Interleukin-6 increases the expression and activity of insulin-degrading enzyme

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOImpairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and act7112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2014/24719-7; 2015/12611-

Anastomose esofagogástrica cervical em dois tempos: 5 anos de experiência do Hospital de Clínicas de Porto Alegre

OBJECTIVE: Cervical esophagogastric anastomosis (CEA) is a common procedure used to restore the continuity of the digestive tract following curative or palliative surgery for esophageal cancer. At the HCPA, we carry out CEA procedures in two steps: first, we carry out a lateral cervical esophagostomy and position the esophageal substitute in the neck; second, after one week, the esophageal remnant is sutured to the esophageal substitute. The choice of esophageal substitute is made according to gastric pull-up (GP) or greater curvature gastric tube (GCGT), depending on the possibility of resection of the lesion. The objective of this paper is to describe the early results (up to 30 days) of delayed cervical esophagogastric anastomosis after resection or esophageal bypass procedures due to esophageal neoplasia. MATERIAL AND METHODS: Fifty-nine patients fulfilled the criteria for inclusion in our study, out of which there were 49 male and 55 white patients; the age average was of 51.5 years. Twenty-two patients were submitted to gastric pull-up. The risk factors for postoperative complications were similar for both groups. Tumor staging was the only difference between the two groups in preoperative examination; this difference was expected according to the criteria used for choosing the procedure. RESULTS: Seven patients (31.8%) of the GP group and in 9 patients (34.3%) from the GCGT group (RR 1.3; CI 95%: 0.5-3.0, P = 0.54) presented leakage. Two patients (9.1%) from the GP group and 1 (2.7%) from the GCGT group died (RR 3.4; CI 95%: 0.3-34.9, P = 0.54). One patient (4.5%) from the GP group and 7 (18.9%) patients from the GCGT group (RR 0.2; CI 95%: 0.1-1.8, P = 0.23) presented infections. There were no differences between the groups regarding occurrence of leakage, short-term postoperative death (until 30 days after surgery), and infections. CONCLUSIONS: Our results are similar to those of other services of reference for the treatment of esophageal cancer. In this study, we did not find any differences between the GP and GCGT groups regarding short-term postoperative complications.OBJETIVO: A anastomose esofagogástrica cervical é um procedimento utilizado para restaurar a continuidade do trato digestivo após cirurgias curativas ou paliativas para o câncer esofágico. O Grupo de Cirurgia do Esôfago, Estômago e Intestino Delgado do Hospital de Clínicas de Porto Alegre realiza o procedimento em 2 tempos cirúrgicos. No primeiro tempo, realiza-se uma esofagostomia cervical lateral e posiciona-se o substituto esofágico no pescoço. O segundo tempo é realizado uma semana após, com a sutura do esôfago remanescente no substituto elevado ao pescoço. Este substituto é escolhido entre os procedimentos de levantamento gástrico (LG) e tubo gástrico de grande curvatura (TGC), conforme a possibilidade ou não de ressecção da lesão esofágica. O objetivo do presente trabalho é de descrever os resultados precoces (até 30 dias) obtidos com a realização de anastomose esôfago-gástrica cervical retardada (postergada) após procedimento cirúrgico de ressecção ou bypass esofágico por neoplasia de esôfago. MATERIAIS E MÉTODOS: Cinqüenta e nove pacientes preencheram os critérios de inclusão, sendo 49 homens, 55 brancos, com uma média de idade de 51,5 anos. Vinte e dois pacientes realizaram cirurgia de levantamento gástrico. Os fatores de risco conhecidos para complicações pós-operatórias foram similares entre os dois grupos. A única diferença entre os grupos na avaliação pré-operatória foi o estágio do tumor, o que era esperado, tendo em vista os critérios usados para a escolha do procedimento. RESULTADOS: A fístula cervical foi detectada em sete pacientes (31,8%) do grupo LG e em nove pacientes (34,3%) do grupo TGC (RR 1,3; IC 95%: 0,5-3,0, P = 0.54). Dois pacientes (9,1%) do grupo LG e um paciente (2,7%) do grupo TGC foram a óbito (RR 3,4; IC 95%: 0,3-34,9, P = 0,54). As complicações infecciosas ocorreram em um paciente (4,5%) do grupo LG e 7 pacientes (18,9%) do grupo TGC (RR 0,2; IC 95%: 0,1-1,8, P = 0,23). Não houve diferenças entre os grupos, levando em conta a ocorrência de fístula cervical no pós-operatório, mortalidade hospitalar precoce (30 dias após a cirurgia) e infecções. CONCLUSÕES: Os dados apresentados nesta série são semelhantes a outros serviços de referência para o tratamento do câncer de esôfago, e nessa série não houve diferença entre os LG e TGC em relação às complicações no pós-operatório precoce

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

Live Phylogeny.

The live phylogeny problem generalizes the phylogeny problem while admitting the existence of living ancestors among the taxonomic objects. This problem suits the case of fast-evolving species, like virus, and the construction of phylogenies for nonbiological objects like documents, images, and database records. In this article, we formalize the live phylogeny problem for distances and character states and introduce polynomial-time algorithms for particular versions of the problems. We believe that more general versions of the problems are NP-hard and that many heuristic and approximation approaches may be developed as solution strategies.2030-