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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Objective : The hemodynamic parameters used to accurately predict fluid responsiveness (FR) in spontaneously breathing patients (SB) require specific material and expertise. Measurements of the central venous pressure (CVP) are relatively simple and, importantly, are feasible in many critically ill patients. We analyzed the accuracy of respiration-related variations in CVP (vCVP) to predict FR in SB patients and examined the optimization of its measurement using a standardized, deep inspiratory maneuver. ⋯ A vCVP-st < -4.7 mm Hg predicted FR with 89.5% sensitivity, a specificity of 56.0%, and an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.58 to 0.86) ( P = 0.004). Conclusion : When a central venous catheter is present, elevated values for vCVP-st may be useful to identify spontaneously breathing patients unresponsive to volume expansion. Nevertheless, the necessity of performing a standardized, deep-inspiration maneuver may limit its clinical application.
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As a multifunctional protein, nucleolin can participate in a variety of cellular processes. Nucleolin also has multiple protective effects on heart disease. Previous studies have shown that nucleolin could not only resist oxidative stress damage and inflammatory damage, but also regulate autophagy to play a protective role in cardiac ischemia. ⋯ Finally, we also found that inhibition of autophagy can reduce mitochondrial biogenesis as well as increase apoptosis, which demonstrated the importance of autophagy. Therefore, we can speculate that nucleolin can protect LPS-induced myocardial injury by regulating autophagy, and this protective effect may be mediated by the interaction with PGC-1α, which can positively regulate the ULK1, an autophagy-related protein. Our study provides a new clue for the cardioprotective effect of nucleolin, and may provide new evidence for the treatment of LPS-induced myocardial injury through the regulation of autophagy.
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Background : Overall outcomes for trauma patients have improved over time. However, mortality for postinjury sepsis is unchanged. The use of relevant preclinical studies remains necessary to understand mechanistic changes after injury and sepsis at the cellular and molecular level. ⋯ PT/CS + PNA right and left lung injury scores were worse than PT + PNA ( P < 0.01). Conclusions : Sepsis, with postinjury pneumonia, induced significant systemic inflammation, organ dysfunction following polytrauma and chronic stress. Advanced animal models that replicate the critically ill human condition will help overcome the classic limitations of previous experimental models and enhance their translational value.
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Background: Hyperbilirubinemia is a common perioperative complication, which is associated with acute kidney injury. Bilirubin permeabilizes mitochondrial membranes leading to mitochondrial swelling and dysfunction. In this study, we aimed to determine the association between PINK1-PARKIN-mediated mitophagy and renal ischemia-reperfusion (IR) injury aggravated by hyperbilirubinemia. ⋯ In addition, hyperbilirubinemia increased mitophagosomes and autophagosomes and disrupted mitochondrial cristae in the IR kidney. Inhibition of PINK1 or autophagy reduced histological damages by alleviating apoptosis in renal IR injury, aggravated by hyperbilirubinemia. 3-MA or PINK1-shRNA-AAV9 treatment decreased the area of collagen and proteins related to fibrosis in renal IR injury, aggravated by hyperbilirubinemia. Conclusions: We have demonstrated that hyperbilirubinemia aggravated oxidative stress, apoptosis, mitochondrial damage, and fibrosis in renal IR injury by exacerbating PINK1-PARKIN-mediated mitophagy.
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Background: In sepsis, neutrophil extracellular traps (NETs) are an important interface between innate immunity and coagulation. The major structural component of neutrophil extracellular traps is nucleosomes (DNA-histone complexes). In vitro, DNA and histones exert procoagulant/cytotoxic effects whereas nucleosomes are not harmful. ⋯ In vivo, administration of histones to septic mice increased markers of inflammation (IL-6) and coagulation (thrombin-anti-thrombin), which was not observed in sham or septic mice administered DNA or nucleosomes. Conclusions: Our studies suggest that DNA masks the harmful effects of histones in vitro and in vivo. Although administration of histones contributed to the pathogenesis of sepsis, administration of nucleosomes or DNA was not harmful in healthy or septic mice.