Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Sepsis, or systemic inflammatory response to infection, is a major childhood disease and a common cause of death in children. Despite its importance, a global perspective on the epidemiology and mortality of pediatric sepsis across the world is still lacking. ⋯ Educational efforts aiming to increase the awareness on sepsis by the general public and the adherence to the treatment guidelines by healthcare providers may result in significant improvements in sepsis survival. The global attention to pediatric sepsis, however, can only be achieved with the standardization of the definitions and the use of simple and sensitive diagnostic criteria that incorporate the differences in the necessities among different settings and the availability of local resources.
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The aim of the study was to determine if melanocortin-1 receptor (MC1R) single nucleotide polymorphisms (SNPs) are associated with complicated sepsis after trauma. ⋯ MC1RR163Q is associated with a lower risk of complicated sepsis after trauma. Therapeutic targeting of MC1R may be beneficial for trauma patients at risk for complicated sepsis.
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The hypermetabolic stress response after burn contributes to multi-organ failure, sepsis, morbidity, and mortality. The cytokine interleukin 6 (IL-6) has been hypothesized to mediate not only white adipose tissue (WAT) browning in burns, but also other hypermetabolic conditions. In addition to its inflammatory effects, IL-6 also acts as a metabolic mediator that affects metabolic tissues. ⋯ Conversely, transplanting irradiated WT mice with BM from IL-6 KO mice impaired burn induced browning with no significant expression of UCP1. Together, our findings implicate BM derived IL-6 as the source controlling browning of WAT post burn injury. Thus, targeting IL-6 is a promising target for hypermetabolism in burns.
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Delayed neutrophil apoptosis has been demonstrated in sepsis and may contribute to organ damage. It has recently been proposed that apolipoprotein L (ApoL) may be involved in programmed cell death, but the expression and functions of ApoLs in leukocytes (especially neutrophils) during sepsis and other inflammatory conditions are currently unknown. In this prospective observational study in a 36-bed university hospital medicosurgical intensive care unit (ICU), we included 78 adult ICU patients with (n = 41) or without (n = 37) sepsis and 47 healthy volunteers. ⋯ Apolipoprotein L mRNA was downregulated in whole blood leukocytes and neutrophils in ICU patients compared with in healthy volunteers, and this effect translated at the protein level as indicated by Western blot analysis of neutrophils. There was a negative correlation between ApoL expression in neutrophils and C-reactive protein levels and a positive correlation between the number of apoptotic neutrophils and mRNA levels of ApoL1 and ApoL2. The degree of neutrophil apoptosis in critically ill patients is therefore correlated with modified expression profiles of ApoLs.
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Muscle wasting (MW) in catabolic conditions (e.g., burn injury [BI]) is a major risk factor affecting prognosis. Activation of interleukin-1β (IL-1β)/nuclear factor-kappa B (NF-κB), interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), and/or forkhead box O transcriptional factor (FOXO)-mediated gene transcription pathways is the pivotal trigger of inflammatory response-induced protein catabolic processes in muscle. The α7 acetylcholine receptors (α7AChRs) are upregulated in macrophages and peripheral tissues including skeletal muscle during MW conditions. Stimulation of α7AChRs mitigates inflammatory responses. Hypothesis tested is that attenuation of inflammation by α7AChR stimulation with specific α7AChR agonist, GTS-21, will reverse BI-induced body mass and MW by modulating inflammatory and proteolytic signals. ⋯ GTS-21 stimulation of α7AChRs, by modulating multiple molecular signals related to inflammation and proteolysis, attenuates protein wasting, evidenced by maintenance of body weight and attenuation of distant muscle mass loss after BI. GTS-21 can be a novel, potent therapeutic option for reversal of BI-induced MW.