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Oxygen Carrier (oxygen + carrier)
Kinds of Oxygen Carrier Selected AbstractsHemoCD as an Artificial Oxygen Carrier: Oxygen Binding and AutoxidationARTIFICIAL ORGANS, Issue 2 2009Koji Kano Abstract Despite many attempts to construct completely artificial systems for carrying oxygen (O2) in aqueous solution, no successful example had been reported until quite recently except for picket fence porphinatoiron(II) embedded in liposomal membrane. We newly prepared a 1:1 complex (hemoCD) of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphinatoiron(II) (Fe[II]TPPS) and a per- O -methylated ,-cyclodextrin dimer having a pyridine linker (Py3CD). HemoCD binds O2 reversibly in aqueous solution. The oxygen affinity corresponding to the partial O2 pressure, at which half of the hemoCD molecules are oxygenated, was 16.9 torr in phosphate buffer at pH 7.0 and 25°C. Oxy-hemoCD was gradually autoxidized (t1/2 = 30.1 h) due to nucleophilic attack of a water molecule to the O2,Fe bond. Encapsulation of the iron center of Fe(II)TPPS by two cyclodextrin truncated cones is essential for binding of O2 to the ferrous center of the porphyrin. This manuscript reports the basic characteristics of hemoCD and the possible future utility of a totally artificial O2 carrier. [source] Hepatocyte Function in a Radial-flow Bioreactor Using a Perfluorocarbon Oxygen CarrierARTIFICIAL ORGANS, Issue 11 2005Martin J. Nieuwoudt Abstract:, The aims of this study were, first, to indicate the metabolic activity of hepatocytes in a radial-flow polyurethane foam matrix bioreactor relative to monocultures, and second, to evaluate the effect on the hepatocytes of including a synthetic perfluorocarbon (PFC) oxygen carrier to the recirculating medium. The efficient O2 -carrying ability of PFCs may be beneficial to bioreactors employed in stressed cellular environments. Thus, they may also be useful in the treatment of an acute liver failure patient with a bioartificial liver support system (BALSS). Data on the function of three-dimensional (3-D) hepatocyte cultures exposed to emulsified PFCs are lacking. Results: the metabolic functions of the 3-D hepatocyte cultures were improved relative to monocultures. Three-dimensional cultures with and without PFC behaved similarly, and no adverse effects could be detected when PFC was included in the recirculating medium. The addition of PFC significantly improved lidocaine clearance possibly due to the presence of higher O2 tension in the medium. Imaging indicated that large aggregates formed and that seeding had followed flow through the matrix. Simulations indicated first, that the cell numbers used in this study had been insufficient to challenge the bioreactor O2 supply explaining the similarity in performance of the 3-D cultures, and second, that the benefit of adding PFC would be more pronounced at the cell densities likely to be used in a BALSS bioreactor. [source] Perfluorocarbon-Based Oxygen Carriers: Review of Products and TrialsARTIFICIAL ORGANS, Issue 8 2010Camila Irene Castro Abstract A viable blood substitute is still of great necessity throughout the world. Perfluorocarbon-based oxygen carriers (PFCOCs) are emulsions that take advantage of the high solubility of respiratory gases in perfluorocarbons (PFCs). Despite attractive characteristics, no PFCOC is currently approved for clinical uses. Some PFCOCs have failed due to secondary effects of the surfactants employed, like Fluosol DA, whereas others to adverse cerebrovascular effects on cardiopulmonary bypass, such as Oxygent. Further in-depth, rigorous work is needed to overcome the annotated failures and to obtain a safe PFCOC approved for human use. The aim of this study is to review in detail the most-used PFCOCs, their formulation, and preclinical and clinical trials, and to reflect upon causes of failure and strategies to overcome such failures. [source] Artificial Oxygen Carriers: Scientific and Biotechnological Points of ViewARTIFICIAL ORGANS, Issue 2 2009Dr. Jan Simoni Research ProfessorPrincipal Investigator of the Texas Tech Blood Substitute Program First page of article [source] Artificial Oxygen Carriers: A Clinical Point of ViewARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi MD No abstract is available for this article. [source] Possible Role of Artificial Oxygen Carriers in Transfusion Medicine: A Retrospective Analysis on the Current Transfusion PracticeARTIFICIAL ORGANS, Issue 2 2009Fumiaki Yoshiba Abstract Artificial oxygen carriers (AOC) are under development as a substitute for red blood cells (RBC) in homologous transfusion (Tx). The lack of surface antigen in AOC makes ABO-typing and antibody-screening (T/S) unnecessary. Pathogen elimination renders it much safer, and long-term stability allows ubiquitous storage for emergency use. To delineate the utility of AOC, we retrospectively examined current Tx practices in Tokai University and the Japanese Red Cross Society. The emergency department of Tokai University Hospital has been using O(+)Rh(+) RBC in patients with hemorrhagic shock before Tx becomes available. Those who received the RBCs within 60 min of injury had a significantly higher survival rate than those who received it later (,60 min). The Red Cross Blood Center provided 411 units of RBC for 138 urgent requests for rare blood types. Our analysis suggests that if an AOC were available for the initial six units, 96% of such requests could have been covered to avoid urgent donor allocation, preparation, and Tx. Among 2079 surgical cases who ordered T/S, only 29% actually required Tx, rendering >70% of the T/S unnecessary. Because only 7.4% required nine units or more, more than 92% of T/S and Tx could have been avoided in retrospect if an AOC were available for the initial eight units. The results suggest that an AOC might be useful in various situations to alleviate problems, concerns, and technical burden in the current Tx practices. Because the expected utility is based mainly on physical characteristics, AOC may remain advantageous even when biogenetically derived RBC becomes available. [source] Review of Hemoglobin-Vesicles as Artificial Oxygen CarriersARTIFICIAL ORGANS, Issue 2 2009Hiromi Sakai Abstract Blood transfusion systems have greatly benefited human health and welfare. Nevertheless, some problems remain: infection, blood type mismatching, immunological response, short shelf life, and screening test costs. Blood substitutes have been under development for decades to overcome such problems. Plasma component substitutes have already been established: plasma expanders, electrolytes, and recombinant coagulant factors. Herein, we focus on the development of red blood cell (RBC) substitutes. Side effects hindered early development of cell-free hemoglobin (Hb)-based oxygen carriers (HBOCs) and underscored the physiological importance of the cellular structure of RBCs. Well-designed artificial oxygen carriers that meet requisite criteria are expected to be realized eventually. Encapsulation of Hb is one idea to shield the toxicities of molecular Hbs. However, intrinsic issues of encapsulated Hbs must be resolved: difficulties related to regulating the molecular assembly, and management of its physicochemical and biochemical properties. Hb-vesicles (HbV) are a cellular type of HBOC that overcome these issues. The in vivo safety and efficacy of HbV have been studied extensively. The results illustrate the potential of HbV as a transfusion alternative and promise its use for other clinical applications that remain unattainable using RBC transfusion. [source] Nickel- and Copper-Based Oxygen Carriers for Chemical Looping CombustionCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 3 2009A. Hoteit Abstract Chemical looping combustion (CLC) is a combustion process in which the different fuels can be burnt with inherent separation of CO2. A CLC system has two interconnected reactors named as fuel and air reactor. In the fuel reactor, metal oxides supply oxygen for the combustion of the gaseous fuel, and the metal oxides are regenerated (oxidized) with air in the air reactor. The feasibility of a CLC system greatly depends on the selection of appropriate metal oxides as oxygen carriers. In the present study, NiO/NiAl2O4 and Cu0.95Fe1.05AlO4 were tested experimentally in a fluidized-bed reactor as a function of number of oxidation-reduction cycles, temperature and effect of steam mixed with methane as a fuel. A 30-MWfuel CLC system was simulated for the combustion of biogas, syngas and methane on the basis of the experimental results. [source] Parametric study of chemical looping combustion for tri-generation of hydrogen, heat, and electrical power with CO2 captureINTERNATIONAL JOURNAL OF ENERGY RESEARCH, Issue 8 2005J. Wolf Abstract In this article, a novel cycle configuration has been studied, termed the extended chemical looping combustion integrated in a steam-injected gas turbine cycle. The products of this system are hydrogen, heat, and electrical power. Furthermore, the system inherently separates the CO2 and hydrogen that is produced during the combustion. The core process is an extended chemical looping combustion (exCLC) process which is based on classical chemical looping combustion (CLC). In classical CLC, a solid oxygen carrier circulates between two fluidized bed reactors and transports oxygen from the combustion air to the fuel; thus, the fuel is not mixed with air and an inherent CO2 separation occurs. In exCLC the oxygen carrier circulates along with a carbon carrier between three fluidized bed reactors, one to oxidize the oxygen carrier, one to produces and separate the hydrogen, and one to regenerate the carbon carrier. The impacts of process parameters, such as flowrates and temperatures have been studied on the efficiencies of producing electrical power, hydrogen, and district heating and on the degree of capturing CO2. The result shows that this process has the potential to achieve a thermal efficiency of 54% while 96% of the CO2 is captured and compressed to 110 bar. Copyright © 2005 John Wiley & Sons, Ltd. [source] Syngas chemical looping gasification process: Bench-scale studies and reactor simulationsAICHE JOURNAL, Issue 8 2010Fanxing Li Abstract The syngas chemical looping process co-produces hydrogen and electricity from syngas through the cyclic reduction and regeneration of an iron oxide based oxygen carrier. In this article, the reducer, which reduces the oxygen carrier with syngas, is investigated through thermodynamic analysis, experiments, and ASPEN Plus® simulation. The thermodynamic analysis indicates that the countercurrent moving-bed reducer offers better gas and solids conversions when compared to the fluidized-bed reducer. The reducer is continuously operated for 15 h in a bench scale moving-bed reactor. A syngas conversion in excess of 99.5% and an oxygen carrier conversion of nearly 50% are obtained. An ASPEN Plus® model is developed which simulates the reducer performance. The results of simulation are consistent with those obtained from both the thermodynamic analysis and experiments. Both the experiments and simulation indicate that the proposed SCL reducer concept is feasible. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Fe2O3 on Ce-, Ca-, or Mg-stabilized ZrO2 as oxygen carrier for chemical-looping combustion using NiO as additiveAICHE JOURNAL, Issue 8 2010Magnus Rydén Abstract Oxygen-carrier particles for chemical-looping combustion have been manufactured by freeze granulation. The particles consisted of 60 wt % Fe2O3 as active phase and 40 wt % stabilized ZrO2 as support material. Ce, Ca, or Mg was used to stabilize the ZrO2. The hardness and porosity of the particles were altered by varying the sintering temperature. The oxygen carriers were examined by redox experiments in a batch fluidized-bed reactor at 800,950°C, using CH4 as fuel. The experiments showed good reactivity between the particles and CH4. NiO was used as an additive and was found to reduce the fraction of unconverted CH4 with up to 80%. The combustion efficiency was 95.9% at best and was achieved using 57 kg oxygen carrier per MW fuel. Most produced oxygen carriers appear to have been decently stable, but using Ca as stabilizer resulting in uneven results. Further, particles sintered at high temperatures had a tendency to defluidize. © 2010 American Institute of Chemical Engineers AIChE J, 2010 [source] Chemical-looping combustion process: Kinetics and mathematical modelingAICHE JOURNAL, Issue 4 2010Ion Iliuta Abstract Chemical Looping Combustion technology involves circulating a metal oxide between a fuel zone where methane reacts under anaerobic conditions to produce a concentrated stream of CO2 and water and an oxygen rich environment where the metal is reoxidized. Although the needs for electrical power generation drive the process to high temperatures, lower temperatures (600,800°C) are sufficient for industrial processes such as refineries. In this paper, we investigate the transient kinetics of NiO carriers in the temperature range of 600 to 900°C in both a fixed bed microreactor (WHSV = 2-4 g CH4/h/g oxygen carrier) and a fluid bed reactor (WHSV = 0.014-0.14 g CH4/h per g oxygen carrier). Complete methane conversion is achieved in the fluid bed for several minutes. In the microreactor, the methane conversion reaches a maximum after an initial induction period of less than 10 s. Both CO2 and H2O yields are highest during this induction period. As the oxygen is consumed, methane conversion drops and both CO and H2 yields increase, whereas the CO2 and H2O concentrations decrease. The kinetics parameter of the gas,solids reactions (reduction of NiO with CH4, H2, and CO) together with catalytic reactions (methane reforming, methanation, shift, and gasification) were estimated using experimental data obtained on the fixed bed microreactor. Then, the kinetic expressions were combined with a detailed hydrodynamic model to successfully simulate the comportment of the fluidized bed reactor. © 2010 American Institute of Chemical Engineers AIChE J, 2010 [source] A novel dual circulating fluidized bed system for chemical looping processesAICHE JOURNAL, Issue 12 2009Tobias Pröll Abstract A fluidized bed system combining two circulating fluidized bed reactors is proposed and investigated for chemical looping combustion. Direct hydraulic communication of the two circulating fluidized bed reactors via a fluidized loop seal allows for high rates of global solids circulation and results in a stable solids distribution in the system. A 120 kW fuel power bench scale unit was designed, built, and operated. Experimental results are presented for natural gas as fuel using a nickel-based oxygen carrier. No carbon was lost to the air reactor under any conditions operated. It is shown from fuel power variations that a turbulent/fast fluidized bed regime in the fuel reactor is advantageous. Despite the relatively low riser heights (air reactor: 4.1 m, fuel reactor: 3.0 m), high CH4 conversion and CO2 yield of up to 98% and 94%, respectively, can be reported for the material tested. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Evaluation of hematological, chemistry and blood gas values in dogs receiving hemoglobin glutamer-200JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2007DACVECC, DACVIM, Marie E. Kerl DVM Abstract Objective: To evaluate the degree of interference that administration of hemoglobin glutamer-200 (Hb-200) caused for complete blood counts (CBC), biochemical profiles, cooximetry, and point of care (POC) testing in healthy dogs. Design: Prospective, longitudinal experimental study. Setting: Veterinary medical teaching hospital. Animals: Six purpose-bred research hounds. Interventions: Dogs were administered FDA-approved hemoglobin-based oxygen carrier (Hb-200) intravenously at 7.5 mL/kg over 2 hours. Arterial and venous blood samples were obtained before administration (Time 0) and at 3, 8, 14, 26, 50, 74, 98, 122, and 146 hours following administration. Measurements and main results: No adverse health effects were observed in any of the dogs. Characteristic mucous membrane, serum, and plasma color changes occurred following administration of Hb-200. Laboratory values that were significantly lower than baseline included packed cell volume, red blood cell count, hemoglobin, hematocrit, creatinine, cholesterol, alanine aminotransferase, and alkaline phosphatase. Laboratory values that were significantly greater than baseline included mean corpuscular hemoglobin concentration, arterial pH, arterial total carbon dioxide, arterial bicarbonate, amylase, albumin, total protein, globulin, calcium, phosphorous, total bilirubin, carboxyhemoglobin, and methemoglobin. All values returned to baseline by the completion of the 146-hour monitoring period. Conclusions: In normal dogs, administration of Hb-200 resulted in statistically significant changes in multiple laboratory parameters; however, these changes are not likely to be clinically significant in the care of critically ill dogs. [source] Fluid resuscitation from severe hemorrhagic shock using diaspirin cross-linked hemoglobin fails to improve pancreatic and renal perfusionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2004A. Pape Background:, Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas. Methods:, In 20 anesthetized domestic pigs with an experimentally induced coronary stenosis, shock (mean arterial pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). Completion of resuscitation was followed by a 60-min observation period. Regional blood flow to the kidneys and the pancreas was measured by use of the radioactive microspheres method at baseline, after shock and 60 min after fluid resuscitation. Results:, All animals (10/10) resuscitated with DCLHb survived the 60-min observation period, while 5/10 control animals died within 20 min due to persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and kidneys of DCLHb-treated animals revealed lower total and regional organ perfusion and regional oxygen delivery. Renal and pancreatic blood flow heterogeneity was higher in the DCLHb group. Conclusion:, DCLHb-induced vasoconstriction afforded superior myocardial perfusion, but impaired regional perfusion of the kidneys and the pancreas. [source] Radical Producing and Consuming Reactions of Hemoglobin: How Can We Limit Toxicity?ARTIFICIAL ORGANS, Issue 2 2009Chris E. Cooper Abstract Hemoglobin has a range of enzymatic activities that can affect its putative pharmacological role as an extracellular oxygen carrier. In the presence of peroxides, deoxyhemoglobin and methemoglobin can produce free radicals and induce lipid peroxidation. Oxyhemoglobin can oxidize the free radical nitric oxide to nitrate, yet deoxyhemoglobin can produce nitric oxide from nitrite. These enzymatic reactions can induce or diminish toxic side reactions when hemoglobin is added in vivo. For example the removal of the free radical vasodilator nitric oxide, or the addition of the lipid-derived vasoconstrictor F2-isoprostane, will both alter blood flow and blood pressure. In order to determine the dominant effects it is necessary to design molecules with differing radical reactivities. Molecules have been designed with these modifications and this article will review their role in determining mechanism as well as their possible functionality as blood substitutes. [source] Effects of Liposome-Encapsulated Hemoglobin on Human Immune System: Evaluation in Immunodeficient Mice Reconstituted With Human Cord Blood Stem CellsARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi Abstract As preclinical evaluation in animals does not necessarily portray human responses, liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier, was tested in immunodeficient mice reconstituted with human hematopoietic stem cells (cord blood-transfused NOD/SCID/IL-2R,null[CB-NOG] mice). Changes in immunocompetent T-cell and B-cell composition in peripheral blood, spleen, and bone marrow were examined 2 and 7 days after 10 mL/kg of intravenous administration of LEH, empty liposome (EL), or saline using immunohistochemical and flow cytometrical techniques in wild-type mice and CB-NOG mice. Responses to intraperitoneal administration of toxic shock syndrome toxin-1 (TSST-1) under the absence or presence of LEH (10 mL/kg) were also determined 4 h and 3 days later in terms of lymphocyte composition and IL-2 plasma level in wild-type as well as CB-NOG mice. When liposome (LEH or EL) was administered to wild-type or CB-NOG mice, the composition of B-cells and T-cells in the spleen or peripheral blood failed to show any consistent or significant changes. The responses to a bacterial antigen (TSST-1) measured by IL-2 production were comparable regardless of the presence or absence of LEH in wild-type as well as in CB-NOG mice. Cellularity, distribution, and maturation of these human cells in peripheral blood, spleen, and bone marrow were comparable among the groups. The results suggest that simple LEH administration may not change immune cellularity, and LEH presence may not largely affect the early T-cell response to bacterial enterotoxins in murine as well as in reconstituted human immune systems. [source] Hepatocyte Function in a Radial-flow Bioreactor Using a Perfluorocarbon Oxygen CarrierARTIFICIAL ORGANS, Issue 11 2005Martin J. Nieuwoudt Abstract:, The aims of this study were, first, to indicate the metabolic activity of hepatocytes in a radial-flow polyurethane foam matrix bioreactor relative to monocultures, and second, to evaluate the effect on the hepatocytes of including a synthetic perfluorocarbon (PFC) oxygen carrier to the recirculating medium. The efficient O2 -carrying ability of PFCs may be beneficial to bioreactors employed in stressed cellular environments. Thus, they may also be useful in the treatment of an acute liver failure patient with a bioartificial liver support system (BALSS). Data on the function of three-dimensional (3-D) hepatocyte cultures exposed to emulsified PFCs are lacking. Results: the metabolic functions of the 3-D hepatocyte cultures were improved relative to monocultures. Three-dimensional cultures with and without PFC behaved similarly, and no adverse effects could be detected when PFC was included in the recirculating medium. The addition of PFC significantly improved lidocaine clearance possibly due to the presence of higher O2 tension in the medium. Imaging indicated that large aggregates formed and that seeding had followed flow through the matrix. Simulations indicated first, that the cell numbers used in this study had been insufficient to challenge the bioreactor O2 supply explaining the similarity in performance of the 3-D cultures, and second, that the benefit of adding PFC would be more pronounced at the cell densities likely to be used in a BALSS bioreactor. [source] Effect of a perfluorocarbon-Pluronic F 68-based emulsion on a Phanerochaete chrysosporium biofilm immobilised in a membrane gradostat bioreactorASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 1 2010S. K. O. Ntwampe Abstract The present study highlights the application of perfluorooctyl bromide (PFOB), an oxygen carrier, in a fixed-film membrane gradostat reactors (MGRs) in which biofilms of Phanerochaete chrysosporium BKMF-1767 (ATCC 24725) were immobilised. The nutrient medium used in the MGRs was supplemented with PFOB and Pluronic F 68 (PF 68) to alleviate limitations associated with the performance of the immobilised fungus. Lower lignin peroxidase production in PFOB/PF 68 cultures was observed compared to manganese peroxidase production, suggesting an insignificant generation of reactive oxygen species (ROS). Lipid peroxidation, quantified by the formation of malondialdehyde, was lower in the immobilised cultures. After successfully applying PFOB and PF 68 to immobilised P. chrysosporium biofilms in the MGRs, the following results were obtained:1 reduced ethanol production,2 reduced trace element accumulation,3 lower ,-glucan production and4 an improved dissolved oxygen penetration ratio in the immobilised biofilms. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd. [source] Heterologous expression of the biosynthetic gene clusters of coumermycin A1, clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strainsBIOPOLYMERS, Issue 9 2010Katrin Flinspach Abstract The biosynthetic gene clusters of the aminocoumarin antibiotics clorobiocin and coumermycin A1 and of the liponucleoside antibiotic caprazamycin were stably integrated into the genomes of different host strains derived from Streptomyces coelicolor A3(2). For the heterologous expression of clorobiocin derivatives in a chemically defined medium, inclusion of 0.6% of the siloxylated ethylene oxide/propylene oxide copolymer Q2-5247 into the growth medium proved to result in a 4.8-fold increase of productivity. Presumably, this copolymer acts as an oxygen carrier. The additional inclusion of cobalt chloride (0.2,2 mg l,1) dramatically increased the percentage of the desired compound clorobiocin within the total produced clorobiocin derivatives. This is very likely due to a stimulation of a cobalamin-dependent methylation reaction catalyzed by the enzyme CloN6 of clorobiocin biosynthesis. All three investigated host strains (S. coelicolor M512, M1146 and M1154) gave similar production rates of total clorobiocin derivatives (on average, 158 mg l,1 in the presence of 0.6% Q2-5247 and 0.2 mg l,1 CoCl2). In contrast, heterologous production of caprazamycin derivatives was optimal in strain M1154 (amounts of 152 mg l,1 on average). © 2010 Wiley Periodicals, Inc. Biopolymers 93: 823,832, 2010. [source] Enhanced radiation response of a solid tumor with the artificial oxygen carrier ,albumin-heme'CANCER SCIENCE, Issue 6 2008Hirohisa Horinouchi Tumor-cell hypoxia is one of the main factors inducing radioresistance. Enhanced tumor oxygenation has previously been achieved in an animal model using the synthetic heme-based oxygen carrier ,albumin-heme' (recombinant human serum albumin-Fe cyclohexanoil heme; rHSA-FeP). The present study was done to determine whether rHSA-FeP enhances the radiation response in an experimental tumor model. Male Donryu rats and LY80, a variant of the syngenic liver ascites tumor, were used. A total of 1 × 106 cells were injected into the subfascial tissue of the right thigh. The rats were divided randomly into five groups: sham (tumor implantation and sham operation); rHSA-FeP; irradiation; rHSA + irradiation; and rHSA-FeP + irradiation. Six days after, under general anesthesia, intra-arterial administration of 10 mL/kg of either 5% rHSA solution or oxygenated rHSA-FeP solution at 2.5 mL/min was done and a dose of 20 Gy was given. There were significant differences in tumor growth between the sham and irradiation groups, and between the sham and rHSA-FeP + irradiation groups. Tumor growth delay was observed and differences were significant between the sham and irradiation groups, and between the irradiation and rHSA-FeP + irradiation groups. In the present study, rHSA-FeP itself had a slight effect on tumor growth without irradiation. Enhancing the effect of rHSA-FeP on the radiation response is responsible in part for the oxygen-carrying property of rHSA-FeP. In conclusion, rHSA-FeP is a candidate radiation-enhancing drug. Arterial infusion of rHSA-FeP may serve as a local oxygenation method that enhances the radiation effect. (Cancer Sci 2008; 99: 1274,1278) [source] Eine erweiterte Evaluation der Neurolept-Anästhesie für Meerschweinchen mit einer Analyse gemischt-exspiratorischer Gase während Spontanatmung.JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2004Wirkung des Fastens auf das kardiorespiratorische System und den Metabolismus Zusammenfassung Das beatmete Meerschweinchen wurde oft für neurophysiologische und respiratorische Studien eingesetzt. Diese Spezies ist auch für eine Evaluation künstlicher Sauerstoffträger, entwickelt aus Hämoglobin, geeignet, weil seine Sauerstoff-Hämoglobin-Bindung der des Menschen sehr ähnlich ist. Andererseits ist eine Narkose dieser Tiere wegen kardio-respiratorischer Depression mit herkömmlichen Verfahren schwierig. Bewährt hat sich die folgende intraperitoneal zu verabreichende Neurolept-Anästhesie: 0,2 mg Fentanyl (Janssen/D), 10 mg Droperidol (Janssen/D) sowie 400 mg Urethan in 10 ml isotonischer Natriumchlorid-Lösung pro kg Körpergewicht. Unser neues Tier-Modell ermöglicht, mit einem speziellen Ventilsystem den Gasaustausch unter Spontanatmung, kardiovaskuläre wie auch Blutgaswerte und damit den Säure-Basen-Status zu messen. Die vitalen Parameter der Tiere, blieben über mehr als 6 Stunden stabil und nahe bei Werten wacher Tiere, insbesondere der mittlere arterielle Blutdruck. Deswegen ist diese etablierte Neurolept-Anästhesie des Meerschweinchens für Forschungszweck zu bevorzugen. Nüchterne Tiere zeigten signifikant erniedrigte Blut-pH- (7,345 bzw. 7,401) sowie Herzfrequenz- (244 bzw. 277 min,1) und Ventilationswerte (167 bzw. 205 ml/min) im Vergleich zu nicht nüchternen Tieren. Summary An Extended Evaluation of a Neuroleptanesthesia for the Guinea Pig with Analysis of Mixed Expiratory Gases during Spontaneous Breathing. Effects of Fasting on the Cardiorespiratory System and Metabolism The artificially ventilated guinea pig was frequently used for neurophysiological and respiratory studies. This species is also preferable for an evaluation of hemoglobin based artificial oxygen carriers, because its oxygen hemoglobin binding is very similar to that of man. But the narcosis of this animal-species is very difficult, because of cardiorespiratory depression induced by conventional procedures. The following intraperitoneal administered neuroleptanesthesia was proved in guinea pigs: 0,2 mg Fentanyl (Janssen/D), 10 mg Droperidol (Janssen/D) and 400 mg Urethan in 10 ml isotonic sodium chloride solution per kg body weight. Our new animal model with a special valve system enables to assess the gas exchange under spontaneous breathing, cardiovascular and the acid-base parameters. The vital parameters of animals were stable over 6 hours and very close to those of awake animals, especially the arterial average blood pressure. For that reason, this established neuroleptanesthesia of guinea pigs is preferable for research purpose. The fasted animals show significantly decreased values of arterial blood pH (7,345 vs. 7,401), of heart frequency (244 vs. 277 min,1), and of ventilation value (167 vs. 205 ml/min) compared to non-fasted animals. [source] Fe2O3 on Ce-, Ca-, or Mg-stabilized ZrO2 as oxygen carrier for chemical-looping combustion using NiO as additiveAICHE JOURNAL, Issue 8 2010Magnus Rydén Abstract Oxygen-carrier particles for chemical-looping combustion have been manufactured by freeze granulation. The particles consisted of 60 wt % Fe2O3 as active phase and 40 wt % stabilized ZrO2 as support material. Ce, Ca, or Mg was used to stabilize the ZrO2. The hardness and porosity of the particles were altered by varying the sintering temperature. The oxygen carriers were examined by redox experiments in a batch fluidized-bed reactor at 800,950°C, using CH4 as fuel. The experiments showed good reactivity between the particles and CH4. NiO was used as an additive and was found to reduce the fraction of unconverted CH4 with up to 80%. The combustion efficiency was 95.9% at best and was achieved using 57 kg oxygen carrier per MW fuel. Most produced oxygen carriers appear to have been decently stable, but using Ca as stabilizer resulting in uneven results. Further, particles sintered at high temperatures had a tendency to defluidize. © 2010 American Institute of Chemical Engineers AIChE J, 2010 [source] Perfluorocarbon-Based Oxygen Carriers: Review of Products and TrialsARTIFICIAL ORGANS, Issue 8 2010Camila Irene Castro Abstract A viable blood substitute is still of great necessity throughout the world. Perfluorocarbon-based oxygen carriers (PFCOCs) are emulsions that take advantage of the high solubility of respiratory gases in perfluorocarbons (PFCs). Despite attractive characteristics, no PFCOC is currently approved for clinical uses. Some PFCOCs have failed due to secondary effects of the surfactants employed, like Fluosol DA, whereas others to adverse cerebrovascular effects on cardiopulmonary bypass, such as Oxygent. Further in-depth, rigorous work is needed to overcome the annotated failures and to obtain a safe PFCOC approved for human use. The aim of this study is to review in detail the most-used PFCOCs, their formulation, and preclinical and clinical trials, and to reflect upon causes of failure and strategies to overcome such failures. [source] Intrinsic Toxicity of Hemoglobin: How to Counteract ItARTIFICIAL ORGANS, Issue 2 2009Jan Simoni Abstract The development of safe and effective blood substitutes is of great importance in both civilian and military medicine. The currently tested hemoglobin (Hb)-based oxygen carriers, however, have toxicity and efficacy problems. A number of unwanted effects have been observed in human trials, creating doubts about their clinical usefulness. In some subjects, vasoconstriction and decreased blood flow to the vital organs, heart attack, stroke, systemic inflammation, organ damage, and even death, have been attributed to the transfusion of these experimental products. Hb is a well-known pressor agent and strong oxidant, although the full understanding of its intrinsic toxicity is yet to be uncovered. In particular, the complete mechanism of Hb-induced vasoconstriction needs full elucidation. Knowledge of the biological events that trigger the induction of genes upon treatment with redox-active Hb, as well as its catabolism, is still incomplete. It seems that our limited knowledge of free Hb effects in vivo is the main reason for not yet having a viable substitute of human blood. The future for universal red cell substitutes is in the new-generation products that address all of Hb's intrinsic toxicity issues. [source] Possible Role of Artificial Oxygen Carriers in Transfusion Medicine: A Retrospective Analysis on the Current Transfusion PracticeARTIFICIAL ORGANS, Issue 2 2009Fumiaki Yoshiba Abstract Artificial oxygen carriers (AOC) are under development as a substitute for red blood cells (RBC) in homologous transfusion (Tx). The lack of surface antigen in AOC makes ABO-typing and antibody-screening (T/S) unnecessary. Pathogen elimination renders it much safer, and long-term stability allows ubiquitous storage for emergency use. To delineate the utility of AOC, we retrospectively examined current Tx practices in Tokai University and the Japanese Red Cross Society. The emergency department of Tokai University Hospital has been using O(+)Rh(+) RBC in patients with hemorrhagic shock before Tx becomes available. Those who received the RBCs within 60 min of injury had a significantly higher survival rate than those who received it later (,60 min). The Red Cross Blood Center provided 411 units of RBC for 138 urgent requests for rare blood types. Our analysis suggests that if an AOC were available for the initial six units, 96% of such requests could have been covered to avoid urgent donor allocation, preparation, and Tx. Among 2079 surgical cases who ordered T/S, only 29% actually required Tx, rendering >70% of the T/S unnecessary. Because only 7.4% required nine units or more, more than 92% of T/S and Tx could have been avoided in retrospect if an AOC were available for the initial eight units. The results suggest that an AOC might be useful in various situations to alleviate problems, concerns, and technical burden in the current Tx practices. Because the expected utility is based mainly on physical characteristics, AOC may remain advantageous even when biogenetically derived RBC becomes available. [source] Hemospan: Design Principles for a New Class of Oxygen TherapeuticARTIFICIAL ORGANS, Issue 2 2009Kim D. Vandegriff Abstract Hemoglobin-based oxygen carriers have been under development for decades, but safety concerns have prevented commercial approval. Early designs for modified hemoglobins by polymerization or intramolecular cross-linking reactions increased molecular size and decreased oxygen affinity, but all exhibited side effects of vasoconstriction and reduced blood flow. A new strategy has been established by applying principles of oxygen transport to cell-free hemoglobin. Sangart has developed a new oxygen therapeutic, Hemospan, using site-specific, poly(ethylene) glycol conjugation chemistry designed on two principles: (i) increased macromolecular size to prolong intravascular retention time, and (ii) increased oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast to early-generation products, Hemospan infusion maintains normal arteriolar vascular tone and capillary flow. Phase I and Phase II clinical trials have been completed, showing that Hemospan is well-tolerated in humans, with evidence of efficacy to impart hemodynamic stability in surgical patients under anesthesia. Phase III trials in orthopedic surgery have recently completed enrollment in Europe. [source] Review of Hemoglobin-Vesicles as Artificial Oxygen CarriersARTIFICIAL ORGANS, Issue 2 2009Hiromi Sakai Abstract Blood transfusion systems have greatly benefited human health and welfare. Nevertheless, some problems remain: infection, blood type mismatching, immunological response, short shelf life, and screening test costs. Blood substitutes have been under development for decades to overcome such problems. Plasma component substitutes have already been established: plasma expanders, electrolytes, and recombinant coagulant factors. Herein, we focus on the development of red blood cell (RBC) substitutes. Side effects hindered early development of cell-free hemoglobin (Hb)-based oxygen carriers (HBOCs) and underscored the physiological importance of the cellular structure of RBCs. Well-designed artificial oxygen carriers that meet requisite criteria are expected to be realized eventually. Encapsulation of Hb is one idea to shield the toxicities of molecular Hbs. However, intrinsic issues of encapsulated Hbs must be resolved: difficulties related to regulating the molecular assembly, and management of its physicochemical and biochemical properties. Hb-vesicles (HbV) are a cellular type of HBOC that overcome these issues. The in vivo safety and efficacy of HbV have been studied extensively. The results illustrate the potential of HbV as a transfusion alternative and promise its use for other clinical applications that remain unattainable using RBC transfusion. [source] Liposome-Encapsulated Hemoglobin, TRM-645: Current Status of the Development and Important Issues for Clinical ApplicationARTIFICIAL ORGANS, Issue 2 2009Shinichi Kaneda Abstract Clinical application of artificial oxygen carriers as a substitute for blood transfusion has long been expected to solve some of the problems associated with blood transfusion. Use for oxygen delivery treatment for ischemic disease by oxygen delivery has also been examined. These prospective applications of artificial oxygen carriers are, however, still in development. We have developed liposome-encapsulated hemoglobin (LEH), developmental code TRM-645, using technologies for encapsulation of concentrated hemoglobin (Hb) with high encapsulation efficiency as well as surface modification to achieve stability in circulating blood and a long shelf life. We have confirmed the basic efficacy and safety of TRM-645 as a red blood cell substitute in studies on the efficacy of oxygen delivery in vivo, and the safety of TRM-645 has been studied in some animal species. We are now examining various issues related to clinical studies, including further preclinical studies, management of manufacturing and the quality assurance for the Hb solution and liposome preparations manufactured by the GMP facility. [source] In Vivo Distribution of Liposome-Encapsulated Hemoglobin Determined by Positron Emission TomographyARTIFICIAL ORGANS, Issue 2 2009Takeo Urakami Abstract Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome-encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [15O]H2O imaging, distribution of 18F-labeled LEH in the region was gradually increased during 60-min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real-time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution. [source] | ||||||||||||||||