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hemoglobin based oxygen carriers

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https://www.readbyqxmd.com/read/28884612/conjugation-with-20%C3%A2-kda-dextran-decreases-the-autoxidation-rate-of-bovine-hemoglobin
#1
Jun Zhang, Ying Wang, Guo-Xing You, Quan Wang, Shan Zhang, Wei-Li Yu, Tao Hu, Lian Zhao, Hong Zhou
Haemoglobin-based oxygen carrier (HBOC) is highly susceptible to autoxidation that renders a series of tissue and cellular toxicities. HBOC is prepared by chemical modification of haemoglobin (Hb), which typically increases the autoxidation rate of Hb. Thus, it is necessary to decrease the autoxidation of HBOC. In the present study, two dextran-bHb conjugates (dex20-bHb and dex40-bHb) were prepared by conjugation with 20 kDa or 40 kDa dextrans, where the thiol group of Cys-93(β) was reversibly protected...
September 8, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28794333/development-of-time-course-oxygen-binding-analysis-for-hemoglobin-based-oxygen-carriers
#2
Yukihiro Okamoto, Shigenori Sugisaki, Keishi Suga, Hiroshi Umakoshi
Developing blood substitutes is in urgent demand for chronic blood shortage all over the world. In this connection, the oxygen binding behavior of hemoglobin-based oxygen carriers (HBOCs) is one of the most important characteristics. However, present methods available for estimating oxygen binding behavior have need of expensive apparatus, and also are not suitable for high-throughput and the time-course analysis. To overcome these problems, we proposed a simple analysis method for the time-course oxygen binding behavior of HBOCs, which employs a general UV-Vis microplate reader and a common reagent, sodium dithionite, as a reductant for HBOCs and an oxygen scavenger...
2017: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/28755016/numerical-investigation-of-oxygen-transport-by-hemoglobin-based-carriers-through-microvessels
#3
Toru Hyakutake, Takumi Kishimoto
The small size of hemoglobin-based oxygen carriers (HBOCs) may expand the realm of new treatment possibilities for various circulatory diseases. The parametric evaluation of HBOC performance for oxygen transport within tissue is essential for effectively characterizing its performance for each circulatory disease assessed. Thus, the overarching objective of this present study was to numerically investigate the reaction-diffusion phenomenon of oxygenated HBOCs and oxygen on tissues through microvessels. We considered dissociation rate coefficients, oxygen affinity, and diffusion coefficients due to Brownian motion as the biophysical parameters for estimating HBOC performance for oxygen transport...
July 28, 2017: Journal of Artificial Organs: the Official Journal of the Japanese Society for Artificial Organs
https://www.readbyqxmd.com/read/28744782/storage-of-nitroglycerin-ntg-admixed-with-hboc-201-for-30%C3%A2-days-in-polyolefin-plastic-bags-a-pilot-study
#4
Savita Nigam, Richard McCarron, Francoise Arnaud
Hemorrhaged animals have benefited from resuscitation with the hemoglobin-based oxygen carrier (HBOC-201). Co-infusion of nitric oxide (NO) via separate intravascular lines is effective in attenuating HBOC-induced elevation of blood pressure. We tested whether nitroglycerin (NTG) and HBOC-201 can be packaged together as a single drug for resuscitation. Since NTG binds easily to plastics such as polyvinylchloride, we assessed the stability of this combination in oxygen barrier double-layer ethylene-vinyl alcohol/polyolefin bags over a 30-day period...
July 25, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28685467/characterization-of-protein-protein-interactions-in-recombinant-hemoglobin-producing-escherichia-coli-cells-using-molecularly-imprinted-polymers
#5
Ka Zhang, Tongchang Zhou, Lei Ye, Leif Bülow
The worldwide blood shortage has generated demands for alternatives to transfusible human blood. One such important option is based on recombinant hemoglobin-based oxygen carriers (rHBOCs). Most efforts have been focused on various E. coli based production systems. One of the key challenges in these systems is to devise an efficient and economical protein production strategy involving selection of suitable host cell and Hb variant, growth conditions and media engineering. Hb also influences the heterologous host cell metabolism and therefore the identification of modified protein-protein interactions is critical for optimizing Hb production...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28685464/hemoglobin-based-oxygen-carrier-hboc-development-in-trauma-previous-regulatory-challenges-lessons-learned-and-a-path-forward
#6
Peter E Keipert
Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. This included the early trauma trials with HemAssist (®) (BAXTER), Hemopure (®) (BIOPURE) and PolyHeme (®) (NORTHFIELD) for resuscitating hypotensive shock...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28601310/hemoglobin-based-oxygen-carriers-promote-systemic-hyperfibrinolysis-that-is-both-dependent-and-independent-of-plasmin
#7
Alexander P Morton, Ernest E Moore, Hunter B Moore, Eduardo Gonzalez, Michael P Chapman, Erik Peltz, Anirban Banerjee, Christopher Silliman
BACKGROUND: Hyperfibrinolysis plays an integral role in the genesis of trauma-induced coagulopathy. Recent data demonstrate that red blood cell lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOCs) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy because of the presence of free hemoglobin. MATERIALS AND METHODS: WB was sampled from healthy donors (n = 6)...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28521553/glutaraldehyde-polymerized-hemoglobin-and-tempol-polyhb-tempol-has-superoxide-dismutase-activity-that-can-attenuate-oxidative-stress-on-endothelial-cells-induced-by-superoxide-anion
#8
Mengdi Wu, Kun Feng, Qiuhui Li, Huiya Ma, Hongli Zhu, Yudou Xie, Gaofei Yan, Chao Chen, Kunping Yan
A Tempol compound with an amine group (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, NH2-Tempol) was cross-linked to hemoglobin in a one-step polymerization reaction to produce a novel hemoglobin-based oxygen carrier (HBOC) designated PolyHb-Tempol. The reaction parameters, including the reaction time, pH, temperature, and ratio of reactants, were optimized, and the physiochemical properties of the resulting product were characterized. PolyHb-Tempol didn't show any toxicity towards endothelial cells. Furthermore, from observations of cell morphology and viability, PolyHb-Tempol showed a significant ability to inhibit or eliminate oxidative stress induced by superoxide free radicals...
May 18, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28520579/the-use-of-an-acellular-oxygen-carrier-in-a-human-liver-model-of-normothermic-machine-perfusion
#9
Richard W Laing, Ricky H Bhogal, Lorraine Wallace, Yuri Boteon, Desley A H Neil, Amanda Smith, Barney T F Stephenson, Andrea Schlegel, Stefan G Hübscher, Darius F Mirza, Simon C Afford, Hynek Mergental
BACKGROUND: Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions whilst maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L. METHODS: Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers...
May 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28463811/a-facile-way-to-prepare-functionalized-dextran-nanogels-for-conjugation-of-hemoglobin
#10
Xing Wei, Hejian Xiong, Shasha He, Yupeng Wang, Dongfang Zhou, Xiabin Jing, Yubin Huang
Nanogels with several special advantages have been widely applied in protein delivery. However, biocompatible and biodegradable nanogels used for hemoglobin (Hb) delivery are far less explored. Herein, we developed a facile method to prepare functionalized dextran nanogels for conjugation of Hb. In situ cross-linked and aldehyde group functionalized nanogels (FNGs) were prepared from dextran-g-succinic anhydride-g-dopamine conjugate (Dex-SA-DA) assembly by simple pH adjustion and oxidization in water. Hb was further conjugated into the swelling FNGs by Schiff base reaction under mild condition...
April 23, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28457331/beneficial-effects-of-novel-cross-linked-hemoglobin-yq23-on-hemorrhagic-shock-in-rats-and-pigs
#11
Tao Li, Guangming Yang, Yu Zhu, Fei Chuen Tzang, Sze-Hang Lau, Sui-Yi Kwok, Bing L Wong, Liangming Liu
BACKGROUND: To overcome the problems of previously reported hemoglobin-based oxygen carriers, we developed a stabilized nonpolymeric cross-linked tetrameric hemoglobin solution (YQ23). The aims of this study were to investigate the oxygen carrying and releasing properties of this novel hemoglobin-based oxygen carrier and to determine whether it has beneficial effects for hemorrhagic shock. METHODS: Using a hemorrhagic shock model in Sprague-Dawley rats and mini-pigs, we tested the effects of infusing 0...
April 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28335469/comparison-of-the-pharmacokinetic-properties-of-hemoglobin-based-oxygen-carriers
#12
REVIEW
Kazuaki Taguchi, Keishi Yamasaki, Toru Maruyama, Masaki Otagiri
Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier in view of its innate biological properties. However, the vascular retention of free Hb is too short to permit a full therapeutic effect because Hb is rapidly cleared from the kidney via glomerular filtration or from the liver via the haptogloblin-CD 163 pathway when free Hb is administered in the blood circulation. Attempts have been made to develop alternate acellular and cellular types of Hb based oxygen carriers (HBOCs), in which Hb is processed via various routes in order to regulate its pharmacokinetic properties...
March 18, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/28323418/bioinspired-polydopamine-coated-hemoglobin-as-potential-oxygen-carrier-with-antioxidant-properties
#13
Quan Wang, Ruirui Zhang, Mingzi Lu, Guoxing You, Ying Wang, Gan Chen, Caiyan Zhao, Zhen Wang, Xiang Song, Yan Wu, Lian Zhao, Hong Zhou
Oxidative side reaction is one of the major factors hindering the development of hemoglobin-based oxygen carriers (HBOCs). To avoid the oxidative toxicity, we designed and synthesized polydopamine-coated hemoglobin (Hb-PDA) nanoparticles via simple one-step assemblage without any toxic reagent. Hb-PDA nanoparticles showed oxidative protection of Hb by inhibiting the generation of methemoglobin (MetHb) and ferryl (Fe IV) Hb, as well as excellent antioxidant properties by scavenging free radicals and reactive oxygen species (ROS)...
April 10, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28321886/-inside-out-pegylation-of-bovine-%C3%AE-cross-linked-hemoglobin
#14
Kyle D Webster, Dana Dahhan, Abigail M Otto, Cheyanne L Frosti, William L Dean, Jonathan B Chaires, Kenneth W Olsen
The development of a blood substitute is urgent due to blood shortages and potential communicable diseases. A novel method, inside-out PEGylation, has been used here to conjugate a multiarm maleimide-PEG (Mal-PEG) to β-cross-linked (βXL-Hb) hemoglobin (Hb) tetramers through the Cys β93 residues. This method produces a polymer with a single PEG backbone that is surrounded by multiple proteins, rather than coating a single protein with multiple PEG chains. Electrophoresis under denaturing conditions showed a large molecular weight species...
April 2017: Artificial Organs
https://www.readbyqxmd.com/read/28294960/overview-of-potential-clinical-applications-of-hemoglobin-vesicles-hbv-as-artificial-red-cells-evidenced-by-preclinical-studies-of-the-academic-research-consortium
#15
REVIEW
Hiromi Sakai
Hemoglobin (Hb) is the most abundant protein in whole blood. This fact implies that the oxygen binding and releasing function of Hb is the most vital for sustaining life. All Hb is compartmentalized in red blood cells (RBCs) with corpuscular Hb concentration of about 35 g/dL, covered with a thin biomembrane. In spite of its abundance, Hb sometimes shows toxicity once it is leaked from RBCs. The shielding effect of the RBC membrane is physiologically important. Based on this structural importance, we have studied artificial red cells (Hb vesicles, HbV) as artificial oxygen carriers, which encapsulate a purified and concentrated Hb solution in phospholipid vesicles, mimicking the cellular structure of RBCs...
March 15, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/28288573/hemoglobin-vesicles-prolong-the-time-to-circulatory-collapse-in-rats-during-apnea
#16
Yusuke Naito, Hiromi Sakai, Satoki Inoue, Masahiko Kawaguchi
BACKGROUND: Hemoglobin vesicles (HbV) are hemoglobin-based oxygen carriers manufactured by liposome encapsulation of hemoglobin molecules. We hypothesised that the infusion of oxygenated HbV could prolong the time to circulatory collapse during apnea in rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into four groups (Air, Oxy, NS and HbV). The rats were anaesthetized with isoflurane and the trachea was intubated using 14-gauge intravenous catheters...
March 14, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28188676/hemoglobin-based-oxygen-carrier-rescues-double-transplant-patient-from-life-threatening-anemia
#17
M F Gomez, O Aljure, G Ciancio, M Lynn
This case describes a 46-year-old male recipient of a kidney-pancreas transplant who is Jehovah's Witness. Early in the postoperative period, he was found to have splenic vein thrombosis requiring heparin infusion. Two days later, he developed severe symptomatic anemia (hemoglobin <6 g/dL). Standard medical therapy for bloodless surgical patients with severe anemia was instituted. Nevertheless, the patient's hemoglobin concentration continued to decline to critical levels (2 g/dL). Because he was Jehovah's Witness, transfusion of allogeneic blood products was not an option, prompting use of a hemoglobin-based oxygen carrier (HBOC)...
July 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28188434/bloodless-reperfusion-with-the-oxygen-carrier-hboc-201-in-acute-myocardial-infarction-a-novel-platform-for-cardioprotective-probes-delivery
#18
Jose M García-Ruiz, Carlos Galán-Arriola, Rodrigo Fernández-Jiménez, Jaume Aguero, Javier Sánchez-González, Ana García-Alvarez, Mario Nuno-Ayala, Gregory P Dubé, Zafiris Zafirelis, Gonzalo J López-Martín, Juan A Bernal, Enrique Lara-Pezzi, Valentín Fuster, Borja Ibáñez
Reperfusion, despite being required for myocardial salvage, is associated with additional injury. We hypothesize that infarct size (IS) will be reduced by a period of bloodless reperfusion with hemoglobin-based oxygen carriers (HBOC) before blood-flow restoration. In the pig model, we first characterized the impact of intracoronary perfusion with a fixed volume (600 ml) of a pre-oxygenated acellular HBOC, HBOC-201, on the healthy myocardium. HBOC-201 was administered through the lumen of the angioplasty balloon (i...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28183818/normalization-of-hemoglobin-based-oxygen-carrier-201-induced-vasoconstriction-roles-of-nitric-oxide-scavenging-and-endothelin
#19
Yannick J Taverne, Daphne P M de Wijs-Meijler, Maaike Te Lintel Hekkert, Paula F Moon-Massat, Greg P Dubé, Dirk Jan Duncker, Daphne Merkus
BACKGROUND: Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore we aimed to 1) determine the possibility of counteracting HBOC-201-induced pressor effects with adenosine (ADO), 2) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS) and endothelin (ET) in mediating the observed vasoconstriction and 3) compare these effects in resting and exercising swine...
February 9, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28099525/polyethylene-glycol-camouflaged-earthworm-hemoglobin
#20
Vivek P Jani, Alborz Jelvani, Selamawit Moges, Parimala Nacharaju, Camille Roche, David Dantsker, Andre Palmer, Joel M Friedman, Pedro Cabrales
Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris...
2017: PloS One
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