Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
Front Cardiovasc Med ; 9: 847809, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35811697

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1-7), and angiotensin (1-9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1-7), and angiotensin (1-9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.

2.
Viruses ; 13(2)2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33669276

RESUMEN

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.


Asunto(s)
Bradiquinina/análogos & derivados , Tratamiento Farmacológico de COVID-19 , Proteína Inhibidora del Complemento C1/uso terapéutico , Sistema Calicreína-Quinina/efectos de los fármacos , Calicreínas/antagonistas & inhibidores , Adulto , Anciano , Bradiquinina/uso terapéutico , Estudios de Casos y Controles , Reposicionamiento de Medicamentos , Femenino , Humanos , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Persona de Mediana Edad
3.
Trials ; 22(1): 71, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33472675

RESUMEN

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.


Asunto(s)
Bradiquinina/análogos & derivados , Tratamiento Farmacológico de COVID-19 , Proteína Inhibidora del Complemento C1/administración & dosificación , Insuficiencia Respiratoria/tratamiento farmacológico , Adulto , Enzima Convertidora de Angiotensina 2/metabolismo , Bradiquinina/administración & dosificación , Bradiquinina/efectos adversos , Bradiquinina/antagonistas & inhibidores , Bradiquinina/inmunología , Bradiquinina/metabolismo , Antagonistas del Receptor de Bradiquinina B2/administración & dosificación , Antagonistas del Receptor de Bradiquinina B2/efectos adversos , Brasil , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/virología , Ensayos Clínicos Fase II como Asunto , Proteína Inhibidora del Complemento C1/efectos adversos , Esquema de Medicación , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Humanos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Calicreínas/antagonistas & inhibidores , Calicreínas/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Respiratoria/inmunología , Insuficiencia Respiratoria/virología , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/patogenicidad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA