Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as "genomic storm" in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous "danger" signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. online address: http://www.molmed.org
Summary — The effect of a complex of propolis constituents, cinnamic acid and L-lysine, on host defence mechanisms was investigated. After intraperitoneal (ip) application of cinnamic acid lysine complex (CN ·Ly) to mice at a dose of 3 mg/kg for 3 consecutive days prior to inoculation with Klebsiella pneumoniae, a protective effect was observed. The action of CN ·Ly was associated with its ability to provoke proliferation of thymic and splenic lymphocytes and to augment mitogen-induced proliferation, and the release of interleukin-1 (IL-1) and interleukin-2 (IL-2). In all experiments, a solution of L-lysine in a concentration equivalent to the lysine content in the complex was used for comparison. The results indicated that free lysine acted in a mitogen-like manner predominantly on T-lymphocytes. In the complex, lysine played the role of a carrier and exhibited a less pronounced effect.propolis / cinnamic acid / cytokine release / Klebsiella infection
Neuroeconomics has the potential to fundamentally change the way economics is done. This article identifies the ways in which this will occur, pitfalls of this approach, and areas where progress has already been made. The value of neuroeconomics studies for social policy lies in the quality, replicability, and relevance of the research produced. While most economists will not contribute to the neuroeconomics literature, we contend that most economists should be reading these studies.
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