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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N-Formyl-Met-Leu-Phe (fMLP), a mimic of N-formyl oligopeptides that are released from bacteria, is a potent leukocyte chemotactic factor. It induces intracellular calcium ([Ca]i) transient that is important for various neutrophil biological functions, e.g., adhesion, ROS, and cytokine productions. Toll-like receptors (TLRs), an essential part of host innate immunity, regulate neutrophil activities, but their role in [Ca]i signaling is less clear. ⋯ Surprisingly, deletion of TLR2 or MyD88 in neutrophils had no impact on the Pam3Cys4's effect, suggesting a TLR2-MyD88-independent mechanism. Finally, using the pan PKC activator and inhibitor, we demonstrated that PKC negatively regulated fMLP-induced [Ca]i transients and that inhibition of PKC did not prohibit Pam3Cys4's synergistic effect on the fMLP-induced calcium influx. In conclusion, the present study identified a novel synergistic effect of Pam3Cys4 on fMLP-induced [Ca]i transients, a process important for many neutrophil biological functions.
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Absence of fever is associated with higher mortality in septic patients, but the reason for this is unknown. Immune dysfunction may be a potential link between failure to mount a fever and poor outcomes. The purpose of this study was to evaluate monocyte function and clinical surrogates of immunity (i.e., mortality and acquisition of secondary infections) in febrile and afebrile septic patients. ⋯ Absence of fever is associated with suppressed HLA-DR expression over time, a finding suggestive of monocyte dysfunction in sepsis, as well as worse clinical outcomes.
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Secretome Conveys the Protective Effects of ASCs: Therapeutic Potential Following Hemorrhagic Shock?
We tested whether resuscitation supplemented with rat adipose-derived stem cells (ASCs) or secretome (conditioned media) of ASCs can ameliorate inflammation, cell/organ injury, and/or improve outcome after hemorrhagic traumatic shock (HTS). ⋯ Our data suggest that the ASC-secretome supplemented resuscitation following HTS, in the absence of the stem cells, exerts anti-inflammatory and liver protective effects. Given its ease of preparation, storage, availability, and application (in contrast to the stem cells) we believe that the cell-free secretome has a better therapeutic potential in the early phase of an acute hemorrhagic shock scenario.
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The tidal volume setting as well as colloid transfusion during the peri-operative period after intracranial aneurysm is controversial. A multicenter retrospective study was conducted to determine whether or not an increased tidal volume setting and colloid transfusion are associated with poor outcomes and postoperative pulmonary complications after intracranial aneurysm. ⋯ Decreased tidal volume with increased height, but not colloid transfusion, was independently associated with worse outcomes and postoperative pneumonia across a spectrum of risk profiles. These findings may help to improve practice decisions regarding tidal volume settings.
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Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. ⋯ These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.