchange HPLC. On genomic level, coding regions were amplified by polymerase chain reaction (PCR) followed by a sequencing of the purified PCR products using the dye terminator method. Seven uncommon Hb variants were detected and described for the first time among Tunisians. HbA2-Tunis [δ46(CD5), Gly → Glu, GGG → GAG] is the newly described δ-chain variant in our laboratory, and some other variants (Hb Constant Spring, G San Jose, and Hb J-Bangkok) are very uncommon in the Mediterranean region. We present here an updated review of the Hb variants detected among Tunisians. Twenty-one rare Hb variants were detected affecting the α1-, α2-, δ-, γ-, and β-globin genes, leading in some cases to a severe phenotype especially when the stability is completely altered. The ethnical history of Tunisia could explain this important variability of the observed rare Hb variants. PMID:24905386

  1. Liposome-encapsulated hemoglobin processing methods.

    PubMed

    Zheng, S; Zheng, Y; Beissinger, R L; Fresco, R

    1992-01-01

    An effective and safe red blood cell substitute is being developed based on double emulsion/evaporation techniques followed by high pressure homogenization to form liposome-encapsulated hemoglobin (LEH). Formulations are made up of hydrogenated phosphatidylcholine (PC, soy or egg), cholesterol, phosphatidylinositol (PI), and alpha-tocopherol in a molar ratio of 1:1:0.2:0.02, respectively. Resulting LEH-encapsulated hemoglobin (Hb) concentrations are greater than 80% of precursor Hb solutions. Met-Hb generation accompanying LEH processing appears to be small with only a 3% increase for encapsulated over precursor. These results correspond to an oxygen content for an LEH suspension sample (50% by volume LEH) of 15 volume% oxygen. Oxygen affinity and cooperativity values for LEH suspensions appear to be near the normal values expected for whole blood. The viscosity of LEH suspension samples (50% by volume LEH in phosphate-buffered saline containing 7.5 wt% albumin) were slightly higher than that of whole blood. The effect of shear rate on leakage of encapsulated Hb from LEH was small, i.e. 0.5% or less. Nearly total isovolemic exchange transfusion using a cannulated rat model demonstrates efficacy of LEH suspension samples. There appears to be no difference in rat internal organ weights between rats exchanged with control compared to rats exchanged with LEH. Circulation half-life following 50% isovolemic exchange-transfusion is about 15 to 18 hours. PMID:1391451

  2. Formation of protoporphyrin IX in mouse skin after topical application of 5-aminolevulinic acid and its methyl esther

    NASA Astrophysics Data System (ADS)

    Sorensen, Roar; Juzenas, Petras; Iani, Vladimir; Moan, Johan

    1999-02-01

    Normal skin of nude mice (Balb/c) was treated topically with 5-aminolevulinic acid (ALA) and its methyl ester (ALA-Me) for 24 hours. Approximately 0.1 gram of freshly prepared cream was applied to a spot of 1 cm2 on the flank of the mice, which was then covered with a transparent dressing. The ALA induced protoporphyrin IX (PpIX) was studied by means of a noninvasive fiber-optic fluorescence probe connected to a luminescence spectrometer. The excitation wavelength was 407 nm, and the emission wavelength was 637 nm. For the first hour a slight lag in PpIX production was observed for the mice treated with ALA-Me compared to the mice treated with ALA. After approximately 12 hours the ALA and the ALA-Me treated mice showed the same PpIX fluorescence intensity. From 12 hours until 24 hours the PpIX fluorescence intensity decreased for both treatment modalities, even though ALA and ALA-Me were continuously present. At 24 hours ALA-Me-treated mice had less than half the amount of PpIX in their skin compared with ALA- treated mice.

  3. Clearance of protoporphyrin IX from mouse skin after topical application of 5-aminolevulinic acid and its methyl ester

    NASA Astrophysics Data System (ADS)

    Juzenas, Petras; Sorensen, Roar; Iani, Vladimir; Moan, Johan

    1999-02-01

    The clearance of protoporphyrin IX (PpIX) from the skin of hairless BALB/c mice after topical application of 5- aminolevulinic acid (ALA) and its methyl ester (ALA-Me) was investigated. Creams containing 2 or 20% of ALA or ALA-Me were topically applied on spots of approximately 1 cm2 for 12 hours. The PpIX fluorescence was detected by the means of a Perkin Elmer LS50B luminescence spectrometer equipped with a fiber-optic probe. The emission spectrum was identical with that of cell-bound PpIX. After 12 hours application of ALA and ALA-Me similar amounts of PpIX were found. After creme removal the ALA-induced PpIX fluorescence decayed with a half-life of about 20 hours (20% ALA cream). The ALA-Me-induced PpIX was faster cleared from the skin than ALA-induced PpIX, and had a half-life of about 7 hours (20% ALA-Me cream).

  4. Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection

    NASA Astrophysics Data System (ADS)

    Jiang, Ching-Fen; Wang, Chih-Yu; Chiang, Chun-Ping

    2011-07-01

    Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R/B ratio, and R/G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R/G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer.

  5. Levels of delta-aminolevulinate dehydratase, uroporphyrinogen-I synthase, and protoporphyrin IX in erythrocytes from anemic mutant mice.

    PubMed Central

    Sassa, S; Bernstein, S E

    1977-01-01

    Levels of erythrocyte delta-aminolevulinate dehydratase [ALA-dehydratase; porphobilinogen synthase; 5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2.1.24], UROPORPHYRINOGEN-I synthase [Uro-synthase; porphobilinogen ammonia-lyase (polymerizing), EC 4.3;1.8], AND PROTOPORPHYRIN IX (Proto) were measured by sensitive semimicroassays using 2-5 mul of whole blood obtained from normal and anemic mutant mice. The levels of erythrocyte ALA-dehydratase and Uro-synthase showed marked developmental changes and ALA-dehydratase was influenced by the Lv gene. Mice with overt hemolytic diseases (ja/ja, sph/sph, nb/nb, ha/ha) had 10- to 20-fold increases in ALA-dehydratase, Uro-synthase, and Proto compared with their normal controls. Mice with an iron deficiency (mk/mk) and mice with hypoplastic anemias (W/Wv, Sl/Sld, an/an) had mild to moderate increases in these parameters. Elevated enzyme activities and Proto correlated well with the number of reticulocytes. Because all mice with anemias possessed elevated levels of ALA-dehydratase, Uro-synthase, and Proto independent of differences in their genotypes, the increase in these parameters is not likely to be the result of a specific gene defect. The increased enzyme activities and Proto concentration probably reflect increased frequency of young red cells that are still active in heme biosynthesis. PMID:265562

  6. The effect of air cooling pain relief on protoporphyrin IX photobleaching and clinical efficacy during dermatological photodynamic therapy.

    PubMed

    Tyrrell, J; Campbell, S M; Curnow, A

    2011-04-01

    Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized to successfully treat licensed indications (e.g. actinic keratosis (AK), superficial basal cell carcinoma (sBCC) and Bowen's disease (BD)) in the UK. Air cooling devices (ACD) are commonly utilized as a method of pain relief, however the effect of this on treatment outcome has never been extensively investigated. This non-randomized, retrospective observational controlled study investigated whether the application of the ACD limited photosensitiser (protoporphyrin IX - PpIX) photobleaching during irradiation and/or subsequent clinical outcome. Patients utilizing the ACD throughout treatment were observed to undergo significantly less PpIX photobleaching than the control group (P<0.001) and complete clinical clearances observed at 3 months were also reduced within the ACD group. Separate analysis of the different lesion types indicated that significantly less photobleaching occurred in AK lesions with ACD and all lesion types failed to fully utilize the accumulated PpIX when ACD was employed. The application of the ACD as pain relief during light irradiation therefore resulted in lower PpIX photobleaching which corresponded to a reduction in the efficacy of PDT treatment. Whilst the ACD is an effective method of dermatological PDT analgesia it should be utilized as sparingly as possible to minimize any deleterious effects on treatment outcome.

  7. Oxygen Availability for Porphyrin Biosynthesis Enzymes Determines the Production of Protoporphyrin IX (PpIX) during Hypoxia.

    PubMed

    Otsuka, Shimpei; Matsumoto, Kentaro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-Ichiro

    2015-01-01

    5-Aminolevulinic acid (ALA), a precursor of porphyrin, is specifically converted to the fluorescent substance protoporphyrin IX (PpIX) in tumors to be used as a prodrug for photodynamic therapy and diagnosis. Hypoxia, a common feature of solid tumors, decreases the efficacy of ALA-based photodynamic therapy and diagnosis. This decrease results from the excretion of porphyrin precursor coproporphyrinogen III (CPgenIII), an intermediate in the biosynthesis of PpIX. However, the mechanism of CPgenIII excretion during hypoxia remains unclear. In this study, we revealed the importance of mitochondrial respiration for the production of PpIX during hypoxia. Porphyrin concentrations were estimated in human gastric cancer cell lines by HPLC. Expression levels of porphyrin biosynthesis genes were measured by qRT-PCR and immunoblotting. Blockage of porphyrin biosynthesis was an oxygen-dependent phenomenon resulting from decreased PpIX production in mitochondria under hypoxic conditions. PpIX production was increased by the inhibition of mitochondrial respiration complexes, which indicates that the enzymes of porphyrin biosynthesis compete with respiration complexes for molecular oxygen. Our results indicate that targeting the respiration complexes is a rationale for enhancing the effect of ALA-mediated treatment and diagnosis. PMID:26717566

  8. Sensitization and photodynamic therapy of esophageal,duodenal, and colonic tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX)

    NASA Astrophysics Data System (ADS)

    Mlkvy, Peter; Messmann, Helmut; Regula, Jaroslaw; Conio, M.; Pauer, M.; Millson, Charles E.; MacRobert, Alexander J.; Bown, Stephen G.

    1995-03-01

    Five aminolaevulinic acid (ALA) is a promising agent for PDT sensitization as it can be given orally and only causes skin photosensitivity for 1 - 2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors (M 17, F 9; mean age 79) were given 30 - 60 mg ALA orally (single or divided doses) and biopsies taken of tumor and normal tissue at 1 - 24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in oesophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in the colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare fiber or diffuser, 50 - 100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5 - 1.5 mm depth. PDT with ALA is simple, safe, and promising for tumors in the GI tract. Modification of treatment parameters may make it suitable for larger lesions.

  9. Photoinactivation of Staphylococcus aureus using protoporphyrin IX: the role of haem-regulated transporter HrtA.

    PubMed

    Nakonieczna, Joanna; Kossakowska-Zwierucho, Monika; Filipiak, Michalina; Hewelt-Belka, Weronika; Grinholc, Mariusz; Bielawski, Krzysztof Piotr

    2016-02-01

    Light- and photosensitiser-based antimicrobial photodynamic therapy is a very promising approach to the control of microbial infections. How the phenotypic features of a microorganism affect its response to photosensitiser-based photokilling represents an area of substantial research interest. To understand the mechanisms governing the phenomenon of a strain-dependent response to photodynamic inactivation (PDI), we analysed the possible role of the membrane-located haem transporter HrtA in Staphylococcus aureus. We used a S. aureus strains with an inactivated component of the haem-regulated transporter, HrtA, along with its wild-type counterpart to determine differences in PDI outcome and photosensitiser uptake between the studied isogenic strains. We observed that a lack of HrtA protein potentiates the phototoxic effect towards S. aureus but only when extracellular protoporphyrin IX is used. The observed effect may depend on the function of the HrtA transporter but is likely to result from changed membrane properties following the absence of the protein in the membrane. This indicates that disturbing the membrane properties is an attractive method for improving the efficacy of the photodynamic inactivation of microorganisms.

  10. In-vitro study on ALA-induced endogenous protoporphyrin IX as photosensitizer for photodynamic tumor diagnosis and therapy

    NASA Astrophysics Data System (ADS)

    Ueberriegler, K.; Fiedler, D.; Verwanger, Thomas; Schnitzhofer, Gerlinde; Banieghbal, E.; Krammer, Barbara E.

    1998-07-01

    Photodynamic tumor diagnosis and therapy is efficiently carried out by endogenous protoporphyrin IX as photosensitizer, induced by external addition of the precursor 5-aminolevulinic acid (ALA). In the present study, PpIX localization and photodynamically induced damage was investigated in normal and transformed human fibroblasts. PpIX formation reaches its maximum after incubation for at least 20 h with 700 (mu) g/m1 ALA, and increases with the pH- value. ALA has to be given 20-30 times more than external PpIX in order to produce the same cytotoxic damage. As detected by Low Light Imaging, PpIX is generated in the mitochondria, released to the cytoplasm and distributed to cytoplasma and nuclear membranes.The nucleus is not stained. Intracellular targets of PpIX damage after irradiation are mainly mitochondria, ER and nuclear membrane. The organelles show a decomposition pattern, which resembles apoptotic morphology and occurs faster in the co-cultivated transformed than in the normal cells. ALA-treated hepatocytes produce micronuclei and chromosomal aberrations, which indicates some mutagenic potential. Expression studies of the (proto)oncogenes c-myc and bcl-2 sublethally treated fibroblasts by quantitative RT-PCR show high deviations from the constitutive expression level, which are accompanied by cell cycle disturbances, indicating a possible precursor role to apoptosis introduction.

  11. Oxygen Availability for Porphyrin Biosynthesis Enzymes Determines the Production of Protoporphyrin IX (PpIX) during Hypoxia

    PubMed Central

    Otsuka, Shimpei; Matsumoto, Kentaro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    5-Aminolevulinic acid (ALA), a precursor of porphyrin, is specifically converted to the fluorescent substance protoporphyrin IX (PpIX) in tumors to be used as a prodrug for photodynamic therapy and diagnosis. Hypoxia, a common feature of solid tumors, decreases the efficacy of ALA-based photodynamic therapy and diagnosis. This decrease results from the excretion of porphyrin precursor coproporphyrinogen III (CPgenIII), an intermediate in the biosynthesis of PpIX. However, the mechanism of CPgenIII excretion during hypoxia remains unclear. In this study, we revealed the importance of mitochondrial respiration for the production of PpIX during hypoxia. Porphyrin concentrations were estimated in human gastric cancer cell lines by HPLC. Expression levels of porphyrin biosynthesis genes were measured by qRT-PCR and immunoblotting. Blockage of porphyrin biosynthesis was an oxygen-dependent phenomenon resulting from decreased PpIX production in mitochondria under hypoxic conditions. PpIX production was increased by the inhibition of mitochondrial respiration complexes, which indicates that the enzymes of porphyrin biosynthesis compete with respiration complexes for molecular oxygen. Our results indicate that targeting the respiration complexes is a rationale for enhancing the effect of ALA-mediated treatment and diagnosis. PMID:26717566

  12. Proton-Coupled Electron Transfer Reactions at a Heme-Propionate in an Iron-Protoporphyrin-IX Model Compound

    PubMed Central

    2011-01-01

    A heme model system has been developed in which the heme-propionate is the only proton donating/accepting site, using protoporphyrin IX-monomethyl esters (PPIXMME) and N-methylimidazole (MeIm). Proton-coupled electron transfer (PCET) reactions of these model compounds have been examined in acetonitrile solvent. (PPIXMME)FeIII(MeIm)2-propionate (FeIII~CO2) is readily reduced by the ascorbate derivative 5,6-isopropylidine ascorbate to give (PPIXMME)FeII(MeIm)2-propionic acid (FeII~CO2H). Excess of the hydroxylamine TEMPOH or of hydroquinone similarly reduce FeIII~CO2, and TEMPO and benzoquinone oxidize FeII~CO2H to return to FeIII~CO2. The measured equilibrium constants, and the determined pKa and E1/2 values, indicate that FeII~CO2H has an effective bond dissociation free energy (BDFE) of 67.8 ± 0.6 kcal mol–1. In these PPIX models, electron transfer occurs at the iron center and proton transfer occurs at the remote heme propionate. According to thermochemical and other arguments, the TEMPOH reaction occurs by concerted proton-electron transfer (CPET), and a similar pathway is indicated for the ascorbate derivative. Based on these results, heme propionates should be considered as potential key components of PCET/CPET active sites in heme proteins. PMID:21524059

  13. Photophysical studies of tin(IV)-protoporphyrin: Potential phototoxicity of a chemotherapeutic agent proposed for the prevention of neonatal jaundice

    SciTech Connect

    Land, E.J.; McDonagh, A.F.; McGarvey, D.J.; Truscott, T.G. )

    1988-07-01

    The strongly light-absorbing metalloporphyrin tin(IV)-protoporphyrin IX (SnPP) is currently being considered as a chemotherapeutic agent for preventing severe hyperbilirubinemia in newborns, a condition usually treated by phototherapy with visible light. To assess the potential phototoxicity of SnPP the authors studied the photophysics of the drug in aqueous and nonaqueous solutions using laser flash photolysis and pulse radiolysis. Quantum yields for formation of triplet-state excited SnPP were measured, along with triplet lifetimes and extinction coefficients. In addition, they measured quantum yields for the SnPP-photosensitized formation of singlet oxygen in MeO{sup 2}H and in {sup 2}H{sub 2}O containing cetyltrimethylammonium bromide, using a time-resolved luminescence technique. Quantum yields for formation of triplet SnPP from monomeric ground-state SnPP are high, and triplet lifetimes are long. SnPP-photosensitized formation of singlet oxygen in aqueous and nonaqueous solvents was confirmed by the detection of the characteristic luminescence at 1270 nm. These observations suggest that cutaneous photosensitivity arising from singlet-oxygen damage is likely to be an undesirable side-effect of SnPP therapy.

  14. Hemoglobin switching in sheep and goats: occurrence of hemoglobins A and C in the same red cell.

    PubMed

    Nienhuis, A W; Bunn, H F

    1974-09-13

    Sheep and goats switch from the synthesis of hemoglobin A (alpha(2)beta(2)(A)) to hemoglobin C (alpha(2)beta(2)(C)) when made anemic. We have demonstrated the existence of the asymmetrical hybrid hemoglobin, alpha(2)beta(A)beta(C), in the circulating red cells of anemic sheep. These erythroid cells, therefore, synthesized both A and C hemoglobin simultaneously. Thus, the switch appears to be mediated by selective gene expression rather than by a clonal or cellular selective mechanism. PMID:4469671

  15. [Impact of fortified milk on the iron and zinc levels in Mexican preschool children].

    PubMed

    Grijalva-Haro, María Isabel; Chavarria, Elsa Yolanda; Artalejo, Elizabeth; Nieblas, Amparo; Ponce, José Antonio; Robles-Sardin, Alma E

    2014-02-01

    The aim of this study was to assess the efficacy of a national program of consumption of fortified milk "Liconsa" on the nutritional status of iron and zinc in pre-school children (3-5 y). The study was conducted in 77 healthy children of both genders. 54 of them consumed Liconsa fortified milk (GCLFL) and 23 consumed no fortified milk (GR). Iron status was determined by measuring hemoglobin and ferritin and zinc status by serum zinc. The consumption of milk was on free demand and it was estimated at baseline and 6 mo after. Through 24-h recall of measured consumption of iron and zinc in the total diet. Descriptive statistics, Student's t test for independent samples and chi-square test for differences in proportions. Children who consumed fortified milk showed an increase of hemoglobin and ferritin levels [1.13 g/dL (p < 0.05) and 5.83 μg/L (p < 0.05) respectively]. Additionally, a decrease was found of the prevalence of low iron stores from 20.4 to 4.1% (p < 0.05). The serum zinc level showed an increase of 45.2 μg/dL (p < 0.05). At the end of the study no child showed a micronutrient deficiency. Children who did not consume fortified milk Liconsa showed no significant change in their serum iron and zinc values. The average consumption of milk powder Liconsa was 22.7 ± 14.5 g, providing 2.5 mg of daily iron and zinc. Supplied diet 9.2 ± 3.4 mg of iron and 6.9 ± 3 mg of zinc. The consumption of fortified milk had a beneficial effect on the serum levels of iron and zinc in children's social welfare program Liconsa.

  16. Is iron and zinc nutrition a concern for vegetarian infants and young children in industrialized countries?

    PubMed

    Gibson, Rosalind S; Heath, Anne-Louise M; Szymlek-Gay, Ewa A

    2014-07-01

    Well-planned vegetarian diets are considered adequate for all stages of the life cycle, despite limited data on the zinc status of vegetarians during early childhood. The bioavailability of iron and zinc in vegetarian diets is poor because of their higher content of absorption inhibitors such as phytate and polyphenols and the absence of flesh foods. Consequently, children as well as adult vegetarians often have lower serum ferritin concentrations than omnivores, which is indicative of reduced iron stores, despite comparable intakes of total iron; hemoglobin differences are small and rarely associated with anemia. However, data on serum zinc concentrations, the recommended biomarker for identifying population groups at elevated risk of zinc deficiency, are sparse and difficult to interpret because recommended collection and analytic procedures have not always been followed. Existing data indicate no differences in serum zinc or growth between young vegetarian and omnivorous children, although there is some evidence of low serum zinc concentrations in vegetarian adolescents. Some vegetarian immigrants from underprivileged households may be predisposed to iron and zinc deficiency because of nondietary factors such as chronic inflammation, parasitic infections, overweight, and genetic hemoglobin disorders. To reduce the risk of deficiency, the content and bioavailability of iron and zinc should be enhanced in vegetarian diets by consumption of fortified cereals and milk, by consumption of leavened whole grains, by soaking dried legumes before cooking and discarding the soaking water, and by replacing tea and coffee at meals with vitamin C-rich drinks, fruit, or vegetables. Additional recommended practices include using fermented soy foods and sprouting at least some of the legumes consumed. Fortified foods can reduce iron deficiency, but whether they can also reduce zinc deficiency is less certain. Supplements may be necessary for vegetarian children following very

  17. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids. Measurements of free hemoglobin aid in the diagnosis of various hematologic disorders, such as sickle cell anemia, Fanconi's anemia (a rare inherited disease), aplastic anemia (bone marrow does not produce...

  18. Hemoglobin Screening Independently Predicts All-Cause Mortality.

    PubMed

    Fulks, Michael; Dolan, Vera F; Stout, Robert L

    2015-01-01

    Objective .- Determine if the addition of hemoglobin testing improves risk prediction for life insurance applicants. Method .- Hemoglobin results for insurance applicants tested from 1993 to 2007, with vital status determined by Social Security Death Master File follow-up in 2011, were analyzed by age and sex with and without accounting for the contribution of other test results. Results .- Hemoglobin values ≤12.0 g/dL (and possibly ≤13.0 g/dL) in females age 50+ (but not age <50) and hemoglobin values ≤13.0 g/dL in all males are associated with progressively increasing mortality risk independent of the contribution of other test values. Increased risk is also noted for hemoglobin values >15.0 g/dL (and possibly >14.0 g/dL) for all females and for hemoglobin values >16.0 g/dL for males. Conclusion .- Hemoglobin testing can add additional independent risk assessment to that obtained from other laboratory testing, BP and build in this relatively healthy insurance applicant population. Multiple studies support this finding at older ages, but data (and the prevalence of diseases impacting hemoglobin levels) are limited at younger ages. PMID:27584842

  19. Computation Of Facilitated Transport of O2 In Hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1991-01-01

    Report describes computations of unsteady facilitated transport of oxygen through liquid membrane of hemoglobin. Used here, "facilitated transport" means diffusion of permeant through membrane in which that diffusion enhanced by reversible chemical reaction between permeant and membrane. In this case, reversible reactions between hemoglobin and oxygen.

  20. Hemoglobin Screening Independently Predicts All-Cause Mortality.

    PubMed

    Fulks, Michael; Dolan, Vera F; Stout, Robert L

    2015-01-01

    Objective .- Determine if the addition of hemoglobin testing improves risk prediction for life insurance applicants. Method .- Hemoglobin results for insurance applicants tested from 1993 to 2007, with vital status determined by Social Security Death Master File follow-up in 2011, were analyzed by age and sex with and without accounting for the contribution of other test results. Results .- Hemoglobin values ≤12.0 g/dL (and possibly ≤13.0 g/dL) in females age 50+ (but not age <50) and hemoglobin values ≤13.0 g/dL in all males are associated with progressively increasing mortality risk independent of the contribution of other test values. Increased risk is also noted for hemoglobin values >15.0 g/dL (and possibly >14.0 g/dL) for all females and for hemoglobin values >16.0 g/dL for males. Conclusion .- Hemoglobin testing can add additional independent risk assessment to that obtained from other laboratory testing, BP and build in this relatively healthy insurance applicant population. Multiple studies support this finding at older ages, but data (and the prevalence of diseases impacting hemoglobin levels) are limited at younger ages.

  1. Improved zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, P.N. Jr.

    1988-06-21

    The invention comprises an improved rechargeable zinc-air cell/battery having recirculating alkaline electrolyte and a zinc electrode comprising a porous foam support material which carries the active zinc electrode material. 5 figs.

  2. Combinatorics of giant hexagonal bilayer hemoglobins.

    PubMed

    Hanin, L G; Vinogradov, S N

    2000-01-01

    The paper discusses combinatorial and probabilistic models allowing to characterize various aspects of spacial symmetry and structural heterogeneity of the giant hexagonal bilayer hemoglobins (HBL Hb). Linker-dodecamer configurations of HBL are described for two and four linker types (occurring in the two most studied HBL Hb of Arenicola and Lumbricus, respectively), and the most probable configurations are found. It is shown that, for HBL with marked dodecamers, the number of 'normal-marked' pairs of dodecamers in homological position follows a binomial distribution. The group of symmetries of the dodecamer substructure of HBL is identified with the dihedral group D6. Under natural symmetry assumptions, the total dipole moment of the dodecamer substructure of HBL is shown to be zero. Biological implications of the mathematical findings are discussed.

  3. Stroma-free hemoglobin from bovine blood.

    PubMed

    Lima, Maria Celiana P; Andrade, Cristina T

    2007-01-01

    Isolation and purification of bovine hemoglobin (HbBv) was carried out after reaction of whole blood with carbon monoxide. Washing/centrifugation steps were used to eliminate leukocytes, platelets, and plasma proteins. Hypotonic media and ultrasound radiation were used to lyse red blood cells. Lyse by ultrasound was shown to lead to solutions at the highest concentrations in HbBv, and the least concentrations in major phospholipids contaminants. Additional purification procedures were performed to remove membrane proteins and phospholipids. In the first case, proteins were denatured by thermal treatment, and filtered. To eliminate phospholipids, liquid chromatography was used with strong anion exchangers. Purity of HbBv was evaluated by normal phase high performance liquid chromatography (HPLC), electrophoresis, and size-exclusion HPLC. PMID:17701489

  4. Separation and characterization of Menhaden hemoglobin components.

    PubMed

    Pokrywka, G S; Gold, F

    1980-01-01

    Hemolysate from Brevoortia tyrannus (Atlantic Menhaden) consists of two major and two minor components, as determined by ion-exchange chromatography. Oxygen equilibria, flash photolysis and rapid mixing techniques are used to detect functional differences between the two major components, revealing a system analogous to the Trout I-IV system. Menhaden IV exhibits a moderate Root effect and is sensitive to organic phosphate inhibition. Menhaden I exhibits little sensitivity to pH changes or the presence of organic phosphates. These differences are probably based on contrasting kinetic behavior, subunit heterogeneity and replacement of a COOH-terminal histidine residue. Theories accounting for the significance of functional hemoglobin multiplicity are reviewed. By bypassing the normal physiological unloading mechanisms, Menhaden I may be functioning as an oxygen reservoir, perhaps for red muscle during periods of high activity. PMID:7353958

  5. Computational Study on Hemoglobin Protein Family

    NASA Astrophysics Data System (ADS)

    Craciun, Dana; Isvoran, Adriana; Avram, Nicolae M.

    2009-05-01

    We have analyzed 19 proteins belonging to hemoglobin protein family: 3 for plants, 4 for invertebrates and the others for vertebrates. For every protein we have determined the following parameters: the fractal dimension of its backbone, the fractal dimension of its surface, the radius of gyration, the area of its molecular surface and the area of the surface of its cavities. At global level, we did not notice significant differences for the fractal parameters for proteins belonging to different organisms and it underlines that all these proteins perform the same biological function. We have obtained different values of the local and global surface fractal dimensions reflecting distinct roughness of protein pockets in comparison to the entire surface, also in good correlation with the biological function. The geometric characteristics are distinct for the three investigated families of proteins.

  6. [Zinc and autophagy].

    PubMed

    Qiaoyun, Liu; Hanming, Shen; Dajing, Xia

    2016-05-25

    Autophagy refers to a catabolic process,in which the damaged organelles or biological macromolecules, such as protein aggregates, are degraded via lysosome. The completion of autophagy depends on a series of autophagy-related genes (Atgs) and many upstream regulatory molecules. Zinc is an essential trace element, and plays an important role in the process of autophagy as a component of enzymes and structural proteins like zinc transporters or zinc finger protein. The regulation of autophagy is closely associated with the zinc ion homeostasis. In addition, many studies suggest that the protective effects of zinc on cells are likely to be done by autophagy. This review aims to summarize the current research progress and discuss the reciprocal regulation mechanism between zinc and autophagy, which may provide insights into the intricate roles of autophagy in diseases and find novel strategies for treatment and prevention of human diseases. PMID:27651198

  7. Effect of hydrostatic pressure on ligand binding to hemoglobin.

    PubMed

    Carey, F G; Knowles, F; Gibson, Q H

    1977-06-25

    Increase in hydrostatic pressure to 1000 atm increased the affinity of human and menhaden (Brevoortia tyrannus) hemoglobins for oxygen. With necessary assumptions about the form of the equilibrium curve, and after correction for changes in pH and volume due to pressure, the increase in affinity is about 2-fold for both hemoglobins. At pH 6.5, Hill's n for menhaden hemoglobin is near 1, and it is believed to remain in the T state, whereas human hemoglobin undergoes a T to R transition. This suggests that the R-T equilibrium is not disturbed by pressure. In direct experiments the binding of a fluorescent effector (8 hydroxy-1,3,6-pyrene (trisulfonic acid) to deoxyhemoglobin was not changed by pressure. The binding of n-butylisocyanide to hemoglobin and to myoglobin is also greater at high pressures, similarly suggesting that the R-T transition is not involved in the pressure effect. PMID:16924

  8. Hydroxylation and dealkylation reactions catalyzed by hemoglobin.

    PubMed

    Mieyal, J J; Starke, D W

    1994-01-01

    Red blood cells contain many enzymes that are akin to those that catalyze xenobiotic metabolism in liver and other tissues. An obvious exception is the cytochrome P-450 system that is found in virtually all other tissues. In vitro studies, however, have shown that hemoglobin can be a broad monooxygenase catalyst, exhibiting the properties of a monooxygenase enzyme. Thus, catalysis by Hb displays typical Michaelis-Menten kinetics, dependence on the native protein, coupling to NADPH-dependent flavoprotein reductases, and inhibition by carbon monoxide. The reconstituted system containing Hb along with P-450 reductase utilizes NADPH and O2 to catalyze typical monooxygenase reactions, including O- and N-demethylations as well as aromatic and aliphatic hydroxylations, and the catalytic cycle appears to mimic the typical P-450 mechanism. Turnover numbers for aniline hydroxylation are similar for Hb and P-450 reconstituted systems, whereas P-450 systems are more effective for other reactions. Catalysis by Hb seems to be restricted to the beta-heme sites of the tetramer, reflecting more facile substrate access. Overall the similarities and differences between Hb and P-450 provide an opportunity to examine the basis for their differential monooxygenase or peroxidase/peroxygenase activities in a comparative manner. Hb may be especially useful in delineating the early events in the respective reaction schemes, because it can be studied in various stable redox/ligand states, including the oxyferrous form. Similar hemoglobin-catalyzed oxidative biotransformations occur within intact erythrocytes, but apparent turnover numbers are much lower than those with the reconstituted Hb system, suggesting different mechanisms of catalysis. Although Hb-mediated oxidase activity in erythrocytes is low relative to other sites of xenobiotic metabolism, it may contribute to in situ activation of xenobiotics leading to oxidative stress, disruption of sulfhydryl homeostasis in the erythrocytes

  9. Zinc electrode and rechargeable zinc-air battery

    SciTech Connect

    Ross, P.N. Jr.

    1989-06-27

    This patent describes an improved zinc electrode for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed.

  10. Zinc in Entamoeba invadens.

    NASA Technical Reports Server (NTRS)

    Morgan, R. S.; Sattilaro, R. F.

    1972-01-01

    Atomic absorption spectroscopy, electron microprobe analysis, and dithizone staining of trophozoites and cysts of Entamoeba invadens demonstrate that these cells have a high concentration of zinc (approximately one picogram per cell or 1% of their dry weight). In the cysts of this organism, the zinc is confined to the chromatoid bodies, which previous work has shown to contain crystals of ribosomes. The chemical state and function of this zinc are unknown.

  11. Bohr effect of hemoglobins: Accounting for differences in magnitude.

    PubMed

    Okonjo, Kehinde O

    2015-09-01

    The basis of the difference in the Bohr effect of various hemoglobins has remained enigmatic for decades. Fourteen amino acid residues, identical in pairs and located at specific 'Bohr group positions' in human hemoglobin, are implicated in the Bohr effect. All 14 are present in mouse, 11 in dog, eight in pigeon and 13 in guinea pig hemoglobin. The Bohr data for human and mouse hemoglobin are identical: the 14 Bohr groups appear at identical positions in both molecules. The dog data are different from the human because three Bohr group positions are occupied by non-ionizable groups in dog hemoglobin; the pigeon data are vastly different from the human because six Bohr group positions are occupied by non-ionizable groups in pigeon hemoglobin. The guinea pig data are quite complex. Quantitative analyses showed that only the pigeon data could be fitted with the Wyman equation for the Bohr effect. We demonstrate that, apart from guinea pig hemoglobin, the difference between the Bohr effect of each of the other hemoglobins and of pigeon hemoglobin can be accounted for quantitatively on the basis of the occupation of some of their Bohr group positions by non-ionizable groups in pigeon hemoglobin. We attribute the anomalous guinea pig result to a new salt-bridge formed in its R2 quaternary structure between the terminal NH3(+) group of one β-chain and the COO(-) terminal group of the partner β-chain in the same molecule. The pKas of this NH3(+) group are 6.33 in the R2 and 4.59 in the T state.

  12. Insights into Hemoglobin Assembly through in Vivo Mutagenesis of α-Hemoglobin Stabilizing Protein*

    PubMed Central

    Khandros, Eugene; Mollan, Todd L.; Yu, Xiang; Wang, Xiaomei; Yao, Yu; D'Souza, Janine; Gell, David A.; Olson, John S.; Weiss, Mitchell J.

    2012-01-01

    α-Hemoglobin stabilizing protein (AHSP) is believed to facilitate adult Hemoglobin A assembly and protect against toxic free α-globin subunits. Recombinant AHSP binds multiple forms of free α-globin to stabilize their structures and inhibit precipitation. However, AHSP also stimulates autooxidation of αO2 subunit and its rapid conversion to a partially unfolded bishistidyl hemichrome structure. To investigate these biochemical properties, we altered the evolutionarily conserved AHSP proline 30 in recombinantly expressed proteins and introduced identical mutations into the endogenous murine Ahsp gene. In vitro, the P30W AHSP variant bound oxygenated α chains with 30-fold increased affinity. Both P30W and P30A mutant proteins also caused decreased rates of αO2 autooxidation as compared with wild-type AHSP. Despite these abnormalities, mice harboring P30A or P30W Ahsp mutations exhibited no detectable defects in erythropoiesis at steady state or during induced stresses. Further biochemical studies revealed that the AHSP P30A and P30W substitutions had minimal effects on AHSP interactions with ferric α subunits. Together, our findings indicate that the ability of AHSP to stabilize nascent α chain folding intermediates prior to hemin reduction and incorporation into adult Hemoglobin A is physiologically more important than AHSP interactions with ferrous αO2 subunits. PMID:22287545

  13. Insights into hemoglobin assembly through in vivo mutagenesis of α-hemoglobin stabilizing protein.

    PubMed

    Khandros, Eugene; Mollan, Todd L; Yu, Xiang; Wang, Xiaomei; Yao, Yu; D'Souza, Janine; Gell, David A; Olson, John S; Weiss, Mitchell J

    2012-03-30

    α-Hemoglobin stabilizing protein (AHSP) is believed to facilitate adult Hemoglobin A assembly and protect against toxic free α-globin subunits. Recombinant AHSP binds multiple forms of free α-globin to stabilize their structures and inhibit precipitation. However, AHSP also stimulates autooxidation of αO(2) subunit and its rapid conversion to a partially unfolded bishistidyl hemichrome structure. To investigate these biochemical properties, we altered the evolutionarily conserved AHSP proline 30 in recombinantly expressed proteins and introduced identical mutations into the endogenous murine Ahsp gene. In vitro, the P30W AHSP variant bound oxygenated α chains with 30-fold increased affinity. Both P30W and P30A mutant proteins also caused decreased rates of αO(2) autooxidation as compared with wild-type AHSP. Despite these abnormalities, mice harboring P30A or P30W Ahsp mutations exhibited no detectable defects in erythropoiesis at steady state or during induced stresses. Further biochemical studies revealed that the AHSP P30A and P30W substitutions had minimal effects on AHSP interactions with ferric α subunits. Together, our findings indicate that the ability of AHSP to stabilize nascent α chain folding intermediates prior to hemin reduction and incorporation into adult Hemoglobin A is physiologically more important than AHSP interactions with ferrous αO(2) subunits.

  14. Zinc: An Essential Micronutrient

    PubMed Central

    SAPER, ROBERT B.; RASH, REBECCA

    2009-01-01

    Zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression. Patients with malnutrition, alcoholism, inflammatory bowel disease, and malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of zinc deficiency are nonspecific, including growth retardation, diarrhea, alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in males. In developing countries, zinc supplementation may be effective for the prevention of upper respiratory infection and diarrhea, and as an adjunct treatment for diarrhea in malnourished children. Zinc in combination with antioxidants may be modestly effective in slowing the progression of intermediate and advanced age-related macular degeneration. Zinc is an effective treatment for Wilson disease. Current data do not support zinc supplementation as effective for upper respiratory infection, wound healing, or human immunodeficiency virus. Zinc is well tolerated at recommended dosages. Adverse effects of long-term high-dose zinc use include suppressed immunity, decreased high-density lipoprotein cholesterol levels, anemia, copper deficiency, and possible genitourinary complications. PMID:20141096

  15. Zinc and Chlamydia trachomatis

    SciTech Connect

    Sugarman, B.; Epps, L.R.

    1985-07-01

    Zinc was noted to have significant effects upon the infection of McCoy cells by each of two strains of Chlamydia trachomatis. With a high or low Chlamydia inoculant, the number of infected cells increased up to 200% utilizing supplemental zinc (up to 1 x 10/sup -4/ M) in the inoculation media compared with standard Chlamydia cultivation media (8 x 10/sup -6/ M zinc). Ferric chloride and calcium chloride did not effect any such changes. Higher concentrations of zinc, after 2 hr of incubation with Chlamydia, significantly decreased the number of inclusions. This direct effect of zinc on the Chlamydia remained constant after further repassage of the Chlamydia without supplemental zinc, suggesting a lethal effect of the zinc. Supplemental zinc (up to 10/sup -4/ M) may prove to be a useful addition to inoculation media to increase the yield of culturing for Chlamydia trachomatis. Similarly, topical or oral zinc preparations used by people may alter their susceptibility to Chamydia trachomatis infections.

  16. Use of Protoporphyrin Fluorescence to Determine Clinical Target Volume for Non-melanotic Skin Cancers Treated with Primary Radiotherapy

    PubMed Central

    Best, Lara; Vujovic, Olga; Jordan, Kevin; Fisher, Barbara; Carey, Deborah; Bourdeau, Deborah; Yu, Edward

    2016-01-01

    Purpose  Non-melanotic skin cancers remain the most commonly diagnosed cancers. Radiotherapy and surgery are the most common treatment options. Radiotherapy has a recurrence rate of up to 20% for basal or squamous cell cancers. One of the difficulties is to determine the extent of disease for poorly demarcated tumors. This study utilizes protoporphyrin (PpIX) fluorescence to provide information on the extent of subclinical disease for poorly demarcated tumors treated with radiotherapy. Materials and Methods  For 33 patients, PpIX photo-delineation was used to determine the clinical target volume (CTV2), which was compared to current conventional margins used to account for microscopic disease. Results  The use of PpIX photo-delineation demonstrated a significantly larger CTV of 15 mm compared to the conventional 10 mm (p = 0.03) for poorly demarcated lesions. A larger CTV was also demonstrated with PpIX photo-delineation for all basal cell carcinomas (13 mm, p = 0.03) as well as for non-nasal lesions (14 mm, p = 0.04). A trend towards an increased CTV was also noted for squamous cell carcinomas (16 mm, p = 0.19) and nasal primary sites (14 mm, p = 0.11). Nasal primary malignancies had multifocal PpIX uptake in 94% of cases. There was one case of local recurrence and one case of distant recurrence, with an average follow-up time of 22 months. Conclusions  The margins currently used to account for subclinical disease may underestimate the extent of microscopic spread for poorly demarcated tumors. Longer follow-up with larger pools of patients are necessary to determine if using PpIX photo-delineation translates into significantly improved clinical outcomes. PMID:27725923

  17. Absorption spectral change of peripheral-light harvesting complexes 2 induced by magnesium protoporphyrin IX monomethyl ester association.

    PubMed

    Yue, Huiying; Zhao, Chungui; Li, Kai; Yang, Suping

    2015-02-25

    Several spectrally different types of peripheral light harvesting complexes (LH) have been reported in anoxygenic phototrophic bacteria in response to environmental changes. In this study, two spectral forms of LH2 (T-LH2 and U-LH2) were isolated from Rhodobacter azotoformans. The absorption of T-LH2 was extremely similar to the LH2 isolated from Rhodobacter sphaeroides. U-LH2 showed an extra peak at ∼423 nm in the carotenoid region. To explore the spectral origin of this absorption peak, the difference in pigment compositions of two LH2 was analyzed. Spheroidene and bacteriochlorophyll aP were both contained in the two LH2. And magnesium protoporphyrin IX monomethyl ester (MPE) was only contained in U-LH2. It is known that spheroidene and bacteriochlorophyll aP do not produce ∼423 nm absorption peak either in vivo or in vitro. Whether MPE accumulation was mainly responsible for the formation of the ∼423 nm peak? The interactions between MPE and different proteins were further studied. The results showed that the maximum absorption of MPE was red-shifted from ∼415 nm to ∼423 nm when it was mixed with T-LH2 and its apoproteins, nevertheless, the Qy transitions of the bound bacteriochlorophylls in LH2 were almost unaffected, which indicated that the formation of the ∼423 nm peak was related to MPE-LH2 protein interaction. MPE did not bind to sites involved in the spectral tuning of BChls, but the conformation of integral LH2 was affected by MPE association, the alkaline stability of U-LH2 was lower than T-LH2, and the fluorescence intensity at 860 nm was decreased after MPE combination.

  18. Chelators for investigating zinc metalloneurochemistry.

    PubMed

    Radford, Robert J; Lippard, Stephen J

    2013-04-01

    The physiology and pathology of mobile zinc signaling has become an important topic in metalloneurochemistry. To study the action of mobile zinc effectively, specialized tools are required that probe the temporal and positional changes of zinc ions within live tissue and cells. In the present article we describe the design and implementation of selective zinc chelators as antagonists to interrogate the function of mobile zinc, with an emphasis on the pools of vesicular zinc in the terminals of hippocampal mossy fiber buttons.

  19. The role of hemoglobin heme loss in Heinz body formation: studies with a partially heme-deficient hemoglobin and with genetically unstable hemoglobins

    PubMed Central

    Jacob, Harry S.; Winterhalter, Kaspar H.

    1970-01-01

    A number of mutant hemoglobins are inordinately unstable, denaturing in circulating red cells into Heinz bodies, resulting in congenital Heinz body hemolytic anemia (CHBHA). We have emphasized that most such hemoglobins involve amino acid substitutions at sites neighboring the heme group of the β-polypeptide chain, and have shown that heme binding to globin is diminished thereby. Thus, hemes were progressively lost from four unstable hemoglobins (Köln, Hammersmith, San Francisco, and Zürich) as they precipitated into Heinz bodies at 50°C. The role of heme loss, especially from beta chains, in Heinz body formation was supported by studies with a hemoglobin synthesized to contain hemes only on its alpha chains (α2hemeβ20). The behavior of this compound, postulated to be an intermediary in the formation of Heinz bodies, mimicked that of the genetically unstable hemoglobins in several ways: (a) it precipitated at 50°C into typical coccoid Heinz bodies; (b) as also observed with CHBHA hemoglobins this denaturation was virtually prevented by the heme ligands, cyanide or carbon monoxide, which inhibit further heme loss; it was potentiated by oxidation of hemes to the ferri- state, which accentuates heme loss; (c) the thiol groups of α2hemeβ20 were hyperreactive, forming mixed disulfides with glutathione and membrane sulfhydryls at rates similar to those of CHBHA hemoglobins and 10 or more times that of normal hemoglobin A; (d) heme repletion of the protein molecules by the addition of crystalline hemin to either α2hemeβ20 or to the genetically unstable hemoglobins, prevented their precipitation into Heinz bodies and normalized their aberrant electrophoretic behaviors; and (e) during Heinz body formation at 50°C both α2hemeβ20 and the genetically unstable hemoglobins released free αheme-chains into solution, suggesting that the bulk of the whitish, Heinz body precipitate is naked β8-chains. We conclude that heme loss from mutant beta chains is an early step

  20. Development of an immunoassay to detect benzene adducts in hemoglobin

    SciTech Connect

    Grassman, J.A.

    1993-01-01

    The purpose of this project was to develop an immunoassay to detect the adducts formed in hemoglobin after exposure to benzene, which is known to cause bone marrow degeneration and acute myelogenous leukemia. The use of benzene-adduct detection as a biological monitoring method would permit measurement of low exposures and exposures sustained weeks earlier. The reactivity of hydroquinone, an important benzene metabolite, with blood proteins and amino acids was investigated in order to decide which antigens and analytes were likely to be suitable for immunoassay development. The second section determined the combination of benzene-metabolite and antigen need to produce an immunoassay with the requisite low detection limit and specificity. The immunoassays with the best performance were tested on hemoglobin from benzene-exposed mice. In vitro studies showed that hydroquinone efficiently formed adducts with erythrocyte membranes and hemoglobin but not with albumin. Adduction efficiency was greater in incubations using purified hemoglobin than whole blood. Cysteine accounted for 15 to 27% of the adducts formed by hydroquinone. The site of the other adducts were not identified although there was evidence that the hemoglobin heme was adducted. Adducts were found on only 1 of the 2 globin chains. Tryptic digestion of the globin failed to associate the adducts with a specific peptide. Antigens made from hydroquinone-adducted hemoglobin but not hydroquinone-adducted cysteines coupled to carrier proteins effectively elicited adduct-specific antibodies. Interference due to reactivity to hemoglobin was controlled by using uniform quantities of hemoglobin in all wells. The mid-range of the best assays were approximately 12 pmoles HQ per well. Antibodies directed toward hemoglobin adducted with the benzene metabolites phenol, catechol and 1,2,4-trihydroxybenzene were also made. The performance of the anti-1,2,4-trihydroxybenzene were suitable for quantitative immunoassays.

  1. Zinc Inhibits Hedgehog Autoprocessing

    PubMed Central

    Xie, Jian; Owen, Timothy; Xia, Ke; Singh, Ajay Vikram; Tou, Emiley; Li, Lingyun; Arduini, Brigitte; Li, Hongmin; Wan, Leo Q.; Callahan, Brian; Wang, Chunyu

    2015-01-01

    Zinc is an essential trace element with wide-ranging biological functions, whereas the Hedgehog (Hh) signaling pathway plays crucial roles in both development and disease. Here we show that there is a mechanistic link between zinc and Hh signaling. The upstream activator of Hh signaling, the Hh ligand, originates from Hh autoprocessing, which converts the Hh precursor protein to the Hh ligand. In an in vitro Hh autoprocessing assay we show that zinc inhibits Hh autoprocessing with a Ki of 2 μm. We then demonstrate that zinc inhibits Hh autoprocessing in a cellular environment with experiments in primary rat astrocyte culture. Solution NMR reveals that zinc binds the active site residues of the Hh autoprocessing domain to inhibit autoprocessing, and isothermal titration calorimetry provided the thermodynamics of the binding. In normal physiology, zinc likely acts as a negative regulator of Hh autoprocessing and inhibits the generation of Hh ligand and Hh signaling. In many diseases, zinc deficiency and elevated level of Hh ligand co-exist, including prostate cancer, lung cancer, ovarian cancer, and autism. Our data suggest a causal relationship between zinc deficiency and the overproduction of Hh ligand. PMID:25787080

  2. Preparation of zinc orthotitanate

    NASA Technical Reports Server (NTRS)

    Gates, D. W.; Gilligan, J. E.; Harada, Y.; Logan, W. R.

    1977-01-01

    Use of decomposable precursors to enhance zinc oxide-titanium dioxide reaction and rapid fixing results in rapid preparation of zinc orthotitanate powder pigment. Preparation process allows production under less stringent conditions. Elimination of powder grinding results in purer that is less susceptible to color degradation.

  3. Functional differentiation in trematode hemoglobin isoforms.

    PubMed

    Rashid, A K; Weber, R E

    1999-03-01

    The Hbs and the major electrophoretic Hb components (isoHbs) were isolated from three species of the trematodes, Explanatum explanatum (Ee), Gastrothylax crumenifer (Gc) and Paramphistomum epiclitum (Pe), that parasitise the common Indian water buffalo Bubalus bubalis. The Hbs are monomeric and resemble the so-called nonfunctional mutant hemoglobins that have Tyr at B10 or E7 positions (replacing Leu and the His residues, respectively). However, they are capable of binding with O2 and CO. O2 equilibrium studies of trematode Hb isoforms reveal extremely high O2 affinities, with half-saturation O2 tension (P50) values up to 800 times lower than those of human hemoglobins. This correlates with Tyr residues at B10 and at the distal position (E7) that decrease the O2 dissociation rate by contributing hydrogen bonds (H-bonds) to the bound O2. These substitutions also increase the O2 association rates either due to orientation of E7-Tyr towards the solvent and/or by sterically hindering the entry of water molecules into the heme pocket. The latter may account for the low rate of autoxidation of trematode Hbs. The Hbs and their isoforms from different species exhibited pronounced variation in O2 affinity, which may relate to subtle differences in the structure of the heme pocket. The O2 affinities of the composite (unfractionated) Hbs were intermediate to those of the individual Hb isoform. The P50 values of Hbs here obtained by direct O2 equilibrium measurements differed from those calculated from kinetic data already published [Kiger, L., Rashid, A. K., Griffon, N., Haque, M., Moens, L.,Gibson, Q. H., Poyart, C., & Marden, M. C. (1998). Biophys. J. 75, 990-998.] Intermediate state(s) due to slow reorientation of E7-Tyr may account for this difference. Some Hb isoforms showed slight (either normal or reverse) Bohr effects. The hyperbolic O2 equilibrium curve, Hill coefficient (n) values near unity accord with a monomeric nature of trematode Hbs. In marked contrast to

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

    SciTech Connect

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

    1986-08-01

    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.

  5. Co-ordination of iron acquisition, iron porphyrin chelation and iron-protoporphyrin export via the cytochrome c biogenesis protein CcmC in Pseudomonas fluorescens.

    PubMed

    Baysse, Christine; Matthijs, Sandra; Schobert, Max; Layer, Gunhild; Jahn, Dieter; Cornelis, Pierre

    2003-12-01

    The cytoplasmic membrane protein CcmC is, together with other Ccm proteins, a component for the maturation of c-type cytochromes in Gram-negative bacteria. A Pseudomonas fluorescens ATCC 17400 ccmC mutant is cytochrome c-deficient and shows considerably reduced production of the two siderophores pyoverdine and quinolobactin, paralleled by a general inability to utilize various iron sources, with the exception of haem. The ccmC mutant accumulates in a 5-aminolevulinic acid-dependent synthesis a reddish, fluorescent pigment identified as protoporphyrin IX. As a consequence a visA phenotype similar to that of a ferrochelatase-deficient hemH mutant characterized by drastically reduced growth upon light exposure was observed for the ccmC mutant. The defect of iron-protoporphyrin formation was further demonstrated by the failure of ccmC cell-free proteinase K-treated extracts to stimulate the growth of a haem auxotrophic hemH indicator strain, compared to similarly prepared wild-type extracts. In addition, the ccmC mutant did not sustain hemH growth in cross-feeding experiments while the wild-type did. Significantly reduced resistance to oxidative stress mediated by haem-containing catalases was observed for the ccmC mutant. A double hemH ccmC mutant could not be obtained in the presence of external haem without the hemH gene in trans, indicating that the combination of the two mutations is lethal. It was concluded that CcmC, apart from its known function in cytochrome c biogenesis, plays a role in haem biosynthesis. A function in the regulatory co-ordination of iron acquisition via siderophores, iron insertion into porphyrin via ferrochelatase and iron-protoporphyrin export for cytochrome c formation is predicted. PMID:14663086

  6. Effects of cerebral ischemia on neuronal hemoglobin

    PubMed Central

    He, Yangdong; Hua, Ya; Liu, Wenquan; Hu, Haitao; Keep, Richard F.; Xi, Guohua

    2009-01-01

    Summary The present study examined whether or not neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 minutes of transient middle cerebral artery occlusion with 24 hours of reperfusion, an IPC stimulus, or 24 hours of permanent middle cerebral artery occlusion (pMCAO), or IPC followed three days later by 24 hours of pMCAO. In vitro, primary cultured neurons were exposed to 2 hours of oxygen-glucose deprivation with 22 hours of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hb expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hb levels also increased in more penumbral cortex and the contralateral hemisphere 24 hours after pMCAO, but expression in the ipsilateral caudate and cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 hours of oxygen-glucose deprivation and 22 hours of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia. PMID:19066615

  7. Influences of genetic variation on fetal hemoglobin.

    PubMed

    He, Yunyan; Lin, Weixiong; Luo, Jianming

    2011-11-01

    Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. The authors performed a replicated study following the genome-wide association study (GWAS) guidelines to identify the genetic mechanics that influence HbF. The authors recruited and phenotyped 312 unrelated β-thalassemia subjects. Single-nucleotide polymorphism (SNP) analysis was performed by using polymerase chain reaction (PCR)/restriction enzymes. Four independent regions of interest were identified: HBS1L-MYB intergenic region, BCL11A locus, β-globin gene cluster, and the CSNK2A1 gene. There were 10 SNPs associated with HbF levels. In addition, haplotypes of HBS1L-MYB and BCL11A were identified and showed association with HbF production. Three independent regions, including HBS1L-MYB intergenic region, BCL11A locus, and β-globin gene cluster, were associated with HbF levels. This study can significantly improve the GWAS findings in Chinese cohorts and is useful for further research in the field of common predictors of the erythropoiesis.

  8. Structure and evolution of Paramecium hemoglobin genes.

    PubMed

    Yamauchi, K; Tada, H; Usuki, I

    1995-10-17

    Hemoglobin (Hb) genes have been cloned from three different species of ciliated protists, P. multimicronucleatum, P. triaurelia and P. jenningsi. Southern blotting of the genomic DNAs using the P. caudatum Hb cDNA showed both intraspecies variation in different stocks of P. caudatum and interspecies variation within the genus Paramecium. The isolated Hb genes were composed of 118, 117 and 117 codons, and interrupted by a short intron with 27, 29 and 29 bp at the same position, in P. multimicronucleatum, P. triaurelia and P. jenningsi, respectively. This suggests that the one-intron and two-exon structure has been conserved in the Hb genes in this genus. The amino acid sequences of the Paramecium Hbs were more than 87% identical to one another and homologous to those from the other ciliated protists Tetrahymena thermophila and T. pyriformis, the green alga Chlamydomonas eugametos, and the cyanobacterium Nostoc commune Hbs, all of which consist of about 120 amino acid residues (120-aa group). In particular, the amino acid sequences of the P. triaurelia and P. jenningsi Hbs were the same, although there were 20 nucleotide differences between the coding regions in the two genes. A maximum likelihood inference as to the phylogenetic relationships among these genes suggests that the Paramecium Hbs genes have evolved more rapidly than the other genes in the 120-aa group, and that P. triaurelia and P. genningsi are sibling species and the P. aurelia complex became a small cell after it separated from P. jenningsi.

  9. Exploring zinc coordination in novel zinc battery electrolytes.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2014-06-14

    The coordination of zinc ions by tetraglyme has been investigated here to support the development of novel electrolytes for rechargeable zinc batteries. Zn(2+) reduction is electrochemically reversible from tetraglyme. The spectroscopic data, molar conductivity and thermal behavior as a function of zinc composition, between mole ratios [80 : 20] and [50 : 50] [tetraglyme : zinc chloride], all suggest that strong interactions take place between chloro-zinc complexes and tetraglyme. Varying the concentration of zinc chloride produces a range of zinc-chloro species (ZnClx)(2-x) in solution, which hinder full interaction between the zinc ion and tetraglyme. Both the [70 : 30] and [50 : 50] mixtures are promising electrolyte candidates for reversible zinc batteries, such as the zinc-air device.

  10. Exploring zinc coordination in novel zinc battery electrolytes.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2014-06-14

    The coordination of zinc ions by tetraglyme has been investigated here to support the development of novel electrolytes for rechargeable zinc batteries. Zn(2+) reduction is electrochemically reversible from tetraglyme. The spectroscopic data, molar conductivity and thermal behavior as a function of zinc composition, between mole ratios [80 : 20] and [50 : 50] [tetraglyme : zinc chloride], all suggest that strong interactions take place between chloro-zinc complexes and tetraglyme. Varying the concentration of zinc chloride produces a range of zinc-chloro species (ZnClx)(2-x) in solution, which hinder full interaction between the zinc ion and tetraglyme. Both the [70 : 30] and [50 : 50] mixtures are promising electrolyte candidates for reversible zinc batteries, such as the zinc-air device. PMID:24760367

  11. Solid hemoglobin-polymer phantoms for evaluation of biophotonic systems.

    PubMed

    Jang, Hyounguk; Pfefer, T Joshua; Chen, Yu

    2015-09-15

    Stable tissue phantoms that incorporate the spectral absorption properties of hemoglobin would benefit a wide range of biophotonic technologies. Toward this end, we have developed and validated a novel polymer material incorporating hemoglobin. Our solid hemoglobin-polymer (SHP) material is fabricated by mixing liquid silicone base with a hemoglobin solution, followed by sonication and low temperature curing. The optical properties of samples were determined over 450-1000 nm using the inverse adding-doubling method and the Beer-Lambert law. Measurements indicated SHP optical stability over four months. Near-infrared spectroscopy and hyperspectral imaging measurements of SHP samples were performed to demonstrate the utility of this approach. SHP materials have the potential to improve tissue-simulating phantoms used for development, evaluation, and standardization of optical devices for oximetry and other applications. PMID:26371926

  12. Reverse engineering the cooperative machinery of human hemoglobin.

    PubMed

    Ren, Zhong

    2013-01-01

    Hemoglobin transports molecular oxygen from the lungs to all human tissues for cellular respiration. Its α2β2 tetrameric assembly undergoes cooperative binding and releasing of oxygen for superior efficiency and responsiveness. Over past decades, hundreds of hemoglobin structures were determined under a wide range of conditions for investigation of molecular mechanism of cooperativity. Based on a joint analysis of hemoglobin structures in the Protein Data Bank (Ren, companion article), here I present a reverse engineering approach to elucidate how two subunits within each dimer reciprocate identical motions that achieves intradimer cooperativity, how ligand-induced structural signals from two subunits are integrated to drive quaternary rotation, and how the structural environment at the oxygen binding sites alter their binding affinity. This mechanical model reveals the intricate design that achieves the cooperative mechanism and has previously been masked by inconsistent structural fluctuations. A number of competing theories on hemoglobin cooperativity and broader protein allostery are reconciled and unified.

  13. Weak binding gases as modulators of hemoglobin function

    SciTech Connect

    Schoenborn, B P; Saxena, A; North, B E

    1980-01-01

    Studies are reported in which the mechanisms of binding of inert gaseous agents to hemoglobin and myoglobin are investigated. Specific binding sites are mapped. Possible effects on sickle cell formation and oxygen binding are discussed. (ACR)

  14. In Vitro Comparison of Hypericin and 5-Aminolevulinic Acid-Derived Protoporphyrin IX for Photodynamic Inactivation of Medulloblastoma Cells

    PubMed Central

    Ritz, Rainer; Scheidle, Christian; Noell, Susan; Roser, Florian; Schenk, Martin; Dietz, Klaus; Strauss, Wolfgang S. L.

    2012-01-01

    Background Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX). Methods In 3 medulloblastoma cell lines (D283 Med, Daoy, and D341 Med) the time- and concentration-dependent intracellular accumulation of HYP and 5-ALA-derived PpIX was analyzed by fluorescence microscopy (FM) and FACS. Photocytotoxicity was measured after illumination at 595 nm (HYP) and 635 nm (5-ALA-derived PpIX) in D283 Med cells and compared to U373 MG glioma cells. Results All medulloblastoma cell lines exhibited concentration- and time-dependent uptake of HYP. Incubation with HYP up to 10 µM resulted in a rapid increase in fluorescence intensity, which peaked between 2 and 4 hours. 5-ALA-derived PpIX accumulation increased in D283 Med cells by 22% over baseline after 5-ALA incubation up to 1.2 mM. Photocytotoxicity of 5-ALA-derived PpIX was higher in D283 Med medulloblastoma compared to U373MG glioma. The [lethal dose (light dose that is required to reduce cell survival to 50% of control)] of 5-ALA-derived PpIX was 3.8 J/cm2 in D283 Med cells versus 5.7 J/cm2 in U373MG glioma cells. Photocytotoxicity of HYP in D283 Med cells was determined at 2.5 µM after an incubation time of 2 h and an illumination wavelength of 595 nm. The value was 0.47 J/cm2. Conclusion By its 5-fold increase in fluorescence over autofluorescence levels HYP has excellent properties for tumor visualization in medulloblastomas. The high photocytotoxicity of HYP, compared to 5-ALA-derived PpIX, is convincingly demonstrated by its 8- to 13-fold lower . Therefore HYP might be a promising molecule for intraoperative visualization and photodynamic treatment of medulloblastomas. PMID:23251668

  15. [Relationship between blood lead and free erythrocyte-protoporphyrin of female workers exposed to low concentration of lead operating environment].

    PubMed

    Wang, X; Liu, L; Yang, J

    2000-11-01

    The thesis focused in the research on whether low-lead operation would have effects on female workers. Based on investigation of 82 female workers under an operation environment with lead concentration of 0.0315 mg/m3, the following report indicated that differences did exist in terms of free erythrocyte-protoporphyrin(FEP), lead-blood(Pb-B) and lead-urine(Pb-U) values between the exposure and control groups. Pb-B, FEP and Pb-U were found closely interrelated and comparatively sensitive. Dose-response relationship was discovered in the process, positive percentage of Pb-B and FEP were 20.73% and 21.95% respectively, 13.4% above the maximal standard in both cases. In consequence, it was concluded that exposure to the 0.0315 mg/m3 lead concentration (0.03 mg/m3 being the normal) was still harmful to the female workers. Apart from that, the article suggested that the upper limit of lead in blood for common women (in Changchun city) was properly defined at 1.46 mumol/L. With FEP as the standard, the article made repective comparisons on the female workers' intelligence quotient (IQ) and the symptom occurrence of the neural system. People with IQ value between 60 to 79, 80 to 89, 90 to 109 or 110 to 119, the rates of showing positive report with FEP > or = 0.90 mumol/L were 27.6%, 22.6% and 15.0% respectively. The general occurrence rate on various level of FEP was obviously higher than that of the control group. The highest occurrence rate of 208.32% and 58.74% appeared when the FEP value was between 0.36 mumol/L to 0.54 mumol/L. When we made the comparison according to different symptoms as headache, dizziness, hypomnesis, somnipathy, palpitation and ephidrosis, the occurrence rate of headache was distinctively highger than that of the somnipathy.

  16. Interstitial zinc clusters in zinc oxide

    NASA Astrophysics Data System (ADS)

    Gluba, M. A.; Nickel, N. H.; Karpensky, N.

    2013-12-01

    Doped zinc oxide (ZnO) exhibits anomalous Raman modes in the range of 270 to 870 cm-1. Commonly, the resonance at 275 cm-1 is attributed to the local vibration of Zn atoms in the vicinity of extrinsic dopants. We revisit this assignment by investigating the influence of isotopically purified zinc oxide thin films on the frequency of the vibrational mode around 275 cm-1. For this purpose, undoped and nitrogen-doped ZnO thin-films with Zn isotope compositions of natural Zn, 64Zn, 68Zn, and a 1:1 mixture of 64Zn and 68Zn were grown by pulsed laser deposition. The isotopic shift and the line shape of the Raman resonance around 275 cm-1 are analyzed in terms of three different microscopic models, which involve the vibration of (i) interstitial zinc atoms bound to extrinsic defects, (ii) interstitial diatomic Zn molecules, and (iii) interstitial zinc clusters. The energy diagram of interstitial Zn-Zn bonds in a ZnO matrix is derived from density functional theory calculations. The interstitial Zn-Zn bond is stabilized by transferring electrons from the antibonding orbital into the ZnO conduction band. This mechanism facilitates the formation of interstitial Zn clusters and fosters the common n-type doping asymmetry of ZnO.

  17. Designing hydrolytic zinc metalloenzymes.

    PubMed

    Zastrow, Melissa L; Pecoraro, Vincent L

    2014-02-18

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  18. Designing Hydrolytic Zinc Metalloenzymes

    PubMed Central

    2015-01-01

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  19. The Stepwise Mutation Model: An Experimental Evaluation Utilizing Hemoglobin Variants

    PubMed Central

    Fuerst, Paul A.; Ferrell, Robert E.

    1980-01-01

    The stepwise mutation model of Ohta and Kimura (1973) was proposed to explain patterns of genetic variability revealed by means of electrophoresis. The assumption that electrophoretic mobility was principally determined by unit changes in net molecular charge has been criticized by Johnson (1974, 1977). This assumption has been tested directly using hemoglobin. Twenty-seven human hemoglobin variants with known amino acid substitutions, and 26 nonhuman hemoglobins with known sequences were studied by starch gel electrophoresis. Of these hemoglobins, 60 to 70% had electrophoretic mobilities that could be predicted solely on the basis of net charge calculated from the amino acid composition alone, ignoring tertiary structure. Only four hemoglobins showed a mobility that was clearly different from an expected mobility calculated using only the net charge of the molecule. For the remaining 30% of hemoglobins studied, mobility was determined by a combination of net charge and other unidentified components, probably reflecting changes in ionization of some amino acid residues as a result of small alterations in tertiary structure due to the amino acid substitution in the variant. For the nonhuman hemoglobins, the deviation of a sample from its expected mobility increased with increasing amino acid divergence from human hemoglobin A.—It is concluded that the net electrostatic charge of a molecule is the principal determinant of electrophoretic mobility under the conditions studied. However, because of the significant deviation from strict stepwise mobility detected for 30 to 40% of the variants studied, it is further concluded that the infinite-allele model of Kimura and Crow (1964) or a "mixed model" such as that proposed by Li (1976) may be more appropriate than the stepwise mutation model for the analysis of much of the available electrophoretic data from natural populations. PMID:17248992

  20. Monoclonal antibodies recognizing single amino acid substitutions in hemoglobin

    SciTech Connect

    Stanker, L.H.; Branscomb, E.; Vanderlaan, M.; Jensen, R.H.

    1986-06-01

    Four monoclonal antibodies (mAb) to non-human primate hemoglobin referred to as Cap-4, Cap-5, Rh-2, and Rh-4, and two mAb to human hemoglobin, referred to as H-1 and H-3 were isolated and were partially characterized. Binding studies with these mAb on a panel of hemoglobins and isolated ..cap alpha.. and ..beta.. globin chains revealed a unique reactivity pattern for each mAb. Amino acid sequence analysis of the antigens used to generate the binding data suggests that the specific recognition of certain hemoglobin antigens by each mAb is controlled by the presence of a particular amino acid at a specific position within the epitope. The use of synthetic peptides as antigens confirmed this observation for five of the mAb. No synthetic peptides were tested with the sixth mAb, Rh-2. The amino acids required for binding of mAb Cap-4, Cap-5, Rh-4, and Rh-2 to hemoglobin are alanine at ..beta..5, threonine at ..beta..13, glutamine at ..beta..125, and leucine at ..cap alpha..68. The non-human primate hemoglobin antibodies require a specific amino acid that is not present in human hemoglobin. The amino acid required for binding of Cap-4, Cap-5, and Rh-4 could arise by a single base change in the ..beta.. globin gene, whereas the amino acid required for Rh-2 binding could only occur if two base changes occurred. Thus these mAb are candidate probes for a somatic cell mutation assay on the basis of the detection of peripheral blood red cells that possess single amino acid substituted hemoglobin as a result of single base substitutions in the globin genes of precursor cells.

  1. The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins.

    PubMed

    Kasperczyk, Aleksandra; Prokopowicz, Adam; Dobrakowski, Michał; Pawlas, Natalia; Kasperczyk, Sławomir

    2012-12-01

    The study objective was to evaluate the effect of occupational lead exposure on blood concentrations of zinc, iron, copper, selenium and proteins related to them, such as transferrin, caeruloplasmin and haptoglobin. The examined group consisted of 192 healthy male employees of zinc-lead works. By the degree of lead exposure, the exposed group was subdivided into three subgroups. The control group was composed of 73 healthy male administrative workers. The markers of lead exposure (blood levels of lead and zinc protoporphyrin) were significantly elevated in the exposed group compared with the control group. Additionally, concentrations of copper and caeruloplasmin were raised. The significant increase in haptoglobin level was observed only in the low exposure group. Selenium levels were significantly decreased, whereas iron, zinc and transferrin levels were unchanged in the exposed group compared with the control group. There were positive correlations between the lead toxicity parameters and the copper and caeruloplasmin levels. In conclusion, the effect of occupational exposure to lead on the metabolism of trace metals appears to be limited. However, significant associations between lead exposure and levels of copper and selenium were shown. Changed levels of positive acute-phase proteins, such as caeruloplasmin and haptoglobin, were also observed.

  2. Automated quantitation of hemoglobin-based blood substitutes in whole blood samples.

    PubMed

    Kunicka, J; Malin, M; Zelmanovic, D; Katzenberg, M; Canfield, W; Shapiro, P; Mohandas, N

    2001-12-01

    It is necessary to develop methods for accurate monitoring of cell-free hemoglobin in circulation. Routine monitoring of circulating cell-free hemoglobin will be useful for evaluating the efficacy of blood substitute administration andfor determining the clearance rates of the blood substitute from circulation. In addition, discriminating between cell-free hemoglobin and cell-associated hemoglobin will enable accurate determination of RBC indices, mean cell hemoglobin and mean corpuscular hemoglobin concentration, in individuals receiving hemoglobin-based blood substitutes. As colorimetric methods used by hematology analyzers to quantitate the hemoglobin value of a blood sample cannot distinguish between cell-associated and cell-free hemoglobin, it is currently not feasible to quantitate the levels of hemoglobin substitutes in circulation. The advent of a technology that measures volume and hemoglobin concentration of individual RBCs provides an alternative strategy for quantitating the cell-associated hemoglobin in a blood sample. We document that the combined use of cell-based and colorimetric hemoglobin measurements provides accurate discrimination between cell-associated and cell-free hemoglobin over a wide range of hemoglobin levels. This strategy should enable rapid and accurate monitoring of the levels of cell-free hemoglobin substitutes in the circulation of recipients of these blood substitutes.

  3. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, T.

    1997-02-18

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate {alpha}-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal. 33 figs.

  4. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, Toshifumi

    1997-01-01

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate .alpha.-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal.

  5. Iron nitrosyl hemoglobin formation from the reaction of hydroxylamine and hemoglobin under physiological conditions.

    PubMed

    Lockamy, Virginia L; Shields, Howard; Kim-Shapiro, Daniel B; King, S Bruce

    2004-11-01

    Sickle cell disease patients receiving hydroxyurea (HU) therapy have shown increases in the production of nitric oxide (NO) metabolites, which include iron nitrosyl hemoglobin (HbNO), nitrite, and nitrate. However, the exact mechanism by which HU forms HbNO in vivo is not understood. Previous studies indicate that the reaction of oxyhemoglobin (oxyHb) or deoxyhemoglobin (deoxyHb) with HU are too slow to account for in vivo HbNO production. In this study, we show that the reaction of methemoglobin (metHb) with HU to form HbNO could potentially be fast enough to account for in vivo HbNO formation but competing reactions of either excess oxyHb or deoxyHb during the reaction reduces the likelihood that HbNO will be produced from the metHb-HU reaction. Using electron paramagnetic resonance (EPR) spectroscopy we have detected measurable amounts of HbNO and metHb during the reactions of oxyHb, deoxyHb, and metHb with excess hydroxylamine (HA). We also demonstrate HbNO and metHb formation from the reactions of excess oxyHb, deoxyHb, or metHb and HA, conditions that are more likely to mimic those in vivo. These results indicate that the reaction of hydroxylamine with hemoglobin produces HbNO and lend chemical support for a potential role for hydroxylamine in the in vivo metabolism of hydroxyurea.

  6. Relative phase of oscillations of cerebral oxy-hemoglobin and deoxy-hemoglobin concentrations during sleep

    NASA Astrophysics Data System (ADS)

    Pierro, Michele L.; Sassaroli, Angelo; Bergethon, Peter R.; Fantini, Sergio

    2012-02-01

    We present a near-infrared spectroscopy study of the instantaneous phase difference between spontaneous oscillations of cerebral deoxy-hemoglobin and oxy-hemoglobin concentrations ([Hb] and [HbO], respectively) in the low-frequency range, namely 0.04-0.12 Hz. We report phase measurements during the transitions between different sleep stages in a whole-night study of a human subject. We have found that the phase difference between [Hb] and [HbO] low-frequency oscillations tends to be greater in deep sleep (by ~96° on average) and REM sleep (by ~77° on average) compared to the awake state. In particular, we have observed progressive phase increases as the subject transitions from awake conditions into non-REM sleep stages N1, N2, and N3. Corresponding phase decreases were recorded in the reversed transitions from sleep stages N3 to N2, and N2 to awake. These results illustrate the physiological information content of phase measurements of [Hb] and [HbO] oscillations that reflect the different cerebral hemodynamic conditions of the different sleep stages, and that can find broader applicability in a wide range of near-infrared spectroscopy brain studies.

  7. Toxicity of hemoglobin solutions: hemoglobin is a lipopolysaccharide (LPS) binding protein which enhances LPS biological activity.

    PubMed

    Roth, R I; Kaca, W

    1994-01-01

    Administration of alpha alpha-crosslinked stroma-free hemoglobin (SFH) as a cell-free resuscitation fluid is associated with multiple organ toxicities. Many of these toxicities are characteristic of the pathophysiological effects of bacterial endotoxins (lipopolysaccharide, LPS). To better understand the potential role of LPS in the observed in vivo toxicities of SFH, we examined mixtures of SFH and E. coli LPS for evidence of LPS-SFH complex formation. LPS-SFH complexes were demonstrated by three techniques: ultrafiltration through 300 kDa cut-off membranes, which distinguished LPS in complexes (87-89% < 300 kDa) from LPS alone (90% > 300 kDa); density centrifugation through 5% sucrose, which distinguished denser LPS alone from LPS-SFH complexes; and precipitation by 67% ethanol, which demonstrated 2-3 fold increased precipitability of complexes compared to SFH alone. Interaction of LPS with SFH was also associated with markedly increased biological activity of LPS, as manifested by enhancement of LPS activation of Limulus amebocyte lysate (LAL), increased release of human mononuclear cell tissue factor, and enhanced production of cultured human endothelial cell tissue factor. These results demonstrated that hemoglobin can serve as an endotoxin binding protein, and that this interaction results in the alteration of several LPS physical characteristics and enhancement of LPS biological activities.

  8. Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

    PubMed

    Moffat, A D; Worth, E R; Weaver, L K

    2015-01-01

    Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded. PMID:26152104

  9. Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

    PubMed

    Moffat, A D; Worth, E R; Weaver, L K

    2015-01-01

    Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded.

  10. Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains.

    PubMed Central

    Vallee, B L; Coleman, J E; Auld, D S

    1991-01-01

    We now recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a "zinc cluster" akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is approximately 3.5 A. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is approximately 13 A, and in this instance, a "zinc twist" is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native "zinc fingers," structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent. Images PMID:1846973

  11. Control of zinc transfer between thionein, metallothionein, and zinc proteins

    PubMed Central

    Jacob, Claus; Maret, Wolfgang; Vallee, Bert L.

    1998-01-01

    Metallothionein (MT), despite its high metal binding constant (KZn = 3.2 × 1013 M−1 at pH 7.4), can transfer zinc to the apoforms of zinc enzymes that have inherently lower stability constants. To gain insight into this paradox, we have studied zinc transfer between zinc enzymes and MT. Zinc can be transferred in both directions—i.e., from the enzymes to thionein (the apoform of MT) and from MT to the apoenzymes. Agents that mediate or enhance zinc transfer have been identified that provide kinetic pathways in either direction. MT does not transfer all of its seven zinc atoms to an apoenzyme, but apparently contains at least one that is more prone to transfer than the others. Modification of thiol ligands in MT zinc clusters increases the total number of zinc ions released and, hence, the extent of transfer. Aside from disulfide reagents, we show that selenium compounds are potential cellular enhancers of zinc transfer from MT to apoenzymes. Zinc transfer from zinc enzymes to thionein, on the other hand, is mediated by zinc-chelating agents such as Tris buffer, citrate, or glutathione. Redox agents are asymmetrically involved in both directions of zinc transfer. For example, reduced glutathione mediates zinc transfer from enzymes to thionein, whereas glutathione disulfide oxidizes MT with enhanced release of zinc and transfer of zinc to apoenzymes. Therefore, the cellular redox state as well as the concentration of other biological chelating agents might well determine the direction of zinc transfer and ultimately affect zinc distribution. PMID:9520393

  12. Inhibitory zinc sites in enzymes.

    PubMed

    Maret, Wolfgang

    2013-04-01

    Several pathways increase the concentrations of cellular free zinc(II) ions. Such fluctuations suggest that zinc(II) ions are signalling ions used for the regulation of proteins. One function is the inhibition of enzymes. It is quite common that enzymes bind zinc(II) ions with micro- or nanomolar affinities in their active sites that contain catalytic dyads or triads with a combination of glutamate (aspartate), histidine and cysteine residues, which are all typical zinc-binding ligands. However, for such binding to be physiologically significant, the binding constants must be compatible with the cellular availability of zinc(II) ions. The affinity of inhibitory zinc(II) ions for receptor protein tyrosine phosphatase β is particularly high (K i = 21 pM, pH 7.4), indicating that some enzymes bind zinc almost as strongly as zinc metalloenzymes. The competitive pattern of zinc inhibition for this phosphatase implicates its active site cysteine and nearby residues in the coordination of zinc. Quantitative biophysical data on both affinities of proteins for zinc and cellular zinc(II) ion concentrations provide the basis for examining the physiological significance of inhibitory zinc-binding sites in proteins and the role of zinc(II) ions in cellular signalling. Regulatory functions of zinc(II) ions add a significant level of complexity to biological control of metabolism and signal transduction and embody a new paradigm for the role of transition metal ions in cell biology.

  13. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets.

    PubMed

    Hunt, Janet R

    2003-09-01

    Iron and zinc are currently the trace minerals of greatest concern when considering the nutritional value of vegetarian diets. With elimination of meat and increased intake of phytate-containing legumes and whole grains, the absorption of both iron and zinc is lower with vegetarian than with nonvegetarian, diets. The health consequences of lower iron and zinc bioavailability are not clear, especially in industrialized countries with abundant, varied food supplies, where nutrition and health research has generally supported recommendations to reduce meat and increase legume and whole-grain consumption. Although it is clear that vegetarians have lower iron stores, adverse health effects from lower iron and zinc absorption have not been demonstrated with varied vegetarian diets in developed countries, and moderately lower iron stores have even been hypothesized to reduce the risk of chronic diseases. Premenopausal women cannot easily achieve recommended iron intakes, as modified for vegetarians, with foods alone; however, the benefit of routine iron supplementation has not been demonstrated. It may be prudent to monitor the hemoglobin of vegetarian children and women of childbearing age. Improved assessment methods are required to determine whether vegetarians are at risk of zinc deficiency. In contrast with iron and zinc, elements such as copper appear to be adequately provided by vegetarian diets. Although the iron and zinc deficiencies commonly associated with plant-based diets in impoverished nations are not associated with vegetarian diets in wealthier countries, these nutrients warrant attention as nutritional assessment methods become more sensitive and plant-based diets receive greater emphasis.

  14. Oral zinc supplementation decreases the serum iron concentration in healthy schoolchildren: a pilot study.

    PubMed

    de Brito, Naira Josele Neves; Rocha, Érika Dantas; de Araújo Silva, Alfredo; Costa, João Batista Sousa; França, Mardone Cavalcante; das Graças Almeida, Maria; Brandão-Neto, José

    2014-09-04

    The recognized antagonistic actions between zinc and iron prompted us to study this subject in children. A convenience sample was used. Thirty healthy children between 8 and 9 years of age were studied with the aim of establishing the effect of a 3-mo oral zinc supplementation on iron status. Fifteen individuals were given a placebo (control group), and 15 were given 10 mg Zn/day (experimental group). Blood samples were collected at 0, 60, 120, 180 and 210 min after a 12-h overnight fast, before and after placebo or zinc supplementation. This supplementation was associated with significant improvements in energy, protein, fat, carbohydrate, fiber, calcium, iron, and zinc intake in accordance with the recommendations for age and sex. The basal serum zinc concentration significantly increased after oral zinc supplementation (p < 0.001). However, basal serum iron concentrations and area under the iron curves significantly decreased in the experimental group (p < 0.0001) and remained at the same level throughout the 210-min study. The values obtained for hemoglobin, mean corpuscular volume, ferritin, transferrin, transferrin saturation, ceruloplasmin and total protein were within normal reference ranges. In conclusion, the decrease in serum iron was likely due to the effects of chronic zinc administration, and the decrease in serum iron was not sufficient to cause anemia.

  15. Interaction of the chlorite-based drug WF10 and chlorite with hemoglobin, methemoglobin and ferryl hemoglobin.

    PubMed

    Pichert, Annelie; Arnhold, Jürgen

    2015-11-01

    The interaction of the chlorite-based drug solution WF10 with human oxyhemoglobin and oxidized hemoglobin forms was investigated monitoring the corresponding spectral changes in heme states. The chlorite component of WF10 converts oxyhemoglobin into methemoglobin with a rate of 35.4 M(-1)s(-1). Methemoglobin is also formed upon the interaction of ferryl hemoglobin and WF10/chlorite. The rate of this interconversion depends on the oxidation state of ferryl hemoglobin. This rate is 114 M(-1)s(-1), when ferryl hemoglobin was generated upon reaction of oxyhemoglobin and hydrogen peroxide. A considerable higher rate (6600 M(-1)s(-1)) is measured between the chlorite components of WF10 and ferryl hemoglobin after formation of the latter species from methemoglobin. WF10/chlorite inactivates also methemoglobin as evidenced by the continuous decrease of the Soret band and all other absorbances with a rate of 8.3 M(-1)s(-1). In all interconversions, the chlorite component of WF10 was the active principle as shown in experiments applying pure chlorite at the same concentration as in WF10. Thus, WF10 is able to diminish efficiently the yield of cytotoxic hemoglobin species that might appear after excessive hemolysis of red blood cells under pathologic situations.

  16. Evaluation of metallothionein formation as a proxy for zinc absorption in an in vitro digestion/caco-2 cell culture model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Caco-2 cell metallothionein (MT) formation was studied to determine if MT could be used as a proxy for zinc (Zn) absorption in a cell culture model. MT intracellular concentration was determined by using a cadmium/hemoglobin affinity assay. Cellular Zn uptake was determined in acid digests (5% HNO3)...

  17. Zinc in diet

    MedlinePlus

    ... Zinc is also needed for the senses of smell and taste. During pregnancy, infancy, and childhood the ... sense of taste Problems with the sense of smell Skin sores Slow growth Trouble seeing in the ...

  18. Zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, Jr., Philip N.

    1989-01-01

    An improved zinc electrode is disclosed for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed which utilizes the improved zinc electrode and further includes an alkaline electrolyte within said battery circulating through the passageways in the zinc electrode and an external electrolyte circulation means which has an electrolyte reservoir external to the battery case including filter means to filter solids out of the electrolyte as it circulates to the external reservoir and pump means for recirculating electrolyte from the external reservoir to the zinc electrode.

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

    PubMed Central

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

    1990-01-01

    Synthetic genes encoding the human alpha- and beta-globin polypeptides have been expressed from a single operon in Escherichia coli. The alpha- and beta-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to greater than 5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of alpha- and beta-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 C4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A0 and comigrates with hemoglobin A0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A0. The recombinant protein shows a reduction in Bohr and phosphate effects, which may be attributed to the presence of methionine at the amino termini of the alpha and beta chains. We have also expressed the alpha- and beta-globin genes separately and found that the expression of the alpha-globin gene alone results in a marked decrease in the accumulation of alpha-globin in the cell. Separate expression of the beta-globin gene results in high levels of insoluble beta-globin. These observations suggest that the presence of alpha- and beta-globin in the same cell stabilizes alpha-globin and aids the correct folding of beta-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. Images PMID:2236062

  20. Zinc deficiency in elderly patients.

    PubMed

    Prasad, A S; Fitzgerald, J T; Hess, J W; Kaplan, J; Pelen, F; Dardenne, M

    1993-01-01

    Zinc is needed for growth and development, DNA synthesis, neurosensory functions, and cell-mediated immunity. Although zinc intake is reduced in elderly people, its deficiency and effects on cell-mediated immunity of the elderly have not been established. Subjects enrolled in "A Model Health Promotion and Intervention Program for Urban Middle Aged and Elderly Americans" were assessed for nutrition and zinc status. One hundred eighty healthy subjects were randomly selected for the study. Their mean dietary zinc intake was 9.06 mg/day, whereas the recommended dietary allowance is 15 mg/day. Plasma zinc was normal, but zinc in granulocytes and lymphocytes were decreased compared with younger control subjects. Of 118 elderly subjects in whom zinc levels in both granulocytes and lymphocytes were available, 36 had deficient levels. Plasma copper was increased, and interleukin 1 (IL-1) production was significantly decreased. Reduced response to the skin-test antigen panel and decreased taste acuity were observed. Thirteen elderly zinc-deficient subjects were supplemented with zinc, and various variables were assessed before and after zinc supplementation. Zinc supplementation corrected zinc deficiency and normalized plasma copper levels. Serum thymulin activity, IL-1 production, and lymphocyte ecto-5'-nucleotidase increased significantly after supplementation. Improvement in response to skin-test antigens and taste acuity was observed after zinc supplementation. A mild zinc deficiency appears to be a significant clinical problem in free-living elderly people. PMID:8353362

  1. Treatment of zinc deficiency without zinc fortification

    PubMed Central

    Oberleas, Donald; Harland, Barbara F.

    2008-01-01

    Zinc (Zn) deficiency in animals became of interest until the 1950s. In this paper, progresses in researches on physiology of Zn deficiency in animals, phytate effect on bioavailability of Zn, and role of phytase in healing Zn deficiency of animals were reviewed. Several studies demonstrated that Zn is recycled via the pancreas; the problem of Zn deficiency was controlled by Zn homeostasis. The endogenous secretion of Zn is considered as an important factor influencing Zn deficiency, and the critical molar ratio is 10. Phytate (inositol hexaphosphate) constituted up to 90% of the organically bound phosphorus in seeds. Great improvement has been made in recent years on isolating and measuring phytate, and its structure is clear. Phytate is considered to reduce Zn bioavailability in animal. Phytase is the enzyme that hydrolyzes phytate and is present in yeast, rye bran, wheat bran, barley, triticale, and many bacteria and fungi. Zinc nutrition and bioavailability can be enhanced by addition of phytase to animal feeds. Therefore, using phytase as supplements, the most prevalent Zn deficiency in animals may be effectively corrected without the mining and smelting of several tons of zinc daily needed to correct this deficiency by fortification worldwide. PMID:18357621

  2. Studies in red blood cell preservation: 4. Plasma vesicle hemoglobin exceeds free hemoglobin.

    PubMed

    Greenwalt, T J; McGuinness, C G; Dumaswala, U J

    1991-01-01

    Studies were designed to find out how much of the plasma hemoglobin ( Hb) in whole blood was in microvesicles and how much was free Hb after 21 days of storage in citrate-phosphate-dextrose anticoagulant and to determine the effect of the plasticizer, di-(2-ethylhexyl)phthalate (DEHP). The total plasma Hb in polyolefin (PO) containers without DEHP was much higher than in polyvinyl chloride (PVC) with the plasticizer (p = 0.004). Less than 30% of the Hb was in free solution in either type of container. The addition of 300 micrograms/ml of DEHP to the plasma in the PO containers resulted in marked reduction in the microvesiculation (p less than 0.01) but did not affect the level of free Hb. RBC hypotonic fragility and morphology scores were significantly improved. It is concluded that microvesiculation contributes more to plasma Hb concentration than free Hb during storage. Some hemolysis of red blood cells (RBC) is expected during blood bank storage. It has been shown that part of the hemoglobin (Hb) in the suspending medium is free and part is encapsulated in microvescicles shed by the RBC [1]. The amount of hemolysis and microvesiculation that occurs has been noted to be less when blood is stored in polyvinyl chloride (PVC) containers in which di-(2-ethylhexyl)phthalate (DEHP) is used as the plasticizer [1]. The DEHP that leaches into the plasma has been shown to decrease hemolysis, microvesiculation, and the increase in osmotic fragility which RBC undergo during refrigerated storage [2-9].(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1949704

  3. Endogenous zinc in neurological diseases.

    PubMed

    Koh, Jae-Yong

    2005-10-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized.

  4. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  5. Hemoglobin variability after renal transplantation is associated with mortality

    PubMed Central

    Kainz, Alexander; Wilflingseder, Julia; Függer, Reinhold; Kramar, Reinhard; Oberbauer, Rainer

    2012-01-01

    Summary Anemia is a common problem after renal transplantation. Therefore, the patients are treated with erythropoietin stimulating agents (ESAs). The varying response to treatment contributes to hemoglobin variability, which might be associated with mortality. We conducted a retrospective cohort study of first kidney allograft recipients between 1990 and 2008 represented in the Austrian Transplant Registry. We included 1441 patients of whom 683 received ESAs at any time after transplantation. Cox regression with cubic splines and linear estimates and the purposeful selection algorithm of covariables were used. The measure of variability was the moving standard deviation computed at three monthly intervals for the entire graft life. The hazard ratio (HR) of mortality and graft loss in the spline models increased with hemoglobin variability. The linear HR for mortality was 2.35 (95% confidence interval 1.75–3.17, P < 0.001) and functional graft loss 2.45 (1.76–3.40, P < 0.001). In an adjusted Cox model (ESA use, hemoglobin, age, diabetes, days on dialysis, eGFR, biopsy confirmed acute rejection and year of transplantation), hemoglobin variability was associated with mortality (HR: 2.11; 1.51–2.94; P < 0.001). No association with functional graft loss could be detected (HR: 1.34; 0.93-1.93; P = 0.121). These findings suggest that hemoglobin variability is associated with mortality of renal allograft recipients. PMID:22313094

  6. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.

    PubMed

    Kelkitli, Engin; Ozturk, Nurinnisa; Aslan, Nevin Alayvaz; Kilic-Baygutalp, Nurcan; Bayraktutan, Zafer; Kurt, Nezahat; Bakan, Nuri; Bakan, Ebubekir

    2016-04-01

    Iron deficiency anemia (IDA) is a major public health problem especially in underdeveloped and developing countries. Zinc is the co-factor of several enzymes and plays a role in iron metabolism, so zinc deficiency is associated with IDA. In this study, it was aimed to investigate the relationship of symptoms of IDA and zinc deficiency in adult IDA patients. The study included 43 IDA patients and 43 healthy control subjects. All patients were asked to provide a detailed history and were subjected to a physical examination. The hematological parameters evaluated included hemoglobin (Hb); hematocrit (Ht); red blood cell (erythrocyte) count (RBC); and red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (МСН), mean corpuscular hemoglobin concentration (МСНС), and red cell distribution width (RDW). Anemia was defined according to the criteria defined by the World Health Organization (WHO). Serum zinc levels were measured in the flame unit of atomic absorption spectrophotometer. Symptoms attributed to iron deficiency or depletion, defined as fatigue, cardiopulmonary symptoms, mental manifestations, epithelial manifestations, and neuromuscular symptoms, were also recorded and categorized. Serum zinc levels were lower in anemic patients (103.51 ± 34.64 μ/dL) than in the control subjects (256.92 ± 88.54 μ/dL; <0.001). Patients with zinc level <99 μ/dL had significantly more frequent mental manifestations (p < 0.001), cardiopulmonary symptoms (p = 0.004), restless leg syndrome (p = 0.016), and epithelial manifestations (p < 0.001) than patients with zinc level > 100 μ/dL. When the serum zinc level was compared with pica, no statistically significant correlation was found (p = 0.742). Zinc is a trace element that functions in several processes in the body, and zinc deficiency aggravates IDA symptoms. Measurement of zinc levels and supplementation if necessary should be considered for IDA patients.

  7. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, ...

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

    ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, LOOKING NORTH. NOTE ONE STYLE OF DENVER AGITATOR IN LOWER RIGHT CELL. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

  8. Suppression of zinc dendrites in zinc electrode power cells

    NASA Technical Reports Server (NTRS)

    Damjanovic, A.; Diggle, J. W.

    1970-01-01

    Addition of various tetraalkyl quarternary ammonium salts, to alkaline zincate electrolyte of cell, prevents formation of zinc dendrites during charging of zinc electrode. Electrode capacity is not impaired and elimination of dendrites prolongs cell life.

  9. COPPER AND COBALT RELATED HEMOGLOBIN PRODUCTION IN EXPERIMENTAL ANEMIA

    PubMed Central

    Robscheit-Robbins, F. S.; Whipple, G. H.

    1942-01-01

    Copper added to a standard diet often effects a moderate increase in hemoglobin production in anemia due to blood loss. The copper response is quite irregular in contrast to the iron response. In these dogs there is no lack of copper held in reserve stores (liver and spleen) so the reaction is not related to an actual deficiency of the element. An effect upon enzyme complexes related to globin and hemoglobin production is to be considered. Cobalt under similar conditions causes no stimulus to hemoglobin production, rather an inhibitory effect when more than minimal doses are given. The claim that cobalt causes a polycythemia in dogs receives no support from our experiments. PMID:19871199

  10. Hemoglobin - a novel ligand of hepatocyte ectopic F1-ATPase.

    PubMed

    Gburek, J; Konopska, B; Juszczynska, K; Piwowar, A; Dziegiel, P; Borska, S; Tolosano, E; Golab, K

    2015-12-01

    The liver is largely responsible for free hemoglobin uptake, but the molecular mechanism of this phenomenon has never been revealed. This paper presents the results of the study on hemoglobin binding components of the hepatocyte membrane that were purified using affinity chromatography on a hemoglobin matrix and identified by peptide mass fingerprinting. Both F1-ATPase alpha and beta subunits were retrieved. The binding was confirmed via an intrinsic fluorescence quenching study using a purified recombinant F1-ATPase beta subunit, and the dissociation constant for the complex was estimated from the saturation binding curve (Kd = 7.5 x 10(-7) M). The results indicate that haemoglobin binds to hepatocyte ectopic F1-ATPase. We suggested the plausible role of the receptor in endocytosis of haemoglobin by the hepatocyte.

  11. Conformational changes monitored by fluorescence study on reconstituted hemoglobins

    NASA Astrophysics Data System (ADS)

    Venkateshrao, S.; Manoharan, P. T.

    2004-09-01

    Intrinsic steady state fluorescence measurements were performed on a series of reconstituted metal ion and hybrid hemoglobins (Hbs). At 296 nm excitation, the spectrum exhibits a broad and asymmetric feature in the case of copper and nickel reconstituted hemoglobins. Deconvolution of the fluorescence bands clearly reveals the existence of two definite peaks. A similar trend was also observed for hybrid hemoglobins (CuNi, NiCu, CuFe-CO, and NiFe-CO). A guassian fit of the fluorescence bands in these proteins again yields two prominent peaks, which are assigned as due to two different tryptophan (Trp) environments. A relative ratio of the amplitudes of these peaks indicates the percentage of T-character in these molecules. This is in support to our previous findings by other spectroscopic studies on the same molecules. These studies therefore, suggest the presence of two different environments of a tryptophan thereby revealing structural heterogeneity among the subunits.

  12. Erythrocyte phosphates and hemoglobin function in monotremes and some marsupials.

    PubMed

    Isaacks, R; Nicol, S; Sallis, J; Zeidler, R; Kim, H D

    1984-02-01

    Hematologic values, red blood cell (RBC) organic phosphate composition, hemoglobin function, and hemoglobin composition have been determined on blood from the monotremes, the duckbill platypus and the echidna, and three species of marsupials, the Tasmanian devil, the wallaby, and the brush-tail possum. Blood from the platypus had a RBC count of 8.63 X 10(6)/mm3, a mean corpuscular volume of 49.1 millemicron3, and a white blood cell count of 26.0 X 10(3)/mm3. The RBCs from the monotremes and the three marsupials exhibited hemoglobin polymorphism, each with three hemoglobin components. Addition of ATP, 2,3-bisphosphoglycerate (2,3-P2-glycerate), or inositol pentakisphosphate (inositol-P5) to phosphate-free hemoglobin from each species decreased hemoglobin oxygen affinity; the order of effect of these compounds was ATP less than 2,3-P2-glycerate less than inositol-P5. The RBCs of all species had concentrations of 2,3-P2-glycerate ranging from 6.02 mumol/ml RBCs in the wallaby to 10.39 mumol/ml RBCs in the possum. The RBCs from the three species of marsupials had concentrations of ATP ranging from 0.24 mumol/ml RBCs in the possum to 0.80 mumol/ml RBCs in the Tasmanian devil. The level of ATP in RBCs of the platypus and echidna were 0.06 and 0.03 mumol/ml RBCs, respectively.

  13. Independency of Fe ions in hemoglobin on immunomagnetic reduction assay

    NASA Astrophysics Data System (ADS)

    Yang, S. Y.; Lan, C. B.; Chen, C. H.; Horng, H. E.; Hong, Chin-Yih; Yang, H. C.; Lai, Y. K.; Lin, Y. H.; Teng, K. S.

    2009-10-01

    Immunomagnetic reduction (IMR), which involves measuring the reduction in the ac magnetic susceptibility of magnetic reagents, is due to the association between bio-functionalized magnetic nanoparticles and target bio-molecules. This has been demonstrated for assaying proteins in solutions free of Fe ions, such as serum. In this work, the validity of IMR assay for samples rich in Fe ions like hemoglobin (Hb) is investigated. According to the results, there is no magnetic signal contributed by Fe-ion-rich Hb. Furthermore, the results show a high sensitivity in assaying hemoglobin A1c (HbA1c) by using IMR.

  14. Structural significance of the amino terminal residues in human hemoglobin

    SciTech Connect

    Hefta, S.A.

    1986-01-01

    The amino terminal valine residues on the alpha chains of human hemoglobin are known to be important for the function of the molecule. Allosteric effectors such as protons, chloride ions and metabolic anions such as 2,3-diphosphoglycerate bind or associate with these residues and facilitate the release of oxygen. Carbon dioxide also functions as an effector as it is partly transported from the tissues to the lungs by binding to the amino terminal residues. This research describes the semisynthetic alteration of this region and the hemoglobin analogs produced were analyzed by /sup 13/C NMR.

  15. Clinical manifestations of zinc deficiency.

    PubMed

    Prasad, A S

    1985-01-01

    The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal diseases, following uses of certain drugs such as penicillamine for Wilson's disease and diuretics in some cases, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. In pregnancy and during periods of growth the requirement of zinc is increased. The clinical manifestations in severe cases of zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males; it is fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. Its deficiency adversely affects growth in many animal species and humans. Inasmuch as zinc is needed for protein and DNA synthesis and for cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Whether or not zinc is required for the metabolism of somatomedin needs to be investigated in the future. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level; the hypothalamic-pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in cell division, its deficiency may adversely affect testicular size and thus affect its functions. Zinc is required for the functions of several enzymes and whether or not it has an enzymatic role in steroidogenesis is not known at present

  16. Fortified juice drink improved iron and zinc status of schoolchildren.

    PubMed

    Angeles-Agdeppa, Imelda; Magsadia, Clarita R; Capanzana, Mario V

    2011-01-01

    Energy and micronutrient deficiency remain prevalent among Filipino children. Juice drinks are commonly consumed and could be a viable vehicle for fortification to supplement the nutrient gap. This study determined the effects of a newly developed non-carbonated fortified juice drink on the iron, zinc and nutritional status of schoolchildren. One hundred randomly selected anemic children were randomly allocated into two groups in a doubly-masked placebo controlled manner: Group 1 received the fortified juice, Group 2 received the non-fortified juice for 100 days, five days a week under strict supervision. The juice drink was fortified with vitamin A, zinc, iron, vitamin C and lysine. The non-fortified juice was fortified only with vitamin C. All children were dewormed prior to the intervention. Hemoglobin, plasma ferritin and plasma zinc, weight and height were assessed using standard methods before and after intervention. A two-day 24-hour food recall was also collected. The basal prevalence of anemia was significantly reduced in both the fortified group (100% to 13%) and the non-fortified group (100% to 40%) at endline. The mean plasma ferritin levels were similar in both groups at baseline and endline. At endline, mean plasma zinc in the fortified group has significantly increased by 20 μg/dL from a baseline value of 83.9 μg/dL to 103.9 μg/dL, while the non-fortified group remained at similar levels with baseline. Basal weight and height significantly increased among all children at endline. The fortified juice drink was effective in reducing the prevalence of anemia and improved the zinc status of children. PMID:22094838

  17. Neurotransmitter transporter family including SLC6A6 and SLC6A13 contributes to the 5-aminolevulinic acid (ALA)-induced accumulation of protoporphyrin IX and photodamage, through uptake of ALA by cancerous cells.

    PubMed

    Tran, Tai Tien; Mu, Anfeng; Adachi, Yuka; Adachi, Yasushi; Taketani, Shigeru

    2014-01-01

    δ-Aminolevulinic acid (ALA)-induced protoporphyrin accumulation is widely used in the treatment of cancer, as photodynamic therapy (PDT). To clarify the mechanisms of ALA uptake by tumor cells, we have examined the ALA-induced accumulation of protoporphyrin by the treatment of colon cancer DLD-1 and epithelial cancer HeLa cells with γ-aminobutyric acid (GABA)-related compounds. When the cells were treated with GABA, taurine and β-alanine, the level of protoporphyrin was decreased, suggesting that plasma membrane transporters involved in the transport of neurotransmitters contribute to the uptake of ALA. By transfection with neurotransmitter transporters SLC6A6, SLC6A8 and SLC6A13 cDNA, the ALA- and ALA methylester-dependent accumulation of protoporphyrin markedly increased in HEK293T cells, dependent on an increase in the uptake of ALA. When ALA-treated cells were exposed to white light, the extent of photodamage increased in SLC6A6- and SLC6A13-expressing cells. Conversely, knockdown of SLC6A6 or SLC6A13 with siRNAs in DLD-1 and HeLa cells decreased the ALA-induced accumulation. The expression of SLC6A6 and SLC6A13 was found in some cancer cell lines. Immunohistochemical studies revealed that the presence of these transporters was elevated in colon cancerous cells. These results indicated that neurotransmitter transporters including SLC6A6 and SLC6A13 mediate the uptake of ALA and can play roles in the enhancement of ALA-induced accumulation of protoporphyrin in cancerous cells.

  18. Zinc titanate sorbents

    DOEpatents

    Gupta, Raghubir P.; Gangwal, Santosh K.; Jain, Suresh C.

    1998-01-01

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750.degree. C. to about 950.degree. C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 .mu., and about 1 part titanium dioxide having a median particle size of less than about 1 .mu.. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  19. Zinc titanate sorbents

    DOEpatents

    Gupta, R.P.; Gangwal, S.K.; Jain, S.C.

    1998-02-03

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750 to about 950 C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 microns, and about 1 part titanium dioxide having a median particle size of less than about 1 micron. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  20. Nrf2-mediated haeme oxygenase-1 up-regulation induced by cobalt protoporphyrin has antinociceptive effects against inflammatory pain in the formalin test in mice.

    PubMed

    Rosa, Angelo O; Egea, Javier; Lorrio, Silvia; Rojo, Ana I; Cuadrado, Antonio; López, Manuela G

    2008-07-15

    This study investigated the effect of haeme oxygenase-1 (HO-1) in nociception induced by formalin injection in the mice hind paw. Intraperitoneal (i.p.) administration of cobalt protoporphyrin (CoPP, an HO-1 inducer, 5mg/kg) 24h before the test, inhibited the nociceptive response during the second phase, but not during the first phase of the formalin test. The effect of CoPP was prevented by treatment with tin protoporphyrin (SnPP, an inhibitor of HO-1 activity) administered either by i.p. (25mg/kg, 30 min before the test) or intraplantar (400 nmol/paw, 5 min before the test) routes. Human embryonic kidney (HEK) 293T cells treated with 10 microM CoPP expressed 20-fold higher HO-1 levels when compared to controls; this effect was suppressed by transfection with the dominant negative for the nuclear factor-erythroid 2-related factor 2 (Nrf2). Western blot analysis also revealed that CoPP treatment induced a similar 20-fold increase in HO-1 expression in the paw; this effect was attenuated in knockout mice for Nrf2. CoPP treatment of wild-type, but not in Nrf2 knockout mice, resulted in a striking increase of HO-1 stained cells surrounding the muscular tissues of the hind limbs. HO-1 positive cells were scarce in wild-type and in Nrf2 knockout untreated mice. CoPP-induced HO-1 expression in Nrf2 knockout mice was lost and correlated with the loss of antinociceptive effects. In conclusion, Nrf2-mediated HO-1 expression induced an antinociceptive effect at peripheral sites. These results suggest that HO-1 modulates the inflammatory pain pathways. Hence, the development of drugs that could raise peripheral HO-1 could be relevant in inflammatory pain treatment.

  1. Determination of cytochrome c and other heme proteins using the reduction wave of mercury protoporphyrin IX groups generated by a hydroxylamine induced replacement reaction.

    PubMed

    Luo, Dengbai; Huang, Jinxiang

    2009-03-01

    We have found that in the presence of hydroxylamine, the heme prosthetic group of the heme protein adsorbed at the mercury electrode surface reacts with mercury ion produced by the electrochemical oxidation of mercury and is quantitatively converted into the mercury protoporphyrin IX group using single-sweep polarography. As a result, the small redox peak P(0) of the heme prosthetic group at about -0.46 V (vs SCE) disappears and a large new reduction peak P of mercury protoporphyrin IX group at -0.89 V comes out in a pH 9.6 NaHCO(3)-Na(2)CO(3) solution. Peak P is extremely sensitive to heme protein concentration. On the basis of the reduction peak P, a unique electrochemical method for heme protein assays is constructed. For the cytochrome c determination, the peak height is linearly proportional to the concentration in the range of 0.005-15 mg L(-1) (correlation coefficient 0.999). The detection limit is 0.003 mg L(-1). In contrast with peak P(0), the detection limit of cytochrome c is only 0.6 mg L(-1). The voltammograms of heme proteins in the absence and presence of hydroxylamine can serve as a reliable qualitative analytical method. The chemical reaction is peculiar to the heme prosthetic group. Without hydroxylamine it cannot occur. Thereby the method is highly specific and free from interference. The performance takes only a few minutes. These advantages make the method attractive for heme protein detecting.

  2. [Hemoglobins, XLVIII: the primary structure of hemoglobin of the Indian elephant (Elephas maximus, Proboscidea): beta 2 = Asn].

    PubMed

    Braunitzer, G; Jelkmann, W; Stangl, A; Schrank, B; Krombach, C

    1982-07-01

    The primary structure of the hemoglobin of the Indian Elephant (Elephas maximus) is given. The sequence was determined automatically in a sequenator. By homologous comparison with adult human HbA, the alpha-chains differ by 24 exchanges and the beta-chains by 27 exchanges. Furthermore, we report p(O2)50 values with regard to altered contact sites with 2,3-bisphosphoglycerate in Indian elephant hemoglobin. Our findings explain the low p(O2)50 and the reduced interaction with 2,3-bisphosphoglycerate. Elephant hemoglobin has, like that of the Llama, only five phosphate binding sites. In addition, we have made an attempt to relate these results to aspects of respiratory physiology. Some implications of these biochemical and physiological results, concerning the Second Punic War and Hannibal's Alp transition, are given.

  3. A recombinant human hemoglobin with anti-sickling properties greater than fetal hemoglobin.

    PubMed

    Levasseur, Dana N; Ryan, Thomas M; Reilly, Michael P; McCune, Steven L; Asakura, Toshio; Townes, Tim M

    2004-06-25

    A new recombinant, human anti-sickling beta-globin polypeptide designated beta(AS3) (betaGly(16) --> Asp/betaGlu(22) --> Ala/betaThr(87) --> Gln) was designed to increase affinity for alpha-globin. The amino acid substitutions at beta22 and beta87 are located at axial and lateral contacts of the sickle hemoglobin (HbS) polymers and strongly inhibit deoxy-HbS polymerization. The beta16 substitution confers the recombinant beta-globin subunit (beta(AS3)) with a competitive advantage over beta(S) for interaction with the alpha-globin polypeptide. Transgenic mouse lines that synthesize high levels of HbAS3 (alpha(2)beta(AS3)(2)) were established, and recombinant HbAS3 was purified from hemolysates and then characterized. HbAS3 binds oxygen cooperatively and has an oxygen affinity that is comparable with fetal hemoglobin. Delay time experiments demonstrate that HbAS3 is a potent inhibitor of HbS polymerization. Subunit competition studies confirm that beta(AS3) has a distinct advantage over beta(S) for dimerization with alpha-globin. When equal amounts of beta(S)- and beta(AS3)-globin monomers compete for limiting alpha-globin chains up to 82% of the tetramers formed is HbAS3. Knock-out transgenic mice that express exclusively human HbAS3 were produced. When these mice were bred with knock-out transgenic sickle mice the beta(AS3) polypeptides corrected all hematological parameters and organ pathology associated with the disease. Expression of beta(AS3)-globin should effectively lower the concentration of HbS in erythrocytes of patients with sickle cell disease, especially in the 30% percent of these individuals who coinherit alpha-thalassemia. Therefore, constructs expressing the beta(AS3)-globin gene may be suitable for future clinical trials for sickle cell disease. PMID:15084588

  4. Serum concentrations of micronutrients, packed cell volume, and blood hemoglobin during the first two gestations and lactations of sows.

    PubMed Central

    Girard, C L; Robert, S; Matte, J J; Farmer, C; Martineau, G P

    1996-01-01

    The objective of the present work was to describe the changes in serum concentrations of some micronutrients during the first 2 gestations and lactations of 33 gilts in order to establish blood reference values for a rapid assessment of nutritional status. In both parities, blood samples were taken from the jugular vein at mating, 5, 10 and 15 wk of gestation and l d and 4 wk after parturition (weaning). Reference values (mean, standard deviation, minimum, maximum) for serum folates, vitamin B12, vitamin B6 metabolites (pyridoxal and pyridoxal-5-phosphate), calcium, phosphorus, sodium, zinc, copper and iron, as well as blood hemoglobin and packed cell volume are reported for each studied time. Differences between parities and between each time are also reported. Results from the present report demonstrate that knowledge of the physiological state of the sows is critical for the assessment of nutritional status of an individual or a breeding herd by interpretation of analyses of blood constituents. PMID:8809380

  5. Observations of interstellar zinc

    NASA Technical Reports Server (NTRS)

    Jura, M.; York, D.

    1981-01-01

    The International Ultraviolet Explorer observations of interstellar zinc toward 10 stars are examined. It is found that zinc is at most only slightly depleted in the interstellar medium; its abundance may serve as a tracer of the true metallicity in the gas. The local interstellar medium has abundances that apparently are homogeneous to within a factor of two, when integrated over paths of about 500 pc, and this result is important for understanding the history of nucleosynthesis in the solar neighborhood. The intrinsic errors in detecting weak interstellar lines are analyzed and suggestions are made as to how this error limit may be lowered to 5 mA per target observation.

  6. Photovoltaic cells employing zinc phosphide

    DOEpatents

    Barnett, Allen M.; Catalano, Anthony W.; Dalal, Vikram L.; Masi, James V.; Meakin, John D.; Hall, Robert B.

    1984-01-01

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  7. Recovering Zinc From Discarded Tires

    NASA Technical Reports Server (NTRS)

    Du Fresne, E. R.

    1984-01-01

    Zinc sulfate monohydrate sold at profit. Shredded tire material steeped in three sulfuric acid baths to extract zinc. Final product removed by evaporating part of solution until product crystallizes out. Recovered as zinc sulfate monohydrate and sold as fertilizer or for general use.

  8. Photovoltaic cells employing zinc phosphide

    SciTech Connect

    Barnett, A.M.; Catalano, A.W.; Dalal, V.L.; Hall, R.B.; Masi, J.V.; Meakin, J.D.

    1984-10-16

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  9. Zinc requirements and zinc intakes of breast-fed infants.

    PubMed

    Krebs, N F; Hambidge, K M

    1986-02-01

    Longitudinal changes in dietary zinc requirements for infants at different levels of net absorption were estimated using a factorial approach. Apart from variations in net absorption, the zinc needed for new lean body mass is the major determinant of requirements. As growth velocity declines progressively, estimated zinc requirements for growth and for replacement of urine and sweat losses decrease from a high for male infants of 780 micrograms/day at 1 mo to 480 micrograms/day in the 5th mo and then remain quite constant through the 1st yr. Calculated percentage absorption of zinc from human milk necessary to meet estimated requirements increases with duration of lactation. For infants of mothers whose zinc intake approximated 25 mg/day the calculated percentage absorption remained within plausible limits. It is suggested that the progressive decrease in milk zinc concentrations provides a mechanism for conserving maternal zinc while meeting infant needs. PMID:3946293

  10. Hemoglobin Birmingham and hemoglobin Galicia: two unstable beta chain variants characterized by small deletions and insertions.

    PubMed

    Wilson, J B; Webber, B B; Hu, H; Kutlar, A; Kutlar, F; Codrington, J F; Prchal, J T; Hall, K M; de Pablos, J M; Rodriguez, I

    1990-05-01

    Two unstable hemoglobins (Hbs) causing rather severe hemolytic anemia have been characterized. The beta chain of Hb Birmingham, found in an adult black man, is characterized by the loss of -Leu-Ala-His-Lys- at positions 141, 142, 143, and 144 and their replacement by one Gln residue. These changes are the result of a deletion of nine nucleotides, namely two base pairs (bp) of codon 141, all of codons 142 and 143, and one bp of codon 144; the remaining CAG triplet (C from codon 141 and AG from codon 144) codes for the inserted glutamine. In the beta chain of Hb Galicia from a Spanish patient, His and Val at positions 97 and 98 are replaced by one Leu residue. This is due to an ACG deletion in codons 97 and 98, which causes the removal of one His and one Val residue, while the remaining CTG triplet (C from codon 97 and TG from codon 98) codes for the inserted leucine residue. Two mechanisms, namely slipped mispairing in the presence of short repeats, and misreading by DNA polymerase due to a local distortion of the DNA helix, are considered in explaining the origin of the small deletions.

  11. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  12. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  13. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  14. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  15. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  16. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  17. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  18. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  19. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  20. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  1. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  2. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  3. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  4. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  5. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  6. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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...

  7. Ultrasonic processing for recovery of chicken erythrocyte hemoglobin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hemoglobin from chicken blood has been shown to be a good substitute for synthetic polymeric flocculants. One stage of processing the blood entails breaking open the cells and releasing the cytoplasmic contents; in the present study, we investigate the use of ultrasonic processing at this stage. Was...

  8. Rapid and sensitive quantitation of heme in hemoglobinized cells.

    PubMed

    Marcero, Jason R; Piel Iii, Robert B; Burch, Joseph S; Dailey, Harry A

    2016-01-01

    Rapid and accurate heme quantitation in the research lab has become more desirable as the crucial role that intracellular hemoproteins play in metabolism continues to emerge. Here, the time-honored approaches of pyridine hemochromogen and fluorescence heme assays are compared with direct absorbance-based technologies using the CLARiTY spectrophotometer. All samples tested with these methods were rich in hemoglobin-associated heme, including buffered hemoglobin standards, whole blood from mice, and murine erythroleukemia (MEL) and K562 cells. While the pyridine hemochromogen assay demonstrated the greatest linear range of heme detection, all 3 methods demonstrated similar analytical sensitivities and normalized limits of quantitation of ∼1 µM. Surprisingly, the fluorescence assay was only shown to be distinct in its ability to quantitate extremely small samples. Using the CLARiTY system in combination with pyridine hemochromogen and cell count data, a common hemoglobin extinction coefficient for blood and differentiating MEL and K562 cells of 0.46 µM-1 cm-1 was derived. This value was applied to supplemental experiments designed to measure MEL cell hemoglobinization in response to the addition or removal of factors previously shown to affect heme biosynthesis (e.g., L-glutamine, iron). PMID:27528073

  9. Human macrophage hemoglobin-iron metabolism in vitro

    SciTech Connect

    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 /sup 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 /sup 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 /sup 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.

  10. Effect of Some High Consumption Spices on Hemoglobin Glycation

    PubMed Central

    Naderi, G. H.; Dinani, Narges J.; Asgary, S.; Taher, M.; Nikkhoo, N.; Boshtam, M.

    2014-01-01

    Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes. PMID:25593391

  11. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Indications for use. For the treatment of anemia in dogs by increasing systemic oxygen content (plasma hemoglobin concentration) and improving the clinical signs associated with anemia, regardless of the cause of anemia (hemolysis, blood loss, or ineffective erythropoiesis). (3) Limitations. For intravenous use...

  12. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Indications for use. For the treatment of anemia in dogs by increasing systemic oxygen content (plasma hemoglobin concentration) and improving the clinical signs associated with anemia, regardless of the cause of anemia (hemolysis, blood loss, or ineffective erythropoiesis). (3) Limitations. For intravenous use...

  13. Effect of some high consumption spices on hemoglobin glycation.

    PubMed

    Naderi, G H; Dinani, Narges J; Asgary, S; Taher, M; Nikkhoo, N; Boshtam, M

    2014-01-01

    Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes.

  14. Correlations between oxygen affinity and sequence classifications of plant hemoglobins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants express three phylogenetic classes of hemoglobins (Hb) based on sequence analyses. Class 1 and 2 Hbs are full length globins with the classical 8 helix Mb-like fold, whereas Class 3 plant Hbs resemble the truncated globins found in bacteria. With the exception of the specialized leghemoglobin...

  15. Occult hemoglobin as an indicator of impingement stress in fishes

    SciTech Connect

    Not Available

    1980-01-01

    During the process of impingement on cooling system intake screens, fish may be subject to different types of stress, the total of which often results in the death of individual fish. This report assesses the use of occult hemoglobin in fish demand mucus as an indicator of impingement stress. (ACR)

  16. Using a Poetry Reading on Hemoglobin to Enhance Subject Matter

    ERIC Educational Resources Information Center

    Herrick, Richard S.; Cording, Robert K.

    2013-01-01

    student interest in the beauty and mystery of chemistry. A reading of the poem "Jerry-Built Forever" (on various aspects of hemoglobin) is used as an example; the poem is included in the article. Details of how the reading was performed and reactions of the…

  17. Influence of hemoglobin on non-invasive optical bilirubin sensing

    NASA Astrophysics Data System (ADS)

    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.

  18. The Relationship Between Hemoglobin Level and Intellectual Function.

    ERIC Educational Resources Information Center

    Munro, Nancy

    In a study to learn whether or not poor nutrition, as indicated by low hemoglobin levels, affects intelligence and behavior, 113 Head Start children in Missoula, Montana took part. Group testing with the Lorge Thorndike Intelligence Test and individual testing with the Wechsler and Primary Scale of Intelligence or Wechsler Intelligence Scale for…

  19. Effect of some high consumption spices on hemoglobin glycation.

    PubMed

    Naderi, G H; Dinani, Narges J; Asgary, S; Taher, M; Nikkhoo, N; Boshtam, M

    2014-01-01

    Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes. PMID:25593391

  20. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  1. 21 CFR 864.7400 - Hemoglobin A 2 assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin A 2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  2. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  3. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Code of Federal Regulations, 2010 CFR

    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... polypeptide chains). (b) Classification. Class II (performance standards)....

  4. 21 CFR 864.7400 - Hemoglobin A 2 assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemoglobin A 2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  5. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemoglobin immunological test system. 866.5470 Section 866.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  6. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hemoglobin immunological test system. 866.5470 Section 866.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  7. Hemoglobin, Growth, and Attention of Infants in Southern Ethiopia

    ERIC Educational Resources Information Center

    Aubuchon-Endsley, Nicki L.; Grant, Stephanie L.; Berhanu, Getenesh; Thomas, David G.; Schrader, Sarah E.; Eldridge, Devon; Kennedy, Tay; Hambidge, Michael

    2011-01-01

    Male and female infants from rural Ethiopia were tested to investigate relations among hemoglobin (Hb), anthropometry, and attention. A longitudinal design was used to examine differences in attention performance from 6 (M = 24.9 weeks, n = 89) to 9 months of age (M = 40.6 weeks, n = 85), differences hypothesized to be related to changes in iron…

  8. Imaging Mobile Zinc in Biology

    PubMed Central

    Tomat, Elisa; Lippard, Stephen J.

    2009-01-01

    Summary Trafficking and regulation of mobile zinc pools influence cellular functions and pathological conditions in multiple organs, including brain, pancreas, and prostate. The quest for a dynamic description of zinc distribution and mobilization in live cells fuels the development of increasingly sophisticated probes. Detection systems that respond to zinc binding with changes of their fluorescence emission properties have provided sensitive tools for mobile zinc imaging, and fluorescence microscopy experiments have afforded depictions of zinc distribution within live cells and tissues. Both small-molecule and protein-based fluorescent probes can address complex imaging challenges, such as analyte quantification, site-specific sensor localization, and real-time detection. PMID:20097117

  9. Zinc and Compounds

    Integrated Risk Information System (IRIS)

    Zinc and Compounds ; CASRN 7440 - 66 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  10. Creep Resistant Zinc Alloy

    SciTech Connect

    Frank E. Goodwin

    2002-12-31

    This report covers the development of Hot Chamber Die Castable Zinc Alloys with High Creep Strengths. This project commenced in 2000, with the primary objective of developing a hot chamber zinc die-casting alloy, capable of satisfactory service at 140 C. The core objectives of the development program were to: (1) fill in missing alloy data areas and develop a more complete empirical model of the influence of alloy composition on creep strength and other selected properties, and (2) based on the results from this model, examine promising alloy composition areas, for further development and for meeting the property combination targets, with the view to designing an optimized alloy composition. The target properties identified by ILZRO for an improved creep resistant zinc die-casting alloy were identified as follows: (1) temperature capability of 1470 C; (2) creep stress of 31 MPa (4500 psi); (3) exposure time of 1000 hours; and (4) maximum creep elongation under these conditions of 1%. The project was broadly divided into three tasks: (1) Task 1--General and Modeling, covering Experimental design of a first batch of alloys, alloy preparation and characterization. (2) Task 2--Refinement and Optimization, covering Experimental design of a second batch of alloys. (3) Task 3--Creep Testing and Technology transfer, covering the finalization of testing and the transfer of technology to the Zinc industry should have at least one improved alloy result from this work.

  11. Doped zinc oxide microspheres

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

  12. Doped zinc oxide microspheres

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-12-14

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

  13. Zinc sulfide liquefaction catalyst

    DOEpatents

    Garg, Diwakar

    1984-01-01

    A process for the liquefaction of carbonaceous material, such as coal, is set forth wherein coal is liquefied in a catalytic solvent refining reaction wherein an activated zinc sulfide catalyst is utilized which is activated by hydrogenation in a coal derived process solvent in the absence of coal.

  14. Liposome-encapsulated hemoglobin: an oxygen-carrying fluid.

    PubMed

    Rabinovici, R; Rudolph, A S; Ligler, F S; Yue, T L; Feuerstein, G

    1990-09-01

    From the original concept of encapsulating hemoglobin in an inert shell, LEH has evolved into a fluid proven to carry oxygen, capable of surviving for reasonable periods in the circulation, and amenable to large-scale production. The formula for the outer shell evolved from synthetic, nonlipid materials, to egg-lecithin-based lipid mixtures, to distearoyl-phosphatidylcholine-based blends. The fabrication technology started with the production of milliliter quantities and methods detrimental to the hemoglobin and developed into high-pressure extrusion systems producing multi-liter quantities without damaging the hemoglobin. The development of methods for analysis and quality control of LEH has been difficult: even techniques for measuring basic characteristics of size and methemoglobin are still being standardized. In vivo studies have established that LEH has a circulation half-life of 16-20 hr and can carry oxygen sufficient to sustain life, but safety has yet to be proven. In each of the general areas mentioned above, there are opportunities for further improvement and characterization. The source of the hemoglobin and the coencapsulation of hemoglobin modifiers needs to be reassessed now that human hemoglobin has been cloned and functional hemoglobin can be produced by using fermentation techniques. The development of routine methods for quality control and assurance must accompany the production of large quantities of LEH for preclinical studies. Whether or not the LEH can and should be manufactured as a lyophilized product must be assessed. Animal studies must done to prove safety as well as efficacy in a variety of clinical models, including hemorrhagic and septic shock as well as various levels of isovolemic exchange. One approach toward the improvement of the LEH is to alter the liposome surface to increase its biocompatibility. The evolution of biocompatible liposome surfaces has included carbohydrate moieties, as carbohydrates are expressed on the

  15. Plant hemoglobins: a molecular fossil record for the evolution of oxygen transport.

    PubMed

    Hoy, Julie A; Robinson, Howard; Trent, James T; Kakar, Smita; Smagghe, Benoit J; Hargrove, Mark S

    2007-08-01

    The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.

  16. Plant Hemoglobins: A Molecular Fossil Record for the Evolutin of Oxygen Transport

    SciTech Connect

    Hoy,J.; Robinson, H.; Trent, lll, J.; Kakar, S.; Smagghe, B.; Hargrove, M.

    2007-01-01

    The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport 'leghemoglobins' evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.

  17. Zinc, the brain and behavior.

    PubMed

    Pfeiffer, C C; Braverman, E R

    1982-04-01

    The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.

  18. Purification of diverse hemoglobins by metal salt precipitation.

    PubMed

    Zimmerman, Devon; Dienes, Jack; Abdulmalik, Osheiza; Elmer, Jacob J

    2016-09-01

    Although donated blood is the preferred material for transfusion, its limited availability and stringent storage requirements have motivated the development of blood substitutes. The giant extracellular hemoglobin (aka erythrocruorin) of the earthworm Lumbricus terrestris (LtEc) has shown promise as a blood substitute, but an efficient purification method for LtEc must be developed to meet the potential large demand for blood substitutes. In this work, an optimized purification process that uses divalent and trivalent metal salts to selectively precipitate human, earthworm, and bloodworm hemoglobin (HbA, LtEc, and GdHb, respectively) from crude solutions was developed. Although several metal ions were able to selectively precipitate LtEc, Zn(2+) and Ni(2+) provided the lowest heme oxidation and highest overall yield of LtEc. In contrast, Zn(2+) was the only metal ion that completely precipitated HbA and GdHb. Polyacrylamide gel electrophoresis (PAGE) analysis shows that metal precipitation removes several impurities to provide highly pure hemoglobin samples. Heme oxidation levels were relatively low for Zn(2+)-purified HbA and LtEc (2.4±1.3% and 5.3±2.1%, respectively), but slightly higher for Ni(2+)-purified LtEc (8.4±1.2%). The oxygen affinity and cooperativity of the precipitated samples are also identical to samples purified with tangential flow filtration (TFF) alone, indicating the metal precipitation does not significantly affect the function of the hemoglobins. Overall, these results show that hemoglobins from several different species can be highly purified using a combination of metal (Zn(2+)) precipitation and tangential flow filtration. PMID:26363116

  19. Purification of diverse hemoglobins by metal salt precipitation.

    PubMed

    Zimmerman, Devon; Dienes, Jack; Abdulmalik, Osheiza; Elmer, Jacob J

    2016-09-01

    Although donated blood is the preferred material for transfusion, its limited availability and stringent storage requirements have motivated the development of blood substitutes. The giant extracellular hemoglobin (aka erythrocruorin) of the earthworm Lumbricus terrestris (LtEc) has shown promise as a blood substitute, but an efficient purification method for LtEc must be developed to meet the potential large demand for blood substitutes. In this work, an optimized purification process that uses divalent and trivalent metal salts to selectively precipitate human, earthworm, and bloodworm hemoglobin (HbA, LtEc, and GdHb, respectively) from crude solutions was developed. Although several metal ions were able to selectively precipitate LtEc, Zn(2+) and Ni(2+) provided the lowest heme oxidation and highest overall yield of LtEc. In contrast, Zn(2+) was the only metal ion that completely precipitated HbA and GdHb. Polyacrylamide gel electrophoresis (PAGE) analysis shows that metal precipitation removes several impurities to provide highly pure hemoglobin samples. Heme oxidation levels were relatively low for Zn(2+)-purified HbA and LtEc (2.4±1.3% and 5.3±2.1%, respectively), but slightly higher for Ni(2+)-purified LtEc (8.4±1.2%). The oxygen affinity and cooperativity of the precipitated samples are also identical to samples purified with tangential flow filtration (TFF) alone, indicating the metal precipitation does not significantly affect the function of the hemoglobins. Overall, these results show that hemoglobins from several different species can be highly purified using a combination of metal (Zn(2+)) precipitation and tangential flow filtration.

  20. Manipulation of hemoglobin expression affects Arabidopsis shoot organogenesis.

    PubMed

    Wang, Yaping; Elhiti, Mohamed; Hebelstrup, Kim H; Hill, Robert D; Stasolla, Claudio

    2011-10-01

    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 in vitro 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 by culturing root explants on an initial auxin-rich callus induction medium (CIM) followed by a transfer onto a cytokinin-containing shoot induction medium (SIM). While the repression of GLB2 inhibited organogenesis the over-expression of GLB1 or GLB2 enhanced the number of shoots produced in culture, and altered the transcript levels of genes participating in cytokinin perception and signalling. The up-regulation of GLB1 or GLB2 activated CKI1 and AHK3, genes encoding cytokinin receptors and affected the transcript levels of cytokinin responsive regulators (ARRs). The expression of Type-A ARRs (ARR4, 5, 7, 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 to cytokinin allowing the 35S::GLB1 and 35S::GLB2 lines to produce shoots at low cytokinin concentrations which did not promote organogenesis in the WT line. These results show that manipulation of hemoglobin can modify shoot organogenesis in Arabidopsis and possibly in those systems partially or completely unresponsive to applications of exogenous cytokinins. PMID:21741261

  1. Near-infrared absorbance measurements of hemoglobin solutions incubated with glucose

    NASA Astrophysics Data System (ADS)

    Zhernovaya, Olga S.; Tuchin, Valery V.; Meglinski, Igor; Ritchie, Laurie

    2007-02-01

    It is known that glucose influences on spectral properties of blood and hemoglobin and interacts with plasma proteins and hemoglobin in erythrocytes. Changes of optical properties of blood and hemoglobin at glucose concentration within physiological level are important for diagnosis and monitoring of diabetes. The purpose of this study is to investigate the effect of presence of glucose and glycation of hemoglobin on absorbance of aqueous hemoglobin solutions with different glucose concentrations. Measurements were taken using spectrophotometer EQUINOX 55 (Bruker Optic GmbH) in a range 1000-1800 nm. Water has absorption bands in the near-infrared region which may be influenced by glucose presence. We have hypothesized that glucose and hemoglobin, especially glycated hemoglobin, may influence the absorption band of water in solution. The hemoglobin solutions with different amount of glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) were incubated up to 28 days. Our measurements show that presence of glucose affects the spectra of aqueous hemoglobin solutions. The magnitude of absorbance depends on glucose concentration. At the beginning of incubation hemoglobin solution without glucose has the lowest absorbance magnitude, but after a rather long time of incubation (28 days) the absorbance of hemoglobin solutions with glucose become smaller compared to the absorbance of hemoglobin solution without glucose. This fact may be explained by assumption of hemoglobin glycation, when glucose molecules chemically bind to hemoglobin, and water binding to hemoglobin. In the case of water binding to hemoglobin molecules the amount of free water molecules in solution decreases, so the water aborbance is excepted to decrease.

  2. Identification of chloride-binding sites in hemoglobin by nuclear-magnetic-resonance quadrupole-relaxation studies of hemoglobin digests.

    PubMed

    Chiancone, E; Norne, J E; Forsén, S; Bonaventura, J; Brunori, M; Antonini, E; Wyman, J

    1975-07-01

    35Cl minus-nuclear magnetic resonance (NMR) studies indicate that various digests of human hemoglobin with carboxypeptidase A and B, or a combination of the two, may be used for the identification of chloride binding sites. All the digestion products contain, like hemoglobin itself, at least two classes of binding sites, one of high, the others of low affinity. The pH dependence of the excess linewidth of the 35Cl minus NMR signal indicates that in the simple digests with either carboxypeptidase A or B, chloride is bound with high affinity at or near His-beta146-Asp-beta94 and at or near Val-alpha1-Arg-alpha141. The high-affinity sites show, in the case of the simple digests, a strong oxygen linkage which is lost in the forms digested with both carboxypeptidase A and B; this linkage may thus be correlated to the presence of conformational changes. Organic phosphates, like inositol hexaphosphate, show competition for some of the high-affinity chloride binding sites in hemoglobin and in the simple digests. This competition is likewise lost in the doubly digested hemoglobins. PMID:236

  3. Phase characterization of oscillatory components of the cerebral concentrations of oxy-hemoglobin and deoxy-hemoglobin

    NASA Astrophysics Data System (ADS)

    Pierro, Michele; Sassaroli, Angelo; Zheng, Feng; Fantini, Sergio

    2011-02-01

    We present a study of the relative phase of oscillations of cerebral oxy- and deoxy-hemoglobin concentrations in the low-frequency range, namely 0.04-0.12 Hz. We have characterized the potential contributions of noise to the measured phase distributions, and we have performed phase measurements on the brain of a human subject at rest, and on the brain of a human subject during stage I sleep. While phase distributions of pseudo hemodynamic oscillations generated from noise (obtained by applying to two independent sets of random numbers the same linear transformation that converts absorption coefficients at 690 and 830 nm into concentrations of oxy- and deoxy-hemoglobin) are peaked at 180º, those associated with real hemodynamic changes can be peaked around any value depending on the underlying physiology and hemodynamics. In particular, preliminary results reported here indicate a greater phase lead of deoxy-hemoglobin vs. oxy-hemoglobin low-frequency oscillations during stage I sleep (82º +/- 55º) than while the subject is awake (19º +/- 58º).

  4. ESA frequency and hemoglobin levels in patients on peritoneal dialysis: 2002 vs. 2008.

    PubMed

    Kruger, Ann; Trowbridge, Lynette; York, Jane; Butcher, Belinda; Bradley, Jennifer

    2013-01-01

    This study examined whether a change infrequency of administration of erythropoietin-stimulating agent affected hemoglobin levels in patients on peritoneal dialysis. Data were extracted from the Australian Renal Anaemia Management database for the years 2002 and 2008. Less frequent dosing and increasing age were associated with higher hemoglobin levels, while increasing ferritin levels and later years were associated with lower hemoglobin levels.

  5. Comparable application of the OCT and Abbe refractometers for measurements of glycated hemoglobin portion in blood

    NASA Astrophysics Data System (ADS)

    Zhernovaya, Olga S.; Tuchin, Valery V.; Wang, Ruikang K.

    2006-02-01

    It is known that glucose interacts with plasma proteins and hemoglobin in erythrocytes. Glycated (glycosylated) hemoglobin is the result of an irreversible non-enzymatic fixation of glucose on the beta chain of hemoglobin A. The amount of glycated hemoglobin depends on blood glucose concentration and reflects the mean glycemia of about the previous 2-3 months. Glycated hemoglobin is a useful marker for long-term glucose control in diabetic patients. Therefore, the search of quick and high sensitive methods for measurement of glycated hemoglobin portion in blood is important. This study is focused on the determination of refractive index of hemoglobin solution at different glucose concentrations. Measurements were performed using Abbe refractometer at 589 nm and optical coherence tomography (OCT) at 820 nm. The different amount of glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) was added to hemoglobin solution. Theoretical values of refractive index of hemoglobin solutions with glucose were calculated supposing non-interacting hemoglobin and glucose molecules. There is a difference between measured and calculated values of refractive index. This difference is due to glucose binding to hemoglobin. It is shown that the refractive index measurements can be applied for the evaluation of glycated hemoglobin amount.

  6. Comparative toxicity of a zinc salt, zinc powder and zinc oxide to Eisenia fetida, Enchytraeus albidus and Folsomia candida.

    PubMed

    Lock, Koen; Janssen, Colin R

    2003-12-01

    The pore water zinc concentration and the calcium chloride extracted zinc fraction are higher in the soils spiked with a zinc salt (ZnCl2) compared to soils spiked with zinc oxide or zinc powder. Based on total zinc concentrations in the soil, the acute toxicity of zinc salt to the compost worm Eisenia fetida, the potworm Enchytraeus albidus and the springtail Folsomia candida was lower compared to zinc oxide and zinc powder. However, when expressed on the basis of pore water concentrations or calcium chloride extracted fractions, acute toxicity was higher for zinc salt, which indicated that dermal uptake via the pore water is not the only route of uptake. Chronic toxicity of zinc salt, zinc oxide and zinc powder was similar when based on total concentrations in the soil which again indicates that the pore water route of uptake is not the only route of exposure but that oral uptake is also important.

  7. [Biochemical evaluation of damage due to lead: importance and significance of erythrocyte zinc-protoporhyrin IX and urinary amino acid determination].

    PubMed

    Sanguinetti, F; Dompè, M; Ronca, G

    1977-01-01

    The early detection of lead intoxitation needs practical, simple, reproducible and diagnostically valid screening test. The determination of ALA-D (delta-amino-levulinic acid-dehydratase) in erythrocytes is one of the most reliable test for the evaluation of the occupational exposure to lead. However this test is difficult to standardize, sensible to lead contamination of laboratory glassware and the activity of enzyme decreases rapidly if stored. The determination of erythrocytes ZPP (zinco-protoporphyrin IX) was proposed as useful, alternative test. The protoporphyrin IX is a metabolic intermediate in heme biosynthesis; in erythrocytes is present as free form and zinc-boundend compound. The ZPP give high values only in lead intoxication and sideropenic anemia. The ALA-D and ZPP in erythrocytes were measured and compared in a group of workers exposed to lead. We have shown a good correlation between these two biochemical parameters. Aminoacid excretion in urine from workers exposed to lead was measured and compared with other biochemical parameters of intoxication. All lead workers examined had excessive urinary CP (coproporphyrin) and ALA (delta-amino-levulinic acid) excretion. An abnormal excretion of glycine was present in eight workers (32%), whereas in other four (15%) the glycinuria was at limit of normal values. An abnormal excretion of lysine was present in six workers (21%). The last data appear very interesting because the action of lead in lysine metabolism was not known. PMID:603137

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

    PubMed

    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 < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003

  9. [Hemoglobins, XLVII. Hemoglobins of the bar-headed goose (Anser indicus): primary structure and physiology of respiration, systematic and evolution].

    PubMed

    Oberthür, W; Braunitzer, G; Würdinger, I

    1982-06-01

    The primary structures of the alpha- and beta-chains of the main component of Bar-headed Goose (Anser indicus) are given. By homologous comparison with the hemoglobin of the Grey-Lag Goose (Anser anser) 3 differences were found in the alpha-chains, 1 difference in the beta-chains. In position alpha 119 H2Ala and beta 125 H3Asp alpha 1 beta 2-contact points are changed. The mutation alpha 63 E12Val brings a drastic change in tertiary structure of the alpha-chains of Bar-headed Goose: the helices E and B are moved apart by 1.5 A as there is no room for the larger side chain. This is probably the reason for a slightly higher intrinsic oxygen affinity of Bar-headed Goose hemoglobin. The bindings of inositol pentaphosphate on hemoglobin are identical in Grey-Lag Goose and Bar-headed Goose (contact points are not mutated). The reason for the increased difference in oxygen affinity by binding of inositol pentaphosphate is probably caused by two mutations in alpha 1 beta 2-contact points. It suggests that these two mutations are the reason for a different interaction between alpha- and beta-chains under the influence of inositol pentaphosphate by Grey-Lag and Bar-headed Goose hemoglobins. The difference in the primary structure of the Grey-Lag and Bar-headed Goose hemoglobins suggests that the Bar-headed Goose is not the genus of anser. Unfinished experiments (about 80% of the sequences) of White-fronted Goose (Anser albifrons a.) and Snow Goose (Anser caerulescens c.) show no exchanges with Grey-Lag Goose hemoglobin. The Canada Goose (Branta canadensis), however, which belongs to the genus Branta, has a number of substitutions similar to the Bar-headed Goose hemoglobin. These changes in primary structure suggest that Grey-Lag Goose and Bar-headed Goose are separated by a period of 9-15 Million years. This would support the hypothesis that the two species of goose became geographically separated by the elevation of the Himalayas. PMID:7106705

  10. Phenotypic expression of hemoglobins A₂, E and F in various hemoglobin E related disorders.

    PubMed

    Sae-ung, Nattaya; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Yamsri, Supawadee; Sanchaisuriya, Kanokwan; Fucharoen, Supan

    2012-01-15

    Study on the phenotypic expression of hemoglobin (Hb) A(2) and Hb E in Hb E disorders has been difficult due to the co-separation of Hb A(2) and Hb E in most Hb analysis assays. Because these two Hbs are separated on capillary electrophoresis, we studied phenotypic expression of Hbs A(2), E and F in various Hb E disorders using this system. This was done on 362 subjects with several Hb E disorders including heterozygous Hb E, homozygous Hb E, β-thalassemia/Hb E, δβ-thalassemia/Hb E, and Hb Lepore/Hb E and those of these disorders with several forms of α-thalassemia. Normal controls showed Hb A(2) of 2.7 ± 0.3%. Heterozygous Hb E and homozygous Hb E had elevated Hb A(2) i.e. 3.8 ± 0.3% and 4.8 ± 0.5%, respectively. Further elevations were observed for β(0)-thalassemia/Hb E (6.1 ± 1.9%) and β(+)-thalassemia/Hb E (7.1 ± 1.2%). Interestingly, no elevation of Hb A(2) was found in the δβ-thalassemia/Hb E, and Hb Lepore/Hb E (2.3 ± 0.3%) but higher Hb F levels were noted which could be useful diagnostic markers. The levels of Hb E were variable. Co-inheritance of these Hb E disorders with α-thalassemia were associated with lower outputs of Hb E and Hb F but the levels of Hb A(2) were not altered. Different phenotypic expression of Hb A(2), Hb E and Hb F could help in differential diagnosis of these Hb E related disorders commonly encountered in the regions where access to molecular techniques is limited.

  11. Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

    PubMed

    Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

    2015-12-01

    A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

  12. Longitudinal association between toenail zinc levels and the incidence of diabetes among American young adults: The CARDIA Trace Element Study.

    PubMed

    Park, Jong Suk; Xun, Pengcheng; Li, Jing; Morris, Steve J; Jacobs, David R; Liu, Kiang; He, Ka

    2016-01-01

    Data on primary prevention of zinc status and diabetes risk are sparse and inconsistent. Of note, the previous studies measured either dietary zinc intake with questionnaire or zinc status in serum or hair. Toenail zinc levels are reliable biomarkers of a relatively long-term exposure. A total of 3,960 American young adults, aged 20-32 years, free of diabetes at baseline in 1987 when toenail clippings were collected, were examined for incident diabetes through 2010. Toenail zinc levels were measured with an inductively-coupled-plasma mass spectroscopy method. Incident diabetes cases were identified by fasting or non-fasting plasma glucose levels, oral glucose tolerance tests, hemoglobin A1C levels, and/or antidiabetic medications. During the 23-year follow-up, 418 incident diabetes occurred. After adjusted for age, sex, ethnicity, study center, body mass index, education, smoking status, alcohol consumption, physical activity, family history of diabetes, homeostasis model assessment of insulin resistance, and other dietary and non-dietary potential confounders, the hazard ratio of incident diabetes comparing the highest to the lowest quartile of toenail zinc levels was 1.21 (95% CI: 0.90-1.63; Ptrend = 0.20). Findings from this study do not support the hypothesis that zinc status is inversely and longitudinally associated with the incidence of diabetes in American young adults. PMID:26980156

  13. Longitudinal association between toenail zinc levels and the incidence of diabetes among American young adults: The CARDIA Trace Element Study

    PubMed Central

    Park, Jong Suk; Xun, Pengcheng; Li, Jing; Morris, Steve J.; Jacobs, David R.; Liu, Kiang; He, Ka

    2016-01-01

    Data on primary prevention of zinc status and diabetes risk are sparse and inconsistent. Of note, the previous studies measured either dietary zinc intake with questionnaire or zinc status in serum or hair. Toenail zinc levels are reliable biomarkers of a relatively long-term exposure. A total of 3,960 American young adults, aged 20–32 years, free of diabetes at baseline in 1987 when toenail clippings were collected, were examined for incident diabetes through 2010. Toenail zinc levels were measured with an inductively-coupled-plasma mass spectroscopy method. Incident diabetes cases were identified by fasting or non-fasting plasma glucose levels, oral glucose tolerance tests, hemoglobin A1C levels, and/or antidiabetic medications. During the 23-year follow-up, 418 incident diabetes occurred. After adjusted for age, sex, ethnicity, study center, body mass index, education, smoking status, alcohol consumption, physical activity, family history of diabetes, homeostasis model assessment of insulin resistance, and other dietary and non-dietary potential confounders, the hazard ratio of incident diabetes comparing the highest to the lowest quartile of toenail zinc levels was 1.21 (95% CI: 0.90–1.63; Ptrend = 0.20). Findings from this study do not support the hypothesis that zinc status is inversely and longitudinally associated with the incidence of diabetes in American young adults. PMID:26980156

  14. Interaction Between Yeasts and Zinc

    NASA Astrophysics Data System (ADS)

    Nicola, Raffaele De; Walker, Graeme

    Zinc is an essential trace element in biological systems. For example, it acts as a cellular membrane stabiliser, plays a critical role in gene expression and genome modification and activates nearly 300 enzymes, including alcohol dehydrogenase. The present chapter will be focused on the influence of zinc on cell physiology of industrial yeast strains of Saccharomyces cerevisiae, with special regard to the uptake and subsequent utilisation of this metal. Zinc uptake by yeast is metabolism-dependent, with most of the available zinc translocated very quickly into the vacuole. At cell division, zinc is distributed from mother to daughter cells and this effectively lowers the individual cellular zinc concentration, which may become zinc depleted at the onset of the fermentation. Zinc influences yeast fermentative performance and examples will be provided relating to brewing and wine fermentations. Industrial yeasts are subjected to several stresses that may impair fermentation performance. Such stresses may also impact on yeast cell zinc homeostasis. This chapter will discuss the practical implications for the correct management of zinc bioavailability for yeast-based biotechnologies aimed at improving yeast growth, viability, fermentation performance and resistance to environmental stresses

  15. Zinc hydroxide sulphate and its transformation to crystalline zinc oxide.

    PubMed

    Moezzi, Amir; Cortie, Michael B; McDonagh, Andrew M

    2013-10-28

    The thermal transformation of zinc hydroxide sulphate hydrate to zinc oxide has been examined using synchrotron X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, and surface area measurements. By collecting X-ray diffraction data in situ, we found that the dehydration of zinc hydroxide sulphate pentahydrate proceeded in discrete steps to form anhydrous zinc hydroxide sulphate. This compound then decomposed to a mixture of zinc oxide and a compound tentatively identified as Zn3(OH)2(SO4)2 at ~235 °C. At ~360 °C, the final dehydroxylation occurred with the formation of zinc oxy-sulphate, Zn3O(SO4)2, which then decomposed to ZnO at about ~800 °C. Interruption of the dehydration process can be used to synthesize the intermediate compounds.

  16. Experimental phasing using zinc anomalous scattering

    SciTech Connect

    Cha, Sun-Shin; An, Young Jun; Jeong, Chang-Sook; Kim, Min-Kyu; Lee, Sung-Gyu; Lee, Kwang-Hoon; Oh, Byung-Ha

    2012-09-01

    The surface of proteins can be charged with zinc ions and the anomalous signals from these zinc ions can be used for structure determination of proteins. Zinc is a suitable metal for anomalous dispersion phasing methods in protein crystallography. Structure determination using zinc anomalous scattering has been almost exclusively limited to proteins with intrinsically bound zinc(s). Here, it is reported that multiple zinc ions can easily be charged onto the surface of proteins with no intrinsic zinc-binding site by using zinc-containing solutions. Zn derivatization of protein surfaces appears to be a largely unnoticed but promising method of protein structure determination.

  17. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  18. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  19. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  20. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  1. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  2. Noninvasive investigation of skin local hypothermia influence upon local oxygenation and hemoglobin concentration

    NASA Astrophysics Data System (ADS)

    Douplik, Alexandre Y.; Kessler, Manfred D.; Kakihana, Yasuyuki; Krug, Alfons

    1997-08-01

    Functional evaluation of local hemoglobin concentration and hemoglobin oxygenation based on back scattering spectra from human skin in vivo have been obtained in visible range (502 - 628 nm) by a rapid microlightguide spectrometer (EMPHO II) with step 250 micrometer. Analysis of received results has shown that during local cooling there is two nearly simultaneous reactions: reduction of hemoglobin concentration and increase of hemoglobin oxygenation level. In a case when one has used previous heating of planning place for cooling, reduction of hemoglobin concentration is expressed higher by 22 - 33%.

  3. Concurrent measurement of cellular turbidity and hemoglobin to evaluate the antioxidant activity of plants.

    PubMed

    Bellik, Yuva; Iguer-Ouada, Mokrane

    2016-01-01

    In past decades, a multitude of analytical methods for measuring antioxidant activity of plant extracts has been developed. However, when using methods to determine hemoglobin released from human erythrocytes treated with ginger extracts, we found hemoglobin concentrations were significantly higher than in untreated control samples. This suggests in the presence of antioxidants that measuring hemoglobin alone is not sufficient to determine hemolysis. We show concurrent measurement of erythrocyte concentration and hemoglobin is essential in such assays, and describe a new protocol based on simultaneous measurement of cellular turbidity and hemoglobin.

  4. Observations of interstellar zinc

    NASA Technical Reports Server (NTRS)

    York, D. G.; Jura, M.

    1982-01-01

    IUE observations toward 10 stars have shown that zinc is not depleted in the interstellar medium by more than a factor of two, suggesting that its abundance may serve as a tracer of the true metallicity in the gas. A result pertinent to the history of nucleosynthesis in the solar neighborhood is that the local interstellar medium has abundances that appear to be homogeneous to within a factor of two, when integrated over paths of about 500 pc.

  5. Surface energy of zinc

    SciTech Connect

    Bilello, J.C.; Dew-Hughes, D.; Pucino, A.T.

    1983-04-01

    The influence of temperature and associated dislocation microstructure on the energetics of basal plane cleavage in zinc crystals has been investigated using the method of Hull, Beardmore, and Valentine (HBV). A marked temperature dependence was observed in the zinc surface energy, over the range 77--298 /sup 0/K, contrary to previous expectations. Plastic relaxation was associated with crack initiation at 77 /sup 0/K, but not propagation; while at room temperature a plastic zone of 1200--1500 ..mu..m in depth was produced by crack extension. The surface energy could be estimated, independent of the usual Griffith analysis, by measuring the energy dissipation in a fully relaxed deformed zone associated with an explosively formed precursor crack. This method yielded surface energies of 0.066 to 0.079 J m/sup -2/ which was in good agreement with previous work. It is demonstrated that the cleavage surface energy of zinc is well below the thermodynamic surface energy and that this discrepancy is not related to plastic deformation.

  6. Virucidal levels of ozone induce hemolysis and hemoglobin degradation

    SciTech Connect

    Wagner, S.J.; Wagner, K.F.; Friedman, L.I.; Benade, L.F. )

    1991-10-01

    The animal virus, vesicular stomatitis virus (VSV), and the bacterial virus, phi 6, were inactivated by greater than 4 log10 in response to incubation with 13 to 14 mL of 1.4 mmol per L (65 micrograms/mL) to 1.6 mmol per L (75 micrograms/mL) of overlaid ozone in virus-spiked, dilute, red cell suspensions. Virus inactivation was greatly inhibited when ozone was overlaid in the presence of high-hematocrit red cells or, to a lesser degree, high levels of plasma. At hematocrits at which 5 to 6 log10 of VSV were inactivated, ozone caused 30-percent hemolysis, as measured by the loss of total cellular hemoglobin. Unexpectedly, this level of hemolysis could not be observed in supernatants because of the ozone-induced destruction (bleaching) of extracellular hemoglobin. These results suggest that ozone may have little biological specificity for damaging viruses over red cells.

  7. Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09*

    PubMed Central

    Chen, Yun-mei; Xu, Hai-yang; Wang, Yang; Zhang, Jian-fa; Wang, Shi-ming

    2014-01-01

    Salecan is a novel exopolysaccharide produced by the strain Agrobacterium sp. ZX09, and it is composed of only glucose monomers. The unique chemical composition and excellent physicochemical properties make Salecan a promising material for applications in coagulation, lubrication, protection against acute liver injury, and alleviating constipation. In this study, we cloned the Vitreoscilla hemoglobin gene into a broad-host-range plasmid pCM158. Without antibiotic selection, there was negligible loss of the plasmid in the host Agrobacterium sp. ZX09 after one passage of cultivation. The expression of Vitreoscilla hemoglobin was demonstrated by carbon monoxide (CO) difference spectrum. The engineered strain Agrobacterium sp. ZX09 increased Salecan yield by 30%. The other physiological changes included its elevated respiration rate and cellular invertase activity. PMID:25367790

  8. First Reported Case of Proliferative Retinopathy in Hemoglobin SE Disease

    PubMed Central

    Yang, Christopher; Fantin, Aldo; Darnley-Fisch, Deborah; Desai, Uday

    2014-01-01

    We report the first case of proliferative sickle cell retinopathy in a patient with hemoglobin SE (Hb SE) disease. Only a few dozen cases of Hb SE disease have been reported previously, and none had evidence of proliferative retinopathy. A 56-year-old African American man presented to our clinic for routine examination and was found to have sea-fan peripheral neovascularization bilaterally without maculopathy. Hemoglobin analysis revealed Hb SE heterozygosity. Sector laser photocoagulation to areas of nonperfusion in both eyes resulted in regression of the peripheral neovascularization over a period of 6 months. Although Hb SE disease is rare, the incidence of Hb SE disease is postulated to rise in the future. Awareness of its potential ocular complications is needed to appropriately refer these patients for screening. PMID:25210638

  9. Neonatal Cyanosis Due to Hemoglobin Variant: Hb F-Sarajevo.

    PubMed

    Lozar-Krivec, Jana; Stepic, Maja; Hovnik, Tinka; Krsnik, Mladen; Paro-Panjan, Darja

    2016-10-01

    Neonatal cyanosis is rarely due to hemoglobin variants with low oxygen affinity. We describe the clinical course and results of molecular genetic analysis of a boy who presented after birth with severe cyanosis. Arterial blood-gas analysis demonstrated a pronounced shift of the oxygen-hemoglobin dissociation curve to the right and molecular genetic analysis revealed a γ-globin variant, Hb F-Sarajevo. The patient presented is the second reported case of neonatal cyanosis due to this mutation, which was first described in 2012 by Zimmermann-Baer and coauthors. With the introduction of universal screening for congenital heart disease, the finding of low oxygen saturation will uncover more neonates with hemoglobinopathies with low oxygen affinity. PMID:27571121

  10. The Linkage Between Oxygenation and Subunit Dissociation in Human Hemoglobin

    PubMed Central

    Ackers, Gary K.; Halvorson, Herbert R.

    1974-01-01

    The use of subunit dissociation as a means of probing intersubunit contact energy changes which accompany cooperative ligand binding has been studied for the case of human hemoglobin. An analysis is presented delineating the information that can be obtained from the linkage relationships between ligand binding and subunit dissociation of hemoglobin tetramers into dimers. The analysis defines (a) the variation of the saturation function, Ȳ, with total protein concentration, (b) the variation of the subunit dissociation constant xK2 with ligand concentration (X) and (c) the correlations between changes in dimer-dimer contact energy and the sequential ligand binding steps. Sensitivity of the linkage function has been explored by numerical simulation. It is shown that subunit dissociation may appreciably affect oxygenation curves under usual conditions of measurement and that relying solely on either xK2 or Ȳ may lead to incorrect picutres of the energetics, whereas the combination defines the system much more exactly. PMID:4530985

  11. Double filaments in fibers and crystals of deoxygenated hemoglobin S

    SciTech Connect

    Magdoff-Fairchild, B.; Chiu, C.C.

    1980-10-01

    Sickle cell hemoglobin (HbS) molecules in solution or in SS erythrocytes (those from individuals homozygous for the sickle hemoglobin gene), when deoxygenated, aggregate to form fibers that pack into paracrystalline arrays. The diminished oxygen affinity of HbS is produced by the polymerization, and the distortion of the pliant erythrocyte membrane is produced by the polymerization, and the distortion of the pliant erythrocyte membrane in sickle cell disease results from the elongation of polymers and their subsequent alignment. One of the important problems to be solved in sickle cell disease is the definition of the intermolecular interactions that stabilize the fiber structure. Knowledge of these interactions might lead to the design of stereospecific antisickling agents for clinical use that could inhibit polymerization or could at least destabilize the fiber.

  12. Bitter peptide from hemoglobin hydrolysate: isolation and characterization.

    PubMed

    Aubes-Dufau, I; Capdevielle, J; Seris, J L; Combes, D

    1995-05-01

    Two separation methods, ultrafiltration and 2-butanol extraction, have shown that a peptide is the major agent responsible for bitterness in peptic hemoglobin hydrolysates. It was easily purified from these complex mixtures by specific hydrophobic adsorption on Superose 12, a gel-filtration column, which could constitute an original and interesting method for bitterness detection. The bitter peptide which corresponded to VV-hemorphin 7, the fragment 32-40 of the beta chain of bovine hemoglobin, is first generated during proteolysis, then hydrolysed by pepsin. It exhibited a strong bitterness at 0.25 mM equivalent to 0.073 mM quinine sulfate or 21 mM caffeine.

  13. Water buffalo (Bubalus bubalis) hemoglobins: an electrophoretic and chromatographic study.

    PubMed

    Di Luccia, A; Iannibelli, L; Ferranti, P; Iorio, M; Annunziata, M; Ferrara, L

    1989-01-01

    1. Hemoglobins from three phenotypes of Italian water buffalo (Bubalus bubalis), named AA, AB and BB, were selected by starch gel electrophoresis at alkaline pH and analyzed using polyacrylamide gel isoelectric focusing and subsequent analysis of titration curves to reveal differences between two types of hemoglobin identified as Hb fast and Hb slow. 2. Globins from Hb fast and Hb slow were purified by fast protein liquid chromatography (FPLC). Electrophoretic differences were found in the respective alpha-chains using polyacrylamide gel disc-electrophoresis at acid pH, polyacrylamide gel isoelectric focusing and by subsequently analyzing titration curves. 3. The results suggest that the alpha chains of Hb fast and Hb slow, called I alpha and II alpha, respectively, differ in at least two aminoacid residues. Subsequently, these amino acids were identified as lysine and cysteine.

  14. A Membrane-bound Hemoglobin from Gills of the Green Shore Crab Carcinus maenas*

    PubMed Central

    Ertas, Beyhan; Kiger, Laurent; Blank, Miriam; Marden, Michael C.; Burmester, Thorsten

    2011-01-01

    Most hemoglobins serve for the transport or storage of O2. Although hemoglobins are widespread in “entomostracan” Crustacea, malacostracans harbor the copper-containing hemocyanin in their hemolymph. Usually, only one type of respiratory protein occurs within a single species. Here, we report the identification of a hemoglobin of the shore crab Carcinus maenas (Malacostraca, Brachyura). In contrast to the dodecameric hemocyanin of this species, C. maenas hemoglobin does not reside in the hemolymph but is restricted to the gills. Immunofluorescence studies and cell fractioning showed that C. maenas hemoglobin resides in the membrane of the chief cells of the gill. To the best of our knowledge, this is the first time that a membrane-bound hemoglobin has been identified in eukaryotes. Bioinformatic evaluation suggests that C. maenas hemoglobin is anchored in the membrane by N-myristoylation. Recombinant C. maenas hemoglobin has a hexacoordinate binding scheme at the Fe2+ and an oxygen affinity of P50 = 0.5 Torr. A rapid autoxidation rate precludes a function as oxygen carrier. We rather speculate that, analogous to prokaryotic membrane-globins, C. maenas hemoglobin carries out enzymatic functions to protect the lipids in cell membrane from reactive oxygen species. Sequence comparisons and phylogenetic studies suggested that the ancestral arthropod hemoglobin was most likely an N-myristoylated protein that did not have an O2 supply function. True respiratory hemoglobins of arthropods, however, evolved independently in chironomid midges and branchiopod crustaceans. PMID:21118803

  15. IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus.

    PubMed

    Pishchany, Gleb; Sheldon, Jessica R; Dickson, Claire F; Alam, Md Tauqeer; Read, Timothy D; Gell, David A; Heinrichs, David E; Skaar, Eric P

    2014-06-01

    Staphylococcus aureus is a Gram-positive pathogen responsible for tremendous morbidity and mortality. As with most bacteria, S. aureus requires iron to cause disease, and it can acquire iron from host hemoglobin. The current model for staphylococcal hemoglobin-iron acquisition proposes that S. aureus binds hemoglobin through the surface-exposed hemoglobin receptor IsdB. IsdB removes heme from bound hemoglobin and transfers this cofactor to other proteins of the Isd system, which import and degrade heme to release iron in the cytoplasm. Here we demonstrate that the individual components of the Isd system are required for growth on low nanomolar concentrations of hemoglobin as a sole source of iron. An in-depth study of hemoglobin binding by IsdB revealed key residues that are required for hemoglobin binding. Further, we show that these residues are necessary for heme extraction from hemoglobin and growth on hemoglobin as a sole iron source. These processes are found to contribute to the pathogenicity of S. aureus in a murine model of infection. Together these results build on the model for Isd-mediated hemoglobin binding and heme-iron acquisition during the pathogenesis of S. aureus infection.

  16. IsdB-dependent Hemoglobin Binding Is Required for Acquisition of Heme by Staphylococcus aureus

    PubMed Central

    Pishchany, Gleb; Sheldon, Jessica R.; Dickson, Claire F.; Alam, Md Tauqeer; Read, Timothy D.; Gell, David A.; Heinrichs, David E.; Skaar, Eric P.

    2014-01-01

    Staphylococcus aureus is a Gram-positive pathogen responsible for tremendous morbidity and mortality. As with most bacteria, S. aureus requires iron to cause disease, and it can acquire iron from host hemoglobin. The current model for staphylococcal hemoglobin-iron acquisition proposes that S. aureus binds hemoglobin through the surface-exposed hemoglobin receptor IsdB. IsdB removes heme from bound hemoglobin and transfers this cofactor to other proteins of the Isd system, which import and degrade heme to release iron in the cytoplasm. Here we demonstrate that the individual components of the Isd system are required for growth on low nanomolar concentrations of hemoglobin as a sole source of iron. An in-depth study of hemoglobin binding by IsdB revealed key residues that are required for hemoglobin binding. Further, we show that these residues are necessary for heme extraction from hemoglobin and growth on hemoglobin as a sole iron source. These processes are found to contribute to the pathogenicity of S. aureus in a murine model of infection. Together these results build on the model for Isd-mediated hemoglobin binding and heme-iron acquisition during the pathogenesis of S. aureus infection. PMID:24338348

  17. Urinary excretion of zinc and metabolic control of patients with diabetes type 2.

    PubMed

    Marreiro, Dilina do Nascimento; do Perpetuo Socorro C Martins, Maria; de Sousa, Simone Sady Ribeiro; Ibiapina, Véritas; Torres, Silva; Pires, Liliane Viana; do Nascimento Nogueira, Nadir; Lima, José Maria Correia; do Monte, Semíramis Jamil Hadad

    2007-01-01

    The objective of this study was to assess urinary excretion of zinc and evaluation parameters of metabolic control in type 2 diabetic patients. Thirty-one type 2 diabetic patients, of both genders, with 5.8 +/- 5.6 years average time of the disease, age range 20-60 years, were selected. Evaluation of the nutritional status was performed using anthropometric measurements. To evaluate food consumption, the 3-day alimentary log method was used, and its analysis was performed using a software. Determination of urinary zinc was by atomic absorption spectrophotometry. From the obtained results, it was concluded that 51.6% of the patients were overweight. The mean of found waist circumference was 100.4 and 92.2 cm for men and women, respectively. Blood glucose and glycated hemoglobin values were higher than reference values, and plasma albumin concentration was adequate. The median of found urinary zinc excretion was 474.9 mug/24 h, within normal standards (300-600 mug/day). Regarding diet composition, calorie and protein concentration were above recommendation, while mean zinc concentration was adequate. This data allow the conclusion that the evaluated patients presented adequate urinary zinc excretion in comparison with reference values.

  18. Comparison of the hemoglobins of the platyhelminths Gastrothylax crumenifer and Paramphistomum epiclitum (Trematoda: Paramphistomatidae).

    PubMed

    Haque, M; Rashid, K A; Stern, M S; Sharma, P K; Siddiqi, A H; Vinogradov, S N; Walz, D A

    1992-04-01

    1. Gastrothylax crumenifer and Paramphistomum epiclitum parasitize the water buffalo Bubalus bubalis. 2. Gastrothylas hemoglobin consisted of two fractions of ca 30,000 and ca 18,000 by gel filtration. SDS-electrophoresis showed both to be single, ca 15,000 chains. 3. Paramphistomum hemoglobin was ca 16,000 by both gel filtration and SDS-electrophoresis. 4. Reversed-phase chromatography of carboxymethylated trematode and buffalo globins gave single peaks and two peaks, respectively. Although Paramphistomum hemoglobin provided and N-terminal sequence, Gastrothylax hemoglobin did not, suggesting blocked N-terminals. The buffalo sequences were found to be identical to the sequences of the alpha and beta chains of bovine hemoglobin. 5. Although Paramphistomum hemoglobin consists of only one chain, Gastrothylax hemoglobin consists either of one chain which aggregates to a dimer or of two different chains, only one of which aggregates to a dimer.

  19. Chemical modifications that inhibit gelation of sickle hemoglobin.

    PubMed

    Benesch, R; Benesch, R E; Yung, S

    1974-04-01

    Substitution of the N-terminal amino groups with pyridoxal compounds inhibits gelation and increases the solubility of deoxy sickle hemoglobin (Hb S). Pyridoxylation of the alpha chains has considerably more effect than that of the beta chains. The increase in minimum gelling concentration of Hb S that results from modification of the alpha N-termini is the same as that produced by dilution of Hb S with an equal amount of Hb A. PMID:4524653

  20. Hemoglobin Status and Externalizing Behavioral Problems in Children

    PubMed Central

    Su, Jianhua; Cui, Naixue; Zhou, Guoping; Ai, Yuexian; Sun, Guiju; Zhao, Sophie R.; Liu, Jianghong

    2016-01-01

    Background: Still considered one of the most prevalent nutritional problems in the world, anemia has been shown in many studies to have deleterious effects on neurobehavioral development. While most research efforts have focused on investigating the effects of anemia on social and emotional development of infants by using a cross-sectional design, research is still needed to investigate whether early childhood anemia, beyond infantile years, is linked with behavioral problems. Objective: This study assessed whether (1) hemoglobin (Hb) levels in early childhood are associated with externalizing behavior; and (2) this relationship is confounded by social adversity. Methods: Hemoglobin levels were taken from children (N = 98) of the China Jintan Cohort Study at age 4 years, and externalizing behaviors (attention and aggression) were assessed with the Child Behavior Checklist (ASEBA-CBCL) at age 6 years (mean age 5.77 ± 0.39 years old). Results: Compared with other children in the sample, children with relatively lower Hb levels at age 4 had more behavioral problems in both attention and aggression at age 6, independent of social adversity. For boys, this association was significant for attention problems, which did not interact with social adversity. For girls, the association was significant for aggression, which interacted with social adversity. While girls on average exhibited higher social adversity than boys, the main effect of Hb was only significant in girls with low social adversity. Conclusions: These results indicate that there is an inverse association between hemoglobin levels and later behavioral problems. Findings of this study suggest that regular monitoring of children’s hemoglobin levels and appropriate intervention may help with early identification of behavioral problems. PMID:27472352

  1. Multimeric hemoglobin of the Australian brine shrimp Parartemia.

    PubMed

    Coleman, M; Matthews, C M; Trotman, C N

    2001-04-01

    The hemoglobin molecule of the commercially important brine shrimp Artemia sp. has been used extensively as a model for the study of molecular evolution. It consists of nine globin domains joined by short linker sequences, and these domains are believed to have originated through a series of duplications from an original globin gene. In addition, in Artemia, two different polymers of hemoglobin, called C and T, are found which differ by 11.7% at the amino acid level and are believed to have diverged about 60 MYA. This provides a set of data of 18 globin domain sequences that have evolved in the same organism. The pattern of amino acid substitution between these two polymers is unusual, with pairs of equivalent domains displaying differences of up to 2.7-fold in total amino acid substitution. Such differences would reflect a similar range of molecular-clock rates in what appear to be duplicate, structurally equivalent domains. In order to provide a reference outgroup, we sequenced the cDNA for a nine-domain hemoglobin (P) from another genus of brine shrimp, Parartemia zietziana, which differs morphologically and ecologically from Artemia and is endemic to Australia. Parartemia produces only one hundredth the amount of hemoglobin that Artemia produces and does not upregulate production in response to low oxygen partial pressure. Comparison of the globin domains at the amino acid and DNA levels suggests that the Artemia globin T gene has accumulated substitutions differently from the Parartemia P and Artemia C globin genes. We discuss the questions of accelerated evolution after duplication and possible functions for the Parartemia globin. PMID:11264409

  2. Hemoglobin-based red blood cell substitutes and nitric oxide.

    PubMed

    Yu, Binglan; Bloch, Kenneth D; Zapol, Warren M

    2009-04-01

    Hemoglobin-based oxygen carriers (HBOCs) have been studied for decades as red blood cell substitutes. Profound vasoconstrictor effects have limited the clinical utility of HBOCs and are attributable to avid scavenging of nitric oxide (NO). Inhaling NO can charge the body's stores of NO metabolites without producing hypotension and can prevent systemic hypertension induced when HBOCs are subsequently infused. Concurrent breathing of low NO doses can prevent pulmonary vasoconstriction after HBOC infusion without augmenting plasma methemoglobinemia.

  3. Initial studies of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    SciTech Connect

    Hill, R.P.; Porter, L.S.; Ives, S.A.; Wong, J.T.F.

    1984-03-01

    Initial studies were performed to examine the potential of perfused dextran-hemoglobin to protect pig skin or mouse bone marrow cells against radiation damage. Some protection was indicated in both systems. In the pig skin a protection factor of 1.5 was observed for moist desquamation, and 2.0 for necrosis. These results suggest the possibility of using blood substitutes to induce tissue hypoxia for therapeutic purposes.

  4. Hemoglobin s polymerization and red cell membrane changes.

    PubMed

    Kuypers, Frans A

    2014-04-01

    Different pathways lead from the simple point mutation in hemoglobin to the membrane changes that characterize the altered interaction of the sickle red blood cell with its environment, including endothelial cells, white blood cells, and platelets. Polymerization and oxidation-induced damage to both lipid and protein components of the red cell membrane, as well as the generation of bioreactive membrane material (microparticles), has a profound effect on all tissues and organs, and defines the vasculopathy of the patient with sickle cell disease.

  5. Direct estimation of evoked hemoglobin changes by multimodality fusion imaging

    PubMed Central

    Huppert, Theodore J.; Diamond, Solomon G.; Boas, David A.

    2009-01-01

    In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be −0.55% ± 0.40% signal change per micromolar change of deoxyhemoglobin. PMID:19021411

  6. Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

    PubMed Central

    Bustamante, Juan P.; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A.; ten Have, Arjen; Martí, Marcelo A.

    2016-01-01

    Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends. PMID:26788940

  7. Modulating hemoglobin nitrite reductase activity through allostery: a mathematical model.

    PubMed

    Rong, Zimei; Alayash, Abdu I; Wilson, Michael T; Cooper, Chris E

    2013-11-30

    The production of nitric oxide by hemoglobin (Hb) has been proposed to play a major role in the control of blood flow. Because of the allosteric nature of hemoglobin, the nitrite reductase activity is a complex function of oxygen partial pressure PO2. We have previous developed a model to obtain the micro rate constants for nitrite reduction by R state (kR) and T state (kT) hemoglobin in terms of the experimental maximal macro rate constant kNmax and the corresponding oxygen concentration PO2max. However, because of the intrinsic difficulty in obtaining accurate macro rate constant kN, from available experiments, we have developed an alternative method to determine the micro reaction rate constants (kR and kT) by fitting the simulated macro reaction rate curve (kN versus PO2) to the experimental data. We then use our model to analyze the effect of pH (Bohr Effect) and blood ageing on the nitrite reductase activity, showing that the fall of bisphosphoglycerate (BPG) during red cell storage leads to increase NO production. Our model can have useful predictive and explanatory power. For example, the previously described enhanced nitrite reductase activity of ovine fetal Hb, in comparison to the adult protein, may be understood in terms of a weaker interaction with BPG and an increase in the value of kT from 0.0087M(-1)s(-1) to 0.083M(-1)s(-1).

  8. Vibrational modes of hemoglobin in red blood cells.

    PubMed

    Martel, P; Calmettes, P; Hennion, B

    1991-02-01

    Equine red blood cells were washed in saline heavy water (2H2O) to exchange the hydrogen atoms of the non-hemoglobin components with deuterons. This led to novel neutron scattering measurements of protein vibrations within a cellular system and permitted a comparison with inelastic neutron scattering measurements on purified horse hemoglobin, either dry or wetted with 2H2O. As a function of wavevector transfer Q and the frequency transfer v the neutron response typified by the dynamic structure factor S(Q, v) was found to be similar for extracted and cellular hemoglobin at low and high temperatures. At 77 K, in the cells, a peak in S(Q, v) due to the protein was found near 0.7 THz, approximately half the frequency of a strong peak in the aqueous medium. Measurements at higher temperatures (170 and 230 K) indicated similar small shifts downwards in the peak frequencies of both components. At 260 K the low frequency component became predominantly quasielastic, but a significant inelastic component could still be ascribed to the aqueous scattering. Near 295 K the frequency responses of both components were similar and centered near zero. When scattering due to water is taken into account it appears that the protein neutron response in, or out of, red blood cells is little affected by hydration in the low frequency regime where Van der Waals forces are thought to be effective. PMID:1849028

  9. Evolutionary and Functional Relationships in the Truncated Hemoglobin Family.

    PubMed

    Bustamante, Juan P; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A; Ten Have, Arjen; Martí, Marcelo A

    2016-01-01

    Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends.

  10. Short-lived intermediates in hemoglobin/O2 systems.

    PubMed

    Czerlinski, G; Levin, R; Ypma, T

    1998-01-01

    The kinetics of the reaction of hemoglobin with molecular oxygen, in which rapid mixing is followed by a very fast temperature jump, is numerically simulated. Values for rate constants are used to the extent known, otherwise interpolated or extrapolated. It is shown that reaction steps not resolvable by rapid mixing can be resolved by subsequent chemical relaxation at appropriate points in time. Four different mechanisms are considered, all assuming no distinction between the two kinds of chains of hemoglobin. Bimolecular rate constants for oxygen binding are either the same for all four sites, or are governed by "frequency factors" (the kinetic equivalent of statistical factors for equilibrium constants in allosteric models). Furthermore, either the third or the fourth measured (Adair) dissociation constant is composed of the product of a "local" dissociation constant and an allosteric interconversion constant. These two pairs of choices give rise to four different mechanisms. Can these mechanisms be distinguished experimentally? As the final parameter values are so similar for the first two binding steps, discrimination is essentially impossible at low oxygen concentration levels (less than 100 microM with 50 microM hemoglobin). Discrimination becomes possible at higher oxygen concentrations, but high resolution in time and concentration amplitude are required. Much depends upon the differences in molar extinction coefficients of components over the accessible wave length range. Some of these values are as yet unknown or not known to a sufficient precision. Nevertheless, distinction between mechanistic alternatives is possible in principle.

  11. Depleted zinc: Properties, application, production.

    PubMed

    Borisevich, V D; Pavlov, A V; Okhotina, I A

    2009-01-01

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  12. Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-04-01

    Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation

  13. Innovative uses for zinc in dermatology.

    PubMed

    Bae, Yoon Soo; Hill, Nikki D; Bibi, Yuval; Dreiher, Jacob; Cohen, Arnon D

    2010-07-01

    Severe zinc deficiency states, such as acrodermatitis enteropathica, are associated with a variety of skin manifestations, such as perioral, acral, and perineal dermatitis. These syndromes can be reversed with systemic zinc repletion. In addition to skin pathologies that are clearly zinc-dependent, many dermatologic conditions (eg, dandruff, acne, and diaper rash) have been associated and treated with zinc. Success rates for treatment with zinc vary greatly depending on the disease, mode of administration, and precise zinc preparation used. With the exception of systemic zinc deficiency states, there is little evidence that convincingly demonstrates the efficacy of zinc as a reliable first-line treatment for most dermatologic conditions. However, zinc may be considered as an adjunctive treatment modality. Further research is needed to establish the indications for zinc treatment in dermatology, optimal mode of zinc delivery, and best type of zinc compound to be used. PMID:20510767

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

    PubMed

    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 <0.001) for 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

  15. Comparative effects of zinc-nano complexes, zinc-sulphate and zinc-methionine on performance in broiler chickens.

    PubMed

    Mohammadi, V; Ghazanfari, S; Mohammadi-Sangcheshmeh, A; Nazaran, M H

    2015-01-01

    Micronutrients, especially zinc, have an important role in normal metabolism and growth of broilers. Using novel technologies helps to synthesise novel zinc complexes to deliver this micronutrient more efficiently. In the present study, the effects of different zinc complexes and nano complexes on broiler performance were compared. Broilers in 6 groups were given basal diet (without zinc) and basal diet supplemented with zinc-sulphate, zinc-methionine, zinc-nano-sulphate, zinc-nano-methionine and zinc-nano-max (that was synthesised based on nanochelating technology) at a concentration of 80 mg/kg of diet. At 1-42 d of age, dietary zinc-nano-sulphate supplementation decreased weight gain and feed intake. However, feed conversion ratio was not influenced by treatments. Carcass yield (%) of birds in the zinc-nano-sulphate and control groups were dramatically reduced at 42 d of age and abdominal fat (%) increased in these groups. Relative to the control group, the antibody titre, spleen and bursa of Fabricius (%) were significantly higher in groups supplemented with zinc. Heterophil (%) was also significantly higher in the zinc-nano-methionine group in blood on d 42 compared to the control, zinc-sulphate and zinc-nano-sulphate. Compared to the controls, the mean malondialdehyde content in thigh tissue was significantly reduced in groups supplemented with zinc at the time 0, 50, 100 and 150 min after oxidation. Tibia zinc concentration in nanoparticle zinc samples was significantly higher relative to the control and zinc-sulphate groups. Taken together, our data indicate that delivery of zinc in the structure of zinc-nano-methionine and zinc-nano-max at concentrations of 80 mg/kg of diet improves growth performance. However, dietary zinc-nano-sulphate decreased growth performance in broilers.

  16. Noninvasive fluorescence monitoring of protoporphyrin IX production and clinical outcomes in actinic keratoses following short-contact application of 5-aminolevulinate

    NASA Astrophysics Data System (ADS)

    Warren, Christine B.; Lohser, Sara; Wene, Lauren C.; Pogue, Brian W.; Bailin, Philip L.; Maytin, Edward V.

    2010-09-01

    Topical 5-aminolevulinic acid (ALA) is widely used in photodynamic therapy (PDT) of actinic keratoses (AK), a type of premalignant skin lesion. However, the optimal time between ALA application and exposure to light has not been carefully investigated. Our objective is to study the kinetics of protoporphyrin IX (PpIX) accumulation in AK after short contact ALA and relate this to erythemal responses. Using a noninvasive dosimeter, PpIX fluorescence measurements (5 replicates) were taken at 20-min intervals for 2 h following ALA application, in 63 AK in 20 patients. Data were analyzed for maximal fluorescent signal obtained, kinetic slope, and changes in erythema. Our results show that PpIX accumulation was linear over time, becoming statistically higher than background in 48% of all lesions by 20 min, 92% of lesions by 1 h, and 100% of lesions by 2 h. PpIX accumulation was roughly correlated with changes in lesional erythema post-PDT. We conclude that significant amounts of PpIX are produced in all AK lesions by 2 h. The linear kinetics of accumulation suggest that shorter ALA application times may be efficacious in many patients. Noninvasive fluorescence monitoring of PpIX may be useful to delineate areas of high PpIX accumulation within precancerous areas of the skin.

  17. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis

    NASA Astrophysics Data System (ADS)

    Kanick, Stephen Chad; Davis, Scott C.; Zhao, Yan; Hasan, Tayyaba; Maytin, Edward V.; Pogue, Brian W.; Chapman, M. Shane

    2014-07-01

    Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of >0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

  18. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy.

    PubMed

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-01-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 10(6) M(-1)). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy. PMID:27150264

  19. Molecular modeling and evaluation of binding mode and affinity of artemisinin-quinine hybrid and its congeners with Fe-protoporphyrin-IX as a putative receptor

    PubMed Central

    Mahapatra, Rajani Kanta; Behera, Niranjan; Naik, Pradeep Kumar

    2012-01-01

    A recent rational approach to anti-malarial drug design is characterized as “covalent biotherapy” involves linking of two molecules with individual intrinsic activity into a single agent, thus packaging dual activity into a single hybrid molecule. In view of this background and reported anti malaria synergism between artemisinin and quinine; we describe the computer-assisted docking to predict molecular interaction and binding affinity of Artemisinin-Quinine hybrid and its derivatives with the intraparasitic haeme group of human haemoglobin. Starting from a crystallographic structure of Fe-protoporphyrin-IX, binding modes, orientation of peroxide bridge (Fe-O distance), docking score and interaction energy are predicted using the docking molecular mechanics based on generalized Born/surface area (MM-GBSA) solvation model. Seven new ligands were identified with a favourable glide score (XP score) and binding free energy (ΔG) with reference to the experimental structure from a data set of thirty four hybrid derivatives. The result shows the conformational property of the drug-receptor interaction and may lead to rational design and synthesis of improved potent artemisinin based hybrid antimalarial that target haemozoin formation. PMID:22570518

  20. Combination of Protoporphyrin IX-mediated Sonodynamic Treatment with Doxorubicin Synergistically Induced Apoptotic Cell Death of a Multidrug-Resistant Leukemia K562/DOX Cell Line.

    PubMed

    Wang, Xiaobing; Jia, Yali; Su, Xiaomin; Wang, Pan; Zhang, Kun; Feng, Xiaolan; Liu, Quanhong

    2015-10-01

    The main objective of this study was to evaluate the efficacy of administration of doxorubicin (DOX) in combination with protoporphyrin IX (PpIX)-assisted low-level therapeutic ultrasound (US) in K562/DOX cells as a potential strategy in cancer therapy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the cytotoxicity of different treatments. Apoptosis was analyzed using annexin V-PE/7-amino-actinomycin D staining. Changes in DNA fragmentation, intracellular reactive oxygen species production, cellular membrane permeability, P-glycoprotein expression and DOX uptake were analyzed with flow cytometry. Under optimal conditions, PpIX-US significantly aggravated DOX-induced K562/DOX cell death, compared with either monotherapy. Synergistic potentiation of DNA damage, generation of reactive oxygen species and P-glycoprotein inhibition were observed. Plasma membrane integrity changed slightly after US exposure, and DOX uptake was notably improved after PpIX-US exposure. The results indicate that PpIX-US could increase the susceptibility of tumors to antineoplastic drugs, suggesting a clinical potential method for sonodynamic therapy-mediated tumor chemotherapy. PMID:26166458

  1. Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

    PubMed Central

    Lange, N; Jichlinski, P; Zellweger, M; Forrer, M; Marti, A; Guillou, L; Kucera, P; Wagnières, G; Bergh, H van den

    1999-01-01

    Exogenous administration of 5-aminolaevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of protoporphyrin IX (PpIX) in photodynamic therapy (PDT) and fluorescence photodetection (PD). Recently, results have shown that the chemical modification of ALA into its more lipophilic esters circumvents limitations of ALA-induced PpIX like shallow penetration depth into deep tissue layers and inhomogeneous biodistribution and enhances the total PpIX formation. The present clinical pilot study assesses the feasibility and the advantages of a topical ALA ester-based fluorescence photodetection in the human bladder. In this preliminary study 5-aminolaevulinic acid hexylester (h-ALA) solutions, containing concentrations ranging from 4 to 16 mM, were applied intravesically to 25 patients. Effects of time and drug dose on the resulting PpIX fluorescence level were determined in vivo with an optical fibre-based spectrofluorometer. Neither local nor systemic side-effects were observed for the applied conditions. All conditions used yielded a preferential PpIX accumulation in the neoplastic tissue. Our clinical investigations indicate that with h-ALA a twofold increase of PpIX fluorescence intensity can be observed using 20-fold lower concentrations as compared to ALA. © 1999 Cancer Research Campaign PMID:10389995

  2. A new application of Gompertz function in photohemolysis: the effect of temperature on red blood cell hemolysis photosensitized by protoporphyrin IX.

    PubMed

    Al-Akhras, M

    2006-08-01

    Photosensitization by protoporphyrin IX (PpIX) is accelerated at different irradiation temperatures, different dark incubation temperatures (Tinc) and different irradiation times. The applicability of Gompertz function to the fractional photohemolysis ratio, a and the rate of fractional photohemolysis, b is found to be the most appropriate model to fit the experimental data with minimum parameters and minimum errors. The reduction in Gompertz parameters, the fractional ratio values of a, and increase in the fractional rate values b, for 20 microM PpIX irradiated with black light at low irradiation temperature 5 degrees C and higher Tinc 37 degrees C was noticed. The parameter a has higher values at lower irradiation time and lower irradiation temperatures which indicates a longer photohemolysis process and longer t 50. Values of the parameter b were found to be strongly temperature-dependent, and always increase with increasing irradiation time and Tinc with lower values at lower irradiation time and lower Tinc. There are no significant changes in the lysis of RBCs process at irradiation temperatures equal to or higher than 35 degrees C. Similarly, no significant change on t50 at higher irradiation time at Tinc 24 and 37 degrees C. In conclusion, Gompertz analysis technique adapts to study the photohemolysis process at different conditions as a best-fit model. PMID:16937212

  3. A new application of Gompertz function in photohemolysis: the effect of temperature on red blood cell hemolysis photosensitized by protoporphyrin IX.

    PubMed

    Al-Akhras, M

    2006-08-01

    Photosensitization by protoporphyrin IX (PpIX) is accelerated at different irradiation temperatures, different dark incubation temperatures (Tinc) and different irradiation times. The applicability of Gompertz function to the fractional photohemolysis ratio, a and the rate of fractional photohemolysis, b is found to be the most appropriate model to fit the experimental data with minimum parameters and minimum errors. The reduction in Gompertz parameters, the fractional ratio values of a, and increase in the fractional rate values b, for 20 microM PpIX irradiated with black light at low irradiation temperature 5 degrees C and higher Tinc 37 degrees C was noticed. The parameter a has higher values at lower irradiation time and lower irradiation temperatures which indicates a longer photohemolysis process and longer t 50. Values of the parameter b were found to be strongly temperature-dependent, and always increase with increasing irradiation time and Tinc with lower values at lower irradiation time and lower Tinc. There are no significant changes in the lysis of RBCs process at irradiation temperatures equal to or higher than 35 degrees C. Similarly, no significant change on t50 at higher irradiation time at Tinc 24 and 37 degrees C. In conclusion, Gompertz analysis technique adapts to study the photohemolysis process at different conditions as a best-fit model.

  4. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-05-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M‑1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.

  5. Core-shell AgSiO2-protoporphyrin IX nanoparticle: Effect of the Ag core on reactive oxygen species generation

    NASA Astrophysics Data System (ADS)

    Lismont, M.; Pá; ez-Martinez, C.; Dreesen, L.

    2015-03-01

    Photodynamic therapy (PDT) for cancer is based on the use of a light sensitive molecule to produce, under specific irradiation, toxic reactive oxygen species (ROS). A way to improve the therapy efficiency is to increase the amount of produced ROS near cancer cells. This aim can be achieved by using a metal enhanced process arising when an optically active molecule is located near a metallic nanoparticle (NP). Here, the coupling effect between silver (Ag) NPs and protoporphyrin IX (PpIX) molecules, a clinically approved photosensitizer, is studied compared first, to PpIX fluorescence yield and second, to ROS production efficiency. By applying a modified Stöber process, PpIX was encapsulated into a silica (SiO2) shell, surrounding a 60 nm sized Ag core. We showed that, compared to SiO2-PpIX NPs, Ag coated SiO2-PpIX NPs dramatically decreased PpIX fluorescence together with singlet oxygen production efficiency. However, after incubation time in the dark, the amount of superoxide anions generated by the Ag doped sample was higher than the control sample one.

  6. Wavelength-dependent in-vitro and in-vivo photodynamic effects after sensitization with 5-aminolevulinic acid induced protoporphyrin IX

    NASA Astrophysics Data System (ADS)

    Szeimies, Rolf-Markus; Abels, Christoph; Fritsch, Clemens; Steinbach, Pia; Baeumler, Wolfgang; Messmann, Helmut; Goetz, Alwin E.; Goerz, Guenter; Landthaler, Michael

    1996-01-01

    Photodynamic therapy (PDT) with topically applied 5-aminolevulinic acid (ALA) is of growing interest, in particular in dermatology. Due to the fact that PDT with intravenously administered Photofrin is the only clinically approved sensitizer so far and is performed at a wavelength of 630 nm, this wavelength is also used in most experimental and clinical trials with ALA. In this study influence of irradiation with coherent light from a tunable dye laser at different wavelengths ranging from 625 to 649 nm was investigated. In in vitro experiments HaCaT immortalized human keratinocytes were sensitized with 30 (mu) g/ml ALA for 24 hrs. By determination of cell viability with the MTT test, best cell-killing effects were observed following irradiation at 635 nm. In an in vivo setting using an amelanotic melanoma (A-Mel-3) grown subcutaneously in Syrian Golden hamsters, these results were confirmed: tumor growth determined by measuring tumor volume increase after 28 days was less pronounced in animals treated with 100 mg/kg ALA i.v. and irradiated 2.5 hrs. later at 635 nm, as compared to animals receiving an equal dose and irradiated at 630 nm. This observation in vitro is probably due to large amounts of photosensitizing protoporphyrin IX (PP) localized in cell membranes which is visualized by confocal laser scanning microscopy (CLSM) and determined by HPLC analysis. These results suggest that in ALA-PDT when a coherent light source is used probably better results are achieved irradiating at 635 nm.

  7. Role of the Chemical Environment beyond the Coordination Site: Structural Insight into Fe(III) Protoporphyrin Binding to Cysteine-Based Heme-Regulatory Protein Motifs.

    PubMed

    Brewitz, Hans Henning; Kühl, Toni; Goradia, Nishit; Galler, Kerstin; Popp, Jürgen; Neugebauer, Ute; Ohlenschläger, Oliver; Imhof, Diana

    2015-10-12

    The importance of heme as a transient regulatory molecule has become a major focus in biochemical research. However, detailed information about the molecular basis of transient heme-protein interactions is still missing. We report an in-depth structural analysis of Fe(III) heme-peptide complexes by a combination of UV/Vis, resonance Raman, and 2D-NMR spectroscopic methods. The experiments reveal insights both into the coordination to the central iron ion and into the spatial arrangement of the amino acid sequences interacting with protoporphyrin IX. Cysteine-based peptides display different heme-binding behavior as a result of the existence of ordered, partially ordered, and disordered conformations in the heme-unbound state. Thus, the heme-binding mode is clearly the consequence of the nature and flexibility of the residues surrounding the iron ion coordinating cysteine. Our analysis reveals scenarios for transient binding of heme to heme-regulatory motifs in proteins and demonstrates that a thorough structural analysis is required to unravel how heme alters the structure and function of a particular protein. PMID:26260099

  8. Real-time analysis of endogenous protoporphyrin IX fluorescence from δ-aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent characteristics in vitro

    NASA Astrophysics Data System (ADS)

    Kiesslich, Tobias; Helander, Linda; Illig, Romana; Oberdanner, Christian; Wagner, Andrej; Lettner, Herbert; Jakab, Martin; Plaetzer, Kristjan

    2014-08-01

    Photodynamic therapy (PDT) and photodiagnosis based on the intracellular production of the photosensitizer protoporphyrin IX (PPIX) by administration of its metabolic precursor δ-aminolevulinic acid (ALA) achieved their breakthrough upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester). For newly developed ALA derivatives or application in new tumor types, in vitro determination of PPIX formation involves multiparametric experiments covering variable pro-drug concentrations, medium composition, time points of analysis, and cell type(s). This study uses a fluorescence microplate reader with a built-in temperature and atmosphere control to investigate the high-resolution long-term kinetics (72 h) of cellular PPIX fueled by administration of either ALA, MAL, or HAL for each 10 different concentrations. For simultaneous proliferation correction, A431 cells were stably transfected with green fluorescent protein. The results indicate that the peak PPIX level is a function of both, incubation concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or 0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with increasing pro-drug concentrations. The results underline the need for detailed temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or photodiagnosis and highlight the value of environment-controlled microplate readers for automated in vitro analysis.

  9. A Label-free, Highly Sensitive and Selective Detection of Hemin Based on the Competition between Hemin and Protoporphyrin IX Binding to G-Quadruplexes.

    PubMed

    Kang, Bei Hua; Li, Na; Liu, Shi Gang; Li, Nian Bing; Luo, Hong Qun

    2016-01-01

    Herein is reported a simple and label-free fluorescent detection method for hemin based on using protoporphyrin IX (PPIX) as a fluorescent signal reporter. PPIX emits weak fluorescence in an aqueous solution. When PPIX binds to G-quadruplexes, the fluorescence intensity of PPIX is greatly increased. While in the presence of target hemin, hemin competes with PPIX toward G-quadruplexes because its affinity to G-quadruplexes is higher than that of PPIX. With the formation of the hemin-G-quadruplex complex, PPIX is released to the solution from the G-quadruplex accompanied by quenching of the fluorescence of the system. This fluorescence change of the system can be used to monitor hemin with a low detection limit of 36 nM. In addition, the possible binding sites for PPIX binding to the G-quadruplex are discussed based on competition between hemin and PPIX. What is more, this method might pave the way for applying G-quadruplexes and PPIX to more sensing systems. PMID:27506716

  10. UV-vis spectroscopic study of Co(II)/Co(III) oxidation in poly[M-protoporphyrins] films and their interaction with axial ligands

    NASA Astrophysics Data System (ADS)

    Campo Dall'Orto, V.; Carballo, R.; Hurst, J. A.; Rezzano, I.

    2005-07-01

    A bathochromic shift for both Soret and Q bands in the polyCo(III)PP were indicative of Co(III) oxidation state in film. The presence of an isosbestic point indicates a chemical equilibrium between polyCo(III)PP (band I) in polyCo(III)PP with water as axial neutral ligand (band II). Concentration levels of iodide of 10 -1 M showed irreversible broadening of Soret band with a maximum shift from 400 nm to 380 nm attributed to film reduction. The thiocyanate anion shows a remarkable effect on polyCo(III)PP spectra. The degree of configuration interaction for Q and B transitions is nearly constant in air and water for Ni(II)PP, Cu(II)PP and Zn(II)PP films. The poly[Co(III)-protoporphyrin IX] showed strong deviation from the pattern. This result indicates that the Co atom does not present a planar conformation in polyCo(III)PP which is consistent with the less packed structure of this film. The apparent diffusion coefficients ( D') were calculated for electroactive species using the polyNi(II)PP chemically modified electrode, with an experiment short enough to avoid preconcentration. D' was compared with D (diffusion coefficient), obtained with the bare working electrode. Apparent diffusion coefficients ( D') changed regularly with molecular volume indicating certain molecular sieving effect.

  11. Role of the Chemical Environment beyond the Coordination Site: Structural Insight into Fe(III) Protoporphyrin Binding to Cysteine-Based Heme-Regulatory Protein Motifs.

    PubMed

    Brewitz, Hans Henning; Kühl, Toni; Goradia, Nishit; Galler, Kerstin; Popp, Jürgen; Neugebauer, Ute; Ohlenschläger, Oliver; Imhof, Diana

    2015-10-12

    The importance of heme as a transient regulatory molecule has become a major focus in biochemical research. However, detailed information about the molecular basis of transient heme-protein interactions is still missing. We report an in-depth structural analysis of Fe(III) heme-peptide complexes by a combination of UV/Vis, resonance Raman, and 2D-NMR spectroscopic methods. The experiments reveal insights both into the coordination to the central iron ion and into the spatial arrangement of the amino acid sequences interacting with protoporphyrin IX. Cysteine-based peptides display different heme-binding behavior as a result of the existence of ordered, partially ordered, and disordered conformations in the heme-unbound state. Thus, the heme-binding mode is clearly the consequence of the nature and flexibility of the residues surrounding the iron ion coordinating cysteine. Our analysis reveals scenarios for transient binding of heme to heme-regulatory motifs in proteins and demonstrates that a thorough structural analysis is required to unravel how heme alters the structure and function of a particular protein.

  12. eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy

    PubMed Central

    Fan, Zhichao; Cui, Xiaojun; Wei, Dan; Liu, Wei; Li, Buhong; He, Hao; Ye, Huamao; Zhu, Naishuo; Wei, Xunbin

    2016-01-01

    Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 106 M−1). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy. PMID:27150264

  13. Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyse the quaternary state of oxidized hemoglobins

    PubMed Central

    Mueser, Timothy C.; Griffith, Wendell P.; Kovalevsky, Andrey Y.; Guo, Jingshu; Seaver, Sean; Langan, Paul; Hanson, B. Leif

    2010-01-01

    Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-­state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons. PMID:21041946

  14. Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyse the quaternary state of oxidized hemoglobins

    SciTech Connect

    Mueser, Timothy C. Griffith, Wendell P.; Kovalevsky, Andrey Y.; Guo, Jingshu; Seaver, Sean; Langan, Paul; Hanson, B. Leif

    2010-11-01

    X-ray and neutron diffraction studies of cyanomethemoglobin are being used to evaluate the structural waters within the dimer–dimer interface involved in quaternary-state transitions. Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons.

  15. Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyse the quaternary state of oxidized hemoglobins.

    PubMed

    Mueser, Timothy C; Griffith, Wendell P; Kovalevsky, Andrey Y; Guo, Jingshu; Seaver, Sean; Langan, Paul; Hanson, B Leif

    2010-11-01

    Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons.

  16. Lipid peroxidation and hemoglobin degradation in red blood cells exposed to t-butyl hydroperoxide. Dependence on glucose metabolism and hemoglobin status.

    PubMed

    Trotta, R J; Sullivan, S G; Stern, A

    1981-12-01

    Changes in hemoglobin status and lipid peroxidation were followed in red cells containing either oxy-met-, or carbonmonoxyhemoglobin, incubated with t-butyl hydroperoxide in a medium with or without glucose. Loss of intact hemoglobin (the sum of oxyhemoglobin and methemoglobin) was inversely proportional to the degree of lipid peroxidation in red cells containing either oxy- or methemoglobin. When glucose was added to the medium, lipid peroxidation increased while there was a decreased loss of intact hemoglobin in red cells containing either oxy- or methemoglobin, while both lipid peroxidation and changes in hemoglobin decreased in red cells containing carbonmonoxyhemoglobin. Methemoglobin formation and loss of intact hemoglobin were directly proportional to the degree of lipid peroxidation in red cells containing carbonmonoxyhemoglobin. The greatest amount of lipid peroxidation occurred in red cells containing carbonmonoxyhemoglobin, incubated without glucose. These results indicate that methemoglobin and non-intact hemoglobin may protect the membrane against lipid peroxidation. We propose that, depending on the availability of glucose and the liganded state of hemoglobin, lipid peroxidation and hemoglobin alterations represent extremes of a spectrum of oxidative damage.

  17. Uptake and partitioning of zinc in Lemnaceae.

    PubMed

    Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

    2011-11-01

    Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility. PMID:21755349

  18. Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.

    PubMed

    Moezzi, Amir; Cortie, Michael; McDonagh, Andrew

    2016-04-25

    Thermal decomposition of layered zinc hydroxide double salts provides an interesting alternative synthesis for particles of zinc oxide. Here, we examine the sequence of changes occurring as zinc hydroxide chloride monohydrate (Zn5(OH)8Cl2·H2O) is converted to crystalline ZnO by thermal decomposition. The specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A complicating and important factor in this process is that the thermal decomposition of zinc hydroxide chloride is also accompanied by the formation of volatile zinc-containing species under certain conditions. We show that this volatile compound is anhydrous ZnCl2 and its formation is moisture dependent. Therefore, control of atmospheric moisture is an important consideration that affects the overall efficiency of ZnO production by this process. PMID:27030646

  19. Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

    PubMed

    Yan, S; Nègre, E; Cashel, J A; Guo, N; Lyman, C A; Walsh, T J; Roberts, D D

    1996-08-01

    Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis. PMID:8757815

  20. Hemoglobin E: a common hemoglobinopathy among children of Southeast Asian origin.

    PubMed

    Katsanis, E; Luke, K H; Hsu, E; Yates, J R

    1987-07-01

    With the recent immigration of Southeast Asians to Canada, hemoglobin E has become a frequent diagnosis. The clinical and hematologic findings in 42 children (mean age 4.3 years) with hemoglobin E are presented. There were 33 heterozygotes (having hemoglobin E trait), 6 homozygotes (having hemoglobin EE) and 3 double heterozygotes (having hemoglobin E-beta-thalassemia). The heterozygotes had low-normal hemoglobin levels and mean corpuscular volumes; coexisting iron deficiency, present in 62% of these children, resulted in substantially lower hemoglobin levels, very low mean corpuscular volumes and lower than expected levels of hemoglobin E on electrophoresis. The children with hemoglobin EE were only slightly anemic, but those with hemoglobin E-beta-thalassemia had severe anemia and required long-term transfusion therapy. Nutritional factors and parasitic infestations were the main causes of iron depletion, which was common, particularly in children less than 2 years old (87%). Physicians of patients of Southeast Asian origin should be aware of the clinical and hematologic presentation of these hemoglobinopathies.

  1. Arsenic doped zinc oxide

    SciTech Connect

    Volbers, N.; Lautenschlaeger, S.; Leichtweiss, T.; Laufer, A.; Graubner, S.; Meyer, B. K.; Potzger, K.; Zhou Shengqiang

    2008-06-15

    As-doping of zinc oxide has been approached by ion implantation and chemical vapor deposition. The effect of thermal annealing on the implanted samples has been investigated by using secondary ion mass spectrometry and Rutherford backscattering/channeling geometry. The crystal damage, the distribution of the arsenic, the diffusion of impurities, and the formation of secondary phases is discussed. For the thin films grown by vapor deposition, the composition has been determined with regard to the growth parameters. The bonding state of arsenic was investigated for both series of samples using x-ray photoelectron spectroscopy.

  2. Zinc Oxide Nanophotonics

    NASA Astrophysics Data System (ADS)

    Choi, Sumin; Aharonovich, Igor

    2015-12-01

    The emerging field of nanophotonics initiated a dedicated study of single photon sources and optical resonators in new class of materials. One such material is zinc oxide (ZnO) that has been long considered only for classical light-emitting applications. However, it recently showed promise for quantum photonics technologies. In this review, we highlight the recent advances in studying single emitters in ZnO, engineering of optical cavities and practical nanophotonics devices including nanolasers and electrically triggered devices. We finalize with an outlook at this promising area, as well as provide perspectives and open questions in solid state nanophotonics employing ZnO.

  3. Associations among dietary zinc intakes and biomarkers of zinc status before and after a zinc supplementation program in Guatemalan schoolchildren

    PubMed Central

    Bui, Vinh Q.; Marcinkevage, Jessica; Ramakrishnan, Usha; Flores-Ayala, Rafael C.; Ramirez-Zea, Manuel; Villalpando, Salvador; Martorell, Reynaldo; DiGirolamo, Ann M.; Stein, Aryeh D.

    2015-01-01

    Background The associations among dietary zinc intakes and biomarkers of zinc status are unknown in apparently healthy children at high risk for zinc deficiency. Objective To assess associations among zinc-related parameters in a sample of Guatemalan school-aged children. Methods We assessed total dietary intakes and biomarkers of zinc status before and after receiving 6 months of zinc supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years. Most of the children also received zinc-fortified milk from a government program that started shortly after the trial began. We assessed associations between zinc intakes and serum zinc, alkaline phosphatase (ALP), and albumin. Results At baseline, the prevalence of serum zinc < 65 μg/dL and dietary zinc intake below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9 and ≥ 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson correlations between serum zinc concentration and dietary zinc intake, serum ALP, and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes were observed in 1.2% and 0.0% of children in the zinc-supplemented group and 4.0% and 34.1% in the placebo group, respectively. Pearson correlations between serum zinc concentration and total zinc intake, serum ALP, and serum albumin were 0.10, 0.06, and −0.11 in the zinc-supplemented group and −0.04, 0.05, and 0.01 in the placebo group, respectively. Conclusions Zinc intake was inconsistently associated with markers of serum zinc concentration. Zinc fortification or supplementation attenuated the associations. PMID:23964387

  4. Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: a systematic review.

    PubMed

    Verhovsek, Madeleine; Henderson, Matthew P A; Cox, Gerard; Luo, Hong-yuan; Steinberg, Martin H; Chui, David H K

    2010-11-01

    Pulse oximetry estimates arterial blood oxygen saturation based on light absorbance of oxy- and deoxy-hemoglobin at 660 and 940 nm wavelengths. Patients with unexpectedly low SpO₂ often undergo cardio-pulmonary testing to ascertain the cause of their hypoxemia. However, in a subset of patients, a variant hemoglobin is responsible for low SpO₂ measurements. The extent of this problem is unclear. We performed a systematic literature review for reports of low SpO₂ associated with variant hemoglobins. We also reviewed unpublished cases from an academic hemoglobin diagnostic reference laboratory. Twenty-five publications and four unpublished cases were identified, representing 45 patients with low SpO₂ and confirmed variant hemoglobin. Fifty-seven family members of patients had confirmed or suspected variant hemoglobin. Three low oxygen affinity variant hemoglobins had concordantly low SpO₂ and SaO₂. Eleven variant hemoglobins were associated with unexpectedly low SpO₂ measurements but normal SaO₂. Hemoglobin light absorbance testing was reported in three cases, all of which showed abnormal absorption spectra between 600 and 900 nm. Seven other variant hemoglobins had decreased SpO₂, with unreported or uncertain SaO₂. Twenty-one variant hemoglobins were found to be associated with low SpO₂. Most variant hemoglobins were associated with spuriously low SpO₂. Abnormal absorption spectra explain the discrepancy between SpO₂ and SaO(2) for some variants. The differential diagnosis of possible variant hemoglobin ought to be considered in asymptomatic patients found to have unexpectedly low SpO₂. The correct diagnosis will help to spare patients from unnecessary investigations and anxiety.

  5. Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

    PubMed Central

    Bjurström, Carmen F; Mojadidi, Michelle; Phillips, John; Kuo, Caroline; Lai, Stephen; Lill, Georgia R; Cooper, Aaron; Kaufman, Michael; Urbinati, Fabrizia; Wang, Xiaoyan; Hollis, Roger P; Kohn, Donald B

    2016-01-01

    We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.

  6. Oxygen equilibria of ectotherm blood containing multiple hemoglobins.

    PubMed

    Maginniss, L A; Song, Y K; Reeves, R B

    1980-12-01

    Complete isocapnic O2 equilibrium curves (O2EC's) and related blood-gas properties are reported for whole blood of the bullfrog (Rana catesbeiana) and the aquatic turtle (Pseudemys scripta) at temperatures ranging from 5 to 35 degrees C. P50's for bullfrog and turtle blood at physiological pH and 25 degrees C were 36.6 Torr (pH 7.83) and 19.3 Torr (pH 7.55), respectively. Elevation of blood temperature significantly reduced hemoglobin oxygen affinity in both species (delta H = -8.1 and -7.8 kcal/mol O2 for Rana and Pseudemys, respectively). Bullfrog and turtle oxygen equilibrium data revealed non-standard curve shapes when compared with the Severinghaus curve for human blood (1979); ectotherm O2EC's rose more steeply below P50 (less sigmoid) and were distinctly flattened (linear) above 50% saturation. The CO2-Bohr effect for bullfrog and turtle blood varied significantly as a function of saturation. In addition, both species exhibited non-linear Hill relationships (logS/1-s vs. log PO2). These results indicate that the oxygen binding properties of the multiple hemoglobin bloods of Rana and Pseudemys (demonstrated by isoelectric focusing) are more complex than those exhibited by normal human blood. As a consequence, these ectotherm blood oxygen data are not well characterized by the limited number of simple descriptive parameters (P50, Hill's n and delta log P50/delta pH) commonly used to delineate predominantly single hemoglobin systems.

  7. Mass Spectra and Ion Collision Cross Sections of Hemoglobin

    NASA Astrophysics Data System (ADS)

    Kang, Yang; Terrier, Peran; Douglas, D. J.

    2011-02-01

    Mass spectra of commercially obtained hemoglobin (Hb) show higher levels of monomer and dimer ions, heme-deficient dimer ions, and apo-monomer ions than hemoglobin freshly prepared from blood. This has previously been attributed to oxidation of commercial Hb. Further, it has been reported that that dimer ions from commercial bovine Hb have lower collision cross sections than low charge state monomer ions. To investigate these effects further, we have recorded mass spectra of fresh human Hb, commercial human and bovine Hb, fresh human Hb oxidized with H2O2, lyophilized fresh human Hb, fresh human Hb both lyophilized and chemically oxidized, and commercial human Hb oxidized with H2O2. Masses of α-monomer ions of all hemoglobins agree with the masses expected from the sequences within 3 Da or better. Mass spectra of the β chains of commercial Hb and oxidized fresh human Hb show a peak or shoulder on the high mass side, consistent with oxidation of the protein. Both commercial proteins and oxidized fresh human Hb produce heme-deficient dimers with masses 32 Da greater than expected and higher levels of monomer and dimer ions than fresh Hb. Lyophilization or oxidation of Hb both produce higher levels of monomer and dimer ions in mass spectra. Fresh human Hb, commercial human Hb, commercial bovine Hb, and oxidized commercial human Hb all give dimer ions with cross sections greater than monomer ions. Thus, neither oxidation of Hb or the difference in sequence between human and bovine Hb make substantial differences to cross sections of ions.

  8. New-old hemoglobin-like proteins of symbiotic dinoflagellates

    PubMed Central

    Rosic, Nedeljka N; Leggat, William; Kaniewska, Paulina; Dove, Sophie; Hoegh-Guldberg, Ove

    2013-01-01

    Symbiotic dinoflagellates are unicellular photosynthetic algae that live in mutualistic symbioses with many marine organisms. Within the transcriptome of coral endosymbionts Symbiodinium sp. (type C3), we discovered the sequences of two novel and highly polymorphic hemoglobin-like genes and proposed their 3D protein structures. At the protein level, four isoforms shared between 87 and 97% sequence identity for Hb-1 and 78–99% for Hb-2, whereas between Hb-1 and Hb-2 proteins, only 15–21% sequence homology has been preserved. Phylogenetic analyses of the dinoflagellate encoding Hb sequences have revealed a separate evolutionary origin of the discovered globin genes and indicated the possibility of horizontal gene transfer. Transcriptional regulation of the Hb-like genes was studied in the reef-building coral Acropora aspera exposed to elevated temperatures (6–7°C above average sea temperature) over a 24-h period and a 72-h period, as well as to nutrient stress. Exposure to elevated temperatures resulted in an increased Hb-1 gene expression of 31% after 72 h only, whereas transcript abundance of the Hb-2 gene was enhanced by up to 59% by both 1-day and 3-day thermal stress conditions. Nutrient stress also increased gene expression of Hb-2 gene by 70%. Our findings describe the differential expression patterns of two novel Hb genes from symbiotic dinoflagellates and their polymorphic nature. Furthermore, the inducible nature of Hb-2 gene by both thermal and nutrient stressors indicates a prospective role of this form of hemoglobin in the initial coral–algal responses to changes in environmental conditions. This novel hemoglobin has potential use as a stress biomarker. PMID:23610627

  9. Differential expression of murine adult hemoglobins in early ontogeny

    SciTech Connect

    Wawrzyniak, C.J.; Lewis, S.E.; Popp, R.A.

    1985-01-01

    A hemoglobin mutation is described that permits study of the expression of the two adult ..beta..-globin genes throughout fetal and postnatal development. Mice with a mutation at the Hbb/sup s/, ..beta..-globin locus, were used to study the relative levels of ..beta..-s2major and ..beta..-sminor globins specified by the mutant Hbb/sup s2/ haplotype during development. At 11.5 days of gestation ..beta..-sminor comprised over 80% and ..beta..-s2major under 20% of the adult beta-globin. The relative level of ..beta..-sminor decreased through fetal development; at birth ..beta..-sminor represented 33.7% of the ..beta..-globin. The adult values of 71.0% ..beta..-s2major and 29.0% ..beta..-sminor globin are expressed in mice six days after birth. Because the two ..beta..-globin genes are expressed in mice of the Hbb/sup 2s/ haplotype, both the ..beta..-smajor and ..beta..-sminor genes must be expressed in mice of the Hbb/sup s/ haplotype. Expression of the ..beta..-sminor gene is elevated to 35.6% in Hbb/sup s2/ mice that have been bled repeatedly. Thus, the 5' ..beta..-s2major and 3' ..beta..-sminor genes of the Hbb/sup s2/ haplotype and, presumably the 5' ..beta..-smajor and 3' ..beta..-sminor genes of the Hbb/sup s/ haplotype, are regulated independently and are homologous to the 5' ..beta..-dmajor and 3' ..beta..-dminor genes of the Hbb/sup d/ haplotype. Mice of the Hbb/sup s2/ haplotype are better than mice of the Hbb/sup d/ haplotytpe for studying the mechanisms of hemoglobin switching because the Hbb/sup s2/ each of the three embryonic and two adult hemoglobins can be separated by electrophoresis. 17 refs., 3 figs.

  10. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOEpatents

    Jensen, R.H.; Vanderlaan, M.; Bigbee, W.L.; Stanker, L.H.; Branscomb, E.W.; Grabske, R.J.

    1984-11-29

    The present invention provides monoclonal antibodies specific to and distinguishing between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype. 4 figs.

  11. Sickle cell anemia: targeting the role of fetal hemoglobin in therapy.

    PubMed

    Coleman, Emma; Inusa, Baba

    2007-06-01

    Sickle cell anemia results from the single amino acid substitution of valine for glutamic acid in the beta-chain owing to a nucleotide defect that causes the production of abnormal beta-chains in hemoglobin S. Abnormal hemoglobin chains form polymers in the deoxygenated state, leading to the characteristic sickle cells. The polymerization of deoxygenated hemoglobin S accounts for the pathologic changes in sickle cell disease. The main-stay of therapy in sickle cell disease aims to reduce the amount of sickled hemoglobin present through the prevention of polymerization and reversal of this process. One way of discouraging polymerization is to increase the level of fetal hemoglobin, which because of its high oxygen affinity, does not participate in the polymerization process. Fetal hemoglobin production may be induced pharmacologically or by the use of gene therapy and genetic engineering techniques. PMID:17556734

  12. Long-term variation in hemoglobin concentration in nestling great tits Parus major.

    PubMed

    Kaliński, Adam; Bańbura, Mirosława; Glądalski, Michał; Markowski, Marcin; Skwarska, Joanna; Wawrzyniak, Jarosław; Zieliński, Piotr; Cyżewska, Iwona; Bańbura, Jerzy

    2015-07-01

    Several studies have previously proposed that blood hemoglobin concentration in nestling passerines is a reliable index of individual condition and nutritional state. In this paper we present results concerning variation in hemoglobin concentration in the blood of ca. 14-day-old nestling great tits Parus major in central Poland in an 11-year-long period, 2003-2013, in two distinct habitat types: urban park and deciduous forest. The most important findings of the study were: (i) variation in hemoglobin concentration was consistent within broods, (ii) hemoglobin concentration of nestlings varied markedly across years, (iii) hemoglobin concentration was significantly higher in the forest study site which is richer in terms of food abundance during the short period of tits breeding season and (iv) high hemoglobin level was a predictor of nestling survival from hatching to fledging.

  13. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOEpatents

    Jensen, Ronald H.; Vanderlaan, Martin; Bigbee, William L.; Stanker, Larry H.; Branscomb, Elbert W.; Grabske, Robert J.

    1988-01-01

    The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

  14. Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method.

    PubMed

    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.

  15. Electron Transfer Dissociation Mass Spectrometry of Hemoglobin on Clinical Samples

    NASA Astrophysics Data System (ADS)

    Coelho Graça, Didia; Lescuyer, Pierre; Clerici, Lorella; Tsybin, Yury O.; Hartmer, Ralf; Meyer, Markus; Samii, Kaveh; Hochstrasser, Denis F.; Scherl, Alexander

    2012-10-01

    A mass spectrometry-based assay combining the specificity of selected reaction monitoring and the protein ion activation capabilities of electron transfer dissociation was developed and employed for the rapid identification of hemoglobin variants from whole blood without previous proteolytic cleavage. The analysis was performed in a robust ion trap mass spectrometer operating at nominal mass accuracy and resolution. Subtle differences in globin sequences, resulting with mass shifts of about one Da, can be unambiguously identified. These results suggest that mass spectrometry analysis of entire proteins using electron transfer dissociation can be employed on clinical samples in a workflow compatible with diagnostic applications.

  16. Computation of the unsteady facilitated transport of oxygen in hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1990-01-01

    The transport of a reacting permeant diffusing through a thin membrane is extended to more realistic dissociation models. A new nonlinear analysis of the reaction-diffusion equations, using implicit finite-difference methods and direct block solvers, is used to study the limits of linearized and equilibrium theories. Computed curves of molecular oxygen permeating through hemoglobin solution are used to illustrate higher-order reaction models, the effect of concentration boundary layers at the membrane interfaces, and the transient buildup of oxygen flux.

  17. Carbon monoxide binding to a fish hemoglobin under photostationary conditions.

    PubMed

    Torkelson, S J; Gibson, Q H

    1978-10-25

    Determinations of carbon monoxide binding curves for hemoglobin from Brevoortia tyrannus under equilibrium and photostationary conditions show that in the light, the curve is shifted to the right and altered in shape. The Bohr effect is much less in the light. The kinetics of the transition between equilibrium and photostationary states has been examined. All of the results are satisfactorily described using the two-state model of Monod, J. Wyman, J., and Changeux, J.P. (1965) J. Mol. Biol. 12, 88-118 with the assumption that light produces an additive increase in the rate of dissociation of ligand from the R and T states. PMID:701255

  18. Broadband diffuse optical spectroscopy assessment of hemorrhage- and hemoglobin-based blood substitute resuscitation

    NASA Astrophysics Data System (ADS)

    Lee, Jangwoen; Kim, Jae G.; Mahon, Sari; Tromberg, Bruce J.; Mukai, David; Kreuter, Kelly; Saltzman, Darin; Patino, Renee; Goldberg, Robert; Brenner, Matthew

    2009-07-01

    Hemoglobin-based oxygen carriers (HBOCs) are solutions of cell-free hemoglobin (Hb) that have been developed for replacement or augmentation of blood transfusion. It is important to monitor in vivo tissue hemoglobin content, total tissue hemoglobin [THb], oxy- and deoxy-hemoglobin concentrations ([OHb], [RHb]), and tissue oxygen saturation (StO2=[OHb]/[THb]×100%) to evaluate effectiveness of HBOC transfusion. We designed and constructed a broadband diffuse optical spectroscopy (DOS) prototype system to measure bulk tissue absorption and scattering spectra between 650 and 1000 nm capable of accurately determining these tissue hemoglobin component concentrations in vivo. Our purpose was to assess the feasibility of using DOS to optically monitor tissue [OHb], [RHb], StO2, and total tissue hemoglobin concentration ([THb]=[OHb]+[RHb]) during HBOC infusion using a rabbit hypovolemic shock model. The DOS prototype probe was placed on the shaved inner thigh muscle of the hind leg to assess concentrations of [OHb], [RHb], [THb], as well as StO2. Hemorrhagic shock was induced in intubated New Zealand white rabbits (N=6) by withdrawing blood via a femoral arterial line to 20% blood loss (10-15 cc/kg). Hemoglobin glutamer-200 (Hb-200) 1:1 volume resuscitation was administered following the hemorrhage. These values were compared against traditional invasive measurements, serum hemoglobin concentration (sHGB), systemic blood pressure, heart rate, and blood gases. DOS revealed increases of [THb], [OHb], and tissue hemoglobin oxygen saturation after Hb-200 infusion, while blood total hemoglobin values continued did not increase; we speculate, due to hyperosmolality induced hemodilution. DOS enables noninvasive in vivo monitoring of tissue hemoglobin and oxygenation parameters during shock and volume expansion with HBOC and potentially enables the assessment of efficacy of resuscitation efforts using artificial blood substitutes.

  19. Genetic and developmental variation of hemoglobin in the deermouse, Peromyscus maniculatus.

    PubMed

    Maybank, K M; Dawson, W D

    1976-04-01

    A genetic investigation of electrophoretic hemoglobin variants of the deermouse, Peromyscus maniculatus, shows three alleles, Hblf, Hblr, and Hblo, at a duplicated site controlling the six adult phenotypes. The Hblf allele has not been described previously. The hemoglobin locus is not closely linked to the albino locus. Fetal hemoglobin is distinct from any of the adult components and has a slower electrophoretic mobility. The fetal phenotype changes to the adult type between the days 15 and 18 of prenatal life. PMID:962849

  20. 76 FR 51992 - Determination That PENTETATE ZINC TRISODIUM (Zinc Trisodium Diethylenetriaminepentaacetate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... HUMAN SERVICES Food and Drug Administration Determination That PENTETATE ZINC TRISODIUM (Zinc Trisodium... Administration (FDA) has determined that PENTETATE ZINC TRISODIUM (zinc trisodium diethylenetriaminepentaacetate... PENTETATE ZINC TRISODIUM (Zn-DTPA) solution for intravenous or inhalation administration (EQ 1 g base/5...