Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation Mariana L. Lafetá, Vitor C. Souza, Thaís C.F. Menezes, Carlos G.Y. Verrastro, Frederico J. Mancuso, et al. Erj Open Research, 2023 RationalePost-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation.MethodsThis prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis.Measurements and main results87 patients were evaluated; mean±sdpeak oxygen consumption was 19.5±5.0 mL·kg−1·min−1, and the tertiles were ≤17.0, 17.1–22.2 and ≥22.3 mL·kg−1·min−1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg−1·min−1reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg−1·min−1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption.ConclusionsExercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.
New potential antiproliferative monophosphoester 2-aminoethyl dihydrogen phosphate in K-562 and K-562 MDR+ leukemia cells TO. Conceição, LGS. Cabral, MG. Laveli-Silva, JC. Pacheco, MG. Alves, et al. Biomedicine and Pharmacotherapy, 2021 The main obstacle in the treatment of cancer patients has been resistance to multiple drugs, leading to the need to develop molecules with a higher specificity target. The liposomal formulation DODAC/2-AEH2P has antitumor potential, inducing apoptosis in several tumor types. Human chronic myeloid leukemia K-562 and K-562 Lucena (MDR+) cells were treated with the DODAC carrier and the liposomal formulation 2-AEH2P. Viability, cell cycle phases, apoptosis, marker expression and mitochondrial potential were analyzed. Significant reduction in viability was observed for all treatments. Changes in the distribution of the cell cycle phases and expression of markers involved in the apoptosis pathways were observed. Reduction of the mitochondrial electrical potential mediated by Bcl-2, being regulated by the reduction of the MTCH2 protein linked to the progression of myeloid leukemia and an increase in the pro-apoptotic proteins Bad and Bax, dependent on p53. This study demonstrated a significant therapeutic potential through apoptotic effects in leukemic cells, regardless of the molecular resistance profile (MDR+).
