The Experts below are selected from a list of 5442 Experts worldwide ranked by ideXlab platform
Florina Moldovan - One of the best experts on this subject based on the ideXlab platform.
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nociceptive tolerance is improved by Bradykinin Receptor B1 antagonism and joint morphology is protected by both endothelin type a and Bradykinin Receptor B1 antagonism in a surgical model of osteoarthritis
Arthritis Research & Therapy, 2011Co-Authors: Gabriel N Kaufman, Charlotte Zaouter, Barthelemy Valteau, Pierre Sirois, Florina MoldovanAbstract:Introduction Endothelin-1, a vasoconstrictor peptide, influences cartilage metabolism mainly via endothelin Receptor type A (ETA). Along with the inflammatory nonapeptide vasodilator Bradykinin (BK), which acts via Bradykinin Receptor B1 (BKB1) in chronic inflammatory conditions, these vasoactive factors potentiate joint pain and inflammation. We describe a preclinical study of the efficacy of treatment of surgically induced osteoarthritis with ETA and/or BKB1 specific peptide antagonists. We hypothesize that antagonism of both Receptors will diminish osteoarthritis progress and articular nociception in a synergistic manner.
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nociceptive tolerance is improved by Bradykinin Receptor B1 antagonism and joint morphology is protected by both endothelin type a and Bradykinin Receptor B1 antagonism in a surgical model of osteoarthritis
Arthritis Research & Therapy, 2011Co-Authors: Gabriel N Kaufman, Charlotte Zaouter, Barthelemy Valteau, Pierre Sirois, Florina MoldovanAbstract:Endothelin-1, a vasoconstrictor peptide, influences cartilage metabolism mainly via endothelin Receptor type A (ETA). Along with the inflammatory nonapeptide vasodilator Bradykinin (BK), which acts via Bradykinin Receptor B1 (BKB1) in chronic inflammatory conditions, these vasoactive factors potentiate joint pain and inflammation. We describe a preclinical study of the efficacy of treatment of surgically induced osteoarthritis with ETA and/or BKB1 specific peptide antagonists. We hypothesize that antagonism of both Receptors will diminish osteoarthritis progress and articular nociception in a synergistic manner. Osteoarthritis was surgically induced in male rats by transection of the right anterior cruciate ligament. Animals were subsequently treated with weekly intra-articular injections of specific peptide antagonists of ETA and/or BKB1. Hind limb nociception was measured by static weight bearing biweekly for two months post-operatively. Post-mortem, right knee joints were analyzed radiologically by X-ray and magnetic resonance, and histologically by the OARSI histopathology assessment system. Single local BKB1 antagonist treatment diminished overall hind limb nociception, and accelerated post-operative recovery after disease induction. Both ETA and/or BKB1 antagonist treatments protected joint radiomorphology and histomorphology. Dual ETA/BKB1 antagonism was slightly more protective, as measured by radiology and histology. BKB1 antagonism improves nociceptive tolerance, and both ETA and/or BKB1 antagonism prevents joint cartilage degradation in a surgical model of osteoarthritis. Therefore, they represent a novel therapeutic strategy: specific Receptor antagonism may prove beneficial in disease management.
Christoph Kleinschnitz - One of the best experts on this subject based on the ideXlab platform.
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blocking of Bradykinin Receptor B1 protects from focal closed head injury in mice by reducing axonal damage and astroglia activation
Journal of Cerebral Blood Flow and Metabolism, 2012Co-Authors: Christiane Albertweissenberger, Michael Bader, Sven G Meuth, Annaleena Siren, Christian Stetter, Kerstin Gobel, Christoph KleinschnitzAbstract:The two Bradykinin Receptors B1R and B2R are central components of the kallikrein–kinin system with different expression kinetics and binding characteristics. Activation of these Receptors by kinins triggers inflammatory responses in the target organ and in most situations enhances tissue damage. We could recently show that blocking of B1R, but not B2R, protects from cortical cryolesion by reducing inflammation and edema formation. In the present study, we investigated the role of B1R and B2R in a closed head model of focal traumatic brain injury (TBI; weight drop). Increased expression of B1R in the injured hemispheres of wild-type mice was restricted to the later stages after brain trauma, i.e. day 7 (P 0.05). Mice lacking the B1R, but not the B2R, showed less functional deficits on day 3 (P<0.001) and day 7 (P<0.001) compared with controls. Pharmacological blocking of B1R in wild-type mice had similar effects. Reduced axonal injury and astroglia activation could be identified as underlying mechanisms, while inhibition of B1R had only little influence on the local inflammatory response in this model. Inhibition of B1R may become a novel strategy to counteract trauma-induced neurodegeneration.
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inhibition of Bradykinin Receptor B1 protects mice from focal brain injury by reducing blood brain barrier leakage and inflammation
Journal of Cerebral Blood Flow and Metabolism, 2010Co-Authors: Furat Raslan, Thomas Renne, Madeleine Austinat, Guido Stoll, Michael Bader, Tobias Schwarz, Sven G Meuth, K Roosen, Annaleena Siren, Christoph KleinschnitzAbstract:Kinins are proinflammatory and vasoactive peptides that are released during tissue damage and may contribute to neuronal degeneration, inflammation, and edema formation after brain injury by acting on discrete Bradykinin Receptors, B1R and B2R. We studied the expression of B1R and B2R and the effect of their inhibition on lesion size, blood–brain barrier (BBB) disruption, and inflammatory processes after a focal cryolesion of the right parietal cortex in mice. B1R and B2R gene transcripts were significantly induced in the lesioned hemispheres of wild-type mice (P<0.05). The volume of the cortical lesions and neuronal damage at 24 h after injury in B1R−/− mice were significantly smaller than in wild-type controls (2.5±2.6 versus 11.5±3.9 mm3, P<0.001). Treatment with the B1R antagonist R-715 1 h after lesion induction likewise reduced lesion volume in wild-type mice (2.6±1.4 versus 12.2±6.1 mm3, P<0.001). This was accompanied by a remarkable reduction of BBB disruption and tissue inflammation. In contrast, genetic deletion or pharmacological inhibition of B2R had no significant impact on lesion formation or the development of brain edema. We conclude that B1R inhibition may offer a novel therapeutic strategy after acute brain injuries.
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blockade of Bradykinin Receptor B1 but not Bradykinin Receptor b2 provides protection from cerebral infarction and brain edema
Stroke, 2009Co-Authors: Madeleine Austinat, Stefan Braeuninger, Thomas Renne, Marc Brede, Joao Bosco Pesquero, Guido Stoll, Michael Bader, Christoph KleinschnitzAbstract:Background and Purpose— Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different Receptors (B1 and B2 Receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators. Methods— Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan’s blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin Receptor blockade, B1R and B2R inhibitors were injected. Results— B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8±4.7 mm3 vs 50.1±9.1 m...
Gabriel N Kaufman - One of the best experts on this subject based on the ideXlab platform.
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nociceptive tolerance is improved by Bradykinin Receptor B1 antagonism and joint morphology is protected by both endothelin type a and Bradykinin Receptor B1 antagonism in a surgical model of osteoarthritis
Arthritis Research & Therapy, 2011Co-Authors: Gabriel N Kaufman, Charlotte Zaouter, Barthelemy Valteau, Pierre Sirois, Florina MoldovanAbstract:Introduction Endothelin-1, a vasoconstrictor peptide, influences cartilage metabolism mainly via endothelin Receptor type A (ETA). Along with the inflammatory nonapeptide vasodilator Bradykinin (BK), which acts via Bradykinin Receptor B1 (BKB1) in chronic inflammatory conditions, these vasoactive factors potentiate joint pain and inflammation. We describe a preclinical study of the efficacy of treatment of surgically induced osteoarthritis with ETA and/or BKB1 specific peptide antagonists. We hypothesize that antagonism of both Receptors will diminish osteoarthritis progress and articular nociception in a synergistic manner.
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nociceptive tolerance is improved by Bradykinin Receptor B1 antagonism and joint morphology is protected by both endothelin type a and Bradykinin Receptor B1 antagonism in a surgical model of osteoarthritis
Arthritis Research & Therapy, 2011Co-Authors: Gabriel N Kaufman, Charlotte Zaouter, Barthelemy Valteau, Pierre Sirois, Florina MoldovanAbstract:Endothelin-1, a vasoconstrictor peptide, influences cartilage metabolism mainly via endothelin Receptor type A (ETA). Along with the inflammatory nonapeptide vasodilator Bradykinin (BK), which acts via Bradykinin Receptor B1 (BKB1) in chronic inflammatory conditions, these vasoactive factors potentiate joint pain and inflammation. We describe a preclinical study of the efficacy of treatment of surgically induced osteoarthritis with ETA and/or BKB1 specific peptide antagonists. We hypothesize that antagonism of both Receptors will diminish osteoarthritis progress and articular nociception in a synergistic manner. Osteoarthritis was surgically induced in male rats by transection of the right anterior cruciate ligament. Animals were subsequently treated with weekly intra-articular injections of specific peptide antagonists of ETA and/or BKB1. Hind limb nociception was measured by static weight bearing biweekly for two months post-operatively. Post-mortem, right knee joints were analyzed radiologically by X-ray and magnetic resonance, and histologically by the OARSI histopathology assessment system. Single local BKB1 antagonist treatment diminished overall hind limb nociception, and accelerated post-operative recovery after disease induction. Both ETA and/or BKB1 antagonist treatments protected joint radiomorphology and histomorphology. Dual ETA/BKB1 antagonism was slightly more protective, as measured by radiology and histology. BKB1 antagonism improves nociceptive tolerance, and both ETA and/or BKB1 antagonism prevents joint cartilage degradation in a surgical model of osteoarthritis. Therefore, they represent a novel therapeutic strategy: specific Receptor antagonism may prove beneficial in disease management.
Kuoshyan Lin - One of the best experts on this subject based on the ideXlab platform.
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in vivo radioimaging of Bradykinin Receptor B1 a widely overexpressed molecule in human cancer
Cancer Research, 2015Co-Authors: Kuoshyan Lin, Jinhe Pan, Guillaume Amouroux, Gulisa Turashvili, Felix Mesak, Navjit Hundaljabal, Maral Pourghiasian, Joseph Lau, Silvia JenniAbstract:The Bradykinin Receptor B1R is overexpressed in many human cancers where it might be used as a general target for cancer imaging. In this study, we evaluated the feasibility of using radiolabeled kallidin derivatives to visualize B1R expression in a preclinical model of B1R-positive tumors. Three synthetic derivatives were evaluated in vitro and in vivo for Receptor binding and their ability to visualize tumors by PET. Enalaprilat and phosphoramidon were used to evaluate the impact of peptidases on tumor visualization. While we found that radiolabeled peptides based on the native kallidin sequence were ineffective at visualizing B1R-positive tumors, peptidase inhibition with phosphoramidon greatly enhanced B1R visualization in vivo . Two stabilized derivatives incorporating unnatural amino acids ( 68 Ga-SH01078 and 68 Ga-P03034) maintained Receptor-binding affinities that were effective, allowing excellent tumor visualization, minimal accumulation in normal tissues, and rapid renal clearance. Tumor uptake was blocked in the presence of excess competitor, confirming that the specificity of tumor accumulation was Receptor mediated. Our results offer a preclinical proof of concept for noninvasive B1R detection by PET imaging as a general tool to visualize many human cancers. Cancer Res; 75(2); 387–93. ©2014 AACR.
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in vivo radioimaging of Bradykinin Receptor B1 a widely overexpressed molecule in human cancer
Cancer Research, 2015Co-Authors: Kuoshyan Lin, Jinhe Pan, Guillaume Amouroux, Gulisa Turashvili, Felix Mesak, Navjit Hundaljabal, Maral Pourghiasian, Joseph Lau, Silvia Jenni, Samuel AparicioAbstract:The Bradykinin Receptor B1R is overexpressed in many human cancers where it might be used as a general target for cancer imaging. In this study, we evaluated the feasibility of using radiolabeled kallidin derivatives to visualize B1R expression in a preclinical model of B1R-positive tumors. Three synthetic derivatives were evaluated in vitro and in vivo for Receptor binding and their ability to visualize tumors by PET. Enalaprilat and phosphoramidon were used to evaluate the impact of peptidases on tumor visualization. While we found that radiolabeled peptides based on the native kallidin sequence were ineffective at visualizing B1R-positive tumors, peptidase inhibition with phosphoramidon greatly enhanced B1R visualization in vivo. Two stabilized derivatives incorporating unnatural amino acids ((68)Ga-SH01078 and (68)Ga-P03034) maintained Receptor-binding affinities that were effective, allowing excellent tumor visualization, minimal accumulation in normal tissues, and rapid renal clearance. Tumor uptake was blocked in the presence of excess competitor, confirming that the specificity of tumor accumulation was Receptor mediated. Our results offer a preclinical proof of concept for noninvasive B1R detection by PET imaging as a general tool to visualize many human cancers.
Francois Benard - One of the best experts on this subject based on the ideXlab platform.
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in vivo radioimaging of Bradykinin Receptor B1 a widely overexpressed molecule in human cancer
Cancer Research, 2015Co-Authors: Guillaume Amouroux, Gulisa Turashvili, Felix Mesak, Navjit Hundaljabal, Maral Pourghiasian, Silvia Jenni, Samuel Aparicio, Francois BenardAbstract:The Bradykinin Receptor B1R is overexpressed in many human cancers where it might be used as a general target for cancer imaging. In this study, we evaluated the feasibility of using radiolabeled kallidin derivatives to visualize B1R expression in a preclinical model of B1R-positive tumors. Three synthetic derivatives were evaluated in vitro and in vivo for Receptor binding and their ability to visualize tumors by PET. Enalaprilat and phosphoramidon were used to evaluate the impact of peptidases on tumor visualization. While we found that radiolabeled peptides based on the native kallidin sequence were ineffective at visualizing B1R-positive tumors, peptidase inhibition with phosphoramidon greatly enhanced B1R visualization in vivo . Two stabilized derivatives incorporating unnatural amino acids ( 68 Ga-SH01078 and 68 Ga-P03034) maintained Receptor-binding affinities that were effective, allowing excellent tumor visualization, minimal accumulation in normal tissues, and rapid renal clearance. Tumor uptake was blocked in the presence of excess competitor, confirming that the specificity of tumor accumulation was Receptor mediated. Our results offer a preclinical proof of concept for noninvasive B1R detection by PET imaging as a general tool to visualize many human cancers. Cancer Res; 75(2); 387–93. ©2014 AACR.