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Artificial Oxygen Carriers (artificial + 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] 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] 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] 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] 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] 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] | ||||||||||