Sepse: o papel das selectinas e do óxido nítrico

Sepsis-a state of systemic bacterial infection-often leads to multiorgan failure and is associated with high mortality despite the recent advances achieved in intensive care treatment. Many of the ill effects of sepsis are attributed to an abnormally enhanced host inflammatory response that leads to neutrophil recruitment and activation involving selectins, a class of adhesion molecules, in the initial stages. Nitric oxide and its various isoforms have also been implicated in various vascular alterations and directly participate in the cellular toxicity in sepsis. This review briefly describes the role of selectins and nitric oxide in experimental and clinical sepsis as well as the therapeutic outcomes of blocking therapies.Sepse - um estado de infecção bacteriana sistêmica - frequentemente leva à falência múltipla de órgãos e associa-se a altos índices de mortalidade, apesar de progressos recentes no manejo de pacientes em unidades de terapia intensiva. Muitos dos efeitos maléficos associados à sepse são atribuídos a uma resposta inflamatória patologicamente ampliada que leva a recrutamento neutrofílico e ativação das moléculas de adesão do grupo das selectinas, durante as fases iniciais do processo . O óxido nítrico e sua diversas isoformas também foram implicados nas diversas manifestações vasculares da sepse como participantes diretos da toxicidade celular. Esta revisão descreve o papel das selectinas e do óxido nítrico em situações clínicas e experimentais de sepse, bem como os respectivos efeitos de processos terapêuticos de bloqueio

Recombinant human activated protein C attenuates cardiovascular and microcirculatory dysfunction in acute lung injury and septic shock

Introduction: This prospective, randomized, controlled, experimental animal study looks at the effects of recombinant human activated protein C (rhAPC) on global hemodynamics and microcirculation in ovine acute lung injury (ALI) and septic shock, resulting from smoke inhalation injury

Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study

Introduction: We hypothesized that maintaining physiological plasma levels of antithrombin attenuates myocardial dysfunction and inflammation as well as vascular leakage associated with burn and smoke inhalation injury. Therefore, the present prospective, randomized experiment was conducted using an established ovine model. Methods: Following 40% of total body surface area, third degree flame burn and 4 × 12 breaths of cold cotton smoke, chronically instrumented sheep were randomly assigned to receive an intravenous infusion of 6 IU/kg/h recombinant human antithrombin (rhAT) or normal saline (control group; n = 6 each). In addition, six sheep were designated as sham animals (not injured, continuous infusion of vehicle). During the 48 h study period the animals were awake, mechanically ventilated and fluid resuscitated according to standard formulas. Results: Compared to the sham group, myocardial contractility was severely impaired in control animals, as suggested by lower stroke volume and left ventricular stroke work indexes. As a compensatory mechanism, heart rate increased, thereby increasing myocardial oxygen consumption. In parallel, myocardial inflammation was induced via nitric oxide production, neutrophil accumulation (myeloperoxidase activity) and activation of the p38-mitogen-activated protein kinase pathway resulting in cytokine release (tumor necrosis factor-alpha, interleukin-6) in control vs. sham animals. rhAT-treatment significantly attenuated these inflammatory changes leading to a myocardial contractility and myocardial oxygen consumption comparable to sham animals. In control animals, systemic fluid accumulation progressively increased over time resulting in a cumulative positive fluid balance of about 4,000 ml at the end of the study period. Contrarily, in rhAT-treated animals there was only an initial fluid accumulation until 24 h that was reversed back to the level of sham animals during the second day. Conclusions: Based on these findings, the supplementation of rhAT may represent a valuable therapeutic approach for cardiovascular dysfunction and inflammation after burn and smoke inhalation injury.<br

Phenolic, polysaccharidic and lipidic fractions of mushrooms from northeast Portugal: chemical compounds with antioxidant properties

Mushrooms do not constitute a significant portion of the human diet, but their consumption continues to increase due to their functional benefits and presence of bioactive compounds. Some of those compounds can be found in the phenolic, polysaccharidic and lipidic fractions of edible and inedible species. Herein, those fractions of five wild mushrooms (Coprinopsis atramentaria, Lactarius bertillonii, Lactarius vellereus, Rhodotus palmatus and Xerocomus chrysenteron) from Northeast Portugal were studied for their chemical composition and antioxidant properties. Protocatechuic, p-hydroxybenzoic, p-coumaric and cinnamic acids were found in the phenolic fraction, ramnose, xylose, fucose, arabinose, fructose, glucose, manose, mannitol, sucrose, maltose and trehalose were quantified in polysaccharidic fraction, linoleic and stearic (only in Lactarius sp.) acids, and β- and γ-tocopherols were the main compounds in the lipidic fraction. C. atramentaria and X. chrysenteron phenolic fractions gave the highest free radical scavenging activity, reducing properties and lipid peroxidation inhibition in brain homogenates, which is in agreement with its highest content in total phenolics. Furthermore, among the polysaccharidic fractions C. atramentaria also gave the highest antioxidant activity, which is accordingly with its highest total polysaccharides content and sugars obtained after hydrolysis.The authors are grateful to Fundação para a Ciência e a Tecnologia (FCT, Portugal) and COMPETE/QREN/EU (research project PTDC/AGR-ALI/110062/2009) for financial support. L. Barros (BPD/4609/2008) and S.A. Heleno (BD/70304/2010) also thank FCT, POPH-QREN and FSE. The GIP-USAL is financially supported by the Spanish Ministerio de Ciencia e Innovación through the Consolider-Ingenio 2010 Programme (FUN-C-FOOD, CSD2007-00063), and Junta de Castilla y León (Grupo de Investigación de Excelencia, GR133)