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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Clinical Trial
Splenic Doppler resistive index for early detection of occult hemorrhagic shock after polytrauma in adult patients.
The objective of this study was to evaluate whether direct assessment of splenic circulation by splenic Doppler resistive index (Doppler RI) is a clinically useful noninvasive method for an early detection of occult hemorrhagic shock after polytrauma in adult patients. Splenic Doppler RI was measured in 49 hemodynamically stable adult patients admitted to the emergency department because of polytrauma. Renal Doppler RI was also determined in 20 patients. ⋯ Patients who developed hemorrhagic shock had significantly higher splenic and renal Doppler RI, higher Injury Severity Score, and lower standard base excess at admission. By multivariate logistic regression, splenic Doppler RI resulted to be a predictor of hemorrhagic shock development within the first 24 h from admission. Splenic Doppler RI may represent a clinically useful noninvasive method for early detection of occult hemorrhagic shock and persistent occult hypoperfusion after polytrauma in adult patients.
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Clinical Trial
Factors influencing compliance with early resuscitation bundle in the management of severe sepsis and septic shock.
The Surviving Sepsis Campaign guidelines recommend implementing a 6-h resuscitation bundle, which has been associated with reduced mortality of patients presenting with severe sepsis or septic shock. However, this resuscitation bundle has not yet become a widely implemented treatment protocol. It is still unclear what factors are associated with the rate of compliance with the resuscitation bundle. ⋯ Factors related with lower compliance were cryptic shock (adjusted OR, 0.26; 95% CI, 0.13-0.52) and higher serum lactate levels (adjusted OR, 0.90; 95% CI, 0.82-0.98). Furthermore, we found several potential factors that influence compliance with the sepsis resuscitation bundle. To improve the compliance with the resuscitation bundle, interventions focusing on those factors will be needed.
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Reactive nitrogen species such as peroxynitrite play a significant role in burn and smoke inhalation injury. The bronchial circulation increases more than 10-fold in response to this combination injury. We hypothesized that direct delivery of low-dose WW-85, a peroxynitrite decomposition catalyst, into the bronchial artery would attenuate burn- and smoke inhalation-induced acute lung injury. ⋯ All these alterations were significantly attenuated in the WW-85 group. We demonstrated that a low dosage of WW-85 directly administered into the bronchial artery attenuated pulmonary dysfunction to the same extent as higher systemically administered doses in previous experiments. Our data strongly suggest that local airway production of peroxynitrite contributes to pulmonary dysfunction following smoke inhalation and burn injury.
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Idiopathic pulmonary fibrosis is a progressive, life-threatening, interstitial lung disease with no effective therapy. In this study, we evaluated the effects of fluorofenidone (FD), a novel pyridone agent, on a murine model of bleomycin-induced pulmonary inflammation and fibrosis. Institute for Cancer Research mice were intravenously injected with BLM or saline for 14 consecutive days. ⋯ Inversely, FD restored caveolin 1 protein and mRNA expression, which was significantly downregulated in BLM-induced lung fibrosis. Fluorofenidone also inhibited phosphorylation of extracellular signal-regulated kinase, P38, and c-Jun N-terminal kinase. These findings collectively suggest that FD is an effective agent with antifibrotic and anti-inflammatory properties, and the mechanisms of its antifibrotic effect include regulating caveolin 1 expression and blocking mitogen-activated protein kinase signaling pathways.
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Although prostaglandins (PGs) were reported to exert proinflammatory and anti-inflammatory effects in macrophages, their action mechanisms remain unclear. The effects of PGs including PGJ2 (J2), Δ-PGJ2 (Δ), 15-deoxy-Δ PGJ2 (15d), PGE2 (E2), and PGF2α (F2α) on lipopolysaccharide (LPS)-, lipoteichoic acid (LTA)-, and peptidoglycan (PGN)-induced inducible nitric oxide (NO) synthase (iNOS)/NO production by RAW264.7 macrophages were investigated. First, we found that induction of cyclooxygenase 2 (COX-2) protein occurred at a time earlier than that of heme oxygenase 1 (HO-1) protein, and the addition of the COX-2 inhibitor NS398 reduced HO-1 protein expression in LPS-, LTA-, and PGN-treated RAW264.7 macrophages. ⋯ Knockdown of HO-1 protein expression by HO-1 small interfering RNA blocked Δ and 15d inhibition of LPS- and LTA-induced events. Moreover, the compound, cyclopentenone (CP), which mimics the CP moiety of 15d, and its analog cyclohexenone were used, and cyclohexenone showed more potent induction of the HO-1 protein with effective inhibition of LPS-, LTA-, and PGN-induced iNOS/NO production than CP in macrophages. Reactive oxygen species-dependent HO-1 protein expression by PGs, which inhibited LPS-, LTA-, and PGN-induced iNOS/NO production, was identified in macrophages.