The Experts below are selected from a list of 4845 Experts worldwide ranked by ideXlab platform
Rafael Ludemann Camargo - One of the best experts on this subject based on the ideXlab platform.
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safety and outcomes associated with the pharmacological inhibition of the kinin kallikrein System in severe covid 19
Viruses, 2021Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
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pharmacological inhibition of the kinin kallikrein System in severe covid 19 a proof of concept study
medRxiv, 2020Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
Eli Mansour - One of the best experts on this subject based on the ideXlab platform.
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safety and outcomes associated with the pharmacological inhibition of the kinin kallikrein System in severe covid 19
Viruses, 2021Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
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pharmacological inhibition of the kinin kallikrein System in severe covid 19 a proof of concept study
medRxiv, 2020Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
Bjoern B Burckhardt - One of the best experts on this subject based on the ideXlab platform.
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sensitive mass spectrometric determination of kinin kallikrein System peptides in light of covid 19
Scientific Reports, 2021Co-Authors: Tanja Gangnus, Bjoern B BurckhardtAbstract:The outbreak of COVID-19 has raised interest in the Kinin-Kallikrein System. Viral blockade of the angiotensin-converting enzyme 2 impedes degradation of the active kinin des-Arg(9)-bradykinin, which thus increasingly activates bradykinin receptors known to promote inflammation, cough, and edema-symptoms that are commonly observed in COVID-19. However, lean and reliable investigation of the postulated alterations is currently hindered by non-specific peptide adsorption, lacking sensitivity, and cross-reactivity of applicable assays. Here, an LC-MS/MS method was established to determine the following kinins in respiratory lavage fluids: kallidin, bradykinin, des-Arg(10)-kallidin, des-Arg(9)-bradykinin, bradykinin 1-7, bradykinin 2-9 and bradykinin 1-5. This method was fully validated according to regulatory bioanalytical guidelines of the European Medicine Agency and the US Food and Drug Administration and has a broad calibration curve range (up to a factor of 103), encompassing low quantification limits of 4.4-22.8 pg/mL (depending on the individual kinin). The application of the developed LC-MS/MS method to nasal lavage fluid allowed for the rapid (~ 2 h), comprehensive and low-volume (100 µL) determination of kinins. Hence, this novel assay may support current efforts to investigate the pathophysiology of COVID-19, but can also be extended to other diseases.
Marcus V Agrela - One of the best experts on this subject based on the ideXlab platform.
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safety and outcomes associated with the pharmacological inhibition of the kinin kallikrein System in severe covid 19
Viruses, 2021Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
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pharmacological inhibition of the kinin kallikrein System in severe covid 19 a proof of concept study
medRxiv, 2020Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
Milena Monfortpires - One of the best experts on this subject based on the ideXlab platform.
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safety and outcomes associated with the pharmacological inhibition of the kinin kallikrein System in severe covid 19
Viruses, 2021Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
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pharmacological inhibition of the kinin kallikrein System in severe covid 19 a proof of concept study
medRxiv, 2020Co-Authors: Eli Mansour, Andre Palma, Raisa G Ulaf, Luciana C Ribeiro, Ana Flavia Bernardes, Thyago A Nunes, Marcus V Agrela, Bruna Bombassaro, Milena Monfortpires, Rafael Ludemann CamargoAbstract:Coronavirus disease-19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to accumulation of bradykinin. In this open-label, randomized clinical trial, we tested two pharmacological inhibitors of the Kinin-Kallikrein System that are currently approved for the treatment of hereditary angioedema, icatibant and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in significant changes in disease mortality and time to clinical improvement. However, both compounds promoted significant improvement of lung computed tomography scores and increased blood eosinophils, which has been reported as an indicator of disease recovery. In this small cohort, we found evidence for a beneficial role of pharmacological inhibition of the Kinin-Kallikrein System in two markers that indicate improved disease recovery.
