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hemoglobin based oxygen carriers

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https://www.readbyqxmd.com/read/28188676/hemoglobin-based-oxygen-carrier-rescues-double-transplant-patient-from-life-threatening-anemia
#1
M F Gomez, O Aljure, G Ciancio, M Lynn
This is a case of a 46-year-old male, Jehovah's Witness kidney-pancreas transplant recipient found to have early in the postoperative period, splenic vein thrombosis requiring heparin infusion. Two days later, he developed severe symptomatic anemia (Hb < 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). Transfusion of allogeneic blood products was not an option, prompting use of a hemoglobin-based oxygen carrier (HBOC)...
February 11, 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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28054978/hemoglobin-based-blood-substitutes-and-the-treatment-of-sickle-cell-disease-more-harm-than-help
#5
REVIEW
Abdu I Alayash
Intense efforts have been made by both industry and academia over the last three decades to produce viable hemoglobin (Hb)-based oxygen carriers (HBOCs), also known as "blood substitutes". Human trials conducted so far by several manufactures in a variety of clinical indications, including trauma, and elective surgeries have failed and no product has gained the Food and Drug Administration approval for human use. Safety concerns due to frequent incidences of hemodynamic, cardiac events, and even death led to the termination of some of these trials...
January 4, 2017: Biomolecules
https://www.readbyqxmd.com/read/27908199/hemoglobin-extravasation-in-the-brain-of-rats-exchange-transfused-with-hemoglobin-based-oxygen-carriers
#6
Laura Terraneo, Paola Bianciardi, Ashok Malavalli, Gnel Mkrtchyan, Stephanie N Spann, Jeff Lohman, Michele Samaja, Kim D Vandegriff
Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb...
December 1, 2016: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/27867357/machine-perfusion-of-porcine-livers-with-oxygen-carrying-solution-results-in-reprogramming-of-dynamic-inflammation-networks
#7
David Sadowsky, Ruben Zamora, Derek Barclay, Jinling Yin, Paulo Fontes, Yoram Vodovotz
Background:Ex vivo machine perfusion (MP) can better preserve organs for transplantation. We have recently reported on the first application of an MP protocol in which liver allografts were fully oxygenated, under dual pressures and subnormothermic conditions, with a new hemoglobin-based oxygen carrier (HBOC) solution specifically developed for ex vivo utilization. In those studies, MP improved organ function post-operatively and reduced inflammation in porcine livers. Herein, we sought to refine our knowledge regarding the impact of MP by defining dynamic networks of inflammation in both tissue and perfusate...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27859328/addressing-the-unmet-need-of-life-threatening-anemia-with-hemoglobin-based-oxygen-carriers
#8
Richard B Weiskopf, Andrei M Beliaev, Aryeh Shander, Nicole R Guinn, Andrew P Cap, Paul M Ness, Toby A Silverman
No abstract text is available yet for this article.
January 2017: Transfusion
https://www.readbyqxmd.com/read/27798697/long-term-stored-hemoglobin-vesicles-a-cellular-type-of-hemoglobin-based-oxygen-carrier-has-resuscitative-effects-comparable-to-that-for-fresh-red-blood-cells-in-a-rat-model-with-massive-hemorrhage-without-post-transfusion-lung-injury
#9
Masahiro Tokuno, Kazuaki Taguchi, Keishi Yamasaki, Hiromi Sakai, Masaki Otagiri
Hemoglobin-vesicles (HbV), encapsulating highly concentrated human hemoglobin in liposomes, were developed as a substitute for red blood cells (RBC) and their safety and efficacy in transfusion therapy has been confirmed in previous studies. Although HbV suspensions are structurally and physicochemically stabile for least 1-year at room temperature, based on in vitro experiments, the issue of whether the use of long-term stored HbV after a massive hemorrhage can be effective in resuscitations without adverse, post-transfusion effects remains to be clarified...
2016: PloS One
https://www.readbyqxmd.com/read/27787946/application-of-hbocs-electrophoretic-method-to-detect-a-new-blood-substitute-derived-from-the-giant-extracellular-hemoglobin-of-lugworm
#10
A Marchand, N Crepin, I Roulland, F Semence, V Domergue, F Zal, V Polard, A Coquerel
Manipulation of blood and blood components is prohibited in sports by the World Anti-Doping Agency (WADA). This includes the use of blood substitutes to increase oxygen transport, like hemoglobin-based oxygen carriers (HBOCs), which are compounds derived from hemoglobin. Despite their medical interest, the first generation of HBOCs had serious adverse effects and was abandoned. However, new studies are now exploiting the properties of marine worm hemoglobins, which circulate as giant extracellular complexes with high oxygen-binding capacities...
October 27, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27728906/carbon-monoxide-saturated-hemoglobin-based-oxygen-carriers-attenuate-high-altitude-induced-cardiac-injury-by-amelioration-of-the-inflammation-response-and-mitochondrial-oxidative-damage
#11
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...
2017: Cardiology
https://www.readbyqxmd.com/read/27714247/strain-promoted-azide-alkyne-cycloaddition-for-protein-protein-coupling-in-the-formation-of-a-bis-hemoglobin-as-a-copper-free-oxygen-carrier
#12
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
https://www.readbyqxmd.com/read/27696787/a-pegylated-bovine-hemoglobin-as-a-potent-hemoglobin-based-oxygen-carrier
#13
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
https://www.readbyqxmd.com/read/27679789/hemoglobin-based-oxygen-carrier-for-traumatic-hemorrhagic-shock-treatment-in-a-jehovah-s-witness
#14
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
https://www.readbyqxmd.com/read/27658499/hemoglobin-glutamer-250-bovine-in-south-africa-consensus-usage-guidelines-from-clinician-experts-who-have-treated-patients
#15
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
https://www.readbyqxmd.com/read/27626360/exploring-oxidative-reactions-in-hemoglobin-variants-using-mass-spectrometry-lessons-for-engineering-oxidatively-stable-oxygen-therapeutics
#16
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
https://www.readbyqxmd.com/read/27526872/management-of-the-jehovah-s-witness-in-obstetrics-and-gynecology-a-comprehensive-medical-ethical-and-legal-approach
#17
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
https://www.readbyqxmd.com/read/27471729/transcriptional-suppression-of-renal-antioxidant-enzyme-systems-in-guinea-pigs-exposed-to-polymerized-cell-free-hemoglobin
#18
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
https://www.readbyqxmd.com/read/27470146/engineering-tyrosine-electron-transfer-pathways-decreases-oxidative-toxicity-in-hemoglobin-implications-for-blood-substitute-design
#19
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
https://www.readbyqxmd.com/read/27453782/oxygen-delivering-biomaterials-for-tissue-engineering
#20
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
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