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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Background: The kidney is the most common extrapulmonary organ injured in sepsis. The current study examines the ability of aerosolized nanochemically modified tetracycline 3 (nCMT-3), a pleiotropic anti-inflammatory agent, to attenuate acute kidney injury (AKI) caused by intratracheal LPS. Methods: C57BL/6 mice received aerosolized intratracheal nCMT-3 (1 mg/kg) or saline, followed by intratracheal LPS (2.5 mg/kg) to induce acute lung injury-induced AKI. ⋯ Lipopolysaccharide-treated mice demonstrated renal injury with increased levels of inflammatory cytokines (IL-1β, IL-6), active MMP-2 and MMP-9, proapoptotic proteins (cytochrome C, Bax/Bcl-2 ratio, cleaved caspase-3), apoptotic cells, inflammasome activation (NLRP3, caspase-1), and p38 signaling. Intratracheal nCMT-3 significantly attenuated all the measured markers of renal injury, inflammation, and apoptosis. Conclusions: Pretreatment with aerosolized nCMT-3 attenuates LPS-induced AKI by inhibiting renal NLRP3 inflammasome activation, renal inflammation, and apoptosis.
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Background : Systemic inflammation acts as a contributor to neurologic deficits after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Extracellular cold-inducible RNA-binding, protein (CIRP) has been demonstrated to be responsible in part for the inflammation through binding to toll-like receptor 4 (TLR4) after cerebral ischemia. The short peptide C23 derived from CIRP has a high affinity for TLR4, we hypothesize that C23 reduces systemic inflammation after CA/CPR by blocking the binding of CIRP to TLR4. ⋯ In addition, C23 treatment can reduce the apoptosis of hippocampus neurons ( P < 0.05). Finally, the rats in the C23 group have improved survival rate and neurological prognosis ( P < 0.05). Conclusions: These findings suggest that C23 can reduce systemic inflammation and it has the potential to be developed into a possible therapy for post-CA syndrome.
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Sepsis is a multisystem disease process, which constitutes a significant public health challenge and is associated with high morbidity and mortality. Among other systems, sepsis is known to affect the cardiovascular system, which may manifest as myocardial injury, arrhythmias, refractory shock, and/or septic cardiomyopathy. Septic cardiomyopathy is defined as the reversible systolic and/or diastolic dysfunction of one or both ventricles. ⋯ Given the importance of timely detection of septic cardiomyopathy and its bearing on prognosis of patients, the role of RV dysfunction has come into renewed focus. Hence, through this review, we sought to describe the pathophysiology of RV dysfunction in sepsis and what have we learnt so far about its multifactorial nature. We also elucidate the roles of different biomarkers for its detection and prognosis, along with appropriate management of such patient population.
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Objective: Sepsis is a complex disease characterized by an inflammatory response and tissue hypoxia. Hypoxia-inducible factor 1α (HIF-1α) expression level is regulated by hypoxia and inflammation. This study aimed to explore the correlation between HIF-1α expression level and sepsis by bioinformatics analysis and clinical investigation. ⋯ The results of the restricted cubic splines model indicated a U-shaped relationship between HIF-1α expression level and intensive care unit (ICU) mortality. Univariate and multivariate linear regression analyses indicated that septic patients with the elevated HIF-1α expression levels had shorter length of ICU stay versus those with the lower HIF-1α expression levels. Conclusion: Hypoxia-inducible factor 1α expression level can be used for diagnosing disease, assessing severity, and predicting length of ICU stay in septic patients.
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Background: The Society for Cardiovascular Angiography and Intervention (SCAI) Shock Classification can define shock severity. We evaluated the vasoactive-inotropic score (VIS) combined with the SCAI Shock Classification for mortality risk stratification. Methods: This was a single-center retrospective cohort analysis including Mayo Clinic cardiac intensive care unit patients from 2007 to 2015. ⋯ A gradient of in-hospital mortality was observed according to the VIS at 1 h and the increase in VIS from 1 to 24 h. Conclusions: Higher vasoactive drug requirements portend a higher risk of mortality, particularly a high VIS early after admission. The VIS provides incremental prognostic information beyond the SCAI Shock Classification, emphasizing the continuum of risk that exists across the spectrum of shock severity.