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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Intra-abdominal infection is the second most common cause of sepsis, and the mortality rate from abdominal sepsis remains high. High molecular weight (HMW) hyaluronic acid (HA) has been studied in sterile injury models as an anti-inflammatory and anti-permeability agent. This study evaluated the therapeutic effects of intraperitoneal HMW HA administration in mice with peritonitis-induced sepsis. ⋯ At 6 h after CLP, HA significantly decreased bacterial burden in the peritoneal lavage fluid. HMW HA administration significantly increased E coli bacterial phagocytosis by RAW264.7 cells in part through increased phosphorylation of ezrin/radixin/moesin, a known downstream target of CD44 (a HA receptor); ezrin inhibition abolished the enhanced phagocytosis by RAW264.7 cells induced by HA. Intraperitoneal administration of HMW HA had therapeutic effects against CLP-induced sepsis in terms of suppressing inflammation and increasing antimicrobial activity.
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Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock. ⋯ These results show a beneficial curative role of UT antagonism on cytokine response (especially IL-3), cardiac dysfunction, and survival during endotoxic shock in mice, highlighting a potential new therapeutic target for septic patients.
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Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by Coronavirus Disease 2019 (COVID-19) and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments. ⋯ Specifically, focus is given on SARS-CoV-2 immunopathogenesis in the context of experimental therapies and preclinical evidence and their applicability in supporting efficacious clinical trial planning. The review discusses the existing challenges of SARS-CoV-2 diagnostics and the potential application of translational technology for epidemiological predictions, patient monitoring, and treatment decision-making in COVID-19. Furthermore, solutions for enhancing international strategies in translational research, cooperative networks, and regulatory partnerships are contemplated.
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The world is currently embroiled in a pandemic of coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of COVID-19 disease ranges from asymptomatic to fatal acute respiratory distress syndrome. In few patients, the disease undergoes phenotypic differentiation between 7 and 14 days of acute illness, either resulting in full recovery or symptom escalation. ⋯ Elevated IL-6 and hypoxia together predisposes patients to pulmonary hypertension, and the presence of asymptomatic hypoxia in COVID-19 further compounds this problem. Due to the similar downstream mediators, we discuss the potential synergistic effects and systemic ramifications of SARS-CoV-2 and influenza virus during co-infection, a phenomenon we have termed "COVI-Flu." Additionally, the differences between CRS and cytokine storm are highlighted. Finally, novel management approaches, clinical trials, and therapeutic strategies toward both SARS-CoV-2 and COVI-Flu infection are discussed, highlighting host response optimization and systemic inflammation reduction.
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Trauma and hemorrhagic shock trigger mobilization of hematopoietic progenitor cells (HPC) from bone marrow to peripheral blood. Hepatocyte growth factor (HGF), tyrosine-protein kinase Met (c-Met), matrix metallopeptidase 9 (MMP-9), and corticosterone regulate this mobilization process. We hypothesized that beta-blockade with propranolol and sympathetic outflow inhibition with clonidine following trauma and chronic stress would decrease hematopoietic progenitor cell mobilization. ⋯ Severe injury was associated with increased bone marrow HGF, c-Met, and MMP-9, circulating corticosterone, HPC mobilization, and persistent anemia. Attenuating the neuroendocrine response to injury and stress with propranolol and clonidine reduced MMP-9 expression, corticosterone levels, HPC mobilization, and the degree of anemia.