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Thomas Ming Swi Chang - One of the best experts on this subject based on the ideXlab platform.
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nanobiotechnology for hemoglobin based Blood Substitutes
Critical Care Clinics, 2009Co-Authors: Thomas Ming Swi ChangAbstract:Nanobiotechnology is the assembling of biological molecules into nanodimension complexes. This has been used for the preparation of polyhemoglobin formed by the assembling of hemoglobin molecules into a soluble nanodimension complex. New generations of this approach include the nanobiotechnological assembly of hemoglobin, catalase, and superoxide dismutase into a soluble nanodimension complex. This acts as an oxygen carrier and an antioxidant for those conditions with potential for ischemiareperfusion injuries. Another recent novel approach is the assembling of hemoglobin and fibrinogen into a soluble nanodimension polyhemoglobin-fibrinogen complex that acts as an oxygen carrier with platelet-like activity. This is potentially useful in cases of extensive Blood loss requiring massive replacement using Blood Substitutes, resulting in the need for the replacement of platelets and clotting factors. A further step is the preparation of nanodimension artificial red Blood cells that contain hemoglobin and all the enzymes present in red Blood cells.
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Blood Substitutes based on nanobiotechnology
Trends in Biotechnology, 2006Co-Authors: Thomas Ming Swi ChangAbstract:Stimulated by concerns of potential infective agents in donated Blood, commercial enterprises have attempted to develop Blood Substitutes since the 1900s. After several years of development, a few of the many leads are showing promise. In this article, nanobiotechnological approaches that are now in phase III clinical trials are reviewed, followed by a discussion of how important basic knowledge gained is being used to develop new generations of Blood Substitutes based on nanobiotechnology.
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present status of modified hemoglobin as Blood Substitutes and oral therapy for end stage renal failure using artificial cells containing genetically engineered cells
Annals of the New York Academy of Sciences, 2006Co-Authors: Thomas Ming Swi ChangAbstract:: Artificial cell or bioencapsulation has been developed for use in bioartificial organs, drug delivery, Blood Substitutes, and other areas. Recent rapid advances in modified hemoglobin Blood Substitutes have resulted in advance stages of Phase III clinical trials. Another area of use is in oral therapy, using artificial cells microencapsulated with genetically engineered cells for use in end stage renal failure and other conditions.
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Blood Substitutes principles methods products and clinical trials
1998Co-Authors: Thomas Ming Swi ChangAbstract:Part I Present status of Blood Substitutes in phase II and phase III clinical trials: donor Blood uses in surgery and the potential for "Blood substitues" the clinical development of human polymerized haemoglobin Blood and HemAssist (DCLHb) - potentially a complementary therapeutic team Hemolink, an o-Raffinose crosslinked haemoglobin-based oxygen carrier overview of preclinical and clinical efficacy of biopure's HBOC's fluorocarbon-based oxygen-delivery - basic principles and product development perfluorochemical emulations - future alternatives to transfusion. Part II Future generations of Blood Substitutes: cell-free haeomoglobin and tissue oxidants - probing the mechanisms of haemoglobin cytotoxicity crosslinked haeomglobin-superoxide dismutase-catalase - a second generation haeomoglobin based substitute with antioxidant activities lipsome delivery of haemoglobin - molecular and cellular interactions in the vascular pool nanoencapsulation of haemoglobin and red Blood cell enzymes based on nanotechnology and biodegradable polymer.
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in vitro method to determine the safety of modified hemoglobin Blood Substitutes for human prior to clinical use
1992Co-Authors: Thomas Ming Swi Chang, Colin ListerAbstract:The present invention relates to an in vitro method to determine the safety of modified hemoglobin Blood Substitutes for human subjects prior to their clinical usages, wherein the method is based on complement activation reaction from adding modified hemoglobin Blood Substitutes to a human plasma sample and comprises the steps of: a) obtaining at least one plasma sample from at least one human subject by i) taking a Blood sample and immediately centrifugating; and ii) separating the centrifuged Blood sample of step i) and retaining the supernatant plasma; b) mixing the plasma of step ii) with the modified hemoglobin Blood Substitutes or control-ringer in a weight/volume ratio of about 4:1; c) incubating for a time sufficient to allow for a complement activation reaction to occur; d) adding the product of step c) to an appropriate volume of saline in an EDTA tube; and e) analyzing the degree of complement activation by analysis of the product of step d); thereby determining the safety of the modified hemoglobin Blood Substitutes relative to the human subject plasma sample based on the detection of complement activation.
Kenneth C. Lowe - One of the best experts on this subject based on the ideXlab platform.
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Blood Substitutes from chemistry to clinic
Journal of Materials Chemistry, 2006Co-Authors: Kenneth C. LoweAbstract:Blood Substitutes are oxygen-carrying fluids that aim to provide an alternative to the transfusion of Blood. Strategies for developing such Substitutes have involved the production of materials based on the naturally occurring respiratory pigment, haemoglobin (Hb), or synthetic, chemically inert, fluorinated liquids called perfluorochemicals (PFCs). Commercial products in both categories have been developed and some approved for clinical use, primarily to facilitate oxygen supply to tissues during surgery or therapy. The latest research is focused on using microbial and plant ‘cell factories’ to express recombinant Hb, understanding the properties of polymeric Hbs from invertebrate animals, and the use of feedback from stakeholders to inform the development of new educational materials to assist patients to make informed choices on future transfusion options.
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benefit and risk perceptions in transfusion medicine Blood and Blood Substitutes
Journal of Internal Medicine, 2003Co-Authors: Kenneth C. Lowe, Eamonn FergusonAbstract:Blood transfusion is a remarkably safe, routine procedure in clinical medicine. However, little attention has focused on the perceptions of risk associated with the receipt of Blood, Blood products or 'Blood Substitutes'. It is pertinent to ask (i) what key stakeholder groups know about transfusion, (ii) how safe they perceive Blood/Blood products to be, (iii) how the latter information might influence their own and others' perceptions of risk linked to transfusion, and (iv) the extent to which approved Blood Substitutes might be preferred over autologous or donor Blood. An appreciation of what stakeholders perceive to be the benefits and risks of the receipt of Blood and Blood Substitutes will inform future transfusion strategies. To obtain such information, a programme of research has been initiated at Nottingham. Surveys have targeted key stakeholder groups, namely, UK adult Blood donors and non-donors, anaesthetists, general practitioners and health care journalists. Experimental studies examining message framing and cueing have also been conducted with undergraduate students. Such research will improve misunderstandings about current issues associated with Blood donation and transfusion against the backdrop of changing public trust of health care professionals and attitudes and expectations on Blood safety and benefits of Blood Substitutes.
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fluorinated Blood Substitutes and oxygen carriers
Journal of Fluorine Chemistry, 2001Co-Authors: Kenneth C. LoweAbstract:Abstract Perfluorochemicals (PFCs) are highly fluorinated, inert organic compounds that can dissolve large volumes of O 2 and other respiratory gases. PFCs are unreactive in the body and excreted primarily as a vapour by exhalation. However, PFC liquids are immiscible with aqueous systems, including Blood, but can be injected safely into the Bloodstream as emulsions. Such emulsions are currently being assessed clinically as temporary, intravascular respiratory gas-carriers and tissue oxygenating fluids (so-called ‘Blood Substitutes’). One such emulsion, a commercial perflubron-based formulation, Oxygent™, is in advanced clinical trials as an alternative to allogeneic (donor) Blood transfusion during surgery. Basic and clinical studies indicate that Oxygent™ can support O 2 delivery to tissues during acute Blood loss with no abnormal haemodynamic changes.
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second generation perfluorocarbon emulsion Blood Substitutes
Artificial Cells Blood Substitutes and Biotechnology, 2000Co-Authors: Kenneth C. LoweAbstract:A novel series of perfluorocarbon (PFC) emulsions, based on perfluorodecalin (C10F18) and stabilised with up to 2.5% (w/v) of lecithin have been produced for evaluation as injectable, temporary respiratory gas-carrying Blood Substitutes. Some formulations contained 1.0% (w/v) of perfluorodimorpholinopropane (C11F22N2O3) to retard droplet growth through molecular diffusion (Ostwald Ripening). Other emulsions contained novel, amphiphilic fluorinated surfactants, such as, for example, the monocarbamate, C8F17C2H4NHC(O)(CH2CH2O)2Me (designated compound P6), at 0.1% (w/v) to enhance stability. Emulsions were prepared by homogenisation, were steam sterilisable and were stable for >300 days (25°C). Injection of rats (7.5 ml kg−1 b.w.) with emulsions produced significant (P < 0.05), transient increases in liver and spleen weights. One emulsion inhibited phorbol 12-myristate 13-acetate (PMA)-stimulated, Luminol®-enhanced, chemiluminescence of human polymorphonuclear leucocytes (PMNL) in vitro, suggesting possible ...
A. P. Shepherd - One of the best experts on this subject based on the ideXlab platform.
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co oximetry interference by hemoglobin based Blood Substitutes
Anesthesia & Analgesia, 2001Co-Authors: Aaron Ashoka Ali, Genevieve Shepherd Ali, J M Steinke, A. P. ShepherdAbstract:The Blood Substitutes now being developed from molecularly modified hemoglobin interfere with a wide variety of clinical analyzers, but their effects on cooximeters are unknown. Therefore, we investigated the effects of five hemoglobin-based Blood Substitutes on the measurements of eight different oximeters and cooximeters: the AVL Omni 6, the AVOXimeters 1000 and 4000, the Ciba Corning (now Bayer) CC270 CO-Oximeter, the Instrumentation Laboratory Synthesis 35, the IL482 and IL682 CO-Oximeters, and the Radiometer OSM3 Hemoximeter. The five Blood Substitutes in this study were obtained from Apex Bioscience (Research Triangle Park, NC), Baxter Healthcare Corp. (Deerfield, IL), Biopure Corp. (Cambridge, MA), Hemoglobin Therapeutics, and Hemosol, Inc. (Etobicoke, Ontario, Canada). A cooximeter control was used to compare the eight different instruments’ measurements on unaltered human hemoglobin. The instruments yielded measurements of total hemoglobin concentration in undiluted Blood Substitutes that were generally not more variable than those on the control material. By contrast, when compared with readings on controls, the test instruments yielded measurements of the fractional concentrations of oxy-, deoxy-, carboxy-, and methemoglobin that showed greater instrument-to-instrument disparities and larger standard deviations about the all-instrument means. In some cases, the interference was even more obvious: five of six cooximeters gave negative carboxyhemoglobin readings on one particular product. Our findings indicate that the instruments will give less accurate but clinically useful measurements in the presence of these hemoglobin-based Blood Substitutes.
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co oximetry interference by hemoglobin based Blood Substitutes
Anesthesia & Analgesia, 2001Co-Authors: J M Steinke, A. P. ShepherdAbstract:UNLABELLED: The Blood Substitutes now being developed from molecularly modified hemoglobin interfere with a wide variety of clinical analyzers, but their effects on cooximeters are unknown. Therefore, we investigated the effects of five hemoglobin-based Blood Substitutes on the measurements of eight different oximeters and cooximeters: the AVL Omni 6, the AVOXimeters 1000 and 4000, the Ciba Corning (now Bayer) CC270 CO-Oximeter, the Instrumentation Laboratory Synthesis 35, the IL482 and IL682 CO-Oximeters, and the Radiometer OSM3 Hemoximeter. The five Blood Substitutes in this study were obtained from Apex Bioscience (Research Triangle Park, NC), Baxter Healthcare Corp. (Deerfield, IL), Biopure Corp. (Cambridge, MA), Hemoglobin Therapeutics, and Hemosol, Inc. (Etobicoke, Ontario, Canada). A cooximeter control was used to compare the eight different instruments' measurements on unaltered human hemoglobin. The instruments yielded measurements of total hemoglobin concentration in undiluted Blood Substitutes that were generally not more variable than those on the control material. By contrast, when compared with readings on controls, the test instruments yielded measurements of the fractional concentrations of oxy-, deoxy-, carboxy-, and methemoglobin that showed greater instrument-to-instrument disparities and larger standard deviations about the all-instrument means. In some cases, the interference was even more obvious: five of six cooximeters gave negative carboxyhemoglobin readings on one particular product. Our findings indicate that the instruments will give less accurate but clinically useful measurements in the presence of these hemoglobin-based Blood Substitutes. IMPLICATIONS: We investigated the effects of five hemoglobin-based Blood Substitutes on the measurements of eight different cooximeters. Some Blood Substitutes caused obvious interference, such as negative carboxyhemoglobin readings; however, the findings indicate that cooximeters will generally give less accurate but clinically useful measurements in the presence of the hemoglobin-based Blood Substitutes that were tested.
Duncan S. Pepper - One of the best experts on this subject based on the ideXlab platform.
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haemoglobin based Blood Substitutes and sepsis
The Lancet, 1995Co-Authors: Elwyn Griffiths, Angeles Cortes, Nick Gilbert, Pauline Stevenson, Shirley L Macdonald, Duncan S. PepperAbstract:Abstract An important concern that has received little attention is the possible increased susceptibility to bacterial infections of patients infused with cell-free haemoglobin-based Blood Substitutes. We show that pyridoxalated polymerised human haemoglobin promotes fulminating Escherichia coli septicaemia in mice, which draws attention to the potential danger of such products in the clinic.
Yang Yang - One of the best experts on this subject based on the ideXlab platform.
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construction and evaluation of hemoglobin based capsules as Blood Substitutes
Advanced Functional Materials, 2012Co-Authors: Yi Jia, Mingchun Du, Luru Dai, Jinbo Fei, Yue Cui, Junbai Li, Yang YangAbstract:Hemoglobin-based capsules for use as Blood Substitutes are successfully fabricated by covalent layer-by-layer assembly. Dialdehyde heparin (DHP) is used both as one of the wall components and a cross-linker without employing other extraneous or toxic crosslinking agents. The biocompatibility of (Hb/DHP)6 microcapsules is evaluated through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and cell experiments. The hemocompatibility of (Hb/DHP)6 microcapsules is characterized in terms of prothrombin time, thrombin time, activated partial thromboplastin time, and hemolysis rate. The oxygen-carrying capacity of the microcapsules is demonstrated by converting the deoxy-Hb state of the microcapsules into the oxy-Hb state. All these results demonstrate that the hemoglobin-based microcapsules exhibit oxygen-carrying capacity as well as biocompatibility and hemocompatility, indicating that the as-prepared capsules have great potential to function as Blood Substitutes.
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Construction and Evaluation of Hemoglobin‐Based Capsules as Blood Substitutes
Advanced Functional Materials, 2012Co-Authors: Yi Jia, Mingchun Du, Luru Dai, Jinbo Fei, Yue Cui, Junbai Li, Yang YangAbstract:Hemoglobin-based capsules for use as Blood Substitutes are successfully fabricated by covalent layer-by-layer assembly. Dialdehyde heparin (DHP) is used both as one of the wall components and a cross-linker without employing other extraneous or toxic crosslinking agents. The biocompatibility of (Hb/DHP)6 microcapsules is evaluated through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and cell experiments. The hemocompatibility of (Hb/DHP)6 microcapsules is characterized in terms of prothrombin time, thrombin time, activated partial thromboplastin time, and hemolysis rate. The oxygen-carrying capacity of the microcapsules is demonstrated by converting the deoxy-Hb state of the microcapsules into the oxy-Hb state. All these results demonstrate that the hemoglobin-based microcapsules exhibit oxygen-carrying capacity as well as biocompatibility and hemocompatility, indicating that the as-prepared capsules have great potential to function as Blood Substitutes.
