Compostos inibidores de serina protease, processo de obtenção e uso para tratamento de flaviviroses

Em 02/09/2016: Anuidade de pedido de patente de invenção no prazo ordinário.DepositadaRefere-se a presente invenção a compostos inibidores de serina protease sintéticos tendo um eixo de simetria C~2~, possuindo na porção central uma estrutura do tipo 1,4:3,6- dianidromanitol e, nas porções laterais, ligações peptidomiméticas com aminoácidos, como por exemplo, lisina (Lis), fenilalanina (Phe), dentre outros, utilizados como base para a preparação de formulações antivirais capazes de cessar a proliferação dos vírus responsáveis pela maioria das flaviviroses, como por exemplo, hepatite C, Dengue e febre do oeste do Nilo

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Maria\'s Cayapó? A study of the material culture of a Jê site in the Fartura River basin in Goiás.

A presente pesquisa procura trazer à tona a compreensão de alguns aspectos culturais inerentes ao povo Cayapó Meridional, que ocupou o sertão goiano, na Bacia do Rio Fartura, região onde foi criado na segunda metade do século XVIII o icônico Aldeamento Maria I que após sua desativação ocorrida em 1813, teria se perdido no tempo. Baseando-se em documentação histórica, foram identificadas cinco áreas potenciais com a provável localização do referido aldeamento. Cada uma dessas áreas foi investigada, mas em apenas uma foram encontrados vestígios que se assemelham ao material costumeiramente atribuído a povos integrantes da família linguística Macro-Jê, à qual pertencem os Cayapó. Tais vestígios estariam ligados ao antigo aldeamento? A luz das evidências encontradas não foi possível responder essa pergunta, no entanto, a cultura material do sítio arqueológico MI, certamente pertence ao povo Cayapó que em algum momento da história viveu a desventura do contato e dos aldeamentos impostos pelos colonizadores.The present research seeks to bring to light the understanding of some cultural aspects inherent to the Cayapó Meridional people, who occupied the goiano hinterland, in the Fartura river basin, a region where the iconic Aldeamento Maria I was created in the second half of the 18th century, which after its deactivation occurred in 1813, it would have been lost in time. Based on historical documentation, five potential areas were identified with the probable location of the village. Each of these areas was investigated, but in only one were found traces that resemble the material usually attributed to peoples belonging to the Macro-Jê linguistic family, to which the Cayapó belong. Would such traces be linked to the old village? In light of the evidence found, it was not possible to answer this question, however, the material culture of the archaeological site MI, certainly belongs to the Cayapó people who, at some point in history, experienced the misfortune of contact and settlements imposed by the colonizers

Memórias do patrimônio colonial - o caso do sobrado dos Toledos, Iguape-SP

Este artigo trata-se de um palimpsesto do patrimônio colonial de Iguape-SP. Nosso objetivo é trazer, por meio do estudo arqueológico, as diversas ocupações do Sobrado dos Toledos,  edifício histórico tombado pelo IPHAN, parte importante da paisagem de Iguape e símbolo neoclássico de um importante contexto colonial. Temos o intuito de ressaltar os agentes sociais que fizeram e fazem parte das histórias recuperadas neste contexto, de restaurar e exaltar as diversas memórias ali vividas, reconstruindo e refazendo uma biografia do local através de uma arqueologia histórica

Pseudo-Peptides Derived from Isomannide as Potential Inhibitors of Serine Proteases

Hepatitis C, dengue and West Nile virus are among of the most important flaviviruses that share one important serine protease enzyme. Serine proteases belong to the most studied class of proteolytic enzymes, and are a primary target in the drug development field. In this paper, we describe the synthesis and preliminary molecular modeling studies of a novel class of N-t-Boc amino acid amides derived of isomannide as potential serine proteases inhibitors