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hemoglobin based oxygen carriers

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https://www.readbyqxmd.com/read/29156721/a-hemoglobin-based-oxygen-carrier-sensitized-cisplatin-based-chemotherapy-in-hepatocellular-carcinoma
#1
Xiang Qi, Bing L Wong, Sze Hang Lau, Kevin Tak-Pan Ng, Sui Yi Kwok, Chris Kin-Wai Sun, Fei Chuen Tzang, Yan Shao, Chang Xian Li, Wei Geng, Chang Chun Ling, Yuen Yuen Ma, Xiao Bing Liu, Hui Liu, Jiang Liu, Wai Ho Yeung, Chung Mau Lo, Kwan Man
Background and Objective: Our previous study showed that liver graft injury not only promotes tumor recurrence, but also induces chemoresistance in recurrent HCC after liver transplantation. Recently, we found that the hemoglobin-based oxygen carrier"YQ23" significantly ameliorates hepatic IR injury and prevent tumor recurrence. Here, we intended to explore the novel therapeutic strategy using oxygen carrier "YQ23"to sensitize chemotherapy in HCC. Methods: To investigate the role of YQ23 combined with Cisplatin, the proliferation of HCC cells was examined under combined treatment by MTT and colony formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29140831/relative-efficacies-of-hboc-201-and-polyheme-to-increase-oxygen-transport-compared-to-blood-and-crystalloids-2017-military-supplement
#2
Gregory P Dubé, Arkadiy N Pitman, Colin F Mackenzie
BACKGROUND: Because total hemoglobin in circulation ([THb]) is an established predictor of clinical outcomes in anemic individuals, the relative efficacies of resuscitation fluids to increase [THb] can be used to design better hemoglobin-based oxygen carrier (HBOC) clinical trials. METHODS: Expected efficacies of HBOC-201 (13 g Hb/dL) and packed RBCs (pRBCs, 24 g Hb/dL) to increase [THb] were calculated and interpreted in the context of SAEs in the HEM-0115 phase III clinical trial...
November 14, 2017: Shock
https://www.readbyqxmd.com/read/29140548/a-phase-ib-open-label-single-arm-study-to-assess-the-safety-pharmacokinetics-and-impact-on-humoral-sensitization-of-sanguinate-infusion-in-patients-with-end-stage-renal-disease
#3
Bassam G Abu Jawdeh, E Steve Woodle, Abbie D Leino, Paul Brailey, Simon Tremblay, Tonya Dorst, Mouhamad H Abdallah, Amit Govil, Daniel Byczkowski, Hemant Misra, Abraham Abuchowski, Rita R Alloway
The endeavor to study desensitization in kidney transplantation hasn't been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive 3 weekly infusions of SG (320mg/Kg)...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29112633/2017-military-supplement-current-challenges-in-the-development-of-acellular-hemoglobin-oxygen-carriers-by-protein-engineering
#4
Andres S Benitez Cardenas, Premila P Samuel, John S Olson
This article reviews the key biochemical mechanisms that govern O2 transport, NO scavenging, and oxidative degradation of acellular hemoglobin and how these ideas have been used to try to develop strategies to engineer safer and more effective hemoglobin-based oxygen carriers (HBOCs). Significant toxicities due to acellular hemoglobin (Hb) have been observed after the administration of HBOCs or after the lysis of red cells, and include: (a) rapid clearance and kidney damage due to dissociation into dimers, haptoglobin binding, and macrophage activation; (b) early O2 release leading to decreased tissue perfusion in capillary beds; (c) interference with endothelial and smooth muscle signaling due to nitric oxide (NO) scavenging; (d) autooxidization of heme iron followed by production of reactive oxygen species; and (e) iron overload symptoms due to hemin loss, globin denaturation, iron accumulation, and further inflammation...
November 6, 2017: Shock
https://www.readbyqxmd.com/read/29112106/mechanisms-of-toxicity-and-modulation-of-hemoglobin-based-oxygen-carriers-hbocs
#5
Abdu I Alayash
Several adverse events have been associated with the infusion of hemoglobin-based oxygen carriers (HBOCs) including transient hypertension, gastrointestinal, pancreatic/liver enzyme elevation, and cardiac/renal injury in humans. Although several mechanisms have been suggested, the basis of HBOC toxicity is still poorly understood. Scavenging of vascular endothelial nitric oxide (NO) and heme-mediated oxidative side reactions are thought to be the major causes of toxicity. However, based on more recent preclinical studies, oxidative pathways (driven by the heme prosthetic group) appear to play a more prominent role in the overall toxicity of free Hb or HBOCs...
November 3, 2017: Shock
https://www.readbyqxmd.com/read/29081812/peptide-inhibitor-of-complement-c1-inhibits-the-peroxidase-activity-of-hemoglobin-and-myoglobin
#6
Pamela S Hair, Kenji M Cunnion, Neel K Krishna
Hemoglobin is the natural carrier of oxygen in red blood cells (RBCs). While intracellular hemoglobin provides life-sustaining oxygen transport, extracellular free hemoglobin displays toxicity due to inherent peroxidase activity generating reactive oxygen species that subsequently react with the hemoglobin molecule to produce toxic heme degradation products resulting in free radicals, oxidative stress damage, and lipid peroxidation. We have recently demonstrated that Peptide Inhibitor of Complement C1 (PIC1) inhibits peroxidase activity of the heme-based enzyme myeloperoxidase...
2017: International Journal of Peptides
https://www.readbyqxmd.com/read/29076972/users-guide-to-pitfalls-and-lessons-learned-about-hboc-201-during-clinical-trials-expanded-access-and-clinical-use-in-1-701-patients
#7
Colin F Mackenzie, Gregory P Dubé, Arkaidy Pitman, Melissa Zafirelis
Lessons learned during 1,701 clinical uses of HBOC-201, a polymerized bovine hemoglobin-based oxygen carrier (HBOC), were identified to provide management lessons and training material for future clinical trials and use. HBOC-201 contains 13 g/dL hemoglobin (Hb), is iso-oncotic, stable at 2°C to 30°C with shelf-life of 3 years, requires no cross-matching with half-life of 19 h, and plasma volume distribution. Adverse effects include increased blood pressure, oliguria, gastrointestinal (GI) symptoms, yellow skin and scleral discoloration, decreased pulse oximetry measurements, and transient increases in methemoglobin, hepatic, and pancreatic enzymes...
October 25, 2017: Shock
https://www.readbyqxmd.com/read/29076161/use-of-the-blood-substitute-hboc-201-in-critically-ill-patients-during-sickle-crisis-a-three-case-series
#8
Jonathan M Davis, Nura El-Haj, Nimish N Shah, Garry Schwartz, Margaret Block, James Wall, Mark Tidswell, Ernest DiNino
BACKGROUND: Red blood cell (RBC) transfusion is an important treatment modality during severe sickle cell crisis (SCC). SCC patients who refuse, or cannot accept, RBCs present a unique challenge. Acellular hemoglobin (Hb)-based oxygen carriers (HBOCs) might be an alternative for critically ill patients in SCC with multiorgan failure due to life-threatening anemia. HBOC-201 (HbO2 Therapeutics) has been administered to more than 800 anemic patients in 22 clinical trials, but use of any HBOCs in critically ill sickle cell patients with organ failure is exceedingly rare...
October 26, 2017: Transfusion
https://www.readbyqxmd.com/read/29049260/a-quantitative-analysis-of-microcirculation-in-skin-defects-covered-with-topical-wound-dressings-or-a-newly-developed-collagen-matrix
#9
Manuel Held, Fabian Medved, Wiebke Petersen, Dascha Sophie Tolzmann, Afshin Rahmanian-Schwarz, Hans-Eberhard Schaller, Jens Rothenberger
OBJECTIVE: Innovative skin substitutes and temporary wound dressings are frequently used in the treatment of superficial and partial-thickness wounds. The aim of this study was to compare 2 commonly used temporary skin dressings with a newly developed collagen matrix to determine changes in microcirculation as measured by blood flow, hemoglobin oxygenation, and relative hemoglobin values during healing of partial-thickness skin defects. METHODS: This animal study involved 28 adult male Lewis rats...
November 2017: Advances in Skin & Wound Care
https://www.readbyqxmd.com/read/28986211/in-vivo-evaluation-of-hemerythrin-based-oxygen-carriers-similarities-with-hemoglobin-based-counterparts
#10
Vlad Al Toma, Anca D Farcas, Ioana Roman, Bogdan Sevastre, Denisa Hathazi, Florina Scurtu, Grigore Damian, Radu Silaghi-Dumitrescu
We have previously proposed the annelid-derived protein, hemerythrin, as a viable replacement for hemoglobin in the synthesis of semi-synthetic oxygen carriers ("blood substitutes"). Here, we report the first in vivo tests for potential hemerythrin-based oxygen carriers (HrBOC), using a battery of experiments involving Wistar rats and previously tested on a series of hemoglobin-based oxygen carrier candidates (HBOC). At the concentrations tested, hemerythrin appears to behave similarly to hemoglobin - including, importantly, immunological effects...
October 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28985606/preparation-of-artificial-red-cell-and-its-application-on-alleviation-of-tumor-hypoxia
#11
Jiaxin Qu, Xiaomeng Guo, Wei Li, Wanqing Hou, Hanbo Zhang, Lihua Luo, Chunqi Zhu, Jie Yang, Xiaoyi Yin, Yuan Tao, Yongzhong Du, Yan Lou, Dawei Chen, Jian You
Hemoglobin-based oxygen carriers were developed as an alternative for blood transfusion. However, the research progress for their further clinic applications was slow in recent several years. Hypoxia is found in most solid tumors, which is responsible for the tumor formation, increased metastasis, drug resistance during therapeutic process as well as poor patient survival. In this work, novel hemoglobin (Hb) loaded nanoliposomes, as artificial red cells for oxygen delivery, were optimized by screening various types of phospholipids and analyzing different mole ratio of phospholipid to cholesterol...
September 20, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28968286/2017-military-supplement-hemoglobin-based-oxygen-carriers-current-state-of-the-art-and-novel-molecules
#12
Anirban Sen Gupta
In blood, the primary role of RBCs is to transport oxygen via highly regulated mechanisms involving hemoglobin (Hb). Hb is a tetrameric porphyrin protein comprising of two α- and two β-polypeptide chains, each containing an iron-containing heme group capable of binding one oxygen molecule. In military as well as civilian traumatic exsanguinating hemorrhage, rapid loss of RBCs can lead to sub-optimal tissue oxygenation and subsequent morbidity and mortality. In such cases, transfusion of whole blood or RBCs can significantly improve survival...
September 29, 2017: Shock
https://www.readbyqxmd.com/read/28884612/conjugation-with-20%C3%A2-kda-dextran-decreases-the-autoxidation-rate-of-bovine-hemoglobin
#13
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
#14
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
#15
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...
December 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
#16
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...
October 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
#17
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
#18
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
#19
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
#20
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
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