The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Zeneng Cheng - One of the best experts on this subject based on the ideXlab platform.
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Pharmacodynamic analysis of intravenous Recombinant Urate Oxidase using an indirect pharmacological response model in healthy subjects
2014Co-Authors: Ning-fang Cai, Zeneng Cheng, Xi Luo, Xin Guo, Zhi Liu, Liyun ZhengAbstract:Pharmacodynamic analysis of intravenous Recombinant Urate Oxidase using an indirect pharmacological response model in healthy subjects
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Development of a new LC-MS/MS based enzyme activity assay for Recombinant Urate Oxidase in plasma and its application to pharmacokinetics in human.
2013Co-Authors: Xi Luo, Ning-fang Cai, Zeneng ChengAbstract:A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Recombinant Urate Oxidase in human plasma. This assay was based on the determination of enzyme reaction product, (15)N-allantoin, and phenacetin was used as an internal standard (IS). Separation was achieved on a C18 column by the mobile phase of 30% water (containing 0.5% formic acid) and 70% methanol. Quantification was done using multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 161 → m/z 118 for (15)N-allantoin and m/z 180 → m/z 110.1 for IS at positive ionization mode. The calibration curve was established over the range of 2.077-42.06 U/l and the correlation coefficient was larger than 0.99. The intra-day and inter-day relative standard deviations were less than 10.6%. Accuracy determined at three concentrations ranged between 98.6% and 109.2%. This method was successfully applied to a pharmacokinetic study of intravenous Recombinant Urate Oxidase produced from Escherichia coli in Chinese healthy volunteers.
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Determination of uric acid in plasma by LC-MS/MS and its application to an efficacy evaluation of Recombinant Urate Oxidase.
2013Co-Authors: Xi Luo, Ning-fang Cai, Zeneng ChengAbstract:A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of uric acid in human plasma was developed and validated. Separation was achieved on a C18 column by the mobile phase of 30% water (containing 0.5% formic acid) and 70% methanol. Quantification was done using a multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 169.1 → m/z 141.1 for uric acid and m/z 171 → m/z 143 for 1,3-(15)N uric acid (IS) at a positive ionization mode. The calibration curve was established over the range of 0.4096 - 100 mg/L, and the correlation coefficient was better than 0.99. The intra-day and inter-day relative standard deviations were less than 5.1%. The accuracy determined at three concentrations ranged between 92.7 and 102.3%. This method was successfully applied to an efficacy study of intravenous Recombinant Urate Oxidase produced by Escherichia coli in a clinical phase I study.
R Hehlmann - One of the best experts on this subject based on the ideXlab platform.
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recurrent chemotherapy induced tumor lysis syndrome tls with renal failure in a patient with chronic lymphocytic leukemia successful treatment and prevention of tls with low dose rasburicase
2005Co-Authors: Margit Hummel, Dieter Buchheidt, Sebastian Reiter, Jorg Bergmann, Katja Adam, R HehlmannAbstract:: Introduction: Rasburicase is a Recombinant Urate Oxidase that is produced by a genetically modified Saccharomyces cerevisiae and has been approved for prophylaxis and treatment of tumor lysis syndrome in 2001. In several studies, rasburicase, given at a dose of 0.15–0.2 mg/kg for up to 7 d, proved to be highly effective in lowering Urate levels. Case report: We report the case of a patient with chronic lymphatic leukemia (CLL) who experienced tumor lysis syndrome (TLS) with acute renal failure after fludarabine/cyclophosphamide chemotherapy and after bendamustine treatment. During the first episode of TLS, after fludarabine/cyclophosphamide (creatinine 3.3 mg/dL, Urate 24.6 mg/dL), the patient received rasburicase 0.2 mg/kg for 3 d. Urate levels decreased below the lower limit of normal and renal function recovered. After bendamustine therapy, given for disease progression 8 months later, TLS with acute oliguric renal failure re-occurred (creatinine 3.1 mg/dL, Urate 20.8 mg/dL). The patient was treated with hyperhydration and two doses of rasburicase (0.056 mg/kg), resulting in a prompt decrease of the Urate level and recovery of renal function. Both episodes of TLS were successfully treated with rasburicase in a lower dose than recommended by the manufacturer. During a second bendamustine course, TLS was successfully treated by low doses of rasburicase (0.056 mg/kg for 2 d). Conclusion: This is the first report of TLS in CLL after bendamustine chemotherapy reported in the literature. Treatment and prevention of TLS by low doses of rasburicase is possible and cost-effective.
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successful treatment of hyperuricemia with low doses of Recombinant Urate Oxidase in four patients with hematologic malignancy and tumor lysis syndrome
2003Co-Authors: Margit Hummel, Dieter Buchheidt, Sebastian Reiter, Jorg Bergmann, Ralfdieter Hofheinz, R HehlmannAbstract:Successful treatment of hyperuricemia with low doses of Recombinant Urate Oxidase in four patients with hematologic malignancy and tumor lysis syndrome
F. Bonnete - One of the best experts on this subject based on the ideXlab platform.
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Polymorphism of microcrystalline Urate Oxidase from Aspergillus flavus
2010Co-Authors: I. Collings, F. Bonnete, Y. Watier, M. Giffard, S. Dagogo, R. Kahn, J.p. Wright, A.n. Fitch, I. MargiolakiAbstract:Different polymorphs of rasburicase, a Recombinant Urate Oxidase enzyme (Uox) from Aspergillus flavus, were obtained as a series of polycrystalline precipitates. Different crystallization protocols were followed in which the salt type, pH and polyethylene glycol 8000 (PEG 8000) concentration were varied. The related crystalline phases were characterized by means of high-resolution synchrotron X-ray powder diffraction. In all cases, Uox complexed with the inhibitor 8-azaxanthine (AZA) was not altered from its robust orthorhombic I222 phase by variation of any of the factors listed above. However, in the absence of AZA during crystallization ligand-free Uox was significantly affected by the type of salt, resulting in different crystal forms for the four salts tested: sodium chloride, potassium chloride, ammonium chloride and ammonium sulfate. Remarkable alterations of some of these phases were observed upon gradual increase of the exposure time of the sample to the synchrotron beam in addition to variation of the PEG 8000 concentration. When Uox was crystallized in Tris buffer or pure water in the absence of salt, a distinct polymorph of orthorhombic symmetry (P2(1)2(1)2) was obtained that was associated with significantly altered lattice dimensions in comparison to a previously reported isosymmetrical structure. The latter form of Uox exhibits enhanced stability to variation of pH and PEG 8000 concentration accompanied by minor modifications of the unit-cell dimensions in the ranges under study. AccUrate lattice parameters were extracted for all crystalline phases. This study reveals the rich phase diagram of Uox, a protein of high pharmaceutical importance, which is associated with an enhanced degree of polymorphism. The outcome of our analysis verifies previously reported results as well as demonstrating polymorphs that have altered unit-cell dimensions with respect to known structural models.
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Salting-In Effects on Urate Oxidase Crystal Design
2008Co-Authors: Marion Giffard, B. Castro, N. Ferte, Nathalie Colloc'h, F. BonneteAbstract:In this paper, solubility and interactions in solution of the Recombinant Urate Oxidase from Aspergillus flavus, rasburicase, are studied both in the absence and in the presence of salt at a pH close to the pI. An intense salting-in effect is demonstrated first by an increased solubility when various salts are added. Thus, merely adding salt does not induce rasburicase crystallization. Second virial coefficient measurements also confirm this effect by exhibiting repulsive interactions over a large range of salt concentrations. Therefore, the salting-in effect enables the stabilization of rasburicase solution at high concentrations. Moreover, it enables crystals of improved size and habit to be grown when polymer is added to a solution of rasburicase concentrated with salt, or when salt is removed from it. We also show, with the example of high pressure macromolecular crystallography, that salt enables the stabilization of the desired polymorph under the highly concentrated polyethylene glycol conditions required by this technique.
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A preliminary neutron diffraction study of Rasburicase, a Recombinant Urate Oxidase enzyme, complexed with 8-azaxanthin
2006Co-Authors: M. Budayova-spano, F. Bonnete, N. Ferte, F. Meilleur, M. Blakeley, B. CastroAbstract:Crystallization and preliminary neutron diffraction measurements of rasburicase, a Recombinant Urate Oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 angstrom resolution using the LADI instrument from a crystal (grown in D2O) with volume 1.8 mm(3). The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high- resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, Urate Oxidase has one of the largest primitive unit- cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 angstrom) and molecular weights (135 kDa for the homotetramer) so far successfully studied with neutrons.
Xi Luo - One of the best experts on this subject based on the ideXlab platform.
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Pharmacodynamic analysis of intravenous Recombinant Urate Oxidase using an indirect pharmacological response model in healthy subjects
2014Co-Authors: Ning-fang Cai, Zeneng Cheng, Xi Luo, Xin Guo, Zhi Liu, Liyun ZhengAbstract:Pharmacodynamic analysis of intravenous Recombinant Urate Oxidase using an indirect pharmacological response model in healthy subjects
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Development of a new LC-MS/MS based enzyme activity assay for Recombinant Urate Oxidase in plasma and its application to pharmacokinetics in human.
2013Co-Authors: Xi Luo, Ning-fang Cai, Zeneng ChengAbstract:A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Recombinant Urate Oxidase in human plasma. This assay was based on the determination of enzyme reaction product, (15)N-allantoin, and phenacetin was used as an internal standard (IS). Separation was achieved on a C18 column by the mobile phase of 30% water (containing 0.5% formic acid) and 70% methanol. Quantification was done using multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 161 → m/z 118 for (15)N-allantoin and m/z 180 → m/z 110.1 for IS at positive ionization mode. The calibration curve was established over the range of 2.077-42.06 U/l and the correlation coefficient was larger than 0.99. The intra-day and inter-day relative standard deviations were less than 10.6%. Accuracy determined at three concentrations ranged between 98.6% and 109.2%. This method was successfully applied to a pharmacokinetic study of intravenous Recombinant Urate Oxidase produced from Escherichia coli in Chinese healthy volunteers.
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Determination of uric acid in plasma by LC-MS/MS and its application to an efficacy evaluation of Recombinant Urate Oxidase.
2013Co-Authors: Xi Luo, Ning-fang Cai, Zeneng ChengAbstract:A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of uric acid in human plasma was developed and validated. Separation was achieved on a C18 column by the mobile phase of 30% water (containing 0.5% formic acid) and 70% methanol. Quantification was done using a multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 169.1 → m/z 141.1 for uric acid and m/z 171 → m/z 143 for 1,3-(15)N uric acid (IS) at a positive ionization mode. The calibration curve was established over the range of 0.4096 - 100 mg/L, and the correlation coefficient was better than 0.99. The intra-day and inter-day relative standard deviations were less than 5.1%. The accuracy determined at three concentrations ranged between 92.7 and 102.3%. This method was successfully applied to an efficacy study of intravenous Recombinant Urate Oxidase produced by Escherichia coli in a clinical phase I study.
B. Castro - One of the best experts on this subject based on the ideXlab platform.
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Salting-In Effects on Urate Oxidase Crystal Design
2008Co-Authors: Marion Giffard, B. Castro, N. Ferte, Nathalie Colloc'h, F. BonneteAbstract:In this paper, solubility and interactions in solution of the Recombinant Urate Oxidase from Aspergillus flavus, rasburicase, are studied both in the absence and in the presence of salt at a pH close to the pI. An intense salting-in effect is demonstrated first by an increased solubility when various salts are added. Thus, merely adding salt does not induce rasburicase crystallization. Second virial coefficient measurements also confirm this effect by exhibiting repulsive interactions over a large range of salt concentrations. Therefore, the salting-in effect enables the stabilization of rasburicase solution at high concentrations. Moreover, it enables crystals of improved size and habit to be grown when polymer is added to a solution of rasburicase concentrated with salt, or when salt is removed from it. We also show, with the example of high pressure macromolecular crystallography, that salt enables the stabilization of the desired polymorph under the highly concentrated polyethylene glycol conditions required by this technique.
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A preliminary neutron diffraction study of Rasburicase, a Recombinant Urate Oxidase enzyme, complexed with 8-azaxanthin
2006Co-Authors: M. Budayova-spano, F. Bonnete, N. Ferte, F. Meilleur, M. Blakeley, B. CastroAbstract:Crystallization and preliminary neutron diffraction measurements of rasburicase, a Recombinant Urate Oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 angstrom resolution using the LADI instrument from a crystal (grown in D2O) with volume 1.8 mm(3). The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high- resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, Urate Oxidase has one of the largest primitive unit- cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 angstrom) and molecular weights (135 kDa for the homotetramer) so far successfully studied with neutrons.