The Experts below are selected from a list of 87 Experts worldwide ranked by ideXlab platform
Ernst Mutschler - One of the best experts on this subject based on the ideXlab platform.
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Effects of a new Pteridine Derivative on urinary sodium, potassium and magnesium excretion in conscious saline‐loaded rats
British Journal of Pharmacology, 1992Co-Authors: Tim Netzer, Mariusz Majewski, H. Priewer, F Ullrich, Ernst MutschlerAbstract:Abstract 1. Two recently synthesized Pteridine Derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.
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effects of a new Pteridine Derivative on urinary sodium potassium and magnesium excretion in conscious saline loaded rats
British Journal of Pharmacology, 1992Co-Authors: Tim Netzer, Mariusz Majewski, H. Priewer, F Ullrich, Ernst MutschlerAbstract:Abstract 1. Two recently synthesized Pteridine Derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.
Louis Boon - One of the best experts on this subject based on the ideXlab platform.
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immunosuppressive activity of a new Pteridine Derivative 4aza1378 alleviates severity of tnbs induced colitis in mice
Clinical Immunology, 2007Co-Authors: Chong Shen, Ellen Dillissen, Ahmad Kasran, Yuan Lin, Jean Herman, Ilse Sienaert, Steven De Jonghe, Luk Kerremans, Karel Geboes, Louis BoonAbstract:Besides TNF, activated T cells play a central role in the pathogenesis of inflammatory bowel diseases such as Crohn's disease. New therapies are still awaited to cure these often debilitating diseases. Natural occurring Pteridines such as tetrahydrobiopterin (BH4) and neopterin have been reported to have immune modulating activities. Starting from a Pteridine scaffold library, we intended to select compounds with potent in vitro inhibitory effects on T cells and to evaluate in vivo efficacy of selected compounds on trinitrobenzenesulphonate (TNBS) colitis in mice. Compound 4AZA1378 was selected because it potently inhibits human T cell proliferation at low nM concentrations (IC50 4 nM) while an almost 50-fold higher concentration was needed to inhibit LPS-induced TNF production. Mice treated with 4AZA1378 had less severe signs of colitis after TNBS rectal administration, with a more rapid weight recovery. Myeloperoxidase (MPO) activity and intralesional cytokine production were lower in mice of the treated groups. Furthermore anti-TNBS antibody responses were completely inhibited by treatment with 4AZA1378. In conclusion, we identified a Pteridine analogue 4AZA1378 with immunosuppressive activity and a strong remission-inducing effect in TNBS colitis, supporting further pre-clinical and clinical development of this novel molecule for treatment of inflammatory diseases.
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anti inflammatory activity of a Pteridine Derivative 4aza2096 alleviates tnbs induced colitis in mice
Journal of Interferon and Cytokine Research, 2006Co-Authors: Chong Shen, Ellen Dillissen, Ahmad Kasran, Yuan Lin, Ilse Sienaert, Steven De Jonghe, Karel Geboes, Gavin Clydesdale, Lingjie Gao, Louis BoonAbstract:Elevated production of tumor necrosis factor (TNF) plays a central role in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis and Crohn's disease. Naturally occurring Pteridine analogs have been reported to have potent immunomodulatory activity, especially on TNF production. The aim of this study is to identify small molecule TNF inhibitiors derived from Pteridine and to prove their in vivo efficacy in an inflammatory model. A focused chemical library based on the Pteridine scaffold was screened in vitro on lipopolysaccharide (LPS)-induced TNF production in peripheral blood mononuclear cells (PBMC). One synthetic Pteridine analog (4AZA2096), shown to have strong inhibitory activity, was selected and tested for its efficacy to treat trinitrobenzenesulfonate (TNBS)-induced colitis in mice, a model of Crohn's disease. Colitis was induced by rectal administration of 1 mg TNBS in 50% ethanol after presensitization via the skin. The synthetic Pteridine analog 4AZA2096 was shown to pote...
Tim Netzer - One of the best experts on this subject based on the ideXlab platform.
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Effects of a new Pteridine Derivative on urinary sodium, potassium and magnesium excretion in conscious saline‐loaded rats
British Journal of Pharmacology, 1992Co-Authors: Tim Netzer, Mariusz Majewski, H. Priewer, F Ullrich, Ernst MutschlerAbstract:Abstract 1. Two recently synthesized Pteridine Derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.
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effects of a new Pteridine Derivative on urinary sodium potassium and magnesium excretion in conscious saline loaded rats
British Journal of Pharmacology, 1992Co-Authors: Tim Netzer, Mariusz Majewski, H. Priewer, F Ullrich, Ernst MutschlerAbstract:Abstract 1. Two recently synthesized Pteridine Derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.
Chong Shen - One of the best experts on this subject based on the ideXlab platform.
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immunosuppressive activity of a new Pteridine Derivative 4aza1378 alleviates severity of tnbs induced colitis in mice
Clinical Immunology, 2007Co-Authors: Chong Shen, Ellen Dillissen, Ahmad Kasran, Yuan Lin, Jean Herman, Ilse Sienaert, Steven De Jonghe, Luk Kerremans, Karel Geboes, Louis BoonAbstract:Besides TNF, activated T cells play a central role in the pathogenesis of inflammatory bowel diseases such as Crohn's disease. New therapies are still awaited to cure these often debilitating diseases. Natural occurring Pteridines such as tetrahydrobiopterin (BH4) and neopterin have been reported to have immune modulating activities. Starting from a Pteridine scaffold library, we intended to select compounds with potent in vitro inhibitory effects on T cells and to evaluate in vivo efficacy of selected compounds on trinitrobenzenesulphonate (TNBS) colitis in mice. Compound 4AZA1378 was selected because it potently inhibits human T cell proliferation at low nM concentrations (IC50 4 nM) while an almost 50-fold higher concentration was needed to inhibit LPS-induced TNF production. Mice treated with 4AZA1378 had less severe signs of colitis after TNBS rectal administration, with a more rapid weight recovery. Myeloperoxidase (MPO) activity and intralesional cytokine production were lower in mice of the treated groups. Furthermore anti-TNBS antibody responses were completely inhibited by treatment with 4AZA1378. In conclusion, we identified a Pteridine analogue 4AZA1378 with immunosuppressive activity and a strong remission-inducing effect in TNBS colitis, supporting further pre-clinical and clinical development of this novel molecule for treatment of inflammatory diseases.
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anti inflammatory activity of a Pteridine Derivative 4aza2096 alleviates tnbs induced colitis in mice
Journal of Interferon and Cytokine Research, 2006Co-Authors: Chong Shen, Ellen Dillissen, Ahmad Kasran, Yuan Lin, Ilse Sienaert, Steven De Jonghe, Karel Geboes, Gavin Clydesdale, Lingjie Gao, Louis BoonAbstract:Elevated production of tumor necrosis factor (TNF) plays a central role in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis and Crohn's disease. Naturally occurring Pteridine analogs have been reported to have potent immunomodulatory activity, especially on TNF production. The aim of this study is to identify small molecule TNF inhibitiors derived from Pteridine and to prove their in vivo efficacy in an inflammatory model. A focused chemical library based on the Pteridine scaffold was screened in vitro on lipopolysaccharide (LPS)-induced TNF production in peripheral blood mononuclear cells (PBMC). One synthetic Pteridine analog (4AZA2096), shown to have strong inhibitory activity, was selected and tested for its efficacy to treat trinitrobenzenesulfonate (TNBS)-induced colitis in mice, a model of Crohn's disease. Colitis was induced by rectal administration of 1 mg TNBS in 50% ethanol after presensitization via the skin. The synthetic Pteridine analog 4AZA2096 was shown to pote...
H. Priewer - One of the best experts on this subject based on the ideXlab platform.
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Effects of a new Pteridine Derivative on urinary sodium, potassium and magnesium excretion in conscious saline‐loaded rats
British Journal of Pharmacology, 1992Co-Authors: Tim Netzer, Mariusz Majewski, H. Priewer, F Ullrich, Ernst MutschlerAbstract:Abstract 1. Two recently synthesized Pteridine Derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.
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effects of a new Pteridine Derivative on urinary sodium potassium and magnesium excretion in conscious saline loaded rats
British Journal of Pharmacology, 1992Co-Authors: Tim Netzer, Mariusz Majewski, H. Priewer, F Ullrich, Ernst MutschlerAbstract:Abstract 1. Two recently synthesized Pteridine Derivatives (RPH 3036; RPH 3038) were tested in conscious saline-loaded rats and showed natriuretic and antimagnesiuretic properties but hardly reduced potassium excretion. 2. In the same model a dose-response curve was performed for RPH 3036. ED50 and Emax values were calculated for the natriuretic (ED50 = 13.4 mumol kg-1; Emax = 1.08 mmol kg-1) and antimagnesiuretic (ED50 = 11.3 mumol kg-1; Emax = -0.099 mmol kg-1) properties of RPH 3036. There were no significant changes of potassium and calcium excretion. 3. After a single dose of RPH 3036 (100 mumol kg-1) the time course of electrolyte excretion was analysed over 6 h. RPH 3036 did not show any significant effects on renal potassium and calcium excretion whereas a pronounced decrease (P less than 0.01) in renal magnesium excretion was evident during the 6 h. A moderate increase of sodium excretion was observed only after 3, 5 and 6 h. 4. A selective reduction of magnesium secretion in the late distal tubule and collecting duct was proposed as a possible mechanism of action of RPH 3036. This would explain the fast onset of action as well as the lack of antikaliuretic and anticalciuretic effects. The high selectivity of RPH 3036 makes it potentially valuable for the future investigation of renal magnesium transport.