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hemoglobin based oxygen carriers

Qingshu Wang, Ling Hu, Yu Hu, Gu Gong, Hua Tan, Li Deng, Xiaoqin Sun, Xiaobo Yi, Yangyang Sun, Wei Wu, Tao Li
OBJECTIVE: To investigate the therapeutic effect of carbon monoxide (CO) on high-altitude hypoxia-induced cardiac damage. METHODS: Forty male C57BL/6 mice were randomly divided into 4 groups. The mice were exposed to normoxia or simulated 5,500-meter high-altitude hypoxia in a hypobaric chamber for 7 days. During the first 3 days, the mice were pretreated with CO-saturated hemoglobin (Hb)-based oxygen carrier (CO-HBOC), oxygen-saturated hemoglobin-based oxygen carrier (O2-HBOC) at a dose of 0...
October 12, 2016: Cardiology
Serena Singh, Ina S Dubinsky-Davidchik, Ronald Kluger
Conventional chemical approaches to protein-protein coupling present challenges due to the intrinsic competition between the desired interactions of reagents with groups of the protein as well as reactions with water. Biorthogonal Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC)-processes provide a basis to direct reactivity without functional group interference. However, the requirement for Cu(i) in CuAAC leads to complications that result from the metal ion's interactions with the protein. In principle, a similar but metal-free alternative approach to coupling could employ the reaction of an alkyne that is strained in combination with an azide (strain-promoted azide-alkyne cycloaddition, SPAAC)...
October 5, 2016: Organic & Biomolecular Chemistry
Ying Wang, Linli Wang, Weili Yu, Dawei Gao, Guoxing You, Penglong Li, Shan Zhang, Jun Zhang, Tao Hu, Lian Zhao, Hong Zhou
Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been used as blood substitutes in surgery medicine and oxygen therapeutics for ischemic stroke. As a potent HBOC, the PEGylated Hb has received much attention for its oxygen delivery and plasma expanding ability. Two PEGylated Hbs, Euro-Hb and MP4 have been developed for clinical trials, using human adult hemoglobin (HbA) as the original substrate. However, HbA was obtained from outdated human blood and its quantity available from this source may not be sufficient for mass production of PEGylated HbA...
October 3, 2016: Biotechnology Progress
Joseph A Posluszny, Lena M Napolitano
INTRODUCTION: Treatment of severe hemorrhagic shock due to acute blood loss from traumatic injuries in a Jehovah's witness (JW) trauma patient is very challenging since hemostatic blood product resuscitation is limited by refusal of the transfusion of allogeneic blood products. CASE PRESENTATION: We describe a multifaceted approach to the clinical care of a severely anemic JW trauma patient including the early administration of a bovine hemoglobin-based oxygen carrier (HBOC) as a bridge to resolution of critical anemia (nadir hemoglobin 3...
June 2016: Archives of Trauma Research
Mervyn Mer, Eric Hodgson, Lee Wallis, Barry Jacobson, Lewis Levien, Jacques Snyman, Martin J Sussman, Mike James, Antoine van Gelder, Rachel Allgaier, Jonathan S Jahr
Hemopure (hemoglobin glutamer-250 [bovine]; HBOC-201) is a hemoglobin (Hb)-based oxygen carrier registered with the Medicines Control Council of South Africa. It is indicated for the treatment of adult patients who are acutely anemic, for the purpose of maintaining tissue oxygen delivery thus eliminating, delaying, or reducing the need for allogeneic red blood cells (RBCs). Hemopure is a volume expander, and circulatory volume must be carefully monitored for signs of fluid overload. Hemopure is not as effective as RBCs for restoring Hb content and concentration, but in cases of severe anemia where allogeneic blood is not an option or is unavailable, it may offer an immediate alternative for improving oxygen transport...
October 2016: Transfusion
Michael Brad Strader, Abdu I Alayash
SIGNIFICANCE: Worldwide demand has driven the development of hemoglobin (Hb)-based oxygen carriers (HBOCs) as potential acellular oxygen therapeutics. HBOCs have the potential to provide an oxygen bridge to patients and minimize current problems associated with supply and storage of donated blood. However, to date, safety and efficacy issues have hampered the approval of viable HBOCs in the United States. These previous efforts have underscored the need for a better molecular understanding of toxicity in order to design safe and oxidatively stable HBOCs...
September 14, 2016: Antioxidants & Redox Signaling
Burak Zeybek, Andrew M Childress, Gokhan S Kilic, John Y Phelps, Luis D Pacheco, Michele A Carter, Mostafa A Borahay
IMPORTANCE: Obstetricians and gynecologists frequently deal with hemorrhage so they should be familiar with management of patients who refuse blood transfusion. Although there are some reports in the literature about management of Jehovah's Witness patients in obstetrics and gynecology, most of them are case reports, and a comprehensive review about these patients including ethicolegal perspective is lacking. OBJECTIVE: This review outlines the medical, ethical, and legal implications of management of Jehovah's Witness patients in obstetrical and gynecological settings...
August 2016: Obstetrical & Gynecological Survey
Otgonchimeg Rentsendorj, Xiaoyuan Zhang, Matthew C Williams, Paul W Buehler, Felice D'Agnillo
Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on the transcriptional regulation, activity, and expression of the renal antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms 1-3, GPx1, GPx3, GPx4, and CAT...
2016: Toxics
Gary G A Silkstone, Rebecca S Silkstone, Michael T Wilson, Michelle Simons, Leif Bülow, Kristian Kallberg, Khuanpiroon Ratanasopa, Luca Ronda, Andrea Mozzarelli, Brandon J Reeder, Chris E Cooper
Hemoglobin (Hb)-based oxygen carriers (HBOC) have been engineered to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects linked to intrinsic heme-mediated oxidative toxicity and nitric oxide (NO) scavenging. Redox-active tyrosine residues can facilitate electron transfer between endogenous antioxidants and oxidative ferryl heme species. A suitable residue is present in the α-subunit (Y42) of Hb, but absent from the homologous position in the β-subunit (F41)...
October 1, 2016: Biochemical Journal
Ashley L Farris, Alexandra N Rindone, Warren L Grayson
Tissue engineering (TE) has provided promising strategies for regenerating tissue defects, but few TE approaches have been translated for clinical applications. One major barrier in TE is providing adequate oxygen supply to implanted tissue scaffolds, since oxygen diffusion from surrounding vasculature in vivo is limited to the periphery of the scaffolds. Moreover, oxygen is also an important signaling molecule for controlling stem cell differentiation within TE scaffolds. Various technologies have been developed to increase oxygen delivery in vivo and enhance the effectiveness of TE strategies...
May 28, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Vlad Al Toma, Anca D Farcaș, Ioana Roman, Bogdan Sevastre, Denisa Hathazi, Florina Scurtu, Grigore Damian, Radu Silaghi-Dumitrescu
A series of hemoglobin-based oxygen carrier candidates (HBOC), previously noted for their differences in prooxidative and physiological reactivity, were compared in terms of the negative effects displayed upon injection in Wistar rats. At the concentrations tested, antioxidant strategies based on albumin as well as based on rubrerythrin appear to offer observable physiological advantages.
2016: PloS One
Narendranath Epperla, Christopher Strouse, Amanda M VanSandt, Patrick Foy
BACKGROUND: The acute treatment of severe warm autoimmune hemolytic anemia (wAIHA) is focused on maximizing the oxygen delivery capacity of the patient's circulation and reversal of the underlying autoimmune process. The most effective means of preventing ischemic injury acutely is replacement of red blood cells (RBCs) via allogeneic RBC transfusion. However, in cases where this is not an option, other strategies must be considered including the use of hemoglobin-based oxygen carriers (HBOCs)...
July 2016: Transfusion
Francoise Arnaud, Adam Higgins, Richard McCarron, Paula F Moon-Massat
Background/aims Hemoglobin-based oxygen carriers (HBOCs) have been previously studied as resuscitation fluids. Due to HBOCs specific molecular conformation, hemoglobin (Hb) and methemoglobin (MetHb) determination is not always possible with automated apparatus. A practical technique was designed that allows simultaneous reading of MetHb and Hb in small volume samples. Methods A spectrophotometric method for measuring low levels of MetHb and Hb from limited volume samples was developed using a 96-well-plate by downsizing the Evelyn-Malloy and Drabkin methods...
March 2, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Song Guo, Pei Wang, Chen Chen, Zhengyan Meng, Donglai Qi, Xiang Wang
The application of hemoglobin-based oxygen carriers (HBOCs) remains stagnant because a large number of reactive oxygen species (ROS) will be produced in organisms when HBOCs are used. Ferulic acid (FA) has a known effect on quenching oxygen free radicals and relieving vasospasm. Thus a kind of FA modified hemoglobin (BAEGF-Hb) is expected to produce the anti-oxidation effect on HBOCs spontaneously, and reduce toxicity. Isoelectric focusing electrophoresis, UV-vis wavelength scanning, and oxygen affinity curve showed that hemoglobin (Hb) was successfully modified and this modification had no effect on the structure of Hb and P50...
June 2016: Artificial Cells, Nanomedicine, and Biotechnology
A Abuchowski
Oxygen transfer agents have long been sought as a means to treat hypoxia caused by congenital or acquired conditions. Hemoglobin-based oxygen carriers were in clinical development as blood substitutes, but development was halted due to the finding of significant vasoactivity. Rather than develop a blood substitute, a product for indications characterized by hypoxia is in development. PEGylated bovine carboxyhemoglobin (SANGUINATE™) is both a carbon monoxide releasing molecule and an oxygen transfer agent...
2016: Advances in Experimental Medicine and Biology
R S Silkstone, G Silkstone, J A Baath, B Rajagopal, P Nicholls, B J Reeder, L Ronda, L Bulow, C E Cooper
It has been proposed that introducing tyrosine residues into human hemoglobin (e.g. βPhe41Tyr) may be able to reduce the toxicity of the ferryl heme species in extracellular hemoglobin-based oxygen carriers (HBOC) by facilitating long-range electron transfer from endogenous and exogenous antioxidants. Surface-exposed residues lying close to the solvent exposed heme edge may be good candidates for mutations. We therefore studied the properties of the βLys66Tyr mutation. Hydrogen peroxide (H2O2) was added to generate the ferryl protein...
2016: Advances in Experimental Medicine and Biology
Khuanpiroon Ratanasopa, Tommy Cedervall, Leif Bülow
The expression levels of fetal hemoglobin (HbF) in bacterial recombinant systems are higher compared with normal adult hemoglobin (HbA). However, heme disorientation in globins are often observed in recombinant production processes, both for HbA and HbF, although the degree of heme oriental disorder is much lower for HbF. In addition, the heme disorientation can be converted to a normal conformation by an oxidation-reduction process. A chromatographic cleaning process involving a strong anion exchanger can be utilized to remove such unstable and nondesirable forms of Hb...
2016: Advances in Experimental Medicine and Biology
Mingzi Lu, Caiyan Zhao, Quan Wang, Guoxing You, Ying Wang, Hongzhang Deng, Gan Chen, Sha Xia, Jingxiang Zhao, Bo Wang, Xianlei Li, Leihou Shao, Yan Wu, Lian Zhao, Hong Zhou
Although many attempts have been made to design advanced hemoglobin-based oxygen carriers (HBOCs), no clinically viable product has been widely approved, because they do not perform normal blood functions, such as coagulation, hematologic reactions and stability. Additionally, the in vivo oxygenation of hemoglobin-loaded nanoparticles (HbPs) encapsulated with polymers has seldom been proved. Herein, HbPs of approximately 200nm with good stability were successfully fabricated and exhibited oxygen-carrying capacity...
March 1, 2016: Colloids and Surfaces. B, Biointerfaces
Gang Chen, Ling Mo, Feng Lin, Xuejun Zhang, Jiaxin Liu, Hong Wang, Chengmin Yang
A rapid and sensitive high-performance liquid chromatography (HPLC) method for vitamin C (Vc) determination was developed in hemoglobin-based oxygen carriers (HBOCs) solution. After polymerized hemoglobin precipitation, Vc could be tested out within 5 min. The standard curve was linear in Vc quantity of 0.00-3.00 μg. Vc recovery was 103.56-108.68%, and relative standard deviation values of the repeatability and precision were below 1.00%. The limits of detection and limits of quantification were 0.002 ppm and 0...
2016: Artificial Cells, Nanomedicine, and Biotechnology
Yi Jia, Li Duan, Junbai Li
Safe and effective artificial oxygen carriers are the subject of great interest due to the problems of traditional blood transfusion and enormous demand in clinical use. In view of its unique oxygen-transport ability and normal metabolic pathways, hemoglobin is regarded as an ideal oxygen-carrying unit. With advances in nano-biotechnology, hemoglobin assemblies as artificial oxygen carriers achieve great development. Here, recent progress on hemoglobin-based oxygen carriers is highlighted in view of two aspects: acellular hemoglobin-based oxygen carriers and cellular hemoglobin-based oxygen carriers...
February 10, 2016: Advanced Materials
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