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.

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.

RESUMO: É notório o desperdício de materiais na construção civil, o que resulta na geração de resíduos de construção. Com a normalização ambiental recente, não se pode mais descartar esses resíduos de forma indiscriminada, porém deve-se dar aos mesmos uma destinação final adequada ou, sempre que possível, buscar a sua reutilização. Em grande parte, o resíduo gerado na indústria da construção civil é formado por concreto e argamassa, denominados de resíduos “cinzas”. Assim, este trabalho tem como objetivo analisar a substituição dos agregados graúdos naturais por agregados graúdos oriundos da reciclagem de resíduos “cinzas” da construção. Para isso, foram analisados traços de concreto contendo vários níveis de substituição (0%, 19%, 43%, 75%, 100%) do agregado natural pelo agregado reciclado. Foi verificada a influência dos agregados reciclados em algumas propriedades do concreto nos estados fresco e endurecido, com destaque para a resistência à compressão e o módulo de elasticidade. Os resultados mostraram ser possível a substituição de até 100% do agregado natural pelo agregado reciclado sem prejuízo da resistência mecânica do concreto e com redução de apenas 12% no módulo de elasticidade, o que indica a possibilidade do mesmo ser utilizado na produção de concretos com fins estruturais. ABSTRACT: The material loss in civil construction is large, which results in a great amount of construction waste. The latest environmental standards in Brazil do not allow that wastes are indiscriminately disposed of, and it is necessary to ensure their adequate final destination or, whenever possible, their reuse. The greater amount of construction waste is made up of concrete and mortar, called “grey waste”. The aim of this paper is analyze the replacement of natural aggregates with coarse recycled aggregates from grey construction waste. Several concrete mixes were produced with various substitution percentages (0%, 19%, 43%, 75%, 100%) of natural aggregates with coarse recycled aggregates to evaluate the influence of this substitution on the fresh and mechanical properties of the concrete. The most important mechanical properties analyzed are the compressive strength and modulus of elasticity. The results show that it is possible to replace up to 100% of the natural aggregate with recycled aggregates without reducing the compressive strength. In this case, the modulus of elasticity is reduced by only 12%. This suggests that recycled aggregates can be used in the production of structural concretes.

RBR-4t35tk.

No abstract