Intensive care medicine experimental
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Intensive Care Med Exp · Dec 2014
Genetic and pharmacologic inhibition of Tpl2 kinase is protective in a mouse model of ventilator-induced lung injury.
Mechanical stress induced by injurious ventilation leads to pro-inflammatory cytokine production and lung injury. The extracellular-signal-regulated-kinase, ERK1/2, participates in the signaling pathways activated upon mechanical stress in the lungs to promote the inflammatory response. Tumor progression locus 2 (Tpl2) is a MAP3kinase that activates ERK1/2 upon cytokine or TLR signaling, to induce pro-inflammatory cytokine production. The role of Tpl2 in lung inflammation, and specifically in the one caused by mechanical stress has not been investigated. The aim of the study was to examine if genetic or pharmacologic inhibition of Tpl2 could ameliorate ventilator-induced lung injury. ⋯ Genetic and pharmacologic inhibition of Tpl2 is protective in a mouse model of ventilator-induced lung injury, ameliorating both high-permeability pulmonary edema and lung inflammation.
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Intensive Care Med Exp · Dec 2014
The receptor for advanced glycation end products in ventilator-induced lung injury.
Mechanical ventilation (MV) can cause ventilator-induced lung injury (VILI). The innate immune response mediates this iatrogenic inflammatory condition. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that can amplify immune and inflammatory responses. We hypothesized that RAGE signaling contributes to the pro-inflammatory state induced by MV. ⋯ RAGE was not a crucial contributor to the pro-inflammatory state induced by MV. However, the presence of sRAGE limited the production of pro-inflammatory mediators in our 2-hit model of LPS and high tidal volume MV.
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Intensive Care Med Exp · Dec 2014
Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine.
The design of clinical immunology studies in sepsis presents several fundamental challenges to improving the translational understanding of pathologic mechanisms. We undertook a systematic review of bed-to-benchside studies to test the hypothesis that variable clinical design methodologies used to investigate immunologic function in sepsis contribute to apparently conflicting laboratory data, and identify potential alternatives that overcome various obstacles to improve experimental design. ⋯ We found several important and common limitations in the clinical design of translational immunologic studies in human sepsis. Major elective surgery overcame many of these methodological limitations. The failure of adequate clinical design in mechanistic studies may contribute to the lack of translational therapeutic progress in intensive care medicine.
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Intensive Care Med Exp · Dec 2014
Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis).
Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in Burkholderia pseudomallei infection (melioidosis), an important cause of Gram-negative sepsis in Southeast Asia. ⋯ B. pseudomallei is a potent inducer of NETosis which was reflected by greatly increased levels of NET-related components in melioidosis patients. Although NETs exhibited antibacterial activity against B. pseudomallei, NET formation did not protect against bacterial dissemination and inflammation during B. pseudomallei-induced sepsis.
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Intensive Care Med Exp · Dec 2014
The effect of vitamin C on plasma volume in the early stage of sepsis in the rat.
Previous experimental studies have shown that vitamin C has several beneficial effects in sepsis and burns, such as decreased tissue oedema, improved endothelial barrier function and decreased transcapillary leakage of plasma markers. It has still not been investigated, though, if vitamin C has any impact specifically on plasma volume. The present study aims at testing the hypothesis that vitamin C decreases plasma volume loss in sepsis. ⋯ Vitamin C treatment did not decrease the loss of plasma volume in the septic rat. The diuretic effect of vitamin C was in accordance with previous studies.