Encapsulation of concentrated hemoglobin solution in phospholipid vesicles retards the reaction with NO, but not CO, by intracellular diffusion barrier.

PubMed

Sakai, Hiromi; Sato, Atsushi; Masuda, Kaoru; Takeoka, Shinji; Tsuchida, Eishun

2008-01-18

One physiological significance of the red blood cell (RBC) structure is that NO binding of Hb is retarded by encapsulation with the cell membrane. To clarify the mechanism, we analyzed Hb-vesicles (HbVs) with different intracellular Hb concentrations, [Hb](in), and different particle sizes using stopped-flow spectrophotometry. The apparent NO binding rate constant, k(on)('(NO)), of HbV at [Hb](in) = 1 g/dl was 2.6 x 10(7) m(-1) s(-1), which was almost equal to k(on)((NO)) of molecular Hb, indicating that the lipid membrane presents no obstacle for NO binding. With increasing [Hb](in) to 35 g/dl, k(on)('(NO)) decreased to 0.9 x 10(7) m(-1) s(-1), which was further decreased to 0.5 x 10(7) m(-1) s(-1) with enlarging particle diameter from 265 to 452 nm. For CO binding, which is intrinsically much slower than NO binding, k(on)('(CO)) did not change greatly with [Hb](in) and the particle diameter. Results obtained using diffusion simulations coupled with elementary binding reactions concur with these tendencies and clarify that NO is trapped rapidly by Hb from the interior surface region to the core of HbV at a high [Hb](in), retarding NO diffusion toward the core of HbV. In contrast, slow CO binding allows time for further CO-diffusion to the core. Simulations extrapolated to larger particles (8 mum) showing retardation even for CO binding. The obtained k(on)('(NO)) and k(on)('(NO)) yield values similar to those reported for RBCs. In summary, the intracellular, not extracellular, diffusion barrier is predominant due to the rapid NO binding that induces a rapid sink of NO from the interior surface to the core, retarding further NO diffusion and binding.

Determination of extinction coefficients of human hemoglobin in various redox states

PubMed Central

Meng, Fantao; Alayash, Abdu I.

2017-01-01

The role of hemoglobin (Hb) redox forms in tissue and organ toxicities remain ambiguous despite the well-documented contribution of Hb redox reactivity to cellular and subcellular oxidative changes. Moreover, several recent studies, in which Hb toxicity were investigated, have shown conflicting outcomes. Uncertainties over the potential role of these species may in part be due to the protein preparation method of choice, the use of published extinction coefficients and the lack of suitable controls for Hb oxidation and heme loss. Highly purified and well characterized redox forms of human Hb were used in this study and the extinction coefficients of each Hb species (ferrous/oxy, ferric/met and ferryl) were determined. A new set of equations were established to improve accuracy in determining the transient ferryl Hb species. Additionally, heme concentrations in solutions and in human plasma were determined using a novel reversed phase HPLC method in conjugation with our photometric measurements. The use of more accurate redox-specific extinction coefficients and method calculations will be an invaluable tool for both in vitro and in vivo experiments aimed at determining the role of Hb-mediated vascular pathology in hemolytic anemias and when Hb is used as oxygen therapeutics. PMID:28069451

77 FR 5566 - Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-03

...] Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County, New Mexico... Statement (Final EIS) for the HB In-Situ Solution Mine Project, and by this notice is announcing its... the Federal Register. ADDRESSES: Copies of the HB In-Situ Solution Mining EIS are available for public...

In vitro photoacoustic measurement of hemoglobin oxygen saturation using a single pulsed broadband supercontinuum laser source.

PubMed

Lee, Changho; Jeon, Mansik; Jeon, Min Yong; Kim, Jeehyun; Kim, Chulhong

2014-06-20

We have utilized a single pulsed broadband supercontinuum laser source to photoacoustically sense total hemoglobin concentration (HbT) and oxygen saturation of hemoglobin (SO2) in bloods in vitro. Unlike existing expensive and bulky laser systems typically used for functional photoacoustic imaging (PAI), our laser system is relatively cost-effective and compact. Instead of using two single wavelengths, two wavelength bands were applied to distinguish the concentrations of two different chromophores in the mixture. In addition, we have successfully extracted the total dye concentration and the ratio of the red dye concentration to the total dye concentration in mixed red and blue dye solutions in phantoms. The results indicate that PAI with a cheap and compact fiber based laser source can potentially provide HbT and SO2 in live animals in vivo.

[Study on the interaction of hemoglobin and Cu(II)-ARS complex].

PubMed

Wu, Xiao-Hua; Miao, Ji-Gen; Miao, Yu-Qing; Chen, Jian-Rong

2007-06-01

The reaction of hemoglobin (Hb) with copper(II)-Alizarin red S (ARS) complex was studied in H3PO4-KH2PO4 buffer solution (pH 4. 2) by ultraviolet-visible spectrophotometry. The results show that the interaction of Hb and Cu(II)-ARS complex produces red ionic association complex with its maximum absorption peak at 537 nm. At the maximum absorption, the composition of the complex was determined to be n(Hb) : n(Cu(II)) : n(ARS) =1 : 4 : 8, and the apparent molar absorptivity was 1.52 x 10(5) L x mol(-1) x cm(-1). The concentration of Hb is linear with the absorbency in the range of 1.0 x 10(-7)-2.0 x 10(-6) mol x L(-1) and the regression equation was established as A = 0.026 9 + 151 675c (mol x L(-1)) with the coefficient r = 0.997 2. The effects of solution acidity, reagent amount, reaction time, temperature, ionic strength and the added surfactant were examined on the formation of the Hb-Cu(II)-ARS complex. A preliminary investigation was carried out to elucidate the reaction mechanism, and it could be concluded that the Hb and Cu(II)-ARS complex are combined mainly by electrostatic attraction. Further investigation was also undertaken to find out the effects of common amino acids and metallic ions on the formation of Hb-Cu(II)-ARS complex.

Fluorescent 2D WS2 Nanosheets Bearing Chemical Affinity Elements for the Recognition of Glycated Hemoglobin.

PubMed

Yang, Jin-Kyoung; Lee, Hye-Rim; Hwang, In-Jun; Kim, Hye-In; Yim, DaBin; Kim, Jong-Ho

2018-05-14

It is required to exfoliate and functionalize 2D transition metal dichalcogenides (TMDs) in an aqueous solution for biological and medical applications. Herein, the approach for the simultaneous exfoliation and functionalization of 2D WS 2 nanosheets using boronic acid-modified poly(vinyl alcohol) (B-PVA) in an aqueous solution is reported, and the B-PVA-functionalized WS 2 nanosheets (B-PVA-WS 2 ) are exploited as a fluorescent biosensor for the detection of glycated hemoglobin, HbA1c. The synthetic B-PVA polymer facilitates the exfoliation and functionalization of WS 2 nanosheets from the bulk counterpart in the aqueous solution via a pulsed sonication process, resulting in fluorescent B-PVA-WS 2 nanohybrids with a specific recognition of HbA1c. The fluorescence of the B-PVA-WS 2 is quenched in the presence of HbA1c, whereas PVA-functionalized WS 2 (PVA-WS 2 ), not bearing boronic acid as a recognition moiety, shows no fluorescence changes upon the addition of the target. The B-PVA-WS 2 is able to selectively detect HbA1c at the concentration as low as 3.3 × 10 -8 m based on its specific fluorescence quenching. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increased viscosity of hemoglobin-based oxygen carriers retards NO-binding when perfused through narrow gas-permeable tubes.

PubMed

Sakai, Hiromi; Okuda, Naoto; Takeoka, Shinji; Tsuchida, Eishun

2011-03-01

Increased fluid viscosity of a solution of hemoglobin-based oxygen carriers (HBOCs) reduces vasoconstrictive effects because increased shear stress on the vascular wall enhances the production of vasorelaxation factors such as NO. Nevertheless, on a microcirculatory level, it remains unclear how viscosity affects the reaction of HBOCs and NO. In this study, different HBOCs were perfused through narrow gas-permeable tubes (25 μm inner diameter at 1 mm/s centerline velocity; hemoglobin concentration [Hb]=5 g/dL). The reaction was examined microscopically based on the Hb visible-light absorption spectrum. When immersed in a NO atmosphere, the NO-binding of deoxygenated Hb solution (viscosity, 1.1 cP at 1000 s(-1)) in the tube occurred about twice as rapidly as that of red blood cells (RBCs): 1.6 cP. Binding was reduced by PEGylation (PEG-Hb, 7.7 cP), by addition of a high molecular weight hydroxyethyl starch (HES) (2.8 cP), and by encapsulation to form Hb-vesicles (HbVs, 1.5 cP; particle size 279 nm). However, the reduction was not as great as that shown for RBCs. A mixture of HbVs and HES (6.2 cP) showed almost identical NO-binding to that of RBCs. Higher viscosity and particle size might reduce lateral diffusion when particles are flowing. The HbVs with HES showed the slowest NO-binding. Furthermore, Hb encapsulation and PEGylation, but not HES-addition, tended to retard CO-binding. Increased viscosity reportedly enhances production of endothelium NO. In addition, our results show that the increased viscosity also inhibits the reaction with NO. Each effect might mitigate vasoconstriction. Copyright © 2010 Elsevier Inc. All rights reserved.

76 FR 21401 - Notice of Availability of the Draft EIS for the HB In-Situ Solution Mine Project, Eddy County, NM

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

...] Notice of Availability of the Draft EIS for the HB In-Situ Solution Mine Project, Eddy County, NM AGENCY... prepared a Draft Environmental Impact Statement (EIS) for the HB In- Situ Solution Mine Project, and by... considered, the BLM must receive written comments on the HB In-Situ Solution Mine Project Draft EIS within 60...

Kromoscopic measurement of glucose in the first overtone region of the near-infrared spectrum

NASA Astrophysics Data System (ADS)

Amerov, Airat K.; Sun, Yu; Small, Gary W.; Arnold, Mark A.

2002-05-01

The ability of Kromoscopy to measure glucose selectively is demonstrated in solutions composed glucose, urea, triacetin, bovine serum albumin (BSA), cholesterol, and hemoglobin (Hb). Kromoscopic measurements are made with a four-channel instrument designed for measuring light between 1500 and 1900 nm. The channels are configured to respond to four individual bands of near infrared light centered at 1600, 1700, 1750, and 1800 nm. An equation is proposed that describes the relative response for each channel as a function of relevant experimental parameters. This equation predicts the linear response observed for these types of measurements as a function of solute concentration. In addition, molar absorptivities are provided for glucose, urea, triacetin, BSA, Hb, and water. The non-negligible absorptivity of water demands the consideration of water displacement caused by solute dissolution. Channel responses are measured for a series of thirty-one samples. The chemical composition of these samples is designed to minimize the correlations between glucose concentration and the concentrations of all other solutes. Likewise, these samples provide negligible correlation between the concentration of glucose and the extent of water displacement. A calibration model is constructed for glucose by using a conventional P-matrix multiple linear regression analysis of the four-channel information. The resulting model demonstrates selectivity for glucose with values of 1.27 and 1.34 mM for the standard errors of calibration and prediction, respectively, over a glucose concentration range of 1.9 to 19 mM.

Nanostructured ZnO in a Metglas/ZnO/Hemoglobin Modified Electrode to Detect the Oxidation of the Hemoglobin Simultaneously by Cyclic Voltammetry and Magnetoelastic Resonance.

PubMed

Sagasti, Ariane; Bouropoulos, Nikolaos; Kouzoudis, Dimitris; Panagiotopoulos, Apostolos; Topoglidis, Emmanuel; Gutiérrez, Jon

2017-07-25

In the present work, a nanostructured ZnO layer was synthesized onto a Metglas magnetoelastic ribbon to immobilize hemoglobin (Hb) on it and study the Hb's electrochemical behavior towards hydrogen peroxide. Hb oxidation by H₂O₂ was monitored simultaneously by two different techniques: Cyclic Voltammetry (CV) and Magnetoelastic Resonance (MR). The Metglas/ZnO/Hb system was simultaneously used as a working electrode for the CV scans and as a magnetoelastic sensor excited by external coils, which drive it to resonance and interrogate it. The ZnO nanoparticles for the ZnO layer were grown hydrothermally and fully characterized by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and photoluminescence (PL). Additionally, the ZnO layer's elastic modulus was measured using a new method, which makes use of the Metglas substrate. For the detection experiments, the electrochemical cell was performed with a glass vial, where the three electrodes (working, counter and reference) were immersed into PBS (Phosphate Buffer Solution) solution and small H₂O₂ drops were added, one at a time. CV scans were taken every 30 s and 5 min after the addition of each drop and meanwhile a magnetoelastic measurement was taken by the external coils. The CV plots reveal direct electrochemical behavior of Hb and display good electrocatalytic response to the reduction of H₂O₂. The measured catalysis currents increase linearly with the H₂O₂ concentration in a wide range of 25-350 μM with a correlation coefficient 0.99. The detection limit is 25-50 μM. Moreover, the Metglas/ZnO/Hb electrode displays rapid response (30 s) to H₂O₂, and exhibits good stability and reproducibility of the measurements. On the other hand, the magnetoelastic measurements show a small linear mass increase versus the H₂O₂ concentration with a slope of 152 ng/μM, which is probably due to H₂O₂ adsorption in ZnO during the electrochemical reaction. No such effects were detected during the control experiment when only PBS solution was present for a long time.

FORMATION OF NITRO MUSK ADDUCTS OF RAINBOW ...

EPA Pesticide Factsheets

The high use of nitro musk xylene (MX) and musk ketone (MK) as fragrances, and their persistence and bioaccumulation potential make them ubiquitous environmental contaminants. The 4-amino-MX (AMX) and 2-amino-MK (AMK) metabolites have been detected in trout fish hemoglobin (Hb) samples by gas chromatography-ion trap-mass spectrometry (GC-MS). Twelve Hb samples prepared from rainbow trout that were exposed to MX and MK, over a period of 24 and 72 h, were analyzed. Amino metabolites were liberated by basic hydrolysis and extracted from the fish Hb into n-hexane. The extract was concentrated, analyzed, and spiked with a standard solution (80 pg/uL) of AMX or AMK and reanalyzed. Concentrations of AMX from 10 to 24.7 ng/g were detected in Hb from fish taken 24 and 72 h after MX exposure. At 24 and 72 h after MK exposure, the concentration of AMK was found to be 25.1 to 51, and 9.5 to 25.1 ng/g, respectively. Concentrations of AMK in Hb from two of the three trout were substantially lower after 72 h compared with 24 h exposure. The AMX and AMK metabolites were not detected in four control samples. Average recoveries exceeding 89 and 86% could be achieved for AMX and AMK, respectively, with a coefficient of variation (CV) around 5%. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various r

Red blood cells donate electrons to methylene blue mediated chemical reduction of methemoglobin compartmentalized in liposomes in blood.

PubMed

Sakai, Hiromi; Li, Bing; Lim, Wei Lee; Iga, Yumika

2014-07-16

Electron-energy-rich coenzymes in cells, NADH and NADPH, are re-energized repeatedly through the Embden-Meyerhof and pentose-phosphate glycolytic pathways, respectively. This study demonstrates extraction of their electron energies in red blood cells (RBCs) for in vivo extracellular chemical reactions using an electron mediator shuttling across the biomembrane. Hemoglobin-vesicles (HbVs) are an artificial oxygen carrier encapsulating purified and concentrated Hb solution in liposomes. Because of the absence of a metHb-reducing enzymatic system in HbV, HbO2 gradually autoxidizes to form metHb. Wistar rats received HbV suspension (10 mL/kg body weight) intravenously. At the metHb level of around 50%, methylene blue [MB(+); 3,7-bis(dimethylamino)phenothiazinium chloride] was injected. The level of metHb quickly decreased to around 16% in 40 min, remaining for more than 5 h. In vitro mixing of HbV/MB(+) with RBCs recreated the in vivo metHb reduction, but not with plasma. NAD(P)H levels in RBCs decreased after metHb reduction. The addition of glucose facilitated metHb reduction. Liposome-encapsulated NAD(P)H, a model of RBC, reduced metHb in HbV in the presence of MB(+). These results indicate that (i) NAD(P)H in RBCs reacts with MB(+) to convert it to leukomethylene blue (MBH); (ii) MB(+) and MBH shuttle freely between RBC and HbV across the hydrophobic lipid membranes; and (iii) MBH is transferred into HbV and reduces metHb in HbV. Four other electron mediators with appropriate redox potentials appeared to be as effective as MB(+) was, indicating the possibility for further optimization of electron mediators. We established an indirect enzymatic metHb reducing system for HbV using unlimited endogenous electrons created in RBCs in combination with an effective electron mediator that prolongs the functional lifespan of HbV in blood circulation.

Continuous protein concentration via free-flow moving reaction boundary electrophoresis.

PubMed

Kong, Fanzhi; Zhang, Min; Chen, Jingjing; Fan, Liuyin; Xiao, Hua; Liu, Shaorong; Cao, Chengxi

2017-07-28

In this work, we developed the model and theory of free-flow moving reaction boundary electrophoresis (FFMRB) for continuous protein concentration for the first time. The theoretical results indicated that (i) the moving reaction boundary (MRB) can be quantitatively designed in free-flow electrophoresis (FFE) system; (ii) charge-to-mass ratio (Z/M) analysis could provide guidance for protein concentration optimization; and (iii) the maximum processing capacity could be predicted. To demonstrate the model and theory, three model proteins of hemoglobin (Hb), cytochrome C (Cyt C) and C-phycocyanin (C-PC) were chosen for the experiments. The experimental results verified that (i) stable MRBs with different velocities could be established in FFE apparatus with weak acid/weak base neutralization reaction system; (ii) proteins of Hb, Cyt C and C-PC were well concentrated with FFMRB; and (iii) a maximum processing capacity and recovery ratio of Cyt C enrichment were 126mL/h and 95.5% respectively, and a maximum enrichment factor was achieved 12.6 times for Hb. All of the experiments demonstrated the protein concentration model and theory. In contrast to other methods, the continuous processing ability enables FFMRB to efficiently enrich diluted protein or peptide in large volume solution. Copyright © 2017 Elsevier B.V. All rights reserved.

Fetal hemoglobin in sickle cell anemia: a glass half full?

PubMed

Steinberg, Martin H; Chui, David H K; Dover, George J; Sebastiani, Paola; Alsultan, Abdulrahman

2014-01-23

Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ∼10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease.

Identification of parallel and divergent optimization solutions for homologous metabolic enzymes

DOE PAGES

Standaert, Robert F.; Giannone, Richard J.; Michener, Joshua K.

2018-04-18

Here, metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI, from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neithermore » enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA, duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI, growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.« less

Identification of parallel and divergent optimization solutions for homologous metabolic enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Standaert, Robert F.; Giannone, Richard J.; Michener, Joshua K.

Here, metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI, from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neithermore » enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA, duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI, growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.« less

Identification of parallel and divergent optimization solutions for homologous metabolic enzymes.

PubMed

Standaert, Robert F; Giannone, Richard J; Michener, Joshua K

2018-06-01

Metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI , from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neither enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA , duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI , growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.

HYDRAULICS AND MIXING EVALUATIONS FOR NT-21/41 TANKS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S.; Barnes, O.

2014-11-17

The hydraulic results demonstrate that pump head pressure of 20 psi recirculates about 5.6 liters/min flowrate through the existing 0.131-inch orifice when a valve connected to NT-41 is closed. In case of the valve open to NT-41, the solution flowrates to HB-Line tanks, NT-21 and NT-41, are found to be about 0.5 lpm and 5.2 lpm, respectively. The modeling calculations for the mixing operations of miscible fluids contained in the HB-Line tank NT-21 were performed by taking a three-dimensional Computational Fluid Dynamics (CFD) approach. The CFD modeling results were benchmarked against the literature results and the previous SRNL test resultsmore » to validate the model. Final performance calculations were performed for the nominal case by using the validated model to quantify the mixing time for the HB-Line tank. The results demonstrate that when a pump recirculates a solution volume of 5.7 liters every minute out of the 72-liter tank contents containing two acid solutions of 2.7 M and 0 M concentrations (i.e., water), a minimum mixing time of 1.5 hours is adequate for the tank contents to get the tank contents adequately mixed. In addition, the sensitivity results for the tank contents of 8 M existing solution and 1.5 M incoming species show that the mixing time takes about 2 hours to get the solutions mixed.« less

Responses of normal and sickle cell hemoglobin to S-nitroscysteine: implications for therapeutic applications of NO in treatment of sickle cell disease.

PubMed

Bonaventura, Celia; Godette, Gerald; Ferruzzi, Giulia; Tesh, Shirley; Stevens, Robert D; Henkens, Robert

2002-07-10

Factors which govern transnitrosation reactions between hemoglobin (Hb) and low molecular weight thiols may define the extent to which S-nitrosated Hb (SNO-Hb) plays a role in NO in the control of blood pressure and other NO-dependent reactions. We show that exposure to S-nitrosylated cysteine (CysNO) produces equivalent levels of SNO-Hb for Hb A(0) and sickle cell Hb (Hb S), although these proteins differ significantly in the electron affinity of their heme groups as measured by their anaerobic redox potentials. Dolphin Hb, a cooperative Hb with a redox potential like that of Hb S, produces less SNO-Hb, indicating that steric considerations outweigh effects of altered electron affinity at the active-site heme groups in control of SNO-Hb formation. Examination of oxygen binding at 5-20 mM heme concentrations revealed increases due to S-nitrosation in the apparent oxygen affinity of both Hb A(0) and Hb S, similar to increases seen at lower heme concentrations. As observed at lower heme levels, deoxygenation is not sufficient to trigger release of NO from SNO-Hb. A sharp increase in apparent oxygen affinity occurs for unmodified Hb S at concentrations above 12.5 mM, its minimum gelling concentration. This affinity increase still occurs in 30 and 60% S-nitrosated samples, but at higher heme concentration. This oxygen binding behavior is accompanied by decreased gel formation of the deoxygenated protein. S-nitrosation is thus shown to have an effect similar to that reported for other SH-group modifications of Hb S, in which R-state stabilization opposes Hb S aggregation.

Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taguchi, Kazuaki; Miyasato, Mayumi; Ujihira, Hayato

2010-11-01

The hemoglobin vesicle (HbV) is an artificial oxygen carrier in which a concentrated Hb solution is encapsulated in lipid vesicles. Our previous studies demonstrated that HbV is metabolized by the mononuclear phagocyte system, and the lipid components are excreted from the liver. It is well-known that many hepatically-metabolized and -excreted drugs show altered pharmaceutics under conditions of liver impairment, which results in adverse effects. The aim of this study was to determine whether the administration of HbV causes toxicity in rats with carbon tetrachloride induced liver cirrhosis. Changes in plasma biochemical parameters, histological staining and the pharmacokinetic distribution of HbVmore » were evaluated after an HbV injection of the above model rats at a putative clinical dose (1400 mgHb/kg). Plasma biochemical parameters were not significantly affected, except for a transient elevation of lipase, lipid components and bilirubin, which recovered within 14 days after an HbV infusion. Negligible morphological changes were observed in the kidney, liver, spleen, lung and heart. Hemosiderin, a marker of iron accumulation in organs, was observed in the liver and spleen up to 14 days after HbV treatment, but no evidence of oxidative stress in the plasma and liver were observed. HbV is mainly distributed in the liver and spleen, and the lipid components are excreted into feces within 7 days. In conclusion, even under conditions of hepatic cirrhosis, HbV and its components exhibit the favorable metabolic and excretion profile at the putative clinical dose. These findings provide further support for the safety and effectiveness of HbV in clinical settings.« less

The application of polymerized porcine hemoglobin (pPolyHb) in the rat small bowel preservation.

PubMed

Huang, He; Ma, Jun; Zhu, Wenjin; Sun, Jinghui; Yan, Kunping; Song, Bo; Xue, Yuejin; Xin, Jianguo; Pan, Wencan; Zhu, Hongli; Chen, Chao

2014-10-01

Small bowel transplantation (SBTx) has become a standard clinical treatment for short bowel syndrome or irreversible intestinal function failure. Optimum preservation of the organ is essential for the success of transplantation. In this study, pPolyHb was used as an additive to hypertonic citrate adenine solution (HCA) to provide oxygen for rat small bowel transplant. Rat small bowels were preserved in HCA, HCA with pPolyHb, and University of Wisconsin solution (UW) for 12, 24, and 36 h, respectively. The results suggested that the preservation effect of HCA with pPolyHb was comparable with the UW solution, and more effective than the HCA solution.

Facile synthesis of N-acetyl-L-cysteine capped CdHgSe quantum dots and selective determination of hemoglobin.

PubMed

Wang, Qingqing; Zhan, Guoqing; Li, Chunya

2014-01-03

Using N-acetyl-L-cysteine (NAC) as a stabilizer, well water-dispersed, high-quality and stable CdHgSe quantum dots were facilely synthesized via a simple aqueous phase method. The as-prepared NAC capped CdHgSe quantum dots were thoroughly characterized by fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and transmission electron microscopy. A novel method for the selective determination of hemoglobin (Hb) was developed based on fluorescence quenching of the NAC capped CdHgSe quantum dots. A number of key factors including pH value of phosphate buffer solution, quantum dots concentration, the adding sequence of reagents and reaction time that influence the analytical performance of the NAC capped CdHgSe quantum dots in Hb determination were investigated. Under the optimal experimental conditions, the change of fluorescence intensity (ΔI) was linearly proportional to the concentration of Hb in the range of 4.0×10(-9)-4.4×10(-7) mol L(-1) with a detection limit of 2.0×10(-9) mol L(-1). The developed method has been successfully employed to determine Hb in human urine samples. Copyright © 2013. Published by Elsevier B.V.

Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial

PubMed Central

Zhang, Yiting; Jin, Lei; Liu, Jian-meng; Ye, Rongwei; Ren, Aiguo

2016-01-01

Objective To examine the relationship between maternal hemoglobin (Hb) concentration and the risk of anemia in infancy. Study design This analysis included 17,193 women who entered the trial when they were 20 years of age or older, no more than 20 weeks of gestation, had mild or no anemia, and delivered singleton live births. Maternal Hb concentrations were measured in the first trimester and during 24-28 weeks of gestation; infant Hb concentrations were measured at 5-7 months and 11-13 months of life. The associations between maternal Hb concentrations and infant Hb concentrations were examined. Results Maternal Hb concentrations measured during 24-28 weeks of gestation, but not in the first trimester, were correlated with infant Hb concentrations measured at either of the two post-partum periods. The risk of infant anemia at 5-7 months increased when maternal Hb concentration was ≤109 g/L during 24-28 weeks of gestation ([AOR: 1.95, 95% CI: 1.59-2.40] and 11-13 months [AOR: 1.72, 95% CI: 1.36-2.18]); whereas the risk of anemia during 5-7 months as well as 11-13 months in infancy decreased when maternal Hb level at 24-28 weeks of gestation was 120-129 g/L (AOR for 5-7 months: 0.74, 95% CI: 0.64-0.85; AOR for 11-13 months: 0.72, 95% CI: 0.61-0.85) or ≥130 g/L (AOR for 5-7 months: 0.75, 95% CI: 0.63-0.90; AOR for 11-13 months: 0.89, 95% CI: 0.73-1.08). Conclusion Low maternal Hb concentration during 24-28 weeks of gestation was associated with an increased risk of anemia in infancy, whereas high maternal Hb concentration was associated with a reduced risk of anemia. PMID:27263403

Continuous monitoring of haemoglobin concentration after in-vivo adjustment in patients undergoing surgery with blood loss.

PubMed

Frasca, D; Mounios, H; Giraud, B; Boisson, M; Debaene, B; Mimoz, O

2015-07-01

Non-invasive monitoring of haemoglobin concentration provides real-time measurement of haemoglobin concentration (SpHb) using multi-wavelength pulse co-oximetry. We hypothesised that in-vivo adjustment using the mean of three haemoglobinometer (HemoCue®) measurements from an arterial blood sample at the first SpHb measurement (HCueART) would increase the accuracy of the monitor. The study included 41 adults for a total of 173 measurements of haemoglobin concentration. In-vivo adjusted SpHb was automatically calculated by the following formula: in-vivo adjusted SpHb = unadjusted SpHb - (SpHb - HCueART). The accuracy of in-vivo adjusted SpHb was compared with SpHb retrospectively adjusted using the same formula, except for haemoglobin level which was assessed at the central laboratory and then compared with all other available invasive methods of haemoglobin measurement (co-oximetry, HbSAT; arterial HemoCue, HCueART; capillary HemoCue, HCueCAP). Compared with laboratory measurement of haemoglobin concentration, bias (precision) for unadjusted SpHb, in-vivo adjusted SpHb, retrospectively adjusted SpHb, HbSAT, HCueART and HCueCAP were -0.4 (1.4), -0.3 (1.1), -0.3 (1.1), -0.6 (0.7), 0.0 (0.4) and -0.5 (1.2) g.dl(-1) , respectively. In-vivo adjustment of SpHb values using the mean of three arterial HemoCue measurements improved the accuracy of the device similar to those observed after a retrospective adjustment using central laboratory haemoglobin level. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children.

PubMed

Hinnouho, Guy-Marino; Barffour, Maxwell A; Wessells, K Ryan; Brown, Kenneth H; Kounnavong, Sengchanh; Chanhthavong, Bigphone; Ratsavong, Kethmany; Kewcharoenwong, Chidchamai; Hess, Sonja Y

2017-12-02

Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia screening in both adults and children. However, few studies have compared the diagnostic accuracy of Hemocue with an automated haematology analyser in young children. To compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR. Capillary blood was collected from 6-month-old to 23-month-old children (n=1487) for determination of Hb concentration by Hemocue Hb301. On the same day, venous blood was collected for complete blood count using one of two haematology analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301. Agreement between the two methods was estimated using Bland-Altman plots. Mean capillary Hb by Hemocue was significantly higher than mean venous Hb by haematology analysers combined (108.4±10.3 g/L vs 102.3±13.1 g/L; P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement showed a bias of 6.1 g/L and limits of agreement were -11.5 g/L to 23.7 g/L. Mean venous Hb concentration by Hemocue Hb301 (113.6±14.0 g/L) was significantly higher than mean capillary Hb concentration by Hemocue Hb301 (110.0±10.7; P=0.03 g/L), which in turn was significantly higher than mean venous Hb concentration by the Mindray BC-3000Plus (102.3±17.4 g/L). Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor agreement compared with venous Hb by automated haematology analysers, resulting in significantly different anaemia prevalences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

HCl, KCl and KOH solvation resolved solute-solvent interactions and solution surface stress

NASA Astrophysics Data System (ADS)

Zhang, Xi; Xu, Yan; Zhou, Yong; Gong, Yinyan; Huang, Yongli; Sun, Chang Q.

2017-11-01

An incorporation of the hydrogen bond (O:Hsbnd O or HB) cooperativity notion, contact angle detection, and the differential phonon spectrometrics (DPS) has enabled us to gain refined information on the HCl, KCl and KOH solvation resolved solute-solvent molecular interactions and the solution surface stresses. Results show that ionic polarization stiffens the solvent Hsbnd O bond phonon from 3200 to 3480 cm-1 in the hydration shells. The HO- in alkaline solution, however, shares not only the same Hsbnd O phonon redshift of compressed water from 3200 to < 3100 cm-1 but also the dangling bonds of H2O surface featured at 3610 cm-1. Salt and alkaline solvation enhances the solution surface stress by K+ and Cl- ionic polarization. The excessive H+ proton in acid solution forms a H↔H anti-HB that depresses the solution surface stress, instead. The solute capability of transforming the fraction of the O:Hsbnd O bonds of the solvent matrix is featured by: fH = 0 and fx ∝ 1-exp(-C/C0) (x = HO-, K+ and Cl-) towards saturation. Exercises not only confirm the presence of the H↔H anti-HB point fragilization, the O:⇔:O super-HB point compression, and ionic polarization dominating the performance of the respective HCl, KOH, and KCl solutions, but also demonstrate the power of the DPS that enables high resolution of solute-solute-solvent interactions and correlation between HB relaxation and solution surface stress.

Incorporation of Hydrogen Bond Angle Dependency into the Generalized Solvation Free Energy Density Model.

PubMed

Ma, Songling; Hwang, Sungbo; Lee, Sehan; Acree, William E; No, Kyoung Tai

2018-04-23

To describe the physically realistic solvation free energy surface of a molecule in a solvent, a generalized version of the solvation free energy density (G-SFED) calculation method has been developed. In the G-SFED model, the contribution from the hydrogen bond (HB) between a solute and a solvent to the solvation free energy was calculated as the product of the acidity of the donor and the basicity of the acceptor of an HB pair. The acidity and basicity parameters of a solute were derived using the summation of acidities and basicities of the respective acidic and basic functional groups of the solute, and that of the solvent was experimentally determined. Although the contribution of HBs to the solvation free energy could be evenly distributed to grid points on the surface of a molecule, the G-SFED model was still inadequate to describe the angle dependency of the HB of a solute with a polarizable continuum solvent. To overcome this shortcoming of the G-SFED model, the contribution of HBs was formulated using the geometric parameters of the grid points described in the HB coordinate system of the solute. We propose an HB angle dependency incorporated into the G-SFED model, i.e., the G-SFED-HB model, where the angular-dependent acidity and basicity densities are defined and parametrized with experimental data. The G-SFED-HB model was then applied to calculate the solvation free energies of organic molecules in water, various alcohols and ethers, and the log P values of diverse organic molecules, including peptides and a protein. Both the G-SFED model and the G-SFED-HB model reproduced the experimental solvation free energies with similar accuracy, whereas the distributions of the SFED on the molecular surface calculated by the G-SFED and G-SFED-HB models were quite different, especially for molecules having HB donors or acceptors. Since the angle dependency of HBs was included in the G-SFED-HB model, the SFED distribution of the G-SFED-HB model is well described as compared to that of the G-SFED model.

Monitoring hypoxia induced changes in cochlear blood flow and hemoglobin concentration using a combined dual-wavelength laser speckle contrast imaging and Doppler optical microangiography system.

PubMed

Reif, Roberto; Qin, Jia; Shi, Lei; Dziennis, Suzan; Zhi, Zhongwei; Nuttall, Alfred L; Wang, Ruikang K

2012-01-01

A synchronized dual-wavelength laser speckle contrast imaging (DWLSCI) system and a Doppler optical microangiography (DOMAG) system was developed to determine several ischemic parameters in the cochlea due to a systemic hypoxic challenge. DWLSCI can obtain two-dimensional data, and was used to determine the relative changes in cochlear blood flow, and change in the concentrations of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) in mice. DOMAG can obtain three-dimensional data, and was used to determine the changes in cochlear blood flow with single vessel resolution. It was demonstrated that during a hypoxic challenge there was an increase in the concentrations of Hb, a decrease in the concentrations of HbO and cochlear blood flow, and a slight decrease in the concentration of HbT. Also, the rate of change in the concentrations of Hb and HbO was quantified during and after the hypoxic challenge. The ability to simultaneously measure these ischemic parameters with high spatio-temporal resolution will allow the detailed quantitative analysis of several hearing disorders, and will be useful for diagnosing and developing treatments.

Nanostructured ZnO in a Metglas/ZnO/Hemoglobin Modified Electrode to Detect the Oxidation of the Hemoglobin Simultaneously by Cyclic Voltammetry and Magnetoelastic Resonance

PubMed Central

Sagasti, Ariane; Bouropoulos, Nikolaos; Kouzoudis, Dimitris; Panagiotopoulos, Apostolos; Topoglidis, Emmanuel; Gutiérrez, Jon

2017-01-01

In the present work, a nanostructured ZnO layer was synthesized onto a Metglas magnetoelastic ribbon to immobilize hemoglobin (Hb) on it and study the Hb’s electrochemical behavior towards hydrogen peroxide. Hb oxidation by H2O2 was monitored simultaneously by two different techniques: Cyclic Voltammetry (CV) and Magnetoelastic Resonance (MR). The Metglas/ZnO/Hb system was simultaneously used as a working electrode for the CV scans and as a magnetoelastic sensor excited by external coils, which drive it to resonance and interrogate it. The ZnO nanoparticles for the ZnO layer were grown hydrothermally and fully characterized by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and photoluminescence (PL). Additionally, the ZnO layer’s elastic modulus was measured using a new method, which makes use of the Metglas substrate. For the detection experiments, the electrochemical cell was performed with a glass vial, where the three electrodes (working, counter and reference) were immersed into PBS (Phosphate Buffer Solution) solution and small H2O2 drops were added, one at a time. CV scans were taken every 30 s and 5 min after the addition of each drop and meanwhile a magnetoelastic measurement was taken by the external coils. The CV plots reveal direct electrochemical behavior of Hb and display good electrocatalytic response to the reduction of H2O2. The measured catalysis currents increase linearly with the H2O2 concentration in a wide range of 25–350 μM with a correlation coefficient 0.99. The detection limit is 25–50 μM. Moreover, the Metglas/ZnO/Hb electrode displays rapid response (30 s) to H2O2, and exhibits good stability and reproducibility of the measurements. On the other hand, the magnetoelastic measurements show a small linear mass increase versus the H2O2 concentration with a slope of 152 ng/μM, which is probably due to H2O2 adsorption in ZnO during the electrochemical reaction. No such effects were detected during the control experiment when only PBS solution was present for a long time. PMID:28773209

The Prognostic Value of Hemoglobin Concentration in Postoperative Radiotherapy of 835 Patients With Laryngeal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rutkowski, Tomasz; Suwinski, Rafal; Idasiak, Adam

2007-11-15

Purpose: To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials: The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3-T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (-8.8; 5.0 g/dl).more » Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results: Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC (p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion: Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients.« less

Gas-Phase and Solution-Phase Homolytic Bond Dissociation Energies of H-N(+) Bonds in the Conjugate Acids of Nitrogen Bases.

PubMed

Liu, Wei-Zhong; Bordwell, Frederick G.

1996-07-12

The oxidation potentials of 19 nitrogen bases (abbreviated as B: six primary amines, five secondary amines, two tertiary amines, three anilines, pyridine, quinuclidine, and 1,4-diazabicyclo[2,2,2]octane), i.e., E(ox)(B) values in dimethyl sulfoxide (DMSO) and/or acetonitrile (AN), have been measured. Combination of these E(ox)(B) values with the acidity values of the corresponding acids (pK(HB)(+)) in DMSO and/or AN using the equation: BDE(HB)(+) = 1.37pK(HB)(+) + 23.1 E(ox)(B) + C (C equals 59.5 kcal/mol in AN and 73.3 kcal/mol in DMSO) gave estimates of solution phase homolytic bond dissociation energies of H-B(+) bonds. Gas-phase BDE values of H-B(+) bonds were estimated from updated proton affinities (PA) and adiabatic ionization potentials (aIP) using the equation, BDE(HB(+))(g) = PA + aIP - 314 kcal/mol. The BDE(HB)(+) values estimated in AN were found to be 5-11 kcal/mol higher than the corresponding gas phase BDE(HB(+))(g) values. These bond-strengthening effects in solution are interpreted as being due to the greater solvation energy of the HB(+) cation than that of the B(+*) radical cation.

WAXS studies of the structural diversity of hemoglobin in solution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makowski, L.; Bardhan, J.; Gore, D.

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 hemoglobinmore » 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.« less

Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without causing blood-brain barrier disruption or brain edema in a rat model of transient global brain ischemia-reperfusion.

PubMed

Powanda, D Douglas; Chang, Thomas M S

2002-01-01

In strokes, myocardial infarctions, severe sustained hemorrhagic shock, and donor organs, inadequate blood supply results in lack of oxygen to the tissue (ischemia). If ischemia is sustained, reperfusion with the needed oxygen can result in tissue injury (ischemia-reperfusion injury) due to formation of reactive oxygen species. We are studying an oxygen-carrying solution with anitoxidant activity formed by cross-linking hemoglobin, superoxide dismutase, and catalase to form PolyHb-SOD-CAT. The present report studies its effect on the blood-brain barrier and cerebral edema when used in a transient global brain ischemia-reperfusion rat model. We compare this solution to sham-control, oxygenated saline, stroma-free hemoglobin (SF-Hb), polymerized hemoglobin (PolyHb), and a mixture of SF-Hb, SOD, and CAT in free solution. The results show that the cross-linked PolyHb-SOD-CAT solution, unlike the other solutions, can supply oxygen to ischemic tissues without causing reperfusion injury in the transient global brain ischemia-reperfusion model.

Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary diseases

PubMed Central

Yasuda, H; Yamaya, M; Yanai, M; Ohrui, T; Sasaki, H

2002-01-01

Background: Exhaled carbon monoxide has been reported to increase in inflammatory pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO) concentration. A study was undertaken to determine whether arterial blood Hb-CO increases in patients with inflammatory pulmonary diseases. Methods: The Hb-CO concentration in arterial blood was measured with a spectrophotometer in 34 normal control subjects, 24 patients with bronchial asthma, 52 patients with pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). Results: The mean (SE) Hb-CO concentrations in patients with bronchial asthma during exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52, 1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95% confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma, mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia, and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In 20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia the Hb-CO concentration had decreased after 3 weeks when patients showed evidence of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an acute phase protein, correlated with Hb-CO concentrations in patients with pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients with bronchial asthma changes in Hb-CO concentrations were significantly correlated with those in forced expiratory volume in 1 second (FEV1) after 3 weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). Conclusions: Hb-CO concentrations are increased in inflammatory pulmonary diseases including bronchial asthma, pneumonia, and IPF. Measurement of arterial Hb-CO may be a useful means of monitoring pulmonary inflammation. PMID:12200522

Biophysical Properties and Oxygenation Potential of High-Molecular-Weight Glutaraldehyde-Polymerized Human Hemoglobins Maintained in the Tense and Relaxed Quaternary States

PubMed Central

Zhang, Ning; Jia, Yiping; Chen, Guo; Cabrales, Pedro

2011-01-01

Recent clinical evaluation of commercial glutaraldehyde-polymerized hemoglobins (PolyHbs) as transfusion solutions has demonstrated several adverse side effects. Chief among these is the hypertensive effect. Fortunately, previous studies have shown that the hypertensive effect can be attenuated by removing free hemoglobin (Hb) and low-molecular-weight (low-MW) PolyHbs from the PolyHb mixture. In this work, polymerized human Hb (PolyhHb) solutions were synthesized in two distinct quaternary states with high MW and subjected to extensive diafiltration to remove free Hb and low-MW PolyhHb components (<500 kDa). The resultant PolyhHb solutions possessed high MW, distinct quaternary state, distinct reactivities with O2 and CO, similar NO deoxygenating rate constants, distinct autoxidation rate constants, high viscosity, and low colloid osmotic pressure. To preliminarily assess the ability of PolyhHb solutions to oxygenate surrounding tissues fed by a blood vessel, we evaluated the ability of PolyhHbs to transport O2 to cultured hepatocytes in a mathematical model of a hollow fiber bioreactor. The structure of individual hollow fibers in the bioreactor is similar to that of a blood vessel and provides an easy way to assess the oxygenation potential of PolyhHbs without the need for expensive and time-consuming animal studies. It was observed that PolyhHbs with low O2 affinities were more effective in oxygenating cultured hepatocytes inside the bioreactor than high O2 affinity PolyhHbs. Taken together, our results show that it is possible to synthesize high-MW PolyhHbs with no free Hb and low-MW PolyhHb components that are capable of transporting O2 to cultured cells/tissues. PMID:20979534

Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels.

PubMed

Dash, Ranjan K; Bassingthwaighte, James B

2010-04-01

New mathematical model equations for O(2) and CO(2) saturations of hemoglobin (S(HbO)(2) and S(HbCO)(2) are developed here from the equilibrium binding of O(2) and CO(2) with hemoglobin inside RBCs. They are in the form of an invertible Hill-type equation with the apparent Hill coefficients KHbO(2) and KHbCO(2) in the expressions for SHbO(2) and SHbCO(2) dependent on the levels of O(2) and CO(2) partial pressures (P(O)(2) and P(CO)(2)), pH, 2,3-DPG concentration, and temperature in blood. The invertibility of these new equations allows PO(2) and PCO(2) to be computed efficiently from S(HbO)(2) and S(HbCO)(2) and vice versa. The oxyhemoglobin (HbO(2)) and carbamino-hemoglobin (HbCO(2)) dissociation curves computed from these equations are in good agreement with the published experimental and theoretical curves in the literature. The model solutions describe that, at standard physiological conditions, the hemoglobin is about 97.2% saturated by O(2) and the amino group of hemoglobin is about 13.1% saturated by CO(2). The O(2) and CO(2) content in whole blood are also calculated here from the gas solubilities, hematocrits, and the new formulas for S(HbO)(2) and S(HbCO)(2). Because of the mathematical simplicity and invertibility, these new formulas can be conveniently used in the modeling of simultaneous transport and exchange of O(2) and CO(2) in the alveoli-blood and blood-tissue exchange systems.

Evaluation of Membrane Systems for Washing/Deglycerolizing Packed Red Blood Cells

DTIC Science & Technology

1987-03-20

d process should reduce the ss than 400 mOsm/kg H20 minutes. The plasma should be less than of centrifugal cessfully demonstrated the rane...2000 ml of wash solution in 35 to 45 minutes. The plasma hemoglobin (Hb) concentration in the washed RBCs should be less than 150 mg/dl. During...plasmapheresis, and the concentration of blood plasma applications, the membranes retain blood but remove water and paration that must be accomplished

Dynamical Approach to Multiequilibria Problems for Mixtures of Acids and Their Conjugated Bases

ERIC Educational Resources Information Center

Glaser, Rainer E.; Delarosa, Marco A.; Salau, Ahmed Olasunkanmi; Chicone, Carmen

2014-01-01

Mathematical methods are described for the determination of steady-state concentrations of all species in multiequilibria systems consisting of several acids and their conjugated bases in aqueous solutions. The main example consists of a mixture of a diprotic acid H[subscript 2]A, a monoprotic acid HB, and their conjugate bases. The reaction…

75 FR 1650 - Notice of Intent To Prepare an Environmental Impact Statement for the Proposed HB Potash, LLC-“In...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

...] Notice of Intent To Prepare an Environmental Impact Statement for the Proposed HB Potash, LLC--``In-Situ... HB Potash, LLC--``In- Situ'' Solution Mine Project by any of the following methods: E-mail: Rebecca..., (Intrepid) is proposing to construct and operate an ``in-situ'' solution mining project that would involve...

Trending and accuracy of noninvasive hemoglobin monitoring in pediatric perioperative patients.

PubMed

Patino, Mario; Schultz, Lindsay; Hossain, Monir; Moeller, Jennifer; Mahmoud, Mohamed; Gunter, Joel; Kurth, C Dean

2014-10-01

Rainbow Pulse CO-Oximetry technology (Masimo Corporation, Irvine, CA) provides continuous and noninvasive measurement of arterial hemoglobin concentration (SpHb). We assessed the trending and accuracy of SpHb by this innovative monitoring compared with Hb concentration obtained with conventional laboratory techniques (Hb) in children undergoing surgical procedures with potential for substantial blood loss. Hb concentrations were recorded from Pulse CO-Oximetry and a conventional hematology analyzer. Regression analysis and 4-quadrant plot were used to evaluate the trending for changes in SpHb and Hb measurements (ΔSpHb and ΔHb). Bias, precision, and limits of agreement of SpHb and of in vivo adjusted SpHb (SpHb - first bias to HB) compared with Hb were calculated. One hundred fifty-eight SpHb-Hb data pairs and 105 delta pairs (ΔSpHb and ΔHb) from 46 patients aged 2 months to 17 years with Hb ranging from 16.7 to 7.9 g/dL were collected. To evaluate trending, the delta pairs (ΔSpHb and ΔHb) were plotted, which revealed a positive correlation (ΔSpHb = 0.022 + 0.76ΔHb) with correlation coefficient r = 0.76, 95% CI [confidence interval] = 0.57-0.86. The bias and precision of SpHb to Hb and in vivo adjusted SpHb were 0.4 ± 1.3 g/dL and 0.1 ± 1.2 g/dL, respectively; the limits of agreement were -2.0 to 3.2 g/dL before in vivo adjustment and -2.4 to 2.2 g/dL after in vivo adjustment (P value = 0.04). The mean percent bias (from the reference Hb concentration) decreased from 4.1% ± 11.9% to 0.7% ± 11.3% (P value = 0.01). No drift in bias over time was observed during the study procedure. Of patient demographic and physiological factors tested for correlation with the SpHb, only perfusion index at sensor site showed a weak correlation. The accuracy of SpHb in children with normal Hb and mild anemia is similar to that previously reported in adults and is independent of patient demographic and physiological states except for a weak correlation with perfusion index. The trending of SpHb and Hb in children with normal Hb and mild anemia showed a positive correlation. Further studies are necessary in children with moderate and severe anemia.

Effect of the chest wall on the measurement of hemoglobin concentrations by near-infrared time-resolved spectroscopy in normal breast and cancer.

PubMed

Yoshizawa, Nobuko; Ueda, Yukio; Nasu, Hatsuko; Ogura, Hiroyuki; Ohmae, Etsuko; Yoshimoto, Kenji; Takehara, Yasuo; Yamashita, Yutaka; Sakahara, Harumi

2016-11-01

Optical imaging and spectroscopy using near-infrared light have great potential in the assessment of tumor vasculature. We previously measured hemoglobin concentrations in breast cancer using a near-infrared time-resolved spectroscopy system. The purpose of the present study was to evaluate the effect of the chest wall on the measurement of hemoglobin concentrations in normal breast tissue and cancer. We measured total hemoglobin (tHb) concentration in both cancer and contralateral normal breast using a near-infrared time-resolved spectroscopy system in 24 female patients with breast cancer. Patients were divided into two groups based on menopausal state. The skin-to-chest wall distance was determined using ultrasound images obtained with an ultrasound probe attached to the spectroscopy probe. The apparent tHb concentration of normal breast increased when the skin-to-chest wall distance was less than 20 mm. The tHb concentration in pre-menopausal patients was higher than that in post-menopausal patients. Although the concentration of tHb in cancer tissue was statistically higher than that in normal breast, the contralateral normal breast showed higher tHb concentration than cancer in 9 of 46 datasets. When the curves of tHb concentrations as a function of the skin-to-chest wall distance in normal breast were applied for pre- and post-menopausal patients separately, all the cancer lesions plotted above the curves. The skin-to-chest wall distance affected the measurement of tHb concentration of breast tissue by near-infrared time-resolved spectroscopy. The tHb concentration of breast cancer tissue was more precisely evaluated by considering the skin-to-chest wall distance.

Augmentation of oxygen transport by various hemoglobins as determined by pulsed field gradient NMR.

PubMed

Budhiraja, Vikas; Hellums, J David; Post, Jan F M

2002-11-01

Diffusion of oxyhemoglobin has been shown to augment the oxygen transport inside the red blood cells. Measurement of hemoglobin diffusion coefficients by pulsed-field gradient (PFG) nuclear magnetic resonance (NMR) technique can be used for estimating this augmentation effect. Self-diffusion coefficients of polymerized and unpolymerized bovine hemoglobin (Hb) and several other proteins were measured using this technique. The Hb diffusion coefficient was used to determine the effective permeability of oxygen and augmentation of oxygen transport through samples of Hb solutions due to diffusion of oxyhemoglobin. The values compared well with our previous diffusion cell measurements of effective diffusivity and augmentation. Our NMR studies show that even at low concentrations the augmentation of oxygen transport due to diffusion can be significant. The PFG NMR technique can thus provide an accurate and easy method for measuring augmentation of oxygen transport, especially in dilute samples of Hb. The results on polyhemoglobin and high-molecular-weight hemoglobin are of both basic interest and practical value in assessing the promise and performance of hemoglobin-based blood substitutes.

On the effects of cluster density and concentration on the horizontal branch morphology - The origin of the blue tails

NASA Technical Reports Server (NTRS)

Fusi Pecci, F.; Ferraro, F. R.; Bellazzini, M.; Djorgovski, S.; Piotto, G.; Buonanno, R.

1993-01-01

Possible relationships between horizontal branch (HB) morphology in Galactic globular clusters and the cluster structure and dynamical evolution are investigated. New HB observables are defined and determined using a theoretical framework deduced from HB models. Data for 53 Galactic globular clusters are used to obtain correlations between the observables. It is found that the net length of the HB and the presence and extent of blue tails in particular are correlated with the cluster density and concentrations, in the sense of more concentrated or denser clusters having bluer and longer HB morphologies. This effect is especially strong for the intermediate metallicity clusters. Thus, the cluster environment can affect the stellar evolution leading to the HB and therefore the HB morphology. This result is interpreted in terms of an enhanced mass removal from the HB progenitors.

Potential electron mediators to extract electron energies of RBC glycolysis for prolonged in vivo functional lifetime of hemoglobin vesicles.

PubMed

Kettisen, Karin; Bülow, Leif; Sakai, Hiromi

2015-04-15

Developing a functional blood substitute as an alternative to donated blood for clinical use is believed to relieve present and future blood shortages, and to reduce the risks of infection and blood type mismatching. Hemoglobin vesicle (HbV) encapsulates a purified and concentrated human-derived Hb solution in a phospholipid vesicle (liposome). The in vivo safety and efficacy of HbV as a transfusion alternative have been clarified. Auto-oxidation of ferrous Hb in HbV gradually increases the level of ferric methemoglobin (metHb) and impairs the oxygen transport capabilities. The extension of the functional half-life of HbV has recently been proposed using an electron mediator, methylene blue (MB), which acts as a shuttle between red blood cells (RBC) and HbV. MB transfers electron energies of NAD(P)H, produced by RBC glycolysis, to metHb in HbV. Work presented here focuses on screening of 15 potential electron mediators, with appropriate redox potential and water solubility, for electron transfer from RBC to HbV. The results are assessed with regard to the chemical properties of the candidates. The compounds examined in this study were dimethyl methylene blue (DMB), methylene green, azure A, azure B, azure C, toluidine blue (TDB), thionin acetate, phenazine methosulfate, brilliant cresyl blue, cresyl violet, gallocyanine, toluylene blue, indigo carmine, indigotetrasulfonate, and MB. Six candidates were found to be unsuitable because of their insufficient diffusion across membranes, or overly high or nonexistent reactivity with relevant biomolecules. However, 9 displayed favorable metHb reduction. Among the suitable candidates, phenothiazines DMB and TDB exhibited effectiveness like MB did. In comparison to MB, they showed faster reduction by electron-donating NAD(P)H, coupled with showing a lower rate of reoxidation in the presence of molecular oxygen. Ascertaining the best electron mediator can provide a pathway for extending the lifetime and efficiency of potential blood substitutes.

Validation of a spectrophotometric method for quantification of carboxyhemoglobin.

PubMed

Luchini, Paulo D; Leyton, Jaime F; Strombech, Maria de Lourdes C; Ponce, Julio C; Jesus, Maria das Graças S; Leyton, Vilma

2009-10-01

The measurement of carboxyhemoglobin (COHb) levels in blood is a valuable procedure to confirm exposure to carbon monoxide (CO) either for forensic or occupational matters. A previously described method using spectrophotometric readings at 420 and 432 nm after reduction of oxyhemoglobin (O(2)Hb) and methemoglobin with sodium hydrosulfite solution leads to an exponential curve. This curve, used with pre-established factors, serves well for lower concentrations (1-7%) or for high concentrations (> 20%) but very rarely for both. The authors have observed that small variations on the previously described factors F1, F2, and F3, obtained from readings for 100% COHb and 100% O(2)Hb, turn into significant changes in COHb% results and propose that these factors should be determined every time COHb is measured by reading CO and O(2) saturated samples. This practice leads to an increase in accuracy and precision.

Pseudosickling of hemoglobin Setif.

PubMed

Charache, S; Raik, E; Holtzclaw, D; Hathaway, P J; Powell, E; Fleming, P

1987-07-01

Hemoglobin Setif produces pseudosickling of red cells in vitro; the nature of the process and the conditions that "trigger" it are unknown. Studies of red cells, hemolysates, purified hemoglobin solutions, and artificial mixtures of Hb A and Setif suggest that pseudosickling is produced by intracellular crystallization of insoluble hemoglobin. Increased tonicity of the suspending medium accentuates the process, probably by causing a rise in intracellular hemoglobin concentration. If precipitates from A/Setif mixtures are analyzed, they always contain Hb A, suggesting an unusual mechanism for the process. Despite the fact that osmolality in the renal medulla is similar to that which produces pseudosickling in vitro, carriers do not have renal dysfunction of the type found in patients with sickle cell disease.

Processing of irradiated, enriched uranium fuels at the Savannah River Plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyder, M L; Perkins, W C; Thompson, M C

Uranium fuels containing /sup 235/U at enrichments from 1.1% to 94% are processed and recovered, along with neptunium and plutonium byproducts. The fuels to be processed are dissolved in nitric acid. Aluminum-clad fuels are disssolved using a mercury catalyst to give a solution rich in aluminum. Fuels clad in more resistant materials are dissolved in an electrolytic dissolver. The resulting solutions are subjected to head-end treatment, including clarification and adjustment of acid and uranium concentration before being fed to solvent extraction. Uranium, neptunium, and plutonium are separated from fission products and from one another by multistage countercurrent solvent extraction withmore » dilute tri-n-butyl phosphate in kerosene. Nitric acid is used as the salting agent in addition to aluminum or other metal nitrates present in the feed solution. Nuclear safety is maintained through conservative process design and the use of monitoring devices as secondary controls. The enriched uranium is recovered as a dilute solution and shipped off-site for further processing. Neptunium is concentrated and sent to HB-Line for recovery from solution. The relatively small quantities of plutonium present are normally discarded in aqueous waste, unless the content of /sup 238/Pu is high enough to make its recovery desirable. Most of the /sup 238/Pu can be recovered by batch extraction of the waste solution, purified by counter-current solvent extraction, and converted to oxide in HB-Line. By modifying the flowsheet, /sup 239/Pu can be recovered from low-enriched uranium in the extraction cycle; neptunium is then not recovered. The solvent is subjected to an alkaline wash before reuse to remove degraded solvent and fission products. The aqueous waste is concentrated and partially deacidified by evaporation before being neutralized and sent to the waste tanks; nitric acid from the overheads is recovered for reuse.« less

Different hemodynamic response of prefontal area for men and women to mental arithmetic: a near-infrared spectroscopy study

NASA Astrophysics Data System (ADS)

Yang, Hongyu; Zhou, Zhenyu; Liu, Yun; Ruan, Zongcai; Gong, Hui; Luo, Qingming; Lu, Zuhong

2007-05-01

A 16-channel near-infrared spectroscopy (NIRS) was used to measure concentration changes of oxygenated and deoxygenated hemoglobin (oxy-HB and deoxy-HB) in prefrontal area while the subjects were performing mental works. Thirty healthy college participants were administered two mental arithmetic tasks while the changes of concentration on oxy-HB and deoxy-HB were measured. Oxy-HB increased during the mental works, and the increases of oxy-HB were greater in male subjects than in female subjects during the difficult task. These results suggest that NIRS is sensitive to evaluate the oxy-HB activity of prefrontal cortex during mental works.

Physiological responses to temperature and haeme synthesis modifiers in earthworm Lumbricus terrestris (Annelida: Oligochaeta).

PubMed

Khan, M A Q; Khan, Munawwar Ali; Hurlock, Peter; Ahmed, S A

2012-01-01

Earthworms (Lumbricus terrestris) acclimated at 2° and 6°C above their average habitat temperature (10°C) had respectively 15 and 40% higher rate of respiration than those at habitat temperature. At 14°C, the rate of respiration and blood hemoglobin (Hb) concentration both increased by ∼60 and 50%, respectively, of the values at habitat temperature. At higher temperatures the rate of respiration and Hb synthesis started decreasing. At 20-23°C, the respiration and Hb concentration decreased respectively by about 85% and 35% of that at 14°C. Decrease in blood Hb concentration at higher temperatures appeared to be due to the lowering of the activity of blood enzyme δ-aminolaevulinic acid dehydratase (ALAD). Exposure of 20-23°C-acclimated pale worms to ALAD inhibitor (lead), lowered the already compromised rate of respiration and blood Hb concentration; while exposure to hexachlorobenzene (HCB, inducer of haeme synthesis) and ferric chloride (enhancer of haeme synthesis) did not overcome the inhibitory effect of high temperature on Hb synthesis. At 20-23°C the affinity of Hb for oxygen also decreased as indicated by the lowering of oxy-Hb (HbO) concentration in blood. The lowering of concentration of blood Hb and its affinity for oxygen may lower the amount of oxygen delivered to cells, which may limit the level of aerobic metabolism (glycolysis, oxidative phosphorylation), as indicated by an increase in blood glucose concentration and a decrease in in vitro activities of mitochondrial electron transport system components (ETS) namely NADH-cytochrome c reductase, succinate dehydrogenase, cytochrome c oxidase, and ATPases. Although the oxygen concentration in air, at sea level, does not decrease significantly from 6° to 20-23°C (lack of hypoxia), lowering of both Hb and HbO concentrations by high temperature may cause significant hypoxemia. The latter may lead to inhibition of the activity of muscle mitochondrial respiratory enzymes (ETS). The resulting inhibition of ATP synthesis and hydrolysis may cause deficit of energy needed for peristalsis/fictive locomotion of body and heart muscles (as indicated by a decrease in heart rate) to facilitate diffusion and transport of gases. The upper critical temperature (20-23°C) also slows down the heart rate and causes hyperosmotic stress (hypovolemia). Thus, a rise in soil temperature above 18°C, which inhibits Hb synthesis, Hb oxygenation, and mitochondrial ETS activity, and slows down the heart rate and causes hyperosmotic stress, can make this and higher temperatures lethal to populations of these earthworms, especially in the presence of metabolic inhibitors and respiratory poisons. Copyright © 2010 Wiley Periodicals, Inc.

Mechanism of Interaction between the General Anesthetic Halothane and a Model Ion Channel Protein, II: Fluorescence and Vibrational Spectroscopy Using a Cyanophenylalanine Probe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, J.; Strzalka, J; Tronin, A

2009-01-01

We demonstrate that cyano-phenylalanine (PheCN) can be utilized to probe the binding of the inhalational anesthetic halothane to an anesthetic-binding, model ion channel protein hbAP-PheCN. The Trp to PheCN mutation alters neither the a-helical conformation nor the 4-helix bundle structure. The halothane binding properties of this PheCN mutant hbAP-PheCN, based on fluorescence quenching, are consistent with those of the prototype, hbAP1. The dependence of fluorescence lifetime as a function of halothane concentration implies that the diffusion of halothane in the nonpolar core of the protein bundle is one-dimensional. As a consequence, at low halothane concentrations, the quenching of the fluorescencemore » is dynamic, whereas at high concentrations the quenching becomes static. The 4-helix bundle structure present in aqueous detergent solution and at the air-water interface, is preserved in multilayer films of hbAP-PheCN, enabling vibrational spectroscopy of both the protein and its nitrile label (-CN). The nitrile groups' stretching vibration band shifts to higher frequency in the presence of halothane, and this blue-shift is largely reversible. Due to the complexity of this amphiphilic 4-helix bundle model membrane protein, where four PheCN probes are present adjacent to the designed cavity forming the binding site within each bundle, all contributing to the infrared absorption, molecular dynamics (MD) simulation is required to interpret the infrared results. The MD simulations indicate that the blue-shift of -CN stretching vibration induced by halothane arises from an indirect effect, namely an induced change in the electrostatic protein environment averaged over the four probe oscillators, rather than a direct interaction with the oscillators. hbAP-PheCN therefore provides a successful template for extending these investigations of the interactions of halothane with the model membrane protein via vibrational spectroscopy, using cyano-alanine residues to form the anesthetic binding cavity.« less

Development of hemoglobin typing control materials for laboratory investigation of thalassemia and hemoglobinopathies.

PubMed

Pornprasert, Sakorn; Tookjai, Monthathip; Punyamung, Manoo; Pongpunyayuen, Panida; Jaiping, Kanokwan

2016-01-01

To date, the hemoglobin (Hb) typing control materials for laboratory investigation of thalassemia with low (1.8%-3.2%) and high (4%-6%) levels of HbA2 are available but there are no Hb typing quality control materials for analysis of thalassemia and hemoglobinopathies which are highly prevalent in South-East Asian countries. The main aim of the present study was to develop the lyophilized Hb typing control materials for laboratory investigation of thalassemia and hemoglobinopathies that are commonly found in South-East Asia. Erythrocytes of blood samples containing Hb Bart's, HbH, HbE, HbF, Hb Constant Spring (CS), Hb Hope, and Hb Q-Thailand were washed and dialysed with 0.85% saline solution. The erythrocytes were then lysed in 5% sucrose solution. The lyophilized Hb typing control materials were prepared by using a freeze drying (lyophilization) method. The high performance liquid chromatography (HPLC) analysis of lyophilized Hb was performed after the storage at -20 °C for 1 year and also after reconstitution and storage at 4 or -20 °C for 30 days. In addition, the Hb analysis was compared between the three different methods of HPLC, low pressure liquid chromatography (LPLC) and capillary electrophoresis (CE). Following a year of storage at -20 °C, the HPLC chromatograms of lyophilized Hb typing control materials showed similar patterns to the equivalent fresh whole blood. The stability of reconstituted Hb typing control materials was also observed through 30 days after reconstitution and storage at -20 °C. Moreover, the Hb typing control materials could be analyzed by three methods, HPLC, LPLC and CE. Even a degraded peak of HbCS was found on CE electropherogram. The lyophilized Hb typing control materials could be developed and used as control materials for investigation of thalassemia and hemoglobinopathies.

Association of plasma PCB levels and HbA1c concentration in Iran.

PubMed

Eftekhari, Sahar; Aminian, Omid; Moinfar, Zeinab; Schettgen, Thomas; Kaifie, Andrea; Felten, Michael; Kraus, Thomas; Esser, André

2018-01-01

The rapid increase in prevalence of diabetes mellitus over the last decades warrants more attention to the effects of environmental and occupational exposures on glucose metabolism. Our study aimed to assess the association between the plasma levels of various congeners of polychlorinated biphenyls (PCBs) and the serum concentration of glycated haemoglobin (HbA1c). Our study population consisted of 140 Iranian adults from seven different occupational groups and a group of non-occupationally exposed female participants. The plasma concentration of PCBs were determined at the laboratory of occupational toxicology at RWTH Aachen University, Germany. We considered an HbA1c concentration of 5.7% and more as indicating a disturbed glucose metabolism. Logistic regression was used to assess the association between quartiles of concentrations of PCB congeners and serum HbA1c. Participants with an increased HbA1c value had higher plasma levels of PCB 138, 153, 180 and the PCB sum, although this association was statistically not significant. There was no significant difference between the levels of PCB 138, 153, 180, the sum of these congeners, and PCB 118 in their quartiles when comparing with HbA1c concentrations. For our cohort, we could not demonstrate a significant association between PCB and HbA1c concentrations indicating a disturbance of glucose metabolism.

Effect of hemoglobin polymerization on oxygen transport in hemoglobin solutions.

PubMed

Budhiraja, Vikas; Hellums, J David

2002-09-01

The effect of hemoglobin (Hb) polymerization on facilitated transport of oxygen in a bovine hemoglobin-based oxygen carrier was studied using a diffusion cell. In high oxygen tension gradient experiments (HOTG) at 37 degrees C the diffusion of dissolved oxygen in polymerized Hb samples was similar to that in unpolymerized Hb solutions during oxygen uptake. However, in the oxygen release experiments, the transport by diffusion of dissolved oxygen was augmented by diffusion of oxyhemoglobin over a range of oxygen saturations. The augmentation was up to 30% in the case of polymerized Hb and up to 100% in the case of unpolymerized Hb solution. In experiments performed at constant, low oxygen tension gradients in the range of physiological significance, the augmentation effect was less than that in the HOTG experiments. Oxygen transport in polymerized Hb samples was approximately the same as that in unpolymerized samples over a wide range of oxygen tensions. However, at oxygen tensions lower than 30 mm Hg, there were more significant augmentation effects in unpolymerized bovine Hb samples than in polymerized Hb. The results presented here are the first accurate, quantitative measurements of effective diffusion coefficients for oxygen transport in hemoglobin-based oxygen carriers of the type being evaluated to replace red cells in transfusions. In all cases the oxygen carrier was found to have higher effective oxygen diffusion coefficients than blood.

Glycemic control in diabetes in three Danish counties.

PubMed

Jørgensen, Lone G M; Petersen, Per Hyltoft; Heickendorff, Lene; Møller, Holger Jon; Hendel, Jørn; Christensen, Cramer; Schmitz, Anita; Reinholdt, Birgitte; Lund, Erik D; Christensen, Niels J; Hansen, Erik Kjaersgaard; Hastrup, Jens; Skjødt, Hanne; Eriksen, Ebbe Wendel; Brandslund, Ivan

2005-01-01

Hemoglobin A1c (HbA1c) is a proxy measure for glycemic control in diabetes. We investigated the trend for glycemic control in patients from three Danish counties using HbA1c measurements. We studied 2454 patients from a population of 807,000 inhabitants for whom routine monitoring of diabetes using HbA1c-DCCT aligned was initiated in 2001. We estimated the incidence of monitored patients in the population. The progress in patients with originally diabetic HbA1c levels was investigated by cumulative probability plots, and the individual trend in clinical outcome was investigated by a modified difference plot. The age-standardized incidence of monitored patients was <0.5% in all regions. Patients with diabetic first HbA1c concentrations (>or=6.62% HbA1c) showed on average 15% improved glycemic control in the first year. Further improvement was limited. The overall percentage above the treatment target (>or=6.62% HbA1c) was 51% in 2003 compared to 59% in 2001, and the percentage with poor glycemic control (>or=10.0% HbA1c) was reduced from 19% to 4%. Of patients with originally diabetic HbA1c levels, 15% showed progress in glycemic control, and 28% reached treatment targets. In patients with originally normal HbA1c, 75% showed an upward trend in HbA1c levels, which reached diabetic concentrations in 17%. Patients with diabetic first HbA1c concentrations (>or=6.62% HbA1c) showed on average 15% improved glycemic control in the first year. Further improvement was limited. In individual patients, 75% with originally diabetic HbA1c levels showed improved glycemic control after 3 years, while 78% with originally normal concentrations showed an upward trend in HbA1c levels.

Rapid prototyping of biomimetic vascular phantoms for hyperspectral reflectance imaging

PubMed Central

Ghassemi, Pejhman; Wang, Jianting; Melchiorri, Anthony J.; Ramella-Roman, Jessica C.; Mathews, Scott A.; Coburn, James C.; Sorg, Brian S.; Chen, Yu; Joshua Pfefer, T.

2015-01-01

Abstract. The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by x-ray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements—including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth—were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light–tissue interactions and characterizing biophotonic system performance. PMID:26662064

Rapid prototyping of biomimetic vascular phantoms for hyperspectral reflectance imaging.

PubMed

Ghassemi, Pejhman; Wang, Jianting; Melchiorri, Anthony J; Ramella-Roman, Jessica C; Mathews, Scott A; Coburn, James C; Sorg, Brian S; Chen, Yu; Pfefer, T Joshua

2015-01-01

The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by x-ray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements—including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth—were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light–tissue interactions and characterizing biophotonic system performance.

LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Study of photodissociation parameters of carboxyhemoglobin

NASA Astrophysics Data System (ADS)

Kuz'min, V. V.; Salmin, V. V.; Salmina, A. B.; Provorov, A. S.

2008-07-01

The general properties of photodissociation of carboxyhemoglobin (HbCO) in buffer solutions of whole human blood are studied by the flash photolysis method on a setup with intersecting beams. It is shown that the efficiency of photoinduced dissociation of the HbCO complex virtually linearly depends on the photolytic irradiation intensity for the average power density not exceeding 45 mW cm-2. The general dissociation of the HbCO complex in native conditions occurs in a narrower range of values of the saturation degree than in model experiments with the hemoglobin solution. The dependence of the pulse photolysis efficiency of HbCO on the photolytic radiation wavelength in the range from 550 to 585 nm has a broad bell shape. The efficiency maximum corresponds to the electronic Q transition (porphyrin π—π* absorption) in HbCO at a wavelength of 570 nm. No dissociation of the complex was observed under given experimental conditions upon irradiation of solutions by photolytic radiation at wavelengths above 585 nm.

Relative bioavailability of iron proteinate for broilers fed a casein-dextrose diet.

PubMed

Ma, X Y; Liu, S B; Lu, L; Li, S F; Xie, J J; Zhang, L Y; Zhang, J H; Luo, X G

2014-03-01

An experiment was carried out to determine the bioavailability of organic Fe as Fe proteinate (Alltech, Nicholasville, KY) relative to inorganic Fe source (FeSO4•7H2O) for broiler chicks fed a casein-dextrose diet. A total of 448 1-d-old Arbor Acres commercial male broiler chicks were randomly allotted to 1 of 8 replicate cages (8 chicks per cage) for each of 7 treatments in a completely randomized design involving a 2 × 3 factorial arrangement of treatments with 2 Fe sources (Fe proteinate and Fe sulfate) and 3 levels of added Fe (10, 20, or 40 mg of Fe/kg) plus a Fe-unsupplemented control diet containing 4.56 mg of Fe/kg by analysis. Feed and distilled-deionized water were available ad libitum for an experimental phase of 14 d. At 14 d of age, blood samples were collected for testing hemoglobin (Hb) and hematocrit, and calculating total body Hb Fe, whereas liver and kidney samples were excised for Fe analyses. The results showed that ADG, ADFI, blood Hb, hematocrit, and total body Hb Fe and Fe concentrations in liver and kidney increased linearly (P < 0.0001), whereas mortality decreased linearly (P < 0.0001) as dietary Fe level increased. However, only blood Hb concentration and total body Hb Fe differed (P < 0.004) between the 2 Fe sources. Based on slope ratios from the multiple linear regression of Hb concentration and total body Hb Fe on daily intake of analyzed dietary Fe, the bioavailability of Fe proteinate relative to FeSO4•7H2O (100%) was 117 and 114%, respectively (P < 0.009). The results indicated that blood Hb concentration and total body Hb Fe were sensitive indices in reflecting differences in bioavailability among different Fe sources, and Fe proteinate was significantly more available to broilers than inorganic Fe sulfate in enhancing Hb concentration and total body Hb Fe.

Circulatory oxygen transport in the water flea Daphnia magna.

PubMed

Bäumer, C; Pirow, R; Paul, R J

2002-05-01

To determine the contribution of circulatory convection to tissue oxygen supply in animals of Daphnia magna, heart rate ( f(H)), in-vivo Hb oxygen-saturation ( S(Hb)) and NADH fluorescence intensity ( I(NADH)) as a measure of the tissue oxygenation state were simultaneously measured using digital motion analysis, microabsorption spectroscopy and fluorescence microscopy. In addition, the relationship between stroke volume and body size was established. Groups of differently sized animals (small: 1.4-1.6 mm, medium: 2.7-2.9 mm, large: 3.3 mm) with either low (Hb-poor) or high Hb concentration (Hb-rich) in the hemolymph were exposed to a gradual decrease in ambient oxygen partial pressure ( P(O2amb)) between normoxia and anoxia. In all groups, f(H) increased in response to progressive hypoxia. The hypoxic maximum in f(H) was highest in medium-sized Hb-poor animals, whereas perfusion rate increased continuously with increasing body size in Hb-poor and Hb-rich animals. The P(O2amb) at which Hb in the heart region was half-saturated (in-vivo P(50)) was higher in medium-sized (Hb-poor: 3.2 kPa, Hb-rich: 2.0 kPa) than in small (Hb-poor: 2.1 kPa, Hb-rich: 1.5 kPa) and large animals (Hb-poor: 1.9 kPa). The in-vivo P(50) was always lower in Hb-rich than in Hb-poor animals. The I(NADH) indicated an impairment of tissue oxygenation starting at higher critical P(O2amb) with increasing body size and with lower Hb concentration. Model calculations suggest that at the respective critical P(O2amb), circulatory convection delivers less than half of the oxygen demand in Hb-poor animals. In contrast, in Hb-rich animals, the contribution of circulatory convection to tissue oxygen supply at respective critical P(O2amb) was much greater due to the higher concentration of Hb.

Faecal haemoglobin concentration is related to detection of advanced colorectal neoplasia in the next screening round.

PubMed

Digby, Jayne; Fraser, Callum G; Carey, Francis A; Diament, Robert H; Balsitis, Margaret; Steele, Robert Jc

2017-06-01

Objective To examine associations between faecal haemoglobin concentrations below the cut-off used in colorectal cancer screening and outcomes in the next screening round. Methods In the Scottish Bowel Screening Programme, faecal haemoglobin concentrations and diagnostic outcomes were investigated for participants with a negative result (faecal haemoglobin concentrations < 80.0 µg Hb/g faeces), followed by a positive result within two years. Results Of 37,780 participants with negative results, at the next screening round, 556 (1.5%) screened positive and 30,293 (80.2%) negative. Initial median faecal haemoglobin concentrations (2.1 µg Hb/g faeces, IQR: 0.0-13.2) were higher in those with subsequent positive results than those with subsequent negative results (0.0 µg Hb/g faeces, IQR: 0.0-1.4; p < 0.0001). Using faecal haemoglobin concentrations 0.0-19.9 µg Hb/g faeces as reference, logistic regression analysis showed high adjusted odds ratios for advanced neoplasia (advanced neoplasia: colorectal cancer or higher risk adenoma) detection at the next round of 14.3 (95% CI: 8.9-23.1) in those with initial faecal haemoglobin concentrations 20.0-39.9 µg Hb/g faeces, and 38.0 (95% CI: 20.2-71.2) with 60.0-79.9 µg Hb/g faeces. Conclusions A higher proportion of participants with faecal haemoglobin concentrations of ≥ 20 µg Hb/g faeces had advanced neoplasia detected at the next round than participants with lower faecal haemoglobin concentrations. Although most relevant when using high faecal haemoglobin concentrations cut-offs, studies of faecal haemoglobin concentrations and outcomes over screening rounds may provide strategies to direct available colonoscopy towards those at highest risk.

On the Metabolism of Exogenous Ketones in Humans

PubMed Central

Stubbs, Brianna J.; Cox, Pete J.; Evans, Rhys D.; Santer, Peter; Miller, Jack J.; Faull, Olivia K.; Magor-Elliott, Snapper; Hiyama, Satoshi; Stirling, Matthew; Clarke, Kieran

2017-01-01

Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB. Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min. Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis. PMID:29163194

Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans.

PubMed

Ibaraki, Masanobu; Shinohara, Yuki; Nakamura, Kazuhiro; Miura, Shuichi; Kinoshita, Fumiko; Kinoshita, Toshibumi

2010-07-01

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with (15)O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C(a)O(2)), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO(2)) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO(2) was independent of Hb concentration. Oxygen delivery defined as a product of C(a)O(2) and CBF (C(a)O(2) CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO(2). The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the (15)O PET data in clinical practice.

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

PubMed

Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

2017-01-01

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

Changes in hemodynamics and light scattering during cortical spreading depression

NASA Astrophysics Data System (ADS)

Li, Pengcheng; Yang, Yuanyuan; Luo, Qingming

2005-01-01

Cortical spreading depression (CSD) has been known to play an important role in the mechanism of migraine, stroke and brain injure. Optical imaging of intrinsic signals has been shown a powerful method for characterizing the spatial and temporal pattern of the propagation of CSD. However, the possible physiological mechanisms underlying the intrinsic optical signal (IOS) during CSD still remain incompletely understood. In this study, a spectroscopic recording of the change in optical intrinsic signal during CSD was performed and an analysis method based on the modified Beer-Lambert law was used to estimate the changes in the concentration of HbO2 and Hb, and changes in light scattering from the spectra data. The CSD were induced by pinprick in 10 α-chloralose/urethane anesthetized Sprague-Dawley rats. In all experiments, four-phasic changes in optical reflectance were observed at 450 nm ~ 570 nm, and triphasic changes in optical reflectance were observed in the range of 570 nm ~750 nm. But at 750 nm ~ 850 nm, only biphasic changes of optical signal were detected. Converting the spectra data to the changes in light scattering and concentration of Hb and HbO2, we found that the CSD induced an initial increase in concentration of HbO2 (amplitude: 9.0+/-3.7%), which was 26.2+/-18.6 s earlier than the onset of increase of Hb concentration. Furthermore, the concentration of HbO2 showed a four-phasic change, whereas the concentration of Hb only showed a biphasic change. For the changes in light scattering during CSD, a triphasic change was observed.

Facile electrocatalytic redox of hemoglobin by flower-like gold nanoparticles on boron-doped diamond surface.

PubMed

Li, Mingfang; Zhao, Guohua; Geng, Rong; Hu, Huikang

2008-11-01

The flower-like gold nanoparticles together with spherical and convex polyhedron gold nanoparticles were fabricated on boron-doped diamond (BDD) surface by one-step and simple electrochemical method through easily controlling the applied potential and the concentration of HAuCl(4). The recorded X-ray diffraction (XRD) patterns confirmed that these three shapes of gold nanoparticles were dominated by different crystal facets. The cyclic voltammetric results indicated that the morphology of gold nanoparticles plays big role in their electrochemical behaviors. The direct electrochemistry of hemoglobin (Hb) was realized on all the three different shapes of nanogold-attached BDD surface without the aid of any electron mediator. In pH 4.5 acetate buffer solutions (ABS), Hb showed a pair of well defined and quasi-reversible redox peaks. However, the results obtained demonstrated that the redox peak potential, the average surface concentration of electroactive heme, and the electron transfer rates of Hb are greatly dependent upon the surface morphology of gold nanoparticles. The electron transfer rate constant of hemoglobin over flower-like nanogold/BDD electrode was more than two times higher than that over spherical and convex polyhedron nanogold. The observed differences may be ascribed to the difference in gold particle characteristics including surface roughness, exposed surface area, and crystal structure.

Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Warren, Bethany; Pankow, James S; Matsushita, Kunihiro; Punjabi, Naresh M; Daya, Natalie R; Grams, Morgan; Woodward, Mark; Selvin, Elizabeth

2017-01-01

No consensus on definitions of prediabetes exists among international organisations. Analysis of associations with different definitions and clinical complications can inform the comparative value of different prediabetes definitions. We compared the risk of future outcomes across different prediabetes definitions based on fasting glucose concentration, HbA 1c , and 2 h glucose concentration during over two decades of follow-up in the community-based Atherosclerosis Risk in Communities (ARIC) study. We aimed to analyse the associations of definitions with outcomes to provide a comparison of different definitions. We did a prospective cohort study of participants in the ARIC study who did not have diagnosed diabetes and who attended visit 2 (1990-92; n=10 844) and who attended visit 4 (1996-98; n=7194). ARIC participants were enrolled from four communities across the USA. Fasting glucose concentration and HbA 1c were measured at visit 2 and fasting glucose concentration and 2 h glucose concentration were measured at visit 4. We compared prediabetes definitions based on fasting glucose concentration (American Diabetes Association [ADA] fasting glucose concentration cutoff 5·6-6·9 mmol/L and WHO fasting glucose concentration cutoff 6·1-6·9 mmol/L), HbA 1c (ADA HbA 1c cutoff 5·7-6·4% [39-46 mmol/mol] and International Expert Committee [IEC] HbA 1c cutoff 6·0-6·4% [42-46 mmol/mol]), and 2 h glucose concentration (ADA and WHO 2 h glucose concentration cutoff 7·8-11·0 mmol/L). Prediabetes defined using the ADA fasting glucose concentration cutoff (prevalence 4112 [38%] of 10 844 people; 95% CI 37·0-38·8) was the most sensitive for major clinical outcomes, whereas using the ADA HbA 1c cutoff (2027 [19%] of 10 884 people; 18·0-19·4) and IEC HbA 1c cutoff (970 [9%] of 10 844 people; 8·4-9·5), and the WHO fasting glucose concentration cutoff (1213 [11%] of 10 844 people; 10·6-11·8) were more specific. After demographic adjustment, HbA 1c -based definitions of prediabetes had higher hazard ratios and better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease, and all-cause mortality than did fasting glucose concentration-based definitions (all p<0·05). The C-statistic for incident chronic kidney disease was 0·636 for ADA fasting glucose concentration clinical categories and 0·640 for ADA HbA 1c clinical categories (difference -0·005, 95% CI -0·008 to -0·001). The C-statistics were 0·662 for ADA fasting glucose clinical concentration categories and 0·672 for ADA HbA 1c clinical categories for atherosclerotic cardiovascular disease, 0·701 for ADA fasting glucose concentration clinical categories and 0·722 for ADA HbA 1c clinical categories for peripheral arterial disease, and 0·683 for ADA fasting glucose concentration clinical categories and 0·688 for ADA HbA 1c clinical categories for all-cause mortality. Prediabetes defined using the ADA HbA 1c cutoff showed a significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared with prediabetes defined with glucose-based definitions. ADA fasting glucose concentration clinical categories, WHO fasting glucose concentration clinical categories, and ADA and WHO 2 h glucose concentrations clinical categories were not significantly different in terms of risk discrimination for chronic kidney disease, cardiovascular outcomes, or mortality outcomes. Our results suggest that prediabetes definitions using HbA 1c were more specific and provided modest improvements in risk discrimination for clinical complications. The definition of prediabetes using the ADA fasting glucose concentration cutoff was more sensitive overall. US National Institutes of Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

The double nucleation model for sickle cell haemoglobin polymerization: full integration and comparison with experimental data.

PubMed

Medkour, Terkia; Ferrone, Frank; Galactéros, Frédéric; Hannaert, Patrick

2008-06-01

Sickle cell haemoglobin (HbS) polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, (i) in solution (homogeneous nucleation), (ii) onto existing polymers (heterogeneous nucleation). When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time (Ferrone et al. J Mol Biol 183(4):591-610, 611-631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model (Simulink), The MathWorks). Here, we compare the simulated outputs to experimental progress curves (n = 6-8 different [HbS], 3-6 mM range, from Ferrone's group). Within 10% from start, average root mean square (rms) deviation between simulated and experimental curves is 0.04 +/- 0.01 (25 degrees C, n = 8; mean +/- standard error). Conversely, for complete progress curves, averaged rms is 0.48 +/- 0.04. This figure is improved to 0.13 +/- 0.01 by adjusting heterogeneous pathway parameters (p < 0.01): the nucleus stability (sigma(2) micro( cc ): + 40%), and the fraction of polymer surface available for nucleation (phi), from 5e(-7), (3 mM) to 13 (6 mM). Similar results are obtained at 37 degrees C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process.

Adaption to High Altitude: An Evaluation of the Storage Quality of Suspended Red Blood Cells Prepared from the Whole Blood of Tibetan Plateau Migrants

PubMed Central

Wang, Hong; Li, Xiaojuan; He, Zeng; Gangla, Meiduo; Zhang, Jingdan; Han, Dingding; Liu, Jiaxin

2015-01-01

Hypoxia has been reported to cause the significant enhancement of hemoglobin (Hb) and hematocrit (Hct), which stabilizes at relatively high levels after an individual ascends to a high altitude. However, the quality of the suspended red blood cells (SRBCs) obtained from individuals at high altitudes such as Tibetan plateau migrants after storage has not been studied. In this study, we compared the storage quality of SRBCs prepared from Tibetan plateau and Deyang lowland populations by adding a normal volume of mannitol-adenine-phosphate (MAP), which is a common additive solution used in blood storage in Asian countries. The storage cell characteristics were examined on days1, 7, 14 and 35.We found higher Hct and Hb levels and viscosity in the high altitude samples. The metabolic rates, including those for electrolytes and lactate, were higher in plateau SRBCs than in lowland SRBCs; these findings were consistent with the higher osmotic fragility and hemolysis of plateau SRBCs throughout the entire storage period. In addition, the reduction rates of 2,3-diphosphoglycerate (2,3-DPG) and oxygen tension to attain 50% oxygen saturation of Hb (P50) in plateau SRBCs were higher than those in lowland SRBCs, and the oxygen delivering capacity in plateau SRBCs was weaker than that in lowland SRBCs. We concluded that the storage quality of plateau SRBCs was inferior to that of lowland SRBCs when using the same concentration of MAP. We suggested that the optimal formula, including the MAP concentration or even a new additive solution, to store the plateau SRBCs must be assessed and regulated. PMID:26637115

The decomposition of peroxynitrite to nitroxyl anion (NO−) and singlet oxygen in aqueous solution

PubMed Central

Khan, Ahsan Ullah; Kovacic, Dianne; Kolbanovskiy, Alexander; Desai, Mehul; Frenkel, Krystyna; Geacintov, Nicholas E.

2000-01-01

The mechanism of decomposition of peroxynitrite (OONO−) in aqueous sodium phosphate buffer solution at neutral pH was investigated. The OONO− was synthesized by directly reacting nitric oxide with superoxide anion at pH 13. The hypothesis was explored that OONO−, after protonation at pH 7.0 to HOONO, decomposes into 1O2 and HNO according to a spin-conserved unimolecular mechanism. Small aliquots of the concentrated alkaline OONO− solution were added to a buffer solution (final pH 7.0–7.2), and the formation of 1O2 and NO− in high yields was observed. The 1O2 generated was trapped as the transannular peroxide (DPAO2) of 9,10-diphenylanthracene (DPA) dissolved in carbon tetrachloride. The nitroxyl anion (NO−) formed from HNO (pKa 4.5) was trapped as nitrosylhemoglobin (HbNO) in an aqueous methemoglobin (MetHb) solution. In the presence of 25 mM sodium bicarbonate, which is known to accelerate the rate of decomposition of OONO−, the amount of singlet oxygen trapped was reduced by a factor of ≈2 whereas the yield of trapping of NO− by methemoglobin remained unaffected. Because NO3− is known to be the ultimate decomposition product of OONO−, these results suggest that the nitrate anion is not formed by a direct isomerization of OONO−, but by an indirect route originating from NO−. PMID:10716721

Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5-anhydroglucitol.

PubMed

Inada, Shinya; Koga, Masafumi

2017-11-01

Background The effect of alcohol consumption on glycaemic control indicators is not well known. In this study, we studied the effect of alcohol consumption on the plasma glucose and glycaemic control indicators in non-diabetic men. Methods The study enrolled 300 non-diabetic men who received a complete medical checkup (age: 52.8 ± 6.5 years, body mass index: 24.4 ± 2.8 kg/m 2 ). The subjects were divided into four groups by the amount of alcohol consumed, and the plasma glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) concentrations of the groups were compared. Results As the level of alcohol consumption increased, significantly high concentrations of fasting plasma glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma glucose concentrations tended to rise. While no significant effect of alcohol consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as the level of alcohol consumption increased. In stepwise multivariate regression analysis, alcohol consumption was a significant negative independent variable for HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption increased, the plasma glucose concentrations rose, but the HbA1c and GA concentrations were lower compared with the plasma glucose concentrations. These findings suggest that alcohol consumption may reduce HbA1c and GA concentrations, but not 1,5-AG.

Factors associated with haemoglobin concentration among Timor-Leste children aged 6-59 months.

PubMed

Agho, K E; Dibley, M J; D'Este, C; Gibberd, R

2008-06-01

The study was conducted to assess the prevalence of and factors associated with haemoglobin (Hb) concentrations among children aged 6-59 months in Timor-Leste. The 2003 Demographic and Health Survey was a multi-stage cluster survey of 4,320 households from four different geographic regions in Timor-Leste. In total, 4,514 children aged 6-59 months were included in the analysis. The prevalence of anaemia (Hb concentration <11.0g/dL) was 38.2% (638/1,668) for children aged 6-23 months and 22.6% (644/2,846) for older children (p<0.001). Girls had a higher mean Hb concentration than boys (11.9g/dL vs 11.7g/ dL, p<0.006) and children who had diarrhoea in the previous two weeks had a lower Hb concentration than children without diarrhoea (11.5g/dL vs 11.9g/dL, p<0.001). Children from the richest and middle-class households had a lower average Hb concentration than those from the poorest households (11.8g/ dL, 11.7g/dL vs 12.0g/dL, p<0.001). Children of mothers with some secondary or more education had a lower mean Hb concentration than children of mothers with completed primary, some primary and no education (11.7 g/dL vs 11.9 g/dL, 11.8 g/dL, and 11.9 g/dL, p=0.002). Children from severely-anaemic mothers had a lower mean Hb concentration than children from moderately-, mild and not anaemic mothers (10.5 g/dL vs 11.1 g/dL, 11.6 g/dL, 12.0 g/dL, p<0.001). After backward stepwise hierarchical multiple regression, wasting, male sex, recent diarrhoea, household wealth index (richest and middle-class), maternal educational status (some secondary or more and some primary), and maternal anaemic status were significantly associated with a lower Hb concentration in children and increased age of child and duration of breastfeeding (6 months) with a higher Hb concentration. Anaemia-prevention programmes among children in Timor-Leste should focus on those children aged less than two years, children with recent diarrhoea, wasted children, high socioeconomic status, and anaemic mothers.

Factors Associated with Haemoglobin Concentration among Timor-Leste Children Aged 6–59 Months

PubMed Central

Agho, K.E.; Dibley, M.J.; D'Este, C.; Gibberd, R.

2008-01-01

The study was conducted to assess the prevalence of and factors associated with haemoglobin (Hb) concentrations among children aged 6–59 months in Timor-Leste. The 2003 Demographic and Health Survey was a multi-stage cluster survey of 4,320 households from four different geographic regions in Timor-Leste. In total, 4,514 children aged 6–59 months were included in the analysis. The prevalence of anaemia (Hb concentration <11.0g/dL) was 38.2% (638/1,668) for children aged 6–23 months and 22.6% (644/2,846) for older children (p<0.001). Girls had a higher mean Hb concentration than boys (11.9g/dL vs 11.7g/dL, p<0.006) and children who had diarrhoea in the previous two weeks had a lower Hb concentration than children without diarrhoea (11.5g/dL vs 11.9g/dL, p<0.001). Children from the richest and middle-class households had a lower average Hb concentration than those from the poorest households (11.8g/dL, 11.7g/dL vs 12.0g/dL, p<0.001). Children of mothers with some secondary or more education had a lower mean Hb concentration than children of mothers with completed primary, some primary and no education (11.7 g/dL vs 11.9 g/dL, 11.8 g/dL, and 11.9 g/dL, p=0.002). Children from severely-anaemic mothers had a lower mean Hb concentration than children from moderately-, mild and not anaemic mothers (10.5 g/dL vs 11.1 g/dL, 11.6 g/dL, 12.0 g/dL, p<0.001). After backward stepwise hierarchical multiple regression, wasting, male sex, recent diarrhoea, household wealth index (richest and middle-class), maternal educational status (some secondary or more and some primary), and maternal anaemic status were significantly associated with a lower Hb concentration in children and increased age of child and duration of breastfeeding (6 months) with a higher Hb concentration. Anaemia-prevention programmes among children in Timor-Leste should focus on those children aged less than two years, children with recent diarrhoea, wasted children, high socioeconomic status, and anaemic mothers. PMID:18686553

A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume

PubMed Central

Bian, Yuzhu; Chang, Thomas Ming Swi

2015-01-01

Abstract We crosslink hemoglobin (Hb), superoxide dismutase (SOD), catalase (CAT), and carbonic anhydrase (CA) to form a soluble polyHb-SOD-CAT-CA nanobiotechnological complex. The obtained product is a soluble complex with three enhanced red blood cell (RBC) functions and without blood group antigens. In the present study, 2/3 of blood volume was removed to result in 90-min hemorrhagic shock at mean arterial blood pressure (MAP) of 30 mmHg. This was followed by the reinfusion of different resuscitation fluids, then followed for another 60 min. PolyHb-SOD-CAT-CA maintained the MAP at 87.5 ± 5 mmHg as compared with 3 volumes of lactated Ringer's solution, 43.3 ± 2.8 mmHg; blood, 91.3 ± 3.6 mmHg; polyHb-SOD-CAT, 86.0 ± 4.6 mmHg; poly stroma-free hemolysate (polySFHb), 85.0 ± 2.5 mmHg; and polyHb, 82.6 ± 3.5 mmHg. PolyHb-SOD-CAT-CA was superior to the blood and other fluids based on the following criteria. PolyHb-SOD-CAT-CA reduced tissue pCO2 from 98 ± 4.5 mmHg to 68.6 ± 3 mmHg. This was significantly (p < 0.05) more effective than lactated Ringer's solution (98 ± 4.5 mmHg), polyHb (90.1 ± 4.0 mmHg), polyHb-SOD-CAT (90.9 ± 1.4 mmHg), blood (79.1 ± 4.7 mmHg), and polySFHb (77 ± 5 mmHg). PolyHb-SOD-CAT-CA reduced the elevated ST level to 21.7 ± 6.7% and is significantly (< 0.05) better than polyHb (57.7 ± 8.7%), blood (39.1 ± 1.5%), polySFHb (38.3% ± 2.1%), polyHb-SOD-CAT (27.8 ± 5.6%), and lactated Ringer's solution (106 ± 3.1%). The plasma cardiac troponin T (cTnT) level of polyHb-SOD-CAT-CA group was significantly (P < 0.05) lower than that of all the other groups. PolyHb-SOD-CAT-CA reduced plasma lactate level from 18 ± 2.3 mM/L to 6.9 ± 0.3 mM/L. It was significantly more effective (P < 0.05) than lactated Ringer's solution (12.4 ± 0.6 mM/L), polyHb (9.6 ± 0.7 mM/L), blood (8.1 ± 0.2 mM/L), polySFHb (8.4 ± 0.1 mM/L), and polyHb-SOD-CAT (7.6 ± 0.3 mM/L). PolyHb-SOD-CAT-CA can be stored for 320 days at room temperature. Lyophilized poly-Hb-SOD-CAT-CA can be heat pasteurized at 68F for 2 h. This can be important if there is a need to inactivate human immunodeficiency virus, Ebola virus, and other infectious organisms. PMID:25297052

Interpretation of HbA1c : association with mean cell volume and haemoglobin concentration.

PubMed

Simmons, D; Hlaing, T

2014-11-01

The utility of HbA1c in diabetes diagnosis is reduced in settings associated with altered haemoglobin glycation. We have studied whether HbA1c varies with mean cell volume and mean cell haemoglobin concentration as measures of haemoglobin metabolism. Randomly selected adults from rural Victoria, Australia, were invited for biomedical assessment. After excluding patients with known diabetes and/or serum creatinine ≥ 0.12 mmol/l, 1315 adults were included. Demography, arthropometric measurements, oral glucose tolerance test, analyses of full blood count and HbA1c were undertaken. After adjusting for age, sex, ethnicity, BMI, town and socio-economic status, there were no significant differences in haemoglobin, mean cell volume or mean cell haemoglobin concentration by glycaemic status (defined by oral glucose tolerance test). HbA1c was significantly and independently associated with fasting glucose, town, mean cell haemoglobin concentration, ethnicity, age and BMI among men < 50 years (R² = 33.8%); fasting glucose, 2-h glucose, mean cell haemoglobin concentration and town among men ≥ 50 years (R² = 47.9%); fasting glucose, mean cell volume, mean cell haemoglobin concentration, town, 2-h glucose and age among women < 50 years (R² = 46.3%); fasting glucose, mean cell haemoglobin concentration, mean cell volume and 2-h glucose among women ≥ 50 years (R² = 51.6%). A generalized linear model showed a gradient from an adjusted mean HbA1c of 36 (95% CI 34-38) mmol/mol with a mean cell haemoglobin concentration of ≤ 320 g/l to 30 (95% CI 29-31) mmol/mol with a mean cell haemoglobin concentration of > 370 g/l. The gradient across mean cell volume was negative, but only by 1 mmol/mol (0.1%) HbA1c . A mean HbA1c difference of 5 mmol/mol (0.5%) across the mean cell haemoglobin concentration reference range suggests that an accompanying full blood count examination may be required for its use in the diagnosis of diabetes. Further studies are required to confirm this. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Soil solution extraction techniques for microbial ecotoxicity testing: a comparative evaluation.

PubMed

Tiensing, T; Preston, S; Strachan, N; Paton, G I

2001-02-01

The suitability of two different techniques (centrifugation and Rhizon sampler) for obtaining the interstitial pore water of soil (soil solution), integral to the ecotoxicity assessment of metal contaminated soil, were investigated by combining chemical analyses and a luminescence-based microbial biosensor. Two different techniques, centrifugation and Rhizon sampler, were used to extract the soil solution from Insch (a loamy sand) and Boyndie (a sandy loam) soils, which had been amended with different concentrations of Zn and Cd. The concentrations of dissolved organic carbon (DOC), major anions (F- , CI-, NO3, SO4(2-)) and major cations (K+, Mg2+, Ca2+) in the soil solutions varied depending on the extraction technique used. Overall, the concentrations of Zn and Cd were significantly higher in the soil solution extracted using the centrifugation technique compared with that extracted using the Rhizon sampler technique. Furthermore, the differences observed between the two extraction techniques depended on the type of soil from which the solution was being extracted. The luminescence-based biosensor Escherichia coli HB101 pUCD607 was shown to respond to the free metal concentrations in the soil solutions and showed that different toxicities were associated with each soil, depending on the technique used to extract the soil solution. This study highlights the need to characterise the type of extraction technique used to obtain the soil solution for ecotoxicity testing in order that a representative ecotoxicity assessment can be carried out.

Simulation of NO and O2 transport facilitated by polymerized hemoglobin solutions in an arteriole that takes into account wall shear stress-induced NO production.

PubMed

Zhou, Yipin; Cabrales, Pedro; Palmer, Andre F

2012-03-01

A mathematical model was developed to study nitric oxide (NO) and oxygen (O(2)) transport in an arteriole and surrounding tissues exposed to a mixture of red blood cells (RBCs) and hemoglobin (Hb)-based O(2) carriers (HBOCs). A unique feature of this model is the inclusion of blood vessel wall shear stress-induced production of endothelial-derived NO, which is very sensitive to the viscosity of the RBC and HBOC mixture traversing the blood vessel lumen. Therefore in this study, a series of polymerized bovine Hb (PolyHb) solutions with high viscosity, varying O(2) affinities, NO dioxygenation rate constants and O(2) dissociation rate constants that were previously synthesized and characterized by our group was evaluated via mathematical modeling, in order to investigate the effect of these biophysical properties on the transport of NO and O(2) in an arteriole and its surrounding tissues subjected to anemia with the commercial HBOC Oxyglobin® and cell-free bovine Hb (bHb) serving as appropriate controls. The computer simulation results indicated that transfusion of high viscosity PolyHb solutions promoted blood vessel wall shear stress dependent generation of the vasodilator NO, especially in the blood vessel wall and should transport enough NO inside the smooth muscle layer to activate vasodilation compared to the commercial HBOC Oxyglobin® and cell-free bHb. However, NO scavenging in the arteriole lumen was unavoidable due to the intrinsic high NO dioxygenation rate constant of the HBOCs being studied. This study also observed that all PolyHbs could potentially improve tissue oxygenation under hypoxic conditions, while low O(2) affinity PolyHbs were more effective in oxygenating tissues under normoxic conditions compared with high O(2) affinity PolyHbs. In addition, all ultrahigh molecular weight PolyHbs displayed higher O(2) transfer rates than the commercial HBOC Oxyglobin® and cell-free bHb. Therefore, these results suggest that ultrahigh molecular weight PolyHb solutions could be used as safe and efficacious O(2) carriers for use in transfusion medicine. It also suggests that future generations of PolyHb solutions should possess lower NO dioxygenation reaction rate constants in order to reduce NO scavenging, while maintaining high solution viscosity to take advantage of wall shear stress-induced NO production. Taken together, we suggest that this mathematical model can be used to predict the vasoactivity of HBOCs and help guide the design and optimization of the next generation of HBOCs for use in transfusion medicine. Copyright © 2011 Elsevier B.V. All rights reserved.

Novel noninvasive point-of-care device for real time hemoglobin monitoring

NASA Astrophysics Data System (ADS)

Timm, Ulrich; Gewiss, Helge; Kraitl, Jens; Stuepmann, Kirstin; Hinz, Michael; Koball, Sebastian; Ewald, Hartmut

2014-02-01

During the perioperative period, which includes the period before surgery and after surgery (postoperative), it is essential to measure diagnostic parameters such as: blood oxygen saturation; hemoglobin (Hb) concentration; and pulse rate. The Hb concentration in human blood is an important parameter to evaluate the physiological condition of an individual, as Hb is the oxygen carrying component of red blood cells. By determining the Hb concentration, it is possible, for example, to observe intraoperative or postoperative bleeding, and use this information as a trigger for autologous/ allogenic blood transfusions. In blood donation center it is also an essential parameter for the decision regarding the acceptance of the donor.

Dual production of poly(3-hydroxybutyrate) and glutamate using variable biotin concentrations in Corynebacterium glutamicum.

PubMed

Jo, Sung-Jin; Leong, Chean Ring; Matsumoto, Ken'ichiro; Taguchi, Seiichi

2009-04-01

We previously synthesized poly(3-hydroxybutyrate) [P(3HB)] in recombinant Corynebacterium glutamicum, a prominent producer of amino acids. In this study, a two-step cultivation was established for the dual production of glutamate and P(3HB) due to the differences in the optimal concentration of biotin. Glutamate was extracellularly produced first under the biotin-limited condition of 0.3 microg/L. Production was then shifted to P(3HB) by addition of biotin to a total concentration of 9 microg/L. The final products obtained were 18 g/L glutamate and 36 wt% of P(3HB).

Cardiovascular Morbidity and Pure Red Cell Aplasia Associated With Epoetin Theta Therapy in Patients With Chronic Kidney Disease: A Prospective, Noninterventional, Multicenter Cohort Study.

PubMed

Lammerich, Andreas; Balcke, Peter; Bias, Peter; Mangold, Simone; Wiesholzer, Martin

2016-02-01

The European Medicines Agency recommends limiting the hemoglobin (Hb) concentration to 10 to 12 g/dL in adults with chronic kidney disease (CKD) receiving erythropoiesis-stimulating agents such as epoetin theta. This postauthorization study assessed the incidence and intensity of cardiovascular events, including ischemic stroke, in patients receiving epoetin theta for anemia associated with CKD. A secondary end point was adverse drug reactions, including pure red cell aplasia. In this prospective, noninterventional, multinational cohort study, consecutive patients with advanced or end-stage renal disease and receiving epoetin theta were followed up for 6 months. Data on reportable adverse events (RAEs) (cardiac disorders, cardiac failure, myocardial infarction, and ischemic stroke and respective subterms), epoetin theta dosage, and Hb concentrations were collected. A post hoc exploratory analysis assessed the incidences of RAEs according to tertiles for individual mean Hb concentration (≤10.7, >10.7-11.47, and >11.47 g/dL for low, intermediate, and high, respectively) and mean weekly epoetin theta dosage (≤62, >62-125, and >125 IU/kg/wk for low, intermediate, and high). Data from 1039 patients were included (577 men, 462 women; mean age, 68.7 years). A total of 101 RAEs were documented in 89 patients (8.6%), for an event rate of 0.1985/person-year. Sixty-four patients (6.1%) died; none of the deaths was considered related to epoetin theta use. The incidence of RAEs was lowest at intermediate Hb concentrations (6.2%) compared with low (11.3%) and high (7.8%) Hb concentrations. The incidence of ischemic stroke was 1.5% at high Hb concentrations versus 0.6% at both the low and intermediate Hb concentrations. The incidence of any RAE was greater in the high-dose group (10.1%) than in the intermediate-dose (8.0%) and low-dose (7.6%) groups. The risk for any cardiovascular RAE or ischemic stroke was greatest in the high-dose/high-Hb group (13.3%), followed by high dose/low Hb (12.6%) and low dose/low Hb (12.1%). The risks for RAEs were lowest at high dose/intermediate Hb (3.8%) and low dose/intermediate Hb (5.3%). The event rate of adverse drug reactions other than the predefined RAEs was 0.0161/person-year. No cases of pure red cell aplasia were reported. The findings from the present study suggest that, for maintaining the optimal target Hb concentration (10-12 g/dL according to the current summary of product characteristics for epoetin theta; 10-11.5 g/dL according to the current guideline from Kidney Disease Improving Global Outcomes) in anemic adults with CKD, the lowest approved, effective dose epoetin theta should be used. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease

PubMed Central

Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K. Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

2017-01-01

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 (67Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation. PMID:28321059

Patient blood transfusion management: discharge hemoglobin level as a surrogate marker for red blood cell utilization appropriateness.

PubMed

Edwards, Jason; Morrison, Chris; Mohiuddin, Maleeha; Tchatalbachev, Vladislav; Patel, Charmi; Schwickerath, Vicki L; Menitove, Jay E; Singh, Gurmukh

2012-11-01

Blood transfusion management strategies minimize transfusion-associated risks, enhance outcomes, and reduce costs. We explored an association of discharge hemoglobin (Hb) with pretransfusion Hb, transfusion indications, and red blood cell (RBC) transfusions. We stipulate that patients with discharge Hb concentrations greater than 10.0 g/dL, or even 9.0 g/dL, received excessive RBC transfusions. We examined aggregate data from five hospitals and for one of the hospitals, the focus hospital, we reviewed patient records for a period of 6 months. Data analyses included number of RBC units transfused and Hb values before transfusion, after transfusion, and at discharge. In aggregate, 27% to 47% patients had discharge Hb levels greater than 10.0 g/dL. At the focus hospital, 27% had a discharge Hb level greater than 10 g/dL and 50.3% had a discharge Hb level greater than 9.0 g/dL. At the focus hospital, the mean Hb trigger for transfusion was a Hb level of 7.3 g/dL; the mean posttransfusion Hb level was 9.3 g/dL and mean discharge Hb level was 9.2 g/dL. Overall, 76% of the transfusions were of an even number of RBC units. In aggregate, overutilization exceeded 20%. At the focus hospital, approximately one-quarter of patients receiving transfusions had a Hb concentration greater than 10.0 g/dL at discharge. Transfused patients' discharge Hb concentration represents an effective indicator for retrospective monitoring of transfusion appropriateness. In light of the large number of patients receiving even number transfusions, reviewing Hb levels after transfusion of each RBC unit could reduce unnecessary transfusions. Retrospective review of discharge Hb data focuses providers on transfusion outcomes and affords an educational opportunity for blood utilization management. © 2012 American Association of Blood Banks.

Near-infrared spectroscopy and polysomnography during all-night sleep in human subjects

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Aggarwal, Payal; Chen, Kathleen; Franceschini, Maria Angela; Ehrenberg, Bruce L.

2003-10-01

We have performed cerebral near-infrared spectroscopy (NIRS) and polysomnography (electro-encephalography, electro-oculography, electro-myography, pulse oximetry, and respiratory monitoring) during all-night sleep in five human subjects. Polysomnography data were used for sleep staging, while NIRS data were used to measure the concentration and the oxygen saturation of hemoglobin in the frontal brain region. Immediately after sleep onset we observed a decrease in the cerebral concentration of oxy-hemoglobin ([HbO2]) and an increase in the concentration of deoxy-hemoglobin ([Hb]), consistent with a decrease in the cerebral blood flow velocity or an increase in cerebral metabolic rate of oxygen. An opposite trend (increase in [HbO2] and decrease in [Hb]) was usually observed after transition to deep sleep (stages III and IV). During rapid eye movement (REM) sleep, we observed an increase in [HbO2] and decrease in [Hb], consistent with an increase in the cerebral blood flow that overcompensates the increase in the metabolic rate of oxygen associated with REM sleep.

Hypocrellin B and nano silver loaded polymeric nanoparticles: Enhanced generation of singlet oxygen for improved photodynamic therapy.

PubMed

Natesan, Subramanian; Krishnaswami, Venkateshwaran; Ponnusamy, Chandrasekar; Madiyalakan, Madi; Woo, Thomas; Palanisamy, Rajaguru

2017-08-01

A nanoparticulate photodynamic approach was employed with an objective to achieve enhanced production of singlet oxygen ( 1 O 2 ), for the management of posterior segment eye diseases like age related macular degeneration. The hypocrellin B (HB) loaded poly lactide-co-glycolide nanoparticle formulations were incorporated with nano silver (HBS-NPs). The optimized HBS-NPs contained 2.60±0.06mg/mL of HB and showed (i) 135.6 to 828.2nm size range, and (ii) negative zeta potential with a narrow polydispersity index. The DSC thermograms suggested the amorphous nature of HB inside the HBS-NPs. With the average encapsulation efficiency of 92.9±1.79%, the drug release from the HBS-NPs followed a biphasic pattern with an initial burst of 3.50% during first 8h followed by a sustained release of 47.82% within 3days. The interaction between nano silver and HB as assessed by the increase in spectral intensity of Raman spectrum demonstrates that HB may be attached over the nano silver. Generation of reactive oxygen species (ROS) by HBS-NPs was significantly higher than that of HB/HB-NPs. The singlet oxygen generating efficiency assessed using EPR spectrometer follows the order of nano silver>HB-NPs>pure HB drug solution>HBS-NPs. The HBS-NPs had a concentration and time dependent phototoxicity on A549 (human adeno lung carcinoma) cells in the presence of light providing a superior phototoxic effect (82.2% at 50μM) at 2h irradiation. The CAM treated with HBS-NPs showed a significant anti-angiogenic effect compared to a blank formulation. In vivo biodistribution studies revealed that intravenous administration of HBS-NPs lead into significant exposure to the posterior segment of the eye. This proof of principle study demonstrates that HB based nanoparticles may be a valuable new tool for application in ocular photodynamic therapy for the treatment of AMD in future. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitreous Fluid and/or Urine Glucose Concentrations in 1,335 Civil Aviation Accident Pilot Fatalities

DTIC Science & Technology

2008-05-01

glucose, and in those cases wherein glucose levels are elevated, blood hemoglobin A1c ( HbA1c ) is measured. These analyses are conducted to monitor...diabetes. In this study, the prevalence of elevated glucose concentrations in fatally injured civilian pilots is evaluated. Glucose and HbA1c are measured...whom samples were received during 1998–2005 and whose vitreous fluid and/or urine glucose concentrations were measured. HbA1c levels and information

Visualization of children's mathematics solving process using near infrared spectroscopic approach

NASA Astrophysics Data System (ADS)

Kuroda, Yasufumi; Okamoto, Naoko; Chance, Britton; Nioka, Shoko; Eda, Hideo; Maesako, Takanori

2009-02-01

Over the past decade, the application of results from brain science research to education research has been a controversial topic. A NIRS imaging system shows images of Hb parameters in the brain. Measurements using NIRS are safe, easy and the equipment is portable, allowing subjects to tolerate longer research periods. The purpose of this research is to examine the characteristics of Hb using NIRS at the moment of understanding. We measured Hb in the prefrontal cortex of children while they were solving mathematical problems (tangram puzzles). As a result of the experiment, we were able to classify the children into three groups based on their solution methods. Hb continually increased in a group which could not develop a problem solving strategy for the tangram puzzles. Hb declined steadily for a group which was able to develop a strategy for the tangram puzzles. Hb was steady for a certain group that had already developed a strategy before solving the problems. Our experiments showed that the brain data from NIRS enables the visualization of children's mathematical solution processes.

Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study

PubMed Central

Galle, Jan-Christoph; Addison, Janet; Suranyi, Michael G.; Claes, Kathleen; Di Giulio, Salvatore; Guerin, Alain; Herlitz, Hans; Kiss, István; Farouk, Mourad; Manamley, Nick; Wirnsberger, Gerhard; Winearls, Christopher

2016-01-01

Background Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients. PMID:27190334

Effect of Nitrates, Thiocyanates and Selenium on the Iron and Iodine Status of Postpartum Women.

PubMed

Bivolarska, Anelia V; Maneva, Ana I; Gatseva, Penka D; Katsarova, Mariana N

2016-09-01

To find correlations between high thiocyanate and nitrate levels and low selenium levels and the indicators of the iodine and iron status of postpartum women. The study included 41 mothers aged 26.4±5.9 yrs from Asenovgrad and nearby villages. Urinary iodine was determined by the Sandell-Kolthoff reaction and thiocyanate - by the interaction of these ions with acidic solution of KMnO4; for serum nitrates we used the colorimetric method; serum selenium was assessed by electro-thermal atomic-absorption spectrophotometry; thyroxin (FT4), the thyroid stimulating hormone (TSH), serum ferritin (SF), and serum transferrin receptor (sTfR) were determined using ELISA; Hb levels were determined by hematology analyzer. Assessing the iodine status, we found a negative correlation between the levels of iodine and thiocyanates in urine (R=-0.717, р<0.0001), a positive correlation between nitrates and TSH (R=0.487, р=0.003) and a negative correlation between nitrates and FT4 (R=-0.312, р=0.06). For the iron status, we found a negative correlation between nitrates and SF (R=-0.429, р=0.009) and between nitrates and Hb (R=-0.383, р=0.021). The Mann-Whitney U-test showed that in women with nitrate levels higher than the mean value there was low FT4 level (р=0.06), high TSH level (р=0.013), low Hb concentration (р=0.061) and low SF concentration (р=0.005). The combined effects of environmental factors (elevated nitrate levels and low selenium level) on the iodine and iron status are manifested by low concentrations of FT4 (р=0.033), Hb (р=0.06) and SF (р=0.05) and high level of TSH (р=0.05). In conclusion, we found that environmental factors, especially when combined, have a negative impact on the iron and iodine status of females.

Novel multi wavelength sensor concept to detect total hemoglobin concentration, methemoglobin and oxygen saturation

NASA Astrophysics Data System (ADS)

Timm, Ulrich; Gewiss, Helge; Kraitl, Jens; Stuepmann, Kirstin; Hinz, Michael; Koball, Sebastian; Ewald, Hartmut

2015-03-01

The paper will describe the novel multi-wavelength photometric device OxyTrue Hb® which is capable to measure the hemoglobin (Hb) and methemoglobin (MetHb) concentration non-invasively. Clinic trails in blood donation centers and during the dialysis are done to prove and demonstrate the performance of the system. The results are compared to the gold standard, the BGA measurement.

2,3-DPG-Hb complex: a hypothesis for an asymmetric binding.

PubMed

Pomponi, M; Bertonati, C; Fuglei, E; Wiig, O; Derocher, A E

2000-05-15

This study was undertaken to test the symmetry of 2,3-diphosphoglycerate (2,3-DPG) binding site in hemoglobin (Hb). From Arnone's study [A. Arnone, Nature (London) 237 (1972) 146] the 2,3-DPG binding site is located at the top of the cavity, that runs through the center of the deoxy-Hb molecule. However, it is possible that this symmetry reported by Arnone, for crystals of 2,3-DPG-Hb complex, might not be conserved in solution. In this paper, we report the 31P nuclear magnetic resonances of the 2,3-DPG interaction with Hb. The 2,3-DPG chemical shifts of the P2 and P3 resonance are both pH- and hemoglobin-dependent [protein from man, polar bear (Ursus maritimus), Arctic fox (Alopex lagopus) and bovine]. 2,3-DPG binds tightly to deoxyhemoglobin and weakly, nevertheless significantly, to oxyhemoglobin. In particular, our results suggest similar spatial position of the binding site of 2,3-DPG in both forms of Hb in solutions. However, the most unexpected result was the apparent loss of symmetry in the binding site, which might correlate with the ability of the hemoglobin to modulate its functional behavior. The different interactions of the phosphate groups indicate small differences in the quaternary structure of the different deoxy forms of hemoglobin. Given the above structural perturbation an asymmetric binding in the complex could justify, at least in part, different physiological properties of Hb. Regardless, functionally relevant effects of 2,3-DPG seem to be measured and best elucidated through solution studies.

Characterization of the methemoglobin forming metabolites of benzocaine and lidocaine.

PubMed

Hartman, Neil; Zhou, Hongfei; Mao, Jinzhe; Mans, Daniel; Boyne, Michael; Patel, Vikram; Colatsky, Thomas

2017-05-01

1. Topical anesthesia with benzocaine or lidocaine occasionally causes methemoglobinemia, an uncommon but potentially fatal disorder where the blood has a reduced ability to transport oxygen. Previous in vitro studies using human whole blood have shown that benzocaine causes more methemoglobin (MetHb) formation than lidocaine, and that both compounds require metabolic transformation to form the MetHb producing species. In the current investigation, the active species of benzocaine forming the MetHb was investigated. 2. HPLC analysis of benzocaine samples incubated with human hepatic S9 showed the formation of a peak with the same UV spectrum and retention time as benzocaine hydroxylamine (BenzNOH). To confirm the activity of BenzNOH, MetHb production following exposure to the compound was determined in whole human blood using an Avoximeter 4000 CO-oximeter. 3. BenzNOH produced MetHb in a concentration dependent manner without the need for metabolic activation. Benzocaine in the presence of metabolic activation required a concentration of 500 μM to produce a similar degree of MetHb formation as 20 μM BenzNOH without activation. Previous work suggested that two metabolites of lidocaine may also form MetHb; N-hydroxyxylidine and 4-hydroxyxylidine. Of these two metabolites 4-hydroxyxylidine produced the most MetHb in whole blood in vitro in the absence of metabolic activation, however BenzNOH produced up to 14.2 times more MetHb than 4-hydroxyxylidine at a similar concentration. 4. These results suggest that the ability of benzocaine to form MetHb is likely to be mediated through its hydroxylamine metabolite and that this metabolite is inherently more active than the potentially MetHb-forming metabolites of lidocaine.

Clinical Course of Two Children with Unstable Hemoglobins: The Effect of Hydroxyurea Therapy.

PubMed

Loovers, Harriët M; Tamminga, Nienke; Mulder, André B; Tamminga, Rienk Y J

2016-09-01

Case reports on the effect of hydroxyurea (HU) therapy for unstable hemoglobins (Hbs) are sparse; only three adult cases have been reported. We report for the first time on the effect of HU therapy in children carrying unstable Hbs. The first case concerns a female child with a familial history of chronic hemolytic anemia. She was diagnosed with Hb Volga (HBB: c.83C>A) at the age of 7 months. At age 6, treatment options were reconsidered due to increasing fatigue and decreasing Hb concentration. The second case also concerns a female child with chronic hemolytic anemia and icterus since the age of 5. She was diagnosed with Hb Köln (HBB: c.295G>A) at the age of 9. At age 10, treatment options were reconsidered due to decreased general condition and poor school performance. Both children were started on HU therapy. The child with Hb Volga showed reduced clinical symptoms and increased average Hb concentrations. She has been on HU therapy for over 7 years at preparation of this manuscript. The child with Hb Köln showed decreasing Hb concentrations upon start of therapy; clinical symptoms did not improve. Therapy was discontinued after 3½ months. The Hb Volga case report suggests that HU therapy could improve clinical symptoms in some patients with unstable Hbs. Based on these and previously published cases, it was speculated that response can be predicted by the percentage of Hb F and reticulocyte counts.

Measurements of red cell deformability and hydration reflect HbF and HbA2 in blood from patients with sickle cell anemia.

PubMed

Parrow, Nermi L; Tu, Hongbin; Nichols, James; Violet, Pierre-Christian; Pittman, Corinne A; Fitzhugh, Courtney; Fleming, Robert E; Mohandas, Narla; Tisdale, John F; Levine, Mark

2017-06-01

Decreased erythrocyte deformability, as measured by ektacytometry, may be associated with disease severity in sickle cell anemia (SCA). Heterogeneous populations of rigid and deformable cells in SCA blood result in distortions of diffraction pattern measurements that correlate with the concentration of hemoglobin S (HbS) and the percentage of irreversibly sickled cells. We hypothesize that red cell heterogeneity, as well as deformability, will also be influenced by the concentration of alternative hemoglobins such as fetal hemoglobin (HbF) and the adult variant, HbA 2 . To test this hypothesis, we investigate the relationship between diffraction pattern distortion, osmotic gradient ektacytometry parameters, and the hemoglobin composition of SCA blood. We observe a correlation between the extent of diffraction pattern distortions and percentage of HbF and HbA 2 . Osmotic gradient ektacytometry data indicate that minimum elongation in the hypotonic region is positively correlated with HbF, as is the osmolality at which it occurs. The osmolality at both minimum and maximum elongation is inversely correlated with HbS and HbA 2 . These data suggest that HbF may effectively improve surface-to-volume ratio and osmotic fragility in SCA erythrocytes. HbA 2 may be relatively ineffective in improving these characteristics or cellular hydration at the levels found in this patient cohort. Copyright © 2017. Published by Elsevier Inc.

Leaf Concentrate Fortification of Antenatal Protein-Calorie Snacks Improves Pregnancy Outcomes

PubMed Central

Magon, Anjna; Joshi, Pallavi; Davys (Late), Glyn; Attlee, Amita; Mathur, Beena

2014-01-01

ABSTRACT Ready-to-eat (RTE) snacks are routinely distributed to pregnant women in India. These provide protein and calories but are low in micronutrients. We investigated whether RTE snacks fortified with leaf concentrate (LC) could improve pregnancy outcomes, including maternal haemoglobin (Hb) concentrations and infants’ birthweight. This randomized controlled two-arm trial was conducted over 18 months: control (sRTE) group received standard 120 g RTE snack (102 g wheat flour, 18 g soya flour); intervention (lcRTE) group received the same snack fortified with 7 g LC. The study was conducted in Jaipur, Rajasthan, India. One hundred and five pregnant women aged 18-35 years were studied. Among the 105 women randomized to the two arms of the trial, 2 (1.9%) were severely anaemic (Hb ≤6.0 g/dL); 55 (53.4%) were moderately anaemic (Hb 6.0-8.0 g/dL); 34 (33.0%) were mildly anaemic (Hb 8.6-10.9 g/dL); and 12 (11.7%) were not anaemic (Hb ≥11.0 g/dL). In the final month of pregnancy, 83.0% (39/47) of women in the sRTE group had Hb ≤8.5 g/dL compared to 37.8% (17/45) in the lcRTE group (p<0.001). After adjustment for age and baseline Hb concentration, the difference in Hb concentrations due to LC fortification was 0.94 g/dL (95% CI 6.8-12.0; p<0.001). Mean live birthweight in the lcRTE group was 2,695 g (SD 325 g) compared to 2,545 g (297 g) in the sRTE group (p=0.02). The lcRTE snacks increased infants’ birthweight by 133.7 g (95% CI 7.3-260.2; p=0.04) compared to sRTE snacks. Leaf concentrate fortification of antenatal protein-calorie snacks in a low-income setting in India protected against declining maternal haemoglobin concentrations and increased infants’ birthweight when compared with unfortified snacks. These findings require replication in a larger trial. PMID:25395906

Leaf concentrate fortification of antenatal protein-calorie snacks improves pregnancy outcomes.

PubMed

Magon, Anjna; Collin, Simon M; Joshi, Pallavi; Davys Late, Glyn; Attlee, Amita; Mathur, Beena

2014-09-01

Ready-to-eat (RTE) snacks are routinely distributed to pregnant women in India. These provide protein and calories but are low in micronutrients. We investigated whether RTE snacks fortified with leaf concentrate (LC) could improve pregnancy outcomes, including maternal haemoglobin (Hb) concentrations and infants' birthweight. This randomized controlled two-arm trial was conducted over 18 months: control (sRTE) group received standard 120 g RTE snack (102 g wheat flour, 18 g soya flour); intervention (lcRTE) group received the same snack fortified with 7 g LC. The study was conducted in Jaipur, Rajasthan, India. One hundred and five pregnant women aged 18-35 years were studied. Among the 105 women randomized to the two arms of the trial, 2 (1.9%) were severely anaemic (Hb ≤ 6.0 g/dL); 55 (53.4%) were moderately anaemic (Hb 6.0-8.0 g/dL); 34 (33.0%) were mildly anaemic (Hb 8.6-10.9 g/dL); and 12 (11.7%) were not anaemic (Hb ≥ 11.0 g/dL). In the final month of pregnancy, 83.0% (39/47) of women in the sRTE group had Hb ≤ 8.5 g/dL compared to 37.8% (17/45) in the lcRTE group (p<0.001). After adjustment for age and baseline Hb concentration, the difference in Hb concentrations due to LC fortification was 0.94 g/dL (95% CI 6.8-12.0; p<0.001). Mean live birthweight in the lcRTE group was 2,695 g (SD 325 g) compared to 2,545 g (297 g) in the sRTE group (p=0.02). The lcRTE snacks increased infants' birthweight by 133.7 g (95% CI 7.3-260.2; p=0.04) compared to sRTE snacks. Leaf concentrate fortification of antenatal protein-calorie snacks in a low-income setting in India protected against declining maternal haemoglobin concentrations and increased infants' birthweight when compared with unfortified snacks. These findings require replication in a larger trial.

Hydroxylamine-induced oxidation of ferrous carbonylated truncated hemoglobins from Mycobacterium tuberculosis and Campylobacter jejuni is limited by carbon monoxide dissociation.

PubMed

Ascenzi, Paolo; Ciaccio, Chiara; Gasperi, Tecla; Pesce, Alessandra; Caporaso, Lucia; Coletta, Massimo

2017-08-01

Hydroxylamine (HA) is an oxidant of ferrous globins and its action has been reported to be inhibited by CO, even though this mechanism has not been clarified. Here, kinetics of the HA-mediated oxidation of ferrous carbonylated Mycobacterium tuberculosis truncated hemoglobin N and O (Mt-trHbN(II)-CO and Mt-trHbO(II)-CO, respectively) and Campylobacter jejuni truncated hemoglobin P (Cj-trHbP(II)-CO), at pH 7.2 and 20.0 °C, are reported. Mixing Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO solution with the HA solution brings about absorption spectral changes reflecting the disappearance of the ferrous carbonylated derivatives with the concomitant formation of the ferric species. HA oxidizes irreversibly Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO with the 1:2 stoichiometry. The dissociation of CO turns out to be the rate-limiting step for the oxidation of Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO by HA. Values of the second-order rate constant for HA-mediated oxidation of Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO range between 8.8 × 10 4 and 8.6 × 10 7 M -1 s -1 , reflecting different structural features of the heme distal pocket. This study (1) demonstrates that the inhibitory effect of CO is linked to the dissociation of this ligand, giving a functional basis to previous studies, (2) represents the first comparative investigation of the oxidation of ferrous carbonylated bacterial 2/2 globins belonging to the N, O, and P groups by HA, (3) casts light on the correlation between kinetics of HA-mediated oxidation and carbonylation of globins, and (4) focuses on structural determinants modulating the HA-induced oxidation process.

Residual blood loss in single use dialyzers: effect of different membranes and flux.

PubMed

Kalocheretis, P; Vlamis, I; Belesi, C; Makriniotou, I; Zerbala, S; Savidou, E; Zorbas, S; Arvanitis, N; Iatrou, C

2006-03-01

The aim of this study was to evaluate the residual blood loss in new type single use dialyzers under the usually prevailing conditions during hemodialysis and to investigate whether or not this loss is dependent on dialyzer membrane composition or flux characteristics. In 158 hemodialysis (HD) patients, 158 single used dialyzers were studied in corresponding HD sessions. 52/158 dialyzers were made from modified cellulose (acetate, CA or triacetate, CTA) membrane and 106 from synthetic ones (58 with ethyl-vinyl-alcohol (EVAL), 48 with polyacrilonitrile (AN69)). Of those dialyzers 85/158 (58 EVAL+27CA) were low flux (LF) while the other 73 were high flux (HF). Patients underwent 4 hour HD sessions and at the end of the session blood was drawn for the measurement of hematocrit (Ht) and hemoglobin (Hb). Additionally, after the end of dialysis the used dialyzers were rinsed with 1000 mL of 0.05% NH(3) solution in distilled water. The wash was collected and subsequently Hb was measured using the benzidine method. From the volume of the solution and its concentration of Hb, total Hb of the solution was measured and blood loss in terms of red blood cell (RBC) volume was estimated by the use of the formula: RBC (mL) = Total Hb (g) in the solution x patient's Ht (ml/dL) / Patient's Hb (g/dL). For results to be comparable between dialyzers, RBC volume/m(2) of dialyzer membrane was expressed. In 5/158 patients blood loss was also estimated in 6 consecutive HD sessions using the same type of dialyzer. For the sum of the dialyzers, blood loss / dialyzer in terms of RBC volume, expressed as median (range), was 0.978 mL (0.01-23.9). There was statistically significant (p<0.001 or p<0.05) higher blood loss with the use of AN69 dialyzer than with the other three. RBC HF >RBC LF (p<0.001) constrained the first group of patients to use a 6% higher dosage of ferrum and 3.5% higher dosage of erythropoietin than the other group to achieve the optimal hemoglobulin values. No difference existed regarding RBC between CA, CTA and EVAL membranes. RBC measured in the small group of 5/158 patients for 6 consecutive HD sessions with the same dialyzer showed a wide range of RBC loss indicating an effect of the human factor. Blood loss during HD sessions due to residual blood cell volume inside dialyzers is usually slight using new type single use dialyzers but, sometimes, it can be significant and may contribute to the development or deterioration of preexisting iron deficiency anemia. The results of this study indicated that this loss can be attributed to the membrane composition of the dialyzer or to the human factor and has nothing to do with the ultrafiltration coefficient of the dialyzer.

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

PubMed

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

2001-02-14

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

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

PubMed Central

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

2013-01-01

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

Accuracy of detection of carboxyhemoglobin and methemoglobin in human and bovine blood with an inexpensive, pocket-size infrared scanner.

PubMed

Bickler, Margot P; Rhodes, Laura J

2018-01-01

Detecting life-threatening common dyshemoglobins such as carboxyhemoglobin (COHb, resulting from carbon monoxide poisoning) or methemoglobin (MetHb, caused by exposure to nitrates) typically requires a laboratory CO-oximeter. Because of cost, these spectrophotometer-based instrument are often inaccessible in resource-poor settings. The aim of this study was to determine if an inexpensive pocket infrared spectrometer and smartphone (SCiO®Pocket Molecular Sensor, Consumer Physics Ltd., Israel) accurately detects COHb and MetHb in single drops of blood. COHb was created by adding carbon monoxide gas to syringes of heparinized blood human or cow blood. In separate syringes, MetHb was produced by addition of sodium nitrite solution. After incubation and mixing, fractional concentrations of COHb or MetHb were measured using a Radiometer ABL-90 Flex® CO-oximeter. Fifty microliters of the sample were then placed on a microscope slide, a cover slip applied and scanned with the SCiO spectrometer. The spectrograms were used to create simple linear models predicting [COHb] or [MetHb] based on spectrogram maxima, minima and isobestic wavelengths. Our model predicted clinically significant carbon monoxide poisoning (COHb ≥15%) with a sensitivity of 93% and specificity of 88% (regression r2 = 0.63, slope P<0.0001), with a mean bias of 0.11% and an RMS error of 21%. Methemoglobinemia severe enough to cause symptoms (>20% MetHb) was detected with a sensitivity of 100% and specificity of 71% (regression r2 = 0.92, slope P<0.001) mean bias 2.7% and RMS error 21%. Although not as precise as a laboratory CO-oximeter, an inexpensive pocket-sized infrared scanner/smartphone detects >15% COHb or >20% MetHb on a single drop of blood with enough accuracy to be useful as an initial clinical screening. The SCiO and similar relatively low cost spectrometers could be developed as inexpensive diagnostic tools for developing countries.

Hematological parameters in high altitude residents living at 4,355, 4,660, and 5,500 meters above sea level.

PubMed

León-Velarde, F; Gamboa, A; Chuquiza, J A; Esteba, W A; Rivera-Chira, M; Monge, C C

2000-01-01

There have been a number of reports describing the hematological indicators of Andean residents living at altitudes above 4,000 m, but several confounding factors have made the published results difficult to interpret. To clear up the effect of hypoxia on hemoglobin concentration (Hb, g/dL), hematocrit (Hct, %) and red blood cell concentration (RBC, cells/microL), this publication describes and analyzes these variables in children, men, and women from three large and homogeneous populations living at 4,355 m (n = 151), 4,660 m (n = 400), and 5,500 m (n = 273) in the Southern Peruvian Andes. Hb, Hct, and RBC increase with age in men (p < 0.001), as well as in women (p < 0.001) at the three altitudes of the study. In children (boys and girls) living at 5,500, Hb increases 11% when compared with children living at 4,355 m, and in adults, Hb increases 9.6% when comparing the same altitudes. The maximum percentage increase in Hb with age was 5.6% at 5,500 m, in men and 3.2% at 4,355 m, in women. The average percentage of difference for the Hb concentration between adult men and women is 6.6% at 4,355 m, 9.8% at 4,660 m, and 11.6% at 5,500 m. The differences in Hb concentration between men and women can only be seen after puberty. Finally, Hb is higher in older than younger women, which confirms the role of menopause in the development of erythremia. The result of this analysis reinforces the notion that Hb and Hct seem to be stable and useful parameters for acclimatization only at moderate altitudes; with aging or with increasing altitude, they may become excessive and lose their efficiency to protect the venous oxygen pressure.

Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study.

PubMed

Galle, Jan-Christoph; Addison, Janet; Suranyi, Michael G; Claes, Kathleen; Di Giulio, Salvatore; Guerin, Alain; Herlitz, Hans; Kiss, István; Farouk, Mourad; Manamley, Nick; Wirnsberger, Gerhard; Winearls, Christopher

2016-12-01

Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Single-cell measurement of red blood cell oxygen affinity.

PubMed

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

2015-08-11

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

Single-cell measurement of red blood cell oxygen affinity

PubMed Central

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

2015-01-01

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen–Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2–3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability. PMID:26216973

Burkholderia sacchari DSM 17165: A source of compositionally-tunable block-copolymeric short-chain poly(hydroxyalkanoates) from xylose and levulinic acid.

PubMed

Ashby, Richard D; Solaiman, Daniel K Y; Nuñez, Alberto; Strahan, Gary D; Johnston, David B

2018-04-01

Burkholderia sacchari was used to produce poly-3-hydroxybutyrate-co-3-hydroxyvalerate block copolymers from xylose and levulinic acid. Levulinic acid was the preferred substrate resulting in 3-hydroxyvalerate (3HV) contents as high as 95 mol% at 24 h. The 3HB:3HV ratios were controlled by the initial levulinic acid media concentration and fermentation length. Higher levulinic acid concentrations and longer durations, resulted in polymers with two glass transition temperatures, each approximating those associated with poly-3HB and poly-3HV. 13 C NMR confirmed the presence of high concentrations of 3HB-3HB and 3HV-3HV homopolymeric dyads, while mass spectrometry of the partial hydrolysis products did not conform to Bernoullian statistics for randomness, confirming block sequences. MS/MS analysis of specific oligomers showed the mass-loss of 86 amu (a 3HB unit) and 100 amu (a 3HV unit) attesting to some randomness within the polymers. This study verifies the potential for producing Poly-3HB-block-3HV copolymers from inexpensive biorenewable feedstocks without sequential addition of carbon sources. Published by Elsevier Ltd.

The effects of residual pump blood on patient plasma free haemoglobin levels post cardiac surgery.

PubMed

Schotola, H; Wetz, A J; Popov, A F; Bergmann, I; Danner, B C; Schöndube, F A; Bauer, M; Bräuer, A

2016-09-01

At the end of cardiopulmonary bypass, there are invariably several hundred millilitres of residual pump blood in the reservoir, which can either be re-transfused or discarded. The objective of this prospective observational study was to investigate the quality of the residual pump blood, focusing on plasma free haemoglobin (pfHb) and blood cell counts. Fifty-one consecutive patients were included in the study. Forty-nine units of residual pump blood and 58 units of transfused red blood cell (RBC) concentrates were analysed. The mean preoperative pfHb of the patients was 0.057 ± 0.062 g/l, which increased gradually to 0.55 ± 0.36 g/l on arrival in the intensive care unit postoperatively. On the first postoperative day, the mean pfHb had returned to within the normal range. Our data showed that haemoglobin, haematocrit, and erythrocyte counts of residual pump blood were approximately 40% of the values in standardised RBC concentrates. Plasma free haemoglobin was significantly higher in residual pump blood compared to RBC concentrates, and nearly twice as high as the pfHb in patient blood samples taken contemporaneously. Our findings indicate that residual pump blood pfHb levels are markedly higher compared to patients' blood and RBC concentrates, but that its administration does not significantly increase patients' pfHb levels.

Hemoglobin enhances tissue factor expression on human malignant cells.

PubMed

Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

2001-04-01

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

Classification of variant forms of haemoglobin according to the ratio of glycated haemoglobin to glycated albumin.

PubMed

Miyazaki, Ayako; Kohzuma, Takuji; Kasayama, Soji; Koga, Masafumi

2012-09-01

Asymptomatic variant haemoglobin is increasingly being found in the measurement of glycated haemoglobin (HbA(1c)) for the management of diabetes mellitus. We compared the HbA(1c) concentrations measured by high-performance liquid chromatography (HPLC) and immunoassay and glycated albumin (GA) concentrations and calculated the respective ratios in order to classify the variant haemoglobin. Twenty different haemoglobin variants from 43 subjects were identified by mass spectrometry and DNA analysis. Since GA accurately reflects glycaemic control in patients with variant haemoglobin, we calculated respective ratios of HbA(1c) and GA. Haemoglobin variants causing a low ratio of HbA(1c) measured by HPLC (HPLC-HbA(1c)) to GA with a normal ratio of HbA(1c) measured by immunoassay (IA-HbA(1c)) to GA were classified as C1. A further classification of α and β was used with abnormalities of the α chain or β chain in the haemoglobin gene. Other haemoglobin variants were classified as non-C1. Eight diabetic patients with stable glycaemic control were used as controls. Twenty forms of variant haemoglobins were classified as C1α (2 variants; I-Interlaken and Hb J-Meerut), C1β (15 variants) and non-C1 (3 variants; Hb Himeji, Hb Woolwich, Hb Peterborough). Positive correlations between GA and HPLC-HbA(1c) or IA-HbA(1c) were seen in the C1β patients with diabetes mellitus. The regression line between GA and HPLC-HbA(1c), but not that between GA and IA-HbA(1c), showed a downward shift in comparison with the data obtained from the diabetic controls. Variant haemoglobin could be classified by calculating the ratios of HPLC-HbA(1c), IA-HbA(1c) and GA.

Kinetic studies of lipid oxidation induced by hemoglobin measured by consumption of dissolved oxygen in a liposome model system.

PubMed

Carvajal, Ana Karina; Rustad, Turid; Mozuraityte, Revilija; Storrø, Ivar

2009-09-09

The effect of hemoglobin (Hb) and lipid concentration, pH, temperature, and different antioxidants on heme-mediated lipid oxidation of liposomes from marine phospholipids was studied. The rate of lipid oxidation was measured by consumption of dissolved oxygen. Heme-mediated lipid oxidation at different Hb and lipid concentrations was modeled by Michaelis-Menten kinetics. The maximum rate (V(max)) for the reaction with cod and bovine Hb as a pro-oxidant was 66.2 +/- 3.4 and 56.6 +/- 3.4 microM/min, respectively. The Michaelis-Menten constant (K(m)) for the reaction with cod and bovine Hb was 0.67 +/- 0.09 and 1.2 +/- 0.2 microM, respectively. V(max) for the relationship between the oxygen uptake rate and lipid concentration was 43.2 +/- 1.5 microM/min, while the K(m) was 0.93 +/- 0.14 mg/mL. The effect of the temperature followed Arrhenius kinetics, and there was no significant difference in activation energy between cod and bovine Hb. The rate of lipid oxidation induced by bovine Hb was highest around pH 6. Ethylenediaminetetraacetic acid (EDTA) had no significant effect on heme-mediated lipid oxidation, but alpha-tocopherol and astaxanthin worked well as antioxidants. Kinetic differences were found between iron and Hb as pro-oxidants, and the efficacy of the antioxidants depended upon the pro-oxidant in the system.

Poly(acrylic acid) modifying bentonite with in-situ polymerization for removing lead ions.

PubMed

He, Y F; Zhang, L; Yan, D Z; Liu, S L; Wang, H; Li, H R; Wang, R M

2012-01-01

In this paper, a new kind of poly(acrylic acid) modified clay adsorbent, the poly(acrylic acid)/bentonite composite (PAA/HB) was prepared by in-situ polymerization, and utilized to remove lead(II) ions from solutions. The maximum adsorption of adsorbent is at pH 5 for metal ions, whereas the adsorption starts at pH 2. The effects of contact time (5-60 min), initial concentration of metal ions (200-1,000 mg/L) and adsorbent dosage (0.04-0.12 g/100 mL) have been reported in this article. The experimental data were investigated by means of kinetic and equilibrium adsorption isotherms. The kinetic data were analyzed by the pseudo-first-order and pseudo-second-order equation. The experimental data fitted the pseudo-second-order kinetic model very well. Langmuir and Freundlich isotherms were tried for the system to better understand the adsorption isotherm process. The maximal adsorption capacity of the lead(II) ions on the PAA/HB, as calculated from the Langmuir model, was 769.2 mg/g. The results in this study indicated that PAA/HB was an attractive candidate for removing lead(II) (99%).

Comparison of nitric oxide-induced oxidation of recombinant oxyhemoglobin subunits using a competition experiment.

PubMed

Lin, Yen-Lin; Huang, Kuang-Tse

2009-08-01

A low reaction rate with nitric oxide (NO) is one of the important characteristics of hemoglobin (Hb)-based oxygen carriers. The reaction rate between oxyHb and NO is usually measured by stopped-flow spectrophotometry. However, the reported rates vary due to the difficulty of accurately determining the NO concentration and the limit of the instrument dead time. To circumvent these problems, we developed an experiment using oxymyoglobin (oxyMb) to compete with oxyHb for NO that is released from an NO donor. Determination of the rate constants in the competition experiment no longer depends on accurate measurement of time or NO concentration, since this approach instead measures the ratio of rate constants for the reaction of oxyHb and oxyMb with NO. For recombinant mutant Hb alpha(L29F)beta the rates for alpha(L29F) and beta are approximately 15- and 1.6-fold smaller than for wild-type Hb. In conclusion, the competition experiment provides an alternative method for determination of relative reaction rates of recombinant Hb subunits with NO.

Dynamics of Hydration Water in Sugars and Peptides Solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perticaroli, Stefania; Nakanishi, Masahiro; Pashkovski, Eugene

2013-01-01

We analyzed solute and solvent dynamics of sugars and peptides aqueous solutions using extended epolarized light scattering (EDLS) and broadband dielectric spectroscopies (BDS). Spectra measured with both techniques reveal the same mechanism of rotational diffusion of peptides molecules. In the case of sugars, this solute reorientational relaxation can be isolated by EDLS measurements, whereas its ontribution to the dielectric spectra is almost negligible. In the presented analysis, we characterize the hydration water in terms of hydration number and retardation ratio between relaxation times of hydration and bulk water. Both techniques provide similar estimates of . The retardation imposed on themore » hydration water by sugars is 3.3 1.3 and involves only water molecules hydrogen-bonded (HB) to solutes ( 3 water molecules per sugar OH-group). In contrast, polar peptides cause longer range erturbations beyond the first hydration shell, and between 2.8 and 8, increasing with the number of chemical groups engaged in HB formation. We demonstrate that chemical heterogeneity and specific HB interactions play a crucial role in hydration dynamics around polar solutes. The obtained results help to disentangle the role of excluded volume and enthalpic contributions in dynamics of hydration water at the interface with biological molecules.« less

[Mechanical autologous transfusion in orthopedic surgery in children. Is the use of mechanical autologous transfusion possible even in pediatric orthopedic surgical procedures?].

PubMed

Michaelis, G; Melzer, C; Biscoping, J; Hempelmann, G

1995-07-01

The use of autotransfusion devices is an established method of reducing the need for homologous transfusions in surgery [3, 11, 13], but technical factors still contraindicate the washing and concentration of blood volumes smaller than 300 ml. Therefore, haemoconcentration of small volumes of salvaged blood, as usually found in paediatric surgery, is considered to be a complicated and questionable practice [5]. Whereas these amounts of blood loss are easily tolerated by adults, they may necessitate homologous transfusions in paediatric surgery. In a prospective study, we investigated whether a simple technical modification in the processing of salvaged blood could facilitate the use of autotransfusion devices, especially in children. PATIENTS AND METHODS. Intraoperative blood salvage was performed in children 6 months to 10 years old undergoing surgery for hip dysplasia. Autotransfusion (Dideco STAT) was started when the blood loss was estimated to be more than 20% of the total blood volume (TBV). As a reference, we used a formula based on body weight [10]: for children up to the age of 6 years 80 ml/kg blood volume and for children up to 10 years 75 ml/kg. The total volume of salvaged fluid including blood, anticoagulant solution, and surgical irrigation was collected in a reservoir and transferred to the autotransfusion set, after which the reservoir was rinsed with 500 ml 0.9% saline solution in order to save the remaining blood. After processing, the blood was stored in the retransfusion bag. By adding the same volume of plasma expander (6% hydroxyethyl starch [HES], molecular weight 450,000), spontaneous sedimentation of the washed autologous erythrocytes (RBCs) for 10-15 min led to a concentrate of RBCs. After 10 mu filtration, the RBC suspension was retransfused (Figs. 1-3). RESULTS. Within 12 months, autotransfusion was performed during 6 out of 15 surgical procedures according to the method described above. The calculated blood loss averaged 25.6% of TBV, of which 21.4% (= 272 ml) could be processed by the autotransfusion device (Table 3). The mean values of 2.6 g/dl haemoglobin (Hb) and 6.8% haematocrit (HCt) in the salvaged blood increased to 9.4 g/dl and 27.3% in the processed RBC concentrates. After adding 6% HES solution, spontaneous sedimentation of the RBCs led to values of Hb 22.1 g/dl and HCt 59.8%. An average of 59.5 ml (22-99 ml) sedimented RBCs was retransfused to the patients, including 11.6 ml 6% HES solution (Table 4). In this manner, the need for homologous transfusions could be avoided in these patients both during and after surgery. CONCLUSIONS. This study shows that the use of blood salvaging in paediatric surgery is indicated under certain conditions. With the aid of the simple modification described above, we solved the main problem in paediatric autotransfusion by concentrating RBC suspensions with low Hb and Hct values after using the autotransfusion device.

Prevalence of Inherited Hemoglobin Disorders and Relationships with Anemia and Micronutrient Status among Children in Yaoundé and Douala, Cameroon

PubMed Central

Nankap, Martin; Ndjebayi, Alex; Oyono, Yannick; Tarini, Ann; Brown, Kenneth H.; Green, Ralph

2017-01-01

Information on the etiology of anemia is necessary to design effective anemia control programs. Our objective was to measure the prevalence of inherited hemoglobin disorders (IHD) in a representative sample of children in urban Cameroon, and examine the relationships between IHD and anemia. In a cluster survey of children 12–59 months of age (n = 291) in Yaoundé and Douala, we assessed hemoglobin (Hb), malaria infection, and plasma indicators of inflammation and micronutrient status. Hb S was detected by HPLC, and α+thalassemia (3.7 kb deletions) by PCR. Anemia (Hb < 110 g/L), inflammation, and malaria were present in 45%, 46%, and 8% of children. A total of 13.7% of children had HbAS, 1.6% had HbSS, and 30.6% and 3.1% had heterozygous and homozygous α+thalassemia. The prevalence of anemia was greater among HbAS compared to HbAA children (60.3 vs. 42.0%, p = 0.038), although mean Hb concentrations did not differ, p = 0.38). Hb and anemia prevalence did not differ among children with or without single gene deletion α+thalassemia. In multi-variable models, anemia was independently predicted by HbAS, HbSS, malaria, iron deficiency (ID; inflammation-adjusted ferritin <12 µg/L), higher C-reactive protein, lower plasma folate, and younger age. Elevated soluble transferrin receptor concentration (>8.3 mg/L) was associated with younger age, malaria, greater mean reticulocyte counts, inflammation, HbSS genotype, and ID. IHD are prevalent but contribute modestly to anemia among children in urban Cameroon. PMID:28671630

Association of Sickle Cell Trait With Hemoglobin A1c in African Americans.

PubMed

Lacy, Mary E; Wellenius, Gregory A; Sumner, Anne E; Correa, Adolfo; Carnethon, Mercedes R; Liem, Robert I; Wilson, James G; Sacks, David B; Jacobs, David R; Carson, April P; Luo, Xi; Gjelsvik, Annie; Reiner, Alexander P; Naik, Rakhi P; Liu, Simin; Musani, Solomon K; Eaton, Charles B; Wu, Wen-Chih

2017-02-07

Hemoglobin A1c (HbA1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it. To evaluate the association between SCT and HbA1c for given levels of fasting or 2-hour glucose levels among African Americans. Retrospective cohort study using data collected from 7938 participants in 2 community-based cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). From the CARDIA study, 2637 patients contributed a maximum of 2 visits (2005-2011); from the JHS, 5301 participants contributed a maximum of 3 visits (2000-2013). All visits were scheduled at approximately 5-year intervals. Participants without SCT data, those without any concurrent HbA1c and glucose measurements, and those with hemoglobin variants HbSS, HbCC, or HbAC were excluded. Analysis of the primary outcome was conducted using generalized estimating equations (GEE) to examine the association of SCT with HbA1c levels, controlling for fasting or 2-hour glucose measures. Presence of SCT. Hemoglobin A1c stratified by the presence or absence of SCT was the primary outcome measure. The analytic sample included 4620 participants (mean age, 52.3 [SD, 11.8] years; 2835 women [61.3%]; 367 [7.9%] with SCT) with 9062 concurrent measures of fasting glucose and HbA1c levels. In unadjusted GEE analyses, for a given fasting glucose, HbA1c values were statistically significantly lower in those with (5.72%) vs those without (6.01%) SCT (mean HbA1c difference, -0.29%; 95% CI, -0.35% to -0.23%). Findings were similar in models adjusted for key risk factors and in analyses using 2001 concurrent measures of 2-hour glucose and HbA1c concentration for those with SCT (mean, 5.35%) vs those without SCT (mean, 5.65%) for a mean HbA1c difference of -0.30% (95% CI, -0.39% to -0.21%). The HbA1c difference by SCT was greater at higher fasting (P = .02 for interaction) and 2-hour (P = .03) glucose concentrations. The prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA1c values (29.2% vs 48.6% for prediabetes and 3.8% vs 7.3% for diabetes in 572 observations from participants with SCT and 6877 observations from participants without SCT; P<.001 for both comparisons). Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA1c at any given concentration of fasting or 2-hour glucose compared with participants without SCT. These findings suggest that HbA1c may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.

Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Hallacoglu, Bertan; Sassaroli, Angelo; Wysocki, Michael; Guerrero-Berroa, Elizabeth; Schnaider Beeri, Michal; Haroutunian, Vahram; Shaul, Merav; Rosenberg, Irwin H.; Troen, Aron M.; Fantini, Sergio

2012-08-01

We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85±6 years) and 19 young adults (mean age, 28±4 years). Non-invasive measurements were obtained on the forehead using a commercially available multi-distance frequency-domain system and analyzed using a diffusion theory model for a semi-infinite, homogeneous medium with semi-infinite boundary conditions. Our study included repeat measurements, taken five months apart, on 16 elderly volunteers that demonstrate intra-subject reproducibility of the absolute measurements with cross-correlation coefficients of 0.9 for absorption coefficient (μa), oxy-hemoglobin concentration ([HbO2]), and total hemoglobin concentration ([HbT]), 0.7 for deoxy-hemoglobin concentration ([Hb]), 0.8 for hemoglobin oxygen saturation (StO2), and 0.7 for reduced scattering coefficient (). We found significant differences between the two age groups. Compared to young subjects, elderly subjects had lower cerebral [HbO2], [Hb], [HbT], and StO2 by 10±4 μM, 4±3 μM, 14±5 μM, and 6%±5%, respectively. Our results demonstrate the reliability and robustness of multi-distance near-infrared spectroscopy measurements based on a homogeneous model in the human forehead on a large sample of human subjects. Absolute, non-invasive optical measurements on the brain, such as those presented here, can significantly advance the development of NIRS technology as a tool for monitoring resting/basal cerebral perfusion, hemodynamics, oxygenation, and metabolism.

Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy.

PubMed

Hallacoglu, Bertan; Sassaroli, Angelo; Wysocki, Michael; Guerrero-Berroa, Elizabeth; Schnaider Beeri, Michal; Haroutunian, Vahram; Shaul, Merav; Rosenberg, Irwin H; Troen, Aron M; Fantini, Sergio

2012-08-01

We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85 ± 6 years) and 19 young adults (mean age, 28 ± 4 years). Non-invasive measurements were obtained on the forehead using a commercially available multi-distance frequency-domain system and analyzed using a diffusion theory model for a semi-infinite, homogeneous medium with semi-infinite boundary conditions. Our study included repeat measurements, taken five months apart, on 16 elderly volunteers that demonstrate intra-subject reproducibility of the absolute measurements with cross-correlation coefficients of 0.9 for absorption coefficient (μa), oxy-hemoglobin concentration ([HbO2]), and total hemoglobin concentration ([HbT]), 0.7 for deoxy-hemoglobin concentration ([Hb]), 0.8 for hemoglobin oxygen saturation (StO2), and 0.7 for reduced scattering coefficient (μ's). We found significant differences between the two age groups. Compared to young subjects, elderly subjects had lower cerebral [HbO2], [Hb], [HbT], and StO2 by 10 ± 4 μM, 4 ± 3 μM, 14 ± 5 μM, and 6%±5%, respectively. Our results demonstrate the reliability and robustness of multi-distance near-infrared spectroscopy measurements based on a homogeneous model in the human forehead on a large sample of human subjects. Absolute, non-invasive optical measurements on the brain, such as those presented here, can significantly advance the development of NIRS technology as a tool for monitoring resting/basal cerebral perfusion, hemodynamics, oxygenation, and metabolism.

NITRATE CONVERSION OF HB-LINE REILLEXTM HPQ RESIN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steimke, J.; Williams, M.; Steeper, T.

Reillex{trademark} HPQ ion exchange resin is used by HB Line to remove plutonium from aqueous streams. Reillex{trademark} HPQ resin currently available from Vertellus Specialties LLC is a chloride ionic form, which can cause stress corrosion cracking in stainless steels. Therefore, HB Line Engineering requested that Savannah River National Laboratory (SRNL) convert resin from chloride form to nitrate form in the Engineering Development Laboratory (EDL). To perform this task, SRNL treated two batches of resin in 2012. The first batch of resin from Reilly Industries Batch 80302MA was initially treated at SRNL in 2001 to remove chloride. This batch of resin,more » nominally 30 liters, has been stored wet in carboys since that time until being retreated in 2012. The second batch of resin from Batch 23408 consisted of 50 kg of new resin purchased from Vertellus Specialties in 2012. Both batches were treated in a column designed to convert resin using downflow of 1.0 M sodium nitrate solution through the resin bed followed by rinsing with deionized water. Both batches were analyzed for chloride concentration, before and after treatment, using Neutron Activation Analysis (NAA). The resin specification [Werling, 2003] states the total chlorine and chloride concentration shall be less than 250 ppm. The resin condition for measuring this concentration is not specified; however, in service the resin would always be fully wet. Measurements in SRNL showed that changing from oven dry resin to fully wet resin, with liquid in the particle interstices but no supernatant, increases the total weight by a factor of at least three. Therefore, concentration of chlorine or chloride expressed as parts per million (ppm) decreases by a factor of three. Therefore, SRNL recommends measuring chlorine concentration on an oven dry basis, then dividing by three to estimate chloride concentration in the fully wet condition. Chloride concentration in the first batch (No.80302MA) was nearly the same before the current treatment (759 ppm dry) and after treatment (745 ppm dry or {approx}248 ppm wet). Treatment of the second batch of resin (No.23408) was very successful. Chloride concentration decreased from 120,000 ppm dry to an average of 44 ppm dry or {approx}15ppm wet, which easily passes the 250 ppm wet criterion. Per guidance from HB Line Engineering, SRNL blended Batch 80302 resin with Batch P9059 resin which had been treated previously by ResinTech to remove chloride. The chloride concentrations for the two drums of Batch P9059 were 248 ppm dry ({approx}83 ppm wet) {+-}22.8% and 583 ppm dry ({approx}194 ppm wet) {+-} 11.8%. The blended resin was packaged in five gallon buckets.« less

Dissociation of Heme–Globin Complexes by Blackbody Infrared Radiative Dissociation: Molecular Specificity in the Gas Phase?

PubMed Central

Gross, Deborah S.; Zhao, Yuexing; Williams, Evan R.

2005-01-01

The temperature dependence of the unimolecular kinetics for dissociation of the heme group from holo-myoglobin (Mb) and holo-hemoglobin α-chain (Hb-α) was investigated with blackbody infrared radiative dissociation (BIRD). The rate constant for dissociation of the 9 + charge state of Mb formed by electrospray ionization from a “pseudo-native” solution is 60% lower than that of Hb-α at each of the temperatures investigated. In solutions of pH 5.5–8.0, the thermal dissociation rate for Mb is also lower than that of HB-α (Hargrove, M. S. et al. J. Biol. Chem. 1994, 269, 4207–4214). Thus, Mb is thermally more stable with respect to heme loss than Hb-α both in the gas phase and in solution. The Arrhenius activation parameters for both dissociation processes are indistinguishable within the current experimental error (activation energy 0.9 eV and pre-exponential factor of 108–10 s−1). The 9+ to 12+ charge states of Mb have similar Arrhenius parameters when these ions are formed from pseudo-native solutions. In contrast, the activation energies and pre-exponential factors decrease from 0.8 to 0.3 eV and 107 to 102 s−1, respectively, for the 9 + to 12 + charge states formed from acidified solutions in which at least 50% of the secondary structure is lost. These results demonstrate that gas-phase Mb ions retain clear memory of the composition of the solution from which they are formed and that these differences can be probed by BIRD. PMID:16479269

Dissociation of heme-globin complexes by blackbody infrared radiative dissociation: molecular specificity in the gas phase?

PubMed

Gross, D S; Zhao, Y; Williams, E R

1997-05-01

The temperature dependence of the unimolecular kinetics for dissociation of the heme group from holo-myoglobin (Mb) and holo-hemoglobin alpha-chain (Hb-alpha) was investigated with blackbody infrared radiative dissociation (BIRD). The rate constant for dissociation of the 9 + charge state of Mb formed by electrospray ionization from a "pseudo-native" solution is 60% lower than that of Hb-alpha at each of the temperatures investigated. In solutions of pH 5.5-8.0, the thermal dissociation rate for Mb is also lower than that of HB-alpha (Hargrove, M. S. et al. J. Biol. Chem.1994, 269, 4207-4214). Thus, Mb is thermally more stable with respect to heme loss than Hb-alpha both in the gas phase and in solution. The Arrhenius activation parameters for both dissociation processes are indistinguishable within the current experimental error (activation energy 0.9 eV and pre-exponential factor of 10(8-10) s(-1)). The 9+ to 12+ charge states of Mb have similar Arrhenius parameters when these ions are formed from pseudo-native solutions. In contrast, the activation energies and pre-exponential factors decrease from 0.8 to 0.3 eV and 10(7) to 10(2) s(-1), respectively, for the 9 + to 12 + charge states formed from acidified solutions in which at least 50% of the secondary structure is lost. These results demonstrate that gas-phase Mb ions retain clear memory of the composition of the solution from which they are formed and that these differences can be probed by BIRD.

Determination of size distribution and encapsulation efficiency of liposome-encapsulated hemoglobin blood substitutes using asymmetric flow field-flow fractionation coupled with multi-angle static light scattering.

PubMed

Arifin, Dian R; Palmer, Andre F

2003-01-01

In this study, we investigated the size distribution, encapsulation efficiency, and oxygen affinity of liposome-encapsulated tetrameric hemoglobin (LEHb) dispersions and correlated the data with the variation in extruder membrane pore size, ionic strength of the extrusion buffer, and hemoglobin (Hb) concentration. Asymmetric flow field-flow fractionation (AFFF) in series with multi-angle static light scattering (MASLS) was used to study the LEHb size distribution. We also introduced a novel method to measure the encapsulation efficiency using a differential interferometric refractive index (DIR) detector coupled to the AFFF-MASLS system. This technique was nondestructive toward the sample and easy to implement. LEHbs were prepared by extrusion using a lipid combination of dimyristoyl-phosphatidylcholine, cholesterol, and dimyristoyl-phosphatidylglycerol in a 10:9:1 molar ratio. Five initial Hb concentrations (50, 100, 150, 200, and 300 mg Hb per mL of buffer) extruded through five different membrane pore diameters (400, 200, 100, 80, and 50 nm) were studied. Phosphate buffered saline (PBS) and phosphate buffer (PB) both at pH 7.3 were used as extrusion buffers. Despite the variation, extrusion through 400-nm pore diameter membranes produced LEHbs smaller than the pore size, extrusion through 200-nm membranes produced LEHbs with diameters close to the pore diameter, and extrusion through 100-, 80-, and 50-nm membranes produced LEHbs larger than the pore sizes. We found that the choice of extrusion buffer had the greatest effect on the LEHb size distribution compared to either Hb concentration or extruder membrane pore size. Extrusion in PBS produced larger LEHbs and more monodisperse LEHb dispersions. However, LEHbs extruded in PB generally had higher Hb encapsulation efficiencies and lower methemoglobin (metHb) levels. The choice of extrusion buffer also affected how the encapsulation efficiency correlated with Hb concentration, extruder pore size, and the metHb level. The most optimum encapsulation efficiency and amount of Hb entrapped were achieved at the highest Hb concentration and the largest pore size for both extrusion buffers (62.38% and 187.14 mg Hb/mL of LEHb dispersion extruded in PBS, and 69.98% and 209.94 mg Hb/mL of LEHb dispersion extruded in PB). All LEHbs displayed good oxygen-carrying properties as indicated by their P(50) and cooperativity coefficients. LEHbs extruded in PB had an average P(50) of 23.04 mmHg and an average Hill number of 2.29, and those extruded in PBS had average values of 27.25 mmHg and 2.49. These oxygen-binding properties indicate that LEHbs possess strong potential as artificial blood substitutes. In addition, the metHb levels in PB-LEHb dispersions are significantly low even in the absence of antioxidants such as N-acetyl-L-cysteine.

Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test.

PubMed

Grazzini, Grazia; Ventura, Leonardo; Rubeca, Tiziana; Rapi, Stefano; Cellai, Filippo; Di Dia, Pietro P; Mallardi, Beatrice; Mantellini, Paola; Zappa, Marco; Castiglione, Guido

2017-07-01

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22-28°C) and up to 60% at outside temperature (29°C, range 16-39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

PubMed

Hannemann, A; Rees, D C; Tewari, S; Gibson, J S

2015-11-01

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex

PubMed Central

Prakash, Neal; Biag, Jonathan D.; Sheth, Sameer A.; Mitsuyama, Satoshi; Theriot, Jeremy; Ramachandra, Chaithanya; Toga, Arthur W.

2007-01-01

Background Mechanisms of neurovascular coupling—the relationship between neuronal chemoelectrical activity and compensatory metabolic and hemodynamic changes—appear to be preserved across species from rats to humans despite differences in scale. However, previous work suggests that the highly cellular dense mouse somatosensory cortex has different functional hemodynamic changes compared to other species. Methods We developed novel hardware and software for 2-dimensional optical spectroscopy (2DOS). Optical changes at four simultaneously recorded wavelengths were measured in both rat and mouse primary somatosensory cortex (S1) evoked by forepaw stimulation to create four spectral maps. The spectral maps were converted to maps of deoxy-, oxy-, and total-hemoglobin (HbR, HbO, and HbT) concentration changes using the modified Beer-Lambert law and phantom HbR and HbO absorption spectra. Results Functional hemodynamics were different in mouse versus rat neocortex. On average, hemodynamics were as expected in rat primary somatosensory cortex (S1): the fractional change in the log of HbT concentration increased monophasically 2 s after stimulus, whereas HbO changes mirrored HbR changes, with HbO showing a small initial dip at 0.5 s followed by a large increase 3.0 s post stimulus. In contrast, mouse S1 showed a novel type of stimulus-evoked hemodynamic response, with prolonged, concurrent, monophasic increases in HbR and HbT and a parallel decrease in HbO that all peaked 3.5–4.5 s post stimulus onset. For rats, at any given time point the average size and shape of HbO and HbR forepaw maps were the same, whereas surface veins distorted the shape of the HbT map. For mice, HbO, HbR, and HbT forepaw maps were generally the same size and shape at any post-stimulus time point. Conclusions 2DOS using image splitting optics is feasible across species for brain mapping and quantifying the map topography of cortical hemodynamics. These results suggest that during physiologic stimulation, different species and/or cortical architecture may give rise to different hemodynamic changes during neurovascular coupling. PMID:17574868

Hemoglobin status of non-school going adolescent girls in three districts of Orissa, India.

PubMed

Bulliyy, Gandham; Mallick, Gitanjali; Sethy, Girija Sankar; Kar, Santanu Kumar

2007-01-01

Anemia is a major public health problem in young children and pregnant women in SouthEast Asia, but a paucity of data on anemia in adolescent girls in India. Studies are lacking on the entire non-school going adolescent population. To determine the prevalence of anemia in non-school going adolescent girls and the association between hemoglobin (Hb) concentration and socioeconomic and nutritional factors. A cross-sectional community study conducted on a sample of 1937 healthy adolescent girls aged 11-19 years from three districts of Orissa, India. Sample size was determined using a probability proportionate to size cluster sampling. The adolescent girls were interviewed and anthropometric measurements were collected. The Hb estimation was carried out in capillary blood samples using the cyanmethemoglobin method. Anemia and nutritional status were evaluated according to standard procedures. The mean Hb concentration was 9.7 +/- 1.4 g/dL (range, 4.5-13.4 g/dL). Of the total adolescent girls, 1869 (96.5%) were anemic (Hb < 12.0 g/dL), of which, 45.2%, 46.9% and 4.4% had mild, moderate, and severe anemia, respectively. A significant curvilinear relation was found between Hb concentration and age, with the nadir of the curve occurring in the 12-14 years age group. Girls from Bargarh district had significantly lower mean Hb levels than those from the Jajpur and Khurda districts. Significant positive associations were found between Hb concentration and pre-menarche, community, education levels of girls and their parents' family income, body mass index, and mid-upper arm circumference. This study revealed that prevalence of anemia was extremely high in non-school going adolescent girls (most were moderately anemic) and stressed the need for more research and public health interventions.

Accumulation profiles of parabens and their metabolites in fish, black bear, and birds, including bald eagles and albatrosses.

PubMed

Xue, Jingchuan; Kannan, Kurunthachalam

2016-09-01

Although several studies have reported the ubiquitous occurrence of parabens in human specimens and the environment, little is known about the accumulation of these estrogenic chemicals in fish and birds. In this study, accumulation profiles of six parabens and their metabolites were determined in 254 tissue (including liver, kidney, egg, and plasma) samples from 12 species of fish and seven species of birds collected from inland, coastal, and remote aquatic ecosystems. In addition, liver and kidney tissues from black bears were analyzed. Methyl paraben (MeP) was found in a majority of the tissues, with the highest concentration (796ng/g (wet weight [wet wt])) found in the liver of a bald eagle from Michigan. 4-Hydroxy benzoate (HB) was the major metabolite, found in 91% of the tissue samples analyzed at concentrations as high as 68,600ng/g, wet wt, which was found in the liver of a white-tailed sea eagle from the Baltic Sea coast. The accumulation pattern of MeP and 4-HB varied, depending on the species. The mean concentrations of MeP measured in fishes from Michigan, New York, and Florida waters were <2.01 (fillet), 152 (liver), and 32.0 (liver) ng/g, wet wt, respectively, and the corresponding 4-HB concentrations were 39.5, 10,500, and 642ng/g, wet wt. The mean hepatic and renal concentrations of 4-HB in black bears were 1,720 and 1,330ng/g, wet wt, respectively. The concentrations of MeP and 4-HB were significantly positively correlated with each other in various tissues and species, which suggested a common source of exposure to these compounds in fish and birds. Trace concentrations of MeP and 4-HB also were found in the tissues of albatrosses from Midway Atoll, Northwestern Pacific Ocean, which suggested widespread distribution of these compounds in the marine environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proficiency testing of Hb A1c: a 4-year experience in Taiwan and the Asian Pacific region.

PubMed

Shiesh, Shu-Chu; Wiedmeyer, Hsiao-Mei; Kao, Jau-Tsuen; Vasikaran, Samuel D; Lopez, Joseph B

2009-10-01

The correlation between hemoglobin A(1c) (Hb A(1c)) and risk for complications in diabetic patients heightens the need to measure Hb A(1c) with accuracy. We evaluated the current performance for measuring Hb A(1c) in the Asian and Pacific region by examining data submitted by laboratories participating in the Taiwan proficiency-testing program. Five fresh-pooled blood samples were sent to participating laboratories twice each year. The results were evaluated against target values assigned by the National Glycohemoglobin Standardization Program network laboratories; a passing criterion of +/-7% of the target value was used. Measurement uncertainty at Hb A(1c) concentrations of 7.0% and 8.0% were determined. A total of 276 laboratories from 11 countries took part in the Hb A(1c) survey. At the Hb A(1c) concentrations tested method-specific interlaboratory imprecision (CVs) were 1.1%-13.9% in 2005, 1.3%-10.1% in 2006, 1.2%-8.2% in 2007, and 1.1%-6.1% in 2008. Differences between target values and median values from the commonly used methods ranged from -0.24% to 0.22% Hb A(1c) in 2008. In 2005 83% of laboratories passed the survey, and in 2008 93% passed. At 7.0% Hb A(1c), measurement uncertainty was on average 0.49% Hb A(1c). The use of accuracy-based proficiency testing with stringent quality criteria has improved the performance of Hb A(1c) testing in the Asian and Pacific laboratories during the 4 years of assessment.

Inequality in the hepatitis B awareness level in rural residents from 7 provinces in China.

PubMed

Zheng, Juan; Li, Quan; Wang, Jian; Zhang, Guojie; Wangen, Knut R

2017-05-04

The hepatitis B (HB) awareness level is an important factor affecting the rates of HB virus vaccination. To better understand income-related inequalities in the HB awareness level, it is imperative to identify the sources of inequalities and assess the contribution rates of these influential factors. This study analyzed the unequal distribution of the HB awareness level and the contributions of various influential factors. We performed a cross-sectional household survey with questionnaire-based, face-to-face interviews in 7 Chinese provinces. Responses from 7271 respondents were used in this analysis. Multinomial logistic regression was used for the analysis of contributing factors, and the concentration index was used as a measure of HB awareness inequalities. The HB awareness level varied across participants with different characteristics. Multinomial logistic regression of the explanatory factors of the HB awareness level showed that several estimated coefficients and relative risk ratios were statistically significant for middle- and high-level awareness, except for sex, occupation, and household income. The concentration index of the HB knowledge score was 0.140, indicating inequality gradients disadvantageous to the poor. The contribution rate of socioeconomic factors was the largest (60.8%), followed by demographic characteristics (29.0%) and geographic factors (4.3%). Demographic, socioeconomic, and geographic factors are associated with the HB awareness inequality. Therefore, to reduce inequality, HB-related health education targeting individuals with low socioeconomic status should be performed. Less-developed provinces, especially with high proportions of poor residents, warrant particular attention. Our findings may be beneficial to improve the HB virus vaccination rate for individuals with low socioeconomic status.

Elevated Accumulation of Parabens and their Metabolites in Marine Mammals from the United States Coastal Waters.

PubMed

Xue, Jingchuan; Sasaki, Nozomi; Elangovan, Madhavan; Diamond, Guthrie; Kannan, Kurunthachalam

2015-10-20

The widespread exposure of humans to parabens present in personal care products is well-known. Nevertheless, little is known about the accumulation of parabens in marine organisms. In this study, six parabens and four common metabolites of parabens were measured in 121 tissue samples from eight species of marine mammals collected along the coastal waters of Florida, California, Washington, and Alaska. Methyl paraben (MeP) was the predominant compound found in the majority of the marine mammal tissues analyzed, and the highest concentration found was 865 ng/g (wet weight [wet wt]) in the livers of bottlenose dolphins from Sarasota Bay, FL. 4-Hydroxybenzoic acid (4-HB) was the predominant paraben metabolite found in all tissue samples. The measured concentrations of 4-HB were on the order of hundreds to thousands of ng/g tissue, and these values are some of the highest ever reported in the literature. MeP and 4-HB concentrations showed a significant positive correlation (p < 0.05), which suggested a common source of exposure to these compounds in marine mammals. Trace concentrations of MeP and 4-HB were found in the livers of polar bears from the Chuckchi Sea and Beaufort Sea, which suggested widespread distribution of MeP and 4-HB in the oceanic environment.

The influence of demographic, physical, behavioral, and dietary factors on hemoglobin adduct levels of acrylamide and glycidamide in the general U.S. population.

PubMed

Duke, Tina J; Ruestow, Peter S; Marsh, Gary M

2018-03-24

This study aims to better understand the individual characteristics and dietary factors that affect the relationship between estimated consumption of acrylamide and measured acrylamide hemoglobin adduct levels (HbAA) and glycidamide hemoglobin adduct levels (HbGA). Acrylamide levels in individual food items, estimated by the U.S. Food and Drug Administration, were linked to data collected in the 2003-2004 National Health and Nutrition Examination Survey. Multivariable linear regression was used to evaluate the relationship between estimated consumption of acrylamide and HbAA. A significant association between acrylamide intake and HbAA was observed, after adjustment for gender, race/ethnicity, smoking status, age, and BMI (R 2 = 0.34). Across quartiles of acrylamide consumption, HbAA and HbGA levels increased monotonically. Among nonsmokers, an evaluation of three heavily consumed, high AA concentration foods showed a positive trend between the consumed amount of fried potatoes and HbAA in children, adolescents, and adults. A significant positive trend between the consumed amount of potato chips or coffee was indicated in adolescents, adults, and seniors. Consumption of some individual foods affects HbAA concentrations more strongly and in an age-dependent manner. Our results suggest that effective dietary guidelines for controlling acrylamide intake should be subpopulation specific.

Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute.

PubMed

Sou, Keitaro; Klipper, Robert; Goins, Beth; Tsuchida, Eishun; Phillips, William T

2005-02-01

Phospholipid vesicles encapsulating concentrated human hemoglobin (Hb-vesicles, HbV), also known as liposomes, have a membrane structure similar to that of red blood cells (RBCs). These vesicles circulate in the bloodstream as an oxygen carrier, and their circulatory half-life times (t(1/2)) and biodistribution are fundamental characteristics required for representation of their efficacy and safety as a RBC substitute. Herein, we report the pharmacokinetics of HbV and empty vesicles (EV) that do not contain Hb, in rats and rabbits to evaluate the potential of HbV as a RBC substitute. The samples were labeled with technetium-99m and then intravenously infused into animals at 14 ml/kg to measure the kinetics of HbV elimination from blood and distribution to the organs. The t(1/2) values were 34.8 and 62.6 h for HbV and 29.3 and 57.3 h for EV in rats and rabbits, respectively. At 48 h after infusion, the liver, bone marrow, and spleen of both rats and rabbits had significant concentrations of HbV and EV, and the percentages of the infused dose in these three organs were closely correlated to the circulatory half-life times in elimination phase (t(1/2beta)). Furthermore, the milligrams of HbV per gram of tissue correlated well between rats and rabbits, suggesting that the balance between organ weight and body weight is a fundamental factor determining the pharmacokinetics of HbV. This factor could be used to estimate the biodistribution and the circulation time of HbV in humans, which is estimated to be equal to that in rabbit.

Low modulus biomimetic microgel particles with high loading of hemoglobin.

PubMed

Chen, Kai; Merkel, Timothy J; Pandya, Ashish; Napier, Mary E; Luft, J Christopher; Daniel, Will; Sheiko, Sergei; DeSimone, Joseph M

2012-09-10

We synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With similar shape and size as red blood cells (RBCs), the particles were fabricated using the PRINT (particle replication in nonwetting templates) technique. Low cross-linking of the hydrogel resulted in very low mesh density for these particles, allowing passive diffusion of hemoglobin throughout the particles. Hb was secured in the particles through covalent conjugation of the lysine groups of Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy of particles bound to fluorescent dye-labeled Hb confirmed the uniform distribution of Hb throughout the particle interior, as opposed to the surface conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer by weight, were obtained without a significant effect on particle stability and shape, though particle diameter decreased slightly with Hb conjugation. Analysis of the protein by circular dichroism (CD) spectroscopy showed that the secondary structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in the particles could be maintained at a low level and the loaded Hb could still bind oxygen, as studied by UV-vis spectroscopy. Hb-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with a Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate (1000 1/s) for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into RBC mimics, we will discuss the implications for artificial blood.

Low Modulus Biomimetic Microgel Particles with High Loading of Hemoglobin

PubMed Central

Chen, Kai; Merkel, Timothy J.; Pandya, Ashish; Napier, Mary E.; Luft, J. Christopher; Daniel, Will; Sheiko, Sergei

2012-01-01

We synthesized extremely deformable red blood cell-like microgel particles and loaded them with bovine hemoglobin (Hb) to potentiate oxygen transport. With similar shape and size as red blood cells (RBCs), the particles were fabricated using the PRINT® (Particle Replication In Non-wetting Templates) technique. Low crosslinking of the hydrogel resulted in very low mesh density for these particles, allowing passive diffusion of hemoglobin throughout the particles. Hb was secured in the particles through covalent conjugation of the lysine groups of Hb to carboxyl groups in the particles via EDC/NHS coupling. Confocal microscopy of particles bound to fluorescent dye-labeled Hb confirmed the uniform distribution of Hb throughout the particle interior, as opposed to the surface conjugation only. High loading ratios, up to 5 times the amount of Hb to polymer by weight, were obtained, without a significant effect on particle stability, shape, though particle diameter decreased slightly with Hb conjugation. Analysis of the protein by circular dichroism (CD) spectroscopy showed that the secondary structure of Hb was unperturbed by conjugation to the particles. Methemoglobin in the particles could be maintained at a low level and the loaded Hb could still bind oxygen as studied by UV-vis spectroscopy. Hb-loaded particles with moderate loading ratios demonstrated excellent deformability in microfluidic devices, easily deforming to pass through restricted pores half as wide as the diameter of the particles. The suspension of concentrated particles with Hb concentration of 5.2 g/dL showed comparable viscosity to that of mouse blood, and the particles remained intact even after being sheared at a constant high rate (1,000 1/s) for 10 min. Armed with the ability to control size, shape, deformability, and loading of Hb into RBC mimics, we will discuss the implications for artificial blood. PMID:22852860

Hankel-Bessel laser beams.

PubMed

Kotlyar, Victor V; Kovalev, Alexey A; Soifer, Victor A

2012-05-01

An analytical solution of the scalar Helmholtz equation to describe the propagation of a laser light beam in the positive direction of the optical axis is derived. The complex amplitude of such a beam is found to be in direct proportion to the product of two linearly independent solutions of Kummer's differential equation. Relationships for a particular case of such beams-namely, the Hankel-Bessel (HB) beams-are deduced. The focusing of the HB beams is studied. © 2012 Optical Society of America

Effects of indigo carmine intravenous injection on noninvasive and continuous total hemoglobin measurement with using the Revision L sensor.

PubMed

Isosu, Tsuyoshi; Obara, Shinju; Hakozaki, Takahiro; Imaizumi, Tsuyoshi; Iseki, Yuzo; Mogami, Midori; Ohashi, Satoshi; Ikegami, Yukihiro; Kurosawa, Shin; Murakawa, Masahiro

2017-04-01

The effects of intravenous injection of indigo carmine on noninvasive and continuous total hemoglobin (SpHb) measurement were retrospectively evaluated with the Revision L sensor. The subjects were 18 patients who underwent elective gynecologic surgery under general anesthesia. During surgery, 5 mL of 0.4 % indigo carmine was injected intravenously, and changes in SpHb concentrations between before and after the injection were evaluated. The mean age was 52.4 ± 12.8 years. Before injection, the median SpHb level was 10.1 (range, 6.8-13.4) g/dL. The results demonstrated no change in SpHb concentration between before and after indigo carmine injection as detected by the Revision L sensor. SpHb measurements as determined with the Revision L sensor were not affected, even after the intravenous injection of indigo carmine.

Direct electrochemistry and electrocatalysis of hemoglobin in graphene oxide and ionic liquid composite film.

PubMed

Sun, Wei; Gong, Shixing; Shi, Fan; Cao, Lili; Ling, Luyang; Zheng, Weizhe; Wang, Wencheng

2014-07-01

In this paper a novel sensing platform based on graphene oxide (GO), ionic liquid (IL) 1-ethyl-3-methylimidazolium tetrafluoroborate and Nafion for the immobilization of hemoglobin (Hb) was adopted with a carbon ionic liquid electrode (CILE) as the substrate electrode, which was denoted as Nafion/Hb-GO-IL/CILE. Spectroscopic results suggested that Hb molecules were not denatured in the composite. A pair of well-defined redox peaks appeared on the cyclic voltammogram, which was attributed to the realization of direct electron transfer of Hb on the electrode. Electrochemical behaviors of Hb entrapped in the film were carefully investigated by cyclic voltammetry with the electrochemical parameters calculated. Based on the catalytic ability of the immobilized Hb, Nafion/Hb-GO-IL/CILE exhibited excellent electrocatalytic behavior towards the reduction of different substrates such as trichloroacetic acid in the concentration range from 0.01 to 40.0mM with the detection limit as 3.12 μM (3σ), H2O2 in the concentration range from 0.08 to 635.0 μM with the detection limit as 0.0137 μM (3σ) and NaNO2 in the concentration range from 0.5 to 800.0 μM with the detection limit as 0.0104 μM (3σ). So the proposed bioelectrode could be served as a new third-generation electrochemical sensor without mediator. Copyright © 2014 Elsevier B.V. All rights reserved.

Association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c among women with Type 1 diabetes

PubMed Central

Huang, T.; Brown, F. M.; Curran, A.; James-Todd, T.

2015-01-01

Aim To examine the association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c levels in women with Type 1 diabetes. Methods We longitudinally evaluated 136 women with Type 1 diabetes who received prenatal and postpartum care through the Joslin Diabetes Center’s Diabetes and Pregnancy Program between 2004 and 2009. Weight, BMI and HbA1c concentration were assessed before the index pregnancy and repeatedly monitored after delivery until 12 months postpartum. We used a linear mixed model to assess the association of postpartum HbA1c with pre-pregnancy BMI and postpartum weight retention. Results The mean HbA1c concentration increased from 49 mmol/mol (6.6%) at 6 weeks postpartum to 58 mmol/mol (7.5%) by 10 months postpartum, a level similar to the mean pre-pregnancy HbA1c concentration. Postpartum weight retention showed a linearly decreasing trend of 0.06 kg/week (P<0.0001), with −0.1 kg average postpartum weight retention by 1 year postpartum. Compared with women with a pre-pregnancy BMI≥25 kg/m2, women with a lower pre-pregnancy BMI maintained a 3.4 mmol/mol (0.31%) lower HbA1c concentration, after adjusting for several sociodemographic, reproductive and diabetes-related factors (P=0.03). There was a suggestion of a time-varying positive association between HbA1c and postpartum weight retention, with the most significant difference of 3.7 mmol/mol (0.34%; P=0.05) at 30 weeks postpartum among women with postpartum weight retention ≥5 kg vs those with postpartum weight retention <5 kg. Conclusions Pre-pregnancy BMI and postpartum weight retention were positively associated with HbA1c during the first postpartum year in women with Type 1 diabetes. Interventions to modify the behaviours associated with these body weight factors before pregnancy and after delivery may help women with Type 1 diabetes maintain good glycaemic control after pregnancy. PMID:25346003

Plasma zinc, vitamin B(12) and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh.

PubMed

Shamim, Abu Ahmed; Kabir, Alamgir; Merrill, Rebecca D; Ali, Hasmot; Rashid, Mahbubur; Schulze, Kerry; Labrique, Alain; West, Keith P; Christian, Parul

2013-08-01

The objective of the current analysis was to explore the association of multiple micronutrients with Hb concentration among pregnant women in a South Asian setting, a topic that has not been adequately explored. Sociodemographic, anthropometric and micronutrient status (plasma ferritin, transferrin receptor, retinol, a- and g-tocopherol, folate, vitamin B12, Zn) and Hb concentration were assessed at early pregnancy. The biochemical sub-study was nested within a double-blind, placebo-controlled, community-based vitamin A and b-carotene supplementation trial in rural north-western Bangladesh (JiVitA). All assessments were conducted before trial supplementation was initiated. A systematic sample of 285 women was selected from those enrolled in the biochemical sub-study. Seventeen per cent of women were mildly anaemic; moderate and severe anaemia was uncommon (2.1 %). a-Tocopherol, vitamin B12 and Zn deficiencies were common (43.5%, 19.7% and 14.7%, respectively); however, vitamin A, folate and Fe deficiencies were comparatively rare (7.4%, 2.8% and ,1%,respectively). Plasma Zn, vitamin B12 and a-tocopherol were positively associated and plasma g-tocopherol was negatively associated with Hb (P < 0.05) after adjustment for gestational age, inflammation status, season and nutritional status measured by mid-upper arm circumference. Among pregnant women in rural Bangladesh with minimal Fe deficiency, plasma Zn, vitamin B12, and a- and g-tocopherol concentrations were associated with Hb concentration. Appreciating the influence on Hb of micronutrients in addition to those with known associations with anaemia, such as Fe, folate, and vitamin A, is important when addressing anaemia in similar settings.

Fluid transition layer between rigid solute and liquid solvent: is there depletion or enrichment?

PubMed

Djikaev, Yuri S; Ruckenstein, Eli

2016-03-21

The fluid layer between solute and liquid solvent is studied by combining the density functional theory with the probabilistic hydrogen bond model. This combination allows one to obtain the equilibrium distribution of fluid molecules, taking into account the hydrogen bond contribution to the external potential whereto they are subjected near the solute. One can find the effective width of the fluid solvent-solute transition layer and fluid average density in that layer, and determine their dependence on temperature, solvent-solute affinity, vicinal hydrogen bond (hb) energy alteration ratio, and solute radius. Numerical calculations are performed for the solvation of a plate and spherical solutes of four different radii in two model solvents (associated liquid and non-associated one) in the temperature range from 293 K to 333 K for various solvent-solute affinities and hydrogen bond energy alteration ratios. The predictions of our model for the effective width and average density of the transition layer are consistent with experiments and simulations. The small-to-large crossover lengthscale for hydrophobic hydration is expected to be about 3-5 nm. Remarkably, characterizing the transition layer with the average density, one can observe that for small hydrophobes, the transition layer becomes enriched with rather than depleted of fluid when the solvent-solute affinity and hb-energy alteration ratio become large enough. The boundary values of solvent-solute affinity and hb-energy alteration ratio, needed for the "depletion-to-enrichment" crossover (in the smoothed density sense), are predicted to decrease with increasing temperature.

Voltammetric studies of hemoglobin-coated polystyrene latex bead films on pyrolytic graphite electrodes.

PubMed

Sun, Hong; Hu, Naifei

2004-08-01

A novel hemoglobin (Hb)-coated polystyrene (PS) latex bead film was deposited on pyrolytic graphite (PG) electrode surface. In the first step, positively charged Hb molecules in pH 5.0 buffers were adsorbed on the surface of negatively charged, 500 nm diameter PS latex beads bearing sulfate groups by electrostatic interaction. The aqueous dispersion of Hb-coated PS particles was then deposited on the surface of PG electrodes and, after evaporation of the solvent, Hb-PS films were formed. The Hb-PS film electrodes exhibited a pair of well-defined, quasi-reversible cyclic voltammetric (CV) peaks at about -0.36 V vs. SCE in pH 7.0 buffers, characteristic of Hb heme Fe(III)/Fe(II) redox couples. Positions of Soret absorption band of Hb-PS films suggest that Hb retains its near-native structure in the films in its dry form and in solution at medium pH. The Hb in PS films was also acted as a catalyst to catalyze electrochemical reduction of various substrates such as trichloroacetic acid (TCA), nitrite, oxygen and hydrogen peroxide.

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Fast and reliable symplectic integration for planetary system N-body problems

NASA Astrophysics Data System (ADS)

Hernandez, David M.

2016-06-01

We apply one of the exactly symplectic integrators, which we call HB15, of Hernandez & Bertschinger, along with the Kepler problem solver of Wisdom & Hernandez, to solve planetary system N-body problems. We compare the method to Wisdom-Holman (WH) methods in the MERCURY software package, the MERCURY switching integrator, and others and find HB15 to be the most efficient method or tied for the most efficient method in many cases. Unlike WH, HB15 solved N-body problems exhibiting close encounters with small, acceptable error, although frequent encounters slowed the code. Switching maps like MERCURY change between two methods and are not exactly symplectic. We carry out careful tests on their properties and suggest that they must be used with caution. We then use different integrators to solve a three-body problem consisting of a binary planet orbiting a star. For all tested tolerances and time steps, MERCURY unbinds the binary after 0 to 25 years. However, in the solutions of HB15, a time-symmetric HERMITE code, and a symplectic Yoshida method, the binary remains bound for >1000 years. The methods' solutions are qualitatively different, despite small errors in the first integrals in most cases. Several checks suggest that the qualitative binary behaviour of HB15's solution is correct. The Bulirsch-Stoer and Radau methods in the MERCURY package also unbind the binary before a time of 50 years, suggesting that this dynamical error is due to a MERCURY bug.

Evaluation and diagnosis of brain death by functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Pan, Boan; Zhong, Fulin; Huang, Xiaobo; Pan, Lingai; Lu, Sen; Li, Ting

2017-02-01

Brain death, the irreversible and permanent loss of the brain and brainstem functions, is hard to be judged precisely for some clinical reasons. The traditional diagnostic methods are time consuming, expensive and some are even dangerous. Functional near infrared spectroscopy (FNIRS), using the good scattering properties of major component of blood to NIR, is capable of noninvasive monitoring cerebral hemodynamic responses. Here, we attempt to use portable FNIRS under patients' natural state for brain death diagnosis. Ten brain death patients and seven normal subjects participated in FNIRS measurements. All of them were provided different fractional concentration of inspired oxygen (FIO2) in different time periods. We found that the concentration variation of deoxyhemoglobin concentration (Δ[Hb]) presents the trend of decrease in the both brain death patients and normal subjects with the raise of the FIO2, however, the data in the normal subjects is more significant. And the concentration variation of oxyhemoglobins concentration (Δ[HbO2]) emerges the opposite trends. Thus Δ[HbO2]/Δ[Hb] in brain death patients is significantly higher than normal subjects, and emerges the rising trend as time went on. The findings indicated the potential of FNIRS-measured hemodynamic index in diagnosing brain death.

Effects of milk casein-derived peptides on absolute oxyhaemoglobin concentrations in the prefrontal area and on work efficiency after mental stress loading in male students.

PubMed

Nakamura, H; Iwamoto, M; Ogata, T; Washida, K; Sekine, K; Takase, M; Park, B J; Morikawa, T; Miyazaki, Y

2008-01-01

This study examined the influence of milk casein-derived peptides on cerebral activity after mental stress loading. In a crossover study, 16 male students were given a drink containing peptides (peptide group), or water (control group) before stress loading. The oxyhaemoglobin (HbO(2)) concentration in the prefrontal area of the brain and work efficiency were measured as indicators of cerebral activity and differences in these parameters were examined according to type A or type B personality. Type A behaviour was defined as: aggression-hostility, hard-driving-time-urgency and speed-power, whereas type B behaviour did not have these characteristics. Peptide intake resulted in a significant increase in both HbO(2) concentration and work efficiency, whilst a similar increase was not seen in the control group. When divided into type A or type B personality, the changes in HbO(2) concentration for the control group differed significantly in the right prefrontal area. Moreover, in type A subjects the HbO(2) concentration in the right prefrontal area following intake was significantly different between the peptide and control groups.

Efficient removal of dyes from aqueous solutions using a novel hemoglobin/iron oxide composite.

PubMed

Essandoh, Matthew; Garcia, Rafael A

2018-05-10

Magnetic particles entrapped in different matrices that display high thermal stability, low toxicity, interactive functions at the surface, and high saturation magnetization are of great interest. The objective of this work was to synthesize a novel hemoglobin/iron oxide composite (Hb/Fe 3 O 4 ) for the removal of different dyes (indigo carmine, naphthol blue black, tartrazine, erythrosine, eriochrome black T and bromophenol blue) from aqueous solutions. The Hb/Fe 3 O 4 composite was characterized using scanning electron microscopy (SEM), laser diffraction particle size analysis, FT-IR spectroscopy, isoelectric point determination and thermogravimetric analysis (TGA). The Hb/Fe 3 O 4 composite showed high removal efficiency toward all the different classes of dyes studied and the mechanism of adsorption was dominated by electrostatic interaction. Adsorption was found to follow pseudo-second order kinetic model and Langmuir isotherm. The Langmuir monolayer adsorption capacities for all the dyes range from 80 to 178 mg/g. The Hb/Fe 3 O 4 composite possesses extra advantage of being easily isolated from aqueous suspension using an external magnet. The stability of the prepared Hb/Fe 3 O 4 composite was also demonstrated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype)

PubMed Central

Hannemann, A.; Rees, D.C.; Tewari, S.; Gibson, J.S.

2015-01-01

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease. PMID:26870793

A new approach for the carbon monoxide (CO) exposure diagnosis: measurement of total CO in human blood versus carboxyhemoglobin (HbCO).

PubMed

Varlet, Vincent; De Croutte, Emma Lagroy; Augsburger, Marc; Mangin, Patrice

2013-07-01

The aim of the study is to present the application of a headspace-gas chromatography-mass spectrometry (HS-GC-MS) method for the determination of the carbon monoxide (CO) blood concentration and to compare it with carboxyhemoglobin (HbCO) saturation. In postmortem cases, the HbCO measured by spectrophotometry frequently leads to inaccurate results due to inadequate samples or analyses. The true role of CO intoxication in the death of a person could be misclassified. The estimation of HbCO from HS-GC-MS CO measurements provides helpful information by determining the total CO levels (CO linked to hemoglobin (HbCO) and CO dissociated from hemoglobin). The CO concentrations were converted in HbCO saturation levels to define cutoff blood CO values. CO limits were defined as less than 1 μmol/mL for living persons, less than 1.5 μmol/mL for dead persons without CO exposure, and greater than 3 μmol/mL for dead persons with clear CO poisoning. © 2013 American Academy of Forensic Sciences.

Inequality in the hepatitis B awareness level in rural residents from 7 provinces in China

PubMed Central

Zheng, Juan; Li, Quan; Wang, Jian; Zhang, Guojie; Wangen, Knut R.

2017-01-01

ABSTRACT The hepatitis B (HB) awareness level is an important factor affecting the rates of HB virus vaccination. To better understand income-related inequalities in the HB awareness level, it is imperative to identify the sources of inequalities and assess the contribution rates of these influential factors. This study analyzed the unequal distribution of the HB awareness level and the contributions of various influential factors. We performed a cross-sectional household survey with questionnaire-based, face-to-face interviews in 7 Chinese provinces. Responses from 7271 respondents were used in this analysis. Multinomial logistic regression was used for the analysis of contributing factors, and the concentration index was used as a measure of HB awareness inequalities. The HB awareness level varied across participants with different characteristics. Multinomial logistic regression of the explanatory factors of the HB awareness level showed that several estimated coefficients and relative risk ratios were statistically significant for middle- and high-level awareness, except for sex, occupation, and household income. The concentration index of the HB knowledge score was 0.140, indicating inequality gradients disadvantageous to the poor. The contribution rate of socioeconomic factors was the largest (60.8%), followed by demographic characteristics (29.0%) and geographic factors (4.3%). Demographic, socioeconomic, and geographic factors are associated with the HB awareness inequality. Therefore, to reduce inequality, HB-related health education targeting individuals with low socioeconomic status should be performed. Less-developed provinces, especially with high proportions of poor residents, warrant particular attention. Our findings may be beneficial to improve the HB virus vaccination rate for individuals with low socioeconomic status. PMID:28277091

The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators

PubMed Central

Johansson, Maria E.; Edström-Hägerwall, Anneli; Larsson, Irene; Jälmby, Maya; Hansson, Stefan R.; Åkerström, Bo

2015-01-01

Preeclampsia (PE) complicates 3–8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme defense network. Thus, we have investigated the levels of cell-free HbF (both free, denoted HbF, and in complex with Hp, denoted Hp-HbF) as well as the major human endogenous Hb- and heme-scavenging systems: haptoglobin (Hp), hemopexin (Hpx), α1-microglobulin (A1M) and CD163 in plasma of PE women (n = 98) and women with normal pregnancies (n = 47) at term. A significant increase of the mean plasma HbF concentration was observed in women with PE. Plasma levels of Hp and Hpx were statistically significantly reduced, whereas the level of the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE. The Hpx levels significantly correlated with maternal blood pressure. Furthermore, HbF and the related scavenger proteins displayed a potential to be used as clinical biomarkers for more precise diagnosis of PE and are candidates as predictors of identifying pregnancies with increased risk of obstetrical complications. The results support that PE pathophysiology is associated with increased HbF-concentrations and an activation of the physiological Hb-heme defense systems. PMID:26368565

Measurement of percent oxyhemoglobin by optical densitometry in perfluorocarbon supplemented blood.

PubMed

Murrah, C P; Agnihotri, A K; Spruell, R D; Clymer-Hawk, J J; Ferguson, E R; Wiley, J H; Holman, W L

1996-01-01

A new generation of perfluorocarbon emulsions is being clinically evaluated as erythrocyte substitutes. However, the effect of perfluorocarbon emulsions on optical densitometric measurements of percent oxyhemoglobin (%O2Hb) has not been fully characterized. The purpose of this study is to quantify the effect of blood perfluorochemical concentration and hematocrit (Hct) on %O2Hb measurements. The authors hypothesize that perfluorocarbon emulsions affect the accuracy of %O2Hb measurements, and that the effect of perfluorochemical concentration and Hct on these measurements can be mathematically described. Porcine blood was used in this experiment. Blood with a Hct of 18% or 9% was mixed with a perfluorocarbon emulsion (Oxygent [AF0142]; Alliance Pharmaceutical Corporation, San Diego, CA). The concentrations tested were 0 g (Group I; n = 69 measurements for a Hct of 18%, and n = 35 measurements for a Hct of 9%), 0.73 g (Group II; n = 47 at 18%, n = 33 at 9%), 1.45 g (Group III; n = 46 at 18%, n = 30 at 9%), and 2.90 g (Group IV; n = 45 at 18%, n = 31 at 9%) of perfluorochemical per deciliter of blood (g PFC/dl). A tonometer was used to establish a range of oxygen tensions within each group while maintaining physiologic pH and PCO2. Error in %O2Hb measurements increases with higher perfluorochemical concentrations and lower Hct values. These errors in %O2Hb measurements are predictable; as such, an equation for correcting %O2Hb measurements in perfluorocarbon supplemented blood can be generated.

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

PubMed

Hughes, J T; Barzi, F; Hoy, W E; Jones, G R D; Rathnayake, G; Majoni, S W; Thomas, M A B; Sinha, A; Cass, A; MacIsaac, R J; O'Dea, K; Maple-Brown, L J

2017-12-01

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m 2 . Median bilirubin concentration was lower in females than males (6 v 8μmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5μmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hemoglobin–Albumin Cluster Incorporating a Pt Nanoparticle: Artificial O2 Carrier with Antioxidant Activities

PubMed Central

Hosaka, Hitomi; Haruki, Risa; Yamada, Kana; Böttcher, Christoph; Komatsu, Teruyuki

2014-01-01

A covalent core–shell structured protein cluster composed of hemoglobin (Hb) at the center and human serum albumins (HSA) at the periphery, Hb-HSAm, is an artificial O2 carrier that can function as a red blood cell substitute. Here we described the preparation of a novel Hb-HSA3 cluster with antioxidant activities and its O2 complex stable in aqueous H2O2 solution. We used an approach of incorporating a Pt nanoparticle (PtNP) into the exterior HSA unit of the cluster. A citrate reduced PtNP (1.8 nm diameter) was bound tightly within the cleft of free HSA with a binding constant (K) of 1.1×107 M−1, generating a stable HSA-PtNP complex. This platinated protein showed high catalytic activities for dismutations of superoxide radical anions (O2 •–) and hydrogen peroxide (H2O2), i.e., superoxide dismutase and catalase activities. Also, Hb-HSA3 captured PtNP into the external albumin unit (K = 1.1×107 M−1), yielding an Hb-HSA3(PtNP) cluster. The association of PtNP caused no alteration of the protein surface net charge and O2 binding affinity. The peripheral HSA-PtNP shell prevents oxidation of the core Hb, which enables the formation of an extremely stable O2 complex, even in H2O2 solution. PMID:25310133

Factors affecting poly(3-hydroxybutyrate) production from oil palm frond juice by Cupriavidus necator (CCUG52238(T)).

PubMed

Mohd Zahari, Mior Ahmad Khushairi; Ariffin, Hidayah; Mokhtar, Mohd Noriznan; Salihon, Jailani; Shirai, Yoshihito; Hassan, Mohd Ali

2012-01-01

Factors influencing poly(3-hydroxybutyrate) P(3HB) production by Cupriavidus necator CCUG52238(T) utilizing oil palm frond (OPF) juice were clarified in this study. Effects of initial medium pH, agitation speed, and ammonium sulfate (NH(4))(2)SO(4) concentration on the production of P(3HB) were investigated in shake flasks experiments using OPF juice as the sole carbon source. The highest P(3HB) content was recorded at pH 7.0, agitation speed of 220 rpm, and (NH(4))(2)SO(4) concentration at 0.5 g/L. By culturing the wild-type strain of C. necator under the aforementioned conditions, the cell dry weight (CDW) and P(3HB) content obtained were 9.31 ± 0.13 g/L and 45 ± 1.5 wt.%, respectively. This accounted for 40% increment of P(3HB) content compared to the nonoptimized condition. In the meanwhile, the effect of dissolved oxygen tension (DOT) on P(3HB) production was investigated in a 2-L bioreactor. Highest CDW (11.37 g/L) and P(3HB) content (44 wt.%) were achieved when DOT level was set at 30%. P(3HB) produced from OPF juice had a tensile strength of 40 MPa and elongation at break of 8% demonstrated that P(3HB) produced from renewable and cheap carbon source is comparable to those produced from commercial substrate.

Total haemoglobin mass, but not haemoglobin concentration, is associated with preoperative cardiopulmonary exercise testing-derived oxygen-consumption variables.

PubMed

Otto, J M; Plumb, J O M; Wakeham, D; Clissold, E; Loughney, L; Schmidt, W; Montgomery, H E; Grocott, M P W; Richards, T

2017-05-01

Cardiopulmonary exercise testing (CPET) measures peak exertional oxygen consumption ( V˙O2peak ) and that at the anaerobic threshold ( V˙O2 at AT, i.e. the point at which anaerobic metabolism contributes substantially to overall metabolism). Lower values are associated with excess postoperative morbidity and mortality. A reduced haemoglobin concentration ([Hb]) results from a reduction in total haemoglobin mass (tHb-mass) or an increase in plasma volume. Thus, tHb-mass might be a more useful measure of oxygen-carrying capacity and might correlate better with CPET-derived fitness measures in preoperative patients than does circulating [Hb]. Before major elective surgery, CPET was performed, and both tHb-mass (optimized carbon monoxide rebreathing method) and circulating [Hb] were determined. In 42 patients (83% male), [Hb] was unrelated to V˙O2 at AT and V˙O2peak ( r =0.02, P =0.89 and r =0.04, P =0.80, respectively) and explained none of the variance in either measure. In contrast, tHb-mass was related to both ( r =0.661, P <0.0001 and r =0.483, P =0.001 for V˙O2 at AT and V˙O2peak , respectively). The tHb-mass explained 44% of variance in V˙O2 at AT ( P <0.0001) and 23% in V˙O2peak ( P =0.001). In contrast to [Hb], tHb-mass is an important determinant of physical fitness before major elective surgery. Further studies should determine whether low tHb-mass is predictive of poor outcome and whether targeted increases in tHb-mass might thus improve outcome. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Anaemia, iron deficiency and a common polymorphism of iron-regulation, TMPRSS6 rs855791, in Rwandan children.

PubMed

Danquah, Ina; Gahutu, Jean-Bosco; Zeile, Irene; Musemakweri, Andre; Mockenhaupt, Frank P

2014-01-01

Anaemia in children living in sub-Saharan Africa is common, but its causes are diverse. In 545 children below 5 years of age from rural southern Rwanda, we assessed the role of iron deficiency (ID) and of the TMPRSS6 736(V) (rs855791) allele, known to reduce iron status and haemoglobin (Hb) levels, in anaemia and Hb concentrations. Anaemia (Hb <11 g/dl) was present in 34.4% of the children and ID (ferritin <12 ng/ml) in 17.6%. The TMPRSS6 736(V) allele was uncommon (allele frequency, 0.096) and not associated with ID. In multivariate analysis, ID was positively associated with anaemia (adjusted odds ratio, 1.67) to an extent comparable with α(+) -thalassaemia, breastfeeding, inflammation and low household income, but the odds were substantially higher in Plasmodium falciparum infection (adjusted odds ratio, 10.3). These findings were verified in a multivariate analysis of Hb concentrations. The TMPRSS6 736(V) allele only tended to be associated with low Hb levels. TMPRSS6 736(V) is comparatively rare among Rwandan children and may only slightly contribute to low Hb concentrations. Preventable causes of anaemia, notably ID and P. falciparum infection, largely outweigh its impact and need to be addressed to improve the haematological status of children in the study area. © 2013 John Wiley & Sons Ltd.

A prospective study about the preoperative total blood loss in older people with hip fracture.

PubMed

Wu, Jie-Zhou; Liu, Peng-Cheng; Ge, Wei; Cai, Ming

2016-01-01

Our study is to confirm that hemoglobin (Hb) level is significantly reduced before operation in elderly patients with hip fracture and to specify potential amounts of bleeding and Hb decline in different types of fractures. A prospective analysis was made on the clinical data of 349 patients with both a diagnosis of hip fracture and an operative delay of greater than 72 hours between April 2014 and February 2016. Hb concentration was measured on a daily basis before the surgery. Patients were grouped according to the type of fracture (intracapsular and extracapsular) for calculation of the total blood loss (TBL). All data analyses were done by SPSS version 21 software. There was a significant decrease preoperatively in the Hb concentration of nearly 21.55 g/L (standard error of the mean [SEM] 7.67) in patients with extracapsular hip fractures and nearly 15.63 g/L (SEM 6.01) in patients with intracapsular hip fractures. The preoperative TBL in patients with extracapsular fracture was significantly larger compared to that in patients with intracapsular fracture (790.3 mL and 581.7 mL, respectively, P <0.05 using Student's t -test). We found no significant difference in the preoperative TBL between the male and female groups. Hip fracture patients have an obvious blood loss after the injury, yet prior to the surgery the Hb levels were found to be normal. Anesthetic and orthopedic staff should pay additional attention to the problem of low preoperative Hb concentration, even if the initial Hb level was apparently normal.

Lifetime exposure to low doses of lead in rats: effect on selected parameters of carbohydrate metabolism.

PubMed

Nováková, Jaroslava; Lukačínová, Agnesa; Lovásová, Eva; Cimboláková, Iveta; Rácz, Oliver; Ništiar, František

2015-05-01

The aim of the study was to assess the effects of exposure to low doses of lead dissolved in drinking water (average daily dose of 2.2 mg kg(-1) day(-1)) on selected carbohydrate metabolism parameters in 20 wistar rats. Animals were divided into two groups - control (C) (group drinking clear water) and experimental group (Pb; group exposed to low doses of lead acetate in a concentration of 100 μmol l(-1) of drinking water). In this study, we studied the biochemical parameters (glucose, haemoglobin (Hb), glycated haemoglobin (HbA1c), lactate dehydrogenase (LDH) and amylase (AMS)) in rat blood. Glucose and Hb concentration and AMS activity decreased, LDH activity increased but HbA1c concentration levels did not change in rats exposed to lead. Our results well documented that lifetime exposure to lead affected carbohydrate metabolism of rats. Some parameters like concentration of Hb as well as activities of AMS and LDH are useful markers of intoxication of rats with lead. For the evaluation of results (e.g. AMS), not only the data at the end of the experiment should be taken into account but also the entire duration of trials (i.e. more time steps) that makes results more objective should be considered. © The Author(s) 2013.

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

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

Purification, characterization, and crystallization of Crocodylus siamensis hemoglobin.

PubMed

Jandaruang, Jinda; Siritapetawee, Jaruwan; Songsiriritthigul, Chomphunuch; Preecharram, Sutthidech; Azuma, Taoka; Dhiravisit, Apisak; Fukumori, Yoshihiro; Thammasirirak, Sompong

2014-08-01

Crocodylus siamensis hemoglobin was purified by a size exclusion chromatography, Sephacryl S-100 with buffer containing dithiothreitol. The purified Hb was dissociated to be two forms (α chain and β chain) which observed by SDS-PAGE, indicated that the C. siamensis Hb was an unpolymerized form. The unpolymerized Hb (composed of two α chains and two β chains) showed high oxygen affinity at 3.13 mmHg (P(50)) and 1.96 (n value), and a small Bohr effect (δH(+) = -0.29) at a pH of 6.9-8.4. Adenosine triphosphate did not affect the oxygenation properties, whereas bicarbonate ions strongly depressed oxygen affinity. Crude C. siamensis Hb solutions were showed high O(2) affinity at P(50) of 2.5 mmHg which may assure efficient utilization of the lung O(2) reserve during breath holding and diving. The purified Hbs were changed to cyanmethemoglobin forms prior crystallization. Rod- and plate-shaped crystals were obtained by the sitting-drop vapor-diffusion method at 5 °C using equal volumes of protein solution (37 mg/ml) and reservoir [10-13 % (w/v) PEG 4000, with 0.1 M Tris buffer in present of 0.2 M MgCl(2)·6H(2)O] solution at a pH of 7.0-8.5.

Determination of filter pore size for use in HB line phase II production of plutonium oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shehee, T.; Crowder, M.; Rudisill, T.

2014-08-01

H-Canyon and HB-Line are tasked with the production of plutonium oxide (PuO 2) from a feed of plutonium (Pu) metal. The PuO 2 will provide feed material for the Mixed Oxide (MOX) Fuel Fabrication Facility. After dissolution of the Pu metal in H-Canyon, plans are to transfer the solution to HB-Line for purification by anion exchange. Anion exchange will be followed by plutonium(IV) oxalate precipitation, filtration, and calcination to form PuO 2. The filtrate solutions, remaining after precipitation, contain low levels of Pu ions, oxalate ions, and may include solids. These solutions are transferred to H-Canyon for disposition. To mitigatemore » the criticality concern of Pu solids in a Canyon tank, past processes have used oxalate destruction or have pre-filled the Canyon tank with a neutron poison. The installation of a filter on the process lines from the HB-Line filtrate tanks to H-Canyon Tank 9.6 is proposed to remove plutonium oxalate solids. This report describes SRNL’s efforts to determine the appropriate pore size for the filters needed to perform this function. Information provided in this report aids in developing the control strategies for solids in the process.« less

Predicting Human Subcutaneous Glucose Concentration in Real Time: A Universal Data-Driven Approach

DTIC Science & Technology

2011-09-01

insulin for at least 12 mo, and had glycated hemoglobin ( HbA1c ) >6.1%. In the Guardian study, subjects were included if they were between 3 and 7 yr...old or between 12 and 18 yr old, had been diagnosed with type 1 diabetes for more than 1 yr, had been using an insulin pump, and had HbA1c ≤ 10.0...oral agents, basal insulin, or both for at least 3 mo, and had HbA1c between 7% and 12%. Predicting Human Subcutaneous Glucose Concentration in

Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis.

PubMed

Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

2010-10-01

The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis.

Effect of intravenous infusion of an alpha-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold pressor stimulation.

PubMed

Maekawa, K; Kuboki, T; Miyawaki, T; Shimada, M; Yamashita, A; Clark, G T

1999-04-01

This study evaluated the effect of intravenous infusion of a non-selective alpha-adrenergic blocking agent on masseter muscle haemodynamics induced by 4 degrees C cold pressor stimulation (CPS) of the right foot and ankle, which reportedly evokes a rapidly increasing sympathetic nerve activity in human skeletal muscle. Nine healthy non-smoking males (mean age 23.7+/-2.1 year) with no history of chronic muscle pain or migraine participated. The haemoglobin (Hb) concentration in the right masseter was continuously recorded by non-invasive, near-infrared spectroscopy. Heart rate and blood pressure were also recorded. The experiment involved the following sequence: (1) a placebo (physiological saline) with a CPS trial; (2) a 30-sec maximal voluntary clenching (MVC)-only trial; and (3) an alpha-adrenergic blocking agent with a CPS trial. The saline and drug trials each involved continuous recording for 1 min before, 2 min during and 5 min after the CPS. Physiological saline (20 ml) or phentolamine mesylate (20 ml) were infused at the rate of 2 ml/min. This infusion was begun 15 min before baseline recording and participants were not aware which solution (saline or phentolamine) was being infused. For the MVC trial, each participant performed a 30-sec MVC of his jaw-closing muscles followed by a 15-min rest between each trial. The individual Hb data were adjusted so that the baseline at the beginning of the experiment was equal to zero and all data were normalized as a percentage of the individual's highest absolute Hb change seen after the MVC. The mean baseline Hb concentrations 1 min before CPS were significantly higher in the alpha-blocker trial (83.6%) than in the placebo saline trial (P < 0.001). The change in mean Hb concentration from baseline during CPS in the alpha-blocker trial was significantly less than in the placebo trial (P = 0.006). Mean heart rate before CPS was also significantly higher in the alpha-blocker trial (85.2 beats/min) than in the placebo trial (69.6 beats/min) (P < 0.001). There were no significant differences in the mean systolic and diastolic blood pressures between the placebo and alpha-blocker trials in any time period. The results suggest that non-selective alpha-adrenoceptor blockade increases the blood volume in the masseter muscle. This change might be due to a combination of peripheral vasodilation and an increase in cardiac output.

Effects of quercetin on hemoglobin-dependent redox reactions: relationship to iron-overload rat liver injury.

PubMed

Lu, Nai-Hao; Chen, Chao; He, Ying-Jie; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

2013-01-01

Flavonoids have been widely reported to protect liver injury in iron-overload diseases, where the mechanism of this therapeutic action is dependent on their antioxidant effects, including free radical scavenging and metal-chelating. In this study, in contrast to the significant decrease in iron content, quercetin (Qu) from lower diet (0.3%, w/w) showed pro-oxidant ability on protein carbonyl formation and exhibited unobvious effect on iron-overload rat liver injury. Furthermore, the anti- and pro-oxidant activities of Qu on hemoglobin (Hb)-dependent redox reactions (i.e. the oxidative stability of Hb and its cytotoxic ferryl intermediate, Hb-induced protein oxidation) were investigated to illustrate the elevated protein oxidation in lower Qu-treated iron-overload rat. It was found that superoxide (O₂·⁻) and hydrogen peroxide (H₂O₂) were generated during the reaction between Qu and Hb. Qu, however, effectively reduced ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. Moreover, Qu could significantly aggravate Hb-H₂O₂-induced protein oxidation at low concentrations and exhibit protective effects at high concentrations. Different from the classic antioxidant mechanisms of Qu, the dual effects on Hb redox reactions in vitro, therefore, may provide new insights into the physiological and pharmacological implications of Qu with iron-overload disease.

The accuracy of noninvasive hemoglobin monitoring using the radical-7 pulse CO-Oximeter in children undergoing neurosurgery.

PubMed

Park, Yong-Hee; Lee, Ji-Hyun; Song, Hyun-Gul; Byon, Hyo-Jin; Kim, Hee-Soo; Kim, Jin-Tae

2012-12-01

The most common method for determining the hemoglobin concentration is to draw blood from a patient. However, the Radical-7 Pulse CO-Oximeter (Masimo Corporation, Irvine, CA) can noninvasively provide continuous hemoglobin concentration (SpHb). In our study we compared noninvasive measurements of SpHb with simultaneous laboratory measurements of total hemoglobin in arterial blood samples taken from children (tHb). Arterial blood samples were analyzed using a laboratory CO-oximeter, and SpHb was simultaneously recorded in pediatric patients undergoing neurosurgery. When patients met the criteria for hypovolemia, 10 mL/kg of colloids or red blood cells were administered over 10 minutes. SpHb and tHb data were collected before and after intravascular volume resuscitation. The relationship between SpHb and tHb was assessed using a 4-quadrant plot, linear regression, mixed-effect model, and modified Bland-Altman analyses. One hundred nineteen paired samples were analyzed. The correlation coefficient between SpHb and tHb was 0.53 (P < 0.001), whereas that of change in SpHb versus change in tHb was 0.75 (P < 0.001). The average difference (bias) between tHb and SpHb was 0.90 g/dL (95% confidence interval [CI], 0.48-1.32 g/dL) and 1 standard deviation of the difference (sd) was 1.35 g/dL. The concordance rate (a measure of the number of data points that are in 1 of the 2 quadrants of agreement) determined using a 4-quadrant plot was 93%. The correlation coefficient between SpHb and tHb after intravascular volume resuscitation was 0.58 (P < 0.001), whereas that of changes in SpHb and tHb was 0.87 (P < 0.001). The bias immediately after volume resuscitation was 1.18 g/dL (95% CI, 0.81-1.55 g/dL), and sd was 1.28 g/dL with a concordance rate of 94.4%. The bias was -0.03 g/dL when tHb was ≥11 g/dL, which was significantly lower in comparison with biases when tHb <9 g/dL (1.24 g/dL) and tHb was 9-11 g/dL (1.17 g/dL) (P = 0.004). The Radical-7 Pulse CO-Oximeter can be useful as a trend monitor in children during surgery even immediately after intravascular volume expanders are administered. However, it is advisable to confirm the baseline hemoglobin level and to consider the influence of tHb level on the bias. In addition, one should be cautious with regard to using SpHb alone when making transfusion decisions.

Prevalence of Anemia and Hemoglobin Disorders Among School Children in Myanmar.

PubMed

Wah, Saw Thu; Yi, Yoon Shwe; Khin, Aye Aye; Plabplueng, Chotiros; Nuchnoi, Pornlada

2017-01-01

The prevalence of anemia is high in the population of Myanmar and hypochromic microcytic anemia (HMA) is predominant. The objective of our study was to determine the prevalence of anemia and causes of HMA among school children. A cross-sectional study was conducted on 239 children from Thanlyin and Insein Townships, Yangon Region, Myanmar. Complete blood count (CBC) and blood film morphology was examined on venous blood samples. Hypochromic microcytic anemia cases were subsequently analyzed for serum ferritin and cellulose acetate hemoglobin (Hb) electrophoresis. The prevalence of anemia was 46.4%; 27.6% had mild, while 18.8% had moderate anemia, and no case of severe anemia was detected. The mean Hb concentration was 11.7 ± 0.9 g/dL. The younger age group (8-11 years) had a significantly higher prevalence of anemia than the older age group (12-15 years) (p = 0.029). Blood film morphology revealed a 50.6% red blood cell (RBC) disorder; HMA was the most common type (70.2%). Out of 85 children with HMA, three children (3.5%) had iron deficiency and all had comorbidity with Hb AE (β A /β E ) (Hb E trait). Hemoglobin electrophoresis illustrated that Hb AA (β A /β A ) (31, 36.5%) and Hb AE (β A /β E ) trait (31, 36.5%) were the most common types followed by β-thalassemia (β-thal) trait (19, 22.3%) and Hb EE (β E /β E ) (homozygous Hb E; HBB: c.79G>A) (three, 3.5%). Hematocrit [or packed cell volume (PCV)], mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC), showed a significant difference between Hb AE, Hb EE and β-thal trait (p = 0.029, 0.023, 0.015 and 0.01, respectively). Our findings will provide valuable information for the management of anemia in the Myanmar school-age population.

Factors Affecting Poly(3-hydroxybutyrate) Production from Oil Palm Frond Juice by Cupriavidus necator (CCUG52238T)

PubMed Central

Mohd Zahari, Mior Ahmad Khushairi; Ariffin, Hidayah; Mokhtar, Mohd Noriznan; Salihon, Jailani; Shirai, Yoshihito; Hassan, Mohd Ali

2012-01-01

Factors influencing poly(3-hydroxybutyrate) P(3HB) production by  Cupriavidus necator  CCUG52238T utilizing oil palm frond (OPF) juice were clarified in this study. Effects of initial medium pH, agitation speed, and ammonium sulfate (NH4)2SO4 concentration on the production of P(3HB) were investigated in shake flasks experiments using OPF juice as the sole carbon source. The highest P(3HB) content was recorded at pH 7.0, agitation speed of 220 rpm, and (NH4)2SO4 concentration at 0.5 g/L. By culturing the wild-type strain of C. necator under the aforementioned conditions, the cell dry weight (CDW) and P(3HB) content obtained were 9.31 ± 0.13 g/L and 45 ± 1.5 wt.%, respectively. This accounted for 40% increment of P(3HB) content compared to the nonoptimized condition. In the meanwhile, the effect of dissolved oxygen tension (DOT) on P(3HB) production was investigated in a 2-L bioreactor. Highest CDW (11.37 g/L) and P(3HB) content (44 wt.%) were achieved when DOT level was set at 30%. P(3HB) produced from OPF juice had a tensile strength of 40 MPa and elongation at break of 8% demonstrated that P(3HB) produced from renewable and cheap carbon source is comparable to those produced from commercial substrate. PMID:23133311

Gold nanoparticles-coated magnetic microspheres as affinity matrix for detection of hemoglobin A1c in blood by microfluidic immunoassay.

PubMed

Chen, Shao-Peng; Yu, Xiao-Dong; Xu, Jing-Juan; Chen, Hong-Yuan

2011-08-15

A novel microfluidic immunoassay system for specific detection of hemoglobin A1c (HbA1c) was developed based on a three-component shell/shell/core structured magnetic nanocomposite Au/chitosan/Fe(3)O(4), which was synthesized with easy handling feature of Fe(3)O(4) by magnet, high affinity for gold nanoparticles of chitosan and good immobilization ability for anti-human hemoglobin-A1c antibody (HbA1c mAb) of assembled colloidal gold nanoparticles. The resulting HbA1c mAb/Au/chitosan/Fe(3)O(4) magnetic nanoparticles were then introduced into microfluidic devices coupled with a gold nanoband microelectrode as electrochemical detector. After that, three-step rapid immunoreactions were carried out in the sequence of HbA1c, anti-human hemoglobin antibodies (Hb mAb) and the secondary alkaline phosphatase (AP)-conjugated antibody within 20 min. The current response of 1-naphtol obtained from the reaction between the secondary AP-conjugated antibody and 1-naphthyl phosphate (1-NP) increased proportionally to the HbA1c concentration. Under optimized electrophoresis and detection conditions, HbA1c responded linearly in the concentration of 0.05-1.5 μg mL(-1), with the detection limit of 0.025 μg mL(-1). This system was successfully employed for detection of HbA1c in blood with good accuracy and renewable ability. The proposed method proved its potential use in clinical immunoassay of HbA1c. Copyright © 2011 Elsevier B.V. All rights reserved.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes.

PubMed

Ford, Earl S; Wheaton, Anne G; Chapman, Daniel P; Li, Chaoyang; Perry, Geraldine S; Croft, Janet B

2014-07-01

There is limited information from population-based investigations of the associations between sleep duration and sleep disorders and parameters of glucose homeostasis. The objective of the present study was to examine cross-sectional associations between sleep duration and sleep disordered breathing with concentrations of insulin, fasting and 2-h glucose, and HbA1c. Data from 11 815 adults aged ≥20 years without diagnosed diabetes (5002 with an oral glucose tolerance test) from the National Health and Nutrition Examination Survey 2005-2010 were used. Information about sleep duration (2005-2010) and sleep apnea and sleep-disordered breathing (2005-2008) was obtained via questionnaire. An estimated 36.0% of participants reported sleeping ≤6 h/night, 62.0% reported sleeping 7-9 h/night, and 2.0% reported sleeping ≥10 h/night. In 2005-2008, 33.0% reported snoring ≥5 nights per week, 5.9% reported they snorted, gasped, or stopped breathing ≥5 nights/week, and 4.2% reported sleep apnea. Sleep duration was significantly associated with fasting concentrations of insulin and concentrations of HbA1c only in models that did not adjust for body mass index (BMI). Concentrations of fasting and 2-h glucose were significantly associated with sleep duration in models that adjusted only for age. Snoring frequency was positively associated with concentrations of insulin and HbA1c. Frequency of snorting or stopping breathing and sleep apnea status were associated with concentrations of insulin and of HbA1c only when BMI was not accounted for. In a representative sample of US adults, concentrations of insulin and HbA1c were significantly associated with short sleep duration, possibly mediated by BMI. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Differential effect of blood collection tubes on total free fatty acids (FFA) and total triiodothyronine (TT3) concentration: a model for studying interference from tube constituents.

PubMed

Bowen, Raffick A R; Vu, Chi; Remaley, Alan T; Hortin, Glen L; Csako, Gyorgy

2007-03-01

Besides total triiodothyronine (TT3), total free fatty acids (FFA) concentrations were higher with serum separator tube (SST) than Vacuette tubes. The effects of surfactant, rubber stopper, and separator gel from various tubes were investigated on FFA, beta-hydroxybutyrate (beta-HB), and TT3 with 8 different tube types in blood specimens of apparently healthy volunteers. Compared to Vacuette tubes, serum FFA and TT3 concentrations were significantly higher in SST than glass tubes. Reformulated SST eliminated the increase in TT3 but not FFA. No significant difference was observed for beta-HB concentration among tube types. Surfactant and rubber stoppers from the different tube types significantly increased TT3 but not FFA and beta-HB concentrations. Agitation of whole blood but not serum or plasma specimens with separator gel from SST, reformulated SST and plasma preparation tube (PPT) tubes compared to Vacuette tubes gave higher FFA but not beta-HB levels. Unidentified component(s) from the separator gel in SST, reformulated SST and PPT tubes cause falsely high FFA concentration. In contrast to TT3, falsely high FFA results require exposure of whole blood and not serum to tube constituent(s). The approach employed here may serve as a model for assessing interference(s) from tube constituent(s).

Familial congenital cyanosis caused by Hb-MYantai(α-76 GAC → TAC, Asp → Tyr)

PubMed Central

2010-01-01

Methemoglobin (Hb-M) is a rare hemoglobinopathy in China. We hereby report on a family living in Yantai, East China, with congenital cyanosis due to Hb-M mutation. The proband, a 65-year-old female, presented 63% oxygen saturation. Both Hb-M concentration and arterial oxygen saturation remained unchanged, even following intravenous treatment with methylene blue. There was also no change in blood-color (chocolate-brown) after adding 0.1% KCN. A fast-moving band (Hb-X) in hemolysates was found by cellulose acetate electrophoresis, the Hb-X/Hb-A ratio exceeding 10%. GT transition at 131nt of exon 2, although present in one of the α2 -globin alleles, was not found in α1 -globin alleles as a whole. This mutation leads to the aspartic acid to tyrosine substitution (Asp76Tyr). In this family, the novel mutation in the α2 -globin gene resulted in a rare form of congenital cyanosis due to Hb-M. This hemoglobin was named Hb-M Yantai . PMID:21637412

[Hemodynamic activities in children with autism while imitating emotional facial expressions: a near-infrared spectroscopy study].

PubMed

Mori, Kenji; Mori, Tatsuo; Goji, Aya; Ito, Hiromichi; Toda, Yoshihiro; Fujii, Emiko; Miyazaki, Masahito; Harada, Masafumi; Kagami, Shoji

2014-07-01

To examine the hemodynamic activities in the frontal lobe, children with autistic disorder and matched controls underwent near-infrared spectroscopy (NIRS) while imitating emotional facial expressions. The subjects consisted of 10 boys with autistic disorder without mental retardation (9 - 14 years) and 10 normally developing boys (9 - 14 years). The concentrations of oxyhemoglobin (oxy-Hb) were measured with frontal probes using a 34-channel NIRS machine while the subjects imitated emotional facial expressions. The increments in the concentration of oxy-Hb in the pars opercularis of the inferior frontal gyrus in autistic subjects were significantly lower than those in the controls. However, the concentrations of oxy-Hb in this area were significantly elevated in autistic subjects after they were trained to imitate emotional facial expressions. The increments in the concentration of oxy-Hb in this area in autistic subjects were positively correlated with the scores on a test of labeling emotional facial expressions. The pars opercularis of the inferior frontal gyrus is an important component of the mirror neuron system. The present results suggest that mirror neurons could be activated by repeated imitation in children with autistic disorder.

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.

Influence of Electromagnetic Fields on Lead Toxicity: A Study of Conformational Changes in Human Blood Proteins

PubMed Central

Ansarihadipour, Hadi; Bayatiani, Mohamadreza

2016-01-01

Background Electromagnetic fields (EMF) are associated with oxidative stress, which is in turn associated with reactive oxygen species (ROS), anemia, and hypoxia. Objectives This study focused on the synergistic effects of lead ions and EMF on oxidative modifications in hemoglobin (Hb) and plasma proteins. Patients and Methods In this experimental study, the blood samples were obtained from age- and sex-matched healthy subjects at Arak University of Medical Sciences, Arak, Iran. The collected bloods were prepared as 55 samples and then divided into different groups for incubating with 0 to 100 uM of lead ions in 2 mT and 50 Hz of EMF for 120 minutes. The carbonyl group was determined to be an oxidative biomarker in plasma proteins. The ferric reducing ability of plasma (FRAP) was considered to be an antioxidant power of human plasma. The conformational changes in hemoglobin, met-Hb, and hemichrome were considered to be oxidative markers in red blood cells. To predict the factors affecting the oxyHb, the artificial neural network (MLP: 11,2,2,1) in SPSS software was applied. Results The test subjects showed increased concentrations of metHb (1.8 ± 0.19 vs. 1.36 ± 0.25) and hemichrome (6.01 ± 0.57) in relation to the control subjects. The decreased absorbance at 340 nm (0.88 ± 0.09 vs. 1.07 ± 0.08) demonstrated the reduced interaction between the globin chain and the heme ring. The decreased absorbance at 420 nm (Soret band) (2.96 ± 0.13) and the increased absorbance at 630 nm (0.07 ± 0.002 vs. 0.064 ± 0.005) indicated the conversion of oxyHb to metHb, which confirmed the oxidative damage to the erythrocytes. The linear regression analysis showed significant positive correlations between lead concentration and the percentage of plasma carbonyl content (R2 = 0.96), the relation of plasma carbonyl content to Hb absorbance at 630 nm (R2 = 0.97), and the relation of plasma carbonyl content to metHb concentration (R2 = 0.95) after 120 minutes incubation with lead ions in 20 millitesla and 50 hertz EMF. The artificial neural network analysis showed the significant importance of hemichrome, PCO, metHb, and lead concentration to the oxyHb content of erythrocytes. Conclusions Lead contamination in the presence of an EMF exacerbates the oxidative damage to plasma proteins as well as the conformational changes in Hb. An artificial neural network can be used as a predictive tool for the oxidative danger posed to workers in industrial fields, battery manufacturing companies, and power plants. PMID:27651951

Thermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics

PubMed Central

Stadler, A. M.; Garvey, C. J.; Bocahut, A.; Sacquin-Mora, S.; Digel, I.; Schneider, G. J.; Natali, F.; Artmann, G. M.; Zaccai, G.

2012-01-01

Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the β-subunits. PMID:22696485

Thermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics.

PubMed

Stadler, A M; Garvey, C J; Bocahut, A; Sacquin-Mora, S; Digel, I; Schneider, G J; Natali, F; Artmann, G M; Zaccai, G

2012-11-07

Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the β-subunits.

Diffuse optical tomography changes correlate with residual cancer burden after neoadjuvant chemotherapy in breast cancer patients.

PubMed

Lim, Emerson A; Gunther, Jacqueline E; Kim, Hyun K; Flexman, Molly; Hibshoosh, Hanina; Crew, Katherine; Taback, Bret; Campbell, Jessica; Kalinsky, Kevin; Hielscher, Andreas; Hershman, Dawn L

2017-04-01

Breast cancer (BC) patients who achieve a favorable residual cancer burden (RCB) after neoadjuvant chemotherapy (NACT) have an improved recurrence-free survival. Those who have an unfavorable RCB will have gone through months of ineffective chemotherapy. No ideal method exists to predict a favorable RCB early during NACT. Diffuse optical tomography (DOT) is a novel imaging modality that uses near-infrared light to assess hemoglobin concentrations within breast tumors. We hypothesized that the 2-week percent change in DOT-measured hemoglobin concentrations would associate with RCB. We conducted an observational study of 40 women with stage II-IIIC BC who received standard NACT. DOT imaging was performed at baseline and 2 weeks after treatment initiation. We evaluated the associations between the RCB index (continuous measure), class (categorical 0, I, II, III), and response (RCB class 0/I = favorable, RCB class II/III = unfavorable) with changes in DOT-measured hemoglobin concentrations. The RCB index correlated significantly with the 2-week percent change in oxyhemoglobin [HbO 2 ] (r = 0.5, p = 0.003), deoxyhemoglobin [Hb] (r = 0.37, p = 0.03), and total hemoglobin concentrations [HbT] (r = 0.5, p = 0.003). The RCB class and response significantly associated with the 2-week percent change in [HbO 2 ] (p ≤ 0.01) and [HbT] (p ≤ 0.02). [HbT] 2-week percent change had sensitivity, specificity, positive, and negative predictive values for a favorable RCB response of 86.7, 68.4, 68.4, and 86.7%, respectively. The 2-week percent change in DOT-measured hemoglobin concentrations was associated with the RCB index, class, and response. DOT may help guide NACT for women with BC.

Complete factorial design to adjust pH and sugar concentrations in the inoculum phase of Ralstonia solanacearum to optimize P(3HB) production

PubMed Central

Alves, Mariane Igansi; Rodrigues, Amanda Ávila; Furlan, Lígia; da Silva Rodrigues, Rosane; Diaz de Oliveira, Patrícia; Vendruscolo, Claire Tondo; da Silveira Moreira, Angelita

2017-01-01

Poly(3-hydroxybutyrate) (P(3HB)) is a biodegradable plastic biopolymer that accumulates as lipophilic inclusions in the cytoplasm of some microorganisms. The biotechnological process by which P(3HB) is synthesized occurs in two phases. The first phase involves cell growth in a complex culture medium, while the second phase involves polymer accumulation in the presence of excess carbon sources. As such, the efficiency of the second phase depends on the first phase. The aim of this study was to evaluate culture media with different concentrations of sucrose and glucose and different pH values in the inoculum phase of Ralstonia solanacearum RS with the intention of identifying methods by which the biomass yield could be increased, subsequently enhancing the yield of P(3HB). The culture medium was formulated according to the experimental planning type of central composite rotational design 22. The independent variables were pH and sugar concentration (sucrose and glucose), and the dependent variables were OD600nm, dry cell weight (DCW), and P(3HB) yield. The highest cell growth, estimated by the OD600nm (20.6) and DCW (5.35) values, was obtained when sucrose was used in the culture medium at a concentration above 35 g.L-1 in combination with an acidic pH. High polymer (45%) accumulation was also achieved under these conditions. Using glucose, the best results for OD600nm (12.5) and DCW (2.74) were also obtained at acidic pH but with a sugar concentration at the minimum values evaluated. Due to the significant accumulation of polymer in the cells that were still in the growth phase, the accumulating microorganism P(3HB) Ralstonia solanacearum RS can be classified as having type II metabolism in relation to the polymer accumulation phase, which is different from other Ralstonia spp. studied until this time. PMID:28704411

Whole Blood Donation Affects the Interpretation of Hemoglobin A1c

PubMed Central

Lenters-Westra, Erna; de Kort, Wim; Bokhorst, Arlinke G.; Bilo, Henk J. G.; Slingerland, Robbert J.; Vos, Michel J.

2017-01-01

Introduction Several factors, including changed dynamics of erythrocyte formation and degradation, can influence the degree of hemoglobin A1c (HbA1c) formation thereby affecting its use in monitoring diabetes. This study determines the influence of whole blood donation on HbA1c in both non-diabetic blood donors and blood donors with type 2 diabetes. Methods In this observational study, 23 non-diabetic blood donors and 21 blood donors with type 2 diabetes donated 475 mL whole blood and were followed prospectively for nine weeks. Each week blood samples were collected and analyzed for changes in HbA1c using three secondary reference measurement procedures. Results Twelve non-diabetic blood donors (52.2%) and 10 (58.8%) blood donors with type 2 diabetes had a significant reduction in HbA1c following blood donation (reduction >-4.28%, P < 0.05). All non-diabetic blood donors with a normal ferritin concentration predonation had a significant reduction in HbA1c. In the non-diabetic group the maximum reduction was -11.9%, in the type 2 diabetes group -12.0%. When eligible to donate again, 52.2% of the non-diabetic blood donors and 41.2% of the blood donors with type 2 diabetes had HbA1c concentrations significantly lower compared to their predonation concentration (reduction >-4.28%, P < 0.05). Conclusion Patients with type 2 diabetes contributing to whole blood donation programs can be at risk of falsely lowered HbA1c. This could lead to a wrong interpretation of their glycemic control by their general practitioner or internist. PMID:28118412

Evaluation of total-dose iron sucrose infusions in patients with iron deficiency anemia.

PubMed

Wall, Geoffrey C; Pauly, Rebecca A

2008-01-15

The safety and efficacy of a total-dose iron sucrose infusion protocol used in a large, tertiary care teaching hospital were studied. Nondialysis-dependent patients ages 18 years or older who received > or =250 mg of iron sucrose as a single i.v. infusion between January 2005 and January 2007 were eligible for study inclusion. The protocol for total-dose iron sucrose infusion was the same for all patients. The total dose of iron sucrose for each patient was calculated using an equation that included the desired hemoglobin (Hb) value, observed Hb level, ideal body weight, and sex. The calculated dose was divided into portions, rounded to the nearest 250 mg, and administered over four hours every other day. Outcomes measured included Hb, transferrin saturation, and serum ferritin values. A total of 26 patients met the inclusion criteria. The mean +/- S.D. Hb concentration before total-dose iron sucrose infusion was 9.37 +/- 0.9 g/dL, and the mean +/- S.D. corpuscular volume was 75 +/- 7.1 mum(3). The mean +/- S.D. postinfusion Hb concentration for 19 patients for whom follow-up Hb levels were available was 11.4 +/- 1.2 g/dL, significantly higher than the 9.45 +/- 0.8 g/dL measured before the first infusion (p = 0.03). No significant adverse effects were reported in 47 of 49 infusions, with 2 patients experiencing mild nausea. A treatment protocol consisting of alternate-day total-dose iron sucrose infusions was well tolerated and appeared to be effective in improving Hb concentrations in patients with iron deficiency anemia and without chronic kidney disease.

Preferential role of iron in heme degradation of hemoglobin upon gamma irradiation.

PubMed

Rafiei, Javad; Yavari, Kamal; Moosavi-Movahedi, Ali A

2017-10-01

It is usually believed that γ-ray interaction with biomolecules is intermediately performed by reactive oxygen species (ROS) produced from radiolysis of water. Hemoglobin (Hb) as one of the most abundant biomolecule in blood and well-studied endogenously affected by ROS, was a good candidate for study. Adult human Hb was extracted and irradiated using four distinct 20, 60, 90 and 170Gy doses from Co-60 γ-ray source. UV-vis, fluorescence and FT-IR spectroscopies were used to study the whole conformational changes and partial degradation of heme. Hb species calculated using Benesch equations indicated that the concentration of oxy-Hb was decreased from 9.97μM to 6.56μM, while the total metastable met and deoxy-Hb concentration were just increased 2.39μM and about 8.4% of total heme was diminished. Heme degradation was studied using fluorescence spectra at two 321 and 460nm excitation wavelengths as fully and partially degradation of heme respectively. Inverse behavior of these two fluorescence spectra suggested a new mechanism of heme degradation in which γ-ray preferably absorbed by heme without any intermediary effects of water. It was confirmed by FT-IR spectra at 900-1000cm -1 where the FeN and NH of porphyrin indicate their own stretching vibrational bands. Thermal stability justified that the gamma radiation induced the conformational changes of Hb which is appeared during thermal unfolding. First derivative of thermal spectra indicated that the Tm of 170Gy dose irradiated sample is 2°C lowered and total concentration of Hb was decreased 14%. Copyright © 2017 Elsevier B.V. All rights reserved.

Fetal hemoglobin, α1-microglobulin and hemopexin are potential predictive first trimester biomarkers for preeclampsia.

PubMed

Anderson, Ulrik Dolberg; Gram, Magnus; Ranstam, Jonas; Thilaganathan, Basky; Kerström, Bo; Hansson, Stefan R

2016-04-01

Overproduction of cell-free fetal hemoglobin (HbF) in the preeclamptic placenta has been recently implicated as a new etiological factor of preeclampsia. In this study, maternal serum levels of HbF and the endogenous hemoglobin/heme scavenging systems were evaluated as predictive biomarkers for preeclampsia in combination with uterine artery Doppler ultrasound. Case-control study including 433 women in early pregnancy (mean 13.7weeks of gestation) of which 86 subsequently developed preeclampsia. The serum concentrations of HbF, total cell-free hemoglobin, hemopexin, haptoglobin and α1-microglobulin were measured in maternal serum. All patients were examined with uterine artery Doppler ultrasound. Logistic regression models were developed, which included the biomarkers, ultrasound indices, and maternal risk factors. There were significantly higher serum concentrations of HbF and α1-microglobulin and significantly lower serum concentrations of hemopexin in patients who later developed preeclampsia. The uterine artery Doppler ultrasound results showed significantly higher pulsatility index values in the preeclampsia group. The optimal prediction model was obtained by combining HbF, α1-microglobulin and hemopexin in combination with the maternal characteristics parity, diabetes and pre-pregnancy hypertension. The optimal sensitivity for all preeclampsia was 60% at 95% specificity. Overproduction of placentally derived HbF and depletion of hemoglobin/heme scavenging mechanisms are involved in the pathogenesis of preeclampsia. The combination of HbF and α1-microglobulin and/or hemopexin may serve as a prediction model for preeclampsia in combination with maternal risk factors and/or uterine artery Doppler ultrasound. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

PubMed

Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

2017-10-01

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

Modified HPLC-ESI-MS Method for Glycated Hemoglobin Quantification Based on the IFCC Reference Measurement Procedure and Its Application for Quantitative Analyses in Clinical Laboratories of China.

PubMed

Song, Zhixin; Xie, Baoyuan; Ma, Huaian; Zhang, Rui; Li, Pengfei; Liu, Lihong; Yue, Yuhong; Zhang, Jianping; Tong, Qing; Wang, Qingtao

2016-09-01

The level of glycated hemoglobin (HbA1c ) has been recognized as an important indicator of long-term glycemic control. However, the HbA1c measurement is not currently included as a diagnostic determinant in China. Current study aims to assess a candidate modified International Federation of Clinical Chemistry reference method for the forthcoming standardization of HbA1c measurements in China. The HbA1c concentration was measured using a modified high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) method. The modified method replaces the propylcyanide column with a C18 reversed-phase column, which has a lower cost and is more commonly used in China, and uses 0.1% (26.5 mmol/l) formic acid instead of trifluoroacetic acid. Moreover, in order to minimize matrix interference and reduce the running time, a solid-phase extraction was employed. The discrepancies between HbA1c measurements using conventional methods and the HPLC-ESI-MS method were clarified in clinical samples from healthy people and diabetic patients. Corresponding samples were distributed to 89 hospitals in Beijing for external quality assessment. The linearity, reliability, and accuracy of the modified HPLC-ESI-MS method with a shortened running time of 6 min were successfully validated. Out of 89 hospitals evaluated, the relative biases of HbA1c concentrations were < 8% for 74 hospitals and < 5% for 60 hospitals. Compared with other conventional methods, HbA1c concentrations determined by HPLC methods were similar to the values obtained from the current HPLC-ESI-MS method. The HPLC-ESI-MS method represents an improvement over existing methods and provides a simple, stable, and rapid HbA1c measurement with strong signal intensities and reduced ion suppression. © 2015 Wiley Periodicals, Inc.

Accuracy of predicted haemoglobin concentration on cardiopulmonary bypass in paediatric cardiac surgery: effect of different formulae for estimating patient blood volume.

PubMed

Redlin, Matthias; Boettcher, Wolfgang; Dehmel, Frank; Cho, Mi-Young; Kukucka, Marian; Habazettl, Helmut

2017-11-01

When applying a blood-conserving approach in paediatric cardiac surgery with the aim of reducing the transfusion of homologous blood products, the decision to use blood or blood-free priming of the cardiopulmonary bypass (CPB) circuit is often based on the predicted haemoglobin concentration (Hb) as derived from the pre-CPB Hb, the prime volume and the estimated blood volume. We assessed the accuracy of this approach and whether it may be improved by using more sophisticated methods of estimating the blood volume. Data from 522 paediatric cardiac surgery patients treated with CPB with blood-free priming in a 2-year period from May 2013 to May 2015 were collected. Inclusion criteria were body weight <15 kg and available Hb data immediately prior to and after the onset of CPB. The Hb on CPB was predicted according to Fick's principle from the pre-CPB Hb, the prime volume and the patient blood volume. Linear regression analyses and Bland-Altman plots were used to assess the accuracy of the Hb prediction. Different methods to estimate the blood volume were assessed and compared. The initial Hb on CPB correlated well with the predicted Hb (R 2 =0.87, p<0.001). A Bland-Altman plot revealed little bias at 0.07 g/dL and an area of agreement from -1.35 to 1.48 g/dL. More sophisticated methods of estimating blood volume from lean body mass did not improve the Hb prediction, but rather increased bias. Hb prediction is reasonably accurate, with the best result obtained with the simplest method of estimating the blood volume at 80 mL/kg body weight. When deciding for or against blood-free priming, caution is necessary when the predicted Hb lies in a range of ± 2 g/dL around the transfusion trigger.

Intermediates detected by visible spectroscopy during the reaction of nitrite with deoxyhemoglobin: the effect of nitrite concentration and diphosphoglycerate.

PubMed

Nagababu, Enika; Ramasamy, Somasundaram; Rifkind, Joseph M

2007-10-16

The reaction of nitrite with deoxyhemoglobin (deoxyHb) results in the reduction of nitrite to NO, which binds unreacted deoxyHb forming Fe(II)-nitrosylhemoglobin (Hb(II)NO). The tight binding of NO to deoxyHb is, however, inconsistent with reports implicating this reaction with hypoxic vasodilation. This dilemma is resolved by the demonstration that metastable intermediates are formed in the course of the reaction of nitrite with deoxyHb. The level of intermediates is quantitated by the excess deoxyHb consumed over the concentrations of the final products formed. The dominant intermediate has a spectrum that does not correspond to that of Hb(III)NO formed when NO reacts with methemoglobin (MetHb), but is similar to metHb resulting in the spectroscopic determinations of elevated levels of metHb. It is a delocalized species involving the heme iron, the NO, and perhaps the beta-93 thiol. The putative role for red cell reacted nitrite on vasodilation is associated with reactions involving the intermediate. (1) The intermediate is less stable with a 10-fold excess of nitrite and is not detected with a 100-fold excess of nitrite. This observation is attributed to the reaction of nitrite with the intermediate producing N2O3. (2) The release of NO quantitated by the formation of Hb(II)NO is regulated by changes in the distal heme pocket as shown by the 4.5-fold decrease in the rate constant in the presence of 2,3-diphosphoglycerate. The regulated release of NO or N2O3 as well as the formation of the S-nitroso derivative of hemoglobin, which has also been reported to be formed from the intermediates generated during nitrite reduction, should be associated with any hypoxic vasodilation attributed to the RBC.

Association between sickle cell and β-thalassemia genes and hemoglobin concentration and anemia in children and non-pregnant women in Sierra Leone: ancillary analysis of data from Sierra Leone's 2013 National Micronutrient Survey.

PubMed

Wirth, James P; Ansumana, Rashid; Woodruff, Bradley A; Koroma, Aminata S; Hodges, Mary H

2018-01-17

By measuring the associations between the presence of sickle cell and β-thalassemia genes, we assessed the extent to which these hemoglobinopathies contribute to the high prevalence of anemia observed in preschool-aged children and women of reproductive age in Sierra Leone. The prevalence of anemia was statistically significantly higher in children with homozygous sickle cell genes (HbSS) than in children with normal hemoglobin genes (HbAA or HbAC), but there was no difference in anemia prevalence in those with heterozygous sickle cell trait (HbAS or HbSC) compared with those with normal hemoglobin genes. In women, there was no difference in anemia prevalence by sickle cell status. In both children and women, there was no difference in the anemia prevalence for individuals with or without the β-thalassemia gene. For both sickle cell and β-thalassemia, there was no significant difference in hemoglobin concentrations by sickle cell or β-thalassemia status. Anemia prevalence was higher in children and women with homozygous sickle cell (HbSS). However, as the prevalence of HbSS children (5.4%) and women (1.6%) was quite small, it is unlikely that these hemoglobinopathies substantially contributed to the high anemia prevalence found in the 2013 national micronutrient survey.

Characterizations of individual human red blood cells from patients with diabetes mellitus (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, SangYun; Jang, Seongsoo; Park, HyunJoo; Park, YongKeun

2016-03-01

We systematically measure the morphological, biochemical, and biomechanical properties of individual human red blood cells (RBCs) from patients with diabetes mellitus using quantitative phase imaging technique to characterize the diabetic red cells with respect to those of the healthy. The 3-D refractive index tomograms and 2-D dynamic membrane fluctuation maps of individual RBCs are reconstructed from a set of the retrieved complex optical fields at various laser incidence angles using the Common-path diffraction optical tomography, from which volume, surface area, sphericity, hemoglobin (Hb) concentration, Hb content, and membrane fluctuation are obtained simultaneously. The correlative relations among the retrieved red cell indices of diabetic and healthy RBCs are also investigated with capabilities of individual cell measurement. As expected, there are no significant alterations in morphologies (cellular volumes, surface area, and sphericity) between diabetic and healthy RBCs. However, despite the minute mean corpuscular Hb differences in cell blood count datasheet, the measured Hb concentrations and Hb contents of diabetic RBCs are statistically higher than those of healthy RBCs, which might be related to the glycation of Hb molecules by hyperglycemia. Meanwhile, the membrane fluctuations of diabetic RBCs are clearly diminished compared to healthy red cells, implying the significantly decreased RBC deformability. In particular, it seems that the membrane fluctuations have mild negative relationships with the reported HbA1c levels.

Cyanide binding to hexacoordinate cyanobacterial hemoglobins: hydrogen-bonding network and heme pocket rearrangement in ferric H117A Synechocystis hemoglobin.

PubMed

Vu, B Christie; Nothnagel, Henry J; Vuletich, David A; Falzone, Christopher J; Lecomte, Juliette T J

2004-10-05

The truncated hemoglobin (Hb) from the cyanobacterium Synechocystis sp. PCC 6803 is a bis-histidyl hexacoordinate complex in the absence of exogenous ligands. This protein can form a covalent cross-link between His117 in the H-helix and the heme 2-vinyl group. Cross-linking, the physiological importance of which has not been established, is avoided with the His117Ala substitution. In the present work, H117A Hb was used to explore exogenous ligand binding to the heme group. NMR and thermal denaturation data showed that the replacement was of little consequence to the structural and thermodynamic properties of ferric Synechocystis Hb. It did, however, decelerate the association of cyanide ions with the heme iron. Full complexation required hours, instead of minutes, of incubation at optical and NMR concentrations. At neutral pH and in the presence of excess cyanide, binding occurred with a first-order dependence on cyanide concentration, eliminating distal histidine decoordination as the rate-limiting step. The cyanide complex of the H117A variant was characterized for the conformational changes occurring as the histidine on the distal side, His46 (E10), was displaced. Extensive rearrangement allowed Tyr22 (B10) to insert in the heme pocket and Gln43 (E7) and Gln47 (E11) to come in contact with it. H-bond formation to the bound cyanide was identified in solution with the use of (1)H(2)O/(2)H(2)O mixtures. Cyanide binding also resulted in a change in the ratio of heme orientational isomers, in a likely manifestation of heme environment reshaping. Similar observations were made with the related Synechococcus sp. PCC 7002 H117A Hb, except that cyanide binding was rapid in this protein. In both cases, the (15)N chemical shift of bound cyanide was reminiscent of that in peroxidases and the orientation of the proximal histidine was as in other truncated Hbs. The ensemble of the data provided insight into the structural cooperativity of the heme pocket scaffold and pointed to the reactive 117 site of Synechocystis Hb as a potential determinant of biophysical and, perhaps, functional properties.

Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort

PubMed Central

Obón-Santacana, Mireia; Lujan-Barroso, Leila; Freisling, Heinz; Cadeau, Claire; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Fortner, Renée T.; Boeing, Heiner; Quirós, J. Ramón; Molina-Montes, Esther; Chamosa, Saioa; Huerta Castaño, José María; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Key, Tim; Trichopoulou, Antonia; Lagiou, Pagona; Naska, Androniki; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Vineis, Paolo; Santucci De Magistris, Maria; Bueno-de-Mesquita, H.B.; Peeters, Petra H.; Wennberg, Maria; Bergdahl, Ingvar A.; Vesper, Hubert; Riboli, Elio; Duell, Eric J

2017-01-01

Purpose Acrylamide was classified as ‘probably carcinogenic’ to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from 8 countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by HPLC/MS/MS (high-performance liquid chromatography/tandem mass spectrometry). In this cross-sectional analysis four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA+HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA), and all independent variables were log-transformed (log2) to improve normality. Median (25th-75thpercentile) HbAA and HbGA adducts levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. Results The main food group determinants of HbAA, HbGA, HbAA+HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA explained in this study was 30%, 26%, 29%, and 13%, respectively. Conclusions Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort. PMID:26850269

Experimental exposure of rats to methylene chloride at varying controlled barometric altitudes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lillquist, D.R.

1990-01-01

This study investigated combined effects of three methylene chloride (MC) volume/volume concentrations (0,50, and 500 ppm) at three controlled barometric altitudes (760, 640, and 560 torr). This provided a three by three study design. For each scenario, three altitude acclimated (6 days) adult male rats were studied for eight hours in a nose-only inhalation chamber. Blood (0.35 mL) was drawn from the cannulated left carotid artery of each rat at 0, 0.5, 1, 2, 4, and 8 hours and hematocrit, pO[sub 2], pCO[sub 2], pH , total hemoglobin (Hb) and carboxyhemoglobin (CHb) were measured. Time, MC concentration and altitude hadmore » significant effects on CHb production. CHb increased with increasing MC concentration over time. Increased barometric altitude (reduced partial pressure of MC vapor at altitude for equal ppm concentrations) resulted in lower blood CHb levels. A statistical model was derived to explain variation in CHb levels for these three independent variables (r = 0.983). The data were applied to an equation assessing the impact of altitude, MC concentration and time on the potential oxygen carrying capacity (POCC) of blood. The POCC of HB in the blood was calculated using blood Hb, CHb levels, Hb oxygen saturation (based on the blood pO[sub 2] and the oxygen dissociation curve for rats), and oxygen binding potential of Hb. It was determined for the altitudes and MC concentrations used, polycythemia associated with increased altitude had a greater impact on POCC than decreased pO[sub 2]. A regression equation was derived modeling variation in POCC of blood for the three independent variables (r = 0.995). This study demonstrated that altitude affects airborne ppm MC concentrations. This ultimately impacts CHb levels and oxygen carrying capacity of the blood. These finding indicate that occupationally acceptable ppm MC exposure levels at altitude do need barometric pressure correction.« less

An evaluation of the Diamat HPLC analyser for simultaneous determination of haemoglobins A2 and F

PubMed Central

Carpinelli, Assunta; Majavacca, Rita; Cantu'-Rajnoldi, Angelo; Garatti, Massimo; Paleari, Renata; Ferrari, Maurizio; Agape, Vittorio; Maccioni, Liliana; Pisano, Sandra; Galanello, Renzo

1989-01-01

The authors describe a modification of the instrumental parameters of the Diamat fully automated HPLC system for Hb A2 assay (Bio-Rad Laboratories, Milan, Italy) in order to obtain simultaneous determination of Hb A2 and Hb F. Hb A2 and Hb F measurements are reproducible (within-run CV 2.6%, with Hb A22.7%; 5.1%, with Hb F 1.3%) and accurate (from a comparison with two microchromatographic techniques for Hb A2: r = 0.9639 and 0.9755; with two alkali denaturation procedures for Hb F: r = 0.9990 and 0.9952; with radial immunodiffusion, r = 0.9877). Assay linearity has been confirmed for Hb A2 concentrations between 0 and 6.0%, and for Hb F between 0 and 60%. The data obtained from the analysis of some pathological samples for Hb Bart's, Hb H, Hb J Sardegna, Hb Lepore and Hb S are in agreement with cellulose acetate electrophoresis analysis. The Hb A2 reference intervals for normals (N = 597) and Beta-thalassemia carriers (N = 200) are respectively (95% limits) 2.02-3.27 and 3.92-5.90 in % units. Hb F values measured in normals (N = 968), in β-thal carriers (N = 302) and in δβ-thal carriers (N =3) have been found to be consistent with the usual diagnostic parameters. Some minor limitations emerged: the most relevant concerns Hb A1c, which is overestimated with respect to a reference method (y = 1.217x + 0.16; N = 79; r = 0.9235). A probable interference from labile fractions is responsible for this Hb A1c inaccuracy. PMID:18925255

Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis

PubMed Central

Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

2010-01-01

The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis. PMID:21197233

High-performance liquid chromatographic separation of human haemoglobins. Simultaneous quantitation of foetal and glycated haemoglobins.

PubMed

Bisse, E; Wieland, H

1988-12-29

A high-performance liquid chromatographic system, which uses a weak cation exchanger (PolyCATA) together with Bis-Tris buffer (pH 6.47-7.0) and sodium acetate gradients, is described. Samples from adults and newborns were analysed and a clean separation of many minor and major normal and abnormal haemoglobin (Hb) variants was greatly improved. The method allows the separation of minor foetal haemoglobin (HbF) variants and the simultaneous quantitation of HbF and glycated HbA. HbF values correlated well with those obtained by the alkali denaturation method (r = 0.997). The glycated haemoglobin (HbAIc) levels measured in patients with high HbF concentrations correlated with the total glycated haemoglobin determined by bioaffinity chromatography (r = 0.973). The procedure is useful for diagnostic applications and affords an effective and sensitive way of examining blood samples for haemoglobin abnormalities.

Negative association between acrylamide exposure and body composition in adults: NHANES, 2003–2004

PubMed Central

Chu, P-L; Lin, L-Y; Chen, P-C; Su, T-C; Lin, C-Y

2017-01-01

Background/Objectives: Acrylamide is present in mainstream cigarette smoke and in some food prepared at high temperature. Animal studies have shown that acrylamide exposure reduces body weight. Prenatal exposure to acrylamide also has been linked to reduced birth weight in human. Whether acrylamide exposure is associated with altered body compositions in adults is not clear. Subjects/Methods: We selected 3623 subjects (aged ⩾20 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003–2004 to determine the relationship among hemoglobin adducts of acrylamide (HbAA), hemoglobin adducts of glycidamide (HbGA) and body composition (body measures, bioelectrical impedance analysis (BIA), dual energy x-ray absorptiometry (DXA)). Data were adjusted for potential confounding variables. Results: The geometric means and 95% CI concentrations of HbAA and HbGA were 60.48 (59.32–61.65) pmol/g Hb and 55.64 (54.40–56.92) pmol/g Hb, respectively. After weighting for sampling strategy, we identified that one-unit increase in natural log-HbAA, but not HbGA, was associated with reduction in body measures (body weight, body mass index (BMI), subscapular/triceps skinfold), parameters of BIA (fat-free mass, fat mass, percent body fat, total body water) and parameters of DXA (android fat mass, android percent fat, gynoid fat/lean mass, gynoid percent mass, android to gynoid ratio). Subgroup analysis showed that these associations were more evident in subjects at younger age, male gender, whites, lower education level, active smokers and those with lower BMI. Conclusions: Higher concentrations of HbAA are associated with a decrease in body composition in the US general population. Further studies are warranted to clarify this association. PMID:28287631

Contralateral cerebral hemoglobin oxygen saturation changes in patients undergoing thoracotomy with general anesthesia with or without paravertebral block: a randomized controlled trial.

PubMed

Mukaihara, Keika; Hasegawa-Moriyama, Maiko; Kanmura, Yuichi

2017-12-01

Perioperative analgesia during thoracotomy is often achieved by combining paravertebral block (PVB) with general anesthesia (GA). Functional near-infrared spectroscopy (NIRS) can detect changes in cerebral oxygenation resulting from nociceptive stimuli in the awake state or under sedation. We used NIRS to measure changes in cerebral blood flow provoked by thoracotomy incision made under GA and determine how these changes were influenced by supplementation of GA with PVB. Thirty-four patients undergoing elective thoracotomy were enrolled. Patients were randomly assigned to a group receiving only GA, or GA combined with PVB (GA + PVB). Changes in cerebral oxygenated hemoglobin (ΔO 2 Hb), deoxygenated-Hb (ΔHHb), and total-Hb (ΔtotalHb) were evaluated by NIRS as surgery began. In the GA group, ΔO 2 Hb was significantly higher in the hemisphere contralateral to the side of surgery when the incision was made and 2 min after incision compared with the ipsilateral side (start of surgery, P < 0.01; 2 min, P < 0.05). In contrast, there were no significant changes in the ΔO 2 Hb at any of the time points in the GA + PVB group. Comparable with ΔO 2 Hb, the concentration of ΔtotalHb was significantly higher in the contralateral hemisphere in the GA group at the start of surgery (P < 0.05). Changes in the cerebral O 2 Hb concentration were detected by NIRS immediately after surgical incision under GA, but not in the presence of a PNB. NIRS could be used to monitor surgical pain. PVB inhibited changes in oxygenation induced by incision-provoked pain.

Anemia and deficiencies of folate and vitamin B-6 are common and vary with season in Chinese women of childbearing age.

PubMed

Ronnenberg, A G; Goldman, M B; Aitken, I W; Xu, X

2000-11-01

Little is known about the micronutrient status of Chinese women of childbearing age. We assessed nonfasting plasma concentrations of folic acid, vitamin B-12, vitamin B-6 (as pyridoxal-5'-phosphate), hemoglobin (Hb), ferritin and transferrin receptor (TfR) in 563 nonpregnant textile workers aged 21-34 y from Anqing, China. All women had obtained permission to become pregnant and were participating in a prospective study of pregnancy outcomes. Mean (SD) plasma concentrations were 9.7 (4.1) nmol/L folic acid, 367 (128) pmol/L vitamin B-12, 40.2 (15.8) nmol/L vitamin B-6, 108 (12. 9) g/L Hb, 42.6 (34.2) microgram/L ferritin and 5.2 (2.7) mg/L TfR. Twenty-three percent of women had biochemical evidence of folic acid deficiency, 26% were deficient in vitamin B-6 and 10% had low vitamin B-12. Overall, 44% of women were deficient in at least one B vitamin. Although anemia (Hb < 120 g/L) was detected in 80% of women, only 17% had depleted iron stores (ferritin < 12 microgram/L); 11% had elevated TfR concentrations. Distinct seasonal trends were observed in the prevalence of moderate anemia (Hb < 100 g/L) and deficiencies of folic acid and vitamin B-6, with significantly lower concentrations of folate and Hb occurring in summer and lower concentrations of vitamin B-6 occurring in winter and spring than in other seasons. We conclude that deficiencies of folic acid, vitamin B-6 and iron were relatively common in this sample of Chinese women of childbearing age and were contributing to the high prevalence of anemia. Without appropriate supplementation, these deficiencies could jeopardize the women's health and increase their risk of adverse pregnancy outcomes.

Postpartum iron status in nonlactating participants and nonparticipants in the special supplemental nutrition program for women, infants, and children.

PubMed

Pehrsson, P R; Moser-Veillon, P B; Sims, L S; Suitor, C W; Russek-Cohen, E

2001-01-01

Iron deficiency, a pervasive problem among low-income women of childbearing age, threatens maternal health and pregnancy outcomes. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) was designed to alleviate health problems and provides supplemental nutritious foods, nutrition education, and health care referrals. The aim of this study was to examine the benefits associated with participation in WIC in terms of biochemical tests of postpartum iron status in nonlactating women. WIC participants (n = 57) and eligible nonparticipants (n = 53), matched by race and age, were followed bimonthly over 6 mo postpartum. Finger stick blood samples (500 microL) were collected for measurement of plasma ferritin, transferrin receptor (TfR), and hemoglobin (Hb). The mean (+/-SE) Hb concentration of participants exceeded that of nonparticipants from months 2 through 6. At 6 mo, the mean Hb concentration of participants was significantly higher than that of nonparticipants (8.01+/-0.12 and 7.63+/-0.12 mmol/L, respectively; P< 0.05) and the prevalence of anemia was significantly lower (17% and 51%, respectively; P<0.05). TfR and ferritin concentrations (consistently within the reference ranges) and dietary iron intakes did not differ significantly between participants and nonparticipants and were not correlated with Hb concentrations. Our results suggest that WIC participants were significantly less likely to become anemic if uninterrupted postpartum participation lasted for 6 mo. The lack of correlation among iron status indicators suggests that the lower mean Hb concentration in nonparticipants at 6 mo may not have been related to improved iron status in participants but to other nutrient deficiencies or differences in access to health care and health and nutrition education.

Development and validation of an oxygen dissociation assay, a screening platform for discovering, and characterizing hemoglobin-oxygen affinity modifiers.

PubMed

Patel, Mira P; Siu, Vincent; Silva-Garcia, Abel; Xu, Qing; Li, Zhe; Oksenberg, Donna

2018-01-01

Hemoglobin (Hb) is a critical molecule necessary for all vertebrates to maintain aerobic metabolism. Hb-oxygen (O 2 ) affinity modifiers have been studied to address various diseases including sickle cell disease, hypoxemia, tumor hypoxia, and wound healing. However, drug development of exogenous Hb modifiers has been hindered by the lack of a technique to rapidly screen compounds for their ability to alter Hb-O 2 affinity. We have developed a novel screening assay based upon the spectral changes observed during Hb deoxygenation and termed it the oxygen dissociation assay (ODA). ODA allows for the quantitation of oxygenated Hb at given time points during Hb deoxygenation on a 96-well plate. This assay was validated by comparing the ability of 500 Hb modifiers to alter the Hb-O 2 affinity in the ODA vs the oxygen equilibrium curves obtained using the industry standard Hemox Analyzer instrument. A correlation ( R 2 ) of 0.7 indicated that the ODA has the potential to screen and identify potent exogenous Hb modifiers. In addition, it allows for concurrent comparison of compounds, concentrations, buffers, or pHs on the level of Hb oxygenation. With a cost-effective, simple, rapid, and highly adaptable assay, the ODA will allow researchers to rapidly characterize Hb-O 2 affinity modifiers.

Carboxyhemoglobin and methemoglobin in asthma.

PubMed

Naples, Robert; Laskowski, Dan; McCarthy, Kevin; Mattox, Emmea; Comhair, Suzy A A; Erzurum, Serpil C

2015-04-01

Nitric oxide (NO) and carbon monoxide (CO) are synthesized at high levels in asthmatic airways. NO can oxidize hemoglobin (Hb) to methemoglobin (MetHb). CO binds to heme to produce carboxyhemoglobin (COHb). We hypothesized that MetHb and COHb may be increased in asthma. COHb, MetHb, and Hb were measured in venous blood of healthy controls (n = 32) and asthmatics (n = 31). Arterial COHb and oxyhemoglobin were measured by pulse CO-oximeter. Hb, oxyhemoglobin, and deoxyhemoglobin were similar among groups, but arterial COHb was higher in asthmatics than controls (p = 0.04). Venous COHb was similar among groups, and thus, arteriovenous COHb (a-v COHb) concentration difference was greater in asthma compared with controls. Venous MetHb was lower in asthma compared to controls (p = 0.01) and correlated to venous NO (p = 0.009). The greater a-v COHb in asthma suggests CO offloading to tissues, but lower than normal MetHb suggests countermeasures to avoid adverse effects of high NO on gas transfer.

Carboxyhemoglobin and Methemoglobin in Asthma

PubMed Central

Naples, Robert; Laskowski, Dan; McCarthy, Kevin; Mattox, Emmea; Comhair, Suzy A. A.; Erzurum, Serpil C.

2015-01-01

Nitric oxide (NO) and carbon monoxide (CO) are synthesized at high levels in asthmatic airways. NO can oxidize hemoglobin (Hb) to methemoglobin (MetHb). CO binds to heme to produce carboxyhemoglobin (COHb). We hypothesized that MetHb and COHb may be increased in asthma. COHb, MetHb, and Hb were measured in venous blood of healthy controls (n=32) and asthmatics (n=31). Arterial COHb and oxyhemoglobin were measured by pulse CO-oximeter. Hb, oxyhemoglobin, and deoxyhemoglobin were similar among groups, but arterial COHb was higher in asthmatics than controls (p=0.04). Venous COHb was similar among groups, and thus arteriovenous COHb (a-v COHb) concentration difference was greater in asthma compared with controls. Venous MetHb was lower in asthma compared to controls (p=0.01) and correlated to venous NO (p=0.009). The greater a-v COHb in asthma suggests CO offloading to tissues, but lower than normal MetHb suggests countermeasures to avoid adverse effects of high NO on gas transfer. PMID:25680415

Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control.

PubMed

Soliman, Ashraf T; Omar, Magdi; Assem, Hala M; Nasr, Ibrahim S; Rizk, Mohamed M; El Matary, Wael; El Alaily, Rania K

2002-03-01

Although obesity is a frequent feature of type 2 diabetes mellitus (DM), many patients with type 1 DM are prone to high body mass index (BMI). We measured serum leptin concentrations in a cohort of children (n = 55) with type 1 diabetes mellitus (DM), as well as their anthropometric parameters including BMI, skin fold thickness at multiple sites, and midarm circumference. Glycemic control was assessed by blood glucose (BG) monitoring before meals, and measurement of glycated hemoglobin (HbA1c) and insulin dose/kg/d was recorded. Dietary evaluation and assessment of caloric intake (kg/d) was performed by an expert dietitian. In the newly diagnosed children (n = 10) before initiation of insulin therapy, circulating leptin concentration was significantly lower (1.1 +/- 0.8 ng/dL) versus 5 days after insulin therapy (1.45 +/- 0.7 ng/dL). The decreased leptin level appears to be related to insulinopenia in these patients. In 45 children with type 1 DM on conventional therapy (2 doses of insulin mixture (NPH and regular) subcutaneous (SC) before breakfast and dinner for more than 2 years), serum leptin concentration was significantly higher (2.15 +/- 1 ng/dL) compared with age-matched normal children (1.3 +/- 1 ng/dL). Diabetic children were further divided into 2 groups according to their HbA1c level: group 1 with HbA1C less than 7.5% (less than 2 SD above the mean for normal population) (n = 29) and group 2 with HbA1c greater than 7.5%. (greater than 2 SD above the mean for normal population) (n = 16). Patients with a higher HbA1c level (group 2) had a higher leptin concentration (2.3 +/- 0.8 ng/dL), higher BMI (17.8 +/- 1.7), and were receiving higher insulin dose/kg (0.92 +/- 0.2 U/kg/d) compared with group 1 (lower HbA1c) (1.78 +/- 0.8 ng/dL, 16.7 +/- 1.5, and 0.59 +/- 0.2 U/kg/d, respectively). Group 2 patients had a higher incidence of late morning hypoglycemia (9/29) versus group 1 patients (2/16). Analysis of dietary intake showed that patients with a higher HbA1c (group 2) consumed more calories (73.5 +/- 10.5 kcal/kg/d) versus patients with lower HbA1c (64.2 +/- 8.7 kcal/kg/d). These findings pointed to the unphysiologic nature of injecting a mixture of insulin twice daily. To cover the relatively big lunch meal (40% to 50% of the total caloric intake in the Arab countries) and prevent afternoon hyperglycemia, there is a great tendency to increase NPH dose before breakfast. This, in turn, induces late-morning hypoglycemia and increases appetite and food intake at that time. Multiple regression analysis showed that circulating leptin concentrations (the dependent variable) were best correlated with the mean skinfold thickness (SFT), BMI, and caloric intake/kg/d (together they explained 65% of the variability in leptin concentrations). It appears that oversubstitution by insulin and increased food intake stimulate fat synthesis and subsequently BMI. Increased appetite and BMI contribute to increased leptin secretion and explains the higher leptin levels in undercontrolled diabetic children (higher circulating HbA1c concentrations) who were oversubstituted by insulin. Copyright 2002 by W.B. Saunders Company

Test-Retest Reliability of Graph Metrics in Functional Brain Networks: A Resting-State fNIRS Study

PubMed Central

Niu, Haijing; Li, Zhen; Liao, Xuhong; Wang, Jinhui; Zhao, Tengda; Shu, Ni; Zhao, Xiaohu; He, Yong

2013-01-01

Recent research has demonstrated the feasibility of combining functional near-infrared spectroscopy (fNIRS) and graph theory approaches to explore the topological attributes of human brain networks. However, the test-retest (TRT) reliability of the application of graph metrics to these networks remains to be elucidated. Here, we used resting-state fNIRS and a graph-theoretical approach to systematically address TRT reliability as it applies to various features of human brain networks, including functional connectivity, global network metrics and regional nodal centrality metrics. Eighteen subjects participated in two resting-state fNIRS scan sessions held ∼20 min apart. Functional brain networks were constructed for each subject by computing temporal correlations on three types of hemoglobin concentration information (HbO, HbR, and HbT). This was followed by a graph-theoretical analysis, and then an intraclass correlation coefficient (ICC) was further applied to quantify the TRT reliability of each network metric. We observed that a large proportion of resting-state functional connections (∼90%) exhibited good reliability (0.6< ICC <0.74). For global and nodal measures, reliability was generally threshold-sensitive and varied among both network metrics and hemoglobin concentration signals. Specifically, the majority of global metrics exhibited fair to excellent reliability, with notably higher ICC values for the clustering coefficient (HbO: 0.76; HbR: 0.78; HbT: 0.53) and global efficiency (HbO: 0.76; HbR: 0.70; HbT: 0.78). Similarly, both nodal degree and efficiency measures also showed fair to excellent reliability across nodes (degree: 0.52∼0.84; efficiency: 0.50∼0.84); reliability was concordant across HbO, HbR and HbT and was significantly higher than that of nodal betweenness (0.28∼0.68). Together, our results suggest that most graph-theoretical network metrics derived from fNIRS are TRT reliable and can be used effectively for brain network research. This study also provides important guidance on the choice of network metrics of interest for future applied research in developmental and clinical neuroscience. PMID:24039763

HPLC-ESI-MS/MS analysis of hemoglobin peptides in tryptic digests of dried-blood spot extracts detects HbS, HbC, HbD, HbE, HbO-Arab, and HbG-Philadelphia mutations.

PubMed

Haynes, Christopher A; Guerra, Stephanie L; Fontana, Jessalyn C; DeJesús, Víctor R

2013-09-23

Hemoglobinopathies are mutations resulting in abnormal globin chain structure; some have clinically significant outcomes such as anemia or reduced lifespan. Five β-globin mutations are (c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), and (c.364G>A, p.E121K), resulting in HbS (sickle-cell hemoglobin), HbC, HbE, HbD-Los Angeles, and HbO-Arab, respectively. One α-globin mutation is (c.[207C>G or 207C>A], p.N68K), resulting in HbG-Philadelphia. HPLC-ESI-MS/MS analysis of dried-blood spot (DBS) punches from newborns extracted with a trypsin-containing solution provides greater than 90% coverage of α-, β-, and γ-globin amino acid sequences. Because the (c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), (c.364G>A, p.E121K), and (c.[207C>G or 207C>A], p.N68K) mutations generate globin peptides with novel amino acid sequences, detecting one of these peptides in DBS extracts is indicative of the presence of a hemoglobinopathy in the newborn. The method described here can distinguish normal β-globin peptides from the mutant HbS, HbC, HbE, HbD-Los Angeles and HbO-Arab peptides, as well as normal α-globin peptide from the mutant HbG-Philadelphia peptide, allowing the identification of unaffected heterozygotes such as HbAS, and of compound heterozygotes such as HbASG-Philadelphia. This HPLC-ESI-MS/MS analytical approach provides information that is not available from traditional hemoglobin analyses such as isoelectric focusing and HPLC-UV. It is also capable of determining the amino acid sequence of hemoglobin peptides, potentially allowing the detection of numerous hemoglobinopathies resulting from point mutations. Published by Elsevier B.V.

Accuracy of non-invasive continuous total hemoglobin measurement by Pulse CO-Oximetry in severe traumatized and surgical bleeding patients.

PubMed

Baulig, Werner; Seifert, Burkhardt; Spahn, Donat R; Theusinger, Oliver M

2017-02-01

The Masimo Radical-7 Pulse CO-Oximeter (Masimo Corp., USA) non-invasively computes hemoglobin concentration (SpHb). SpHb was compared to Co-Oximeter readings (CoOxHb) of arterial samples in surgery patients of the emergency department. Forty-six patients were enrolled. The Masimo R1 25L (revision F and G) adult adhesive sensor was attached to the ring finger of the arterially cannulated hand. Before start, every 30 min during surgery and in the case of severe bleeding SpHb and CoOxHb values were documented. SpHb and post hoc adjusted SpHb (AdSpHb) values were analyzed. Linear regression analysis and Bland-Altman plot for agreement were performed. The detection failure rate of SpHb was 24.5 %. CoOxHb and SpHb showed a strong correlation (r = +0.81), but agreement was moderate [bias (LOA) of -0.6 (-3.0; +1.9)] g/dl. Positive and negative predicted value was 0.49 and 0.69. Exclusion of changes of CoOxHb values ≤1 g/dl resulted in a positive and negative predictive value of 0.66 and 1.00. Post hoc adjustment of the SpHb (AdSpHb) improved linear correlation of CoOxHb and AdSpHb [r = +0.90 (p < 0.001)] but less the agreement [bias (LOA) of CoOxHb and AdSpHb = -0.1 (-2.1/+1.9) g/dl]. SpHb agreed only moderately with CoOxHb values and predicted decreases of CoOxHb only if changes of SpHb ≤ 1.0 g/dl were excluded. The detection failure rate of SpHb was high. At present, additional refinements of the current technology are necessary to further improve performance of non-invasive hemoglobin measurement in the clinical setting.

Thyroid Dysfunction and Anemia: A Prospective Cohort Study and a Systematic Review.

PubMed

Floriani, Carmen; Feller, Martin; Aubert, Carole E; M'Rabet-Bensalah, Khadija; Collet, Tinh-Hai; den Elzen, Wendy P J; Bauer, Douglas C; Angelillo-Scherrer, Anne; Aujesky, Drahomir; Rodondi, Nicolas

2018-05-01

Even though the association between thyroid dysfunction and anemia is commonly described, it is not known whether it is clinically relevant. This study set out to quantify the association of thyroid dysfunction on hemoglobin (Hb) concentration and risk of anemia. A systematic review (MEDLINE and EMBASE, from inception until May 15, 2017) was conducted to interpret the findings in context. Participants from the EPIC-Norfolk cohort with available baseline thyrotropin (TSH), free thyroxine (fT4), and Hb were included. Euthyroidism was defined as TSH 0.45-4.49 mIU/L (reference category), hypothyroidism as TSH ≥4.50 mIU/L (subclinical [SHypo] with normal fT4 or overt [OHypo] with low fT4), and hyperthyroidism as TSH ≤0.44 mIU/L (subclinical [SHyper] with normal fT4 or overt [OHyper] with elevated fT4). Anemia was defined as Hb <12 g/dL in women and Hb <13 g/dL in men. In the cross-sectional analyses, multiple linear regression was used to compare Hb across TSH categories. In the prospective analysis, participants with OHypo/OHyper at baseline were excluded, as it was assumed that they were treated for overt thyroid disease. A covariance model was used to determine change in Hb concentration from baseline to last follow-up, and multivariable Cox regression was used to analyze anemia risk. In the cross-sectional population (n = 12,337), the adjusted Hb was 0.22 g/dL lower [confidence interval (CI) 0.07-0.38] in OHypo compared to euthyroids, and 0.08 g/dL lower [CI -0.23 to 0.38] in OHyper. In the prospective analysis, 460/7031 participants developed anemia over a median follow-up of 4.7 years. The adjusted mean Hb change over time was -0.04 g/dL in SHypo [CI -0.14 to 0.06] and 0.05 g/dL in SHyper [CI -0.10 to 0.20]. The adjusted hazard ratio for anemia was 0.99 [CI 0.67-1.48] in SHypo, and 0.52 [CI 0.23-1.16] in SHyper. The systematic review returned no other prospective studies on this association, but cross-sectional and case-control studies showed comparable results. In this first prospective population-based cohort, subclinical thyroid dysfunction was not associated with a change in Hb concentration during follow-up and was not an independent risk factor for developing anemia; variations in Hb concentration in patients with overt thyroid dysfunction were not clinically relevant.

Near infrared spectroscopy study of the frontopolar hemodynamic response and depressive mood in children with major depressive disorder: a pilot study.

PubMed

Usami, Masahide; Iwadare, Yoshitaka; Kodaira, Masaki; Watanabe, Kyota; Saito, Kazuhiko

2014-01-01

The aim of this study was to evaluate the frontopolar hemodynamic response and depressive mood in children with mild or moderate major depressive disorder during six weeks treatment without medication. The subjects were 10 patients with mild or moderate depression. They were depressive drug-naive children and adolescents. The scores of Depression Self Rating Scale (DSRS), the results of the Verbal Fluency Test (VFT), and the concentrations of oxy-hemoglobin (Oxy-Hb) of frontal pole brain assessed by two-channel near infrared spectroscopy (NIRS) after six weeks of treatment was compared with those of initial treatment. The score of DSRS was significantly reduced after six weeks of initial treatment (p<0.001, t-test). The word number of VFT was not significantly changed after six weeks of treatment. The oxy-Hb concentration significantly increased after six weeks of treatment (p<0.001, t-test). This study demonstrated that the concentration of oxy-Hb of frontopolar cortex in children with mild and moderate depression improved along with their depressive mood. These results suggested that concentration of oxy-Hb using NIRS may be used as the state maker for change in depressive mood of children having depression, similar to that in adults.

Affect school and script analysis versus basic body awareness therapy in the treatment of psychological symptoms in patients with diabetes and high HbA1c concentrations: two study protocols for two randomized controlled trials.

PubMed

Melin, Eva O; Svensson, Ralph; Gustavsson, Sven-Åke; Winberg, Agneta; Denward-Olah, Ewa; Landin-Olsson, Mona; Thulesius, Hans O

2016-04-27

Depression is linked with alexithymia, anxiety, high HbA1c concentrations, disturbances of cortisol secretion, increased prevalence of diabetes complications and all-cause mortality. The psycho-educational method 'affect school with script analysis' and the mind-body therapy 'basic body awareness treatment' will be trialled in patients with diabetes, high HbA1c concentrations and psychological symptoms. The primary outcome measure is change in symptoms of depression. Secondary outcome measures are changes in HbA1c concentrations, midnight salivary cortisol concentration, symptoms of alexithymia, anxiety, self-image measures, use of antidepressants, incidence of diabetes complications and mortality. Two studies will be performed. Study I is an open-labeled parallel-group study with a two-arm randomized controlled trial design. Patients are randomized to either affect school with script analysis or to basic body awareness treatment. According to power calculations, 64 persons are required in each intervention arm at the last follow-up session. Patients with type 1 or type 2 diabetes were recruited from one hospital diabetes outpatient clinic in 2009. The trial will be completed in 2016. Study II is a multicentre open-labeled parallel-group three-arm randomized controlled trial. Patients will be randomized to affect school with script analysis, to basic body awareness treatment, or to treatment as usual. Power calculations show that 70 persons are required in each arm at the last follow-up session. Patients with type 2 diabetes will be recruited from primary care. This study will start in 2016 and finish in 2023. For both studies, the inclusion criteria are: HbA1c concentration ≥62.5 mmol/mol; depression, alexithymia, anxiety or a negative self-image; age 18-59 years; and diabetes duration ≥1 year. The exclusion criteria are pregnancy, severe comorbidities, cognitive deficiencies or inadequate Swedish. Depression, anxiety, alexithymia and self-image are assessed using self-report instruments. HbA1c concentration, midnight salivary cortisol concentration, blood pressure, serum lipid concentrations and anthropometrics are measured. Data are collected from computerized medical records and the Swedish national diabetes and causes of death registers. Whether the "affect school with script analysis" will reduce psychological symptoms, increase emotional awareness and improve diabetes related factors will be tried, and compared to "basic body awareness treatment" and treatment as usual. ClinicalTrials.gov: NCT01714986.

Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection

PubMed Central

Ohashi, Jun ; Naka, Izumi ; Patarapotikul, Jintana ; Hananantachai, Hathairad ; Brittenham, Gary ; Looareesuwan, Sornchai ; Clark, Andrew G. ; Tokunaga, Katsushi 

2004-01-01

The hemoglobin E variant (HbE; β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection. PMID:15114532

Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection.

PubMed

Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

2004-06-01

The hemoglobin E variant (HbE; ( beta )26Glu-->Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Modeling of Nitrous Oxide Production from Nitritation Reactors Treating Real Anaerobic Digestion Liquor.

PubMed

Wang, Qilin; Ni, Bing-Jie; Lemaire, Romain; Hao, Xiaodi; Yuan, Zhiguo

2016-04-29

In this work, a mathematical model including both ammonium oxidizing bacteria (AOB) and heterotrophic bacteria (HB) is constructed to predict N2O production from the nitritation systems receiving the real anaerobic digestion liquor. This is for the first time that N2O production from such systems was modeled considering both AOB and HB. The model was calibrated and validated using experimental data from both lab- and pilot-scale nitritation reactors. The model predictions matched the dynamic N2O, ammonium, nitrite and chemical oxygen demand data well, supporting the capability of the model. Modeling results indicated that HB are the dominant contributor to N2O production in the above systems with the dissolved oxygen (DO) concentration of 0.5-1.0 mg O2/L, accounting for approximately 75% of N2O production. The modeling results also suggested that the contribution of HB to N2O production decreased with the increasing DO concentrations, from 75% at DO = 0.5 mg O2/L to 25% at DO = 7.0 mg O2/L, with a corresponding increase of the AOB contribution (from 25% to 75%). Similar to HB, the total N2O production rate also decreased dramatically from 0.65 to 0.25 mg N/L/h when DO concentration increased from 0.5 to 7.0 mg O2/L.

Tangential Flow Filtration of Hemoglobin

PubMed Central

Sun, Guoyong; Harris, David R.

2009-01-01

Bovine and human hemoglobin (bHb and hHb, respectively) was purified from bovine and human red blood cells (bRBCs and hRBCs, respectively) via tangential flow filtration (TFF) in four successive stages. TFF is a fast and simple method to purify Hb from RBCs using filtration through hollow fiber (HF) membranes. Most of the Hb was retained in stage III (100 kDa HF membrane) and displayed methemoglobin levels less than 1%, yielding final concentrations of 318 and 300 mg/mL for bHb and hHb, respectively. Purified Hb exhibited much lower endotoxin levels than their respective RBCs. The purity of Hb was initially assessed via SDS-PAGE, and showed tiny impurity bands for the stage III retentate. The oxygen affinity (P50), and cooperativity coefficient (n) were regressed from the measured oxygen-RBC/Hb equilibrium curves of RBCs and purified Hb. These results suggest that TFF yielded oxygen affinities of bHb and hHb that are comparable to values in the literature. LC-MS was used to measure the molecular weight of the alpha (α) and beta (β) globin chains of purified Hb. No impurity peaks were present in the HPLC chromatograms of purified Hb. The mass of the molecular ions corresponding to the α and β globin chains agreed well with the calculated theoretical mass of the α-and β-globin chains. Taken together, our results demonstrate that HPLC grade Hb can be generated via TFF. In general, this method can be more broadly applied to purify Hb from any source of RBCs. This work is significant, since it outlines a simple method for generating Hb for synthesis and/or formulation of Hb-based oxygen carriers (HBOCs). PMID:19224583

Multicausal etiology of anemia among women of reproductive age in Vietnam.

PubMed

Nguyen, P H; Gonzalez-Casanova, I; Nguyen, H; Pham, H; Truong, T V; Nguyen, S; Martorell, R; Ramakrishnan, U

2015-01-01

Anemia is a significant public health concern, especially among women and young children. An improved understanding of the complex etiology of anemia is crucial for developing appropriate prevention strategies. This paper examines the determinants of anemia in a large sample of Vietnamese women of reproductive age (WRA). We included baseline data from 4986 WRA participating in a randomized controlled trial (PRECONCEPT). Hemoglobin (Hb) concentrations were measured with Hemocue. Plasma ferritin (Fe), retinol binding protein (RBP) and markers of inflammation were assessed using the ELISA technique. We used multivariate logistic regression to describe associations with anemia and structural equation modeling (SEM) to characterize direct and indirect pathways influencing Hb concentrations. Prevalence of anemia, iron deficiency (Fe <12 μg/l), insufficient iron stores (Fe<30 μg/l) and iron deficiency anemia was 19.7, 3.5, 14.4 and 1.9%, respectively. Ferritin concentration (0.29 per log-mg/dl), being an ethnic minority (-0.24 compared with Kinh), number of children (-0.17) and socioeconomic status (0.09) were directly associated with Hb concentration (P<0.05). Similarly, RBP was directly (0.27 per mg/dl) associated with Hb and also indirectly (0.09 mg/dl) with ferritin. Hookworm infection was indirectly associated with Hb (-0.11) through RBP and ferritin. These findings illustrate the complex etiology of anemia and provide a useful framework for designing, targeting and evaluating appropriate strategies for the prevention and control of anemia. Contrary to expectations, iron deficiency accounted for a very small proportion of anemia in Northern Vietnam.

Malaria in Pregnancy Is a Predictor of Infant Haemoglobin Concentrations during the First Year of Life in Benin, West Africa.

PubMed

Accrombessi, Manfred; Ouédraogo, Smaïla; Agbota, Gino Cédric; Gonzalez, Raquel; Massougbodji, Achille; Menéndez, Clara; Cot, Michel

2015-01-01

Anaemia is an increasingly recognized health problem in Africa, particularly in infants and pregnant women. Although malaria is known to be the main risk factor of anaemia in both groups, the consequences of maternal factors, particularly malaria in pregnancy (MiP), on infant haemoglobin (Hb) concentrations during the first months of life are still unclear. We followed-up a cohort of 1005 Beninese pregnant women from the beginning of pregnancy until delivery. A subsample composed of the first 400 offspring of these women were selected at birth and followed until the first year of life. Placental histology and blood smear at 1st clinical antenatal visit (ANC), 2nd ANC and delivery were used to assess malaria during pregnancy. Infant Hb concentrations were measured at birth, 6, 9 and 12 months of age. A mixed multi-level model was used to assess the association between MiP and infant Hb variations during the first 12 months of life. Placental malaria (difference mean [dm] = - 2.8 g/L, 95% CI [-5.3, -0.3], P = 0.03) and maternal peripheral parasitaemia at delivery (dm = - 4.6 g/L, 95% CI [-7.9, -1.3], P = 0.007) were the main maternal factors significantly associated with infant Hb concentrations during the first year of life. Poor maternal nutritional status and malaria infection during infancy were also significantly associated with a decrease in infant Hb. Antimalarial control and nutritional interventions before and during pregnancy should be reinforced to reduce specifically the incidence of infant anaemia, particularly in Sub-Saharan countries.

Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Sun, Tengfei; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.; Piao, Daqing

2017-02-01

In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic AY-27 rat bladder urothelial cell carcinoma model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder tumor cells were intravesically instilled in four rats and allowed to implant and grow for one week, with two additional rats as the control. A total of 107 SfRS measurements were taken from 27 sites on two control bladders and 80 from four AY-27 treated bladders. The spectral profiles obtained from AY-27 treated bladders revealed various levels of a methemoglobin (MetHb) characteristic spectral feature around 635nm. A multisegment spectral analysis method estimated concentrations of five chromophore compositions including oxyhemoglobin, deoxyhemoglobin, MetHb, lipid and water. The total hemoglobin concentration ([HbT]), the MetHb proportion in the total hemoglobin and the lipid volume content showed possible correlations. The 80 measurements from the AY-27 treated bladders could separate to three sub-sets according to the MetHb proportion. Specifically, 72 were in subset 1 with low proportion (5.3%<[MetHb]<7%), 6 in subset 2 with moderate proportion (7%<[MetHb]<30%), and 2 in subset 3 with significant proportion (>30%). When grouped according to [MetHB], the [HbT] increased from 368 μM of subset 1 to 488 μM of subset 2 to 541 μM of subset 3, in comparison to the 285 μM of the control. The increased total hemoglobin and the elevation of MetHb proportion may signify angiogenesis and degradation in hemoglobin oxygen-transport. Additionally, the lipid volume content decreased from 2.58% in the control to <0.2% in the tumor groups, indicating disruption of subepithelium tissue architecture.

Validation and determination of a reference interval for canine HbA1c using an immunoturbidimetric assay.

PubMed

Goemans, Anne F; Spence, Susanna J; Ramsey, Ian K

2017-06-01

Hemoglobin A1c (HbA1c) provides a reliable measure of glycemic control over 2-3 months in human diabetes mellitus. In dogs, presence of HbA1c has been demonstrated, but there are no validated commercial assays. The purpose of the study was to validate a commercially available automated immunoturbidimetric assay for canine HbA1c and determine an RI in a hospital population. The specificity of the assay was assessed by inducing glycosylation in vitro using isolated canine hemoglobin, repeatability by measuring canine samples 5 times in succession, long term inter-assay imprecision by measuring supplied control materials, stability using samples stored at 4°C over 5 days and -20°C over 8 weeks, linearity by mixing samples of known HbA1c in differing proportions, and the effect of anticoagulants with paired samples. An RI was determined using EDTA-anticoagulated blood samples from 60 nondiabetic hospitalized animals of various ages and breeds. Hemoglobin A1c was also measured in 10 diabetic dogs. The concentration of HbA1c increased proportionally with glucose concentration in vitro. For repeat measurements, the CV was 4.08% (range 1.16-6.10%). Samples were stable for 5 days at 4°C. The assay was linear within the assessed range. Heparin- and EDTA-anticoagulated blood provided comparable results. The RI for HbA1c was 9-18.5 mmol/mol. There was no apparent effect of age or breed on HbA1c. In diabetic dogs, HbA1c ranged from 14 to 48 mmol/mol. The assay provides a reliable method for canine HbA1c measurement with good analytic performance. © 2017 American Society for Veterinary Clinical Pathology.

Real time monitoring of pulsatile change in hemoglobin concentrations of cerebral tissue by a portable tissue oximeter with a 10-Hz sampling rate

NASA Astrophysics Data System (ADS)

Shiga, Toshikazu; Chihara, Eiichi; Tanabe, Kazuhisa; Tanaka, Yoshifumi; Yamamoto, Katsuyuki

1998-01-01

A portable CW tissue oximeter of a 10-Hz sampling rate was developed for examination of pulsatile components of the output signals as a mean of checking the signal reliability during long-term monitoring. Feasible studies were performed on a healthy subject. Changes in Hb and HbO2 signals of cerebral tissue were continuously measured by placing a photoprobe on the forehead during 6-hour sleep. Pulsatile changes in Hb and HbO2 were steadily observed over a whole period of the recording. The phase relation of pulsation in Hb and HbO2 was almost inverse. Not only information for reliable monitoring but also physiological parameters with respect to cerebral circulation and metabolism could be obtained by measuring the pulsatile components.

Real time monitoring of pulsatile change in hemoglobin concentrations of cerebral tissue by a portable tissue oximeter with a 10-Hz sampling rate

NASA Astrophysics Data System (ADS)

Shiga, Toshikazu; Chihara, Eiichi; Tanabe, Kazuhisa; Tanaka, Yoshifumi; Yamamoto, Katsuyuki

1997-12-01

A portable CW tissue oximeter of a 10-Hz sampling rate was developed for examination of pulsatile components of the output signals as a mean of checking the signal reliability during long-term monitoring. Feasible studies were performed on a healthy subject. Changes in Hb and HbO2 signals of cerebral tissue were continuously measured by placing a photoprobe on the forehead during 6-hour sleep. Pulsatile changes in Hb and HbO2 were steadily observed over a whole period of the recording. The phase relation of pulsation in Hb and HbO2 was almost inverse. Not only information for reliable monitoring but also physiological parameters with respect to cerebral circulation and metabolism could be obtained by measuring the pulsatile components.

The Effects of Ethanol on the Morphological and Biochemical Properties of Individual Human Red Blood Cells.

PubMed

Lee, Sang Yun; Park, Hyun Joo; Best-Popescu, Catherine; Jang, Seongsoo; Park, Yong Keun

2015-01-01

Here, we report the results of a study on the effects of ethanol exposure on human red blood cells (RBCs) using quantitative phase imaging techniques at the level of individual cells. Three-dimensional refractive index tomograms and dynamic membrane fluctuations of RBCs were measured using common-path diffraction optical tomography, from which morphological (volume, surface area, and sphericity); biochemical (hemoglobin (Hb) concentration and Hb content); and biomechanical (membrane fluctuation) parameters were retrieved at various concentrations of ethanol. RBCs exposed to the ethanol concentration of 0.1 and 0.3% v/v exhibited cell sphericities higher than those of normal cells. However, mean surface area and sphericity of RBCs in a lethal alcoholic condition (0.5% v/v) are not statistically different with those of healthy RBCs. Meanwhile, significant decreases of Hb content and concentration in RBC cytoplasm at the lethal condition were observed. Furthermore, dynamic fluctuation of RBC membranes increased significantly upon ethanol treatments, indicating ethanol-induced membrane fluidization.

Association of Postmortem Blood Hemoglobin A1c Levels With Diabetic Conditions in Aviation Accident Pilot Fatalities

DTIC Science & Technology

2001-07-01

A1c ( HbA1c ) at selected time intervals during the 52-day period. Postmortem blood specimens from 34 aviation accident pilot fatalities were also...analyzed. Some of these pilots had a known history of diabetes. Results. HbA1c values in blood from volunteers did not significantly change for up to 52...days. The HbA1c concentration in postmortem blood samples from pilots ranged from 3.9-10.5%. Only one pilot with a HbA1c over 6.0% did not have a

Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as determinants of ribavirin-associate anemia in patients receiving standard anti-HCV treatment.

PubMed

DʼAvolio, Antonio; Ciancio, Alessia; Siccardi, Marco; Smedile, Antonina; Baietto, Lorena; Simiele, Marco; Marucco, Diego Aguilar; Cariti, Giuseppe; Calcagno, Andrea; de Requena, Daniel Gonzalez; Sciandra, Mauro; Cusato, Jessica; Troshina, Giulia; Bonora, Stefano; Rizzetto, Mario; Di Perri, Giovanni

2012-04-01

Functional variants of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of plasma RBV concentrations on hemoglobin (Hb) decrement. Moreover, no data have been published on the possible interplay between these 2 factors. A retrospective analysis included 167 patients. The ITPA variants rs7270101 and rs1127354 were genotyped and tested using the χ test for association with Hb reduction at week 4. We also investigated, using multivariate logistic regression, the impact of RBV plasma exposure on Hb concentrations. Both single nucleotide polymorphisms were associated with Hb decrease. The carrier of at least 1 variant allele in the functional ITPA single nucleotide polymorphisms was associated with a lower decrement of Hb (-1.1 g/dL), as compared with patients without a variant allele (-2.75 g/dL; P = 4.09 × 10). RBV concentrations were not influenced by ITPA genotypes. A cut-off of 2.3 μg/mL of RBV was found to be associated with anemia (area-under-receiver operating characteristic = 0.630, sensitivity = 50.0%, and specificity = 69.5%, P = 0.008). In multivariate logistic regression analyses, the carrier of a variant allele (P = 0.005) and plasma RBV concentrations <2.3 μg/mL (P = 0.016) were independently associated with protection against clinically significant anemia at week 4. Although no direct relationship was found between ITPA polymorphisms and plasma RBV concentrations, both factors were shown to be significantly associated with anemia. A multivariate regression model based on ITPA genetic polymorphisms and RBV trough concentration was developed for predicting the risk of anemia. By relying upon these 2 variables, an individualized management of anemia seems to be feasible in recipients of pegylated interferon-RBV therapy.

Monitoring of pre-frontal oxygen status in helicopter pilots using near-infrared spectrophotometers

PubMed Central

Kikukawa, Azusa; Kobayashi, Asao; Miyamoto, Yoshinori

2008-01-01

Background There are few in-flight studies of cognition-related cerebral oxygen status in helicopter pilots. Methods Four male helicopter pilots volunteered for nine sorties during visual flight in a BK117 and UH-60J. The pilots' pre-frontal oxy-hemoglobin (O2Hb) and deoxy-hemoglobin (HHb) concentration were continuously monitored from the right/left sections of the forehead using near-infrared spectrophotometers with a consideration of motion artifacts. Results The concentration of O2Hb progressively increased (13.98 μmol•L-1 as a maximum increased concentration) in both the right/left sections of the forehead from the basal level during the heightened cognitive demand of helicopter flight. There was comparatively little change (4.32 μmol•L-1 as a maximum increased concentration) in HHb concentration during measurement of helicopter flight. HHb changes were apparently not affected by a heightened cognitive demand of helicopter pilots. Conclusion These results demonstrate that near-infrared spectroscopy, especially O2Hb measurements, provides a sensitive method for the monitoring of cognitive demand (maneuvers) in helicopter pilots. PMID:18616829

Maternal hemoglobin concentration and adverse pregnancy outcomes at low and moderate altitudes in Peru.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos E

2012-07-01

To identify associations of maternal hemoglobin (Hb) with perinatal outcomes at low and moderate altitudes in Peru. Study of records with sequential information using perinatal database system. The study included 295 651 pregnant women with their products. Using multiple logistic regression analysis, we estimated the probability of stillbirths, preterm and small for gestational age (SGA) births associated with maternal Hb levels at low (0-1999 m) and moderate altitudes (2000-2999 m). Maternal Hb decreased as pregnancy progressed from first to third trimester at both altitudes. Hb was higher at moderate than at low altitude (p < 0.001). Risks for stillbirths increased with low maternal Hb (odds ratio [OR]: 1.39 for Hb 9-9.9; OR: 1.84 for Hb 8-8.9; OR: 3.25 for Hb 7-7.9; and OR: 7.8 for Hb <7 g/dl); with Hb higher than 14.5 g/dl (OR: 1.31) and with altitudes ≥ 2000 m (OR: 1.2). High preterm rates were also observed with low Hbs (OR: 1.16 for Hb 9-9.9; OR: 1.64 for Hb 8-8.9; OR: 2.25 for Hb 7-7.9; and OR:2.87 for Hb<7 g/dl) and with Hb higher than 14.5 g/dl (OR: 1.14). High SGA rates were observed in neonates with maternal Hb of 7-7.9 (OR: 1.35) and <7 g/dl (OR:1.57), and higher than 14.5 g/dl (OR: 1.33), and with moderate altitudes (OR: 1.12). The cut-off points for lower risks of stillbirth and preterm births was 10 g/dl, and for SGA 9 g/dl of hemoglobin. Low and high maternal Hb levels and moderate altitude were independent risk factors for adverse perinatal outcomes.

Dynamic Mass Transfer of Hemoglobin at the Aqueous/Ionic-Liquid Interface Monitored with Liquid Core Optical Waveguide.

PubMed

Chen, Xuwei; Yang, Xu; Zeng, Wanying; Wang, Jianhua

2015-08-04

Protein transfer from aqueous medium into ionic liquid is an important approach for the isolation of proteins of interest from complex biological samples. We hereby report a solid-cladding/liquid-core/liquid-cladding sandwich optical waveguide system for the purpose of monitoring the dynamic mass-transfer behaviors of hemoglobin (Hb) at the aqueous/ionic liquid interface. The optical waveguide system is fabricated by using a hydrophobic IL (1,3-dibutylimidazolium hexafluorophosphate, BBimPF6) as the core, and protein solution as one of the cladding layer. UV-vis spectra are recorded with a CCD spectrophotometer via optical fibers. The recorded spectra suggest that the mass transfer of Hb molecules between the aqueous and ionic liquid media involve accumulation of Hb on the aqueous/IL interface followed by dynamic extraction/transfer of Hb into the ionic liquid phase. A part of Hb molecules remain at the interface even after the accomplishment of the extraction/transfer process. Further investigations indicate that the mass transfer of Hb from aqueous medium into the ionic liquid phase is mainly driven by the coordination interaction between heme group of Hb and the cationic moiety of ionic liquid, for example, imidazolium cation in this particular case. In addition, hydrophobic interactions also contribute to the transfer of Hb.

Phase Separation and Crystallization of Hemoglobin C in Transgenic Mouse and Human Erythrocytes

PubMed Central

Canterino, Joseph E.; Galkin, Oleg; Vekilov, Peter G.; Hirsch, Rhoda Elison

2008-01-01

Individuals expressing hemoglobin C (β6 Glu→Lys) present red blood cells (RBC) with intraerythrocytic crystals that form when hemoglobin (Hb) is oxygenated. Our earlier in vitro liquid-liquid (L-L) phase separation studies demonstrated that liganded HbC exhibits a stronger net intermolecular attraction with a longer range than liganded HbS or HbA, and that L-L phase separation preceded and enhanced crystallization. We now present evidence for the role of phase separation in HbC crystallization in the RBC, and the role of the RBC membrane as a nucleation center. RBC obtained from both human homozygous HbC patients and transgenic mice expressing only human HbC were studied by bright-field and differential interference contrast video-enhanced microscopy. RBC were exposed to hypertonic NaCl solution (1.5–3%) to induce crystallization within an appropriate experimental time frame. L-L phase separation occurred inside the RBC, which in turn enhanced the formation of intraerythrocytic crystals. RBC L-L phase separation and crystallization comply with the thermodynamic and kinetics laws established through in vitro studies of phase transformations. This is the first report, to the best of our knowledge, to capture a temporal view of intraerythrocytic HbC phase separation, crystal formation, and dissolution. PMID:18621841

Erroneous HbA1c results in a patient with elevated HbC and HbF.

PubMed

Adekanmbi, Joy; Higgins, Trefor; Rodriguez-Capote, Karina; Thomas, Dylan; Winterstein, Jeffrey; Dixon, Tara; Gifford, Jessica L; Krause, Richard; Venner, Allison A; Clarke, Gwen; Estey, Mathew P

2016-11-01

HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM. Copyright © 2016 Elsevier B.V. All rights reserved.

Twenty-four-hour variations in blood glucose level in Japanese type 2 diabetes patients based on continuous glucose monitoring.

PubMed

Hajime, Maiko; Okada, Yosuke; Mori, Hiroko; Otsuka, Takashi; Kawaguchi, Mayuko; Miyazaki, Megumi; Kuno, Fumi; Sugai, Kei; Sonoda, Satomi; Tanaka, Kenichi; Kurozumi, Akira; Narisawa, Manabu; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya

2018-01-01

High fluctuations in blood glucose are associated with various complications. The correlation between glycated hemoglobin (HbA1c) level and fluctuations in blood glucose level has not been studied in Japanese patients with type 2 diabetes. In the present study, blood glucose profile stratified by HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type 2 diabetes patients. Our retrospective study included 294 patients with type 2 diabetes who were divided by HbA1c level into five groups (≥6.0 to <7.0%, ≥7.0 to <8.0%, ≥8.0 to <9.0%, ≥9.0 to <10.0% and ≥10%). The correlation between HbA1c level and CGM data was analyzed. The primary end-point was the difference in blood glucose fluctuations among the HbA1c groups. The mean blood glucose level increased significantly with increasing HbA1c (P trend  < 0.01). The standard deviation increased with increases in HbA1c (P trend  < 0.01). The mean amplitude of glycemic excursions did not vary significantly with HbA1c. The levels of maximum blood glucose, minimum blood glucose, each preprandial blood glucose, each postprandial maximum blood glucose, range of increase in postprandial glucose from pre-meal to after breakfast, the area under the blood concentration-time curve >180 mg/dL and percentage of the area under the blood concentration-time curve >180 mg/dL were higher with higher HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant and independent determinants of HbA1c. In Japanese patients treated for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c. Parameters other than HbA1c are required to evaluate fluctuations in blood glucose level in patients receiving treatment for type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

An Algebraic Approach to Guarantee Harmonic Balance Method Using Gröbner Base

NASA Astrophysics Data System (ADS)

Yagi, Masakazu; Hisakado, Takashi; Okumura, Kohshi

Harmonic balance (HB) method is well known principle for analyzing periodic oscillations on nonlinear networks and systems. Because the HB method has a truncation error, approximated solutions have been guaranteed by error bounds. However, its numerical computation is very time-consuming compared with solving the HB equation. This paper proposes an algebraic representation of the error bound using Gröbner base. The algebraic representation enables to decrease the computational cost of the error bound considerably. Moreover, using singular points of the algebraic representation, we can obtain accurate break points of the error bound by collisions.

Evaluation of the efficacy of perorally administered glutamic acid-chelated iron and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.

PubMed

Egeli, A K; Framstad, T

1998-02-01

The goals of this study were to evaluate the effect of orally administered amino acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight gain in two different breeds raised under commercial conditions. Altogether 92 Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were included in the study. The day after birth the litters were divided in two groups (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe-MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The piglets were weighed and bled before treatment the day after birth (day 1) and on days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1 and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the 72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and 80.2 kg, respectively. A significantly lower weight gain in the piglets with a birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess administration of Fe to small piglets may have a detrimental effect on weight gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb levels were also adequate in Gr. 1 in both breeds. There was a negative correlation between changes in Hb during the first weeks and the initial value. Though haematological values seemed to show inter-breed differences, with higher average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D pigs, the ability to avoid Fe deficiency nevertheless appeared to be the same in both breeds.

Direct electrochemistry with enhanced electrocatalytic activity of hemoglobin in hybrid modified electrodes composed of graphene and multi-walled carbon nanotubes.

PubMed

Sun, Wei; Cao, Lili; Deng, Ying; Gong, Shixing; Shi, Fan; Li, Gaonan; Sun, Zhenfan

2013-06-05

A graphene (GR) and multi-walled carbon nanotubes (MWCNT) hybrid was prepared and modified on a 1-hexylpyridinium hexafluorophosphate based carbon ionic liquid electrode (CILE). Hemoglobin (Hb) was immobilized on GR-MWCNT/CILE surface with Nafion as the film forming material and the modified electrode was denoted as Nafion/Hb-GR-MWCNT/CILE. Spectroscopic results revealed that Hb molecules retained its native structure in the GR-MWCNT hybird. Electrochemical behaviors of Hb were carefully investigated by cyclic voltammetry with a pair of well-defined redox peaks obtained, which indicated that direct electron transfer of Hb was realized in the hybrid modified electrode. The result could be attributed to the synergistic effects of GR-MWCNT hybrid with enlarged surface area and improved conductivity through the formation of a three-dimensional network. Electrochemical parameters of the immobilized Hb on the electrode surface were further calculated with the results of the electron transfer number (n) as 1.03, the charge transfer coefficient (a) as 0.58 and the electron-transfer rate constant (ks) as 0.97 s(-1). The Hb modified electrode showed good electrocatalytic ability toward the reduction of different substrates such as trichloroacetic acid in the concentration range from 0.05 to 38.0 mmol L(-1) with a detection limit of 0.0153 mmol L(-1) (3σ), H2O2 in the concentration range from 0.1 to 516.0 mmol L(-1) with a detection limit of 34.9 nmol/L (3σ) and NaNO2 in the concentration range from 0.5 to 650.0 mmol L(-1) with a detection limit of 0.282 μmol L(-1) (3σ). So the proposed electrode had the potential application in the third-generation electrochemical biosensors without mediator. Copyright © 2013 Elsevier B.V. All rights reserved.

Continuous wave optical spectroscopic system for use in magnetic resonance imaging scanners for the measurement of changes in hemoglobin oxygenation states in humans

NASA Astrophysics Data System (ADS)

Hulvershorn, Justin; Bloy, Luke; Leigh, John S.; Elliott, Mark A.

2003-09-01

A continuous wave near infrared three-wavelength laser diode spectroscopic (NIRS) system designed for use in magnetic resonance imaging (MRI) scanners is described. This system measures in vivo changes in the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (Hb) in humans. An algorithm is implemented to map changes in light intensity to changes in the concentrations of Hb and HbO. The system's signal to noise ratio is 3.4×103 per wavelength on an intralipid phantom with 10 Hz resolution. To demonstrate the system's performance in vivo, data taken on the human forearm during arterial occlusion, as well as data taken on the forehead during extended breath holds, are presented. The results show that the instrument is an extremely sensitive detector of hemodynamic changes in human tissue at high temporal resolution. NIRS directly measures changes in the concentrations of hemoglobin species. For this reason, NIRS will be useful in determining the sources of MRI signal changes in the body due to hemodynamic causes, while the precise anatomic information provided by MRI will aid in localizing NIRS contrast and improving the accuracy of models of light transport through tissue.

Approaching the evolutionary advantage of ancillary types of haemoglobin in Daphnia magna by simulation of oxygen supply.

PubMed

Moenickes, S; Richter, O; Pirow, R

2010-02-01

The planktonic crustacean Daphnia magna synthesizes haemoglobin (Hb) macromolecules of variant subunit composition and oxygen affinity. This is one of the strategies by which the animals cope with variations in environmental conditions such as ambient oxygen tension. The enrichment of high-affinity Hb molecules in the haemolymph of hypoxia-exposed animals is thought to reduce Hb synthesis costs due to an enhanced transport efficiency of these molecules in comparison to the low-affinity Hb molecules. How great this economic advantage is, and under which conditions this benefit disappears, is still not fully understood. Here we implemented a rigorously simplified model of the daphnid body and described the transport of oxygen from the environment via the haemolymph to the tissues in terms of the convection-diffusion-reaction equation. The model was validated by comparing various model predictions with experimental data. A sensitivity analysis was used to evaluate the influence of parameter uncertainties on the model predictions. Cost-benefit analysis revealed in which way at the system's level the increase in Hb oxygen affinity improves the oxygen loading at the respiratory surfaces and impairs the release of oxygen to the tissues. The benefit arising from the improved oxygen loading exceeds the disadvantage of impaired unloading only under conditions where the ambient oxygen tension is critically low and the Hb concentration is high. The low-affinity Hb, on the other hand, provides an advantage given that the Hb concentration is low and the ambient oxygen tension is well above the critical level. Computer-aided modelling and simulation therefore provide valuable mechanistic insights into the driving forces that could have shaped the evolution of globin genes in daphnids.

Blood transfusions may impair endothelium-dependent vasodilatation during coronary artery bypass surgery.

PubMed

Rungatscher, Alessio; Milani, Elisabetta; Covajes, Cecilia; Hallström, Seth; Gottin, Leonardo; Guidi, Gian Cesare; Luciani, Giovanni Battista; Faggian, Giuseppe

2017-07-01

The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether administration of different blood transfusions result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood flow in patients undergoing CABG surgery. Ninety-five consecutive patients undergoing elective CABG surgery were prospectively divided in four groups based on blood transfusion requirements during surgery: stored blood cells (SBC, n. 21), intraoperative autologous salvaged blood (ASB, n. 25), SBC and ASB (n.22), no transfusion (control, n. 27). Blood samples were collected before and after intervention to analyse plasma levels of fHb and NO consumption. Endothelium-dependent relaxation was assessed in left internal mammary artery (LIMA) rings harvested before chest closure. Peripheral artery tonometry was assessed after intervention. Transfusions with SBC increased plasma fHb (p<0.05). Transfusions of ASB resulted in higher plasma fHb compared to SBC (p<0.01). fHb concentrations directly correlated with NO consumption (r=0.65, p<0.001). Maximal endothelium-dependent relaxation in LIMA was significantly attenuated in SBC and ASB patients compared to control (15.2±3.1% vs 21.1±2.5% vs 43±5.0% respectively; p<0.01). Significant correlations were identified between the aortic pressure wave velocity, plasma fHb concentration and NO consumption (p<0.01). Intraoperative blood transfusions and particularly autologous salvaged blood impair endothelium-dependent relaxation through NO scavenging by fHb. These findings obtained in vitro and in vivo provide new insights into the adverse relation between blood transfusions and patient outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor.

PubMed

Lane-Serff, Harriet; MacGregor, Paula; Lowe, Edward D; Carrington, Mark; Higgins, Matthew K

2014-12-12

The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50° kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.

Characterization of Storage-Induced Red Blood Cell Hemolysis Using Raman Spectroscopy.

PubMed

Gautam, Rekha; Oh, Joo-Yeun; Marques, Marisa B; Dluhy, Richard A; Patel, Rakesh P

2018-06-11

The therapeutic efficacy and safety of stored red blood cells (RBCs) relies on minimal in-bag hemolysis. The accuracy of current methods of measuring hemolysis can suffer as a result of specimen collection and processing artefacts. To test whether Raman spectroscopy could be used to assess hemolysis. RBCs were stored for as long as 42 days. Raman spectra of RBCs were measured before and after washing, and hemolysis was measured in supernatant by visible spectroscopy. Raman spectra indicated increased concentrations of oxyhemoglobin (oxyHb) and methemoglobin (metHb), and decreased membrane fluidity with storage age. Changes in oxyHb and metHb were associated with the intraerythrocytic and extracellular fractions, respectively. Hemolysis increased in a storage age-dependent manner. Changes in Raman bands reflective of oxyHb, metHb, and RBC membranes correlated with hemolysis; the most statistically significant change was an increased intensity of metHb and decreased membrane fluidity. These data suggest that Raman spectroscopy may offer a new label-free modality to assess RBC hemolysis during cold storage.

The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation.

PubMed

Koda, Michiko; Kitamura, Itsuko; Okura, Tomohiro; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

2016-01-01

Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (<100 cm(2) and ≥100 cm(2)). The serum triglyceride (TG) levels of 835 males were assessed. In the VFA ≥100 cm(2) group, a significantly greater proportion of current smokers (47.3%) exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4%) and non-smokers (18.8%). The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm(2), the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA <100 cm(2) group, significantly higher proportions of current smokers (17.9%) and former smokers (14.9%) demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%). In contrast, in the VFA ≥100 cm(2) group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects' TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA.

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

PubMed

Ferreira, A L; Machado, P E; Matsubara, L S

1999-06-01

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

Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity

NASA Technical Reports Server (NTRS)

Beckman, D. A.; Evans, J. W.; Oyama, J.

1978-01-01

Red cell survival, ferrokinetics, and hematologic parameters were investigated in beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and Cr-51-elution were significantly increased; maximum Fe-59 incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of Cr-51-labeled red cells and Fe-59-labeled transferrin. Red cell count, F(cells), total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

Capillary-scale direct measurement of hemoglobin concentration of erythrocytes using photothermal angular light scattering.

PubMed

Kim, Uihan; Song, Jaewoo; Lee, Donghak; Ryu, Suho; Kim, Soocheol; Hwang, Jaehyun; Joo, Chulmin

2015-12-15

We present a direct, rapid and chemical-free detection method for hemoglobin concentration ([Hb]), based on photothermal angular light scattering. The iron oxides contained in hemoglobin molecules exhibit high absorption of 532-nm light and generate heat under the illumination of 532-nm light, which subsequently alters the refractive index of blood. We measured this photothermal change in refractive index by employing angular light scattering spectroscopy with the goal of quantifying [Hb] in blood samples. Highly sensitive [Hb] measurement of blood samples was performed by monitoring the shifts in angularly dispersed scattering patterns from the blood-loaded microcapillary tubes. Our system measured [Hb] over the range of 0.35-17.9 g/dL with a detection limit of ~0.12 g/dL. Our sensor was characterized by excellent correlation with a reference hematology analyzer (r>0.96), and yielded a precision of 0.63 g/dL for a blood sample of 9.0 g/dL. Copyright © 2015 Elsevier B.V. All rights reserved.

Production of (R)-3-hydroxybutyric acid by fermentation and bioconversion processes with Azohydromonas lata.

PubMed

Ugwu, Charles U; Tokiwa, Yutaka; Ichiba, Toshio

2011-06-01

Feasibility of producing (R)-3-hydroxybutyric acid ((R)-3-HB) using wild type Azohydromonas lata and its mutants (derived by UV mutation) was investigated. A. lata mutant (M5) produced 780 m g/l in the culture broth when sucrose was used as the carbon source. M5 was further studied in terms of its specificity with various bioconversion substrates for production of (R)-3-HB. (R)-3-HB concentration produced in the culture broth by M5 mutant was 2.7-fold higher than that of the wild type strain when sucrose (3% w/v) and (R,S)-1,3-butanediol (3% v/v) were used as carbon source and bioconversion substrate, respectively. Bioconversion of resting cells (M5) with glucose (1% v/w), ethylacetoacetate (2% v/v), and (R,S)-1,3-butanediol (3% v/v), resulted in (R)-3-HB concentrations of 6.5 g/l, 7.3g/l and 8.7 g/l, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sickle Cell Hemoglobin with Mutation at αHis-50 Has Improved Solubility.

PubMed

Tam, Ming F; Tam, Tsuey Chyi S; Simplaceanu, Virgil; Ho, Nancy T; Zou, Ming; Ho, Chien

2015-08-28

The unliganded tetrameric Hb S has axial and lateral contacts with neighbors and can polymerize in solution. Novel recombinants of Hb S with single amino acid substitutions at the putative axial (recombinant Hb (rHb) (βE6V/αH20R) and rHb (βE6V/αH20Q)) or lateral (rHb (βE6V/αH50Q)) or double amino acid substitutions at both the putative axial and lateral (rHb (βE6V/αH20R/αH50Q) and rHb (βE6V/αH20Q/αH50Q)) contact sites were expressed in Escherichia coli and purified for structural and functional studies. The (1)H NMR spectra of the CO and deoxy forms of these mutants indicate that substitutions at either αHis-20 or αHis-50 do not change the subunit interfaces or the heme pockets of the proteins. The double mutants show only slight structural alteration in the β-heme pockets. All mutants have similar cooperativity (n50), alkaline Bohr effect, and autoxidation rate as Hb S. The oxygen binding affinity (P50) of the single mutants is comparable with that of Hb S. The double mutants bind oxygen with slightly higher affinity than Hb S under the acidic conditions. In high salt, rHb (βE6V/αH20R) is the only mutant that has a shorter delay time of polymerization and forms polymers more readily than Hb S with a dextran-Csat value of 1.86 ± 0.20 g/dl. Hb S, rHb (βE6V/αH20Q), rHb (βE6V/αH50Q), rHb (βE6V/αH20R/αH50Q), and rHb (βE6V/αH20Q/αH50Q) have dextran-Csat values of 2.95 ± 0.10, 3.04 ± 0.17, 11.78 ± 0.59, 7.11 ± 0.66, and 10.89 ± 0.83 g/dl, respectively. rHb (βE6V/αH20Q/αH50Q) is even more stable than Hb S under elevated temperature (60 °C). © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Real-time measurement of cerebral blood flow during and after repetitive transcranial magnetic stimulation: A near-infrared spectroscopy study.

PubMed

Park, Eunhee; Kang, Min Jae; Lee, Ahee; Chang, Won Hyuk; Shin, Yong-Il; Kim, Yun-Hee

2017-07-13

To confirm the interhemispheric modulation induced by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex, real-time regional cerebral blood flow (rCBF) was assessed using functional near-infrared spectroscopy (fNIRS) in the contralateral primary motor cortex (M1) and premotor cortex (PM). Ten right-handed healthy subjects completed two experimental sessions that were randomly arranged for real or sham rTMS session. In the real rTMS session, fNIRS data were acquired from the right M1 and PM area, while the motor hot spot of the left M1 was stimulated with 1Hz rTMS for 1200 pulses with two boosters. In the sham stimulation session, stimulation was delivered with a disconnected coil. During the real rTMS session, the concentration of oxyhemoglobin ([oxy-Hb]) in the right M1 increased continuously until the end of the stimulation. These changes lasted for 20min, while the right PM did not show a change in [oxy-Hb] concentration. On the other hand, the concentration of deoxy-hemoglobin ([deoxy-Hb]) decreased continuously in the right M1 and PM during the real rTMS stimulation, and this change lasted for 20min after the stimulation. The sham stimulation did not exhibit any significant change in both [oxy-Hb] and [deoxy-Hb] concentration during or after the stimulation. Application of 1Hz rTMS over M1 resulted in changes of rCBF in contralateral M1 and PM, which seemed to constitute a function of interhemispheric modulation of rTMS. The fNIRS data was able to detect this physiological change of neuromodulatory action of rTMS in real-time. Copyright © 2017. Published by Elsevier B.V.

Malaria in Pregnancy Is a Predictor of Infant Haemoglobin Concentrations during the First Year of Life in Benin, West Africa

PubMed Central

Accrombessi, Manfred; Ouédraogo, Smaïla; Agbota, Gino Cédric; Gonzalez, Raquel; Massougbodji, Achille; Menéndez, Clara; Cot, Michel

2015-01-01

Background Anaemia is an increasingly recognized health problem in Africa, particularly in infants and pregnant women. Although malaria is known to be the main risk factor of anaemia in both groups, the consequences of maternal factors, particularly malaria in pregnancy (MiP), on infant haemoglobin (Hb) concentrations during the first months of life are still unclear. Methods We followed-up a cohort of 1005 Beninese pregnant women from the beginning of pregnancy until delivery. A subsample composed of the first 400 offspring of these women were selected at birth and followed until the first year of life. Placental histology and blood smear at 1st clinical antenatal visit (ANC), 2nd ANC and delivery were used to assess malaria during pregnancy. Infant Hb concentrations were measured at birth, 6, 9 and 12 months of age. A mixed multi-level model was used to assess the association between MiP and infant Hb variations during the first 12 months of life. Results Placental malaria (difference mean [dm] = - 2.8 g/L, 95% CI [-5.3, -0.3], P = 0.03) and maternal peripheral parasitaemia at delivery (dm = - 4.6 g/L, 95% CI [-7.9, -1.3], P = 0.007) were the main maternal factors significantly associated with infant Hb concentrations during the first year of life. Poor maternal nutritional status and malaria infection during infancy were also significantly associated with a decrease in infant Hb. Conclusion Antimalarial control and nutritional interventions before and during pregnancy should be reinforced to reduce specifically the incidence of infant anaemia, particularly in Sub-Saharan countries. PMID:26052704

Impact of poor glycemic control of type 2 diabetes mellitus on serum prostate-specific antigen concentrations in men.

PubMed

Atalay, Hasan Anıl; Akarsu, Murat; Canat, Lutfi; Ülker, Volkan; Alkan, İlter; Ozkuvancı, Unsal

2017-09-01

To evaluate the impact of poor glycemic control of type 2 diabetes mellitus (T2DM) on serum prostate-specific antigen (PSA) concentrations in men. We performed a prospective analysis of 215 consecutive patients affected by erectile dysfunction (ED). ED was evaluated using the IIEF-5 questionnaire and the poor glycemic control (PGC) of T2DM was assessed according to the HbA1c criteria (International Diabetes Federation). Patients were divided into PGC group (HbA1c ≥ 7%) and control group (CG) (HbA1c < 6%). Correlations between serum HbA1c levels and various variables were evaluated and multivariate logistic regression analyses were carried out to identify variables for PGC. We compared 110 cases to 105 controls men ranging from 44 to 81 years of age, lower PSA concentrations were observed in men with PGC (PGC mean PSA: 0.9 ng/dl, CG mean PSA: 2.1 ng/dl, p < 0.001). Also mean prostate volume was 60% was smaller among men with PGC compared with men with CG (PGC mean prostate volume: 26 ml, CG prostate volume: 43 ml, p < 0.001). A strong negative correlation was found between serum HbA1c levels and serum PSA (p < 0.001 and r = -0.665) concentrations in men with PGC. We also found at the multivariate logistic regression model that PSA, prostate volume and peak systolic velocity were independent predictors of PGC. Our results suggest that there is significant impact of PGC on serum PSA levels in T2DM. Poor glycemic control of type 2 diabetes was associated with lower serum PSA levels and smaller prostate volumes.

Prevalence, Incidence, and Factor Concentrate Usage Trends of Hemophiliacs in Taiwan

PubMed Central

Tu, Tsu-Chiang; Liou, Wen-Shyong; Chou, Tsui-Yun; Lin, Tsung-Kun; Lee, Chuan-Fang; Chen, Jye-Daa; Cham, Thau-Ming

2013-01-01

Purpose Hemophilia A and B (HA, HB) are the most common X-linked inherited bleeding disorders. The introduction of factor concentrates has allowed for control of the lifelong chronic disease. However, no studies have been published regarding the epidemiology of hemophilia in Taiwan. Our aim was to determine the prevalence, incidence, and mortality rate, as well as trends in the use of factor concentrates, in individuals with hemophilia in Taiwan. Materials and Methods A retrospective study was conducted using the National Health Insurance Research Database between 1997 and 2007. Results We identified 988 males with hemophilia (HA : HB ratio=5.4 : 1). The mean prevalence per 100000 males was 6.7±0.1 for HA and 1.2±0.1 for HB. The estimated mean annual incidence per live male birth was 1 in 10752 for HA and 1 in 47619 for HB. Standardized mortality ratios for males with hemophilia (all severities) or severe hemophilia were 1.3- and 2.1-fold higher than that of the general male population, respectively. Mean factor VIII (FVIII) and factor IX (FIX) usage was 1.5003±0.4029 and 0.3126±0.0904 international units (IUs) per capita, respectively. Mean FVIII and FIX usage per patient with hemophilia (all severities) or severe hemophilia was 44027±11532 and 72341±17298, respectively, and 49407±13015 and 74369±18411 IUs per person with HA or HB, respectively. Conclusion Our data revealed epidemiologic and factor concentrate usage trends in males with hemophilia in Taiwan, highlighting a need for improvements in the mandatory National Health Insurance registry. A better-designed, patient-centered registry system would enable more detailed patient information collection and analysis, improving subsequent care. PMID:23225801

Role of hemoglobin and capillarization for oxygen delivery and extraction in muscular exercise.

PubMed

Saltin, B; Kiens, B; Savard, G; Pedersen, P K

1986-01-01

Through the years the role of the various links in the transport of oxygen in the human body has been discussed extensively, and especially whether one of these links could be singled out as limiting oxygen uptake during exercise. In his thesis work Lars Hermansen dealt with several of these variables related to oxygen transport and uptake. Two of these were the hemoglobin concentration of the blood (Hb) and skeletal muscle capillarization. These are the focus of this article. It can be demonstrated that variation in arterial oxygen content due to different Hb concentrations is fully compensated for at the level of the muscle, i.e. the amount of oxygen delivered to contracting muscles is adjusted by a variation in the blood flow so that it is the same regardless of Hb concentration in the range of 118-172 g X l-1. At the systemic level, with a large fraction of the muscle exercising, this causes an increase in submaximal heart rate and a lowering in maximal oxygen uptake in people with low as compared to normal or high Hb concentration. The primary significance of an enlarged capillary network in the muscle does not appear to be for accommodating a larger flow, but rather to allow for a long enough mean transit time and large enough surface area for optimal exchange of gases, substrates and metabolites.

Modeling of Nitrous Oxide Production from Nitritation Reactors Treating Real Anaerobic Digestion Liquor

PubMed Central

Wang, Qilin; Ni, Bing-Jie; Lemaire, Romain; Hao, Xiaodi; Yuan, Zhiguo

2016-01-01

In this work, a mathematical model including both ammonium oxidizing bacteria (AOB) and heterotrophic bacteria (HB) is constructed to predict N2O production from the nitritation systems receiving the real anaerobic digestion liquor. This is for the first time that N2O production from such systems was modeled considering both AOB and HB. The model was calibrated and validated using experimental data from both lab- and pilot-scale nitritation reactors. The model predictions matched the dynamic N2O, ammonium, nitrite and chemical oxygen demand data well, supporting the capability of the model. Modeling results indicated that HB are the dominant contributor to N2O production in the above systems with the dissolved oxygen (DO) concentration of 0.5–1.0 mg O2/L, accounting for approximately 75% of N2O production. The modeling results also suggested that the contribution of HB to N2O production decreased with the increasing DO concentrations, from 75% at DO = 0.5 mg O2/L to 25% at DO = 7.0 mg O2/L, with a corresponding increase of the AOB contribution (from 25% to 75%). Similar to HB, the total N2O production rate also decreased dramatically from 0.65 to 0.25 mg N/L/h when DO concentration increased from 0.5 to 7.0 mg O2/L. PMID:27125491

[2,3 diphosphoglycerate in preterm newborns].

PubMed

Scopesi, F; Canini, S; Mazzella, M; Arioni, C; Lantieri, P; Serra, G

2000-01-01

It has been largely shown that during the first month of life, in the preterm neonate Hb levels and Hct percentages rapidly decrease, high HbF concentration persists and a high oxygen affinity occurs. Data are needed to establish the level at which 2,3 dyphosphoglycerate (2,3 DPG) interacts with the regulation of oxygen affinity. 24 samples, from eight uncomplicated preterm newborns (34.1 +/- 1.83 GW, 1869 +/- +/- 291 BW) obtained at the same time as those required for the clinical management of the infants, were collected on the 2nd, 7th and 14th day of life. Blood gases, total hemoglobin and hematocrit were obtained from 0.3 ml arterialised capillary blood. Assays of 2,3 DPG were made separately on 0.4 ml venous blood. As expected tHb concentration and Hct percentages significantly decreased from day 2 to day 14 in all eight cases. On the contrary 2,3 DPG and p50 values remained stable. Subsequently throughout the study period all neonates had an increased 2,3 DPG/Hb ratio that was significantly related with p50 at standard conditions (p < 0.05). Stable 2,3 DPG concentrations during all study period have been detected. The subsequent significant increased 2.3 DPG/Hb, ratio related to increased p50 values, could have a key role in a physiological mechanism aimed to ensure adequate oxygen delivery to the tissues and to counteract the higher oxygen affinity of fetal hemoglobin. A wider sample is needed to validate this hypothesis.

Note: Three wavelengths near-infrared spectroscopy system for compensating the light absorbance by water

NASA Astrophysics Data System (ADS)

Bhutta, M. Raheel; Hong, Keum-Shik; Kim, Beop-Min; Hong, Melissa Jiyoun; Kim, Yun-Hee; Lee, Se-Ho

2014-02-01

Given that approximately 80% of blood is water, we develop a wireless functional near-infrared spectroscopy system that detects not only the concentration changes of oxy- and deoxy-hemoglobin (HbO and HbR) during mental activity but also that of water (H2O). Additionally, it implements a water-absorption correction algorithm that improves the HbO and HbR signal strengths during an arithmetic task. The system comprises a microcontroller, an optical probe, tri-wavelength light emitting diodes, photodiodes, a WiFi communication module, and a battery. System functionality was tested by means of arithmetic-task experiments performed by healthy male subjects.

Note: three wavelengths near-infrared spectroscopy system for compensating the light absorbance by water.

PubMed

Bhutta, M Raheel; Hong, Keum-Shik; Kim, Beop-Min; Hong, Melissa Jiyoun; Kim, Yun-Hee; Lee, Se-Ho

2014-02-01

Given that approximately 80% of blood is water, we develop a wireless functional near-infrared spectroscopy system that detects not only the concentration changes of oxy- and deoxy-hemoglobin (HbO and HbR) during mental activity but also that of water (H2O). Additionally, it implements a water-absorption correction algorithm that improves the HbO and HbR signal strengths during an arithmetic task. The system comprises a microcontroller, an optical probe, tri-wavelength light emitting diodes, photodiodes, a WiFi communication module, and a battery. System functionality was tested by means of arithmetic-task experiments performed by healthy male subjects.

Hair cortisol concentration and glycated hemoglobin in African American adults.

PubMed

Lehrer, H Matthew; Dubois, Susan K; Maslowsky, Julie; Laudenslager, Mark L; Steinhardt, Mary A

2016-10-01

African Americans have higher diabetes prevalence compared to Whites. They also have elevated cortisol levels - indicating possible HPA axis dysregulation - which may raise blood glucose as part of the biological response to physiological and psychosocial stress. Little is known about chronic cortisol levels in African Americans, and even less about the role of chronically elevated cortisol in type 2 diabetes development in this racial group. We used analysis of cortisol in hair to examine associations of long-term (∼3months) cortisol levels with glycated hemoglobin (HbA1c) in a group of African American adults. In exploratory analyses, we also studied the relationship of hair dehydroepiandrosterone (DHEA) with HbA1c. Participants were 61 community-dwelling African American adults (85% female; mean age 54.30 years). The first 3cm of scalp-near hair were analyzed for cortisol and DHEA concentration using enzyme-linked immunoassay analysis. Glycated hemoglobin was assessed, and regression analyses predicting HbA1c from hair cortisol and DHEA were performed in the full sample and in a subsample of participants (n=20) meeting the National Institute of Diabetes and Digestive Kidney Disease (NIDDK) criteria for type 2 diabetes (HbA1c≥6.5%). In the full sample, HbA1c increased with hair cortisol level (β=0.22, p=0.04, f(2)=0.10), independent of age, sex, chronic health conditions, diabetes medication use, exercise, and depressive symptoms. In the subsample of participants with an HbA1c≥6.5%, hair cortisol was also positively related to HbA1c (β=0.45, p=0.04, f(2)=0.32), independent of diabetes medication use. Glycated hemoglobin was unrelated to hair DHEA in both the full sample and HbA1c≥6.5% subsample. Long-term HPA axis dysregulation in the form of elevated hair cortisol is associated with elevated HbA1c in African American adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolution, Three-Dimensional Model and Localization of Truncated Hemoglobin PttTrHb of Hybrid Aspen

PubMed Central

Dumont, Estelle; Jokipii-Lukkari, Soile; Parkash, Vimal; Vuosku, Jaana; Sundström, Robin; Nymalm, Yvonne; Sutela, Suvi; Taskinen, Katariina; Kallio, Pauli T.; Salminen, Tiina A.; Häggman, Hely

2014-01-01

Thus far, research on plant hemoglobins (Hbs) has mainly concentrated on symbiotic and non-symbiotic Hbs, and information on truncated Hbs (TrHbs) is scarce. The aim of this study was to examine the origin, structure and localization of the truncated Hb (PttTrHb) of hybrid aspen (Populus tremula L. × tremuloides Michx.), the model system of tree biology. Additionally, we studied the PttTrHb expression in relation to non-symbiotic class1 Hb gene (PttHb1) using RNAi-silenced hybrid aspen lines. Both the phylogenetic analysis and the three-dimensional (3D) model of PttTrHb supported the view that plant TrHbs evolved vertically from a bacterial TrHb. The 3D model suggested that PttTrHb adopts a 2-on-2 sandwich of α-helices and has a Bacillus subtilis -like ligand-binding pocket in which E11Gln and B10Tyr form hydrogen bonds to a ligand. However, due to differences in tunnel cavity and gate residue (E7Ala), it might not show similar ligand-binding kinetics as in Bs-HbO (E7Thr). The immunolocalization showed that PttTrHb protein was present in roots, stems as well as leaves of in vitro -grown hybrid aspens. In mature organs, PttTrHb was predominantly found in the vascular bundles and specifically at the site of lateral root formation, overlapping consistently with areas of nitric oxide (NO) production in plants. Furthermore, the NO donor sodium nitroprusside treatment increased the amount of PttTrHb in stems. The observed PttTrHb localization suggests that PttTrHb plays a role in the NO metabolism. PMID:24520401

Production of high molecular weight poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer by Cupriavidus malaysiensis USMAA1020 utilising substrate with longer carbon chain.

PubMed

Huong, Kai-Hee; Elina, K A R; Amirul, A A

2018-05-01

Long carbon chain alkanediols are used in the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)], however these substrates possess high toxicity towards bacterial cells. This study demonstrated the effective utilisation of a long carbon chain alkanediol, namely 1,8-octanediol, to enhance the yield and production of a copolymer with a high molecular weight of over 1000 kDa, which is desirable for novel applications in medical and biopharmaceuticals. The increased PHA content (47-61 wt%) and concentration (1.7-4.5 g/L) was achieved by additional feeding of a combination of C4 substrates at C/N 10, with 1,8-octanediol + γ-butyrolactone producing P(3HB-co-22 mol% 4HB) with a high molecular weight (1060 kDa) and elongation at break of 970%. The DO-stat feeding strategy of C/N 10 has shown an increment of PHA concentration for both carbon combination, 0.45-4.27 g/L and 0.32-3.36 g/L for 1,8-octanediol + sodium 4-hydroxybutyrate (4HB-Na) and 1,8-octanediol + γ-butyrolactone, but with a slight reduction on molecular weight and mechanical strength. Nonetheless, further study revealed that a nitrogen-absence feeding strategy could retain the high molecular weight and elongation at break of the copolymer, and simultaneously improving the overall P(3HB-co-4HB) production. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia

PubMed Central

Fowkes, Freya J. I; Allen, Stephen J; Allen, Angela; Alpers, Michael P; Weatherall, David J; Day, Karen P

2008-01-01

Background The heritable haemoglobinopathy α+-thalassaemia is caused by the reduced synthesis of α-globin chains that form part of normal adult haemoglobin (Hb). Individuals homozygous for α+-thalassaemia have microcytosis and an increased erythrocyte count. α+-Thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration < 50 g/l), but does not influence parasite count. We tested the hypothesis that the erythrocyte indices associated with α+-thalassaemia homozygosity provide a haematological benefit during acute malaria. Methods and Findings Data from children living on the north coast of Papua New Guinea who had participated in a case-control study of the protection afforded by α+-thalassaemia against severe malaria were reanalysed to assess the genotype-specific reduction in erythrocyte count and Hb levels associated with acute malarial disease. We observed a reduction in median erythrocyte count of ∼1.5 × 1012/l in all children with acute falciparum malaria relative to values in community children (p < 0.001). We developed a simple mathematical model of the linear relationship between Hb concentration and erythrocyte count. This model predicted that children homozygous for α+-thalassaemia lose less Hb than children of normal genotype for a reduction in erythrocyte count of >1.1 × 1012/l as a result of the reduced mean cell Hb in homozygous α+-thalassaemia. In addition, children homozygous for α+-thalassaemia require a 10% greater reduction in erythrocyte count than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA. We estimated that the haematological profile in children homozygous for α+-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval [CI] 0.24–1.12, p = 0.09). Conclusions The increased erythrocyte count and microcytosis in children homozygous for α+-thalassaemia may contribute substantially to their protection against SMA. A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum. This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia. Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage. PMID:18351796

Socioeconomic inequality in Hepatitis B vaccination of rural adults in China.

PubMed

Zhu, Dawei; Guo, Na; Wang, Jian; Nicholas, Stephen; Wang, Zhen; Zhang, Guojie; Shi, Luwen; Wangen, Knut Reidar

2018-02-01

Hepatitis B (HB) vaccination is the most effective way to prevent HB virus infection. While measures taken to control the prevalence of HB have achieved significant results, HB prevalence in rural China among adults remains problematic. This study sheds new light on the determinants of HB vaccine uptake and its inequality according to socioeconomic status in rural areas of China. We interviewed 22,283 adults, aged 18-59 years, from 8444 households, in 48 villages from 8 provinces. Vaccination status was modeled by using two logistic models: whether take at least one HB vaccine and whether to complete the entire vaccination regime. The Erreygers' concentration index ([Formula: see text]) was used to quantify the degree of inequality and the decomposition approach was used to uncover the determinants of inequality in vaccine uptake. We found that the coverage rate of HB vaccination is 20.2%, and the completion rate is 16.0%. The [Formula: see text] of at least one dose (0.081) and three doses (0.076) revealed a substantial pro-rich inequality. Income contributed the largest percentage to HB vaccination inequalities (52.17% for at least one dose and 52.03% for complete vaccinations). HB awareness was another important cause of inequality in HB vaccination (around 30%). These results imply that rich had a greater tendency to vaccinate and inequality favouring the rich was almost equal for the complete three doses. While the factors associated with HB vaccination uptake and inequalities were multifaceted, income status and HB awareness were the main barriers for the poor to take HB vaccine by adults in rural China.

Haemoglobin dynamics in Papuan and non-Papuan adults in northeast Papua, Indonesia, with acute, uncomplicated vivax or falciparum malaria

PubMed Central

2013-01-01

Background Haemoglobin (Hb) recovers slowly in malaria and may be influenced by naturally acquired immunity. Hb recovery was compared in malaria immune, indigenous Papuan and non-Papuan adults with limited malaria exposure. Methods Hb concentrations were measured on Days (D) 0, 3, 7, and 28 in 57 Papuans and 105 non-Papuans treated with chloroquine, doxycycline or both drugs for acute, uncomplicated Plasmodium vivax (n?=?64) or Plasmodium falciparum (n?=?98). Results Mean (SD, range) D0 Hb was 12.7 (2.2, 7–21.3) g/dL and was similar in P. falciparum infected Papuans and non-Papuans: 12.2 vs. 12.8 g/dL (P?=?0.15) but significantly lower in: (i) P. vivax-infected Papuans vs. P. vivax-infected non-Papuans: 11.4 vs. 13.47 g/dL [∆?=?−2.07 (95% CI: –3.3 – –0.8), P?=?0.0018], (ii) all patients with splenomegaly (vs. those without splenomegaly): 12.16 vs. 13.01 g/dL [∆?=?−0.85 (−1.6– –0.085), P?=?0.029], and (iii) all females vs. all males: 10.18 vs. 13.01 g/dL [∆?=?−2.82 (−3.97 – –1.67), P?

Heart failure and anemia: Effects on prognostic variables.

PubMed

Cattadori, Gaia; Agostoni, Piergiuseppe; Corrà, Ugo; Sinagra, Gianfranco; Veglia, Fabrizio; Salvioni, Elisabetta; Bonomi, Alice; La Gioia, Rocco; Scardovi, Angela B; Ferraironi, Alessandro; Emdin, Michele; Metra, Marco; Di Lenarda, Andrea; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Caravita, Sergio; Magrì, Damiano; Lombardi, Carlo; Frigerio, Maria; Oliva, Fabrizio; Girola, Davide; Mezzani, Alessandro; Farina, Stefania; Mapelli, Massimo; Scrutinio, Domenico; Pacileo, Giuseppe; Apostolo, Anna; Iorio, AnnaMaria; Paolillo, Stefania; Filardi, Pasquale Perrone; Gargiulo, Paola; Bussotti, Maurizio; Marchese, Giovanni; Correale, Michele; Badagliacca, Roberto; Sciomer, Susanna; Palermo, Pietro; Contini, Mauro; Giannuzzi, Pantaleo; Battaia, Elisa; Cicoira, Mariantonietta; Clemenza, Francesco; Minà, Chiara; Binno, Simone; Passino, Claudio; Piepoli, Massimo F

2017-01-01

Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO 2 ), ventilatory efficiency (VE/VCO 2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO 2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO 2 slope was associated with poor prognosis only in patients with low and normal Hb. Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO 2 and LVEF, but not VE/VCO 2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Heparin-binding epidermal growth factor expression in KATO-III cells after Helicobacter pylori stimulation under the influence of strychnos Nux vomica and Calendula officinalis.

PubMed

Hofbauer, Roland; Pasching, Eva; Moser, Doris; Frass, Michael

2010-07-01

Previous studies have shown the stimulating effect of Helicobacter pylori on the gene expression of heparin-binding epidermal growth factor (HB-EGF) using the gastric epithelial cell line KATO-III. Strychnos Nux vomica (Nux vomica) and Calendula officinalis are used in highly diluted form in homeopathic medicine to treat patients suffering from gastritis and gastric ulcers. To investigate the influence of Nux vomica and Calendula officinalis on HB-EGF-like growth factor gene expression in KATO-III cells under the stimulation of H. pylori strain N6 using real-time PCR with and without addition of Nux vomica and Calendula officinalis as a 10c or 12c potency. Baseline expression and stimulation were similar to previous experiments, addition of Nux vomica 10c and Calendula officinalis 10c in a 43% ethanolic solution led to a significant reduction of H. pylori induced increase in gene expression of HB-EGF (reduced to 53.12+/-0.95% and 75.32+/-1.16% vs. control; p<0.05), respectively. Nux vomica 12c reduced HB-EGF gene expression even in dilutions beyond Avogadro's number (55.77+/-1.09%; p<0.05). Nux vomica 12c in a 21.5% ethanol showed a smaller effect (71.80+/-3.91%, p<0.05). This effect was only be observed when the drugs were primarily prepared in ethanol, not in aqueous solutions. The data suggest that both drugs prepared in ethanolic solution are potent inhibitors of H. pylori induced gene expression. 2010 Elsevier Ltd. All rights reserved.

Accuracy of capillary blood 3-β-hydroxybutyrate determination for the detection and treatment of canine diabetic ketoacidosis.

PubMed

Bresciani, Francesca; Pietra, Marco; Corradini, Sara; Giunti, Massimo; Fracassi, Federico

2014-01-01

In human medicine, diagnosis of diabetic ketoacidosis (DKA) is usually based on measurement of capillary 3-β-hydroxybutyrate (3-HB) with a hand held ketone sensor. This study was conducted to determine if measurement of capillary 3-HB could be useful for the diagnosis and monitoring of canine DKA. Fifteen dogs with diabetic ketosis and 10 with DKA were evaluated. Paired measurements of 3-HB of capillary and venous blood samples were analysed by the electrochemical sensor and reference method. Use of capillary 3-HB measurement during DKA management was then evaluated through simultaneous measurements of capillary 3-HB, urinary AcAc and venous blood gas analysis. Good agreement between capillary and venous 3-HB measurement was detected by the electrochemical sensor and reference method. Monitoring treatment of DKA revealed a significant correlation between capillary 3-HB and acidosis markers, while no significant correlation was observed between AcAc and acidosis markers. A cut-off value of capillary blood 3-HB > 3.8 mmol/L for diagnosis of DKA resulted in 70% and 92% sensitivity and specificity. The electrochemical sensor accurately measures 3-HB concentration in both capillary and venous blood samples, is accurate in diagnosing canine DKA, and appears to reflect the patient's metabolic status during DKA treatment.

Thalassemia and Hemoglobin E in Southern Thai Blood Donors

PubMed Central

Kruachan, Kwanta; Sengking, Warachaya; Horpet, Dararat; Sungyuan, Ubol

2014-01-01

Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were recruited for thalassemia and Hb E screening by red blood cell indices/dichlorophenolindophenol precipitation test. β-Thalassemia and Hb E were then identified by high performance liquid chromatography and 4 common α-thalassemia deletions were characterized by a single tube-multiplex gap-polymerase chain reaction. Overall frequency of hemoglobinopathies was 12.9%, classified as follows: homozygous α-thalassemia 2 (1.7%), heterozygous α-thalassemia 1 (1.7%), heterozygous β-thalassemia without α-thalassemia (0.9%), heterozygous Hb E without α-thalassemia (5.2%), double heterozygotes for Hb E/α-thalassemia 1 (1.7%), homozygous Hb E without α-thalassemia (0.9%), and homozygous Hb E with heterozygous α-thalassemia 2 (0.9%). The usefulness of thalassemia screening is not only for receiving highly effective red blood cells in the recipients but also for encouraging the control and prevention program of thalassemia in blood donors. PMID:25050123

Noninvasive optical evaluation of low frequency oscillations in prefrontal cortex hemodynamics during verbal working memory

NASA Astrophysics Data System (ADS)

Li, Ting; Zhao, Yue; Li, Kai; Sun, Yunlong

2014-03-01

The low frequency oscillation (LFO) around 0.1 Hz has been observed recently in cerebral hemodynamic signals during rest/sleep, enhanced breathing, and head- up-tilting, showing that cerebral autoregulation can be accessed by LFOs. However, many brain function researches require direct measurement of LFOs during specified brain function activities. This pilot study explored using near-infrared spectroscopy/imaging (NIRS) to noninvasively and simultaneously detect LFOs of prefrontal cerebral hemodynamics (i.e., oxygenated/deoxygenated/total hemoglobin concentration: △[oxy-Hb]/ △[deoxy-Hb]/ △[tot-Hb]) during N-back visual verbal working memory task. The LFOs were extracted from the measured variables using power spectral analysis. We found the brain activation sites struck clear LFOs while other sites did not. The LFO of △[deoxy-Hb] acted as a negative pike and ranged in (0.05, 0.1) Hz, while LFOs of △[oxy-Hb] and △[tot-Hb] acted as a positive pike and ranged in (0.1, 0.15) Hz. The amplitude difference and frequency lag between △[deoxy-Hb] and △[oxy-Hb]/ △[tot-Hb] produced a more focused and sensitive activation map compare to hemodynamic amplitude-quantified activation maps. This study observed LFOs in brain activities and showed strong potential of LFOs in accessing brain functions.

DETERMINATION OF A BOUND MUSK XYLENE ...

EPA Pesticide Factsheets

Musk xylene (MX) is widely used as a fragrance ingredient in commercial toiletries. Identification and quantification of a bound 4-amino-MX (AMX) metabolite was carried out by gas chromatography-mass spectrometry (GC/MS), with selected ion monitoring (SIM). Detection of AMX occurred after the cysteine adducts in carp hemoglobin, derived from the nitroso metabolite, were released by alkaline hydrolysis. The released AMX metabolite was extracted into n-hexane. The extract was preconcentrated by evaporation, and analyzed by GC-SIM-MS. The concentration of AMX metabolite was found to range from 6.0 to 30.6 ng/g in the carp Hb, collected from the Las Vegas Wash and Lake Mead, Nevada areas. The presence of an AMX metabolite in the carp Hb was confirmed when similar mass spectral features and the same retention time of the AMX metabolite were obtained for both standard AMX and carp Hb extract solutions. In the non-hydrolyzed and reagent blank extracts, the AMX metabolite was not detected. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers,

Noninvasive quantitative documentation of cutaneous inflammation in vivo using spectral imaging

NASA Astrophysics Data System (ADS)

Stamatas, Georgios N.; Kollias, Nikiforos

2006-02-01

Skin inflammation is often accompanied by edema and erythema. While erythema is the result of capillary dilation and subsequent local increase of oxygenated hemoglobin (oxy-Hb) concentration, edema is characterized by an increase in extracellular fluid in the dermis leading to local tissue swelling. Edema and erythema are typically graded visually. In this work we tested the potential of spectral imaging as a non-invasive method for quantitative documentation of both the erythema and the edema reactions. As examples of dermatological conditions that exhibit skin inflammation we imaged patients suffering from acne, herpes zoster, and poison ivy rashes using a hyperspectral-imaging camera. Spectral images were acquired in the visible and near infrared part of the spectrum, where oxy-Hb and water demonstrate absorption bands. The values of apparent concentrations of oxy-Hb and water were calculated based on an algorithm that takes into account spectral contributions of deoxy-hemoglobin, melanin, and scattering. In each case examined concentration maps of oxy-Hb and water can be constructed that represent quantitative visualizations of the intensity and extent of erythema and edema correspondingly. In summary, we demonstrate that spectral imaging can be used in dermatology to quantitatively document parameters relating to skin inflammation. Applications may include monitoring of disease progression as well as efficacy of treatments.

Dietary nucleotide supplementation raises erythrocyte 2, 3-diphosphoglycerate concentration in neonatal rats.

PubMed

Scopesi, F; Verkeste, C M; Paola, D; Gazzolo, D; Pronzato, M A; Bruschettini, P L; Marinari, U M

1999-03-01

The present study was designed to test if dietary intake of nucleotides increases erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in neonatal rats. To this end, rat pups were fed a nucleotide-supplemented formula (S, n = 14) from d 9 until d 16 after birth. The results were compared with those obtained from a group of breast-fed pups (C, n = 14) and a group of pups artificially fed with nucleotide-free formula (NS, n = 14). Neonatal weight, 2,3-DPG concentration, hematocrit (Hct) and hemoglobin concentration (Hb) were determined before the experiment (d 9) and after 7 d of treatment (d 16). In all groups, 2,3-DPG concentration was greater at d 16 than d 9, and the increase was greater in the S group than in the NS group. Alterations in neonatal weight, Hct and Hb concentration did not differ among the groups. On d 16 the 2, 3-DPG/Hb ratio, reflecting the affinity of hemoglobin for oxygen, was significantly higher in the C and S groups than in the NS group. We conclude that in neonatal rats, dietary nucleotides increase erythrocyte 2,3-DPG concentration. Studies need to be conducted in humans to assess the effect of this increase on both neonatal peripheral hemodynamics and metabolism in this species.

Real-time measurement of oxyhemoglobin concentration changes in the frontal micturition area: an fNIRS study.

PubMed

Sakakibara, Ryuji; Tsunoyama, Kuniko; Takahashi, Osamu; Sugiyama, Megumi; Kishi, Masahiko; Ogawa, Emina; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori; Awa, Yusuke; Yamaguchi, Chiharu

2010-06-01

To explore brain activity in the frontal micturition area during natural bladder behavior. Five control subjects (one man and four women; mean age 61 years [38-70]) and four subjects with detrusor overactivity (all men; mean age 55 years [33-65]) were enrolled in the study. We performed real-time measurements of oxyhemoglobin concentration (oxy-Hb) changes in the frontal micturition area using functional near-infrared spectroscopy (fNIRS) in response to quasi-natural, continuous bladder filling, and voiding in a sitting position. In the control group the following results were obtained: (1) a slight increase of oxy-Hb before first sensation occurred, (2) there was a continuous increase of oxy-Hb during bladder filling to the point just after voiding began, (3) there was a continuous decrease of oxy-Hb after voiding, (4) in subjects who were unable to urinate, oxy-Hb also decreased after attempting to void, and (5) the area activated was the bilateral lateral prefrontal area, particularly Brodmann's areas 8, 10, and 46. In the detrusor overactivity group, (6) an increase of oxy-Hb before first sensation was rare and frontal cortical activation was weak, (7) at the moment detrusor overactivity appeared, fNIRS brain activity in the frontal cortex did not change significantly; and otherwise the results were almost the same as those in the control group. This study shows that the frontal micturition area is activated during natural bladder filling and voiding using fNIRS. (c) 2010 Wiley-Liss, Inc.

A diagnostic nomogram for delayed hemolytic transfusion reaction in sickle cell disease.

PubMed

Mekontso Dessap, Armand; Pirenne, France; Razazi, Keyvan; Moutereau, Stéphane; Abid, Shariq; Brun-Buisson, Christian; Maitre, Bernard; Michel, Marc; Galacteros, Frederic; Bartolucci, Pablo; Habibi, Anoosha

2016-12-01

Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso-occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within 1 week following an index transfusion and repeated within 2 months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%), and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post-transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. Am. J. Hematol. 91:1181-1184, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao Jin; State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University, Guangzhou; Department of Radiation Oncology, Anhui provincial hospital, Hefei

2012-03-15

Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease ( White-Up-Pointing-Small-Triangle Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specificmore » survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with White-Up-Pointing-Small-Triangle Hb of >11.5 g/L than in those with White-Up-Pointing-Small-Triangle Hb of {<=}11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.« less

Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women.

PubMed

Outzen, Malene; Egeberg, Rikke; Dragsted, Lars; Christensen, Jane; Olesen, Pelle T; Frandsen, Henrik; Overvad, Kim; Tjønneland, Anne; Olsen, Anja

2011-05-01

Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts. The study included 537 non-smoking women aged 50-65 years who participated in the Diet, Cancer and Health cohort (1993-97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th percentile 8, 95th percentile 49). Of the dietary factors studied, intakes of coffee and chips were statistically significantly associated with a 4 % per 200 g/d (95 % CI 2, 7; P < 0·0001) and an 18 % per 5 g/d (95 % CI 6, 31; P = 0·002) higher Hb-AA, respectively. This model explained 17 % of the variation in Hb-AA. Intakes of coffee and biscuits/crackers were statistically significantly associated with a 3 % per 200 g/d (95 % CI 1, 6; P = 0·005) and 12 % per 10 g/d (95 % CI 3, 23; P = 0·01) higher Hb-GA, respectively. This model explained 12 % of the variation in Hb-GA. In conclusion, only a few dietary determinants of Hb-AA and Hb-GA were identified. Thus, the present study implies that dietary intake measured by an FFQ explains only to a limited extent the variation in Hb-AA and Hb-GA concentrations.

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

PubMed Central

López-Garriga, Juan; Cadilla, Carmen L.

2016-01-01

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

Optical sensor technology for a noninvasive continuous monitoring of blood components

NASA Astrophysics Data System (ADS)

Kraitl, Jens; Timm, Ulrich; Lewis, Elfed; Ewald, Hartmut

2010-02-01

NIR-spectroscopy and Photoplethysmography (PPG) is used for a measurement of blood components. The absorptioncoefficient of blood differs at different wavelengths. This fact is used to calculate the optical absorbability characteristics of blood which is yielding information about blood components like hemoglobin (Hb), carboxyhemoglobin (CoHb) and arterial oxygen saturation (SpO2). The measured PPG time signals and the ratio between the peak to peak pulse amplitudes are used for a measurement of these parameters. Hemoglobin is the main component of red blood cells. The primary function of Hb is the transport of oxygen from the lungs to the tissue and carbon dioxide back to the lungs. The Hb concentration in human blood is an important parameter in evaluating the physiological status of an individual and an essential parameter in every blood count. Currently, invasive methods are used to measure the Hb concentration, whereby blood is taken from the patient and subsequently analyzed. Apart from the discomfort of drawing blood samples, an added disadvantage of this method is the delay between the blood collection and its analysis, which does not allow real time patient monitoring in critical situations. A noninvasive method allows pain free continuous on-line patient monitoring with minimum risk of infection and facilitates real time data monitoring allowing immediate clinical reaction to the measured data.

Comparison of the accuracy of hemoglobin point of care testing using HemoCue and GEM Premier 3000 with automated hematology analyzer in emergency room.

PubMed

Zatloukal, Jan; Pouska, Jiri; Kletecka, Jakub; Pradl, Richard; Benes, Jan

2016-12-01

The laboratory analysis provides accurate, but time consuming hemoglobin level estimation especially in the emergency setting. The reliability of time-sparing point of care devices (POCT) remains uncertain. We tested two POCT devices accuracy (HemoCue ® 201 + and Gem ® Premier™3000) in routine emergency department workflow. Blood samples taken from patients admitted to the emergency department were analyzed for hemoglobin concentration using a laboratory reference Beckman Coulter LH 750 (HB LAB ), the HemoCue (HB HC ) and the Gem Premier 3000 (HB GEM ). Pairwise comparison for each device and Hb LAB was performed using correlation and the Bland-Altman methods. The reliability of transfusion decision was assessed using three-zone error grid. A total of 292 measurements were performed in 99 patients. Mean hemoglobin level were 115 ± 33, 110 ± 28 and 111 ± 30 g/l for Hb HC , Hb GEM and Hb LAB respectively. A significant correlation was observed for both devices: Hb HC versus Hb LAB (r 2  = 0.93, p < 0.001) and HB GEM versus HB LAB (r 2  = 0.86, p < 0.001). The Bland-Altman method revealed bias of -3.7 g/l (limits of agreement -20.9 to 13.5) for HB HC and HB LAB and 2.5 g/l (-18.6 to 23.5) for HB GEM and HB LAB , which significantly differed between POCT devices (p < 0.001). Using the error grid methodology: 94 or 91 % of values (Hb HC and Hb GEM ) fell in the zone of acceptable difference (A), whereas 0 and 1 % (Hb HC and Hb GEM ) were unacceptable (zone C). The absolute accuracy of tested POCT devices was low though reaching a high level of correlation with laboratory measurement. The results of the Morey´s error grid were unfavorable for both POCT devices.

Polymer blends made of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) and epoxidized natural rubber: Thermal and mechanical response

NASA Astrophysics Data System (ADS)

Salim, Yoga Sugama; Han, Chan Chin; Kammer, Hans-Werner; Kumar, Sudesh; Neon, Gan Seng

2015-08-01

The ever-increasing demand of biodegradable over conventional polymers places microbial polyhydroxyalkanoates (PHA) as an ideal choice of research material for specific applications. In this study, polymer blends made of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx) and epoxidized natural rubber (ENR) were prepared using solution casting technique. The influence of ENR on thermal, morphological and mechanical properties of P(3HB-co-3HHx) was investigated. There are two glass transition (Tg) temperatures observed using differential scanning calorimeter. This indicates that P(3HB-co-3HHx) and ENR are immiscible at macroscopic level. Although the Tg of P(3HB-co-3HHx) is seen to shift toward ENR in the least manner, infrared analysis suggests that the crystal structure of P(3HB-co-3HHx) retains its conformational structure. In terms of morphology, ENR exists as droplets in P(3HB-co-3HHx)-rich phase, e.g. at ENR weight fraction (wENR) of 0.3. In dynamic mechanical analysis, all blend compositions exhibit solid-like behavior, with storage moduli larger than loss moduli, across the frequency sweep at room temperature.

Effects of indigo carmine intravenous injection on noninvasive and continuous total hemoglobin measurement.

PubMed

Isosu, Tsuyoshi; Satoh, Tomohiko; Oishi, Rieko; Imaizumi, Tsuyoshi; Hakozaki, Takahiro; Obara, Shinju; Ikegami, Yukihiro; Kurosawa, Shin; Murakawa, Masahiro

2016-06-01

The effects of an intravenous injection of indigo carmine on noninvasive and continuous total hemoglobin (SpHb) measurement were retrospectively evaluated. The subjects were 21 patients who underwent elective gynecologic surgery under general anesthesia. During surgery, 5 mL of 0.4 % indigo carmine was intravenously injected, and subsequent changes in SpHb concentrations were evaluated. The results demonstrate that the pre-injection SpHb level was 10 g/dL, and the minimum post-injection SpHb level was 8.3 g/dL. The amount of decrease was 1.8 g/dL. The time to reach the minimum value was 4 min, and the time to return to the pre-injection value was 15 min. The decrease in SpHb was greater in the group with a perfusion index (PI) < 1.4 than in the group with a PI > 1.4. The assessment of SpHb after an intravenous injection of indigo carmine necessitates caution.

Monitoring of prefrontal cortex activation during verbal n-back task with 24-channel functional NIRS imager

NASA Astrophysics Data System (ADS)

Li, Chengjun; Gong, Hui; Gan, Zhuo; Luo, Qingming

2005-01-01

Human prefrontal cortex (PFC) helps mediate working memory (WM), a system that is used for temporary storage and manipulation of information and is involved with many higher-level cognitive functions. Here, we report a functional near-infrared spectroscopy (NIRS) study on the PFC activation caused by verbal WM task. For investigating the effect of memory load on brain activation, we adopted the "n-back" task in which subjects must decide for each present letter whether it matches the letter presented n items back in sequence. 27 subjects (ages 18-24, 13 females) participated in the work. Concentration changes in oxy-Hb (HbO2), deoxy-Hb (Hb), and total-Hb (HbT) in the subjects" prefrontal cortex were monitored by a 24-channel functional NIRS imager. The cortical activations and deactivations were found in left ventrolateral PFC and bilateral dorsolateral PFC. As memory load increased, subjects showed poorer behavioral performance as well as monotonically increasing magnitudes of the activations and deactivations in PFC.

Use of HbA(1C) testing to diagnose pre-diabetes in high risk African American children: a comparison with fasting glucose and HOMA-IR.

PubMed

Sharma, Sushma; Fleming, Sharon E

2012-01-01

This study aimed to compare the discriminating power of HbA(1C) with other pre-diabetes diagnostic tests specifically in high-risk African American children. A cross-sectional analysis was performed on a sample of 172 children (70 boys and 102 girls) aged 9-11 years with BMI's above the 85th percentile. Fasting glucose, insulin and HbA(1C) were analyzed from the plasma samples. Of the 172 participants included in this analysis, 21 (12.2%) had HbA(1C) concentrations above the cutoff of 5.7 used to identify pre-diabetes. None (0%) of these 21 participants, however, were observed to have a glucose concentration above the pre-diabetes cutoff of 110 mg/dl, and only 13 of 21 participants had HOMA-IR above the pre-diabetes cutoff of 2.5. When compared to the previously identified glucose cutoff of 110 mg/dl and HOMA-IR cutoff of 2.5 for pre-diabetes, HbA(1C) showed high specificity (88 and 93%, respectively) but very low sensitivity (0 and 21%, respectively). Glucose, insulin and HOMA-IR were significantly interrelated, but HbA(1C) was not significantly correlated with these biochemical prediabetes assessment variables, nor with anthropometric (BMIz, WC) risk factors. Our results suggest that HbA(1C) had poor discrimination power to identify prediabetes in overweight and obese 9- to 11-year-old African American children. Future studies are recommended to compare the feasibility, sensitivity and predictive power of different screening tests currently recommended to avoid inadequacy when screening for prediabetes and diabetes. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers.

PubMed

Roux, S; Baudoin, C; Boute, D; Brazier, M; De La Guéronniere, V; De Vernejoul, M C

2004-01-01

To compare the effects of 2 drinking waters containing similar calcium (Ca) concentration in order to analyze the role of ions other than Ca on bone metabolism. These mineral drinking-waters differed by their mineral composition primarily concerning the concentration of bicarbonate (HCO3-), high in the HB, and sulfate, high in HS water. Of 60 included women, 39 completed the study. Patients were randomly assigned to an intake of 1 liter per day of mineral water HB or HS for 28 d, followed by cross-over to the alternative drinking-water for a further 28 d. At baseline and after each period of one month, Ca metabolism parameters, acid-base status, and bone remodeling markers were measured. Changes in Ca metabolism were significant in the HB group where the ionized Ca increased and the PTH decreased. Serum pH showed a similar increase whatever the used drinking water compared to baseline. In the HB group, significant increase in urine pH, and significant decrease in AT-HCO3- and NH4+ were observed. Bone resorption markers, urinary CTx/Cr, Pyr/Cr, and D-Pyr/Cr, significantly decreased in the HB group compared to baseline, and were not significantly modified in the HS group. These results showed a beneficial effect of the bicarbonaterich HB water on bone metabolism. This may account for a better bioavailability of the Ca, a greater alkalinization, and a larger decrease in PTH level secondary to a higher ionized Ca level. The higher content of silica in HB water may have also participated to the positive action on bone balance that was observed. In this short term study, these data underlined the potential role of the mineral drinking water composition on bone metabolism.

Erythrocyte concentrations of B1, B2, B6 but not plasma C and E are reliable indicators of nutrition status in the presence of systemic inflammation.

PubMed

Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Talwar, Dinesh

2017-02-01

There is increasing evidence that the plasma concentration of vitamin D, carotenoids, zinc and selenium are associated with the magnitude of the systemic inflammatory response. In order to examine whether other vitamins may be affected and whether red cell concentrations are less affected by systemic inflammation the aim of the present study was to examine the effect of the systemic inflammatory response on red cell measurements of vitamins B1, B2 and B6, and plasma concentration of vitamin C and E in a large cohort of patients referred for a nutritional screen. Patients referred for nutritional assessment of B1 (n = 551), B2 (n = 251), B6 (n = 313), ascorbic acid (n = 494) and α-tocopherol (n = 395) concentrations. These vitamins were measured using routine laboratory methods. The median concentrations of vitamin B1 grouped according to C-reactive protein concentrations ≤10, 11-80 and >80 mg/L were 543, 664 and 766 ng/g Hb respectively (p < 0.001, 41% higher). The median concentration of vitamin B1 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 547, 664 and 701 ng/g Hb respectively (p < 0.001, 28% higher). The median concentrations of red cell vitamin B2 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 2.2, 2.3 and 2.4 nmol/g Hb respectively (p < 0.001, 9% higher). The median red cell concentrations of vitamin B2 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 2.1, 2.4 and 2.3 nmol/g Hb respectively (p < 0.001, 14% higher). The median concentrations of red cell vitamin B6 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 534, 548 and 767 pmol/g Hb respectively (p < 0.001, 44% higher). The median red cell concentrations of vitamin B6 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 462, 644 and 840 pmol/g Hb respectively (p < 0.001, 82% higher). In contrast, the median plasma concentrations of ascorbic acid grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 25.0, 15.0 and 6.0 μmol/l respectively (78% lower, p < 0.001). The median plasma concentrations of ascorbic acid grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 32.0, 13.0 and 5.0 μmol/l respectively (84% lower, p < 0.001). The median α-tocopherol/cholesterol grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 5.9, 4.6 and 2.1 μmol/l respectively (64% lower, p < 0.001). The median α-tocopherol/cholesterol grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 6.0, 5.5 and 2.1 μmol/l respectively (65% lower, p < 0.001). Red cell concentrations of vitamins B1, B2 and B6 were not lower with an increasing systemic inflammatory response. In contrast, plasma concentrations of vitamin C and E were lower. Therefore, compared with plasma concentration, red cell concentrations of B1, B2 and B6 are likely to be more reliable measures of status in the presence of a systemic inflammatory response. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Screening for intermediate and severe forms of thalassaemia in discarded red blood cells: optimization and feasibility.

PubMed

George, Elizabeth; Lai, Mei I; Teh, Lai Kuan; Ramasamy, Rajesh; Goh, Ern Huei; Asokan, Kamalan; Tan, J A M A; Vasudevan, Maithili; Low, Sharon

2011-12-01

Detection and quantification of Hb subtypes of human blood is integral to presumptive identification of thalassaemias. It has been used in neonatal screening of thalassaemia and Hb variants. The use of discarded red blood cells following processing of the cord blood for stem cells provides readily available diagnostic material for thalassaemia screening. In this study, we determined the range of Hb subtypes in 195 consecutive cord blood samples collected for cord blood banking. The 'cord blood samples' analysed were those of the remaining red blood cells after the cord blood was processed for stem cell storage. Quantification of Hb subtypes by high performance liquid chromatography (HPLC) was done on BioRad Variant II Hb testing system. Only 73 (36.5%) of the samples could be analyzed neat without dilution. With a 1:300 dilution with wash solution the acceptable area as recommended by the manufacturer for reading of a C-gram within the 1 to 3 million ranges were achieved in all. Eighteen (9%) 12 showed classical Hb Barts (y4) prerun peaks were confirmed by Sebia Hydrasys automated Hb gel electrophoresis and quantified by Sebia Capillarys 2 capillary electrophoresis. Only 1 (0.5%) was presumptively identified with HbH disease. Due to the limited number of samples no beta-thalassaemia major, Hb E beta-thalassaemia and Hb Barts hydrops fetalis were found. The HPLC assay was possible at a cost US$ 5 per sample and a turnover time of 10 samples per hour without technical difficulties. This study reports an effective and valuable protocol for thalassaemia screening in red blood cells which would otherwise be discarded during cord blood processing. Cord blood with severe and intermediate forms of thalassaemia can be preselected and not stored.

A new sensitive method of dissociation constants determination based on the isohydric solutions principle.

PubMed

Michałowski, Tadeusz; Pilarski, Bogusław; Asuero, Agustin G; Dobkowska, Agnieszka

2010-10-15

The paper provides a new formulation and analytical proposals based on the isohydric solutions concept. It is particularly stated that a mixture formed, according to titrimetric mode, from a weak acid (HX, C(0)mol/L) and a strong acid (HB, Cmol/L) solutions, assumes constant pH, independently on the volumes of the solutions mixed, provided that the relation C(0)=C+C(2)·10(pK(1)) is valid, where pK(1)=-log K(1), K(1) the dissociation constant for HX. The generalized formulation, referred to the isohydric solutions thus obtained, was extended also to more complex acid-base systems. Particularly in the (HX, HB) system, the titration occurs at constant ionic strength (I) value, not resulting from presence of a basal electrolyte. This very advantageous conjunction of the properties provides, among others, a new, very sensitive method for verification of pK(1) value. The new method is particularly useful for weak acids HX characterized by low pK(1) values. The method was tested experimentally on four acid-base systems (HX, HB), in aqueous and mixed-solvent media and compared with the literature data. Some useful (linear and hyperbolic) correlations were stated and applied for validation of pK(1) values. Finally, some practical applications of analytical interest of the isohydricity (pH constancy) principle as one formulated in this paper were enumerated, proving the usefulness of such a property which has its remote roots in the Arrhenius concept. Copyright © 2010 Elsevier B.V. All rights reserved.

Intravenous infusion of haptoglobin for the prevention of adverse clinical outcome in Sickle Cell Disease.

PubMed

Quimby, Kim R; Hambleton, Ian R; Landis, R Clive

2015-10-01

Sickle Cell Disease (SCD) is a genetic condition which manifests as altered hemoglobin (Hb) protein that can aggregate under hypoxic conditions. The resultant sickled erythrocytes experience premature hemolysis, releasing an estimated 10g of free Hb (fHb) into the intravascular space. FHb participates in redox reactions creating various reactive oxygen species which rapidly and irreversibly scavenge nitric oxide, thereby attenuating its vasodilatory, antithrombotic, and anti-inflammatory properties. FHb also induces endothelial expression of adhesion molecules, triggering leukocyte margination at the vessel wall. These mechanisms participate in diverse SCD-associated clinical events including nephropathy, pulmonary hypertension, chronic leg ulceration, and ischemic events. FHb also exerts a direct reno-toxic effect contributing to albuminuria which is an early, frequent manifestation of glomerular injury. Under normal conditions, fHb is effectively scavenged by the Hb-scavenging mechanism (HSM); this involves binding to haptoglobin (Hp), uptake via the Hb-scavenging receptor (CD163) on monocytes and metabolism by heme-oxygenase-1. This culminates in increased CD163 expression and release of anti-inflammatory by-products e.g. interleukin-10 (IL-10). In SCD, the Hb-binding capacity is overwhelmed by chronic hemolysis; our previous research shows serum Hp as the depleted component. This deficiency could result in the harmful consequences of circulating fHb going unbridled. The hypothesis we explore here is that Hp infusions, in excess of fHb concentration, will allow the HSM to remain functional, and thereby achieve improved clinical outcomes, tracking albuminuria as a sentinel. Albuminuria was selected because of its high prevalence in SCD and its relative ease of diagnosis and monitoring. The hypothesis may be evaluated in four phases: Phase 1 will determine the concentration of Hp needed to trigger the HSM as measured by induction of CD163 and IL-10 and the recovery of hemopexin. Phase 2 will investigate the half-life of HSM induction by analyzing the time-course of CD163 expression and IL-10 and hemopexin serum concentration. Phase 3 will determine patient eligibility for therapy, whether as treatment or prevention. Phase 4 will test the efficacy of Hp transfusions in a randomized control trial as measured by correction of albuminuria. Angiotensin converting enzyme inhibitors (ACEi) are currently the first-line treatment for SCD nephropathy, however hyperkalemia limits its use. Hydroxyurea, which has therapeutic value in many SCD adverse events, has yielded inconsistent effects on albuminuria. We are proposing the addition of an intervention more proximal in the hemolytic cascade. Boosting the exhausted Hb-scavenging capacity via Hp replacement therapy has the potential to modify multiple downstream clinical events. Copyright © 2015 Elsevier Ltd. All rights reserved.

On the Strength and Validity of Hazard Banding.

PubMed

Scheffers, Theo; Doornaert, Blandine; Berne, Nathalie; van Breukelen, Gerard; Leplay, Antoine; van Miert, Erik

2016-11-01

Hazard Banding (HB) is a process of allocating chemical substances in bands of increasing health hazard based on their hazard classifications. Recent Control Banding (CB) tools use the classifications of the United Nations Global Harmonized System (UN GHS) or the European Union Classifications, Labelling and Packaging (EU CLP) which are grouped over 5 HBs. The use of CB is growing worldwide for the risk control of substances without an Occupational Exposure Limit Value (OELV). Well-known CB-tools like HSE-COSHH Essentials, BAuA-Einfaches Maßnahmenkonzept Gefahrstoffe (EMKG), and DGUV-IFA-Spaltenmodell (IFA) use however different GHS/CLP groupings which may lead to dissimilar HBs and control regimes for individual substances. And as the choice for a CB tool seems to be determined by geography and/or local status these differences may hamper a global, aligned HSE approach. Therefore, the HB-engines of the three public CBs and an in-company (Solvay) CB called 'Occupational Exposure Banding' (S-OEB) were compared mutually and ranked in their relation with the OELV as the 'de facto' standard. This was investigated graphically and using a 5 strength indicator, statistical method. A data set of 229 substances with high-quality GHS/CLP classifications and OELVs was used. HB concentration ranges, as linked to S-OEB and COSHH, were validated against the corresponding OELV distributions. The four HB-engines allocate between 23 and 64% of the 229 substances in the same bands. The remaining substances differ at least one band, with IFA placing more substances in a higher hazard band, EMKG doing the opposite and COSHH and S-OEB in between. The overall strength scores of S-OEB, IFA, and EMGK HB-engines are higher than COSHH, with S-OEB having the highest overall strength score. The lower ends of the concentration ranges defined for the 3 'highest' hazard bands of S-OEB were in good agreement with the 10 th percentiles of the corresponding OELV distributions obtained from the substance data set. The lower ends of the COSHH concentration ranges comply with the 10 th percentiles of the COSHH OELV distributions for dust/aerosol but not for vapour/gas substances. Both the S-OEB and COSHH concentration ranges underestimate the overall width of the OELV distributions that can span 2-3 orders of magnitude. As the performance of the S-OEB HB-engine meets our criteria of being at least as good as the public engines, it will be used as a standard within Solvay's global operations. In addition, the method described here to evaluate the strength of HB-engines and the validity of their corresponding concentration ranges is a useful tool enabling further developments and worldwide alignment of HB. © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Episodes of apnea and bradycardia in the preterm newborn: impact on cerebral oxygenation measured by near-infrared spectrophotometry

NASA Astrophysics Data System (ADS)

Van Huffel, Sabine; Craemers, Johan; Lenaerts, Bart; Daniels, Hans; Naulaers, Gunnar; Casaer, Paul

1998-12-01

The objective of this study is to evaluate the effect of episodes of apneas and/or mild bradycardia (heart rate decreases of 10 to 20% or more) on cerebral oxyhemoglobin (HbO2) and reduced hemoglobin (Hb) concentration as measured by Near Infrared Spectrophotometry (NIRS). Measurements were carried out on 7 preterm infants who experienced apneic and bradycardiac events. It is shown how to characterize these events using time-frequency analysis. In addition to NIRS (performed with a NIRO-500 from Hamamatsu, Japan), the heart rate, ECG, peripheral arterial oxygen saturation (measured at the foot) and respiration (abdominal and thoracic pressure, and nasal airflow) were continuously recorded. The impact of apneic events and periodic breathing on these measurements reveals the clinical relevance of NIRS. In particular, we investigate whether these changes in heart rate and respiration also influence HbO2 and reduced Hb concentration in neonatal brain. These changes are characterized, as well as their relationships with the other simultaneously recorded signals such as peripheral arterial oxygen saturation.

High Oxygen Partial Pressure Decreases Anemia-Induced Heart Rate Increase Equivalent to Transfusion

PubMed Central

Feiner, John R.; Finlay-Morreale, Heather E.; Toy, Pearl; Lieberman, Jeremy A.; Viele, Maurene K.; Hopf, Harriet W.; Weiskopf, Richard B.

2011-01-01

Background Anemia is associated with morbidity and mortality and frequently leads to transfusion of erythrocytes. We sought to compare directly the effect of high inspired oxygen fraction vs. transfusion of erythrocytes on the anemia-induced increased heart rate (HR) in humans undergoing experimental acute isovolemic anemia. Methods We combined HR data from healthy subjects undergoing experimental isovolemic anemia in seven studies performed by our group. We examined HR changes associated with breathing 100% oxygen by non-rebreathing face mask vs. transfusion of erythrocytes at their nadir hemoglobin (Hb) concentration of 5 g/dL. Data were analyzed using a mixed-effects model. Results HR had an inverse linear relationship to hemoglobin concentration with a mean increase of 3.9 beats per minute per gram of Hb (beats/min/g Hb) decrease (95% confidence interval [CI], 3.7 – 4.1 beats/min/g Hb), P < 0.0001. Return of autologous erythrocytes significantly decreased HR by 5.3 beats/min/g Hb (95% CI, 3.8 – 6.8 beats/min/g Hb) increase, P < 0.0001. HR at nadir Hb of 5.6 g/dL (95% CI, 5.5 – 5.7 g/dL) when breathing air (91.4 beats/min; 95% CI, 87.6 – 95.2 beats/min) was reduced by breathing 100% oxygen (83.0 beats/min; 95% CI, 79.0 -87.0 beats/min), P < 0.0001. The HR at hemoglobin 5.6 g/dL when breathing oxygen was equivalent to the HR at Hb 8.9 g/dL when breathing air. Conclusions High arterial oxygen partial pressure reverses the heart rate response to anemia, probably owing to its usability, rather than its effect on total oxygen content. The benefit of high arterial oxygen partial pressure has significant potential clinical implications for the acute treatment of anemia and results of transfusion trials. PMID:21768873

The impact of anaemia on treatment outcome in patients with squamous cell carcinoma of anal canal and anal margin.

PubMed

Oblak, Irena; Cesnjevar, Monika; Anzic, Mitja; Hadzic, Jasna But; Ermenc, Ajra Secerov; Anderluh, Franc; Velenik, Vaneja; Jeromen, Ana; Korosec, Peter

2016-03-01

Radiochemotherapy is the main treatment for patients with squamous cell carcinoma of the anal canal. Anaemia is reported to have adverse effect on survival in cancer patients. The aim of the study was to evaluate the influence of anaemia on radiochemotherapy treatment outcome in patients with squamous cell carcinoma of the anal canal. One hundred consecutive patients with histologically confirmed squamous cell carcinoma of the anal canal were treated radically with 3-dimensional conformal or intensity-modulated radiation therapy followed by brachytherapy or external beam radiotherapy boost and with concurrent mitomycin C and 5-fluorouracil. The influence on survival of pre-treatment, mean on-treatment and end-of-treatment haemoglobin (Hb) concentrations was studied. The 5-year locoregional control, disease free survival, disease specific survival and overall survival rates for all patients were 72%, 71%, 77% and 62%, respectively. In univariate analysis, patients with pre-treatment and end-of-treatment Hb > 120 g/L survived statistically significantly better compared to patients with Hb ≤ 120 g/L. Patients with mean on-treatment Hb > 120 g/L only had statistically significant better locoregional control and overall survival than patients with Hb ≤ 120 g/L. In multivariate analysis, independent prognostic factors were pre-treatment Hb (> 120 g/L vs. ≤ 120 g/L) for overall survival (hazard ratio [HR] = 0.419, 95% confidence interval [CI] = 0.190-0.927, p = 0.032) and stage (I & II vs. III) for disease specific (HR = 3.523, 95% CI = 1.375-9.026, p = 0.009) and overall survival (HR = 2.230, 95% CI = 1.167-4.264, p = 0.015). The pre-treatment, mean on-treatment and end-of-treatment Hb concentration > 120 g/L carried better prognosis for patients for with squamous cell carcinoma of the anal canal treated with radiochemotherapy. The pre-treatment Hb > 120 g/L was an independent prognostic factor for overall survival of patients with anal canal cancer.

Reactions of ferric hemoglobin and myoglobin with hydrogen sulfide under physiological conditions.

PubMed

Jensen, Birgitte; Fago, Angela

2018-05-01

Ferric hemoglobin (metHb) and myoglobin (metMb), present at low levels in vivo, have been recently found to oxidize hydrogen sulfide (H 2 S) in excess, thus potentially contributing to removal of toxic H 2 S in blood and heart, respectively. Here, we present a kinetic and thermodynamic study of the reaction of metHb and metMb with H 2 S under physiological conditions, i.e. at low H 2 S concentrations and with protein in excess of H 2 S. We show here that both proteins react with sub-stoichiometric H 2 S:heme ratios following two processes: a fast reversible binding of H 2 S to ferric heme that prevails at high H 2 S and a slow heme reduction to the ferrous state that prevails at low H 2 S. While these two processes are fast for metMb, H 2 S-induced heme reduction is slow for metHb and the metHb-H 2 S complex once formed is therefore relatively stable. We find that metHb binds H 2 S reversibly and cooperatively with a pH-dependent ligand affinity that is within the physiological range of H 2 S concentrations found in blood. Stopped-flow kinetics show identical association rate constants for H 2 S at varying pH, demonstrating that H 2 S and not HS - enters the ferric heme pocket. Dissociation rates of the metHb-H 2 S complex increase when decreasing pH, consistent with the pH-dependent affinity. Taken together, these data are consistent with a novel biological role of metHb as a H 2 S carrier in the blood, in parallel with the oxygen carrier function of the much more abundant ferrous Hb. In contrast, metMb in the heart could participate to redox-signaling involving H 2 S. Copyright © 2018 Elsevier Inc. All rights reserved.

Solute clearance measurement in the assessment of dialysis adequacy among African continuous ambulatory peritoneal dialysis patients.

PubMed

Abdu, Aliyu; Naidoo, Sagren; Malgas, Shirin; Naicker, Jocelyn T; Paget, Graham; Naicker, Saraladevi

2015-01-01

Solute clearance measurement is an objective means of quantifying the dose of peritoneal dialysis (PD). Despite continued debate on the interpretation and precise prognostic value of small solute clearance in PD patients, guidelines based on solute clearance values are common in clinical practice. There is limited information on the solute clearance indices and PD adequacy parameters among this predominantly low socioeconomic status PD population. We investigated the solute clearance among continuous ambulatory peritoneal dialysis (CAPD) patients at the Charlotte Maxeke Johannesburg Academic Hospital and its relationship with other parameters of PD adequacy. Seventy patients on CAPD were studied in this cross-sectional study. Solute clearance was assessed using urea clearance (Kt/V). Linear regression analysis was used to determine factors associated with solute clearance, while analysis of variance was used to test the influence of weekly Kt/V on blood pressure (BP), hemoglobin (Hb) and other biochemical parameters. The mean age of the study population was 37.9 ± 12.4 years, 43% were females and 86% were black Africans. The mean duration on CAPD was 19.7 ± 20.8 months. Mean systolic and diastolic BP were 144 ± 28 and 92 ± 17 mm Hg, respectively. The mean Hb was 11.1 ± 2.2 g/dL and the mean weekly Kt/V was 1.7 ± 0.3. Factors like systolic BP, Hb level, serum levels of cholesterol, calcium, phosphate, parathyroid hormone and albumin were not significantly associated with the weekly Kt/V. We conclude that the dose of PD received by the majority of our patients in terms of the weekly Kt/V is within the recommended values and that this finding is significant considering the low socioeconomic background of our patients. There is no significant association between Kt/V and other indices of dialysis adequacy.

Equations for O2 and CO2 solubilities in saline and plasma: combining temperature and density dependences.

PubMed

Christmas, Kevin M; Bassingthwaighte, James B

2017-05-01

Solubilities of respiratory gasses in water, saline, and plasma decrease with rising temperatures and solute concentrations. Henry's Law, C = α·P, states that the equilibrium concentration of a dissolved gas is solubility times partial pressure. Solubilities in the water of a solution depend on temperature and the content of other solutes. Blood temperatures may differ more than 20°C between skin and heart, and an erythrocyte will undergo that range as blood circulates. The concentrations of O 2 and CO 2 are the driving forces for diffusion, exchanges, and for reactions. We provide an equation for O 2 and CO 2 solubilities, α, that allows for continuous changes in temperature, T, and solution density, ρ, in dynamically changing states:[Formula: see text]This two-exponential expression with a density scalar γ, and a density exponent β, accounts for solubility changes due to density changes of an aqueous solution. It fits experimental data on solubilities in water, saline, and plasma over temperatures from 20 to 40°C, and for plasma densities, ρ sol up to 1.020 g/ml with ~0.3% error. The amounts of additional bound O 2 (to Hb) and CO 2 (bicarbonate and carbamino) depend on the concentrations in the local water space and the reaction parameters. During exercise, solubility changes are large; both ρ sol and T change rapidly with spatial position and with time. In exercise hemoconcentration plasma, ρ sol exceeds 1.02, whereas T may range over 20°C. The six parameters for O 2 and the six for CO 2 are constants, so solubilities are calculable continuously as T and ρ sol change. NEW & NOTEWORTHY Solubilities for oxygen and carbon dioxide are dependent on the density of the solution, on temperature, and on the partial pressure. We provide a brief equation suitable for hand calculators or mathematical modeling, accounting for these factors over a wide range of temperatures and solution densities for use in rapidly changing conditions, such as extreme exercise or osmotic transients, with better than 0.5% accuracy. Copyright © 2017 the American Physiological Society.

Hydrogen bonding-assisted interaction between amitriptyline hydrochloride and hemoglobin: spectroscopic and molecular dynamics studies.

PubMed

Maurya, Neha; Maurya, Jitendra Kumar; Kumari, Meena; Khan, Abbul Bashar; Dohare, Ravins; Patel, Rajan

2017-05-01

Herein, we have explored the interaction between amitriptyline hydrochloride (AMT) and hemoglobin (Hb), using steady-state and time-resolved fluorescence spectroscopy, UV-visible spectroscopy, and circular dichroism spectroscopy, in combination with molecular docking and molecular dynamic (MD) simulation methods. The steady-state fluorescence reveals the static quenching mechanism in the interaction system, which was further confirmed by UV-visible and time-resolved fluorescence spectroscopy. The binding constant, number of binding sites, and thermodynamic parameters viz. ΔG, ΔH, ΔS are also considered; result confirms that the binding of the AMT with Hb is a spontaneous process, involving hydrogen bonding and van der Waals interactions with a single binding site, as also confirmed by molecular docking study. Synchronous fluorescence, CD data, and MD simulation results contribute toward understanding the effect of AMT on Hb to interpret the conformational change in Hb upon binding in aqueous solution.

The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation

PubMed Central

Koda, Michiko; Kitamura, Itsuko; Okura, Tomohiro; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

2016-01-01

Background Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. Methods The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (<100 cm2 and ≥100 cm2). Results The serum triglyceride (TG) levels of 835 males were assessed. In the VFA ≥100 cm2 group, a significantly greater proportion of current smokers (47.3%) exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4%) and non-smokers (18.8%). The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm2, the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA <100 cm2 group, significantly higher proportions of current smokers (17.9%) and former smokers (14.9%) demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%). In contrast, in the VFA ≥100 cm2 group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects’ TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Conclusions Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA. PMID:26616395

Investigation on direct electrochemical and electrocatalytic behavior of hemoglobin on palladium-graphene modified electrode.

PubMed

Chen, Wei; Niu, Xueliang; Li, Xiaoyan; Li, Xiaobao; Li, Guangjiu; He, Bolin; Li, Qiutong; Sun, Wei

2017-11-01

Palladium-graphene (Pd-GR) nanocomposite was acted as modifier for construction of the modified electrode with direct electrochemistry of hemoglobin (Hb) realized. By using Nafion as the immobilization film, Hb was fixed tightly on Pd-GR nanocomposite modified carbon ionic liquid electrode. Electrochemical behaviors of Hb modified electrode were checked by cyclic voltammetry and a pair of redox peaks originated from direct electron transfer of Hb was appeared. The Hb modified electrode had excellent electrocatalytic activity to the reduction of trichloroacetic acid and sodium nitrite in the concentration range from 0.6 to 13.0mmol·L -1 and from 0.04 to 0.5 mmol·L -1 . Therefore Pd-GR nanocomposite was proven to be a good candidate for the fabrication of third-generation electrochemical biosensor. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus

PubMed Central

Sun, Yaping; Zhang, Huaidong; Shi, Jian; Zhang, Zhe; Gong, Rui

2017-01-01

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent. PMID:28906430

Diagnostic and prognostic values of serum exosomal microRNA-21 in children with hepatoblastoma: a Chinese population-based study.

PubMed

Liu, Wanbo; Chen, Sheng; Liu, Bing

2016-11-01

Hepatoblastoma (HB) is the most common primary malignant tumor of the liver in young children. The aim of this study is to identify the diagnostic and prognostic values of serum exosomal miR-21 in Chinese patients with HB. We retrospectively reviewed 32 children with HB. The expressions of miR-21 were detected by real-time PCR. The comparison of diagnostic performance of plasmatic, exosomal miR-21 and AFP levels was measured using the Area Under ROC Curve. For patients in HB group, miR-21 concentration was significantly higher in the exosomes compared with the exosome-depleted supernatants and whole plasma. Expression of miR-21 was significantly higher in patients with HB compared with control group in both plasma and exosomes. With respect to the diagnosis of patients with HB, exosomal miR-21 was significantly more accurate compared with the Alpha-fetoprotein levels. Moreover, exosomal miR-21 was an independent predictor of Even-free survival for patients with HB. In this study, we found that expression of miR-21 was significantly higher in patients with HB compared with control group in both plasma and exosomes, and we confirmed that exosomal miR-21 could be defined as a diagnostic and prognostic biomarker for patients with HB.

Can the Roche hemolysis index be used for automated determination of cell-free hemoglobin? A comparison to photometric assays.

PubMed

Petrova, Darinka Todorova; Cocisiu, Gabriela Ariadna; Eberle, Christoph; Rhode, Karl-Heinz; Brandhorst, Gunnar; Walson, Philip D; Oellerich, Michael

2013-09-01

The aim of this study was to develop a novel method for automated quantification of cell-free hemoglobin (fHb) based on the HI (Roche Diagnostics). The novel fHb method based on the HI was correlated with fHb measured using the triple wavelength methods of both Harboe [fHb, g/L = (0.915 * HI + 2.634)/100] and Fairbanks et al. [fHb, g/L = (0.917 * HI + 2.131)/100]. fHb concentrations were estimated from the HI using the Roche Modular automated platform in self-made and commercially available quality controls, as well as samples from a proficiency testing scheme (INSTAND). The fHb using Roche automated HI results were then compared to results obtained using the traditional spectrophotometric assays for one hundred plasma samples with varying degrees of hemolysis, lipemia and/or bilirubinemia. The novel method using automated HI quantification on the Roche Modular clinical chemistry platform correlated well with results using the classical methods in the 100 patient samples (Harboe: r = 0.9284; Fairbanks et al.: r = 0.9689) and recovery was good for self-made controls. However, commercially available quality controls showed poor recovery due to an unidentified matrix problem. The novel method produced reliable determination of fHb in samples without interferences. However, poor recovery using commercially available fHb quality control samples currently greatly limits its usefulness. © 2013.

A Mass Balance-Based Semiparametric Approach to Evaluate Neonatal Erythropoiesis.

PubMed

Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; Veng-Pedersen, Peter

2016-01-01

Postnatal hemoglobin (Hb) production in anemic preterm infants is determined by several factors including the endogenous erythropoietin levels, allogeneic RBC transfusions administered to treat anemia, and developmental age. As a result, their postnatal Hb production rate can vary considerably. This work introduces a novel Hb mass balance-based semiparametric approach that utilizes infant blood concentrations of Hb from the first 30 postnatal days to estimate the amount of Hb produced and the erythropoiesis rate in newborn infants. The proposed method has the advantage of not relying on specific structural pharmacodynamic model assumptions to describe the Hb production, but instead utilizes simple mass balance principles and nonparametric regression analysis. The developed method was applied to the Hb data from 79 critically ill anemic very low birth weight preterm infants to evaluate the dynamic changes in erythropoiesis during the first month of life and to determine the inter-subject variability in Hb production. The estimated mean (±SD) cumulative amount of Hb produced by the infants over the first month of life was 6.6 ± 3.4 g (mean body weight, 0.768 kg), and the mean estimated body weight-scaled Hb production rate over the same period was 0.23 ± 0.12 g/day/kg. A significant positive correlation was observed between infant gestational age and the mean body weight-scaled Hb production rate over the first month of life (P < 0.05). We conclude that the proposed mathematical approach and its implementation provide a flexible framework to evaluate postnatal erythropoiesis in newborn infants.

Effects of hydroxyurea treatment for patients with hemoglobin SC disease.

PubMed

Luchtman-Jones, Lori; Pressel, Sara; Hilliard, Lee; Brown, R Clark; Smith, Mary G; Thompson, Alexis A; Lee, Margaret T; Rothman, Jennifer; Rogers, Zora R; Owen, William; Imran, Hamayun; Thornburg, Courtney; Kwiatkowski, Janet L; Aygun, Banu; Nelson, Stephen; Roberts, Carla; Gauger, Cynthia; Piccone, Connie; Kalfa, Theodosia; Alvarez, Ofelia; Hassell, Kathryn; Davis, Barry R; Ware, Russell E

2016-02-01

Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/β(0) -thalassemia genotypes, many patients with HbSC experience severe disease complications, including vaso-occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, and poor quality of life. Fully 20 years after the clinical and laboratory efficacy of hydroxyurea was proven in adult SCA patients, the safety and utility of hydroxyurea treatment for HbSC patients remain unclear. Recent NHLBI evidence-based guidelines highlight this as a critical knowledge gap, noting HbSC accounts for ∼30% of sickle cell patients within the United States. To date, only 5 publications have reported short-term, incomplete, or conflicting laboratory and clinical outcomes of hydroxyurea treatment in a total of 71 adults and children with HbSC. We now report on a cohort of 133 adult and pediatric HbSC patients who received hydroxyurea, typically for recurrent vaso-occlusive pain. Hydroxyurea treatment was associated with a stable hemoglobin concentration; increased fetal hemoglobin (HbF) and mean corpuscular volume (MCV); and reduced white blood cell count (WBC), absolute neutrophil count (ANC), and absolute reticulocyte count (ARC). Reversible cytopenias occurred in 22% of patients, primarily neutropenia and thrombocytopenia. Painful events were reduced with hydroxyurea, more in patients >15 years old. These multicenter data support the safety and potentially salutary effects of hydroxyurea treatment for HbSC disease; however, a multicenter, placebo-controlled, Phase 3 clinical trial is needed to determine if hydroxyurea therapy has efficacy for patients with HbSC disease. © 2015 Wiley Periodicals, Inc.

Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats

PubMed Central

Rodríguez-Mañas, Leocadio; Angulo, Javier; Peiró, Concepción; Llergo, José L; Sánchez-Ferrer, Alberto; López-Dóriga, Pedro; Sánchez-Ferrer, Carlos F

1998-01-01

The aim of this work was to study the influence of the metabolic control, estimated by the levels of glycosylated haemoglobin in total blood samples (HbA1c), in developing vascular endothelial dysfunction in streptozotocin-induced diabetic rats. Four groups of animals with different levels of insulin treatment were established, by determining HbA1c values in 5.5 to 7.4%, 7.5 to 9.4%, 9.5 to 12% and >12%, respectively.The parameters analysed were: (1) the endothelium-dependent relaxations to acetylcholine (ACh) in isolated aorta and mesenteric microvessels; (2) the vasodilator responses to exogenous nitric oxide (NO) in aorta; and (3) the existence of oxidative stress by studying the influence of the free radical scavenger superoxide dismutase (SOD) on the vasodilator responses to both ACh and NO.In both isolated aortic segments and mesenteric microvessels, the endothelium-mediated concentration-dependent relaxant responses elicited by ACh were significantly decreased when the vessels were obtained from diabetic animals but only with HbA1c values higher than 7.5%. There was a high correlation between HbA1c levels and the impairment of ACh-induced relaxations, measured by pD2 values.The concentration-dependent vasorelaxant responses to NO in endothelium-denuded aortic segments were significantly reduced only in vessels from diabetic animals with HbA1c values higher than 7.5%. Again, a very high correlation was found between the HbA1c values and pD2 for NO-evoked responses.In the presence of SOD, the responses to ACh or NO were only increased in the segments from diabetic rats with HbA1c levels higher than 7.5%, but not in those from non-diabetic or diabetic rats with a good metabolic control (HbA1c levels <7.5%).These results suggest the existence of: (1) a close relation between the degree of endothelial dysfunction and the metabolic control of diabetes, estimated by the levels of HbA1c; and (2) an increased production of superoxide anions in the vascular wall of the diabetic rats, which is also related to the metabolic control of the disease. PMID:9605553

Labile glycated haemoglobin and carbamylated haemoglobin are still critical points for HbA1c measurement.

PubMed

Desmons, Aurore; Jaisson, Stéphane; Leroy, Nathalie; Gillery, Philippe; Guillard, Emmanuelle

2017-06-15

Haemoglobin A 1c (HbA 1c ) is a key analyte for the monitoring of glycemic balance in diabetic patients and is used for diabetes diagnosis in many countries. The potential interference of carbamylated haemoglobin (cHb) and labile glycated haemoglobin (LA 1c ) on HbA 1c assays must remain a matter of vigilance. Such a situation has occurred in our laboratory with a kit replacement on the Bio-Rad Variant™ II testing system, a cation-exchange high performance liquid chromatography (HPLC) system. With this method, LA 1c and cHb coeluted in a same peak which may have different consequences on HbA 1c values. The influence of increasing LA 1c and cHb values on HbA 1c results was studied with in vitro glycation and carbamylation of samples. Samples from patients with high and normal blood urea concentrations were assayed by HPLC and immunological assay. We observed that the degree of interference greatly varied depending on the nature of the interfering Hb fractions found under the so-called "LA 1c peak". Thus, we have decided to apply a decision tree using "LA 1c " thresholds depending on: (i) the retention time, (ii) the shape of the peak, (iii) other analytes, like urea. If the peak recognized as "LA 1c " is mainly formed by LA 1c, we consider that there is no interference until 4%. If the peak is mainly formed by cHb, we consider an interference threshold equal to 2%. This situation reminds that cHb and LA 1c remain critical issues in chromatography-based HbA 1c assays and that adapted criteria must be set up for result interpretation.

Hemodynamic changes in the breast and frontal cortex of mothers during breastfeeding.

PubMed

Tanimoto, Kimie; Kusaka, Takashi; Nishida, Tomoko; Ogawa, Kayo; Kato, Ikuko; Ijichi, Sonoko; Mikami, Junko; Sobue, Ikuko; Isobe, Kenichi; Itoh, Susumu

2011-10-01

The objective of this study was to confirm physiological reactions in the breast and brain in mothers during breastfeeding and collect basic objective data, aiming at effective support for breastfeeding. Ten healthy women who were exclusively breastfeeding their babies participated in this study. Changes in the concentration of oxygenated Hb (oxyHb) and deoxygenated Hb in the breasts and frontal cortex of these women during breastfeeding lactation were measured using double-channel near-infrared spectroscopy (NIRS). Changes were measured in three conditions: (1) in both breasts; (2) the ipsilateral breast and frontal cortex; and (3) the contralateral breast and frontal cortex. OxyHb and total Hb (totalHb) levels in the bilateral breasts decreased significantly after the onset of breastfeeding in comparison with prebreastfeeding levels. These two values repeatedly increased and decreased thereafter. In the frontal cortex, regardless of which breast was involved, oxyHb and totalHb levels increased significantly in comparison with prebreastfeeding levels. Similar hemodynamic changes occurred simultaneously in the bilateral breasts during breastfeeding regardless of the feeding or nonfeeding side. Hemodynamic changes were also noted in the frontal cortex, but the reactions in the breast and prefrontal cortex were different and not synchronous, confirming that the physiological circulatory dynamics during breastfeeding vary among organs.

A meta-analysis of pica and micronutrient status.

PubMed

Miao, Diana; Young, Sera L; Golden, Christopher D

2015-01-01

Pica is the craving for and consumption of nonfood items, including the ingestion of earth (geophagy), raw starch (amylophagy), and ice (pagophagy). Pica has long been associated with micronutrient deficiencies, but the strength of this relationship is unclear. We aimed to evaluate the association between pica behavior and the risk of being anemic or having low hemoglobin (Hb), hematocrit (Hct), or plasma zinc (Zn) concentrations. We systematically reviewed studies in which micronutrient levels were reported by pica status. We calculated the pooled odds ratio for anemia or weighted mean difference in Hb, Hct, or Zn concentrations between groups practicing or not practicing pica behaviors. Forty-three studies including 6,407 individuals with pica behaviors and 10,277 controls were identified. Pica was associated with 2.35 times greater odds of anemia (95% CI: 1.94-2.85, P < 0.001), lower Hb concentration (-0.65 g/dl, 95% CI: -0.83 to -0.48 g/dl, P < 0.001), lower Hct concentration (-1.15%, 95% CI: -1.61 to -0.70%, P < 0.001), and lower Zn concentration (-34.3 μg/dl, 95% CI: -59.58 to -9.02 μg/dl, P = 0.008). Statistical significance persisted after excluding outliers and in subgroup analyses by pica type and life stage. Pica is significantly associated with increased risk for anemia and low Hb, Hct, and plasma Zn. Although the direction of the causal relationship between pica and micronutrient deficiency is unknown, the magnitude of these relationships is comparable to other well-recognized causes of micronutrient deficiencies. Pica warrants greater public health attention; specifically the potential physiological mechanisms underpinning the relationship between pica and micronutrient deficiencies merit further study. © 2014 Wiley Periodicals, Inc.

A meta-analysis of pica and micronutrient status

PubMed Central

Miao, Diana; Young, Sera L; Golden, Christopher D

2014-01-01

Objectives Pica is the craving for and consumption of non-food items, including the ingestion of earth (geophagy), raw starch (amylophagy), and ice (pagophagy). Pica has long been associated with micronutrient deficiencies, but the strength of this relationship is unclear. We aimed to evaluate the association between pica behavior and the risk of being anemic or having low hemoglobin (Hb), hematocrit (Hct), or plasma zinc (Zn) concentrations. Methods We systematically reviewed studies in which micronutrient levels were reported by pica status. We calculated the pooled odds ratio for anemia or weighted mean difference in Hb, Hct, or Zn concentrations between groups practicing or not practicing pica behaviors. Results Forty-three studies including 6407 individuals with pica behaviors and 10,277 controls were identified. Pica was associated with 2.4 times greater odds of anemia (95% CI: 1.94–2.85, p<0.001), lower Hb concentration (−0.65 g/dL, 95% CI: −0.83–−0.48 g/dL, p<0.001), lower Hct concentration (−1.15%, 95% CI: −1.61–−0.70%, p<0.001), and lower Zn concentration (−34.3 μg/dL, 95% CI: −59.58–−9.02 μg/dL, p=0.008). Statistical significance persisted after excluding outliers and in subgroup analyses by pica type and life stage. Conclusions Pica is significantly associated with increased risk for anemia and low Hb, Hct, and plasma Zn. Although the direction of the causal relationship between pica and micronutrient deficiency is unknown, the magnitude of these relationships is comparable to other well-recognized causes of micronutrient deficiencies. Pica warrants greater public health attention; specifically a potential physiological mechanism causing the relationship between pica and micronutrient deficiencies merits further study. PMID:25156147

The Incidence of Hypogonadotropic Hypogonadism in Type 2 Diabetic Men in Polish Population

PubMed Central

Rabijewski, Michał; Zgliczyński, Wojciech; Piątkiewicz, Paweł

2013-01-01

The aim of this study was to investigate the incidence of hypogonadotropic hypogonadism (HH) in type 2 diabetic men (T2DM) in population of Polish men and examine the possible influence of estradiol levels and glycemic control. We evaluated TT, cfT, estradiol, and glycemic control (HbA1c) in 184 diabetic men and in 149 nondiabetic control group. The mean HbA1c was 8.6 ± 0.2% and 6.1 ± 0.3% and cfT concentration was 0.315 ± 0.08 nmol/L and 0.382 ± 0.07 nmol/L, respectively. T2DM had higher E2 concentration than nonobese control men (29.4 ± 3.7 pg/mL versus 24.5 ± 2.9 pg/mL). Forty-six percent of T2DM were hypogonadal and 93% had HH. We observed inverse relationship between BMI and cfT (r = −0.341, P < 0.01) and positive between BMI and E2 (r = 0.329, P < 0.01). E2 concentration was higher in T2DM with HH versus T2DM with normal TT/cfT concentration (34.5 ± 5.2 versus 27.4 ± 3.4 pg/mL). We observed negative correlation between HbA1c and cfT (r = −0.336, P < 0.005) but positive between HbA1c and E2 levels (r = 0.337, P < 0.002). The prevalence of obesity, hypertension, and CVD was higher in men with hypogonadism. High incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population is associated with poor glycemic control and can be secondary to an increase in estradiol concentrations. PMID:24222915

Effect of CO2, Nd:YAG and Er:YAG Lasers on Microtensile Bond Strength of Composite to Bleached-Enamel.

PubMed

Basir, Mahshid Mohammadi; Rezvani, Mohammad Bagher; Chiniforush, Nasim; Moradi, Zohreh

2016-01-01

Tooth restoration immediately after bleaching is challenging due to the potential problems in achieving adequate bond strength. The aim of this study was to evaluate the effect of surface treatment with ER:YAG, ND:YAG, CO2 lasers and 10% sodium ascorbate solution on immediate microtensile bond strength of composite resin to recently bleached enamel. Ninety sound molar teeth were randomly divided into three main groups (n:30) : NB (without bleaching), HB (bleached with 38% carbamide peroxide) and OB (bleached with Heydent bleaching gel assisted by diode laser). Each group was divided into five subgroups (n:6) : Si (without surface treatment), Er (Er:YAG laser), CO2 (CO2 laser), Nd (Nd:YAG laser) and As (Immersion in 10% sodium ascorbate solution). The bonding system was then applied and composite build-ups were constructed. The teeth were sectioned by low speed saw to obtain enamel- resin sticks and submitted to microtensile bond testing. Statistical analyses were done using two- way ANOVA, Tukey and Tamhane tests. µTBS of bleached teeth irradiated with ND:YAG laser was not significantly different from NB-Nd group. Microtensile bond strength of OB-Er group was higher than NB-Er and HB-Er groups. The mean µTBS of HB-CO2 group was higher than NB-CO2 group; the average µTBS of HB-As and OB-As groups was also higher than NB-As group. Use of Nd:YAG, CO2 lasers and 10% sodium ascorbate solution could improve the bond strength in home-bleached specimens. Application of ND:YAG laser on nonbleached specimens and Er:YAG laser on office-bleached specimens led to the highest µTBS in comparison to other surface treatments in each main group.

Neuroimaging in autism spectrum disorders: 1H-MRS and NIRS study.

PubMed

Mori, Kenji; Toda, Yoshihiro; Ito, Hiromichi; Mori, Tatsuo; Mori, Keiko; Goji, Aya; Hashimoto, Hiroko; Tani, Hiroe; Miyazaki, Masahito; Harada, Masafumi; Kagami, Shoji

2015-01-01

Using proton magnetic resonance spectroscopy ((1)H-MRS), we measured chemical metabolites in the left amygdala and the bilateral orbito-frontal cortex (OFC) in children with autism spectrum disorders (ASD). The concentrations of N-acetylaspartate (NAA) in these regions of ASD were significantly decreased compared to those in the control group. In the autistic patients, the NAA concentrations in these regions correlated with their social quotient. These findings suggest the presence of neuronal dysfunction in the amygdala and OFC in ASD. Dysfunction in the amygdala and OFC may contribute to the pathogenesis of ASD. We performed a near-infrared spectroscopy (NIRS) study to evaluate the mirror neuron system in children with ASD. The concentrations of oxygenated hemoglobin (oxy-Hb) were measured with frontal probes using a 34-channel NIRS machine while the subjects imitated emotional facial expressions. The increments in the concentration of oxy-Hb in the pars opercularis of the inferior frontal gyrus in autistic subjects were significantly lower than those in the controls. However, the concentrations of oxy-Hb in this area were significantly elevated in autistic subjects after they were trained to imitate emotional facial expressions. The results suggest that mirror neurons could be activated by repeated imitation in children with ASD.

A comparative evaluation of the analytical performances of Capillarys 2 Flex Piercing, Tosoh HLC-723 G8, Premier Hb9210, and Roche Cobas c501 Tina-quant Gen 2 analyzers for HbA1c determination.

PubMed

Wu, Xiaobin; Chao, Yan; Wan, Zemin; Wang, Yunxiu; Ma, Yan; Ke, Peifeng; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2016-10-15

Haemoglobin A 1c (HbA 1c ) is widely used in the management of diabetes. Therefore, the reliability and comparability among different analytical methods for its detection have become very important. A comparative evaluation of the analytical performances (precision, linearity, accuracy, method comparison, and interferences including bilirubin, triglyceride, cholesterol, labile HbA 1c (LA 1c ), vitamin C, aspirin, fetal haemoglobin (HbF), and haemoglobin E (Hb E)) were performed on Capillarys 2 Flex Piercing (Capillarys 2FP) (Sebia, France), Tosoh HLC-723 G8 (Tosoh G8) (Tosoh, Japan), Premier Hb9210 (Trinity Biotech, Ireland) and Roche Cobas c501 (Roche c501) (Roche Diagnostics, Germany). A good precision was shown at both low and high HbA 1c levels on all four systems, with all individual CVs below 2% (IFCC units) or 1.5% (NGSP units). Linearity analysis for each analyzer had achieved a good correlation coefficient (R 2 > 0.99) over the entire range tested. The analytical bias of the four systems against the IFCC targets was less than ± 6% (NGSP units), indicating a good accuracy. Method comparison showed a great correlation and agreement between methods. Very high levels of triglycerides and cholesterol (≥ 15.28 and ≥ 8.72 mmol/L, respectively) led to falsely low HbA 1c concentrations on Roche c501. Elevated HbF induced false HbA 1c detection on Capillarys 2FP (> 10%), Tosoh G8 (> 30%), Premier Hb9210 (> 15%), and Roche c501 (> 5%). On Tosoh G8, HbE induced an extra peak on chromatogram, and significantly lower results were reported. The four HbA 1c methods commonly used with commercial analyzers showed a good reliability and comparability, although some interference may falsely alter the result.

The influence of glycemic control on the oral health of children and adolescents with diabetes mellitus type 1.

PubMed

Carneiro, Vera Lúcia; Fraiz, Fabian Calixto; Ferreira, Fernanda de Morais; Pintarelli, Tatiana Pegoretti; Oliveira, Ana Cristina Borges; Boguszewski, Margaret Cristina da Silva

2015-12-01

To evaluate the influence of disease control, expressed by the mean values of glycated hemoglobin (HbA1c), in the oral health of children and adolescents with diabetes mellitus type 1 (T1DM). A cross sectional study involving 87 children and adolescents (59 girls), 10 ± 2.6 years old. The participants were divided into three groups: HbA1c ≤ 8%, 8% < HbA1c ≤ 10% and HbA1c > 10%. The duration of the disease, age and average HbA1c were obtained from their medical records. Oral health was evaluated according to the following indexes: Simplified Oral Hygiene Index (OHI-S); Community Periodontal Index (CPI); Decayed, Missing or Filled Teeth Index (DMFT/dmft) for permanent and deciduous teeth; and the stimulated salivary flow rate (SSFR). The median SSFR was 1.1 mL/min in the group with HbA1c ≤ 8%, 0.7 mL/min in the intermediary group and 0.6 mL/min in the HbA1c > 10% group. A significant decrease in salivary flow was observed with an increase in HbA1c (p = 0.007). The DMFT/dmft and CPI indexes were higher in individuals with higher HbA1c values. More caries-free individuals were found in the group with HbA1c ≤ 8% compared to those with HbA1c > 10%. The group with HbA1c > 10% exhibited more caries and bleeding gums than the other groups. HbA1c values in girls were higher than in boys. Children and adolescents with unsatisfactory glycemic control, represented by higher HbA1c concentrations, exhibited a higher frequency of caries and gingivitis, and a reduction in salivary flow.

Hemoglobin detection using carbon dots as a fluorescence probe.

PubMed

Barati, Ali; Shamsipur, Mojtaba; Abdollahi, Hamid

2015-09-15

Herein, we have described the application of high fluorescent carbon dots (CDs) without any surface modification as a simple and fast responding fluorescence probe for sensitive and selective determination of hemoglobin (Hb) in the presence of H2O2. Although Hb itself was able to quench the fluorescence of CDs, based on the inner filter effect (IFE) of the protein that affects both excitation and emission spectra of CDs, the presence of H2O2 resulted in further improvement of the sensitivity of Hb detection. The assay is based on the reaction of Hb with H2O2 that generates reactive oxygen species including hydroxyl (OH•) and superoxide (O2(•-)) radicals under heme degradation and/or iron release from Hb and the subsequent reaction of hydroxyl radicals, as strong oxidizing agents, with CDs resulting in high fluorescence quenching. The proposed probe was used for determination of Hb in concentration range of 1-100 nM with a detection limit of 0.4 nM. The method was successfully applied to the determination of Hb in human blood samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Hemodynamic and Electrophysiological Connectivity in the Language System: Simultaneous Near-Infrared Spectroscopy and Electrocorticography Recordings during Cortical Stimulation

ERIC Educational Resources Information Center

Sato, Yosuke; Oishi, Makoto; Fukuda, Masafumi; Fujii, Yukihiko

2012-01-01

We applied near-infrared spectroscopy (NIRS) and electrocorticography (ECoG) recordings during cortical stimulation to a temporal lobe epilepsy patient who underwent subdural electrode implantation. Using NIRS, changes in blood concentrations of oxyhemoglobin (HbO[subscript 2]) and deoxyhemoglobin (HbR) during cortical stimulation of the left…

Haemoglobin changes and risk of anaemia following treatment for uncomplicated falciparum malaria in sub-Saharan Africa.

PubMed

Zwang, Julien; D'Alessandro, Umberto; Ndiaye, Jean-Louis; Djimdé, Abdoulaye A; Dorsey, Grant; Mårtensson, Andreas A; Karema, Corine; Olliaro, Piero L

2017-06-23

Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop of -12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15's, the mean Hb decline between day 0-3 was -4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline. Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28. There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia. On presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1-2, followed by a linear increase through follow-up. The degree of the early Hb dip is determined by pre-treatment parasitaemia and parasite clearance rates. Hb trends and rick of anaemia are independent of treatment.

[Oxyhemoglobin dissociation curve and 2,3-diphosphoglycerate in chronic hypoxemia].

PubMed

Koizumi, M

1991-05-01

The measurement of the oxyhemoglobin dissociation curve (ODC) and 2,3-diphosphoglycerate (2,3-DPG) in patients with chronic hypoxemia is important from the view point of tissue oxygenation. However, there have been no consistent results that explain the relation among chronic hypoxemia, 2,3-DPG and P50, which is oxygen pressure at an oxygen saturation of 50 percent. The aim of this study is to clarify what factors affect P50 and 2,3-DPG. 1) Patients with chronic hypoxemia, who showed PaO2 less than 60 Torr, had significantly higher P50 than normal subjects. 2) The concentration of Hb showed significant negative correlation with both P50 and 2,3-DPG. 3) Arterial blood pH showed significant positive correlation with both P50 and 2,3-DPG. 4) In a group with normal levels of Hb and pH, there was significant negative relationship between PaO2 and P50. 5) In a group with normal levels of Hb and pH, there was significant positive relationship between PaCO2 and P50. 6) In a group with normal levels of Hb, pH and PaCO2, there was significant negative relationship between PaO2 and 2,3-DPG. In conclusion, P50 and 2,3-DPG are affected largely by Hb concentration or blood pH, with or without hypoxemia. However there is a mechanism by which P50 and 2,3-DPG are increased by hypoxemia itself in a group with normal levels of Hb, pH and PaCO2.

Burden of anaemia in rural and urban jat women in haryana state, India.

PubMed

Maninder, Kaur; Kochar, G K

2009-09-01

A cross-sectional study was undertaken on 600 Jat women (rural=300, urban=300), aged 40 to 70 years from Haryana state in North India. The aim of the study was to determine the prevalence of anaemia and the dietary intake of rural and urban middle-aged (40-59 years) and older (60 and above) Jat women. The findings indicated that all the subjects exhibited a decline in the mean values of haemoglobin (Hb) concentration with advancement in age. The mean blood Hb concentration of urban middle-aged and older women was 10.1±1.3g/dl and 9.91.4g/dl respectively, which was higher than their rural counterparts at all age groups, although the differences were statistically non-significant (p>0.05). The overall prevalence of anaemia reached 88.7% (rural women= 91.3%, urban women =86%). Daily dietary intake of rural and urban subjects was below the recommended dietary allowances. Physical performance of both groups of the women showed a decline with a decrease in Hb concentration. A significant and positive correlation of Hb status was observed with grip strength and vital capacity while a negative association was witnessed with blood pressure and pulse rate in both the rural and urban women. Anaemia among these women may be attributed to inadequate dietary intake, illiteracy, and poor access to health services.

The effect of prolonged intrauterine hyperinsulinemia on iron utilization in fetal sheep.

PubMed

Georgieff, M K; Widness, J A; Mills, M M; Stonestreet, B S

1989-11-01

Newborn infants of poorly controlled insulin-dependent diabetic mothers demonstrate a redistribution of iron from serum and tissue stores into red blood cells. These changes may be due to increases in iron utilization during augmented Hb synthesis, which compensates for chronic intrauterine hypoxemia induced by prolonged fetal hyperinsulinemia. We tested this hypothesis by measuring plasma iron, total iron-binding capacity, percent iron-binding capacity saturation (total iron-binding capacity saturation), Hb concentration, total red cell Hb, and total red cell iron in the arterial blood of 11 chronically instrumented fetal sheep after 7-12 d of infusion with 15 U/day of insulin (n = 5) or placebo (n = 6). The insulin-infused fetal sheep had higher mean +/- SD plasma insulin concentrations (448 +/- 507 versus 11 +/- 8 mU/L; p less than 0.001) and lower arterial oxygen saturations (38 +/- 7 versus 54 +/- 9%; p less than 0.02). The insulin-infused group had a lower mean plasma iron concentration (20.8 +/- 10.9 versus 42.1 +/- 14.7 microM/L; p less than 0.02) and total iron-binding capacity saturation (36 +/- 20 versus 64 +/- 22%; p less than 0.02) and a higher total red cell Hb (45.4 +/- 8.7 versus 32.6 +/- 8.8 g; p less than 0.02) and total red cell iron content (154 +/- 29 versus 111 +/- 29 mg; p less than 0.02) when compared with the placebo group. Seven to 12 d of intrauterine hyperinsulinemia decreases serum iron and increases total red cell iron, most likely by stimulating increased Hb synthesis in response to low arterial oxygen saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial intelligence based modeling and optimization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) production process by using Azohydromonas lata MTCC 2311 from cane molasses supplemented with volatile fatty acids: a genetic algorithm paradigm.

PubMed

Zafar, Mohd; Kumar, Shashi; Kumar, Surendra; Dhiman, Amit K

2012-01-01

The present work describes the optimization of medium variables for the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] by Azohydromonas lata MTCC 2311 using cane molasses supplemented with propionic acid. Genetic algorithm (GA) has been used for the optimization of P(3HB-co-3HV) production through the simulation of artificial neural network (ANN) and response surface methodology (RSM). The predictions by ANN are better than those of RSM and in good agreement with experimental findings. The highest P(3HB-co-3HV) concentration and 3HV content have been reported as 7.35 g/l and 16.84 mol%, respectively by hybrid ANN-GA. Upon validation, 7.20 g/l and 16.30 mol% of P(3HB-co-3HV) concentration and 3HV content have been found in the shake flask, whereas 6.70 g/l and 16.35 mol%, have been observed in a 3 l bioreactor, respectively. The specific growth rate and P(3HB-co-3HV) accumulation rate of 0.29 per h and 0.16 g/lh determined with cane molasses are comparable to those observed on pure substrates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detection of methaemoglobinaemia and its application in 'poppers' abuse: maintaining the right balance between reduction and autooxidation during storage.

PubMed

Domingo, Olwen; Stöver, Andreas; Roider, Gabriele; Graw, Matthias

2017-03-01

In our study, we analysed the effect of a variety of storage conditions on the methaemoglobin (MetHb) content of blood samples obtained from altogether 110 deceased subjects with diverse causes of death, including three 'poppers'-related fatalities. The obtained results were compared to data from blood samples of six living, healthy subjects. Results obtained from the spectrophotometric measurement of blood MetHb content suggest that storage at room temperature (RT) and storage at -20 °C result in either highly fluctuating values, as was the case for the RT samples, or values much higher than the initial MetHb concentrations when stored at -20 °C. Blood samples at 4 °C showed more stable MetHb levels, which, however, increased with up to 4 % of the initial value after only 3 weeks of storage. These factors pose a problem in forensic toxicology, especially in nitrite abuse cases, where the involvement of such substance abuse is often unknown at the time of blood sampling and thus often requires longer storage times. Nevertheless, even after the storage of blood samples over several months at 4 and -20 °C, 'poppers' cases still show a significantly higher MetHb concentration as compared to non-'poppers' samples that were stored for the same time period under identical conditions.

Blood pressure reduction due to hemoglobin glycosylation in type 2 diabetic patients

PubMed Central

Cabrales, Pedro; Vázquez, Miguel A Salazar; Vázquez, Beatriz Y Salazar; Rodríguez-Morán, Martha; Intaglietta, Marcos; Guerrero-Romero, Fernando

2008-01-01

Objective: To test the hypothesis that glycosylation of hemoglobin constitutes a risk factor for hypertension. Methods: A total of 129 relative uniform diabetic subjects (86 women and 42 men) were enrolled in a cross sectional study. Exclusion criteria included alcohol consumption, smoking, ischemic heart disease, stroke, neoplasia, renal, hepatic, and chronic inflammatory disease. Systolic and diastolic pressures were recorded in subsequent days and mean arterial blood pressure (MAP) was determined. Hemoglobin glycosylation was measured by determining the percentage glycosylated hemoglobin (HbA1c) by means of the automated microparticle enzyme immunoassay test. Results: MAP was found to be independent of the concentration of HbA1c; however, correcting MAP for the variability in hematocrit, to evidence the level of vasoconstriction (or vasodilatation) showed that MAP is negatively correlated with the concentration of HbA1c (p for trend <0.05), when patients treated for hypertension are excluded from the analysis. Patients treated for hypertension showed the opposite trend with increasing MAP as HbA1c increased (p for the difference in trends <0.05). Conclusions: Glycosylation per se appears to lead to blood pressure reduction in type 2 diabetic patients untreated for hypertension. Treatment for hypertension may be associated with a level of endothelial dysfunction that interferes with the antihypertensive effect of HbA1c. PMID:19066010

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

A Mobile App to Improve Self-Management of Individuals With Type 2 Diabetes: Qualitative Realist Evaluation.

PubMed

Desveaux, Laura; Shaw, James; Saragosa, Marianne; Soobiah, Charlene; Marani, Husayn; Hensel, Jennifer; Agarwal, Payal; Onabajo, Nike; Bhatia, R Sacha; Jeffs, Lianne

2018-03-16

The increasing use of Web-based solutions for health prevention and promotion presents opportunities to improve self-management and adherence to guideline-based therapy for individuals with type 2 diabetes (T2DM). Despite promising preliminary evidence, many users stop using Web-based solutions due to the burden of data entry, hidden costs, loss of interest, and a lack of comprehensive features. Evaluations tend to focus on effectiveness or impact and fail to evaluate the nuanced variables that may interact to contribute to outcome success (or failure). This study aimed to evaluate a Web-based solution for improving self-management in T2DM to identify key combinations of contextual variables and mechanisms of action that explain for whom the solution worked best and in what circumstances. A qualitative realist evaluation was conducted with one-on-one, semistructured telephonic interviews completed at baseline, and again toward the end of the intervention period (3 months). Topics included participants' experiences of using the Web-based solution, barriers and facilitators of self-management, and barriers and facilitators to effective use. Transcripts were analyzed using thematic analysis strategies, after which the key themes were used to develop statements of the relationships between the key contextual factors, mechanisms of action, and impact on the primary outcome (glycated hemoglobin, HbA 1c ). Twenty-six interviews (14 baseline, 12 follow-up) were completed with 16 participants with T2DM, and the following 3 key groups emerged: the easiest fit, the best fit, and those who failed to activate. Self-efficacy and willingness to engage with the solution facilitated improvement in HbA 1c , whereas competing priorities and psychosocial issues created barriers to engagement. Individuals with high baseline self-efficacy who were motivated, took ownership for their actions, and prioritized diabetes management were early and eager adopters of the app and recorded improvements in HbA 1c over the intervention period. Individuals with moderate baseline self-efficacy and no competing priorities, who identified gaps in understanding of how their actions influence their health, were slow to adopt use but recorded the greatest improvements in HbA 1c . The final group had low baseline self-efficacy and identified a range of psychosocial issues and competing priorities. These participants were uncertain of the benefits of using a Web-based solution to support self-management, ultimately resulting in minimal engagement and no improvement in HbA 1c . Self-efficacy, competing priorities, previous behavior change, and beliefs about Web-based solutions interact to determine engagement and impact on the clinical outcomes. Considering the balance of these patient characteristics is likely to help health care providers identify individuals who are apt to benefit from a Web-based solution to support self-management of T2DM. Web-based solutions could be modified to incorporate the existing screening measures to identify individuals who are at risk of suboptimal adherence to inform the provision of additional support(s) as needed. ©Laura Desveaux, James Shaw, Marianne Saragosa, Charlene Soobiah, Husayn Marani, Jennifer Hensel, Payal Agarwal, Nike Onabajo, R Sacha Bhatia, Lianne Jeffs. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 16.03.2018.

Influences of casein hydrolysate ingestion on cerebral activity, autonomic nerve activity, and anxiety.

PubMed

Nakamura, Hirohiko; Iwamoto, Mario; Washida, Kenji; Sekine, Kazunori; Takase, Mitsunori; Park, Bum-Jin; Morikawa, Takeshi; Miyazaki, Yoshifumi

2010-01-01

This study examined the influences of the oral ingestion of casein hydrolysate from bovine milk at rest physiologically and psychologically. Eleven male university students were given a casein hydrolysate drink (H) or a maltitol drink as a control (C) in a crossover study. Just before and one hour after ingestion of each drink, the total-hemoglobin (tHb) concentrations at ten points of the prefrontal cortex to evaluate cerebral activity, and heart rate variability (HRV) to evaluate autonomic nerve activity through spectral analysis were measured as physiological indicators. The Japanese version of the State--Trait Anxiety Inventory--state anxiety (STAI-s) score was also used, as a psychological indicator. In comparison between H and C ingestion, a significant difference is observed only in tHb concentrations at one of ten points. At this point, the change in tHb concentration was lower after H ingestion compared to C ingestion. And in comparison between before and after ingestion of each drink, a significant increase in tHb concentration at two points after C ingestion, a significant increase in parasympathetic activity and decrease in sympathetic activity after H ingestion, and a significant decrease in STAI-s score in H ingestion were observed. These results suggest that ingestion of the casein hydrolysate may keep prefrontal cortex activity stable while maltitol ingestion partially increases the activity. Moreover, there is a possibility that casein hydrolysate might decrease sympathetic activity, increase parasympathetic activity, and lower anxiety. We conclude that the bovine milk casein hydrolysate may have more relaxing effects than maltitol.

Thermal stress and diabetic complications

NASA Astrophysics Data System (ADS)

Ohtsuka, Yoshinori; Yabunaka, Noriyuki; Watanabe, Ichiro; Noro, Hiroshi; Fujisawa, Hiroyuki; Agishi, Yuko

1995-06-01

Activities of erythrocyte aldose reductase were compared in 34 normal subjects, 45 diabetic patients, and nine young men following immersion in water at 25, 39, and 42° C. Mean basal enzyme activity was 1.11 (SEM 0.12) U/g Hb and 2.07 (SEM 0.14) U/g Hb in normal controls and diabetic patients, respectively ( P<0.0001). Activities of the enzyme showed a good correlation with hemaglobin A1 (HbA1) concentrations ( P<0.01) but not with fasting plasma glucose concentrations. After immersion at 42° C for 10 min, enzyme activity was increased by 37.6% ( P<0.01); however, the activity decreased by 52.2% ( P<0.005) after immersion for 10 min at 39° C and by 47.0% ( P<0.05) at 25° C. These changes suggest that heat stress might aggravate diabetic complications, and body exposure to hot environmental conditions is not recommended for diabetic patients.

Water properties in a novel thermoswelling poly(vinyl alcohol) derivative hydrogel as studied by nuclear magnetic resonance and Fourier transform infrared spectroscopy.

PubMed

Wang, Jianquan; Satoh, Mitsuru

2010-08-17

Water properties in a novel thermoswelling hydrogel, which was prepared from poly(vinyl alcohol)-trimellitate (PVA-T) by a simple chemical cross-linking and swollen in 0.1-1.0 M Li(2)SO(4) solutions, were investigated through nuclear magnetic resonance and Fourier transform infrared (FTIR) spectroscopies. The spin-spin relaxation of the water proton in the hydrogel was measured at 5-35 degrees C, and the results were analyzed with a two-component model to obtain a long T(2) and a short T(2) as well as their fractions (f(short) = 1 - f(long)). The f(short) values thus obtained proved to be a linear function of the gel swelling ratio, and all of the data, except for an upper deviation at 1.0 M Li(2)SO(4), were found to be on an almost same line irrespective of the temperature and the salt concentration. This dependency of f(short) on the swelling degree strongly suggests that the temperature increment has an equivalent effect as that of the SO(4)(2-) concentration; namely, scission of inter(intra-)molecular hydrogen bonding (HB) between the COOHs on the side group must be responsible for the observed thermoswelling in the sulfate salt solutions. The upper deviation of f(short) at 1.0 M from the "master line" was reasonably interpreted in terms of the salting-out effect by the concentrated sulfate anion. On the other hand, attenuated total reflection-FTIR measurements for a gel plate revealed that an appreciable dissociation of the carboxyl group occurred only in the 1.0 M Li(2)SO(4) system. This finding, in turn, means that gel swelling with an increase in the salt concentration up to 0.5 M is not caused by the ionization of the gel and supports the scission of the intermolecular HB. Hydrophobic hydration around the main chain was investigated via a peak shift of the stretching vibration of -CH(2)-, and the slight red shift observed only at 1.0 M suggested that the salting-out effect onto the hydrophobic hydration is rather limited and the hydration around the main chain still remained even with the significant deswelling at 1.0 M.

Modulation of the pharmacological actions of nitrovasodilators by methylene blue and pyocyanin.

PubMed Central

Gryglewski, R. J.; Zembowicz, A.; Salvemini, D.; Taylor, G. W.; Vane, J. R.

1992-01-01

1. In superfused precontracted strips of rabbit aorta, methylene blue (MeB) or pyocyanin (Pyo, 1-hydroxy-5-methyl phenazinum betaine) at concentrations of 1-10 microM inhibited relaxations induced by endothelium-derived relaxing factor (EDRF), glyceryl trinitrate (GTN), S-nitroso-N-acetyl-penicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1). However, the vasorelaxant actions of sodium nitroprusside (NaNP) or sodium nitrite (NaNO2) were enhanced by MeB or Pyo. Oxyhaemoglobin (HbO2, 1 microM) inhibited the activities of EDRF and all of the nitrovasodilators studied. Vascular preparations were not relaxed by Pyo unless pretreated with NaNP (0.05-10 microM). 2. In bathed, precontracted rings of rabbit aorta, Pyo (10 microM) produced a shift to the left of the cumulative concentration-response curve for NaNP (0.01-10 microM). The rise in guanosine-3':5'-cyclic monophosphate (cyclic GMP) content of aortic tissue was also enhanced. 3. The vasorelaxant potency of NaNP (30 microM) at pH 5-8 and at 37 degrees C remained unchanged over 2.5 h while a solution of SNAP (30 microM) progressively lost its biological activity over 60 min. The in vitro degradation of the biological activity of SNAP was accelerated by MeB (150 microM) or Pyo (150 microM), whereas the vasorelaxant potency NaNP (30 microM) was doubled when incubated with MeB or Pyo. 4. In human platelet-rich plasma, MeB or Pyo (0.3-3.0 microM) uncovered an anti-aggregatory action of subthreshold concentrations of NaNP (4-8 microM). This was abrogated by HbO2 (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1327388

Noninvasive diagnosis and therapeutic effect evaluation of deep vein thrombosis in clinics by near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Li, Ting; Sun, Yunlong; Chen, Xiao; Zhao, Yue; Ren, Rongrong

2015-01-01

Deep vein thrombosis (DVT) has become a severe disease with a rising incidence rate. The conventional diagnosis relies on complicated imaging modalities that may also involve invasive contrast agent injection and ionizing procedures (e.g., venography). Noninvasive near-infrared spectroscopy (NIRS) methods have been explored which required the DVT patients to follow some exercise protocols. Here, we attempt to use portable NIRS under patients' natural state for DVT diagnosis. Nine DVT patients and seven healthy subjects participated in NIRS measurements of concentration of oxy- and deoxy-hemoglobins (Δ[HbO2] and Δ[Hb]) relative to data on a tissue mimicking phantom at six particular sites of calves. It was found that Δ[HbO2] is significantly lower in DVT patients than healthy ones, whereas Δ[Hb] is distinctly higher. Moreover, after thrombolytic therapy, both Δ[HbO2] and Δ[Hb] in DVT calves assume a gradual convergence to the curves of healthy ones. This reveals the potential of NIRS for the noninvasive, continuous, and straightforward monitoring/therapeutic effect evaluation of DVT in clinics with appropriate bedside monitoring capability.

The impact of sickle cell trait on glycated haemoglobin in diabetes mellitus.

PubMed

Bleyer, A J; Vidya, S; Sujata, L; Russell, G B; Akinnifesi, D; Hire, D; Shihabi, Z; Knovich, M A; Daeihagh, P; Calles, J; Freedman, B I

2010-09-01

To determine the effect of sickle cell trait on measurement of glycated haemoglobin (HbA(1c)) in African American patients with diabetes mellitus. This is a retrospective study including 885 outpatients who underwent HbA(1c) testing. Medical record review and sickle cell trait determinations based on the HbA(1c) assay were performed in African American participants. The relationship between HbA(1c) and serum glucose measurements was analysed. Data were obtained from 385 AA (109 with SCT, 22 with haemoglobin C trait and 254 without haemoglobinopathy) and 500 European American patients. In a model created through multivariate repeated-effects regression, the relationship between HbA(1c) and simultaneous serum glucose did not differ between African American subjects with and without the sickle cell trait, but differed between African American subjects without the sickle cell trait and European Americans (P = 0.0002). Sickle cell trait does not impact the relationship between HbA(1c) and serum glucose concentration. In addition, it does not appear to account for ethnic difference in this relationship between African Americans and whites.

Simple diagnosis of HbA1c using the dual-plasmonic platform integrated with LSPR and SERS

NASA Astrophysics Data System (ADS)

Heo, Nam Su; Kwak, Cheol Hwan; Lee, Hoomin; Kim, Dongjoo; Lee, Sunmook; Kim, Gi-bum; Kwon, Soonjo; Kim, Woo Sik; Huh, Yun Suk

2017-07-01

A plasmonic active chip was designed with a transparent polymer film self-assembled with gold nanoparticles (AuNPs). In this study, we demonstrated the feasibility and sensitivity of biosensors by employing a plasmonic resonance technique. AuNPs are widely used as biosensing probes because they facilitate stable immobilization of biomolecules. Transparent polymer film facilitated measurement of changes in absorbance via transmitted light and analysis of Raman scattering via scattered light. The cysteine rich protein G and anti-HbA1c were sequentially conjugated to self-assembled AuNPs on the transparent polymer film to detect a target protein. HbA1c, which is used as an indicator for diabetes diagnosis, was selected for target protein detection. We confirmed the linearly increased absorbance values with increasing HbA1c level (3.19-14.0%) by LSPR detection. We also verified the linear increase in SERS intensity as the concentration of anti-Hb increased from 10 ng mL-1 to 1 μg mL-1 by analyzing the SERS spectra of Cy3 labeled anti-Hb added substrates.

The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading.

PubMed

Beck, Roy W; Connor, Crystal G; Mullen, Deborah M; Wesley, David M; Bergenstal, Richard M

2017-08-01

HbA 1c is a v aluable metric for comparing treatment groups in a randomized trial, for assessing glycemic trends in a population over time, or for cross-sectional comparisons of glycemic control in different populations. However, what is not widely appreciated is that HbA 1c may not be a good indicator of an individual patient's glycemic control because of the wide range of mean glucose concentrations and glucose profiles that can be associated with a given HbA 1c level. To illustrate this point, we plotted mean glucose measured with continuous glucose monitoring (CGM) versus central laboratory-measured HbA 1c in 387 participants in three randomized trials, showing that not infrequently HbA 1c may underestimate or overestimate mean glucose, sometimes substantially. Thus, if HbA 1c is to be used to assess glycemic control, it is imperative to know the patient's actual mean glucose to understand how well HbA 1c is an indicator of the patient's glycemic control. With knowledge of the mean glucose, an estimated HbA 1c (eA1C) can be calculated with the formula provided in this article to compare with the measured HbA 1c . Estimating glycemic control from HbA 1c alone is in essence applying a population average to an individual, which can be misleading. Thus, a patient's CGM glucose profile has considerable value for optimizing his or her diabetes management. In this era of personalized, precision medicine, there are few better examples with respect to the fallacy of applying a population average to a specific patient rather than using specific information about the patient to determine the optimal approach to treatment. © 2017 by the American Diabetes Association.

Familial secondary erythrocytosis due to increased oxygen affinity is caused by destabilization of the T state of hemoglobin Brigham (α2β2Pro100Leu)

PubMed Central

Mollan, Todd L; Abraham, Bindu; Strader, Michael Brad; Jia, Yiping; Lozier, Jay N; Olson, John S; Alayash, Abdu I

2012-01-01

Hemoglobin Brigham (β Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb Brigham and exhibit elevated O2 affinity compared with normal cells (P50 = 23 mm Hg vs. 31 mmHg at pH 7.4 at 37°C). O2 affinities measured for hemolysates were sensitive to changes in pH or chloride concentrations, indicating little change in the Bohr and Chloride effects. Hb Brigham was separated from normal HbA by nondenaturing cation exchange liquid chromatography, and the amino acid substitution was verified by mass spectrometry. The properties of Hb Brigham isolated from the patient's blood were then compared with those of recombinant Hb Brigham expressed in Escherichia coli. Kinetic experiments suggest that the rate constants for ligand binding and release in the high (R) and low (T) affinity quaternary states of Hb Brigham are similar to those of native hemoglobin. However, the Brigham mutation decreases the T to R equilibrium constant (L) which accelerates the switch to the R state during ligand binding to deoxy-Hb, increasing the rate of association by approximately twofold, and decelerates the switch during ligand dissociation from HbO2, decreasing the rate approximately twofold. These kinetic data help explain the high O2 affinity characteristics of Hb Brigham and provide further evidence for the importance of the contribution of Pro100 to intersubunit contacts and stabilization of the T quaternary structure. PMID:22821886

Protonic transport through solitons in hydrogen-bonded systems

NASA Astrophysics Data System (ADS)

Kavitha, L.; Jayanthi, S.; Muniyappan, A.; Gopi, D.

2011-09-01

We offer an alternative route for investigating soliton solutions in hydrogen-bonded (HB) chains. We invoke the modified extended tangent hyperbolic function method coupled with symbolic computation to solve the governing equation of motion for proton dynamics. We investigate the dynamics of proton transfer in HB chains through bell-shaped soliton excitations, which trigger the bio-energy transport in most biological systems. This solitonic mechanism of proton transfer could play functional roles in muscular contraction, enzymatic activity and oxidative phosphorylation.

Novel Luminescent Probe Based on a Terbium(III) Complex for Hemoglobin Determination

NASA Astrophysics Data System (ADS)

Yegorova, A. V.; Leonenko, I. I.; Aleksandrova, D. I.; Scrypynets, Yu. V.; Antonovich, V. P.; Ukrainets, I. V.

2014-09-01

We have studied the spectral luminescent properties of Tb(III) and Eu(III) complexes with a number of novel derivatives of oxoquinoline-3-carboxylic acid amides (L1-L5 ). We have observed quenching of the luminescence of 1:1 Tb(III)-L1-5 complexes by hemoglobin (Hb), which is explained by resonance energy transfer of electronic excitation from the donor (Tb(III)-L1-5 ) to the acceptor (Hb). Using the novel luminescent probe Tb(III)-L1, we have developed a method for determining Hb in human blood. The calibration Stern-Volmer plot is linear in the Hb concentration range 0.6-36.0 μg/mL, detection limit 0.2 μg/mL (3·10-9 mol/L).

Low Volume Aerobic Training Heightens Muscle Deoxygenation in Early Post-Angina Pectoris Patients.

PubMed

Takagi, Shun; Murase, Norio; Kime, Ryotaro; Niwayama, Masatsugu; Osada, Takuya; Katsumura, Toshihito

2016-01-01

The aim of this study was to investigate the effect of low volume aerobic exercise training on muscle O2 dynamics during exercise in early post-angina pectoris (AP) patients, as a pilot study. Seven AP patients (age: 72 ± 6 years) participated in aerobic exercise training for 12 weeks. Training consisted of continuous cycling exercise for 30 min at the individual's estimated lactate threshold, and the subjects trained for 15 ± 5 exercise sessions over 12 weeks. Before and after training, the subjects performed ramp cycling exercise until exhaustion. Muscle O2 saturation (SmO2) and relative changes from rest in deoxygenated hemoglobin concentration (∆Deoxy-Hb) and total hemoglobin concentration (∆Total-Hb) were monitored at the vastus lateralis by near infrared spatial resolved spectroscopy during exercise. The SmO2 was significantly lower and ∆Deoxy-Hb was significantly higher after training than before training, while there were no significant changes in ∆Total-Hb. These results indicated that muscle deoxygenation and muscle O2 extraction were potentially heightened by aerobic exercise training in AP patients, even though the exercise training volume was low.

[Inhibition of HIV-1 mediated cell-cell fusion by saponin fraction from Psidium guajava leaf].

PubMed

Mao, Qin-Chao; Zhou, Ying-Chun; Li, Run-Ming; Hu, Yi-Ping; Liu, Shu-Wen; Li, Xiao-Juan

2010-11-01

To investigate the effects of the total saponin of Psidium guajava leaf (TSGL) on HIV-1 envelop proteins (env) mediated virus entry into target cells. The TSGL was purified and concentrated using SA-1 macropore resin. The effect of TSGL on HIV-1 entry into target cells was tested using a cell-cell fusion assay by mixing CHO-WT and MT-2 cells. The cytotoxicity of TSGL was measured by MTT assay. The activity of TSGL on blocking the HIV-1 gp41 six helical bundle (6-HB) formation was analyzed by ELISA and Native-PAGE (N-PAGE). The TSGL could inhibit HIV env mediated cell-cell fusion with an IC50 of (7.33 +/- 0.40) microg/mL, and displayed little cytotoxicity at that concentration. ELISA assay showed that the TSGL could prevent gp41 6-HB formation with inhibitory activity of 95.93% at 25 microg/mL. N-PAGE study confirmed the inhibitory effect of TSGL on gp41 6-HB formation. The TSGL can inhibit HIV entry target cells by interfering the envelop subunit gp41 form the critical 6-HB structure.

Physical Activity Throughout Adolescence and Hba1c in Early Adulthood: Birth Cohort Study.

PubMed

Nakamura, Priscila M; Mielke, Grégore I; Horta, Bernardo L; Assunção, Maria Cecília; Gonçalves, Helen; Menezes, Ana M B; Barros, Fernando C; Ekelund, Ulf; Brage, Soren; Wehrmeister, Fernando C; Oliveira, Isabel O; Hallal, Pedro C

2017-05-01

Physical inactivity is responsible for 7% of diabetes deaths worldwide, but little is known whether low levels of physical activity (PA) during adolescence increase the risk of diabetes in early adulthood. We evaluated the cross-sectional and longitudinal associations between PA throughout adolescence and HbA1c concentration in early adulthood. HbA1c was measured by high performance liquid chromatography. PA was assessed by self-report at the ages of 11, 15, and 18 years and by accelerometry at the ages of 13 (subsample) and 18 years. The loss percentages of follow up were 12.5% at 11 years, 14.4% at 15 years, and 18.7% at 18 years. At 18 years, boys showed higher HbA1c than girls. At age 18 years, accelerometrybased PA at 18 years was inversely related to HbA1c levels in boys. Self-reported leisure-time PA at ages 11, 15, and 18 were unrelated to HbA1c in both genders. PA at 13 years of age was unrelated to HbA1c among both genders. In trajectory analysis, PA and accelerometer PA trajectories were not associated with later HbA1c. Objectively measured PA at 18 years was cross-sectionally inversely associated with HbA1c in boys only. No prospective associations were identified.

Post-translational Transformation of Methionine to Aspartate Is Catalyzed by Heme Iron and Driven by Peroxide

PubMed Central

Strader, Michael Brad; Hicks, Wayne A.; Kassa, Tigist; Singleton, Eileen; Soman, Jayashree; Olson, John S.; Weiss, Mitchell J.; Mollan, Todd L.; Wilson, Michael T.; Alayash, Abdu I.

2014-01-01

A pathogenic V67M mutation occurs at the E11 helical position within the heme pockets of variant human fetal and adult hemoglobins (Hb). Subsequent post-translational modification of Met to Asp was reported in γ subunits of human fetal Hb Toms River (γ67(E11)Val → Met) and β subunits of adult Hb (HbA) Bristol-Alesha (β67(E11)Val → Met) that were associated with hemolytic anemia. Using kinetic, proteomic, and crystal structural analysis, we were able to show that the Met → Asp transformation involves heme cycling through its oxoferryl state in the recombinant versions of both proteins. The conversion to Met and Asp enhanced the spontaneous autoxidation of the mutants relative to wild-type HbA and human fetal Hb, and the levels of Asp were elevated with increasing levels of hydrogen peroxide (H2O2). Using H218O2, we verified incorporation of 18O into the Asp carboxyl side chain confirming the role of H2O2 in the oxidation of the Met side chain. Under similar experimental conditions, there was no conversion to Asp at the αMet(E11) position in the corresponding HbA Evans (α62(E11)Val → Met). The crystal structures of the three recombinant Met(E11) mutants revealed similar thioether side chain orientations. However, as in the solution experiments, autoxidation of the Hb mutant crystals leads to electron density maps indicative of Asp(E11) formation in β subunits but not in α subunits. This novel post-translational modification highlights the nonequivalence of human Hb α, β, and γ subunits with respect to redox reactivity and may have direct implications to α/β hemoglobinopathies and design of oxidatively stable Hb-based oxygen therapeutics. PMID:24939847

Post-translational transformation of methionine to aspartate is catalyzed by heme iron and driven by peroxide: a novel subunit-specific mechanism in hemoglobin.

PubMed

Strader, Michael Brad; Hicks, Wayne A; Kassa, Tigist; Singleton, Eileen; Soman, Jayashree; Olson, John S; Weiss, Mitchell J; Mollan, Todd L; Wilson, Michael T; Alayash, Abdu I

2014-08-08

A pathogenic V67M mutation occurs at the E11 helical position within the heme pockets of variant human fetal and adult hemoglobins (Hb). Subsequent post-translational modification of Met to Asp was reported in γ subunits of human fetal Hb Toms River (γ67(E11)Val → Met) and β subunits of adult Hb (HbA) Bristol-Alesha (β67(E11)Val → Met) that were associated with hemolytic anemia. Using kinetic, proteomic, and crystal structural analysis, we were able to show that the Met → Asp transformation involves heme cycling through its oxoferryl state in the recombinant versions of both proteins. The conversion to Met and Asp enhanced the spontaneous autoxidation of the mutants relative to wild-type HbA and human fetal Hb, and the levels of Asp were elevated with increasing levels of hydrogen peroxide (H2O2). Using H2(18)O2, we verified incorporation of (18)O into the Asp carboxyl side chain confirming the role of H2O2 in the oxidation of the Met side chain. Under similar experimental conditions, there was no conversion to Asp at the αMet(E11) position in the corresponding HbA Evans (α62(E11)Val → Met). The crystal structures of the three recombinant Met(E11) mutants revealed similar thioether side chain orientations. However, as in the solution experiments, autoxidation of the Hb mutant crystals leads to electron density maps indicative of Asp(E11) formation in β subunits but not in α subunits. This novel post-translational modification highlights the nonequivalence of human Hb α, β, and γ subunits with respect to redox reactivity and may have direct implications to α/β hemoglobinopathies and design of oxidatively stable Hb-based oxygen therapeutics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Sodium metabisulfite–induced polymerization of sickle cell hemoglobin incubated in the extracts of three medicinal plants (Anacardium occidentale, Psidium guajava, and Terminalia catappa)

PubMed Central

Chikezie, Paul Chidoka

2011-01-01

Background: The exploitation and utilization of vast varieties of herbal extracts may serve as alternative measures to deter aggregation of deoxygenated sickle cell hemoglobin (deoxyHbS) molecules. Objective: The present in vitro study ascertained the capacity of three medicinal plants, namely, Anacardium occidentale, Psidium guajava, and Terminalia catappa, to alter polymerization of HbS. Materials and Methods: Spectrophotometric method was used to monitor the level of polymerization of hemolysate HbS molecules treated with sodium metabisulfite (Na2 S2 O5) at a regular interval of 30 s for a period of 180 s in the presence of separate aqueous extracts of A. occidentale, P. guajava, and T. catappa. At time intervals of 30 s, the level of polymerization was expressed as percentage of absorbance relative to the control sample at the 180th s. Results: Although extracts of the three medicinal plants caused significant (P < 0.05) reduction in polymerization of deoxyHbS molecules, the corresponding capacity in this regard diminished with increase in incubation time. Aqueous extract of P. guajava exhibited the highest capacity to reduced polymerization of deoxyHbS molecules. Whereas at t > 60 s, extract concentration of 400 mg% of A. occidentale activated polymerization of deoxyHbS molecules by 6.23±1.34, 14.53±1.67, 21.15±1.89, and 24.42±1.09%, 800 mg% of T. catappa at t > 30 s gave values of 2.50±1.93, 5.09±1.96, 10.00±0.99, 15.38±1.33, and 17.31±0.97%. Conclusion: The capacity of the three medicinal plants to interfere with polymerization of deoxyHbS molecules depended on the duration of incubation and concentration of the extracts. PMID:21716622

D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease.

PubMed

Imamura, Keiko; Takeshima, Takao; Kashiwaya, Yoshihiro; Nakaso, Kazuhiro; Nakashima, Kenji

2006-11-01

It has been postulated that the pathogenesis of Parkinson's disease (PD) is associated with mitochondrial dysfunction. Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro. We investigated the neuroprotective effect of D-beta-hydroxybutyrate (bHB), a ketone body, against rotenone toxicity by using SH-SY5Y dopaminergic neuroblastoma cells. SH-SY5Y cells, differentiated by all-trans-retinoic acid, were exposed to rotenone at concentrations ranging from 0 to 1,000 nM. We evaluated cellular oxidation reduction by the alamarBlue assay, viability by lactate dehydrogenase (LDH) assay, and survival/death ratio by live/dead assays. Exposure to rotenone for 48 hr oxidized cells and decreased their viability and survival rate in a concentration-dependent manner. Pretreatment of cells with 8 mM bHB provided significant protection to SH-SY5Y cells. Whereas rotenone caused the loss of mitochondrial membrane potential, released cytochrome c into the cytosol, and reduced cytochrome c content in mitochondria, addition of bHB blocked this toxic effect. bHB also attenuated the rotenone-induced activation of caspase-9 and caspase-3. Administration of 0-10 mM 3-nitropropionic acid, a complex II inhibitor, also decreased the reducing power of SH-SY5Y cells measured by alamarBlue assay. Pretreatment with 8 mM bHB attenuated the decrease of alamarBlue fluorescence. These data demonstrated that bHB had a neuroprotective effect that supported the mitochondrial respiration system by reversing the inhibition of complex I or II. Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD. Copyright 2006 Wiley-Liss, Inc.

Increased alpha 2-macroglobulin in diabetes: a hyperglycemia related phenomenon associated with reduced antithrombin III activity.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Stante, A; Dello Russo, P; Torella, R

1989-01-01

Increased alpha 2-macroglobulin (alpha 2M) activity and concentration, and decreased antithrombin III (ATIII) plasma concentration are reported in diabetic subjects. In diabetes an inverse correlation between ATIII activity and blood glucose, HbA1, alpha 2M activity and alpha 2M concentration, and a direct correlation between both alpha 2M activity and alpha 2M concentration with blood glucose and HbA1 are found. Moreover, a direct correlation between alpha 2M activity and alpha 2M concentration fails. In both diabetic and normal subjects induced hyperglycemia increases alpha 2M activity and alpha 2M concentration reduces ATIII activity, while ATIII concentration is not affected. These data which show that hyperglycemia may increase alpha 2M molecule levels while altering only the biological function of ATIII, provide evidence that hyperglycemia may decrease, directly, the biological function of some proteins and may condition the levels of some risk factors for the development of diabetic complications such as alpha 2M.

Concentration, ozone formation potential and source analysis of volatile organic compounds (VOCs) in a thermal power station centralized area: A study in Shuozhou, China.

PubMed

Yan, Yulong; Peng, Lin; Li, Rumei; Li, Yinghui; Li, Lijuan; Bai, Huiling

2017-04-01

Volatile organic compounds (VOCs) from two sampling sites (HB and XB) in a power station centralized area, in Shuozhou city, China, were sampled by stainless steel canisters and measured by gas chromatography-mass selective detection/flame ionization detection (GC-MSD/FID) in the spring and autumn of 2014. The concentration of VOCs was higher in the autumn (HB, 96.87 μg/m 3 ; XB, 58.94 μg/m 3 ) than in the spring (HB, 41.49 μg/m 3 ; XB, 43.46 μg/m 3 ), as lower wind speed in the autumn could lead to pollutant accumulation, especially at HB, which is a new urban area surrounded by residential areas and a transportation hub. Alkanes were the dominant group at both HB and XB in both sampling periods, but the contribution of aromatic pollutants at HB in the autumn was much higher than that of the other alkanes (11.16-19.55%). Compared to other cities, BTEX pollution in Shuozhou was among the lowest levels in the world. Because of the high levels of aromatic pollutants, the ozone formation potential increased significantly at HB in the autumn. Using the ratio analyses to identify the age of the air masses and analyze the sources, the results showed that the atmospheric VOCs at XB were strongly influenced by the remote sources of coal combustion, while at HB in the spring and autumn were affected by the remote sources of coal combustion and local sources of vehicle emission, respectively. Source analysis conducted using the Positive Matrix Factorization (PMF) model at Shuozhou showed that coal combustion and vehicle emissions made the two largest contributions (29.98% and 21.25%, respectively) to atmospheric VOCs. With further economic restructuring, the influence of vehicle emissions on the air quality should become more significant, indicating that controlling vehicle emissions is key to reducing the air pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of anaemia on treatment outcome in patients with squamous cell carcinoma of anal canal and anal margin

PubMed Central

Cesnjevar, Monika; Anzic, Mitja; Hadzic, Jasna But; Ermenc, Ajra Secerov; Anderluh, Franc; Velenik, Vaneja; Jeromen, Ana; Korosec, Peter

2016-01-01

Background Radiochemotherapy is the main treatment for patients with squamous cell carcinoma of the anal canal. Anaemia is reported to have adverse effect on survival in cancer patients. The aim of the study was to evaluate the influence of anaemia on radiochemotherapy treatment outcome in patients with squamous cell carcinoma of the anal canal. Patients and methods One hundred consecutive patients with histologically confirmed squamous cell carcinoma of the anal canal were treated radically with 3-dimensional conformal or intensity-modulated radiation therapy followed by brachytherapy or external beam radiotherapy boost and with concurrent mitomycin C and 5-fluorouracil. The influence on survival of pre-treatment, mean on-treatment and end-of-treatment haemoglobin (Hb) concentrations was studied. Results The 5-year locoregional control, disease free survival, disease specific survival and overall survival rates for all patients were 72%, 71%, 77% and 62%, respectively. In univariate analysis, patients with pre-treatment and end-of-treatment Hb > 120 g/L survived statistically significantly better compared to patients with Hb ≤ 120 g/L. Patients with mean on-treatment Hb > 120 g/L only had statistically significant better locoregional control and overall survival than patients with Hb ≤ 120 g/L. In multivariate analysis, independent prognostic factors were pre-treatment Hb (> 120 g/L vs. ≤ 120 g/L) for overall survival (hazard ratio [HR] = 0.419, 95% confidence interval [CI] = 0.190–0.927, p = 0.032) and stage (I & II vs. III) for disease specific (HR = 3.523, 95% CI = 1.375–9.026, p = 0.009) and overall survival (HR = 2.230, 95% CI = 1.167–4.264, p = 0.015). Conclusions The pre-treatment, mean on-treatment and end-of-treatment Hb concentration > 120 g/L carried better prognosis for patients for with squamous cell carcinoma of the anal canal treated with radiochemotherapy. The pre-treatment Hb > 120 g/L was an independent prognostic factor for overall survival of patients with anal canal cancer. PMID:27069457

Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

PubMed

Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

2017-07-01

Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA 1c . Methods HbA 1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA 1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA 1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA 1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

Biosynthesis of Polyhydroxyalkanoate from Steamed Soybean Wastewater by a Recombinant Strain of Pseudomonas sp. 61-3.

PubMed

Hokamura, Ayaka; Yunoue, Yuko; Goto, Saki; Matsusaki, Hiromi

2017-08-08

Pseudomonas sp. 61-3 accumulates a blend of poly(3-hydroxybutyrate) [P(3HB)] homopolymer and a random copolymer, poly(3-hydroxybutyrate- co -3-hydroxyalkanoate) [P(3HB- co -3HA)], consisting of 3HA units of 4-12 carbon atoms. Pseudomonas sp. 61-3 possesses two types of PHA synthases, PHB synthase (PhbC) and PHA synthases (PhaC1 and PhaC2), encoded by the phb and pha loci, respectively. The P(94 mol% 3HB- co -6 mol% 3HA) copolymer synthesized by the recombinant strain of Pseudomonas sp. 61-3 ( phbC :: tet ) harboring additional copies of phaC1 gene is known to have desirable physical properties and to be a flexible material with moderate toughness, similar to low-density polyethylene. In this study, we focused on the production of the P(3HB- co -3HA) copolymer using steamed soybean wastewater, a by-product in brewing miso , which is a traditional Japanese seasoning. The steamed soybean wastewater was spray-dried to produce a powder (SWP) and used as the sole nitrogen source for the synthesis of P(3HB- co -3HA) by the Pseudomonas sp. 61-3 recombinant strain. Hydrolyzed SWP (HSWP) was also used as a carbon and nitrogen source. P(3HB- co -3HA)s with relatively high 3HB fractions could be synthesized by a recombinant strain of Pseudomonas sp. 61-3 ( phbC :: tet ) harboring additional copies of the phaC1 gene in the presence of 2% glucose and 10-20 g/L SWP as the sole nitrogen source, producing a PHA concentration of 1.0-1.4 g/L. When HSWP was added to a nitrogen- and carbon-free medium, the recombinant strain could synthesize PHA without glucose as a carbon source. The recombinant strain accumulated 32 wt% P(3HB- co -3HA) containing 80 mol% 3HB and 20 mol% medium-chain-length 3HA with a PHA concentration of 1.0 g/L when 50 g/L of HSWP was used. The PHA production yield was estimated as 20 mg-PHA/g-HSWP, which equates to approximately 1.0 g-PHA per liter of soybean wastewater.

[Effect of hydrostatic pressure on intracellular free calcium concentration and transient receptor potential vanilloid expression in human bladder smooth muscle cells].

PubMed

Han, Zhenwei; Wang, Kunjie; Chen, Lin; Wei, Tangqiang; Luo, Deyi; Li, Shengfu

2012-04-01

To explore the effect of hydrostatic pressure on intracellular free calcium concentration ([Ca2+]i) and the gene expression of transient receptor potential vanilloid (TRPV) in cultured human bladder smooth muscle cells (hb-SMCs), and to preliminarily probe into the possible molecular mechanism of hb-SMCs proliferation stimulated by hydrostatic pressure. The passage 6-7 hb-SMCs were loaded with Ca2+ indicator Fluo-3/AM. When the hb-SMCs were under 0 cm H2O (1cm H2O = 0.098 kPa) (group A) or 200 cm H2O hydrostatic pressure for 30 minutes (group B) and then removing the 200 cm H2O hydrostatic pressure (group C), the [Ca2+]i was measured respectively by inverted laser scanning confocal microscope. When the hb-SMCs were given the 200 cm H2O hydrostatic pressure for 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, the mRNA expressions of TRPV1, TRPV2, and TRPV4 were detected by RT-PCR technique. The [Ca2+]i of group A, group B, and group C were (100.808 +/- 1.724), (122.008 +/- 1.575), and (99.918 +/- 0.887) U, respectively; group B was significantly higher than groups A and C (P < 0.001). The [Ca2+]i of group C decreased to the base line level of group A after removing the pressure (t = 0.919, P = 0.394). The TRPV1, TRPV2, and TRPV4 genes expressed in hb-SMCs under 200 cm H2O hydrostatic pressure at 0 hour, 2 hours, 6 hours, 12 hours, and 24 hours, but the expressions had no obvious changes with time. There was no significant difference in the expressions of TRPV1, TRPV2, and TRPV4 among 3 groups (P > 0.05). The [Ca2+]i of hb-SMCs increases significantly under high hydrostatic pressure. As possible genes in stretch-activated cation channel, the TRPV1, TRPV2, and TRPV4 express in hb-SMCs under 200 cm H2O hydrostatic pressure. It is possible that the mechanical pressure regulates the [Ca2+]i of hb-SMCs by opening the stretch-activated cation channel rather than up-regulating its expression.

Biosynthesis of Polyhydroxyalkanoate from Steamed Soybean Wastewater by a Recombinant Strain of Pseudomonas sp. 61-3

PubMed Central

Hokamura, Ayaka; Yunoue, Yuko; Goto, Saki; Matsusaki, Hiromi

2017-01-01

Pseudomonas sp. 61-3 accumulates a blend of poly(3-hydroxybutyrate) [P(3HB)] homopolymer and a random copolymer, poly(3-hydroxybutyrate-co-3-hydroxyalkanoate) [P(3HB-co-3HA)], consisting of 3HA units of 4–12 carbon atoms. Pseudomonas sp. 61-3 possesses two types of PHA synthases, PHB synthase (PhbC) and PHA synthases (PhaC1 and PhaC2), encoded by the phb and pha loci, respectively. The P(94 mol% 3HB-co-6 mol% 3HA) copolymer synthesized by the recombinant strain of Pseudomonas sp. 61-3 (phbC::tet) harboring additional copies of phaC1 gene is known to have desirable physical properties and to be a flexible material with moderate toughness, similar to low-density polyethylene. In this study, we focused on the production of the P(3HB-co-3HA) copolymer using steamed soybean wastewater, a by-product in brewing miso, which is a traditional Japanese seasoning. The steamed soybean wastewater was spray-dried to produce a powder (SWP) and used as the sole nitrogen source for the synthesis of P(3HB-co-3HA) by the Pseudomonas sp. 61-3 recombinant strain. Hydrolyzed SWP (HSWP) was also used as a carbon and nitrogen source. P(3HB-co-3HA)s with relatively high 3HB fractions could be synthesized by a recombinant strain of Pseudomonas sp. 61-3 (phbC::tet) harboring additional copies of the phaC1 gene in the presence of 2% glucose and 10–20 g/L SWP as the sole nitrogen source, producing a PHA concentration of 1.0–1.4 g/L. When HSWP was added to a nitrogen- and carbon-free medium, the recombinant strain could synthesize PHA without glucose as a carbon source. The recombinant strain accumulated 32 wt% P(3HB-co-3HA) containing 80 mol% 3HB and 20 mol% medium-chain-length 3HA with a PHA concentration of 1.0 g/L when 50 g/L of HSWP was used. The PHA production yield was estimated as 20 mg-PHA/g-HSWP, which equates to approximately 1.0 g-PHA per liter of soybean wastewater. PMID:28952548

Determinants of Anemia and Hemoglobin Concentration in Haitian School-Aged Children

PubMed Central

Iannotti, Lora L.; Delnatus, Jacques R.; Odom, Audrey R.; Eaton, Jacob C.; Griggs, Jennifer J.; Brown, Sarah; Wolff, Patricia B.

2015-01-01

Anemia diminishes oxygen transport in the body, resulting in potentially irreversible growth and developmental consequences for children. Limited evidence for determinants of anemia exists for school-aged children. We conducted a cluster randomized controlled trial in Haiti from 2012 to 2013 to test the efficacy of a fortified school snack. Children (N = 1,047) aged 3–13 years were followed longitudinally at three time points for hemoglobin (Hb) concentrations, anthropometry, and bioelectrical impedance measures. Dietary intakes, infectious disease morbidities, and socioeconomic and demographic factors were collected at baseline and endline. Longitudinal regression modeling with generalized least squares and logit models with random effects identified anemia risk factors beyond the intervention effect. At baseline, 70.6% of children were anemic and 2.6% were severely anemic. Stunting increased the odds of developing anemia (adjusted odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.05–2.08) and severe anemia (adjusted OR: 2.47, 95% CI: 1.30–4.71). Parent-reported vitamin A supplementation and deworming were positively associated with Hb concentrations, whereas fever and poultry ownership showed a negative relationship with Hb concentration and increased odds of severe anemia, respectively. Further research should explore the full spectrum of anemia etiologies in school children, including genetic causes. PMID:26350448

Intraerythrocytic 2,3-diphosphoglycerate concentration in hypertensive subjects before and following control by anti hypertensive treatment.

PubMed

Kasparian, H; Konstantopoulos, K; Tassiopoulos, S; Papadogiannis, D; Karadzas, N; Tassiopoulos, T

1997-09-01

We measured the 2,3-diphosphoglycerate inraerythrocytic concentration in 24 normal controls and in 24 hypertensives before and following drug therapy. In hypertensives the 2,3-diphosphoglycerate concentration was higher than that of the controls (14.96 mumol/g Hb vs 13.26 mumol/g Hb respectively); the difference is statistically significant (p < 0.001). Following control of the hypertension by drug therapy, the 2,3 DPG levels in the patients studied do not seem to differ statistically from those of the controls. This may be a consequence of lower cardiac output in hypertension which results to a lower tissue perfusion, leading to an increased concentration of deoxygenated haemoglobin in the vein blood. Measurement of 2,3-diphosphoglucerate may prove of value in estimating tissue perfusion in hypertension.

A simple biofuel cell cathode with human red blood cells as electrocatalysts for oxygen reduction reaction.

PubMed

Ayato, Yusuke; Sakurai, Kenichiro; Fukunaga, Saori; Suganuma, Takuya; Yamagiwa, Kiyofumi; Shiroishi, Hidenobu; Kuwano, Jun

2014-05-15

A red blood cell (RBC) from human exhibited direct electron transfer (DET) activity on a bare indium tin oxide (ITO) electrode. A formal potential of -0.152 V vs. a silver-silver chloride saturated potassium chloride (Ag|AgCl|KCl(satd.)) was estimated for the human RBC (type AB) from a pair of redox peaks at around 0.089 and -0.215 V (vs. Ag|AgCl|KCl(satd.)) on cyclic voltammetric (CV) measurements in a phosphate buffered saline (PBS; 39 mM; pH 7.4) solution. The results agreed well with those of a redox couple for iron-bearing heme groups in hemoglobin molecules (HbFe(II)/HbFe(III)) on the bare ITO electrodes, indicated that DET active species were hemoglobin (Hb) molecules encapsulated by a phospholipid bilayer membrane of the human RBC. The quantity of electrochemically active Hb in the human RBC was estimated to be 30 pmol cm(-2). In addition, the human RBC exhibited oxygen reduction reaction (ORR) activity in the dioxygen (O2) saturated PBS solution at the negative potential from ca. -0.15 V (vs. Ag|AgCl|KCl(satd.)). A single cell test proved that a biofuel cell (BFC) with an O2|RBC|ITO cathode showed the open-circuit voltage (OCV) of ca. 0.43 V and the maximum power density of ca. 0.68 μW cm(-2). © 2013 Published by Elsevier B.V.

ITO/gold nanoparticle/RGD peptide composites to enhance electrochemical signals and proliferation of human neural stem cells.

PubMed

Kim, Tae-Hyung; El-Said, Waleed Ahmed; An, Jeung Hee; Choi, Jeong-Woo

2013-04-01

A cell chip composed of ITO, gold nanoparticles (GNP) and RGD-MAP-C peptide composites was fabricated to enhance the electrochemical signals and proliferation of undifferentiated human neural stem cells (HB1.F3). The structural characteristics of the fabricated surfaces were confirmed by both scanning electron microscopy and surface-enhanced Raman spectroscopy. HB1.F3 cells were allowed to attach to various composites electrodes in the cell chip and the material-dependent effects on electrochemical signals and cell proliferation were analyzed. The ITO/60 nm GNP/RGD-MAP-C composite electrode was found to be the best material in regards to enhancing the voltammetric signals of HB1.F3 cells when exposed to cyclic voltammetry, as well as for increasing cell proliferation. Differential pulse voltammetry was performed to evaluate the adverse effects of doxorubicin on HB1.F3 cells. In these experiments, negative correlations between cell viability and chemical concentrations were obseved, which were more sensitive than MTT viability assay especially at low concentrations (<0.1 μg/mL). In this basic science study, a cell chip composed of ITO, gold nanoparticles and RGD-MAP-C peptide composites was fabricated to enhance electrochemical signals and proliferation of undifferentiated human neural stem cells (HB1.F3). The ITO/60 nm GNP/RGD-MAP-C composite electrode was found to best enhance the voltammetric signals of the studied cells. Copyright © 2013 Elsevier Inc. All rights reserved.

HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.

PubMed

Bashir, Tahir; Patgaonkar, Mandar; Kumar, Selvaa C; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

2015-01-01

Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection.

Distribution of Glycated Haemoglobin According to Early-Life and Contemporary Characteristics in Adolescents and Adults without Diabetes: The 1982 and 1993 Pelotas Birth Cohorts.

PubMed

Buffarini, Romina; Restrepo-Méndez, María Clara; Silveira, Vera M; Miranda, Jaime J; Gonçalves, Helen D; Oliveira, Isabel O; Horta, Bernardo L; Gigante, Denise P; Menezes, Ana Maria; Assunção, Maria Cecília F

2016-01-01

Glycated haemoglobin (HbA1c), a marker of glucose control in individuals with diabetes mellitus, is also related with the incidence of cardiometabolic risk in populations free of disease. The aim of this study was to describe the distribution of HbA1c levels according to early-life and contemporary factors in adolescents and adults without diabetes mellitus. HbA1c was measured in adults aged 30 years and adolescents aged 18 years who are participants in the 1982 and 1993 Pelotas Birth Cohorts, respectively. Bivariate and multivariate analyses were performed to describe the HbA1c mean values according to early-life and contemporary characteristics collected prospectively since birth. The distribution of the HbA1c was approximately normal in both cohorts, with a mean (SD) 5.10% (0.43) in the 1982 cohort, and 4.89% (0.50) in the 1993 cohort. HbA1c mean levels were significantly higher in individuals self-reported as black/brown skin color compared to those self-reported as white in both cohorts. Parental history of diabetes was associated with higher HbA1c mean in adults, while stunting at one year old presented an inverse relation with the outcome in adolescents. No other early and contemporary factors were associated with HbA1c levels in adults or adolescents. We found a consistent relationship between HbA1c and skin color in both cohorts. Further research is needed to understand the role of genomic ancestry on levels of HbA1c concentrations which may inform policies and preventive actions for diabetes mellitus and cardiometabolic risk.

HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor

PubMed Central

Bashir, Tahir; Patgaonkar, Mandar; Kumar C, Selvaa; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

2015-01-01

Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection. PMID:25915507

Influence of carotene-rich vegetable meals on the prevalence of anaemia and iron deficiency in Filipino schoolchildren.

PubMed

Maramag, C C; Ribaya-Mercado, J D; Rayco-Solon, P; Solon, J A A; Tengco, L W; Blumberg, J B; Solon, F S

2010-05-01

To determine the effects of eating carotene-rich green and yellow vegetables on the prevalence of anaemia, iron deficiency and iron-deficiency anaemia in schoolchildren. Schoolchildren (n=104), aged 9-12 years, received standardized meals containing 4.2 mg of provitamin A carotenoids/day (mainly beta-carotene) from yellow and green leafy vegetables and at least 7 g dietary fat/day. The meals were provided three times/day, 5 days/week, for 9 weeks at school. Before and after the dietary intervention, total-body vitamin A pool size was assessed by using the deuterated-retinol-dilution method; serum retinol and beta-carotene concentrations were measured by high-performance liquid chromatography; and whole blood haemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations were measured by using a photometer and a hematofluorometer, respectively. After 9 weeks, the mean total-body vitamin A pool size increased twofold (95% confidence interval (CI): -0.11, -0.07 micromol retinol; P<0.001), and serum beta-carotene concentration increased fivefold (95% CI: -0.97, -0.79 micromol/l; P<0.001). Blood Hb (95% CI: -1.02, -0.52 g per 100 ml; P<0.001) and ZnPP increased (95% CI: -11.82, -4.57 microol/mol haem; P<0.001). The prevalence of anaemia (Hb<11.5 g per 100 ml) decreased from 12.5 to 1.9% (P<0.001). There were no significant changes in the prevalence of iron deficiency or iron-deficiency anaemia. Ingestion of carotene-rich yellow and green leafy vegetables improves the total-body vitamin A pool size and Hb concentration, and decreases anaemia rates in Filipino schoolchildren, with no effect on iron deficiency or iron-deficiency anaemia rates.

Formation of methemoglobin and metmyoglobin using 8-aminoquinoline derivatives or sodium nitrite and subsequent reaction with cyanide.

PubMed

Steinhaus, R K; Baskin, S I; Clark, J H; Kirby, S D

1990-10-01

The kinetics of the oxidation of hemoglobin (Hb) and myoglobin (Mb) by sodium nitrite, 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-quinoline diphosphate (primaquine), 6-methoxy-8-(6-diethylaminohexylamino)-4-methyl-quinoline dihydrochloride (WR6026) and 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl- 5-[(3-trifluoromethyl)phenoxy]quinoline succinate (WR238,605) were studied at pH values ranging from 7.4 to 7.6 and at 37 +/- 1 degrees C. The reaction between Hb and primaquine, WR6026 and WR238,605 resulted in precipitation, as did the reaction between Mb and WR238,605. The reaction between nitrite ion (NO2-) and Hb showed a lag period followed by an autocatalytic phase. The data in this study are consistent with and substantiate the proposed mechanism for the Hb-NO2- oxidation reaction. The reaction between Mb and NO2- at higher NO2- concentrations also showed a lag period followed by an autocatalytic period, while at lower NO2- concentrations no lag period was seen. The data suggest a shift in rate constant at these lower NO2- concentrations. The reaction between Mb and both WR6026 and primaquine followed a two-term rate law with oxidant-dependent and -independent terms. Concentration-effect curve data, along with these results, suggest the presence of a catalytic pathway. The rates of formation of cyanomethemoglobin and cyanometmyoglobin complexes from cyanide ion and methemoglobin (MHb) and metmyoglobin (MMb), respectively, were followed in the presence of the heme oxidants. The rate constants were all within a narrow range and suggest that complexation of cyanide by MHb and MMb is not affected by the presence of oxidants.

Expediting red blood cell transfusions by syringing causes significant hemolysis.

PubMed

De Villiers, Willem Lambertus; Murray, Adriaan Albertus; Levin, Andrew Ian

2017-11-01

Techniques commonly used to expedite blood transfusions include pneumatically pressurizing red blood cell (RBC) bags or manual syringing its contents. We compared these techniques on RBC hemolysis using a simulated transfusion model. Fifteen warmed RBC units that were 12.3 ± 4.3 (95% confidence interval [CI], 10.1-14.5) days old were each subjected to two experimental rapid transfusion techniques. RBCs from each technique were directed through 18- and 22-gauge cannulas attached to blood administration sets. One technique involved RBC bag pressurization to 300 mmHg. The other employed a 20-mL syringe to effect forceful, manual aspiration from the RBC bag followed by forceful, manual RBC injection. The control group was gravity driven without cannulas. Free hemoglobin (Hb) concentrations were measured and percent hemolysis was calculated. Free Hb concentrations and percent hemolysis (median [95% CI]) were similar in the control (0.05 [0.03-0.08] g/dL and 0.13% [0.09%-0.17%], respectively) and pressurized experiments (0.06 [0.05-0.09] g/dL; 0.14% [0.12%-0.22%]), respectively. Syringing resulted in 10-fold higher free Hb concentrations (0.55 [0.38-0.92] g/dL) and percent hemolysis (1.28% [1.03%-2.15%]) than when employing the control (p < 0.0001) or pressurization (p < 0.0001) techniques. Cannula sizes studied did not affect hemolysis. Forceful manual syringing caused significant hemolysis and high free Hb concentrations. Pressurizing RBC bags induced no more hemolysis than after gravity-facilitated transfusions. Syringing to expedite RBC transfusions should be avoided in favor of pneumatic RBC bag pressurization. © 2017 AABB.

Relationship between muscle oxygenation by NIRS and blood lactate

NASA Astrophysics Data System (ADS)

Xu, Guodong; Mao, Zongzhen; Ye, Yanjie; Lv, Kunru

2011-01-01

The aim of the study was to investigate the relationship of muscle oxygenation in term of oxy-hemoglobin concentration change (ΔHbO2) by NIRS and blood lactate (BLA) in local skeletal muscle and evaluate the capability of NIRS in the research of exercise physiology Twenty-three athlete in the national fin-swimming team took the increasing load training on the power bicycle while their ΔHbO2 and BLA were simultaneously recorded. The initial powers used in the training were set as 100 w for males and 40 w for females. During the experiment, the power kept constant for 3 min before each abrupt increment of 30 w until the limit of the athlete's capability. Statistical analysis and data visualization were performed. Following the increasing load training, ΔHbO2 step-likely increased in the phase of aerobic metabolism but linearly decreased in the phase of anaerobic metabolism. The variation tendency of BLA was the same as ΔHbO2 and the concurrency of crucial turning points between ΔHbO2 and BLA was revealed. This relationship between ΔHbO2 and BLA presented in the increasing load training suggested that ΔHbO2 might be capable for taking the place of the invasively measured parameter BLA. Considering that ΔHbO2 can be noninvasively measured by NIRS, ΔHbO2 has the potential in the evaluation of athletes' physiological function and training effect on the athletes and accordingly NIRS can be well used in this field.

Hydrogen Bond Donor/Acceptor Cosolvent-Modified Choline Chloride-Based Deep Eutectic Solvents.

PubMed

Pandey, Ashish; Bhawna; Dhingra, Divya; Pandey, Siddharth

2017-04-27

Deep eutectic solvents (DESs) have emerged as nontoxic and inexpensive alternatives not only to the common organic solvents but to the ionic liquids as well. Some of the common and popular, and perhaps the most investigated, DESs are the ones comprising an ammonium salt and an appropriate hydrogen bond (HB) donor in a predetermined mole ratio. The formation of the DES is attributed to the H-bonding interaction(s) present between the salt and the HB donor. Consequently, addition of a predominantly HB donor or a predominantly HB acceptor cosolvent to such DESs may result in intriguing features and properties. We present investigation of two DESs constituted of salt choline chloride along with HB donors urea and glycerol, respectively, in 1:2 mol ratio, named reline and glyceline as the cosolvent of very high HB donating acidity and no HB accepting basicity 2,2,2-trifluoroethanol (TFE) and of very high HB accepting basicity and no HB donating acidity hexamethylphosphoramide (HMPA), respectively, is added. TFE shows up to 0.25 mole fraction miscibility with both reline and glyceline. While up to 0.25 mole fraction HMPA in glyceline results in transparent mixtures, this cosolvent is found to be completely immiscible with reline. From the perspective of the solvatochromic absorbance and fluorescence probes, it is established that the cybotactic region dipolarity within up to 0.25 mole fraction TFE/HMPA-added DES strongly depends on the functionalities present on the solute. Fourier transform infrared absorbance and Raman spectroscopic investigations reveal no major shifts in vibrational transitions as TFE/HMPA is added to the DES; spectral band broadening, albeit small, is observed nonetheless. Excess molar volumes and excess logarithmic viscosities of the mixtures indicate that while TFE may interstitially accommodate itself within H-bonded network of reline, it does appear to form H-bonds with the constituents of the glyceline. Increase in overall net repulsive interactions as HMPA is added to glyceline is suggested by both positive excess molar volumes and excess logarithmic viscosities. The addition of HB donor/acceptor cosolvent appears to disturb the salt-HB donor equilibria within DES via complex interplay of interactions within the system.

Adsorption of virus-like particles on ion exchange surface: Conformational changes at different pH detected by dual polarization interferometry.

PubMed

Yang, Yanli; Mengran Yu; Zhang, Songping; Ma, Guanghui; Su, Zhiguo

2015-08-21

Disassembling of virus-like particles (VLPs) like hepatitis B virus surface antigen (HB-VLPs) during chromatographic process has been identified as a major cause of loss of antigen activity. In this study, dual polarization interferometry (DPI) measurement, together with chromatography experiments, were performed to study the adsorption and conformational change of HB-VLPs on ion exchange surface at three different pHs. Changes in pH values of buffer solution showed only minimal effect on the HB-VLPs assembly and antigen activity, while significantly different degree of HB-VLPs disassembling was observed after ion exchange chromatography (IEC) at different pHs, indicating the conformational change of HB-VLPs caused mainly by its interactions with the adsorbent surface. By creating an ion exchange surface on chip surface, the conformational changes of HB-VLPs during adsorption to the surface were monitored in real time by DPI for the first time. As pH increased from 7.0 to 9.0, strong electrostatic interactions between oppositely charged HB-VLPs and the ion exchange surface make the HB-VLPs spread thinly or even adsorbed in disassembled formation on the surface as revealed by significant decrease in thickness of the adsorbed layer measured by DPI. Such findings were consistent with the results of IEC experiments operated at different pHs, that more disassembled HB-VLPs were detected in the eluted proteins at pH 9.0. At low pH like pH 5.0, however, possible bi-layer adsorption was involved as evidenced by an adsorbed layer thickness higher than average diameter of the HB-VLPs. The "lateral" protein-protein interactions might be unfavorable and would make additional contribution to the disassembling of HB-VLPs besides the primary mechanism related to the protein-surface interactions; therefore, the lowest antigen activity was observed after IEC at pH 5.0. Such real-time information on conformational change of VLPs is helpful for better understanding the real mechanism for the disassembling of VLPs on the solid-liquid interface. Copyright © 2015 Elsevier B.V. All rights reserved.

Temperature stability of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] in the form of a solution or in the lyophilized form during storage at -80 °C, 4 °C, 25 °C and 37 °C or pasteurization at 70 °C.

PubMed

Bian, Y Z; Guo, C; Chang, T M S

2016-01-01

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (Poly-[Hb-SOD-CAT-CA]) contains all three major functions of red blood cells (RBCs) at an enhanced level. It transports oxygen, removes oxygen radicals and transports carbon dioxide. Our previous studies in a 90-min 30 mm Hg Mean Arterial Pressure (MAP) sustained hemorrhagic shock rat model shows that it is more effective than blood in the lowering of elevated intracellular pCO2, recovery of ST-elevation and histology of the heart and intestine. This paper is to analyze the storage and temperature stability. Allowable storage time for RBC is about 1 d at room temperature and 42 d at 4 °C. Also, RBC cannot be pasteurized to remove infective agents like HIV and Ebola. PolyHb can be heat sterilized and can be stored for 1 year even at room temperature. However, Poly-[Hb-SOD-CAT-CA] contains both Hb and enzymes and enzymes are particularly sensitive to storage and heat. We thus carried out studies to analyze its storage stability at different temperatures and heat pasteurization stability. Results of storage stability show that lyophilization extends the storage time to 1 year at 4 °C and 40 d at room temperature (compared to respectively, 42 d and 1 d for RBC). After the freeze-dry process, the enzyme activities of Poly-[SFHb-SOD-CAT-CA] was 100 ± 2% for CA, 100 ± 2% for SOD and 93 ± 3.5% for CAT. After heat pasteurization at 70 °C for 2 h, lyophilized Poly-[Hb-SOD-CAT-CA] retained good enzyme activities of CA 97 ± 4%, SOD 100 ± 2.5% and CAT 63.8 ± 4%. More CAT can be added during the crosslinking process to maintain the same enzyme ratio after heat pasteurization. Heat pasteurization is possible only for the lyophilized form of Poly-[Hb-SOD-CAT-CA] and not for the solution. It can be easily reconstituted by dissolving in suitable solutions that continues to have good storage stability though less than that for the lyophilized form. According to the P50 value, Poly-[SFHb-SOD-CAT-CA] retains its oxygen carrying ability before and after long-term storage.

Noninvasive In Vivo Monitoring of Cyanide Toxicity and Treatment Using Diffuse Optical Spectroscopy in a Rabbit Model

DTIC Science & Technology

2009-06-01

Finally. the tissue concentrations of oxyhe- moglobin (OIIb) dcoxyhcmoglogin ( RHb ). MetHb, and H,O arc calculated by a linear least squares tit of the...coefficients of the mam chro- mophores in the near infrared wmelength range between 600 :o 40 A - - OHb -- RHb IS ..... .. .J ’· · · · · M!!Hb 16 :liE _e...0 ·oo soo 900 1000 \\\\"A\\’EU:NGTH (nm) and I 000 nm. Figure I A show~ the exttnct1on coefficients of OHb. RHb . and MetHb and Figure I B shows the e

In vitro demineralization of tooth enamel subjected to two whitening regimens.

PubMed

Ogura, Kayoko; Tanaka, Reina; Shibata, Yo; Miyazaki, Takashi; Hisamitsu, Hisashi

2013-07-01

The resistance of bleached enamel to demineralization has not been elucidated fully. In this study, the authors aimed to examine the level of in vitro demineralization of human tooth enamel after bleaching by using two common bleaching regimens: home bleaching (HB) and office bleaching (OB) with photoirradiation. The authors bleached teeth to equivalent levels by means of the two bleaching regimens. They used fluorescence spectroscopy to measure the reduction in enamel density and the release of calcium into solution after storing the treated teeth in a demineralizing solution for two weeks. They also visualized and quantified mineral distribution in demineralized bleached enamel over time by using a desktop microcomputed-tomographic analyzer. Enamel subjected to HB or to photoirradiation without bleaching showed increased demineralization. In contrast, enamel treated with OB was more resistant to demineralization. This resistance to demineralization in teeth treated with OB presumably is due to peroxide's permeating to deeper layers of enamel before being activated by photoirradiation, which enhances mineralization. The mineral distribution pattern of enamel after treatment plays a critical role in providing resistance to demineralization in whitened teeth. OB confers to enamel significant resistance to in vitro demineralization. Dentists should supervise the nightguard HB process.

Direct electrochemistry of hemoglobin on graphene and titanium dioxide nanorods composite modified electrode and its electrocatalysis.

PubMed

Sun, Wei; Guo, Yaqing; Ju, Xiaomei; Zhang, Yuanyuan; Wang, Xiuzhen; Sun, Zhenfan

2013-04-15

A biocompatible sensing platform based on graphene (GR) and titanium dioxide (TiO₂) nanorods for the immobilization of hemoglobin (Hb) was adopted in this paper. The GR-TiO₂-Hb composite-modified carbon ionic liquid electrode was constructed through a simple casting method with Nafion as the film forming material. UV-Vis and FT-IR spectra confirmed that Hb retained its native structure in the composite film. Direct electron transfer of Hb incorporated into the composite was realized with a pair of quasi-reversible redox waves appeared, indicating that the presence of GR-TiO₂ nanocomposite on the electrode surface could facilitate the electron transfer rate between the electroactive center of Hb and the substrate electrode. Hb modified electrode showed excellent electrocatalytic activity to the reduction of trichloroacetic acid in the concentration range from 0.6 to 21.0 mmol L⁻¹. These results indicated that GR-TiO₂ nanocomposite could be a friendly biocompatible interface for immobilizing biomolecules and keeping their native structure. The fabricated biosensor displayed the advantages such as high sensitivity, good reproducibility and long-term stability. Copyright © 2012 Elsevier B.V. All rights reserved.

Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia

PubMed Central

Jones, Phill B.; Shin, Hwa Kyoung; Boas, David A.; Hyman, Bradley T.; Moskowitz, Michael A.; Ayata, Cenk; Dunn, Andrew K.

2009-01-01

Real-time investigation of cerebral blood flow (CBF), and oxy- and deoxyhemoglobin concentration (HbO, HbR) dynamics has been difficult until recently due to limited spatial and temporal resolution of techniques like laser Doppler flowmetry and magnetic resonance imaging (MRI). The combination of laser speckle flowmetry (LSF) and multispectral reflectance imaging (MSRI) yields high-resolution spatiotemporal maps of hemodynamic and metabolic changes in response to functional cortical activation. During acute focal cerebral ischemia, changes in HbO and HbR are much larger than in functional activation, resulting in the failure of the Beer-Lambert approximation to yield accurate results. We describe the use of simultaneous LSF and MSRI, using a nonlinear Monte Carlo fitting technique, to record rapid changes in CBF, HbO, HbR, and cerebral metabolic rate of oxygen (CMRO2) during acute focal cerebral ischemia induced by distal middle cerebral artery occlusion (dMCAO) and reperfusion. This technique captures CBF and CMRO2 changes during hemodynamic and metabolic events with high temporal and spatial resolution through the intact skull and demonstrates the utility of simultaneous LSF and MSRI in mouse models of cerebrovascular disease. PMID:19021335

Intermolecular Interactions of Pyridine in Liquid Phase and Aqueous Solution Studied by Soft X-ray Absorption Spectroscopy

NASA Astrophysics Data System (ADS)

Nagasaka, Masanari; Yuzawa, Hayato; Kosugi, Nobuhiro

2018-05-01

Intermolecular interactions of pyridine in liquid and in aqueous solution are studied by using soft X-ray absorption spectroscopy (XAS) at the C, N, and O K-edges. XAS of liquid pyridine shows that the N 1s→π* peak is blue shifted and the C 1s→π* peak of the meta and para sites is red shifted, respectively, as compared with XAS of pyridine gas. These shifts in liquid are smaller than those in clusters, indicating that the intermolecular interaction of liquid pyridine is weaker than that of pyridine cluster, as supported by the combination of quantum chemical calculations of the core excitation and molecular dynamics simulations of the liquid structure. On the other hand, XAS spectra of aqueous pyridine solutions (C5H5N)x(H2O)1-x measured at different molar fractions show that in the pyridine rich region, x>0.7, the C and N 1s→π* peak energies are not so different from pure liquid pyridine (x=1.0). In this region, antiparallel displaced structures of pyridine molecules are dominant as in pure pyridine liquid. In the O K-edge XAS, the pre-edge peaks sensitive to the hydrogen bond (HB) network of water molecules show the red shift of -0.15 eV from that of bulk water, indicating that small water clusters with no large-scale HB network are formed in the gap space of structured pyridine molecules. In the water rich region, 0.7>x, the N 1s→π* peaks and the O 1s pre-edge peaks are blue shifted, and the C 1s→π* peaks of the meta and para sites are red-shifted by increasing molar fraction of water. The HB network of bulk water is dominant, but quantum chemical calculations indicate that small pyridine clusters with the HB interaction between the H atom in water and the N atom in pyridine are still existent even in very dilute pyridine solutions.

HbA1c as a predictor of diabetes after gestational diabetes mellitus.

PubMed

Claesson, Rickard; Ignell, Claes; Shaat, Nael; Berntorp, Kerstin

2017-02-01

We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Mapping the microvascular and the associated absolute values of oxy-hemoglobin concentration through turbid media via local off-set diffuse optical imaging

NASA Astrophysics Data System (ADS)

Chen, Chen; Klämpfl, Florian; Stelzle, Florian; Schmidt, Michael

2014-11-01

An imging resolution of micron-scale has not yet been discovered by diffuse optical imaging (DOI), while a superficial response was eliminated. In this work, we report on a new approach of DOI with a local off-set alignment to subvert the common boundary conditions of the modified Beer-Lambert Law (MBLL). It can resolve a superficial target in micron scale under a turbid media. To validate both major breakthroughs, this system was used to recover a subsurface microvascular mimicking structure under an skin equivalent phantom. This microvascular was included with oxy-hemoglobin solution in variant concentrations to distiguish the absolute values of CtRHb and CtHbO2 . Experimental results confirmed the feasibility of recovering the target vascular of 50 µm in diameter, and graded the values of the concentrations of oxy-hemoglobin from 10 g/L to 50 g/L absolutely. Ultimately, this approach could evolve into a non-invasive imaging system to map the microvascular pattern and the associated oximetry under a human skin in-vivo.

Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy.

PubMed

Ouédraogo, Smaïla; Bodeau-Livinec, Florence; Briand, Valérie; Huynh, Bich-Tram; Koura, Ghislain K; Accrombessi, Manfred M K; Fievet, Nadine; Massougbodji, Achille; Deloron, Philippe; Cot, Michel

2012-10-22

Primigravidity is one of the main risk factors for both malaria and anaemia. Since the implementation of intermittent preventive treatment (IPTp) in sub-Saharan Africa, the relationship between anaemia and gravidity and its evolution during pregnancy has been little explored. This study aimed to evaluate the impact of gravidity on the variation of haemoglobin during pregnancy according to the timing of gestation. Data from three studies carried out in nearby areas in south Benin (Ouidah, Comé, Allada) between 2005 and 2012 were analysed. At inclusion (first antenatal visit, ANV1) women's age, area of residence, schooling, gravidity, gestational age, weight and height were recorded. Thick blood smears were performed on ANV1, second visit (ANV2) and at delivery. In Allada, women's serum ferritin and CRP concentrations were also assessed. The impact of gravidity on maternal haemoglobin (Hb) was analysed using a logistic or linear regression depending on the outcome. The statistical significance was set to P < 0.05. In total, data from 3,591 pregnant women were analysed. Both univariate and multivariate analyses showed a constant association between Hb concentrations and gravidity in the three periods of Hb assessment (ANV1, ANV2 and delivery). Mean Hb concentration was significantly lower in primigravidae than in multigravidae at ANV1 (mean difference = -2.4 g/L, CI 95%: [-3.4, -1.4], P < 0.001). Afterwards, there was a significant increase in primigravidae only, with a tendency to reversal between primigravidae and multigravidae, which was confirmed at delivery (mean difference = 2.8 g/L, CI 95%: [1.3, 4.2], P < 0.001). The prevalence of malaria infection was halved between ANV1 and delivery in primigravidae while it decreased by only 38% among multigravidae, who were less prone to malaria infection (prevalence at ANV1, 20% and 10% respectively). Iron deficiency was more common in multigravidae, and it decreased slightly in this group between ANV1 and delivery. In a context of IPTp, Hb levels improved progressively throughout pregnancy in primigravidae, likely as a result of reduction in malaria infection. In multigravidae, the improvement was less perceptible and anaemia was mainly due to iron deficiency.

Growth and change in blood haemoglobin concentration among underweight Malawian infants receiving fortified spreads for 12 weeks: a preliminary trial.

PubMed

Kuusipalo, Heli; Maleta, Kenneth; Briend, André; Manary, Mark; Ashorn, Per

2006-10-01

Fortified spreads (FSs) have proven effective in the rehabilitation of severely malnourished children. We examined acceptability, growth and change in blood haemoglobin (Hb) concentration among moderately underweight ambulatory infants given FS. This was a randomised, controlled, parallel-group, investigator-blind clinical trial in rural Malawi. Six- to 17-month-old underweight infants (weight for age < -2), whose weight was greater than 5.5 kg and weight-for-height z score greater than -3 received for 12 weeks at home 1 of 8 food supplementation schemes: nothing, 5, 25, 50, or 75 g/day milk-based FS or 25, 50, or 75 g/day soy-based FS. Outcome measures included change in weight, length and blood Hb concentration. A total of 126 infants started and 125 completed the intervention. All infants accepted the spread well, and no intolerance was recorded. Average weight and length gains were higher among infants receiving daily 25 to 75 g FS than among those receiving only 0 to 5 g FS. Mean Hb concentration remained unchanged among unsupplemented controls but increased by 10 to 17 g/L among infants receiving any FS. All average gains were largest among infants receiving 50 g of FS daily: mean difference (95% confidence interval) in the 12-week gain between infants in 50 g milk-based FS group and the unsupplemented group was 290 g (range, -130 to 700 g), 0.9 cm (range, -0.3 to 2.2 cm), and 17 g/L (range, 0 to 34 g/L) for weight, length and blood Hb concentration, respectively. In soy- vs milk-based FS groups, average outcomes were comparable. Supplementation with 25 to 75 g/day of highly fortified spread is feasible and may promote growth and alleviate anaemia among moderately malnourished infants. Further trials should test this hypothesis.

Early Formation of Serum Advanced Glycation End-Products in Children with Type 1 Diabetes Mellitus: Relationship with Glycemic Control.

PubMed

Jaisson, Stéphane; Souchon, Pierre-François; Desmons, Aurore; Salmon, Anne-Sophie; Delemer, Brigitte; Gillery, Philippe

2016-05-01

To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance. Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography-tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance. Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up. Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of therapeutic touch on brain activation of preterm infants in response to sensory punctate stimulus: a near-infrared spectroscopy-based study.

PubMed

Honda, Noritsugu; Ohgi, Shohei; Wada, Norihisa; Loo, Kek Khee; Higashimoto, Yuji; Fukuda, Kanji

2013-05-01

The purpose of this study was to determine whether therapeutic touch in preterm infants can ameliorate their sensory punctate stimulus response in terms of brain activation measured by near-infrared spectroscopy. The study included 10 preterm infants at 34-40 weeks' corrected age. Oxyhaemoglobin (Oxy-Hb) concentration, heart rate (HR), arterial oxygen saturation (SaO2) and body movements were recorded during low-intensity sensory punctate stimulation for 1 s with and without therapeutic touch by a neonatal development specialist nurse. Each stimulation was followed by a resting phase of 30 s. All measurements were performed with the infants asleep in the prone position. sensory punctate stimulus exposure significantly increased the oxy-Hb concentration but did not affect HR, SaO2 and body movements. The infants receiving therapeutic touch had significantly decreased oxy-Hb concentrations over time. Therapeutic touch in preterm infants can ameliorate their sensory punctate stimulus response in terms of brain activation, indicated by increased cerebral oxygenation. Therefore, therapeutic touch may have a protective effect on the autoregulation of cerebral blood flow during sensory punctate stimulus in neonates.

Multiple-wavelength spectroscopic quantitation of light-absorbing species in scattering media

DOEpatents

Nathel, Howard; Cartland, Harry E.; Colston, Jr., Billy W.; Everett, Matthew J.; Roe, Jeffery N.

2000-01-01

An oxygen concentration measurement system for blood hemoglobin comprises a multiple-wavelength low-coherence optical light source that is coupled by single mode fibers through a splitter and combiner and focused on both a target tissue sample and a reference mirror. Reflections from both the reference mirror and from the depths of the target tissue sample are carried back and mixed to produce interference fringes in the splitter and combiner. The reference mirror is set such that the distance traversed in the reference path is the same as the distance traversed into and back from the target tissue sample at some depth in the sample that will provide light attenuation information that is dependent on the oxygen in blood hemoglobin in the target tissue sample. Two wavelengths of light are used to obtain concentrations. The method can be used to measure total hemoglobin concentration [Hb.sub.deoxy +Hb.sub.oxy ] or total blood volume in tissue and in conjunction with oxygen saturation measurements from pulse oximetry can be used to absolutely quantify oxyhemoglobin [HbO.sub.2 ] in tissue. The apparatus and method provide a general means for absolute quantitation of an absorber dispersed in a highly scattering medium.

Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial

PubMed Central

Tarnow, Lise; Frandsen, Merete; Nielsen, Bente B; Hansen, Birgitte V; Pedersen, Oluf; Parving, Hans-Henrik; Vaag, Allan A

2009-01-01

Objectives To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes. Design Randomised, double blind, double dummy, parallel trial. Setting Secondary care in Denmark between 2003 and 2006. Participants Non-obese patients (BMI ≤27) with preserved beta cell function. Interventions After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA1c) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA1c concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached. Main outcome measure HbA1c concentration. Results Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA1c 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments −2.51 kg, 95% confidence interval −4.07 to −0.95). Conclusions In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide. Trial registration NCT00118963 PMID:19900993

Native top-down mass spectrometry for the structural characterization of human hemoglobin

DOE PAGES

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.; ...

2015-06-09

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice.

PubMed

Chatel, Benjamin; Messonnier, Laurent A; Hourdé, Christophe; Vilmen, Christophe; Bernard, Monique; Bendahan, David

2017-05-01

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice ( P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls ( P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice. NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD. Copyright © 2017 the American Physiological Society.

HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial

PubMed Central

2015-01-01

OBJECTIVE Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. CONCLUSIONS HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined. PMID:25336746

Influence of smoking and diet on glycated haemoglobin and 'pre-diabetes' categorisation: a cross-sectional analysis.

PubMed

Vlassopoulos, Antonis; Lean, Michael E J; Combet, Emilie

2013-10-26

The new HbA1c criteria for diagnosis of pre-diabetes have been criticised for misdiagnosis. It is possible that some elevation of HbA1c is not driven by hyperglycaemia. This study assesses associations of HbA1c, commonly assumed to relate solely to glucose concentration, with (i) smoking, a major source of reactive oxygen species (ROS) and (ii) fruit & vegetables consumption associated with improved redox status. One-way ANOVA, Chi-squared and multivariate linear regressions, adjusted for all known confounders were used to explore associations of HbA1c with self-reported smoking status and fruit & vegetables consumptions in the Scottish Health Surveys 2003-2010, among individuals without known diabetes and HbA1c < 6.5%. Compared to non-smokers (n = 2831), smokers (n = 1457) were younger, consumed less fruit & vegetables, had lower physical activity levels, lower BMI, higher HbA1c and CRP (p < 0.05). HbA1c was higher in smokers by 0.25 SDs (0.08%), and 0.38 SDs higher (0.14%) in heavy smokers (>20 cigarettes/day) than non-smokers (p < 0.001 both). Smokers were twice as likely to have HbA1c in the 'pre-diabetic' range (5.7-6.4%) (p < 0.001, adj.model). Pre-diabetes and low grade inflammation did not affect the associations. For every extra 80 g vegetable portion consumed, HbA1c was 0.03 SDs (0.01%) lower (p = 0.02), but fruit consumption did not impact on HbA1c, within the low range of consumptions in this population. This study adds evidence to relate smoking (an oxidative stress proxy) with protein glycation in normoglycaemic subjects, with implications for individuals exposed to ROS and for epidemiological interpretation of HbA1c.

The Importance of Different Frequency Bands in Predicting Subcutaneous Glucose Concentration in Type 1 Diabetic Patients

DTIC Science & Technology

2010-02-01

patients, the amplitude of the second and third harmonics of CGM signals are correlated with mean HbA1c values and that, in type 2 diabetic patients...with insulin for at least 12 mo, had a body mass index of ន.0 kg/m2, and had glycated hemoglobin ( HbA1c ) of >6.1%. Subjects were excluded if

Noninvasive optical diagnosis of low back pain with the aid of Chinese cupping procedure

NASA Astrophysics Data System (ADS)

Li, Nanxi; Li, Ting

2018-02-01

Low back pain (LBP) is a complex disease that can be cause by a variety of reasons. Now LBP has become a very common and severe disease among kinds of occupational groups with showing a younger trend. The traditional diagnosis relies on complicated imaging modalities and other dangerous and invasive methods. Noninvasive near-infrared spectroscopy (NIRS) is noninvasive and convenient, and has been successful used in point-of-care diagnosis. Here, we attempt to explore NIRS's application in in low back pain diagnosis and the effect of aid-use of Chinese cupping procedure. 13 LBP patients and 13 healthy subjects participated in NIRS measurements of concentrations of oxy- and deoxy-hemoglobins (Δ[HbO2] and Δ[Hb]) at the middle of the lumbar spine. It was showed that there was significant differences (p < 0.001) between healthy subjects and LBP patients after cupping procedure, while insignificant before cupping. Moreover, it was found that healthy subjects showed stronger responses to cupping procedure than LBP patients, with prominently higher concentration of Δ[HbO2] and Δ[Hb]. It indicates the potential of NIRS in noninvasive, measurable and straightforward monitoring/therapeutic effect evaluation of LBP with bedside and point-of-care monitoring capability.

Noninvasive imaging of prefrontal activation during attention-demanding tasks performed while walking using a wearable optical topography system

NASA Astrophysics Data System (ADS)

Atsumori, Hirokazu; Kiguchi, Masashi; Katura, Takusige; Funane, Tsukasa; Obata, Akiko; Sato, Hiroki; Manaka, Takaaki; Iwamoto, Mitsumasa; Maki, Atsushi; Koizumi, Hideaki; Kubota, Kisou

2010-07-01

Optical topography (OT) based on near-infrared spectroscopy is a noninvasive technique for mapping the relative concentration changes in oxygenated and deoxygenated hemoglobin (oxy- and deoxy-Hb, respectively) in the human cerebral cortex. In our previous study, we developed a small and light wearable optical topography (WOT) system that covers the entire forehead for monitoring prefrontal activation. In the present study, we examine whether the WOT system is applicable to OT measurement while walking, which has been difficult with conventional OT systems. We conduct OT measurements while subjects perform an attention-demanding (AD) task of balancing a ping-pong ball on a small card while walking. The measured time course and power spectra of the relative concentration changes in oxy- and deoxy-Hb show that the step-related changes in the oxy- and deoxy-Hb signals are negligible compared to the task-related changes. Statistical assessment of the task-related changes in the oxy-Hb signals show that the dorsolateral prefrontal cortex and rostral prefrontal area are significantly activated during the AD task. These results suggest that our functional imaging technique with the WOT system is applicable to OT measurement while walking, and will be a powerful tool for evaluating brain activation in a natural environment.

Do all the patients with gastric parietal cell antibodies have pernicious anemia?

PubMed

Sun, A; Wang, Y P; Lin, H P; Chia, J S; Chiang, C P

2013-05-01

This study evaluated whether all the patients with serum gastric parietal cell antibody (GPCA) positivity had pernicious anemia (PA). The blood hemoglobin (Hb), iron, and vitamin B12 concentrations, and mean corpuscular volume (MCV) in 124 GPCA-positive patients were measured and compared with the corresponding data in 124 age- and sex-matched healthy controls. PA was defined by World Health Organization (WHO) as having an Hb concentration < 13 g dl(-1) for men and < 12 g dl(-1) for women, an MCV ≥ 100 fl, and a serum vitamin B12 level < 200 pg ml(-1) . We found that 20, 25, and 20 GPCA-positive patients had deficiencies of Hb (men < 13 g dl(-1) , women < 12 g dl(-1) ), iron (<60 μg dl(-1) ), and vitamin B12 (<200 pg ml(-1) ), respectively. Moreover, 16 GPCA-positive patients had abnormally high MCV (≥ 100 fl). GPCA-positive patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency and of abnormally high MCV (all P-values < 0.001) than healthy controls. However, only 12.9% of 124 GPCA-positive patients were diagnosed as having PA by the WHO definition. Only 12.9% of GPCA-positive patients are discovered to have PA by the WHO definition. © 2012 John Wiley & Sons A/S.

Internal electron transfer between hemes and Cu(II) bound at cysteine beta93 promotes methemoglobin reduction by carbon monoxide.

PubMed

Bonaventura, C; Godette, G; Tesh, S; Holm, D E; Bonaventura, J; Crumbliss, A L; Pearce, L L; Peterson, J

1999-02-26

Previous studies showed that CO/H2O oxidation provides electrons to drive the reduction of oxidized hemoglobin (metHb). We report here that Cu(II) addition accelerates the rate of metHb beta chain reduction by CO by a factor of about 1000. A mechanism whereby electron transfer occurs via an internal pathway coupling CO/H2O oxidation to Fe(III) and Cu(II) reduction is suggested by the observation that the copper-induced rate enhancement is inhibited by blocking Cys-beta93 with N-ethylmaleimide. Furthermore, this internal electron-transfer pathway is more readily established at low Cu(II) concentrations in Hb Deer Lodge (beta2His --> Arg) and other species lacking His-beta2 than in Hb A0. This difference is consistent with preferential binding of Cu(II) in Hb A0 to a high affinity site involving His-beta2, which is ineffective in promoting electron exchange between Cu(II) and the beta heme iron. Effective electron transfer is thus affected by Hb type but is not governed by the R left arrow over right arrow T conformational equilibrium. The beta hemes in Cu(II)-metHb are reduced under CO at rates close to those observed for cytochrome c oxidase, where heme and copper are present together in the oxygen-binding site and where internal electron transfer also occurs.

Unexpectedly high early prevalence of anaemia in 6-month-old breast-fed infants in rural Bangladesh.

PubMed

Shakur, Yaseer A; Choudhury, Nuzhat; Hyder, S M Ziauddin; Zlotkin, Stanley H

2010-01-01

To determine the prevalence of anaemia and maternal and infant factors associated with Hb values in infants at 6 months of age in rural Bangladesh. Infants (born to mothers supplemented with Fe-folic acid from mid-pregnancy) were visited at birth and 6 months of age. Mothers' anthropometric status, and infants' birth weight, gestational age at birth, weight and Hb concentration at 6 months were measured. Household socio-economic and demographic data, infant feeding practices and health status were collected using a pre-tested structured questionnaire. Rural Bangladesh. Four hundred and two infants. For the total cohort (n 402), the range of anaemia prevalence values was from 30.6 % using a cut-off value of Hb < 95 g/l to 71.9 % using a value of Hb < 110 g/l. Birth weight and month of birth were the only factors positively associated with infant Hb in a linear regression model (P = 0.008 and 0.011, respectively). There was an unexpectedly high prevalence of anaemia in infants at 6 months of age, before the assumed period of vulnerability. Hb at this age tended to be higher in those with higher birth weight. We also found a season effect on Hb, as it tended to be higher as the study progressed. The high prevalence of anaemia at such an early age needs to be addressed to minimize the disease's long-term consequences.

Porewater dynamics of silver, lead and copper in coastal sediments and implications for benthic metal fluxes

USGS Publications Warehouse

Kalnejais, Linda H.; Martin, W. R.; Bothner, Michael H.

2015-01-01

To determine the conditions that lead to a diffusive release of dissolved metals from coastal sediments, porewater profiles of Ag, Cu, and Pb have been collected over seven years at two contrasting coastal sites in Massachusetts, USA. The Hingham Bay (HB) site is a contaminated location in Boston Harbor, while the Massachusetts Bay (MB) site is 11 km offshore and less impacted. At both sites, the biogeochemical cycles include scavenging by Fe-oxyhydroxides and release of dissolved metals when Fe-oxyhydroxides are reduced. Important differences in the metal cycles at the two sites, however, result from different redox conditions. Porewater sulfide and seasonal variation in redox zone depth is observed at HB, but not at MB. In summer, as the conditions become more reducing at HB, trace metals are precipitated as sulfides and are no longer associated with Fe-oxyhydroxides. Sulfide precipitation close to the sediment–water interface limits the trace metal flux in summer and autumn at HB, while in winter, oxidation of the sulfide phases drives high benthic fluxes of Cu and Ag, as oxic conditions return. The annual diffusive flux of Cu at HB is found to be significant and contributes to the higher than expected water column Cu concentrations observed in Boston Harbor. At MB, due to the lower sulfide concentrations, the association of trace metals with Fe-oxyhydroxides occurs throughout the year, leading to more stable fluxes. A surface enrichment of solid phase trace metals was found at MB and is attributed to the persistent scavenging by Fe-oxyhydroxides. This process is important, particularly at sites that are less reducing, because it maintains elevated metal concentrations at the surface despite the effects of bioturbation and sediment accumulation, and because it may increase the persistence of metal contamination in surface sediments.

Colorectal cancer in a second round after a negative faecal immunochemical test.

PubMed

Bujanda, Luis; Sarasqueta, Cristina; Castells, Antoni; Pellisé, María; Cubiella, Joaquín; Gil, Inés; Cosme, Angel; Arana-Arri, Eunate; Mar, Izaskun; Idigoras, Isabel; Portillo, Isabel

2015-07-01

The faecal immunochemical test is one of the tests recommended by scientific societies for colorectal cancer (CRC) screening in average-risk populations. Our aim was to evaluate the characteristics of CRC detected in a second round of screening after negative results in a first round. We studied patients in whom CRC was detected in a screening programme. This programme included asymptomatic individuals between 50 and 69 years old and offered tests every 2 years. A total of 363,792 individuals were invited to participate in the first round of faecal immunochemical test screening and 100,135 individuals in the second round after a first negative result. The screening strategy consisted of faecal testing of a single sample using an automated semiquantitative kit, with a cut-off of 20 μg haemoglobin (Hb)/g faeces. The rate of positive results was 6.9% (16,467/238,647) in the first round and 4.8% (3359/69,193) in the second round (P < 0.0005). Overall, 860 (0.36%) cases of CRC were detected in the first round and 100 (0.14%) in the second round (P < 0.005). The location of the cancer was proximal in 12.5 and 24% of cases detected in the first and second rounds, respectively (P = 0.008). Hb concentrations were higher in the first round (211 vs. 109 μg Hb/g faeces in the second round; P = 0.002). Multivariate analysis confirmed that, in the second round, CRC diagnosed was more often proximal (hazard ratio vs. first round, 2.4; 95% confidence interval, 1.3-4.4; P = 0.003) and the concentration of Hb/g faeces was lower (hazard ratio vs. first round, 2.1; 95% confidence interval, 1.3-3.5; P = 0.003). The CRC detection rate is lower in the second round of screening. Further, in the second round, CRC detected is more often in a proximal location and Hb concentrations are lower.

Efficacy and safety of losartan in treatment of hyperuricemia and posttransplantation erythrocytosis: results of a prospective, open, randomized, case-control study.

PubMed

Zhu, X; Chen, J; Han, F; Cheng, M; Xu, L; Zhang, L; Ding, X; Le, Y

2009-11-01

Hyperuricemia and posttransplantation erythrocytosis (PTE) are frequent complications after kidney transplantation and are important risk factors for cardiovascular events. Losartan decreases serum uric acid and hemoglobin (Hb) concentrations and may be a useful agent for treatment of hyperuricemia and PTE. To evaluate the influence of losartan on serum creatinine (SCr), serum uric acid, and hemoglobin (Hb) concentrations in patients after kidney transplantation and to evaluate the safety profile of losartan in these patients. Sixty-six Han Chinese patients (43 men and 23 women; mean [SD] age, 40.45 [11.50] years) were enrolled in the study. All patients had undergone a first cadaveric donor kidney transplantation at least 3 months previously and had stable graft function with SCr concentration less than 176.8 micromol/L and Hb concentration greater than 110 g/L. The patients were divided into 2 groups (losartan group, n = 34; and control group, n = 32) according to the odevity of patient identification number. Patients in the losartan group received losartan, 50 mg/d; patients in the control group did not receive losartan. Each patient was followed up for 6 months. Nine patients in the losartan group and 5 patients in the control group dropped out because of acute renal insufficiency, anemia, acute rejection, or poor compliance. The serum uric acid concentration in the losartan group continuously decreased at months 1, 2, 3, and 6 (P = .12, P = .01, P = .04, and P = .005 compared with baseline, and P = .02, P = .003, P = .02, and P = .006 compared with control), especially in the patients with hyperuricemia (P = .02, P < .001, P = .003, and P < .001 compared with baseline, and P = .02, P = .002, P = .02, and P = .002 compared with control). The Hb level in the losartan group decreased significantly at months 1, 2, 3, and 6 (P = .003, P < .001, P = .004, and P = 0.02 compared with baseline, and P = .001, P < .001, P = .001, and P = .005 compared with control), especially in patients with PTE. In patients without PTE, there was no significant decline in Hb concentration in the losartan group compared with baseline. There was no significant decline in estimated glomerular filtration rate in the losartan group. Losartan may be an effective agent for treatment of hyperuricemia and PTE in Han Chinese patients after kidney transplantation. However, in some patients, losartan may not be safe.

Pathophysiologically based drug treatment of sickle cell disease.

PubMed

Steinberg, Martin H

2006-04-01

Sickle cell disease is a systemic disorder that is caused by a mutation (Glu6Val) in the gene that encodes beta globin. The sickle hemoglobin molecule (HbS) is a tetramer of two alpha-globin chains and two sickle beta-globin chains, and has the tendency to polymerize when deoxygenated. HbS facilitates abnormal interactions between the sickle erythrocyte and leukocytes and endothelial cells, which trigger a complex pathobiology. This multifaceted pathophysiology provides the opportunity to interrupt the disease at multiple sites, including polymerization of HbS, erythrocyte density and cell-cell interactions. For example, it is possible to induce higher concentrations of fetal hemoglobin, which disrupts the pathology-initiating step of HbS polymerization. Furthermore, it is possible to improve the hydration of sickle erythrocytes and it might be feasible to counteract the endothelial, inflammatory and oxidative abnormalities of sickle cell disease. A therapeutic approach that targets several sites of pathobiology might be most promising.

Significant and sustaining elevation of blood oxygen induced by Chinese cupping therapy as assessed by near-infrared spectroscopy.

PubMed

Li, Ting; Li, Yaoxian; Lin, Yu; Li, Kai

2017-01-01

Cupping therapy has been used in traditional Chinese medicine for thousands of years to relieve muscle pain/tendency/fatigue and to cure or reduce symbols of other diseases. However, its therapeutic effect is sparsely interpreted in the language of modern physiology. To objectively evaluate its therapeutic effect, we focused on dry cupping treatment and utilized near-infrared spectroscopy (NIRS) to assess the concentration change in oxy-hemoglobin ([HbO 2 ]), deoxy-hemoglobin ([Hb]), and blood volume in the course of cupping therapy over 13 volunteers on the infraspinatus muscle, where is usually applied for shoulder pains. Both a prominent drop in [Hb] and a significant elevation in [HbO 2 ] in the tissue surrounding the cupping site were observed during both cupping and post-treatment, manifesting the enhancement of oxygen uptake. This resulting promotion indicates potential positive therapeutic effect of cupping therapy in hemodynamics for facilitating muscular functions.

Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

NASA Astrophysics Data System (ADS)

Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

1996-12-01

A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

Chemical coagulation of combined sewer overflow: heavy metal removal and treatment optimization.

PubMed

El Samrani, A G; Lartiges, B S; Villiéras, F

2008-02-01

The coagulation of combined sewer overflow (CSO) was investigated by jar-testing with two commercial coagulants, a ferric chloride solution (CLARFER) and a polyaluminium chloride (WAC HB). CSO samples were collected as a function of time during various wet-weather events from the inlet of Boudonville retention basin, Nancy, France. Jar-tests showed that an efficient turbidity removal can be achieved with both coagulants, though lower optimum dosages and higher re-stabilization concentrations were obtained with the aluminum-based coagulant. Optimum turbidity removal also yielded effective heavy metal elimination. However, the evolution with coagulant dosage of Cu, Zn, Pb, Cr, soluble and suspended solids contents followed various patterns. The removal behaviors can be explained by a selective aggregation of heavy metal carriers present in CSO and a specific interaction between hydrolyzed coagulant species and soluble metals. Stoichiometric relationships were established between optimal coagulant concentration, range of optimal dosing, and CSO conductivity, thus providing useful guidelines to adjust the coagulant demand during the course of CSO events.

Hypoxia delays hematopoiesis: retention of embryonic hemoglobin and erythrocytes in larval rainbow trout, Oncorhynchus mykiss, during chronic hypoxia exposure.

PubMed

Bianchini, Kristin; Wright, Patricia A

2013-12-01

In rainbow trout development, a switch occurs from high-affinity embryonic hemoglobin (Hb) and round, embryonic erythrocytes to lower-affinity adult Hb and oval, adult erythrocytes. Our study investigated the early ontogeny of rainbow trout blood properties and the hypoxia response. We hypothesized that hypoxia exposure would delay the ontogenetic turnover of Hb and erythrocytes because retention of high-affinity embryonic Hb would facilitate oxygen loading. To test this hypothesis we developed a method of efficiently extracting blood from individual embryos and larvae and optimized several techniques for measuring hematological parameters on microliter (0.5-2.0 μl) blood samples. In chronic hypoxia (30% of oxygen saturation), stage-matched embryos and larvae possessed half the Hb concentration, erythrocyte counts and hematocrit observed in normoxia. Hypoxia-reared larvae also had threefold to sixfold higher mRNA expression of the embryonic Hb α-1, β-1 and β-2 subunits relative to stage-matched normoxia-reared larvae. Furthermore, in hypoxia, the round embryonic erythrocytic shape persisted into later developmental stages. Despite these differences, Hb-oxygen affinity (P50), cooperativity and the Root effect were unaltered in hypoxia-reared O. mykiss. The data support our hypothesis that chronic hypoxia delays the ontogenetic turnover of Hb and erythrocytes, but without the predicted functional consequences (i.e. higher than expected P50). These results also suggest that the Hb-oxygen affinity is protected during development in chronic hypoxia to favor oxygen unloading at the tissues. We conclude that in early trout development, the blood-oxygen transport system responds very differently to chronic hypoxia relative to adults, possibly because respiration depends relatively more on oxygen diffusion than convection.

Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance.

PubMed

Ferrannini, Ele; Natali, Andrea; Camastra, Stefania; Nannipieri, Monica; Mari, Andrea; Adam, Klaus-Peter; Milburn, Michael V; Kastenmüller, Gabi; Adamski, Jerzy; Tuomi, Tiinamaija; Lyssenko, Valeriya; Groop, Leif; Gall, Walter E

2013-05-01

Metabolomic screening of fasting plasma from nondiabetic subjects identified α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of α-HB and L-GPC for incident dysglycemia, α-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, α-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with α-HB reciprocally related to indices of β-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, α-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00-1.60] and 1.26 [1.07-1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48-0.85] and 0.67 [0.54-0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting α-HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, α-HB inhibited and L-GPC stimulated glucose-induced insulin release in INS-1e cells. α-HB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and β-cell dysfunction.

HbA1c in relation to incident diabetes and diabetes-related complications in non-diabetic adults at baseline.

PubMed

Metcalf, Patricia Anne; Kyle, Cam; Kenealy, Tim; Jackson, Rod T

2017-05-01

We compared the utility of glycated hemoglobin (HbA 1c ) and oral glucose tolerance (oGTT) in non-diabetic patients for identifying incident diabetes; all-cause mortality; cardiovascular disease (CVD) mortality; CVD, coronary heart disease (CHD), and ischemic stroke events; and diabetes microvascular complications. Data from a New Zealand community setting were prospectively linked to hospitalization, mortality, pharmaceutical and laboratory test results data. After applying exclusion criteria (prior laboratory diagnosis or history of drug treatment for diabetes or hospitalization for diabetes or CVD event), there were 31,148 adults who had an HbA 1c and 2-h 75g oGTT. HbA 1c was measured by ion-exchange high-performance liquid chromatography, and glucose using a commercial enzymatic method. We compared glycemic measures and outcomes using multivariable Cox proportional hazards regression. The median follow-up time was 4years (range 0 to 13). The mean age was 57·6years and 53·0% were male. After adjusting for other glycemic measures (fasting glucose, 2-h glucose and/or HbA 1c where relevant) in addition to age, sex, ethnicity and smoking habit, the hazard ratios for incident diabetes and diabetes complications of retinopathy and nephropathy were highest for 2-h glucose levels, followed by HbA 1c and lastly by fasting glucose. However, all-cause mortality and CHD were significantly associated with HbA 1c concentrations only, and ischemic stroke and CVD events with 2-h glucose only. Circulatory complications showed a stronger association with HbA 1c . Apart from neuropathy, HbA 1c showed stronger associations with outcomes compared to fasting glucose and provides a convenient alternative to an oGTT. Copyright © 2017 Elsevier Inc. All rights reserved.

Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance

PubMed Central

Ferrannini, Ele; Natali, Andrea; Camastra, Stefania; Nannipieri, Monica; Mari, Andrea; Adam, Klaus-Peter; Milburn, Michael V.; Kastenmüller, Gabi; Adamski, Jerzy; Tuomi, Tiinamaija; Lyssenko, Valeriya; Groop, Leif; Gall, Walter E.

2013-01-01

Metabolomic screening of fasting plasma from nondiabetic subjects identified α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of α-HB and L-GPC for incident dysglycemia, α-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, α-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with α-HB reciprocally related to indices of β-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, α-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00–1.60] and 1.26 [1.07–1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48–0.85] and 0.67 [0.54–0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting α-HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, α-HB inhibited and L-GPC stimulated glucose-induced insulin release in INS-1e cells. α-HB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and β-cell dysfunction. PMID:23160532

Reperfusion response changes induced by repeated, sustained contractions in normal human masseter muscle.

PubMed

Aizawa, Shigeru; Tsukiyama, Yoshihiro; Koyano, Kiyoshi; Clark, Glenn T

2002-07-01

The purpose was to evaluate the intramuscular reperfusion response characteristics associated with repeated isometric contractions in normal human masseter. Intramuscular blood volume was quantified with a near-infrared spectroscopic device that measured the total haemoglobin (Hb) concentration in the muscle. Electromyographic (EMG) activity from the masseter and total bite forces were also recorded. Sixteen healthy volunteers, eight females and eight males, without masticatory muscle pain participated. They were asked first to clench their teeth for as long as possible at 50% of their maximum voluntary contraction (MVC). This was followed by a 60s rest and then immediately by a standard clenching task (50% MVC for 30s) and a 60s recovery period, immediately after which they were asked to repeat exactly the same procedure, with a final 5 min recovery period after the second 30s contraction. Bite force, EMG and Hb concentration were measured continuously and the duration of the two endurance tasks and the amplitudes of all recorded signals were compared (first trial versus second trial). Specifically, the difference between the lowest Hb (trough) seen during the standardised 30s contractions and the highest (peak) seen just after them was assessed. The trough-to-peak difference in Hb concentration of the second standard contraction task was significantly smaller than that of the first standard task (P<0.05, paired t-test). These data show that with sustained effort the post-contraction vasodilatory reperfusion responses of the human masseter are diminished, suggesting a progressive desensitisation of the vasodilatory system.

Anaemia in pregnant women before and after the mandatory fortification of wheat and corn flours with iron.

PubMed

da Silva, Cristina Lúcia; Saunders, Cláudia; Szarfarc, Sophia Cornbluth; Fujimori, Elizabeth; da Veiga, Glória Valéria

2012-10-01

To estimate the frequency of anaemia in pregnant women before and after the fortification of flours with Fe. Retrospective study developed from secondary data obtained from medical records. Two health units in Rio de Janeiro, Brazil. Socio-economic, demographic, obstetric and Hb concentration data were collected of 778 pregnant women attending prenatal care. Two study groups were created: the first referred to the period before fortification (G1, n 391), including women whose parturition happened before June 2004; and the second referred to the period after fortification (G2, n 387), including women whose last menstrual cycle happened after June 2005. The Hb cut-off point adopted for anaemia diagnosis was <11.0 g/dl. In linear regression models, when Hb concentration was expressed as a dependent variable, women in G2 presented Hb concentration 0.26 g/dl and 0.36 g/dl higher during the second and third trimesters of pregnancy, respectively, compared with G1. In logistic regression models where the dependent variable was anaemia during the second and third trimesters, it was verified that being a member of G2 was a protective factor against anaemia in the third trimester. Regarding the presence of anaemia at any gestational moment, it was verified that being a member of G2 represented a protective factor against anaemia during pregnancy. Results indicate the protective effect of the fortification of flours with Fe in the fight against gestational anaemia, contributing to prevention and control of this nutritional disorder among pregnant women.

Fed-Batch Synthesis of Poly(3-Hydroxybutyrate) and Poly(3-Hydroxybutyrate-co-4-Hydroxybutyrate) from Sucrose and 4-Hydroxybutyrate Precursors by Burkholderia sacchari Strain DSM 17165.

PubMed

Miranda De Sousa Dias, Miguel; Koller, Martin; Puppi, Dario; Morelli, Andrea; Chiellini, Federica; Braunegg, Gerhart

2017-04-20

Based on direct sucrose conversion, the bacterium Burkholderia sacchari is an excellent producer of the microbial homopolyester poly(3-hydroxybutyrate) (PHB). Restrictions of the strain's wild type in metabolizing structurally related 3-hydroxyvalerate (3HV) precursors towards 3HV-containing polyhydroxyalkanoate (PHA) copolyester calls for alternatives. We demonstrate the highly productive biosynthesis of PHA copolyesters consisting of 3-hydroxybuytrate (3HB) and 4-hydroxybutyrate (4HB) monomers. Controlled bioreactor cultivations were carried out using saccharose from the Brazilian sugarcane industry as the main carbon source, with and without co-feeding with the 4HB-related precursor γ-butyrolactone (GBL). Without GBL co-feeding, the homopolyester PHB was produced at a volumetric productivity of 1.29 g/(L•h), a mass fraction of 0.52 g PHB per g biomass, and a final PHB concentration of 36.5 g/L; the maximum specific growth rate µmax amounted to 0.15 1/h. Adding GBL, we obtained 3HB and 4HB monomers in the polyester at a volumetric productivity of 1.87 g/(L•h), a mass fraction of 0.72 g PHA per g biomass, a final PHA concentration of 53.7 g/L, and a µmax of 0.18 1/h. Thermoanalysis revealed improved material properties of the second polyester in terms of reduced melting temperature Tm (161 °C vs. 178 °C) and decreased degree of crystallinity Xc (24% vs. 71%), indicating its enhanced suitability for polymer processing.

Hemoglobin measured by Hemocue and a reference method in venous and capillary blood: a validation study.

PubMed

Neufeld, Lynnette; García-Guerra, Armando; Sánchez-Francia, Domingo; Newton-Sánchez, Oscar; Ramírez-Villalobos, María Dolores; Rivera-Dommarco, Juan

2002-01-01

To assess the comparability of hemoglobin concentration (Hb) in venous and capillary blood measured by Hemocue and an automated spectrophotometer (Celldyn) and to document the influence of type of blood (capillary or venous) and analysis method on anemia prevalence estimates. Between February and May 2000, capillary and venous samples were collected from 72 adults and children at Hospital del Niño Morelense (Morelos State Children's Hospital) in Cuernavaca, Morelos, Mexico, and assessed for Hb using the Hemocue and Celldyn methods. Estimated Hb levels were compared using the concordance correlation coefficient and Student's t test for paired data. The sensitivity and specificity for anemia diagnosis were estimated and compared between type of blood and method of assessment. Capillary blood had higher Hb (+0.5 g/dl) than venous blood in adults and children, as did samples assessed by Celldyn compared to Hemocue (+0.3 g/dl). Specificity to detect anemia was adequate (> 0.90) but sensitivity was low for capillary blood assessed by Hemocue (< 0.80). The difference in Hb between venous and capillary blood is likely related to biological variability. Hemoglobin concentration in capillary blood assessed by Hemocue provides an adequate estimation of population anemia prevalence but may result in excess false negative diagnoses among individuals. The results of this study stress the importance of sample collection technique, particularly for children. Method of analysis and sampling site need to be taken into consideration in field studies. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women.

PubMed

Casanueva, Esther; Viteri, Fernando E; Mares-Galindo, Mónica; Meza-Camacho, Carlos; Loría, Alvar; Schnaas, Lourdes; Valdés-Ramos, Roxana

2006-07-01

We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20. Women with singleton pregnancies and blood hemoglobin (Hb) >115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated. Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations <103 g/L at any evaluation point. In contrast, hemoconcentration (Hb >145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74). In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels <100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery.

Biochemical and developmental characterization of carbonic anhydrase II from chicken erythrocytes.

PubMed

Nishita, Toshiho; Tomita, Yuichiro; Imanari, Takao; Ichihara, Nobutsune; Orito, Kensuke; Arishima, Kazuyoshi

2011-03-07

Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes. Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens. The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p<0.01). Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p<0.01). © 2011 Nishita et al; licensee BioMed Central Ltd.

Electrochemistry of hemoglobin entrapped in a Nafion/nano-ZnO film on carbon ionic liquid electrode.

PubMed

Sun, Wei; Zhai, ZiQin; Wang, DanDan; Liu, ShuFeng; Jiao, Kui

2009-02-01

A stable composite film composed of the ionomer Nafion, the ZnO nanoparticle and the protein hemoglobin was cast on the surface of an ionic liquid modified carbon paste electrode (CILE) to establish a modified electrode denoted as Nafion/nano-ZnO/Hb/CILE. UV-vis and FT-IR spectrum showed that hemoglobin in the film retained its native conformation. The electrochemical behaviors of hemoglobin entrapped in the film were carefully investigated with cyclic voltammetry. A pair of well-defined and quasi-reversible redox voltammetric peaks for Hb Fe(III)/Fe(II) was obtained with the standard potential (E(0)') located at -0.344 V (vs. SCE) in phosphate buffer solution (PBS, pH 7.0), which was attributed to the direct electron transfer of Hb with electrode in the microenvironments of ZnO nanoparticle and ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF(6)). The electrochemical parameters of Hb in the composite film were further carefully calculated with the results of the electron-transfer rate constant (k(s)) as 0.139 s(-1), the charge transfer coefficient (alpha) as 0.413 and the number of electron transferred (n) as 0.95. The Hb modified electrode showed good electrocatalytic ability toward the reduction of trichloroacetic acid (TCA).

Dissociation between urinary pyrraline and pentosidine concentrations in diabetic patients with advanced nephropathy.

PubMed

Aso, Yoshimasa; Takanashi, Keishi; Sekine, Kyouichi; Yoshida, Noboru; Takebayashi, Kohzo; Yoshihara, Kazuhiro; Inukai, Toshihiko

2004-08-01

It has been reported that the concentrations of both pyrraline and pentosidine, well-characterized advanced glycation end products, are increased in the urine of diabetic patients. To determine factors that influence the urinary excretion of pyrraline or pentosidine, we compared pyrraline or pentosidine concentrations with glycemic-control indexes, urinary albumin excretion, and urinary beta2-microglobulin in patients with type 2 diabetes. The study was conducted in 39 age-matched healthy control subjects and 50 diabetic patients, including 22 patients with normoalbuminuria, 15 with microalbuminuria, and 13 with macroalbuminuria. Both urinary pyrraline and pentosidine were measured in early-morning urine specimens with the use of high-pressure liquid chromatography. The urinary pentosidine concentration was significantly higher in diabetic patients than in control subjects (P <.01). In contrast, the urinary pyrraline concentration was significantly lower in diabetic patients than in control subjects (P <.001). Urinary pentosidine concentrations were greater in diabetic patients with macroalbuminuria and microalbuminuria than in those with normoalbuminuria. However, urinary pyrraline concentrations were significantly lower in diabetic patients with advanced nephropathy. Both the hemoglobin A(1c) (HbA(1c)) and the preceding year's mean HbA(1c) were lower in patients with macroalbuminuria than in those with normoalbuminuria or microalbuminuria. Urinary pyrraline, but not pentosidine, showed a significantly positive correlation with the preceding year's mean HbA(1c) (P<0.01). Multivariate analysis disclosed that urinary beta-2-microglobulin was independently correlated with the urinary concentrations of pentosidine and pyrraline (P <.05 for both). We conclude that the urinary concentration of pentosidine is greater in diabetic patients with overt nephropathy, whereas the urinary pyrraline concentration is significantly lower in diabetic patients with overt nephropathy. Because urinary pyrraline is more directly influenced by glycemia than by pentosidine, the difference in glycemic control among diabetic patients with various grades of nephropathy may be responsible for a dissociation between urinary pyrraline and pentosidine concentrations in patients with overt diabetic nephropathy.

Experimental recovery of intrinsic fluorescence and fluorophore concentration in the presence of hemoglobin: spectral effect of scattering and absorption on fluorescence

NASA Astrophysics Data System (ADS)

Du Le, Vinh Nguyen; Patterson, Michael S.; Farrell, Thomas J.; Hayward, Joseph E.; Fang, Qiyin

2015-12-01

The ability to recover the intrinsic fluorescence of biological fluorophores is crucial to accurately identify the fluorophores and quantify their concentrations in the media. Although some studies have successfully retrieved the fluorescence spectral shape of known fluorophores, the techniques usually came with heavy computation costs and did not apply for strongly absorptive media, and the intrinsic fluorescence intensity and fluorophore concentration were not recovered. In this communication, an experimental approach was presented to recover intrinsic fluorescence and concentration of fluorescein in the presence of hemoglobin (Hb). The results indicated that the method was efficient in recovering the intrinsic fluorescence peak and fluorophore concentration with an error of 3% and 10%, respectively. The results also suggested that chromophores with irregular absorption spectra (e.g., Hb) have more profound effects on fluorescence spectral shape than chromophores with monotonic absorption and scattering spectra (e.g., black India ink and polystyrene microspheres).

Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers.

PubMed

Kang, Guodong; Ma, Fubao; Chen, Haiping; Yang, Yunkai; Guo, Shaohong; Wang, Zhiguo; Liang, Xiaofeng; Li, Li; Cui, Fuqiang; Zhang, Longhua

2015-08-07

To compare the safety and immunogenicity of two dosages of recombinant hepatitis B (HB) vaccine administered to infants born to HB-uninfected and HB-infected mothers. A phase III, controlled, single-blinded clinical trial was conducted with 506 healthy newborns. The newborns were assigned to three groups based on maternal levels of HB surface antigen (HBsAg) and HB e antigen (HBeAg): Group A, HBsAg negative; Group B, HBsAg positive and HBeAg negative; and Group C, HBsAg positive and HBeAg positive. Three doses of 10 or 5 μg recombinant HB vaccine were randomly administered by 1:1 within 24 h after birth, at 1 month and at 6 months. Safety data and pre- and postvaccination blood samples were collected. A total of 326, 93, and 87 subjects were included in Groups A, B, and C, respectively. Both dosages of HB vaccine were well tolerated by all subjects. The most common injection-site adverse reactions (ARs) and systemic ARs were pain and fever. After 1 month of the third dose, the Group A infants who received the 10 μg HB vaccine achieved a higher geometric mean concentration (GMC) of HB surface antibody (anti-HBs) than those who received the 5 μg dosage. Maternal anti-HBs serostatus did not influence HB vaccine immunogenicity at either dosage. In contrast, there was no significant difference in the anti-HBs seroconversion rate, GMCs, or estimated vaccine efficacy (EVE) against perinatal transmission between Groups B and C, regardless of dosage. However, the seroconversion rate and EVE of the 5 μg HB vaccine was lower in Group C than in Group B. Both dosages of the HB vaccine were well tolerated and elicited a good immune response in infants of Group A, regardless of the maternal anti-HBs serostatus. EVE did not significantly differ between Groups B and C. Clinicaltrials.gov identifier: NCT02152709. Copyright © 2015 Elsevier Ltd. All rights reserved.

Normal and frictional interactions of purified human statherin adsorbed on molecularly-smooth solid substrata.

PubMed

Harvey, Neale M; Carpenter, Guy H; Proctor, Gordon B; Klein, Jacob

2011-09-01

Human salivary statherin was purified from parotid saliva and adsorbed to bare hydrophilic (HP) mica and STAI-coated hydrophobic (HB) mica in a series of Surface Force Balance experiments that measured the normal (F(n)) and friction forces (F(s)*) between statherin-coated mica substrata. Readings were taken both in the presence of statherin solution (HP and HB mica) and after rinsing (HP mica). F(n) measurements showed, for both substrata, monotonic steric repulsion that set on at a surface separation D ~20 nm, indicating an adsorbed layer whose unperturbed thickness was ca 10 nm. An additional longer-ranged repulsion, probably of electrostatic double-layer origin, was observed for rinsed surfaces under pure water. Under applied pressures of ~1 MPa, each surface layer was compressed to a thickness of ca 2 nm on both types of substratum, comparable with earlier estimates of the size of the statherin molecule. Friction measurements, in contrast with F(n) observations, were markedly different on the two different substrata: friction coefficients, μ ≡ ∂F(s)*/∂F(n), on the HB substratum (μ ≈ 0.88) were almost an order of magnitude higher than on the HP substratum (μ ≈ 0.09 and 0.12 for unrinsed and rinsed, respectively), and on the HB mica there was a lower dependence of friction on sliding speed than on the HP mica. The observations were attributed to statherin adsorbing to the mica in multimer aggregates, with internal re-arrangement of the protein molecules within the aggregate dependent on the substratum to which the aggregate adsorbed. This internal re-arrangement permitted aggregates to be of similar size on HP and HB mica but to have different internal molecular orientations, thus exposing different moieties to the solution in each case and accounting for the very different friction behaviour.

Preservation of anemia control and weekly ESA dosage after conversion from PEG-Epoetin beta to darbepoetin alfa in adult hemodialysis patients: the TRANSFORM study.

PubMed

Donck, Jan; Gonzalez-Tabares, Lourdes; Chanliau, Jacques; Martin, Heike; Stamatelou, Kyriaki; Manamley, Nick; Farouk, Mourad; Addison, Janet

2014-11-01

There is scant real-world information on switching treatment for anemia associated with chronic kidney disease (CKD) from methoxy polyethylene glycol-epoetin beta (PEG-Epo) to darbepoetin alfa (DA). TRANSFORM was a multi-center, observational study designed to describe the time course of hemoglobin (Hb) concentration (primary outcome measure) and other parameters of clinical management of anemia in European hemodialysis patients in clinical practice before and after a switch from PEG-Epo to DA. Eligible subjects were adult patients with CKD dialyzed at European dialysis centers for ≥26 weeks and treated with PEG-Epo for ≥14 weeks immediately prior to being switched to DA and no earlier than January 2011. Erythropoiesis-stimulating agent doses and Hb values were recorded for the 14-week pre-switch and 26-week post-switch periods. Of the 1,027 eligible patients enrolled at 42 hemodialysis centers in 7 European countries, 785 were included in analyses. Mean (95% confidence interval [CI]) Hb was generally stable: 11.19 (11.11, 11.26), 11.48 (11.40, 11.57), and 11.29 (11.20, 11.37) g/dL at month -1 pre-switch and months 3 and 6 post-switch, respectively. The geometric mean (95% CI) PEG-Epo dose at month -1 was 27.4 (26.0, 28.8) µg/week; DA dose was 29.4 (27.9, 30.9), 23.3 (21.9, 24.9), and 25.6 (24.1, 27.1) µg/week at months 1, 4, and 6, respectively. The geometric mean (95% CI) dose ratio at switching was 1.06 (1.01, 1.11). When stratifying by dose-ratio categories <0.8, 0.8-1.2, and >1.2 at switching, mean DA dose and Hb converged within narrow ranges by month 6 post-switch: 23.9-27.0 µg/week and 11.1-11.5 g/dL, respectively. Hb excursions <10 g/dL were less frequent post-switch versus pre-switch. Mean Hb values remained within a narrow range following switching from PEG-Epo to DA in this population of hemodialysis patients. Time trends of mean Hb and DA dose indicate that physicians titrated DA doses post-switch, to attain Hb concentrations comparable to those attained pre-switch with PEG-Epo.

A role for iron and oxygen chemistry in preserving soft tissues, cells and molecules from deep time.

PubMed

Schweitzer, Mary H; Zheng, Wenxia; Cleland, Timothy P; Goodwin, Mark B; Boatman, Elizabeth; Theil, Elizabeth; Marcus, Matthew A; Fakra, Sirine C

2014-01-22

The persistence of original soft tissues in Mesozoic fossil bone is not explained by current chemical degradation models. We identified iron particles (goethite-αFeO(OH)) associated with soft tissues recovered from two Mesozoic dinosaurs, using transmission electron microscopy, electron energy loss spectroscopy, micro-X-ray diffraction and Fe micro-X-ray absorption near-edge structure. Iron chelators increased fossil tissue immunoreactivity to multiple antibodies dramatically, suggesting a role for iron in both preserving and masking proteins in fossil tissues. Haemoglobin (HB) increased tissue stability more than 200-fold, from approximately 3 days to more than two years at room temperature (25°C) in an ostrich blood vessel model developed to test post-mortem 'tissue fixation' by cross-linking or peroxidation. HB-induced solution hypoxia coupled with iron chelation enhances preservation as follows: HB + O2 > HB - O2 > -O2 > +O2. The well-known O2/haeme interactions in the chemistry of life, such as respiration and bioenergetics, are complemented by O2/haeme interactions in the preservation of fossil soft tissues.

A role for iron and oxygen chemistry in preserving soft tissues, cells and molecules from deep time

PubMed Central

Schweitzer, Mary H.; Zheng, Wenxia; Cleland, Timothy P.; Goodwin, Mark B.; Boatman, Elizabeth; Theil, Elizabeth; Marcus, Matthew A.; Fakra, Sirine C.

2014-01-01

The persistence of original soft tissues in Mesozoic fossil bone is not explained by current chemical degradation models. We identified iron particles (goethite-αFeO(OH)) associated with soft tissues recovered from two Mesozoic dinosaurs, using transmission electron microscopy, electron energy loss spectroscopy, micro-X-ray diffraction and Fe micro-X-ray absorption near-edge structure. Iron chelators increased fossil tissue immunoreactivity to multiple antibodies dramatically, suggesting a role for iron in both preserving and masking proteins in fossil tissues. Haemoglobin (HB) increased tissue stability more than 200-fold, from approximately 3 days to more than two years at room temperature (25°C) in an ostrich blood vessel model developed to test post-mortem ‘tissue fixation’ by cross-linking or peroxidation. HB-induced solution hypoxia coupled with iron chelation enhances preservation as follows: HB + O2 > HB − O2 > −O2 ≫ +O2. The well-known O2/haeme interactions in the chemistry of life, such as respiration and bioenergetics, are complemented by O2/haeme interactions in the preservation of fossil soft tissues. PMID:24285202

Safety analysis, 200 Area, Savannah River Plant: Separations area operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perkins, W.C.; Lee, R.; Allen, P.M.

1991-07-01

The nev HB-Line, located on the fifth and sixth levels of Building 221-H, is designed to replace the aging existing HB-Line production facility. The nev HB-Line consists of three separate facilities: the Scrap Recovery Facility, the Neptunium Oxide Facility, and the Plutonium Oxide Facility. There are three separate safety analyses for the nev HB-Line, one for each of the three facilities. These are issued as supplements to the 200-Area Safety Analysis (DPSTSA-200-10). These supplements are numbered as Sup 2A, Scrap Recovery Facility, Sup 2B, Neptunium Oxide Facility, Sup 2C, Plutonium Oxide Facility. The subject of this safety analysis, the, Plutoniummore » Oxide Facility, will convert nitrate solutions of {sup 238}Pu to plutonium oxide (PuO{sub 2}) powder. All these new facilities incorporate improvements in: (1) engineered barriers to contain contamination, (2) barriers to minimize personnel exposure to airborne contamination, (3) shielding and remote operations to decrease radiation exposure, and (4) equipment and ventilation design to provide flexibility and improved process performance.« less

Local descriptive body weight and dietary norms, food availability, and 10-year change in glycosylated haemoglobin in an Australian population-based biomedical cohort.

PubMed

Carroll, Suzanne J; Paquet, Catherine; Howard, Natasha J; Coffee, Neil T; Adams, Robert J; Taylor, Anne W; Niyonsenga, Theo; Daniel, Mark

2017-02-02

Individual-level health outcomes are shaped by environmental risk conditions. Norms figure prominently in socio-behavioural theories yet spatial variations in health-related norms have rarely been investigated as environmental risk conditions. This study assessed: 1) the contributions of local descriptive norms for overweight/obesity and dietary behaviour to 10-year change in glycosylated haemoglobin (HbA 1c ), accounting for food resource availability; and 2) whether associations between local descriptive norms and HbA 1c were moderated by food resource availability. HbA 1c , representing cardiometabolic risk, was measured three times over 10 years for a population-based biomedical cohort of adults in Adelaide, South Australia. Residential environmental exposures were defined using 1600 m participant-centred road-network buffers. Local descriptive norms for overweight/obesity and insufficient fruit intake (proportion of residents with BMI ≥ 25 kg/m 2 [n = 1890] or fruit intake of <2 serves/day [n = 1945], respectively) were aggregated from responses to a separate geocoded population survey. Fast-food and healthful food resource availability (counts) were extracted from a retail database. Separate sets of multilevel models included different predictors, one local descriptive norm and either fast-food or healthful food resource availability, with area-level education and individual-level covariates (age, sex, employment status, education, marital status, and smoking status). Interactions between local descriptive norms and food resource availability were tested. HbA 1c concentration rose over time. Local descriptive norms for overweight/obesity and insufficient fruit intake predicted greater rates of increase in HbA 1c . Neither fast-food nor healthful food resource availability were associated with change in HbA 1c . Greater healthful food resource availability reduced the rate of increase in HbA 1c concentration attributed to the overweight/obesity norm. Local descriptive health-related norms, not food resource availability, predicted 10-year change in HbA 1c . Null findings for food resource availability may reflect a sufficiency or minimum threshold level of resources such that availability poses no barrier to obtaining healthful or unhealthful foods for this region. However, the influence of local descriptive norms varied according to food resource availability in effects on HbA 1c . Local descriptive health-related norms have received little attention thus far but are important influences on individual cardiometabolic risk. Further research is needed to explore how local descriptive norms contribute to chronic disease risk and outcomes.

Electrochemistry and electrocatalysis of hemoglobin in Nafion/nano-CaCO3 film on a new ionic liquid BPPF6 modified carbon paste electrode.

PubMed

Sun, Wei; Gao, Ruifang; Jiao, Kui

2007-05-03

Room temperature ionic liquid N-butylpyridinium hexafluorophosphate (BPPF6) was used as a binder to construct a new carbon ionic liquid electrode (CILE), which exhibited enhanced electrochemical behavior as compared with the traditional carbon paste electrode with paraffin. By using the CILE as the basal electrode, hemoglobin (Hb) was immobilized on the surface of the CILE with nano-CaCO3 and Nafion film step by step. The Hb molecule in the film kept its native structure and showed good electrochemical behavior. In pH 7.0 Britton-Robinson (B-R) buffer solution, a pair of well-defined, quasi-reversible cyclic voltammetric peaks appeared with cathodic and anodic peak potentials located at -0.444 and -0.285 V (vs SCE), respectively, and the formal potential (E degrees') was at -0.365 V, which was the characteristic of Hb Fe(III)/Fe(II) redox couples. The formal potential of Hb shifted linearly to the increase of buffer pH with a slope of -50.6 mV pH-1, indicating that one electron transferred was accompanied with one proton transportation. Ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectroscopy studies showed that Hb immobilized in the Nafion/nano-CaCO3 film still remained its native arrangement. The Hb modified electrode showed an excellent electrocatalytic behavior to the reduction of H2O2, trichloroacetic acid (TCA), and NaNO2.

Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling.

PubMed

Habazettl, H; Stahn, Alexander; Nitsche, Andrea; Nordine, Michael; Pries, A R; Gunga, H-C; Opatz, O

2016-01-01

We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling. Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively. Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 ± 1.4 and 26.6 ± 2.6 µmol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component. Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g.

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

PubMed Central

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

2013-01-01

When freshwater turtles acclimatize to winter hibernation, there is a gradual transition from aerobic to anaerobic metabolism, which may require adjustments of blood O2 transport before turtles become anoxic. Here, we report the effects of protons, anionic cofactors, and temperature on the O2-binding properties of isolated hemoglobin (Hb) isoforms, HbA and HbD, in the turtle Trachemys scripta. We determined the primary structures of the constituent subunits of the two Hb isoforms, and we related the measured functional properties to differences in O2 affinity between untreated hemolysates from turtles that were acclimated to normoxia and anoxia. Our data show that HbD has a consistently higher O2 affinity compared with HbA, whereas Bohr and temperature effects, as well as thiol reactivity, are similar. Although sequence data show amino acid substitutions at two known β-chain ATP-binding site positions, we find high ATP affinities for both Hb isoforms, suggesting an alternative and stronger binding site for ATP. The high ATP affinities indicate that, although ATP levels decrease in red blood cells of turtles acclimating to anoxia, the O2 affinity would remain largely unchanged, as confirmed by O2-binding measurements of untreated hemolysates from normoxic and anoxic turtles. Thus, the increase in blood-O2 affinity that accompanies winter acclimation is mainly attributable to a decrease in temperature rather than in concentrations of organic phosphates. This is the first extensive study on freshwater turtle Hb isoforms, providing molecular evidence for adaptive changes in O2 transport associated with acclimation to severe hypoxia. PMID:23986362

Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes

PubMed Central

2012-01-01

Background Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin. Objectives We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter oxygen saturation (SpO2) in type 2 diabetic patients during mechanical ventilation or oxygen therapy. Methods Arterial oxygen saturation (SaO2) and partial pressure of oxygen (PO2) were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation. Results Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 (96.2 ± 2.9%, 95% confidence interval [CI] 95.7-96.7% vs. 95.1 ± 2.8%, 95% CI 94.7-95.6%) and SpO2 (98.0 ± 2.6%, 95% CI 97.6-98.5% vs. 95.3 ± 2.8%, 95% CI 94.9-95.8%) were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% (Data are mean ± SD, all p < 0.01), but PO2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 ±0.55%, 95% CI 1.73% -1.94%) and limits of agreement (0.76% and 2.92%) in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels (Pearson’s r = 0.307, p < 0.01). Conclusions Elevated blood HbA1c levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia. PMID:22985301

Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes.

PubMed

Pu, Li Jin; Shen, Ying; Lu, Lin; Zhang, Rui Yan; Zhang, Qi; Shen, Wei Feng

2012-09-17

Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin. We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter oxygen saturation (SpO2) in type 2 diabetic patients during mechanical ventilation or oxygen therapy. Arterial oxygen saturation (SaO2) and partial pressure of oxygen (PO2) were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation. Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 (96.2 ± 2.9%, 95% confidence interval [CI] 95.7-96.7% vs. 95.1 ± 2.8%, 95% CI 94.7-95.6%) and SpO2 (98.0 ± 2.6%, 95% CI 97.6-98.5% vs. 95.3 ± 2.8%, 95% CI 94.9-95.8%) were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% (Data are mean ± SD, all p < 0.01), but PO2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 ±0.55%, 95% CI 1.73% -1.94%) and limits of agreement (0.76% and 2.92%) in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels (Pearson's r = 0.307, p < 0.01). Elevated blood HbA1c levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia.

Glycated hemoglobin measurement and prediction of cardiovascular disease.

PubMed

Di Angelantonio, Emanuele; Gao, Pei; Khan, Hassan; Butterworth, Adam S; Wormser, David; Kaptoge, Stephen; Kondapally Seshasai, Sreenivasa Rao; Thompson, Alex; Sarwar, Nadeem; Willeit, Peter; Ridker, Paul M; Barr, Elizabeth L M; Khaw, Kay-Tee; Psaty, Bruce M; Brenner, Hermann; Balkau, Beverley; Dekker, Jacqueline M; Lawlor, Debbie A; Daimon, Makoto; Willeit, Johann; Njølstad, Inger; Nissinen, Aulikki; Brunner, Eric J; Kuller, Lewis H; Price, Jackie F; Sundström, Johan; Knuiman, Matthew W; Feskens, Edith J M; Verschuren, W M M; Wald, Nicholas; Bakker, Stephan J L; Whincup, Peter H; Ford, Ian; Goldbourt, Uri; Gómez-de-la-Cámara, Agustín; Gallacher, John; Simons, Leon A; Rosengren, Annika; Sutherland, Susan E; Björkelund, Cecilia; Blazer, Dan G; Wassertheil-Smoller, Sylvia; Onat, Altan; Marín Ibañez, Alejandro; Casiglia, Edoardo; Jukema, J Wouter; Simpson, Lara M; Giampaoli, Simona; Nordestgaard, Børge G; Selmer, Randi; Wennberg, Patrik; Kauhanen, Jussi; Salonen, Jukka T; Dankner, Rachel; Barrett-Connor, Elizabeth; Kavousi, Maryam; Gudnason, Vilmundur; Evans, Denis; Wallace, Robert B; Cushman, Mary; D'Agostino, Ralph B; Umans, Jason G; Kiyohara, Yutaka; Nakagawa, Hidaeki; Sato, Shinichi; Gillum, Richard F; Folsom, Aaron R; van der Schouw, Yvonne T; Moons, Karel G; Griffin, Simon J; Sattar, Naveed; Wareham, Nicholas J; Selvin, Elizabeth; Thompson, Simon G; Danesh, John

2014-03-26

The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

Hemosomegenesis and hemoglobin biosynthesis in vertebrates.

PubMed

Brunner Júnior, A; de Rizzo, E; Morena, D D; Cianciarullo, A M; Jared, C; Morena, P

1992-08-01

1. Ultrastructural observations on maturing rabbit embryo erythroid cells led to the finding of hemoglobinized organelles distinguishable from mitochondria due to their highly dense matrix, two or three longitudinally arranged double lamellae, and smaller diameters. Intraorganellar 50-60 A particles identical to those contained in the hemoglobinized cytoplasm were found. 2. Their hemoglobin (Hb) content was demonstrated by electrophoresis of the concentrated supernatant from the isolated, washed, and osmotically lysed organellar fraction. We have proposed that these organelles are the sites for heme integration into the globin (G) polypeptide chains and subunits assembly. The term hemosome has been suggested for such entities. 3. This hypothesis has been sustained by several analytical and experimental works based on the postulation that hemosomes should be found at higher frequencies where the Hb biosynthesis rate is more intensive, or where the induction of this biosynthesis is always dependent on the formation of hemosomes. 4. Maturing erythroid cells of the circulating embryo blood contain hemosomes in higher frequency than in liver erythroid cells, coinciding with the higher Hb biosynthesis rate in peripheral blood than in the liver. In bleeding anemia, the decay of Hb concentration parallels the reduction of the mean number of hemosomes per reticulocyte, in comparison with normal reticulocytes. 5. In HeLa cells and epithelial cultured cells induced to synthesize Hb, it was shown that this biosynthesis is ever concomitant with the formation of hemosomes and depends on the presence of erythropoietin, as occurs in erythroid cells. 6. Studies on hemosomegenesis and Hb biosynthesis experimentally effected in epithelial cultured cells, allowed the interpretation of the sequence of events leading to hemosome formation in maturing erythroid cells. Simultaneously with iron uptake, mitochondria differentiate to lamellated bodies and, successively, expansions rise for ferruginous compounds and G polypeptides gathering, followed by prehemosome vesicles formation, which condense and change to prohemosomes that afterwards evolve to hemosomes. 7. These dynamics, and organellar Hb have been detected in immature erythrocytes of mammalians, including humans, avians, reptilians, amphibians and representative fish specimens. It appears that these events occur in the erythrocytary maturation of all vertebrate classes.

Gender-specific hemodynamics in prefrontal cortex during a verbal working memory task by near-infrared spectroscopy.

PubMed

Li, Ting; Luo, Qingming; Gong, Hui

2010-05-01

The presence or absence of gender differences in working memory, localized in the prefrontal cortex (PFC), has been debated in a few fMRI studies. However, the hypothesis of gender differences in PFC function has not been elaborated, and comparisons among hemodynamic parameters designed to test for gender differences are scarce. We utilized near-infrared spectroscopy during verbal N-back tasks on 26 male and 24 female healthy volunteers. Changes in the concentrations of oxy- (Delta[oxy-Hb]), deoxy- (Delta[deoxy-Hb]) and total hemoglobin (Delta[tot-Hb]) were recorded simultaneously. Delta[oxy-Hb] and Delta[tot-Hb] exhibited obvious gender differences, but Delta[deoxy-Hb] did not. Males showed bilateral activation with slight left-side dominance, whereas females showed left activation. The activation in males was more wide-spread and stronger than in females. Furthermore, females required a lower hemodynamic supply than males to obtain comparable performance, and only females exhibited positive correlations between hemodynamic parameters and behavioral performance. The results reinforce the existence of a gender effect in hemodynamic-based functional imaging studies. Our findings suggest that females possess more efficient hemodynamics in the PFC during working memory and emphasize the importance of studying the PFC to further a scientific understanding of gender differences.

GADOLINIUM OXALATE SOLUBILITY MEASUREMENTS IN NITRIC ACID SOLUTIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, R. A.

2012-03-12

HB-Line will begin processing Pu solutions during FY2012 that will involve the recovery of Pu using oxalate precipitation and filtration. After the precipitation and filtration processes, the filtrate solution will be transferred from HB-Line to H-Canyon. The presence of excess oxalate and unfiltered Pu oxalate solids in these solutions create a criticality safety issue if they are sent to H-Canyon without controls in H-Canyon. One approach involves H-Canyon receiving the filtrate solution into a tank that is poisoned with soluble gadolinium (Gd). Decomposition of the oxalate will occur within a subsequent H-Canyon vessel. The receipt of excess oxalate into themore » H-Canyon receipt tanks has the potential to precipitate a portion of the Gd poison in the receipt tanks. Because the amount of Gd in solution determines the maximum amount of Pu solids that H-Canyon can receive, H-Canyon Engineering requested that SRNL determine the solubility of Gd in aqueous solutions of 4-10 M nitric acid (HNO{sub 3}), 4-12 g/L Gd, and 0.15-0.25 M oxalic acid (H{sub 2}C{sub 2}O{sub 4}) at 25 °C. The target soluble Gd concentration is 6 g/L. The data indicate that the target can be achieved above 6 M HNO{sub 3} and below 0.25 M H{sub 2}C{sub 2}O{sub 4}. At 25 °C, for 6 M HNO{sub 3}, 11 g/L and 7 g/L Gd are soluble in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. In 4 M HNO{sub 3}, the Gd solubility drops significantly to 2.5 g/L and 0.8 g/L in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. The solubility of Gd at 8-10 M HNO{sub 3} exceeds the solubility at 6 M HNO{sub 3}. The data for 4 M HNO{sub 3} showed good agreement with data in the literature. To achieve a target of 6 g/L soluble Gd in solution in the presence of 0.15-0.25 M oxalate, the HNO{sub 3} concentration must be maintained at or above 6 M HNO{sub 3}. The solubility of Gd in 4 M HNO{sub 3} with 0.15 M oxalate at 10 °C is about 1.5 g/L. For 6 M HNO{sub 3} with 0.15 M oxalate, the solubility of Gd at 10 °C is about 10 g/L. Gadolinium nitrate is very soluble in HNO{sub 3}. The solubility of Gd is linear as a function of HNO{sub 3} from 343 g/L Gd in 2.88 M HNO{sub 3} to 149 g/L in 8.16 M HNO{sub 3}. Below 2.88 M HNO{sub 3}, the solubility of Gd approaches a limit of about 360 g/L. However, there are no data available below 1.40 M HNO{sub 3}, which has a Gd solubility of 353 g/L.« less

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults

PubMed Central

Vijayakumar, Pavithra; Nelson, Robert G.; Hanson, Robert L.; Knowler, William C.

2017-01-01

OBJECTIVE Long-term data validating glycated hemoglobin (HbA1c) in assessing the risk of type 2 diabetes in children are limited. HbA1c, fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. RESEARCH DESIGN AND METHODS Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10–19 years monitored through age 39, and in 2,005 adults ages 20–39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA1c, FPG, and 2hPG in predicting diabetes within 10 years were compared. RESULTS During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA1c ≥5.7% as in those with HbA1c ≤5.3%—greater rate ratios than experienced by adults in the same HbA1c categories. Analyses of ROCs revealed no significant differences between HbA1c, FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. CONCLUSIONS HbA1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. PMID:27810987

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

PubMed

Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L; Knowler, William C; Sinha, Madhumita

2017-01-01

Long-term data validating glycated hemoglobin (HbA 1c ) in assessing the risk of type 2 diabetes in children are limited. HbA 1c , fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA 1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA 1c , FPG, and 2hPG in predicting diabetes within 10 years were compared. During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA 1c ≥5.7% as in those with HbA 1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA 1c categories. Analyses of ROCs revealed no significant differences between HbA 1c , FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. HbA 1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. © 2017 by the American Diabetes Association.

Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

PubMed Central

Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

2016-01-01

To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

Progressive glomerular and tubular damage in sickle cell trait and sickle cell anemia mouse models.

PubMed

Saraf, Santosh L; Sysol, Justin R; Susma, Alexandru; Setty, Suman; Zhang, Xu; Gudehithlu, Krishnamurthy P; Arruda, Jose A L; Singh, Ashok K; Machado, Roberto F; Gordeuk, Victor R

2018-02-02

Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation. Consistent with progressive glomerular damage, we observed progressively greater urine protein concentrations (P = 0.03), glomerular hypertrophy (P = 0.002), and glomerular cellularity (P = 0.01) in HbAA, HbAS, and HbSS mice, respectively. Ultrastructural studies demonstrated progressive podocyte foot process effacement, glomerular basement membrane thickening with reduplication, and tubular villous atrophy with the HbS mutation. Gene expression studies highlighted the differential expression of several genes involved in prostaglandin metabolism (AKR1C18), heme and iron metabolism (HbA-A2, HMOX1, SCL25A37), electrolyte balance (SLC4A1, AQP6), immunity (RSAD2, C3, UBE2O), fatty acid metabolism (FASN), hypoxia hall-mark genes (GCK, SDC3, VEGFA, ETS1, CP, BCL2), as well as genes implicated in other forms of kidney disease (PODXL, ELMO1, FRMD3, MYH9, APOA1). Pathway analysis highlighted increased gene enrichment in focal adhesion, extracellular matrix-receptor interaction, and axon guidance pathways. In summary, using transgenic sickle mice, we observed that inheritance of the HbS mutation is associated with glomerular and tubular damage and identified several candidate genes and pathways for future investigation in sickle cell trait and sickle cell anemia-related kidney disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Prolonged Nightly Fasting and Breast Cancer Risk: Findings from NHANES (2009-2010).

PubMed

Marinac, Catherine R; Natarajan, Loki; Sears, Dorothy D; Gallo, Linda C; Hartman, Sheri J; Arredondo, Elva; Patterson, Ruth E

2015-05-01

A novel line of research has emerged, suggesting that daily feeding-fasting schedules that are synchronized with sleep-wake cycles have metabolic implications that are highly relevant to breast cancer. We examined associations of nighttime fasting duration with biomarkers of breast cancer risk among women in the 2009-2010 U.S. National Health and Nutrition Examination Survey. Dietary, anthropometric, and HbA1c data were available for 2,212 women, and 2-hour postprandial glucose concentrations were available for 1,066 women. Nighttime fasting duration was calculated using 24-hour food records. Separate linear regression models examined associations of nighttime fasting with HbA1c and 2-hour glucose concentrations. Logistic regression modeled associations of nighttime fasting with elevated HbA1c (HbA1c ≥ 39 mmol/mol or 5.7%) and elevated 2-hour glucose (glucose ≥ 140 mg/dL). All models adjusted for age, education, race/ethnicity, body mass index, total kcal intake, evening kcal intake, and the number of eating episodes per day. Each 3-hour increase in nighttime fasting (roughly 1 SD) was associated with a 4% lower 2-hour glucose measurement [β, 0.96; 95% confidence interval (CI), 0.93-1.00; P < 0.05], and a nonstatistically significant decrease in HbA1c. Logistic regression models indicate that each 3-hour increase in nighttime fasting duration was associated with roughly a 20% reduced odds of elevated HbA1c (OR, 0.81; 95% CI, 0.68-0.97; P < 0.05) and nonsignificantly reduced odds of elevated 2-hour glucose. A longer nighttime duration was significantly associated with improved glycemic regulation. Randomized trials are needed to confirm whether prolonged nighttime fasting could improve biomarkers of glucose control, thereby reducing breast cancer risk. ©2015 American Association for Cancer Research.

Poly (3-hydroxybutyrate-co-15 mol% 3hydroxyhexanoate)/ZnO nanocomposites by solvent casting method: a study of optical, surface, and thermal properties

NASA Astrophysics Data System (ADS)

Vishnu Chandar, J.; Shanmugan, S.; Mutharasu, D.; Azlan, A. A.

2017-01-01

Biopolymer nanocomposites are gaining interest due to their biodegradable and biocompatible nature, with exceptional properties which are superior to those of pure polymer and that can be used as a replacement for petroleum-based plastics. Pure poly (3-hydroxybutyrate-co-15 mol% 3hydroxyhexanoate) [P(3HB-co-15 mol% 3HHx)] and ZnO nanoparticles (NPs) reinforced P(3HB-co-15 mol% 3HHx) composite films were prepared and their morphological, optical, and thermal analyses were carried out to study the effect of ZnO NPs on P(3HB-co-15 mol% 3HHx) copolymer. From optical analysis, a strong absorbance peak at ˜358 nm with high intensity for 5%ZnO NPs reinforced P(3HB-co-15 mol% 3HHx) composite sample was observed. Nano-sized particles and their increased trend with increased ZnO NPs concentration were confirmed by UV-Vis spectral analysis. In addition to that, ZnO NPs reduced the reflectance behaviour of P(3HB-co-15 mol% 3HHx) copolymer in the UV region. Field emission scanning electron microscopy analysis evidenced that the pore numbers and their size in the composite matrix was decreased with increased ZnO NPs concentration. Improved thermal stability and melting temperature of the copolymer matrix was confirmed by thermogravimetric analysis and differential scanning calorimetry analysis, respectively. ZnO NPs acted as a retarding agent and showed a low degree of crystallinity (X c ) and enthalpy of melting (ΔH M ). From these observations, ZnO NPs reinforced P(3HB-co-15 mol% 3HHx) composites can be integrated with suitable resin and can be used as an LED encapsulant to block UV rays. They can also be used as a UV blocking coating material in the glass, plastic, and textile industries, for NIR shielding and food packaging applications.

Low haemoglobin concentration in Tibetan males is associated with greater high-altitude exercise capacity.

PubMed

Simonson, T S; Wei, G; Wagner, H E; Wuren, T; Qin, G; Yan, M; Wagner, P D; Ge, R L

2015-07-15

Tibetans living at high altitude have adapted genetically such that many display a low erythropoietic response, resulting in near sea-level haemoglobin (Hb) concentration. We hypothesized that absence of the erythropoietic response would be associated with greater exercise capacity compared to those with high [Hb] as a result of beneficial changes in oxygen transport. We measured, in 21 Tibetan males with [Hb] ranging from 15.2 g dl(-1) to 22.9 g dl(-1) (9.4 mmol l(-1) to 14.2 mmol l(-1) ), [Hb], ventilation, volumes of O2 and CO2 utilized at peak exercise (V̇O2 and V̇CO2), heart rate, cardiac output and arterial blood gas variables at peak exercise on a cycle ergometer at ∼4200 m. Lung and muscle O2 diffusional conductances were computed from these measurements. [Hb] was related (negatively) to V̇O2 kg(-1) (r = -0.45, P< 0.05), cardiac output kg(-1) (QT kg(-1) , r = -0.54, P < 0.02), and O2 diffusion capacity in muscle (DM kg(-1) , r = -0.44, P<0.05), but was unrelated to ventilation, arterial partial pressure of O2 (PaO2) or pulmonary diffusing capacity. Using multiple linear regression, variance in peak V̇O2 kg(-1) was primarily attributed to QT, DM, and PCO2 (R(2) = 0.88). However, variance in pulmonary gas exchange played essentially no role in determining peak V̇O2. These results (1) show higher exercise capacity in Tibetans without the erythropoietic response, supported mostly by cardiac and muscle O2 transport capacity and ventilation rather than pulmonary adaptations, and (2) support the emerging hypothesis that the polycythaemia of altitude, normally a beneficial response to low cellular PO2, may become maladaptive if excessively elevated under chronic hypoxia. The cause and effect relationships among [Hb], QT, DM, and PCO2 remain to be elucidated. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Genotoxic and Antigenotoxic Potential of Momordica charantia Linn (Cucurbitaceae) in the Wing Spot Test of Drosophila melanogaster.

PubMed

Guterres, Zaira Rosa; Zanetti, Thalita Alves; Sennes-Lopes, Tiago Felipe; da Silva, Ana Francisca Gomes

2015-10-01

Momordica charantia, popularly known as bitter melon, is a plant widely used in ethnobotanical medicine. It has antibacterial, antifungal, anthelmintic, antidiabetic, antiviral, and antimalarial activities, among others. The goal of this study was to evaluate the genotoxic and/or antigenotoxic activity of the aqueous extracts obtained from the aerial parts and fruit of this plant by means of the Drosophila melanogaster wing spot test. Third-stage larvae that obtained standard (ST) cross and high bioactivation (HB) cross were treated with aqueous extracts of the aerial parts (IQA) and fruit (IQF) of M. charantia, following two protocols (genotoxicity and antigenotoxicity). The aqueous extracts are not genotoxic in lower concentrations. The frequencies of mutant spots observed in the descendants of the ST and HB crosses treated with doxorubicin (DXR) alone were 8.65 and 9.25, respectively, whereas in those cotreated with IQA and DXR, the frequencies ranged from 15.90 to 29 in the ST cross and from 15.05 to 24.78 in the HB cross. In cotreatment with IQF, the frequencies ranged from 30.10 to 30.65 in the ST cross and from 13.60 to 14.50 in the HB cross, whereas the frequencies obtained with DXR were 32.50 in the ST cross and 26.00 in the HB cross. In conclusion, the IQA has a synergistic effect, enhancing the genotoxicity of DXR in the ST cross and the HB cross, whereas the IQF has antigenotoxic effects in the HB cross.

In Vitro Analysis of d-Lactyl-CoA-Polymerizing Polyhydroxyalkanoate Synthase in Polylactate and Poly(lactate- co-3-hydroxybutyrate) Syntheses.

PubMed

Matsumoto, Ken'ichiro; Iijima, Midori; Hori, Chiaki; Utsunomia, Camila; Ooi, Toshihiko; Taguchi, Seiichi

2018-05-15

Engineered d-lactyl-coenzyme A (LA-CoA)-polymerizing polyhydroxyalkanoate synthase (PhaC1 Ps STQK) efficiently produces poly(lactate- co-3-hydroxybutyrate) [P(LA- co-3HB]) copolymer in recombinant Escherichia coli, while synthesizing tiny amounts of poly(lactate) (PLA)-like polymers in recombinant Corynebacterium glutamicum. To elucidate the mechanisms underlying the interesting phenomena, in vitro analysis of PhaC1 Ps STQK was performed using homo- and copolymerization conditions of LA-CoA and 3-hydroxybutyryl-CoA. PhaC1 Ps STQK polymerized LA-CoA as a sole substrate. However, the extension of PLA chains completely stalled at a molecular weight of ∼3000, presumably due to the low mobility of the generated polymer. The copolymerization of these substrates only proceeded with a low concentration of LA-CoA. In fact, the intracellular LA-CoA concentration in P(LA- co-3HB)-producing E. coli was below the detection limit, while that in C. glutamicum was as high as acetyl-CoA levels. Therefore, it was concluded that the mobility of polymerized products and LA-CoA concentration are dominant factors characterizing PLA and P(LA- co-3HB) biosynthetic systems.

Hemodynamic responses on prefrontal cortex related to meditation and attentional task

PubMed Central

Deepeshwar, Singh; Vinchurkar, Suhas Ashok; Visweswaraiah, Naveen Kalkuni; Nagendra, Hongasandra RamaRao

2015-01-01

Recent neuroimaging studies state that meditation increases regional cerebral blood flow (rCBF) in the prefrontal cortex (PFC). The present study employed functional near infrared spectroscopy (fNIRS) to evaluate the relative hemodynamic changes in PFC during a cognitive task. Twenty-two healthy male volunteers with ages between 18 and 30 years (group mean age ± SD; 22.9 ± 4.6 years) performed a color-word stroop task before and after 20 min of meditation and random thinking. Repeated measures ANOVA was performed followed by a post hoc analysis with Bonferroni adjustment for multiple comparisons between the mean values of “During” and “Post” with “Pre” state. During meditation there was an increased in oxy-hemoglobin (ΔHbO) and total hemoglobin (ΔTHC) concentration with reduced deoxy-hemoglobin (ΔHbR) concentration over the right prefrontal cortex (rPFC), whereas in random thinking there was increased ΔHbR with reduced total hemoglobin concentration on the rPFC. The mean reaction time (RT) was shorter during stroop color word task with concomitant reduction in ΔTHC after meditation, suggestive of improved performance and efficiency in task related to attention. Our findings demonstrated that meditation increased cerebral oxygenation and enhanced performance, which was associated with activation of the PFC. PMID:25741245

Possible determinants and spatial patterns of anaemia among young children in Nigeria: a Bayesian semi-parametric modelling.

PubMed

Gayawan, Ezra; Arogundade, Ekundayo D; Adebayo, Samson B

2014-03-01

Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health and socioeconomic development. This paper examines the possible relationship between Hb concentration and severity of anaemia with individual and household characteristics of children aged 6-59 months in Nigeria; and explores possible geographical variations of these outcome variables. Data on Hb concentration and severity of anaemia in children aged 6-59 months that participated in the 2010 Nigeria Malaria Indicator Survey were analysed. A semi-parametric model using a hierarchical Bayesian approach was adopted to examine the putative relationship of covariates of different types and possible spatial variation. Gaussian, binary and ordinal outcome variables were considered in modelling. Spatial analyses reveal a distinct North-South divide in Hb concentration of the children analysed and that states in Northern Nigeria possess a higher risk of anaemia. Other important risk factors include the household wealth index, sex of the child, whether or not the child had fever or malaria in the 2 weeks preceding the survey, and children under 24 months of age. There is a need for state level implementation of specific programmes that target vulnerable children as this can help in reversing the existing patterns.

A Burkholderia sacchari cell factory: production of poly-3-hydroxybutyrate, xylitol and xylonic acid from xylose-rich sugar mixtures.

PubMed

Raposo, Rodrigo S; de Almeida, M Catarina M D; de Oliveira, M da Conceição M A; da Fonseca, M Manuela; Cesário, M Teresa

2017-01-25

Efficient production of poly-3-hydroxybutyrate (P(3HB)) based on glucose-xylose mixtures simulating different types of lignocellulosic hydrolysate (LCH) was addressed using Burkholderia sacchari, a wild strain capable of metabolizing both sugars and producing P(3HB). Carbon catabolite repression was avoided by maintaining glucose concentration below 10g/L. Xylose concentrations above 30g/L were inhibitory for growth and production. In fed-batch cultivations, pulse size and feed addition rate were controlled in order to reach high productivities and efficient sugar consumptions. High xylose uptake and P(3HB) productivity were attained with glucose-rich mixtures (glucose/xylose ratio in the feed=1.5w/w) using high feeding rates, while with xylose-richer feeds (glucose/xylose=0.8w/w), a lower feeding rate is a robust strategy to avoid xylose build-up in the medium. Xylitol production was observed with xylose concentrations in the medium above 30-40g/L. With sugar mixtures featuring even lower glucose/xylose ratios, i.e. xylose-richer feeds (glucose/xylose=0.5), xylonic acid (a second byproduct) was produced. This is the first report of the ability of Burkholderia sacchari to produce both xylitol and xylonic acid. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiple oxygen entry pathways in globin proteins revealed by intrinsic pathway identification method

NASA Astrophysics Data System (ADS)

Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

2015-12-01

Each subunit of human hemoglobin (HbA) stores an oxygen molecule (O2) in the binding site (BS) cavity near the heme group. The BS is buried in the interior of the subunit so that there is a debate over the O2 entry pathways from solvent to the BS; histidine gate or multiple pathways. To elucidate the O2 entry pathways, we executed ensemble molecular dynamics (MD) simulations of T-state tetramer HbA in high concentration O2 solvent to simulate spontaneous O2 entry from solvent into the BS. By analyzing 128 independent 8 ns MD trajectories by intrinsic pathway identification by clustering (IPIC) method, we found 141 and 425 O2 entry events into the BS of the α and β subunits, respectively. In both subunits, we found that multiple O2 entry pathways through inside cavities play a significant role for O2 entry process of HbA. The rate constants of O2 entry estimated from the MD trajectories correspond to the experimentally observed values. In addition, by analyzing monomer myoglobin, we verified that the high O2 concentration condition can reproduce the ratios of each multiple pathway in the one-tenth lower O2 concentration condition. These indicate the validity of the multiple pathways obtained in our MD simulations.

Cerebrovascular Responses During Lower Body Negative Pressure-Induced Presyncope

NASA Technical Reports Server (NTRS)

Kuriyama, Kana; Watenpaugh, D. E.; Hargens, Alan R.; Ueno, T.; Ballard, R. E.; Fortney, S. M.

1996-01-01

Reduced orthostatic tolerance is commonly observed after space flight, occasionally causing presyncopal conditions. Although the cerebrovascular system may play an important role in presyncope, there have been few reports concerning cerebral hemodynamics during presyncope. The purpose of this study was to investigate cerebrovascular responses during presyncope induced by lower body negative pressure (LBNP). Seven healthy male volunteers were exposed to LBNP in steps of -10 mmHg every 3 min until presyncopal symptoms were detected. Blood pressure (BP) and heart rate (HR) were measured with a finger cuff. Cerebral tissue oxy- and deoxy- hemoglobin (Hb) concentrations were estimated using near infrared spectroscopy (NIRS). Cerebral blood flow (CBF) velocity at the middle cerebral artery was measured with Transcranial Doppler Sonography (TCD). We focused on the data during the 2 min before endpoint. BP marked a gradual decrease (91 to 86 mmHg from 2 min to 30 sec before endpoint), which was accelerated along with HR decrease during the final 30 sec (86 to 71 mmHg). Cerebral oxy-Hb concentration decreases as presyncope is approached while total-Hb concentration remains fairly constant. TCD reveals a decrease in the CBF velocity. The TCD and NIRS results suggest that CBF decreases along with the BP decrease. Cerebrovascular responses during presyncope are closely related to cardiovascular responses.

Human hemoglobin structural and functional alterations and heme degradation upon interaction with benzene: A spectroscopic study.

PubMed

Hosseinzadeh, Reza; Moosavi-Movahedi, Ali Akbar

2016-03-15

Here, the effect of benzene on hemoglobin structure, stability and heme prosthetic group integrity was studied by different methods. These included UV-vis absorption spectrophotometry, normal and synchronous fluorescence techniques, and differential scanning calorimetry (DSC). Our results indicated that benzene has high hemolytic potential even at low concentrations. The UV-vis spectroscopic results demonstrated that benzene altered both the globin chain and the heme prosthetic group of hemoglobin increasing met- and deoxy-Hb, while decreasing oxy-Hb. However, with increasing benzene the concentration of all species decreased due to heme destruction. The spectrophotometric results show that benzene has a high potential for penetrating the hydrophobic pocket of hemoglobin. These results were consistent with the molecular docking simulation results of benzene-hHb. Aggregation and thermal denaturation studies show that the increased benzene concentration induced hemoglobin aggregation with a decrease in stability, which is consistent with the DSC results. Conventional fluorescence spectroscopy revealed that the heme degradation species were produced in the presence of benzene. The results of constant wavelength synchronous fluorescence spectroscopy (CWSFS) indicated that at least five heme-degraded species were produced. Together, our results indicated that benzene has adverse effects on hemoglobin structure and function, and heme degradation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2009-04-01

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

Gender Difference in Aerobic Capacity and the Contribution by Body Composition and Haemoglobin Concentration: A Study in Young Indian National Hockey Players

PubMed Central

Kailashiya, Jyotsna

2016-01-01

Introduction Although gender difference in aerobic capacity is known, the contributing factors have been researched seldom. Aim To investigate the gender gap and the contribution by percentage Body Fat (BF), Body Mass Index (BMI) and haemoglobin concentration Hb. Materials and Methods The study was conducted on 30 (17 males, 13 females) training status matched young hockey players. Healthy players who were playing upto national level competition were included. BW (Body Weight), BF, BMI, LBM (Lean Body Mass), rHR (restring Heart Rate), HRR (Heart Rate Recovery), Hb, a/rVO2max (absolute/relative), a/rPWC (Physical Work Capacity) and RMR (Resting Metabolic Rate) were measured and analysed. Results There was significant gender difference in the measured parameters. Difference in a/rVO2max remained significant even after controlling for BF, BMI and Hb. Multiple regression and correlation analysis revealed gender difference in VO2max/LBM was due to: BMI(31.91%)>BF(27.60%)>Hb(9.91%). BMI also significantly contributed 3.66% of VO2max/LBM variance, independent of that by gender. Difference in RMR was mainly related to LBM, BF and BMI. Conclusion The study provided an understanding for gender gap in aerobic capacity. Differences in BMI & BF were one of the main reasons. PMID:28050360

Maternal and Perinatal Outcomes in Second Hemoglobin Measurement in Nonanemic Women at First Booking: Effect of Altitude of Residence in Peru

PubMed Central

Gonzales, Gustavo F.; Tapia, Vilma; Fort, Alfredo L.

2012-01-01

Objective. To determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes. Methods. This is a secondary analysis of a large database obtained from the Perinatal Information System in Peru which includes 379,816 pregnant women and their babies from 43 maternity units in Peru. Results. Most women remained with normal hemoglobin values at second measurement (75.1%). However, 21.4% of women became anemic at the second measurement. In all, 2.8% resulted with moderate/severe anemia and 3.5% with erythrocytosis (Hb>14.5 g/dL). In all cases Hb was higher as altitude increased. Risk for moderate/severe anemia increased associated with higher gestational age at second measurement of hemoglobin, BMI <19.9 kg/m2, living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe anemia was observed with normal high Hb level at first booking living at moderate and high altitude, and high BMI. Conclusion. Prevalence of anemia increases as pregnancy progress, and that a normal value at first booking may not be considered sufficient as Hb values should be observed throughout pregnancy. BMI was a risk for anemia in a second measurement. PMID:22577573

Maternal and perinatal outcomes in second hemoglobin measurement in nonanemic women at first booking: effect of altitude of residence in peru.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Fort, Alfredo L

2012-01-01

Objective. To determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes. Methods. This is a secondary analysis of a large database obtained from the Perinatal Information System in Peru which includes 379,816 pregnant women and their babies from 43 maternity units in Peru. Results. Most women remained with normal hemoglobin values at second measurement (75.1%). However, 21.4% of women became anemic at the second measurement. In all, 2.8% resulted with moderate/severe anemia and 3.5% with erythrocytosis (Hb>14.5 g/dL). In all cases Hb was higher as altitude increased. Risk for moderate/severe anemia increased associated with higher gestational age at second measurement of hemoglobin, BMI <19.9 kg/m(2), living without partner, <5 antenatal care visits, first parity, multiparity, and preeclampsia. Lower risk for moderate/severe anemia was observed with normal high Hb level at first booking living at moderate and high altitude, and high BMI. Conclusion. Prevalence of anemia increases as pregnancy progress, and that a normal value at first booking may not be considered sufficient as Hb values should be observed throughout pregnancy. BMI was a risk for anemia in a second measurement.

Bioactive natural constituents from lemongrass tea and erythropoiesis boosting effects: potential use in prevention and treatment of anemia.

PubMed

Ekpenyong, Christopher E; Daniel, Nyebuk E; Antai, Atim B

2015-01-01

This study assessed the effects of lemongrass (Cymbopogon citratus) tea on hematologic indices in human volunteers. One hundred five subjects (55 men and 50 women), aged 18 to 35 years, were randomly assigned to groups set to orally receive infusion prepared from 2, 4, or 8 g of C. citratus leaves once daily for 30 days. Assessment of hematologic indices (hemoglobin concentration [Hb], packed cell volume [PCV], red blood cell [RBC] count, mean cell Hb [MCH], mean cell volume [MCV], mean cell Hb concentration [MCHC], total white blood cell [WBC-total] and differentials, and platelets) were performed 1 day before (baseline), and at 10 (acute) and 30 days (subchronic phase) after the initiation of treatment. Results obtained on days 10 and 30 were compared with baseline values. Infusions prepared from C. citratus leaf powder, which tested positive for tannins, saponins, alkaloids, flavonoids, macro- and micronutrients, significantly increased PCV, Hb, and RBC (P<.05) in all subjects, particularly in the subchronic phase of the study. MCH, MCV, and MCHC were not significantly different from baseline values in both the sexes. WBCs and differentials significantly decreased (P<.05) with the exception of neutrophils and lymphocytes, which significantly increased in some or all groups (P<.05), respectively. C. citratus leaf infusion appears to exert an erythropoiesis boosting effect, likely due to some nutritional constituents and its antioxidant and pharmacologic properties.

Assessment of tissue oxygenation of periodontal inflammation in smokers using optical spectroscopy.

PubMed

Liu, Kan-Zhi; Duarte, Poliana Mendes; Santos, Vanessa Renata; Xiang, Xiaoming; Xu, Minqi; Miranda, Tamires Szeremeske; Fermiano, Daiane; Gonçalves, Tiago Eduardo Dias; Sowa, Micheal G

2014-04-01

We have recently developed a periodontal diagnostic tool that was validated in non-smokers with periodontitis. Tobacco smoking is a recognized risk factor for periodontal diseases that can mask gingival bleeding and lead to a false negative diagnosis. Therefore, the purpose of current study is to further validate this instrument in smokers with periodontal diseases. Using a portable optical near-infrared spectrometer, optical spectra were obtained, processed and evaluated from healthy (n = 108), gingivitis (n = 100), and periodontitis (n = 79) sites of 54 systemically healthy smokers. A modified Beer-Lambert unmixing model that incorporates a non-parametric scattering loss function was used to determine the relative contribution of deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2 ) to the overall spectrum. The balance between tissue oxygen delivery and utilization in periodontal tissues was then assessed. Tissue oxygen saturation was significantly decreased in the gingivitis (p = 0.016) and periodontitis (p = 0.007) sites, compared to the healthy sites. There was a trend towards increased concentration of Hb and decreased concentration of HbO2 from healthy to diseased sites, without statistical significance (p > 0.05). Optical spectroscopy can determine tissue oxygenation profiles of healthy and diseased sites in smokers. The spectral profile of periodontal sites in smokers generally resembles those from non-smoking patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In Vivo Interactions Between Cobalt or Ferric Compounds and the Pools of Sulphide in the Blood During and After H2S Poisoning

PubMed Central

Haouzi, Philippe; Sonobe, Takashi; Torsell-Tubbs, Nicole; Prokopczyk, Bogdan; Chenuel, Bruno; Klingerman, Candice M.

2014-01-01

Hydrogen sulphide (H2S), a chemical hazard in oil and gas production, has recently become a dreadful method of suicide, posing specific risks and challenges for the first responders. Currently, there is no proven effective treatment against H2S poisoning and its severe neurological, respiratory or cardiac after-effects. We have recently described that H2S is present in various compartments, or pools, in the body during sulphide exposure, which have different levels of toxicity. The general goals of our study were to (1) determine the concentrations and kinetics of the various pools of hydrogen sulphide in the blood, i.e., gaseous (CgH2S) versus total sulphide, i.e., reacting with monobromobimane (CMBBH2S), during and following H2S exposure in a small and large mammal and (2) establish the interaction between the pools of H2S and a methemoglobin (MetHb) solution or a high dose of hydroxocobalamin (HyCo). We found that CgH2S during and following H2S infusion was similar in sedated sheep and rats at any given rate of infusion/kg and provoked symptoms, i.e., hyperpnea and apnea, at the same CgH2S. After H2S administration was stopped, CgH2S disappeared within 1 min. CMBBH2S also dropped to 2–3μM, but remained above baseline levels for at least 30 min. Infusion of a MetHb solution during H2S infusion produced an immediate reduction in the free/soluble pool of H2S only, whereas CMBBH2S increased by severalfold. HyCo (70 mg/kg) also decreased the concentrations of free/soluble H2S to almost zero; CgH2S returned to pre-HyCo levels within a maximum of 20 min, if H2S infusion is maintained. These results are discussed in the context of a relevant scenario, wherein antidotes can only be administered after H2S exposure. PMID:25015662

An optical material for the detection of β-hydroxybutyrate based on a terbium complex

NASA Astrophysics Data System (ADS)

Wang, Xiaomiao; Chen, Huili; Li, Hua

2014-02-01

A novel Tb3+ complex (Tb(C14H10O4)ṡCl, TbL2) based on benzoic acid (L+H) was successfully synthesized, and gave a weak green emission in methanol-water (V:V, 4:1, pH 4.49). With the addition of β-hydroxybutyrate (β-HB) to a semi-aqueous solution of TbL2, an increment of the luminescent intensity at 545 nm assigned to 5D4 → 7F5 transition of Tb3+ was measured, which was evident to the naked eye. The response showed high selectivity for β-HB compared with other common anions including Cl-, NO3-, CO32-, PO43-, HPO42-, HPO4-, CO42-, PO74-, SO42-, lactate, AcO-, citrate, malate therefore it has the potential to be applied as a luminescent sensor for β-HB.

Boronate-functionalized hydrogel as a novel biosensing interface for the glycated hemoglobin A1c (HbA1c) based on the competitive binding with signaling glycoprotein.

PubMed

Han, Yong Duk; Kim, Ka Ram; Park, Yoo Min; Song, Seung Yeon; Yang, Yong Ju; Lee, Kangsun; Ku, Yunhee; Yoon, Hyun C

2017-08-01

According to recent increases in public healthcare costs associated with diabetes mellitus, the development of new glycemic monitoring techniques based on the biosensing of glycated hemoglobin A1c (HbA 1c ), a promising long-term glycemic biomarker, has become a major challenge. In the development of HbA 1c biosensors for point-of-care applications, the selection of an effective biorecognition layer that provides a high reaction yield and specificity toward HbA 1c is regarded as the most significant issue. To address this, we developed a novel HbA 1c biosensing interfacial material by the integration of boronate hydrogel with glass fiber membrane. In the present study, a new boronate-functionalized hydrogel was designed and spatio-selectively photopolymerized on a hydrophilic glass fiber membrane by using N-hydroxyethyl acrylamide, 3-(acrylamido)phenylboronic acid, and bis(N,N'-methylene-bis-acrylamide). Using this approach, the boronic acid group, which specifically recognizes the cis-diol residue of glucose on the HbA 1c molecule, can be three-dimensionally coated on the surface of the glass fiber network with a high density. Because this network structure of boronate hydrogel-grafted fibers enables capillary-driven fluid control, facile HbA 1c biosensing in a lateral flow assay concept could be accomplished. On the proposed HbA 1c biosensing interface, various concentrations of HbA 1c (5-15%) in blood-originated samples were sensitively measured by a colorimetric assay using horseradish peroxidase, a glycoenzyme can generate chromogenic signal after the competitive binding against HbA 1c to the boronic acid residues. Based on the demonstrated advantages of boronate hydrogel-modified membrane including high analytical performance, easy operation, and cost-effectiveness, we expect that the proposed biorecognition interfacial material can be applied not only to point-of-care HbA 1c biosensors, but also to the quantitative analysis of other glycoprotein biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic approach of Sickled Cell Anemia

NASA Astrophysics Data System (ADS)

Abkarian, Manouk; Loiseau, Etienne; Massiera, Gladys

2012-11-01

Sickle Cell Anemia is a disorder of the microcirculation caused by a genetic point mutation that produces an altered hemoglobin protein called HbS. HbS self-assembles reversibly into long rope like fibers inside the red blood cells. The resulting distorded sickled red blood cells are believed to block the smallest capillaries of the tissues producing anemia. Despite the large amount of work that provided a thorough understanding of HbS polymerization in bulk as well as in intact red blood cells at rest, no consequent cellular scale approaches of the study of polymerization and its link to the capillary obstruction have been proposed in microflow, although the problem of obstruction is in essence a circulatory problem. Here, we use microfluidic channels, designed to mimic physiological conditions (flow velocity, oxygen concentration, hematocrit...) of the microcirculation to carry out a biomimetic study at the cellular scale of sickled cell vaso-occlusion. We show that flow geometry, oxygen concentration, white blood cells and free hemoglobin S are essential in the formation of original cell aggregates which could play a role in the vaso-occlusion events.

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

PubMed

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

2014-12-01

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

Blood circulatory system for noninvasive diagnostics

NASA Astrophysics Data System (ADS)

Fricke, D.; Kraitl, J.; Ewald, H.

2013-02-01

Based on the human circulatory system, an artificial blood circulatory system was developed to allow the controlled variation of the following blood parameters: total hemoglobin concentration (ctHb), oxyhemoglobin (O2Hb) methemoglobin (MetHb) and carboxyhemoglobin (COHb). The optical properties of the blood were observed by online spectrometer measurements. The purpose of this was to observe and quantify the absorption, transmission and scattering properties of human whole blood in the wavelength range of 400 to 1700 nm. All the non-invasive measurements of the whole blood transmission-spectra were compared with sample results obtained by a Blood Gas Analyzer (BGA) to validate the results. For all measurements, donor erythrocyte concentrates were used. The concentration of hemoglobin was changed by adding fixed amounts of blood plasma to the erythrocyte concentrate. Oxygen saturation and COHb were adjusted by a continuous flow of N2, N2-CO and compressed air through a hollow fibre membrane oxygenator. Different methemoglobin concentrations were adjusted by using natrium nitrite. The blood temperature was kept constant at 37 °C via a tube heating mechanism, with a separate circulation of water passing through the membrane Oxygenator. The Temperature and pressure of the system were automatically controlled and monitored. The model was also used to test new non-invasive measurement systems, and for this reason special cuvettes were designed to imitate human tissue and generate plethysmographical signals. In the future, the blood circulatory system has the potential to be used for testing, validating and also to calibrate newly developed optical prototype devices. It can also be used to further investigate blood components of interest.

The effects of arterial carbon dioxide partial pressure and sevoflurane on capillary venous cerebral blood flow and oxygen saturation during craniotomy.

PubMed

Klein, Klaus Ulrich; Glaser, Martin; Reisch, Robert; Tresch, Achim; Werner, Christian; Engelhard, Kristin

2009-07-01

Intraoperative routine monitoring of cerebral blood flow and oxygenation remains a technological challenge. Using the physiological principle of carbon dioxide reactivity of cerebral vasculature, we investigated a recently developed neuromonitoring device (oxygen-to-see, O2C device) for simultaneous measurements of regional cerebral blood flow (rvCBF), blood flow velocity (rvVelo), oxygen saturation (srvO2), and hemoglobin amount (rvHb) at the capillary venous level in patients subjected to craniotomy. Twenty-six neurosurgical patients were randomly assigned to anesthesia with 1.4% or 2.0% sevoflurane end-tidal concentration. After craniotomy, a fiberoptic probe was applied on a macroscopically healthy surface of cerebral tissue next to the site of surgery. Simultaneous measurements in 2 and 8 mm cerebral depth were performed in each patient during lower (35 mm Hg) and higher (45 mm Hg) levels (random order) of arterial carbon dioxide partial pressure (PaCO2). The principle of these measurements relies on the combination of laser-Doppler flowmetry (rvCBF, rvVelo) and photo-spectrometry (srvO2, rvHb). Linear models were fitted to test changes of end points (rvCBF, rvVelo, srvO2, rvHb) in response to lower and higher levels of PaCO2, 1.4% and 2.0% sevoflurane end-tidal concentration, and 2 and 8 mm cerebral depth. RvCBF and rvVelo were elevated by PaCO2 independent of sevoflurane concentration in 2 and 8 mm depth of cerebral tissue (P < 0.001). Higher PaCO2 induced an increase in mean srvO2 from 50% to 68% (P < 0.001). RvVelo (P < 0.001) and srvO2 (P = 0.007) were higher in 8 compared with 2 mm cerebral depth. RvHb was not influenced by alterations in PaCO2 but positively correlated to sevoflurane concentration (P = 0.005). Increases in rvCBF and rvVelo by PaCO2 suggest preserved hypercapnic vasodilation under anesthesia with sevoflurane 1.4% and 2.0% end-tidal concentration. A consecutive increase in srvO2 implies that cerebral arteriovenous difference in oxygen was decreased by elevated PaCO2. Unchanged levels of rvHb signify that there was no blood loss during measurements. Data suggest that the device allows detection of local changes in blood flow and oxygen saturation in response to different PaCO2 levels in predominant venous cerebral microvessels.

Sea-level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m.

PubMed

Wagner, P D; Simonson, T S; Wei, G; Wagner, H E; Wuren, T; Qin, G; Yan, M; Ge, R L

2015-11-01

What is the topic of this review? Recent developments link relatively lower hemoglobin concentration in Tibetans at high altitude to exercise capacity and components of oxygen transport. What advances does it highlight? Haemoglobin concentration (ranging from 15.2 to 22.9 g dl(-1) ) in Tibetan males was negatively associated with peak oxygen (O2 ) uptake per kilogram, cardiac output and muscle O2 diffusion conductance. Most variance in the peak O2 uptake per kilogram of Tibetan males was attributed to cardiac output, muscle diffusional conductance and arterial partial pressure of CO2 . The mechanisms underlying these differences in oxygen transport in Tibetans require additional analyses. Despite residence at >4000 m above sea level, many Tibetan highlanders, unlike Andean counterparts and lowlanders at altitude, exhibit haemoglobin concentration ([Hb]) within the typical sea-level range. Genetic adaptations in Tibetans are associated with this relatively low [Hb], yet the functional relevance of the lower [Hb] remains unknown. To address this, we examined each major step of the oxygen transport cascade [ventilation (VE), cardiac output (QT) and diffusional conductance in lung (DL) and muscle (DM)] in Tibetan males at maximal exercise on a cycle ergometer. Ranging from 15.2 to 22.9 g dl(-1) , [Hb] was negatively associated with peak O2 uptake per kilogram (r = -0.45, P < 0.05) and both cardiac output (QT/kg: r = -0.54, P < 0.02) and muscle O2 diffusion conductance (DM/kg: r = -0.44, P < 0.05) but not ventilation, arterial partial pressure of O2 or pulmonary diffusing capacity. Most variance in peak O2 uptake per kilogram was attributed to QT, DM and arterial partial pressure of CO2 (r(2)  = 0.90). In summary, lack of polycythaemia in Tibetans is associated with increased exercise capacity, which is explained by elevated cardiac, muscle and, to a small extent, ventilatory responses rather than pulmonary gas exchange. Whether lower [Hb] is the cause or result of these changes in O2 transport or is causally unrelated will require additional study. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy

PubMed Central

2012-01-01

Background Primigravidity is one of the main risk factors for both malaria and anaemia. Since the implementation of intermittent preventive treatment (IPTp) in sub-Saharan Africa, the relationship between anaemia and gravidity and its evolution during pregnancy has been little explored. This study aimed to evaluate the impact of gravidity on the variation of haemoglobin during pregnancy according to the timing of gestation. Methods Data from three studies carried out in nearby areas in south Benin (Ouidah, Comé, Allada) between 2005 and 2012 were analysed. At inclusion (first antenatal visit, ANV1) women’s age, area of residence, schooling, gravidity, gestational age, weight and height were recorded. Thick blood smears were performed on ANV1, second visit (ANV2) and at delivery. In Allada, women’s serum ferritin and CRP concentrations were also assessed. The impact of gravidity on maternal haemoglobin (Hb) was analysed using a logistic or linear regression depending on the outcome. The statistical significance was set to P < 0.05. Results In total, data from 3,591 pregnant women were analysed. Both univariate and multivariate analyses showed a constant association between Hb concentrations and gravidity in the three periods of Hb assessment (ANV1, ANV2 and delivery). Mean Hb concentration was significantly lower in primigravidae than in multigravidae at ANV1 (mean difference = -2.4 g/L, CI 95%: [-3.4, -1.4], P < 0.001). Afterwards, there was a significant increase in primigravidae only, with a tendency to reversal between primigravidae and multigravidae, which was confirmed at delivery (mean difference = 2.8 g/L, CI 95%: [1.3, 4.2], P < 0.001). The prevalence of malaria infection was halved between ANV1 and delivery in primigravidae while it decreased by only 38% among multigravidae, who were less prone to malaria infection (prevalence at ANV1, 20% and 10% respectively). Iron deficiency was more common in multigravidae, and it decreased slightly in this group between ANV1 and delivery. Conclusion In a context of IPTp, Hb levels improved progressively throughout pregnancy in primigravidae, likely as a result of reduction in malaria infection. In multigravidae, the improvement was less perceptible and anaemia was mainly due to iron deficiency. PMID:23088844

Unfavorable inflammatory profile in adults at risk of type 2 diabetes identified by hemoglobin A1c levels according to the American Diabetes Association criteria.

PubMed

Fiorentino, T V; Hribal, M L; Perticone, M; Andreozzi, F; Sciacqua, A; Perticone, F; Sesti, G

2015-04-01

We aimed to evaluate the inflammatory profile of individuals with prediabetes defined by HbA1c levels, according to the new American Diabetes Association criteria, and to determine the ability of HbA1c to identify individuals with subclinical inflammation independently of the contribution of other metabolic parameters such as fasting, 1- or 2-h post-load glucose (PG) levels. High sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen, white blood cells (WBC) count and complement C3 (C3) were assessed, and oral glucose tolerance test (OGTT) was performed in 711 adults. Subjects were stratified into three groups according to their HbA1c levels. Poor agreement existed between HbA1c and 2-h PG criteria for identification of individuals with prediabetes (κ coefficient = 0.300). As compared with subjects having HbA1c <5.7 % (39 mmol/mol), individuals with prediabetes (HbA1c 5.7-6.4 %, [39-46 mmol/mol]) exhibited a significant increase of the concentration of five inflammatory markers (hsCRP, ESR, fibrinogen, WBC count, C3) as well as of a cluster of inflammatory markers, as measured by an inflammatory score after adjusting for sex, age, smoking, fasting, 1- and 2-h PG levels. In multiple regression models including sex, age, body mass index, smoking habit, fasting, 1- and 2-h PG levels, and HOMA index, HbA1c levels were significant independent contributors to each of the five inflammatory markers examined. These data suggest that HbA1c is a reliable marker of glucose homeostasis, and may identify individuals at increased risk of diabetes with unfavorable inflammatory profile independently from fasting and 2-h PG levels.

Hemoglobin mass and biological passport for the detection of autologous blood doping.

PubMed

Pottgiesser, Torben; Echteler, Tobias; Sottas, Pierre-Edouard; Umhau, Markus; Schumacher, Yorck Olaf

2012-05-01

The most promising attempt to reveal otherwise undetectable autologous blood doping is the Athlete Biological Passport enabling a longitudinal monitoring of hematological measures. Recently, the determination of hemoglobin mass (tHb) was suggested to be incorporated in the adaptive model of the Athlete Biological Passport. The purpose therefore was to evaluate the performance of tHb as part of the adaptive model for the detection of autologous blood transfusions in a longitudinal blinded study. Twenty-one subjects were divided into a doped group (n = 11) and a control group (n = 10). During the time course of a simulated cycling season (42 wk) including three major competitions (Classics, Grand Tour, World Championships), multiple autologous transfusions of erythrocyte concentrates were assigned in the doped group. A blinded investigator ordered up to 10 tHb measurements (carbon monoxide rebreathing) per subject, mimicking an intelligent doping testing approach in obtaining hematological data (tHb, OFFmass (novel marker including reticulocytes), and respective sequences) for the adaptive model. The final analysis included 199 of 206 overall tHb measurements. The use of tHb, OFFmass, and their sequences as markers of the adaptive model at the 99% specificity level allowed identification of 10 of 11 doped subjects (91% sensitivity) including one false positive in the control group. At the 99.9% specificity level, 8 of 11 subjects were identified without false positives (73% sensitivity). It seems that the problems of tHb determination by carbon monoxide rebreathing limit the application of this method in antidoping. Because of its potential to detect individual abnormalities associated with autologous blood transfusions shown in this study, a method for tHb determination that is compatible with today's standards of testing should be the focus of future research.

Parietal and temporal activity during a multimodal dance video game: an fNIRS study.

PubMed

Tachibana, Atsumichi; Noah, J Adam; Bronner, Shaw; Ono, Yumie; Onozuka, Minoru

2011-10-03

Using functional near infrared spectroscopy (fNIRS) we studied how playing a dance video game employs coordinated activation of sensory-motor integration centers of the superior parietal lobe (SPL) and superior temporal gyrus (STG). Subjects played a dance video game, in a block design with 30s of activity alternating with 30s of rest, while changes in oxy-hemoglobin (oxy-Hb) levels were continuously measured. The game was modified to compare difficult (4-arrow), simple (2-arrow), and stepping conditions. Oxy-Hb levels were greatest with increased task difficulty. The quick-onset, trapezoidal time-course increase in SPL oxy-Hb levels reflected the on-off neuronal response of spatial orienting and rhythmic motor timing that were required during the activity. Slow-onset, bell-shaped increases in oxy-Hb levels observed in STG suggested the gradually increasing load of directing multisensory information to downstream processing centers associated with motor behavior and control. Differences in temporal relationships of SPL and STG oxy-Hb concentration levels may reflect the functional roles of these brain structures during the task period. NIRS permits insights into temporal relationships of cortical hemodynamics during real motor tasks. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Heliotropium bacciferum Forssk. (Boraginaceae) extracts: chemical constituents, antioxidant activity and cytotoxic effect in human cancer cell lines.

PubMed

Aïssaoui, Hanane; Mencherini, Teresa; Esposito, Tiziana; De Tommasi, Nunziatina; Gazzerro, Patrizia; Benayache, Samir; Benayache, Fadila; Mekkiou, Ratiba

2018-02-12

Heliotropium bacciferum (Boraginaceae) is a perennial herb, growing in the Bechar region of Algeria, where it is traditionally used for skin diseases and tonsillitis. Herein, we report the isolation and characterization of sixteen secondary metabolites from the aerial part extracts. They include a sterol (1), megastigman type nor-isoprenoids (2, 3, 4, 6, 8, 10), C-11 terpene lactones (5 and 9), and a monoterpene (7) from the chloroform extract (HB-C); monoterpene glucoside (14), and phenolic compounds (11-13, 15, 16) from the methanol one (HB-M). Their structures were elucidated by spectroscopic methods including 1D and 2D NMR experiments, and ESIMS analysis. HB-M showed a significant and concentration dependent scavenging activity in vitro against the radicals DPPH and ABTS, related to the phenol derivatives (11-13, and 15-16), and HB-C inhibited the growth of colon cancer cell lines, mainly for the presence of the antiproliferative C-11 terpene lactones (5 and 9).

Significant and sustaining elevation of blood oxygen induced by Chinese cupping therapy as assessed by near-infrared spectroscopy

PubMed Central

Li, Ting; Li, Yaoxian; Lin, Yu; Li, Kai

2016-01-01

Cupping therapy has been used in traditional Chinese medicine for thousands of years to relieve muscle pain/tendency/fatigue and to cure or reduce symbols of other diseases. However, its therapeutic effect is sparsely interpreted in the language of modern physiology. To objectively evaluate its therapeutic effect, we focused on dry cupping treatment and utilized near-infrared spectroscopy (NIRS) to assess the concentration change in oxy-hemoglobin ([HbO2]), deoxy-hemoglobin ([Hb]), and blood volume in the course of cupping therapy over 13 volunteers on the infraspinatus muscle, where is usually applied for shoulder pains. Both a prominent drop in [Hb] and a significant elevation in [HbO2] in the tissue surrounding the cupping site were observed during both cupping and post-treatment, manifesting the enhancement of oxygen uptake. This resulting promotion indicates potential positive therapeutic effect of cupping therapy in hemodynamics for facilitating muscular functions. PMID:28101413

Maternal Anemia in Benin: Prevalence, Risk Factors, and Association with Low Birth Weight

PubMed Central

Bodeau-Livinec, Florence; Briand, Valerie; Berger, Jacques; Xiong, Xu; Massougbodji, Achille; Day, Karen P.; Cot, Michel

2011-01-01

We studied the prevalence of anemia during pregnancy and its relationship with low birth weight (LBW; birth weight < 2,500 g) in Benin. We analyzed 1,508 observations from a randomized controlled trial conducted from 2005 to 2008 showing equivalence on the risk of LBW between two drugs for Intermittent Preventive Treatment of malaria during pregnancy (IPTp). Despite IPTp, helminth prophylaxis, and iron and folic acid supplementations, the proportions of women with severe anemia (hemoglobin [Hb] concentration < 80 g/L) and anemia (Hb < 110 g/L) were high throughout pregnancy: 3.9% and 64.7% during the second and 3.7% and 64.1% during the third trimester, but 2.5% and 39.6% at the onset of labor, respectively. Compared with women without anemia (Hb ≥ 110 g/L) during the third trimester, women with severe anemia (Hb < 80 g/L) were at higher risk of LBW after adjustment for potential confounding factors (prevalence ratio [PR] = 2.8; 95% confidence interval [1.4–5.6]). PMID:21896797

Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients.

PubMed

Bataille, Stanislas; Pelletier, Marion; Sallée, Marion; Berland, Yvon; McKay, Nathalie; Duval, Ariane; Gentile, Stéphanie; Mouelhi, Yosra; Brunet, Philippe; Burtey, Stéphane

2017-07-26

The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients. Between June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses. Overall, 240 patients were included in the study. Mean age ± SD was 67.6 ± 16.0 years, 55.4% were men and 42.5% had diabetes mellitus. When compared with ESA treated patients, patients with no ESA had higher hemoglobin (mean 11.4 ± 1.1 versus 10.6 ± 1.2 g/dL; p <0.001), higher transferrin saturation (TSAT, 31.1 ± 16.3% versus 23.1 ± 11.5%; p < 0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In univariate analysis, IAA, IS or PCS plasma concentrations did not differ between the two groups. In the linear model, IAA plasma concentration was not associated with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18) and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R = 0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R = 0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb or ERI was not statistically significant, neither was the association of PCS with ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA, IS or PCS and any anemia parameter did not reach significance. In the third model, univariate analysis showed no intergroup significant differences for IAA and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations. However, when we compared PCS with the other significant characteristics of the five groups to the Low Hb/high ESA (our reference group), the polytomous logistic regression model didn't show any significant difference for PCS. In our study, using three different statistical models, we were unable to show any correlation between IAA, IS and PCS plasmatic concentrations and any anemia parameter in hemodialysis patients. Indolic uremic toxins and PCS have no or a very low effect on anemia parameters.

Reticulocyte and haemoglobin profiles in elite triathletes over four consecutive seasons.

PubMed

Díaz, V; Lombardi, G; Ricci, C; Jacobs, R A; Montalvo, Z; Lundby, C; Banfi, G

2011-12-01

The World Anti-Doping Agency has implemented the Blood Passport in attempt to detect blood doping in athletes. The Blood Passport looks for uncommon changes overtime in reticulocytes percentage (Ret %), as a variable of the OFF-hr score, and haemoglobin concentration ([Hb]) reflecting potential doping violations. Few studies, however, have actually investigated the concurrent stability of Ret % and [Hb] in athletes over extended periods of time, none of which were measured in athletes who undergo strenuous and prolonged physical exercise. Measurements of Ret % and [Hb] were assessed over the course of four competitive seasons in elite triathletes (10 males and seven female). Blood was obtained at the start of the season, precompetitive period, competitive period and at the end of the competitive period. Differences (P<0.001) were observed in both [Hb] and Ret % between genders and there was a high variability between subjects. Neither males nor females exhibited differences in [Hb] across all periods within one season. Within gender, analysis revealed that Ret % varied significantly (P=0.0018) between periods only in female athletes. We conclude that Ret % and [Hb] remain stable over four consecutive seasons in elite triathletes, confirming that both parameters are valid for antidoping purposes based on the Blood Passport. In addition, Ret % fluctuations within one season require further investigation in females. © 2011 Blackwell Publishing Ltd.

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles.

PubMed

Aleluia, Milena Magalhães; Fonseca, Teresa Cristina Cardoso; Souza, Regiana Quinto; Neves, Fábia Idalina; da Guarda, Caroline Conceição; Santiago, Rayra Pereira; Cunha, Bruna Laís Almeida; Figueiredo, Camylla Villas Boas; Santana, Sânzio Silva; da Paz, Silvana Sousa; Ferreira, Júnia Raquel Dutra; Cerqueira, Bruno Antônio Veloso; Gonçalves, Marilda de Souza

2017-01-01

In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the β S -globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α 3.7Kb -thal), as well as the occurrence of clinical events in both SCD genotypes. Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α 3.7Kb -thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

Hyperspectral optical tomography of intrinsic signals in the rat cortex

PubMed Central

Konecky, Soren D.; Wilson, Robert H.; Hagen, Nathan; Mazhar, Amaan; Tkaczyk, Tomasz S.; Frostig, Ron D.; Tromberg, Bruce J.

2015-01-01

Abstract. We introduce a tomographic approach for three-dimensional imaging of evoked hemodynamic activity, using broadband illumination and diffuse optical tomography (DOT) image reconstruction. Changes in diffuse reflectance in the rat somatosensory cortex due to stimulation of a single whisker were imaged at a frame rate of 5 Hz using a hyperspectral image mapping spectrometer. In each frame, images in 38 wavelength bands from 484 to 652 nm were acquired simultaneously. For data analysis, we developed a hyperspectral DOT algorithm that used the Rytov approximation to quantify changes in tissue concentration of oxyhemoglobin (ctHbO2) and deoxyhemoglobin (ctHb) in three dimensions. Using this algorithm, the maximum changes in ctHbO2 and ctHb were found to occur at 0.29±0.02 and 0.66±0.04  mm beneath the surface of the cortex, respectively. Rytov tomographic reconstructions revealed maximal spatially localized increases and decreases in ctHbO2 and ctHb of 321±53 and 555±96  nM, respectively, with these maximum changes occurring at 4±0.2  s poststimulus. The localized optical signals from the Rytov approximation were greater than those from modified Beer–Lambert, likely due in part to the inability of planar reflectance to account for partial volume effects. PMID:26835483

Estimates of the relative and absolute diurnal contributions of fasting and post-prandial plasma glucose over a range of hyperglycaemia in type 2 diabetes.

PubMed

Peter, R; Dunseath, G; Luzio, S D; Owens, D R

2013-09-01

To re-examine the relative and absolute contributions of fasting/pre-prandial glucose (FPG) and post-prandial glucose (PPG) to 24-h hyperglycaemia and HbA1c respectively in non-insulin treated subjects with type 2 diabetes (T2DM). A total of 52 T2DM subjects (37 men) had daytime 12h plasma glucose (PG) profiles determined in response to three serial identical test meals commencing at 08 00h with pre-prandial and frequent post-prandial blood samples collected. The overnight PG profile was derived by projecting the 20 00h glucose concentration to the pre-breakfast value at 08 00h. PPG exposure was calculated above fasting/pre-prandial value for each meal. Excess hyperglycaemia was calculated based on a PG>5.5mmol/L with fasting hyperglycaemia being the difference between the two measurements. The subjects were divided into five groups according to the HbA1c (Group 1<7.0%; Group 2: 7.0-<7.5; Group 3: 7.5-<8.0%; Group 4: 8.0-<9.0%; Group 5:≥9.0%). The 24h relative contribution of PPG exposure and fasting hyperglycaemia to excess hyperglycaemia and the absolute contribution of PPG and fasting hyperglycaemia to excess HbA1c (HbA1c - 5.1%) was calculated. With deteriorating glycaemia, the relative contribution of PPG exposure decreased across the groups from 43.5% (HbA1c<7.0%) to 17.8% (HbA1c≥9.0%), whilst the contributions of fasting hyperglycaemia increased from 56.5% to 82.2% (P=0.004), respectively. The absolute contributions of PPG to excess HbA1c was 0.7%, which remained relatively stable across the spectrum of HbA1c, whilst fasting hyperglycaemia increased significantly from groups 1 to 5 (P<0.001). Fasting hyperglycaemia contributes substantially in all groups, increasing as HbA1c deteriorates. The absolute contribution of PPG to excess HbA1c did not vary across the range of HbA1c, representing a significant relative contribution even in well-controlled subjects with a HbA1c<7.0%. Copyright © 2013. Published by Elsevier Masson SAS.

[Effect of a change in posture on the diurnal variations of fructosamine concentration in diabetic patients].

PubMed

Willms, B; Schumann, E

1990-01-01

Daily profiles of blood glucose, HbA1c, total protein and fructosamine were measured in 10 diabetic patients and the factor fructosamine x 7/g total protein was calculated. Measurements were done at 4 a.m. to be sure that the patients were sleeping for some time, during the day and the following evening at 11 p.m., when the patients were lying again, so that the influence of orthostasis, the difference between bed rest and walking could be demonstrated. The blood glucose profile was typical whereas the HbA1c concentration was very stable and constant. Total protein and fructosamine increased significantly by orthostasis; the correction of fructosamine by total protein diminished the differences, but did not completely eliminate the effect of orthostasis. However, fructosamine should be corrected by the total protein concentration in order to increase the diagnostic value of the parameter.

Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30 year prospective follow-up study.

PubMed

Hokkanen, Laura; Launes, Jyrki; Michelsson, Katarina

2014-01-01

Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood. Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340 µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent's and teacher's assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life. Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR = 4.68). Forty-five per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p < 0.0001) and the ability to complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g., problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse. Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the growth environment of the children, as well as the parents' social groups, education, size of family, type of housing at birth and at 9 years of age. Our findings bear resemblance to disorders of the fronto-striatal network, and also symptoms of the ADHD spectrum were frequent in the HB group suggesting a link of HB to other neurodevelopmental disorders.

Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates—a 30 year prospective follow-up study

PubMed Central

Launes, Jyrki; Michelsson, Katarina

2014-01-01

Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood. Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340 µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent’s and teacher’s assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life. Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR = 4.68). Forty-five per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p < 0.0001) and the ability to complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g., problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse. Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the growth environment of the children, as well as the parents’ social groups, education, size of family, type of housing at birth and at 9 years of age. Our findings bear resemblance to disorders of the fronto-striatal network, and also symptoms of the ADHD spectrum were frequent in the HB group suggesting a link of HB to other neurodevelopmental disorders. PMID:24688870

Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial

PubMed Central

Seferovic, Jelena P; Claggett, Brian; Seidelmann, Sara B; Seely, Ellen W; Packer, Milton; Zile, Michael R; Rouleau, Jean L; Swedberg, Karl; Lefkowitz, Martin; Shi, Victor C; Desai, Akshay S; McMurray, John J V; Solomon, Scott D

2017-01-01

Summary Background Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF. Methods In a post-hoc analysis of the PARADIGM-HF trial, we included 3778 patients with known diabetes or an HbA1c≥6·5% at screening out of 8399 patients with HFrEF who were randomly assigned to treatment with sacubitril/valsartan or enalapril. Of these patients, most (98%) had type 2 diabetes. We assessed changes in HbA1c, triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Times to initiation of oral antihyperglycaemic drugs or insulin in subjects previously not treated with these agents were compared between treatment groups. Findings There were no significant differences in HbA1c concentrations between randomised groups at screening. During the first year of follow-up, HbA1c concentrations decreased by 0·16% (SD 1·40) in the enalapril group and 0·26% (SD 1·25) in the sacubitril/valsartan group (between-group reduction 0·13%, 95% CI 0·05–0·22, p=0·0023). HbA1c concentrations were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-year follow-up (between-group reduction 0·14%, 95% CI 0·06–0·23, p=0·0055). New use of insulin was 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients receiving enalapril (153 [10%]; hazard ratio 0·71, 95% CI 0·56–0·90, p=0·0052). Similarly, fewer patients were started on oral antihyperglycaemic therapy (0·77, 0·58–1·02, p=0·073) in the sacubitril/valsartan group. Interpretation Patients with diabetes and HFrEF enrolled in PARADIGM-HF who received sacubitril/valsartan had a greater long-term reduction in HbA1c than those receiving enalapril. These data suggest that sacubitril/valsartan might enhance glycaemic control in patients with diabetes and HFrEF. PMID:28330649

Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial.

PubMed

Seferovic, Jelena P; Claggett, Brian; Seidelmann, Sara B; Seely, Ellen W; Packer, Milton; Zile, Michael R; Rouleau, Jean L; Swedberg, Karl; Lefkowitz, Martin; Shi, Victor C; Desai, Akshay S; McMurray, John J V; Solomon, Scott D

2017-05-01

Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA 1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF. In a post-hoc analysis of the PARADIGM-HF trial, we included 3778 patients with known diabetes or an HbA 1c ≥6·5% at screening out of 8399 patients with HFrEF who were randomly assigned to treatment with sacubitril/valsartan or enalapril. Of these patients, most (98%) had type 2 diabetes. We assessed changes in HbA 1c , triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Time to initiation of oral antihyperglycaemic drugs or insulin in subjects previously not treated with these agents were compared between treatment groups. There were no significant differences in HbA 1c concentrations between randomised groups at screening. During the first year of follow-up, HbA 1c concentrations decreased by 0·16% (SD 1·40) in the enalapril group and 0·26% (SD 1·25) in the sacubitril/valsartan group (between-group reduction 0·13%, 95% CI 0·05-0·22, p=0·0023). HbA 1c concentrations were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-year follow-up (between-group reduction 0·14%, 95% CI 0·06-0·23, p=0·0055). New use of insulin was 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients receiving enalapril (153 [10%]; hazard ratio 0·71, 95% CI 0·56-0·90, p=0·0052). Similarly, fewer patients were started on oral antihyperglycaemic therapy (0·77, 0·58-1·02, p=0·073) in the sacubitril/valsartan group. Patients with diabetes and HFrEF enrolled in PARADIGM-HF who received sacubitril/valsartan had a greater long-term reduction in HbA 1c than those receiving enalapril. These data suggest that sacubitril/valsartan might enhance glycaemic control in patients with diabetes and HFrEF. Novartis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prefrontal activation in response to emotional words in patients with bipolar disorder and major depressive disorder.

PubMed

Matsubara, Toshio; Matsuo, Koji; Nakashima, Mami; Nakano, Masayuki; Harada, Kenichiro; Watanuki, Toshio; Egashira, Kazuteru; Watanabe, Yoshifumi

2014-01-15

Abnormal emotional processing is involved in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether the neural mechanism underlying this deficit is a trait characteristic of BD and MDD is unclear. The aim of this study was to elucidate the similarities and differences in processing of emotional stimuli between patients with BD and MDD in remission, using functional near-infrared spectroscopy (fNIRS). Thirty-two patients (16 with BD and 16 with MDD) and 20 healthy control subjects matched for age, sex, handedness, and years of education were included. An emotional Stroop task, including happy, sad, and threat words, was used. The relative oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) changes in the frontal region were measured using 52-channels of NIRS. During the threat task, compared to healthy control subjects, patients with BD showed significantly increased [oxy-Hb] in the left inferior frontal region whereas patients with MDD showed significantly increased [oxy-Hb] in the left middle frontal region. During the happy task, compared to healthy control subjects, patients with BD showed significantly decreased [oxy-Hb] in the middle frontal region in both hemispheres. Moreover, patients with BD exhibited decreased [oxy-Hb] and increased [deoxy-Hb] in the superior frontal and middle frontal regions compared to MDD in response to the happy stimulus. No significant differences in [oxy-Hb] or [deoxy-Hb] were seen between the groups during the sad task. These results suggest that abnormal neural responses to emotional stimuli in patients with mood disorders in remission may be a trait characteristic, that negative emotional stimuli are associated with similar prefrontal responses, and that positive emotional stimuli are associated with different prefrontal responses in patients with BD and MDD. These findings indicate that different neural circuits play a role in emotional processing in BD and MDD; this may aid the elucidation of the pathophysiology of these two disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Production and characterization of poly-(3-hydroxybutyrate) from recombinant Escherichia coli grown on cheap renewable carbon substrates.

PubMed

Fonseca, Gustavo Graciano; Fonseca, Gustavo Graciano; de Arruda-Caulkins, Juliana Carvalho; Vasconcellos Antonio, Regina

2008-12-01

Although the biopolymer poly-(3-hydroxybutyrate), P[3HB], presents physicochemical properties that make it an alternative material to conventional plastics, its biotechnological production is quite expensive. As carbon substrates contribute greatly to P[3HB] production cost, the utilization of a cheaper carbon substrate and less demanding micro-organisms should decrease its cost. In the present study a 2(3) factorial experimental design was applied, aiming to evaluate the effects of using hydrolysed corn starch (HCS) and soybean oil (SBO) as carbon substrates, and cheese whey (CW) supplementation in the mineral medium (MM) on the responses, cell dried weigh (DCW), percentage P[3HB] and mass P[3HB] by recombinant Escherichia coli strains JM101 and DH10B, containing the P[3HB] synthase genes from Cupriavidus necator (ex-Ralstonia eutropha). The analysis of effects indicated that the substrates and the supplement and their interactions had positive effect on CDW. Statistically generated equations showed that, at the highest concentrations of HCS, SO and CW, theoretically it should be possible to produce about 2 g L(- 1) DCW, accumulating 50% P[3HB], in both strains. To complement this study, the strain that presented the best results was cultivated in MM added to HCS, SBO and CW (in best composition observed) and complex medium (CM) to compare the obtained P[3HB] in terms of physicochemical parameters. The obtained results showed that the P[3HB] production in MM (1.29 g L( -1)) was approximately 20% lower than in CM (1.63 g L(- 1)); however, this difference can be compensated by the lower cost of the MM achieved by the use of cheap renewable carbon sources. Moreover, using differential scanning calorimetry and thermogravimetry analyses, it was observed that the polymer produced in MM was the one which presented physicochemical properties (Tg and Tf) that were more similar to those found in the literature for P[3HB].

A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong Hill Tracts, Bangladesh.

PubMed

Ley, Benedikt; Alam, Mohammad Shafiul; O'Donnell, James J; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Jahan, Nusrat; Khan, Wasif A; Thriemer, Kamala; Chatfield, Mark D; Price, Ric N; Richards, Jack S

2017-01-01

Glucose-6-phosphate-dehydrogenase-deficiency (G6PDd) is a major risk factor for primaquine-induced haemolysis. There is a need for improved point-of-care and laboratory-based G6PD diagnostics to unsure safe use of primaquine. G6PD activities of participants in a cross-sectional survey in Bangladesh were assessed using two novel quantitative assays, the modified WST-8 test and the CareStart™ G6PD Biosensor (Access Bio), The results were compared with a gold standard UV spectrophotometry assay (Randox). The handheld CareStart™ Hb instrument (Access Bio) is designed to be a companion instrument to the CareStart™ G6PD biosensor, and its performance was compared to the well-validated HemoCue™ method. All quantitative G6PD results were normalized with the HemoCue™ result. A total of 1002 individuals were enrolled. The adjusted male median (AMM) derived by spectrophotometry was 7.03 U/g Hb (interquartile range (IQR): 5.38-8.69), by WST-8 was 7.03 U/g Hb (IQR: 5.22-8.16) and by Biosensor was 8.61 U/g Hb (IQR: 6.71-10.08). The AMM between spectrophotometry and WST-8 did not differ (p = 1.0) but differed significantly between spectrophotometry and Biosensor (p<0.01). Both, WST-8 and Biosensor were correlated with spectrophotometry (rs = 0.5 and rs = 0.4, both p<0.001). The mean difference in G6PD activity was -0.12 U/g Hb (95% limit of agreement (95% LoA): -5.45 to 5.20) between spectrophotometry and WST-8 and -1.74U/g Hb (95% LoA: -7.63 to 4.23) between spectrophotometry and Biosensor. The WST-8 identified 55.1% (49/89) and the Biosensor 19.1% (17/89) of individuals with G6PD activity <30% by spectrophotometry. Areas under the ROC curve did not differ significantly for the WST-8 and Biosensor irrespective of the cut-off activity applied (all p>0.05). Sensitivity and specificity for detecting G6PD activity <30% was 0.55 (95% confidence interval (95%CI): 0.44-0.66) and 0.98 (95%CI: 0.97-0.99) respectively for the WST-8 and 0.19 (95%CI: 0.12-0.29) and 0.99 (95%CI: 0.98-0.99) respectively for the Biosensor. Hb concentrations measured by HemoCue™ and CareStart™ Hb were strongly correlated (rs = 0.8, p<0.001, mean difference = 0.09 g Hb/dL, 95% LoA: -2.15 to 2.34). WST-8 and the CareStart™ G6PD Biosensor represent advances in G6PD diagnostics in resource poor settings, but will require further development before clinical deployment. The CareStart™ Hb instrument produced a precise measure of haemoglobin concentration.

A Comparison of Three Quantitative Methods to Estimate G6PD Activity in the Chittagong Hill Tracts, Bangladesh

PubMed Central

Ley, Benedikt; Alam, Mohammad Shafiul; O’Donnell, James J.; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Jahan, Nusrat; Khan, Wasif A.; Thriemer, Kamala; Chatfield, Mark D.; Price, Ric N.; Richards, Jack S.

2017-01-01

Background Glucose-6-phosphate-dehydrogenase-deficiency (G6PDd) is a major risk factor for primaquine-induced haemolysis. There is a need for improved point-of-care and laboratory-based G6PD diagnostics to unsure safe use of primaquine. Methods G6PD activities of participants in a cross-sectional survey in Bangladesh were assessed using two novel quantitative assays, the modified WST-8 test and the CareStart™ G6PD Biosensor (Access Bio), The results were compared with a gold standard UV spectrophotometry assay (Randox). The handheld CareStart™ Hb instrument (Access Bio) is designed to be a companion instrument to the CareStart™ G6PD biosensor, and its performance was compared to the well-validated HemoCue™ method. All quantitative G6PD results were normalized with the HemoCue™ result. Results A total of 1002 individuals were enrolled. The adjusted male median (AMM) derived by spectrophotometry was 7.03 U/g Hb (interquartile range (IQR): 5.38–8.69), by WST-8 was 7.03 U/g Hb (IQR: 5.22–8.16) and by Biosensor was 8.61 U/g Hb (IQR: 6.71–10.08). The AMM between spectrophotometry and WST-8 did not differ (p = 1.0) but differed significantly between spectrophotometry and Biosensor (p<0.01). Both, WST-8 and Biosensor were correlated with spectrophotometry (rs = 0.5 and rs = 0.4, both p<0.001). The mean difference in G6PD activity was -0.12 U/g Hb (95% limit of agreement (95% LoA): -5.45 to 5.20) between spectrophotometry and WST-8 and -1.74U/g Hb (95% LoA: -7.63 to 4.23) between spectrophotometry and Biosensor. The WST-8 identified 55.1% (49/89) and the Biosensor 19.1% (17/89) of individuals with G6PD activity <30% by spectrophotometry. Areas under the ROC curve did not differ significantly for the WST-8 and Biosensor irrespective of the cut-off activity applied (all p>0.05). Sensitivity and specificity for detecting G6PD activity <30% was 0.55 (95% confidence interval (95%CI): 0.44–0.66) and 0.98 (95%CI: 0.97–0.99) respectively for the WST-8 and 0.19 (95%CI: 0.12–0.29) and 0.99 (95%CI: 0.98–0.99) respectively for the Biosensor. Hb concentrations measured by HemoCue™ and CareStart™ Hb were strongly correlated (rs = 0.8, p<0.001, mean difference = 0.09 g Hb/dL, 95% LoA: -2.15 to 2.34). Conclusion WST-8 and the CareStart™ G6PD Biosensor represent advances in G6PD diagnostics in resource poor settings, but will require further development before clinical deployment. The CareStart™ Hb instrument produced a precise measure of haemoglobin concentration. PMID:28121993

Antenatal Iron Supplementation Regimens for Pregnant Women in Rural Vietnam and Subsequent Haemoglobin Concentration and Anaemia among Their Infants.

PubMed

Tran, Thach Duc; Fisher, Jane; Hanieh, Sarah; Tran, Tuan; Simpson, Julie Anne; Tran, Ha; Biggs, Beverley-Ann

2015-01-01

Little evidence about the effects of antenatal iron supplementation on infant anaemia is available. The aim was to compare effects on six-month-old infants' Haemoglobin (Hb) concentration and anaemia of daily iron-folic acid (IFA), twice-weekly IFA with or without other micronutrients (MMN) and usual antenatal care in rural Vietnam. Secondary data analysis from: a prospective population-based observational study (OS) which examined effects of antenatal psychosocial factors, anaemia and iron deficiency on infant development and health; and a three-arm cluster randomised trial (CRT) of different antenatal iron supplementation regimens. In the OS 497 women (<20 weeks gestation) from 50 randomly-selected communes participated, and in the CRT 1,258 pregnant women (<16 weeks gestation) in 104 communes were allocated randomly to trial arms. The main outcome was six-month-old infant Hb concentration. Baseline data included women's socio-demographic characteristics, reproductive health, Hb and serum ferritin. Mean differences in infant Hb and odds ratios of infant anaemia between CRT arms and OS were calculated by multivariable regression models, controlling for baseline differences and clustering, using robust standard errors. Infant anaemia prevalence was 68.6% in the OS, 47.2% daily IFA, 53.5% weekly IFA, and 50.3% MMN conditions. After adjustment, mean infant haemoglobin levels in daily IFA (mean difference = 0.95 g/dL; 95%CI 0.7-11.18); weekly IFA (0.91; 95%CI 0.69-1.12) and MMN (1.04; 95%CI 0.8-1.27) were higher than in the OS. After adjustment there were lower odds ratios of anaemia among infants in the daily IFA (OR = 0.31; 95% CI 0.22-0.43), weekly IFA (0.38; 95%CI 0.26-0.54) and MMN (0.33; 95%CI 0.23-0.48) groups than in the OS. Infant anaemia is a public health problem in Vietnam and other resource-constrained countries. All supplementation regimens could have clinically significant benefits for Hb and reduce anaemia risk among six-month-old infants. Universal provision of free intermittent iron supplements is warranted.

Antenatal Iron Supplementation Regimens for Pregnant Women in Rural Vietnam and Subsequent Haemoglobin Concentration and Anaemia among Their Infants

PubMed Central

Tran, Thach Duc; Fisher, Jane; Hanieh, Sarah; Tran, Tuan; Simpson, Julie Anne; Tran, Ha; Biggs, Beverley-Ann

2015-01-01

Background Little evidence about the effects of antenatal iron supplementation on infant anaemia is available. The aim was to compare effects on six-month-old infants’ Haemoglobin (Hb) concentration and anaemia of daily iron–folic acid (IFA), twice-weekly IFA with or without other micronutrients (MMN) and usual antenatal care in rural Vietnam. Methods and Findings Secondary data analysis from: a prospective population-based observational study (OS) which examined effects of antenatal psychosocial factors, anaemia and iron deficiency on infant development and health; and a three-arm cluster randomised trial (CRT) of different antenatal iron supplementation regimens. In the OS 497 women (<20 weeks gestation) from 50 randomly-selected communes participated, and in the CRT 1,258 pregnant women (<16 weeks gestation) in 104 communes were allocated randomly to trial arms. The main outcome was six-month-old infant Hb concentration. Baseline data included women’s socio-demographic characteristics, reproductive health, Hb and serum ferritin. Mean differences in infant Hb and odds ratios of infant anaemia between CRT arms and OS were calculated by multivariable regression models, controlling for baseline differences and clustering, using robust standard errors. Infant anaemia prevalence was 68.6% in the OS, 47.2% daily IFA, 53.5% weekly IFA, and 50.3% MMN conditions. After adjustment, mean infant haemoglobin levels in daily IFA (mean difference = 0.95 g/dL; 95%CI 0.7-11.18); weekly IFA (0.91; 95%CI 0.69-1.12) and MMN (1.04; 95%CI 0.8-1.27) were higher than in the OS. After adjustment there were lower odds ratios of anaemia among infants in the daily IFA (OR = 0.31; 95% CI 0.22-0.43), weekly IFA (0.38; 95%CI 0.26-0.54) and MMN (0.33; 95%CI 0.23-0.48) groups than in the OS. Conclusions Infant anaemia is a public health problem in Vietnam and other resource-constrained countries. All supplementation regimens could have clinically significant benefits for Hb and reduce anaemia risk among six-month-old infants. Universal provision of free intermittent iron supplements is warranted. PMID:25928545

Intensive multifactorial treatment modifies the effect of family history of diabetes on glycaemic control in people with Type 2 diabetes: a post hoc analysis of the ADDITION-Denmark randomized controlled trial.

PubMed

Eliraqi, G M; Vistisen, D; Lauritzen, T; Sandbaek, A; Jørgensen, M E; Faerch, K

2015-08-01

To investigate whether intensive multifactorial treatment can reverse the predisposed adverse phenotype of people with Type 2 diabetes who have a family history of diabetes. Data from the randomized controlled trial ADDITION-Denmark were used. A total of 1441 newly diagnosed patients with diabetes (598 with family history of diabetes) were randomized to intensive treatment or routine care. Family history of diabetes was defined as having one parent and/or sibling with diabetes. Linear mixed-effects models were used to assess the changes in risk factors (BMI, waist circumference, blood pressure, lipids and HbA1c ) after 5 years of follow-up in participants with and without a family history of diabetes. An interaction term between family history of diabetes and treatment group was included in the models to test for a modifying effect of the intervention. All analyses were adjusted for age, sex, baseline value of the risk factor and general practice (random effect). At baseline, participants with a family history of diabetes were younger and had a 1.1 mmol/mol (0.1%) higher HbA1c concentration at the time of diagnosis than those without a family history of diabetes. Family history of diabetes modified the effect of the intervention on changes in HbA1c levels. In the group receiving routine care, participants with a family history of diabetes experienced an improvement in HbA1c concentration that was 3.3 mmol/mol (0.3%) lower than the improvement found in those without a family history of diabetes after 5 years of follow-up. In the intensive treatment group, however, there was no difference in HbA1c concentrations between participants with and without a family history of diabetes after 5 years of treatment. Intensive treatment of diabetes may partly remove the adverse effects of family history of diabetes on glycaemic control. The effect of this improvement on long-term diabetic complications warrants further investigation. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Unraveling the interaction of hemoglobin with a biocompatible and cleavable oxy-diester-functionalized gemini surfactant.

PubMed

Akram, Mohd; Anwar, Sana; Bhat, Imtiyaz Ahmad; Kabir-Ud-Din

2017-03-01

Surfactant-protein mixtures have attracted considerable research interest in recent years at the interface of chemical biology and medicinal chemistry. Herein, the interaction between a green gemini surfactant (C 16 -E2O-C 16 ) and a redox protein hemoglobin was examined through a series of in vitro experimental techniques with an attempt to provide a comprehensive knowledge of the surfactant-protein binding interactions. Quantitative appraisal of the fluorescence/CV data showed that the binding of C 16 -E2O-C 16 to Hb leads to the formation of thermodynamically favorable non-covalent adduct with 1:1 stoichiometry. UV-vis spectra demonstrated that the effect of C 16 -E2O-C 16 on Hb is highly concentration dependent. Far-UV and near-UV CD spectra together elucidated the formation of molten globule state of Hb upon C 16 -E2O-C 16 addition. Temperature dependent CD explicated the effect of C 16 -E2O-C 16 on the thermal stability of Hb. Furthermore, the structural investigation of Hb via pyrene/synchronous/three-dimensional fluorescence and FT-IR spectroscopy provided the complementary information related to its microenvironmental and conformational changes. Computational studies delineated that C 16 -E2O-C 16 binds in the vicinity of β-37 Trp at the α 1 β 2 interface of Hb. Overall, this study is expected to clarify the binding mechanism between Hb/other congeners and surfactant at the molecular level that are known to have immense potential in biomedical and industrial areas. Copyright © 2016 Elsevier B.V. All rights reserved.

Monitoring of lower urinary tract function in patients with spinal cord injury using near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Macnab, Andrew; Nigro, Mark; Stothers, Lynn

2012-02-01

Background: One of the most important conditions where there is loss of normal bladder function is spinal cord injury (SCI). Currently, evaluation of bladder function is limited to periodic invasive urodynamic testing (UDS). The purpose of this study was to assess the feasibility and usefulness of near-infrared spectroscopy (NIRS) in monitoring bladder function in patients with SCI during bladder filling and emptying and to investigate the correlations of NIRS measures with simultaneous UDS parameters. NIRS is a non-invasive optical method to study tissue oxygenation, hemodynamics and function by monitoring changes in the chromophore concentrations of oxygenated (O2Hb), deoxygenated (HHb) and total hemoglobin (tHb). Methods: 10 adult paraplegic patients with neurogenic bladder dysfunction who were referred for regular urodynamic evaluation were recruited. Changes in O2Hb, HHb and tHb, and tissue saturation index (TSI%) in the detrusor were monitored and recorded by a wireless NIRS system during the urodynamic evaluation. Time points of urgency and urinary leakage were marked and patterns of change in NIRS parameters were compared to standard urodynamic pressure tracings. Results: Strong consistency between changes in NIRS-derived tHb and changes in intravesical pressure were observed during filling across the subjects. During bladder filling a gradual increase in O2Hb and tHb with minimal changes in HHb was observed. Interestingly, a drop in TSI% was detected seconds before strong urgency and urinary leakage. Conclusions: Our preliminary data suggest a relationship between noninvasive NIRS measures and UDS parameters during bladder filling in SCI patients.

Free hemoglobin enhances tumor necrosis factor-alpha production in isolated human monocytes.

PubMed

Carrillo, Eddy H; Gordon, Laura E; Richardson, J David; Polk, Hiram C

2002-03-01

A systemic inflammatory response (SIR) is seen in approximately 75% of patients with complex blunt liver injuries treated nonoperatively. Many feel this response is caused by blood, bile, and necrotic tissue accumulation in the peritoneal cavity. Our current treatment for these patients is a delayed laparoscopic washout of the peritoneal cavity, resulting in a dramatic resolution of the SIR. Spectrophotometric analysis of the intraperitoneal fluid has confirmed the presence of high concentrations of free hemoglobin (Hb). We hypothesize that free Hb enhances the local peritoneal response by increasing tumor necrosis factor-alpha (TNF-alpha) production by monocytes, contributing to the local inflammatory response and SIR. Monocytes from five healthy volunteers were isolated and cultured in RPMI-1640 for 24 hours. Treatment groups included saline controls, lipopolysaccharide ([LPS], 10 ng/mL, from Escherichia coli), human Hb (25 microg/mL), and Hb + LPS. Supernatants were analyzed by enzyme-linked immunosorbent assay. Student's t test with Mann-Whitney posttest was used for statistical analysis with p < or = 0.05 considered significant. Free Hb significantly increased TNF-alpha production 915 +/- 223 pg/mL versus saline (p = 0.02). LPS and Hb + LPS further increased TNF-alpha production (2294 pg/mL and 2501 pg/mL, respectively, p < 0.001) compared with saline controls. These data confirm that free Hb is a proinflammatory mediator resulting in the production of significant amounts of TNF-alpha. These in vitro findings support our clinical data in which timely removal of intraperitoneal free hemoglobin helps prevent its deleterious local and systemic inflammatory effects in patients with complex liver injuries managed nonoperatively.

Differences in the hemodynamic response to event-related motor and visual paradigms as measured by near-infrared spectroscopy

NASA Technical Reports Server (NTRS)

Jasdzewski, G.; Strangman, G.; Wagner, J.; Kwong, K. K.; Poldrack, R. A.; Boas, D. A.; Sutton, J. P. (Principal Investigator)

2003-01-01

Several current brain imaging techniques rest on the assumption of a tight coupling between neural activity and hemodynamic response. The nature of this neurovascular coupling, however, is not completely understood. There is some evidence for a decoupling of these processes at the onset of neural activity, which manifests itself as a momentary increase in the relative concentration of deoxyhemoglobin (HbR). The existence of this early component of the hemodynamic response function, however, is controversial, as it is inconsistently found. Near infrared spectroscopy (NIRS) allows quantification of levels of oxyhemoglobin (HbO(2)) and HbR during task performance in humans. We acquired NIRS data during performance of simple motor and visual tasks, using rapid-presentation event-related paradigms. Our results demonstrate that rapid, event-related NIRS can provide robust estimates of the hemodynamic response without artifacts due to low-frequency signal components, unlike data from blocked designs. In both the motor and visual data the onset of the increase in HbO(2) occurs before HbR decreases, and there is a poststimulus undershoot. Our results also show that total blood volume (HbT) drops before HbO(2) and undershoots baseline, raising a new issue for neurovascular models. We did not find early deoxygenation in the motor data using physiologically plausible values for the differential pathlength factor, but did find one in the visual data. We suggest that this difference, which is consistent with functional magnetic resonance imaging (fMRI) data, may be attributable to different capillary transit times in these cortices.

Investigation of miscibility of p(3hydroxybutyrate-co-3hydroxyhexanoate) and epoxidized natural rubber blends

NASA Astrophysics Data System (ADS)

Akram, Faridah; Chan, Chin Han; Natarajan, Valliyappan David

2015-08-01

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate [P(3HB-co-3HHx)] produced by C. necator PHB-4 harboring phaCcs from crude palm kernel oil with 21 mol% of 3-hydroxyhexanoate and epoxidized natural rubber with 25 mol% of epoxy content (ENR-25) were used to study the miscibility of the blends by attenuated total reflection-Fourier transform infrared (ATR-FTIR) and differential scanning calorimetry (DSC). The polymers used were purified and the blends were prepared by solution casting method. Nuclear magnetic resonance (NMR) spectra confirm the purity and molecular structures of P(3HB-co-3HHx) and ENR-25. FTIR spectra for different compositions of P(3HB-co-3HHx) and ENR-25 blends show absorbance change of the absorbance bands but with no significant shifting of the absorbance bands as the P(3HB-co-3HHx) content decreases, which shows that there is no intermolecular interaction between the parent polymer blends. On top of that, there are two Tgs present for the blends and both remain constant for different compositions which corresponds to the Tgs of the parent polymers. This indicates that the blends are immiscible.

Commissioning of horizontal-bend superconducting magnet for Jefferson Lab's 11-GeV super high momentum spectrometer

DOE PAGES

Sun, Eric; Brindza, Paul D.; Lassiter, Steven R.; ...

2016-03-02

Commissioning characteristics of the Superconducting High Momentum Spectrometer (SHMS) Horizontal Bend (HB) magnet was presented. Pre-commissioning peer review of the magnet uncovered issues with eddy currents in the thermal shield, resulting in additional testing and modeling of the magnet. A three-stage test plan was discussed. A solution of using a small dump resistor and a warm thermal shield was presented. Analyses illustrated that it was safe to run the magnet to full test current. As a result, the HB magnet was successfully cooled to 4 K and reached its maximum test current of 4000 A.

Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the differential diagnosis of Her-2 negative breast cancer.

PubMed

Shetty, Praveenkumar; Patil, Vidya S; Mohan, Rajashekar; D'souza, Leonard Clinton; Bargale, Anil; Patil, Basavaraj R; Dinesh, U S; Haridas, Vikram; Kulkarni, Shrirang P

2017-07-01

Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model. Results Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P < 0.01) and Her-2 positive cases (217.75 ± 60.59 ng/mL, P < 0.0001). In Her-2 negative cases, the HB-EGF concentrations (179.16 ± 118.81 pg/mL) were highly significant compared with normal (14.92 ± 17.33 pg/mL, P < 0.001). IL-6 concentrations were increased significantly in both the breast cancer phenotypes as compared with normal ( P < 0.001). Conclusion The specific expression pattern of annexinA2 and HB-EGF in triple-negative breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.

Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

PubMed Central

Angelantonio, Emanuele Di; Gao, Pei; Khan, Hassan; Butterworth, Adam S.; Wormser, David; Kaptoge, Stephen; Kondapally Seshasai, Sreenivasa Rao; Thompson, Alex; Sarwar, Nadeem; Willeit, Peter; Ridker, Paul M; Barr, Elizabeth L.M.; Khaw, Kay-Tee; Psaty, Bruce M.; Brenner, Hermann; Balkau, Beverley; Dekker, Jacqueline M.; Lawlor, Debbie A.; Daimon, Makoto; Willeit, Johann; Njølstad, Inger; Nissinen, Aulikki; Brunner, Eric J.; Kuller, Lewis H.; Price, Jackie F.; Sundström, Johan; Knuiman, Matthew W.; Feskens, Edith J. M.; Verschuren, W. M. M.; Wald, Nicholas; Bakker, Stephan J. L.; Whincup, Peter H.; Ford, Ian; Goldbourt, Uri; Gómez-de-la-Cámara, Agustín; Gallacher, John; Simons, Leon A.; Rosengren, Annika; Sutherland, Susan E.; Björkelund, Cecilia; Blazer, Dan G.; Wassertheil-Smoller, Sylvia; Onat, Altan; Marín Ibañez, Alejandro; Casiglia, Edoardo; Jukema, J. Wouter; Simpson, Lara M.; Giampaoli, Simona; Nordestgaard, Børge G.; Selmer, Randi; Wennberg, Patrik; Kauhanen, Jussi; Salonen, Jukka T.; Dankner, Rachel; Barrett-Connor, Elizabeth; Kavousi, Maryam; Gudnason, Vilmundur; Evans, Denis; Wallace, Robert B.; Cushman, Mary; D’Agostino, Ralph B.; Umans, Jason G.; Kiyohara, Yutaka; Nakagawa, Hidaeki; Sato, Shinichi; Gillum, Richard F.; Folsom, Aaron R.; van der Schouw, Yvonne T.; Moons, Karel G.; Griffin, Simon J.; Sattar, Naveed; Wareham, Nicholas J.; Selvin, Elizabeth; Thompson, Simon G.; Danesh, John

2015-01-01

IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5%to <7.5%), and high (≥7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk. PMID:24668104

Far Forward Treatment of Hemorrhagic Shock

DTIC Science & Technology

2007-02-01

Ringer’s solutions on human leukocytes. J Trauma 52(5):872-878, 2002 6. Alam HB, Punzalan CM, Koustova E, Bowyer MW, Rhee P. Hypertonic Saline: Intraosseous ...Fluid Resuscitation. 17. February 2006- Anesthesia Grand Rounds. Massachusetts General Hospital, Boston, MA. Topic: Trauma Resuscitation: New

Effects of lipid-based nutrient supplements v. micronutrient powders on nutritional and developmental outcomes among Peruvian infants.

PubMed

Matias, Susana L; Vargas-Vásquez, Alejandro; Bado Pérez, Ricardo; Alcázar Valdivia, Lorena; Aquino Vivanco, Oscar; Rodriguez Martín, Amelia; Novalbos Ruiz, Jose Pedro

2017-11-01

To determine the effects of lipid-based nutrient supplements (LNS) on children's Hb, linear growth and development, compared with supplementation with micronutrient powder (MNP). The study was a two-arm parallel-group randomized controlled trial, where participants received either LNS or MNP for daily consumption during 6 months. Supplements were delivered by staff at government-run health centres. Hb, anthropometric, motor development, language development and problem-solving indicators were measured by trained research assistants when children were 12 months of age. The study was conducted in five rural districts in the Province of Ambo in the Department of Huánuco, Peru. We enrolled 6-month-old children (n 422) at nineteen health centres. Children who received LNS had a higher mean Hb concentration and lower odds of anaemia than those who received MNP. No significant differences in height-for-age, weight-for-height or weight-for-age Z-score, or stunting and underweight prevalence, were observed. Provision of LNS was associated with a higher pre-verbal language (gestures) score, but such effect lost significance after adjustment for covariates. Children in the LNS group had higher problem-solving task scores and increased odds of achieving this cognitive task than children in the MNP group. No significant differences were observed on receptive language or gross motor development. LNS between 6 and 12 months of age increased Hb concentration, reduced anaemia and improved cognitive development in children, but showed no effects on anthropometric indicators, motor or language development.

Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study.

PubMed

Schaefer, Franz; Hoppe, Bernd; Jungraithmayr, Therese; Klaus, Günter; Pape, Lars; Farouk, Mourad; Addison, Janet; Manamley, Nick; Vondrak, Karel

2016-03-01

Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD). In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded. A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5%) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0%), gastroenteritis (6.0%), and hypertension (4.1%). Six patients (1.9%) died (unrelated to DA). Four patients (1.3%) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4-2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2-11.7 g/dl, respectively. Overall, 48 patients (15.0%) received ≥1 transfusion. No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.

Growth and change in blood haemoglobin concentration among underweight Malawian infants receiving fortified spreads for 12 weeks: a preliminary trial

USDA-ARS?s Scientific Manuscript database

Fortified spreads (FSs) have proven effective in the rehabilitation of severely malnourished children. We examined acceptability, growth and change in blood haemoglobin (Hb) concentration among moderately underweight ambulatory infants given FS. This was a randomised, controlled, parallel-group, inv...

Bioavailability of Pb and Zn from mine tailings as indicated by erythrocyte aminolevulinic acid dehydratase (ALA-D) activity in suckers (Pisces: catostomidae)

USGS Publications Warehouse

Schmitt, Christopher J.; Dwyer, F. James; Finger, Susan E.

1984-01-01

The activity of the erythrocyte enzyme δ-aminolevulinic acid dehydratase (ALA-D) was measured in 35 catostomids (black redhorse, Moxostoma duquesnei; golden redhorse, M. erythrurum; northern hogsucker, Hypentelium nigricans) collected from three sites on a stream contaminated with Pb-, Cd-, and Zn-rich mine tailings and from an uncontaminated site upstream. Enzyme activity was expressed in terms of hemoglobin (Hb), DNA, and protein concentrations; these variables can be determined in the laboratory on once-frozen blood samples. Concentrations of Pb and Zn in blood and of Pb in edible tissues were significantly higher, and ALA-D activity was significantly lower, at all three contaminated sites than upstream. At the most contaminated site, ALA-D activity was 62–67% lower than upstream. Lead concentrations in the edible tissues and in blood were positively correlated (r = 0.80), whereas ALA-D activity was negatively correlated with Pb in blood (r = −0.70) and in edible tissues (r = −0.59). Five statistically significant relations between Pb and Zn in blood and ALA-D activity were determined. The two models that explained the highest percentage (> 74%) of the total variance also included factors related to Hb concentration. All five significant models included negative coefficients for variables that represented Pb in blood and positive coefficients for Zn in blood. The ALA-D assay with results standardized to Hb concentration represents an expedient alternative to the more traditional hematocrit standardization, and the measurement of ALA-D activity by this method can be used to document exposure of fish to environmental Pb.