Intensive care medicine experimental
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Intensive Care Med Exp · Dec 2014
'Chronomics' in ICU: circadian aspects of immune response and therapeutic perspectives in the critically ill.
Complex interrelations exist between the master central clock, located in the suprachiasmatic nuclei of the hypothalamus, and several peripheral clocks, such as those found in different immune cells of the body. Moreover, external factors that are called 'timekeepers', such as light/dark and sleep/wake cycles, interact with internal clocks by synchronizing their different oscillation phases. Chronobiology is the science that studies biologic rhythms exhibiting recurrent cyclic behavior. ⋯ The aims of this article are to describe circadian physiology during acute stress and to discuss the effects of ICU milieu upon circadian rhythms, in order to emphasize the value of considering circadian-immune disturbance as a potential tool for personalized treatment. Thus, besides neoplastic processes, critical illness could be linked to what has been referred as 'chronomics': timing and rhythm. In addition, different therapeutic perspectives will be presented in association with environmental approaches that could restore circadian connection and hasten physical recovery.
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Intensive Care Med Exp · Dec 2014
Macro- and micronutrient disposition in an ex vivo model of extracorporeal membrane oxygenation.
Extracorporeal membrane oxygenation (ECMO) circuits have been shown to sequester circulating blood compounds such as drugs based on their physicochemical properties. This study aimed to describe the disposition of macro- and micronutrients in simulated ECMO circuits. ⋯ Significant alterations in macro- and micronutrient concentrations were observed in this single-dose ex vivo circuit study. Most significantly, there is potential for circuit loss of essential amino acid isoleucine and lipid soluble vitamins (A and E) in the ECMO circuit, and the mechanisms for this need further exploration. While the reductions in glucose concentrations and an increase in other macro- and micronutrient concentrations probably reflect cellular metabolism and breakdown, the decrement in arginine and glutamine concentrations may be attributed to their enzymatic conversion to ornithine and glutamate, respectively. While the results are generally reassuring from a macronutrient perspective, prospective studies in clinical subjects are indicated to further evaluate the influence of ECMO circuit on micronutrient concentrations and clinical outcomes.
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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.