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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The acute respiratory distress syndrome (ARDS) is a major public health problem and a leading source of morbidity in intensive care units. Lung tissue in patients with ARDS is characterized by inflammation, with exuberant neutrophil infiltration, activation, and degranulation that is thought to initiate tissue injury through the release of proteases and oxygen radicals. Treatment of ARDS is supportive primarily because the underlying pathophysiology is poorly understood. ⋯ Pharmacological inhibition of broad-spectrum PKC activity and, more importantly, of specific PKC isoforms (as well as deletion of PKCs in mice) exerts protective effects in various experimental models of lung injury. Furthermore, PKC isoforms have been implicated in inflammatory processes that may be involved in the pathophysiologic changes that result in ARDS, including activation of innate immune and endothelial cells, neutrophil trafficking to the lung, regulation of alveolar epithelial barrier functions, and control of neutrophil proinflammatory and prosurvival signaling. This review focuses on the mechanistic involvement of PKC isoforms in the pathogenesis of ARDS and highlights the potential of developing new therapeutic paradigms based on the selective inhibition (or activation) of specific PKC isoforms.
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Ferritin L (FTL) and ferritin H (FTH) subunits are responsible for intracellular iron storage. Serum ferritin levels are not only dependant on body iron stores. Aims of the present study are to demonstrate nature, source, and major regulatory mediators of serum ferritin in an animal model of acute-phase (AP) response. ⋯ However, an increase of hepatic FTL but not of FTH protein expression was observed in IL-6ko mice after TO injection. Our data demonstrate that FTL is the only rat serum ferritin whose release into circulation from the hepatocytes is increased by the effect of AP cytokines (e.g., IL-6). In contrast, FTH expression is intracellular in both under physiological and AP conditions.
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Early and aggressive treatment of circulatory failure is associated with increased survival, highlighting the need for monitoring methods capable of early detection. Vasoconstriction and decreased oxygenation of the splanchnic circulation are a sentinel response of the cardiovasculature during circulatory distress. Thus, we measured esophageal oxygenation as an index of decreased tissue oxygen delivery caused by three types of ischemic insult, occlusive decreases in mesenteric blood flow, and hemodynamic adaptations to systemic hypoxia and simulated hemorrhagic stress. ⋯ All modes of oximetry monitoring and arterial blood pressure were correlated with mesenteric artery flow during acute hemorrhage. Esophageal StO2 demonstrated a greater decrease from baseline levels as well as a more rapid return to baseline levels during reinfusion of the withdrawn blood. These experiments suggest that monitoring esophageal StO2 may be useful in the detection of decreased mesenteric oxygen delivery as may occur in conditions associated with hypoperfusion or hypoxia.
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Comparative Study
Noninvasive carbon dioxide monitoring in a porcine model of acute lung injury due to smoke inhalation and burns.
In critically ill intubated patients, assessment of adequacy of ventilation relies on measuring partial pressure of arterial carbon dioxide (PaCO2), which requires invasive arterial blood gas analysis. Alternative noninvasive technologies include transcutaneous CO2 (tPCO2) and end-tidal CO2 (EtCO2) monitoring. We evaluated accuracy of tPCO2 and EtCO2 monitoring in a porcine model of acute lung injury (ALI) due to smoke inhalation and burns. ⋯ During hemodynamic instability, EtCO2 did not correlate with PaCO2 (R = 0.03; P = 0.29). tPCO2 monitoring demonstrated strong correlation with PaCO2 during hemodynamic stability (R = 0.80, P < 0.0001), which deteriorated under hemodynamically unstable conditions (R = 0.39; P < 0.0001). Noninvasive carbon dioxide monitors are acceptable for monitoring trends in PaCO2 under conditions of hemodynamic and pulmonary stability. Under unstable conditions, reevaluation of patient status and increased caution in the interpretation of results are required.
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Circulating microRNAs (miRNAs) are an emerging biomarker for sepsis patients. The purpose of this study was to identify novel miRNAs in the sera of sepsis patients and determine their prognostic value. Ninety-four serum samples were collected from sepsis patients within 24 h of intensive care unit admission. ⋯ Conjoint analysis of the six miRNAs and severity scores (Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score) showed that the area under the receiver operating characteristic curve for the predictive value of the six miRNAs was 0.969 (95% confidence interval, 0.930-1.000). When the cutoff point was set at 0.714, the six miRNAs and severity score provided a sensitivity of 100% and a specificity of 82.6%. In conclusion, 41 novel miRNAs were detectable in the sera of sepsis patients, and six of them might be related to sepsis outcome.