Ischemic postconditioning reduces reperfusion arrhythmias by adenosine receptors and protein kinase C activation but is independent of KATP channels or connexin 43

Funding: This study was supported by Secretaría de Investigación, Internacionales y Posgrado, Universidad Nacional de Cuyo (06/J505) and by the Spanish, Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III (CIBERCV), cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe), and by Fundació La Marató de TV3 (n◦. 201536-10). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract. Jose A. Sánchez was supported by the International Research Training Group 1566 on Protecting the Heart from Ischemia (PROMISE).Ischemic postconditioning (IPoC) reduces reperfusion arrhythmias but the antiarrhythmic mechanisms remain unknown. The aim of this study was to analyze IPoC electrophysiological effects and the role played by adenosine A, A and A receptors, protein kinase C, ATP-dependent potassium (K) channels, and connexin 43. IPoC reduced reperfusion arrhythmias (mainly sustained ventricular fibrillation) in isolated rat hearts, an effect associated with a transient delay in epicardial electrical activation, and with action potential shortening. Electrical impedance measurements and Lucifer-Yellow diffusion assays agreed with such activation delay. However, this delay persisted during IPoC in isolated mouse hearts in which connexin 43 was replaced by connexin 32 and in mice with conditional deletion of connexin 43. Adenosine A, A and A receptor blockade antagonized the antiarrhythmic effect of IPoC and the associated action potential shortening, whereas exogenous adenosine reduced reperfusion arrhythmias and shortened action potential duration. Protein kinase C inhibition by chelerythrine abolished the protective effect of IPoC but did not modify the effects on action potential duration. On the other hand, glibenclamide, a K inhibitor, antagonized the action potential shortening but did not interfere with the antiarrhythmic effect. The antiarrhythmic mechanisms of IPoC involve adenosine receptor activation and are associated with action potential shortening. However, this action potential shortening is not essential for protection, as it persisted during protein kinase C inhibition, a maneuver that abolished IPoC protection. Furthermore, glibenclamide induced the opposite effects. In addition, IPoC delays electrical activation and electrical impedance recovery during reperfusion, but these effects are independent of connexin 43

Uso De Filtros De Carvão Ativado Granular Associado A Microrganismos Para Remoção De Fármacos No Tratamento De água De Abastecimento

The way of life of modern societies has originated the daily intake of pharmaceuticals and numerous other molecules of continuous use in aquatic environments, emerging compounds that brings potential risk for human health mainly due to exposure resulted from the inevitable contamination of sources of drinking water supply and its transference to the water treatment plants (WTP) where they are not removed. The use of granular activated carbon in filters proves to be a viable option for WTP, but satisfactory efficiency requires periodic regeneration of the material, burdening the treatment costs. However, it is noted that under low filtration rates, the natural colonization of filters by microorganisms — biofilm formation — may be an alternative for increasing the lifetime of carbon, as well as to decompose these complex molecules into assimilable mineral elements, thereby reintroducing them to the natural biogeochemical cycles. This study evaluated the activated carbon with biofilm as the filter media, during 24 weeks, under laboratory conditions, considering the removal of the pharmaceuticals diclofenac sodium, ibuprofen, naproxen and amoxicillin; experienced under batch system the potential of the microorganisms adhering to the filters in degrade the tested drugs, as well as phylogenetically identified the predominant microorganisms in biodegradation. The results show drug removal over 80%. It was observed the presence of the bacteria genus Bacillus, Burkholderia, Cupriavidus, Pseudomonas, Shinella and Sphingomonas. This study allows us to infer the capacity to remove pharmaceuticals by the bacteria present in the activated carbon filters, and the possible use of this technology as an alternative for control and removal of these substances in drinking water treatment. © 2016, ABES - Associacao Brasileira de Engenharia Sanitaria e Ambiental. All rights reserved.21470972

Elastase-2, a tissue alternative pathway for angiotensin II generation, plays a role in circulatory sympathovagal balance in mice

In vitro and ex vivo experiments indicate that elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, is an alternative pathway for angiotensin II (Ang II) generation. However, the role played by ELA-2 in vivo is unclear. We examined ELA-2 knockout (ELA-2KO) mice compared to wild-type (WT) mice and determined whether ELA-2 played a role in hemodynamics [arterial pressure (AP) and heart rate (HR)], cardiocirculatory sympathovagal balance and baroreflex sensitivity. The variability of systolic arterial pressure (SAP) and pulse interval (PI) for evaluating autonomic modulation was examined for time and frequency domains (spectral analysis), whereas a symbolic analysis was also used to evaluate PI variability. In addition, baroreflex sensitivity was examined using the sequence method. Cardiac function was evaluated echocardiographically under anesthesia. The AP was normal whereas the HR was reduced in ELA-2KO mice (425 ± 17 vs. 512 ± 13 bpm from WT). SAP variability and baroreflex sensitivity were similar in both strains. The LF power from the PI spectrum (33.6 ± 5 vs. 51.8 ± 4.8 nu from WT) and the LF/HF ratio (0.60 ± 0.1 vs. 1.45 ± 0.3 from WT) were reduced, whereas the HF power was increased (66.4 ± 5 vs. 48.2 ± 4.8 nu from WT) in ELA-2KO mice, indicating a shift toward parasympathetic modulation of HR. Echocardiographic examination showed normal fractional shortening and an ejection fraction in ELA-2KO mice; however, the cardiac output, stroke volume, and ventricular size were reduced. These findings provide the first evidence that ELA-2 acts on the sympathovagal balance of the heart, as expressed by the reduced sympathetic modulation of HR in ELA-2KO mice

Modelling the impact of school reopening and contact tracing strategies on Covid-19 dynamics in different epidemiologic settings in Brazil

This study was funded by the Brazilian National Council for Scientific and Technological Development (CNPq) [grant number 402834/2020-8]. MEB received a technological and industrial scholarship from CNPq [grant number 315854/2020-0]. LSF received a master's scholarship from Coordination for the Improvement of Higher Education Personnel (CAPES) [finance code 001]. SP was supported by São Paulo Research Foundation (FAPESP) [grant number 2018/24037-4]. AMB received a technological and industrial scholarship from CNPq [grant number 402834/2020-8]. CF was supported by FAPESP [grant numbers 2019/26310-2 and 2017/26770-8]. MQMR received a postdoctoral scholarship from CAPES [grant number 305269/2020-8]. LMS received a technological and industrial scholarship from CNPq [grant number 315866/2020-9]. RSK has been supported by CNPq [grant number 312378/2019-0]. PIP has been supported by CNPq [grant number 313055/2020-3]. JAFD-F has been supported by CNPq productivity fellowship and the National Institutes for Science and Technology in Ecology, Evolution and Biodiversity Conservation (INCT-EEC), supported by MCTIC/CNPq [grant number 465610/2014-5] and Goiás Research Foundation (FAPEG) [grant number 201810267000023]. RAK has been supported by CNPq [grant number 311832/2017-2] and FAPESP [grant number 2016/01343-7]. CMT has been supported by CNPq productivity fellowship and the National Institute for Health Technology Assessment (IATS) [grant number 465518/2014-1].Peer reviewedPublisher PD

Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant

Acknowledgements We are grateful for the collaborative work of the reviewers and the entire group of the Observatório COVID-19 BR. In particular, we thank Verônica Coelho for critical inputs. We also thank the research funding agencies: the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (Finance Code 001 to F.M.D.M., L.S.F. and T.P.P.), Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brazil (grant number: 315854/2020-0 to M.E.B., 141698/2018-7 to R.L.P.S., 313055/2020-3 to P.I.P., 312559/2020-8 to M.A.S.M.V., 311832/2017-2 to R.A.K., 305703/2019-6 to A.A.M.S.) and Fundação de Amparo à Pesquisa do Estado de São Paulo—Brazil (grant number: 2019/26310-2 and 2017/26770-8 to C.F., 2018/26512-1 to O.C., 2018/24037-4 to S.P. and contract number: 2016/01343-7 to R.A.K.). The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers of Disease Control and Prevention.Peer reviewe