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 cornu ammonis 1 (CA1) region of the hippocampus is specifically vulnerable to global ischemia. We hypothesized that histopathological outcome in a ventricular fibrillation cardiac arrest (VFCA) rat model depends on the time point of the examination. ⋯ The amount and type of brain lesions present after global ischemia depend on the survival time. A consistent reduction in pyramidal cells in the CA1 region was present in all animals 14 days after VFCA, but in two-thirds of animals a repopulation of pyramidal cells seems to have taken place after 140 days.
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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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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.
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Sepsis is one of the most important causes of maternal mortality. In our previous work, we established a polymicrobial sepsis (cecal ligation and puncture [CLP]) model in murine pregnancy and found that pregnant mice had a greater susceptibility to septic shock. In this model, mortality seemed to be associated with the development of early hemodynamic dysfunction and although circulating cytokine levels were similar, "off target" lung inflammatory cell numbers were greater in pregnant mice. ⋯ Both Imipenem and L-257 treatment alone slightly improved mortality rates from 13% (NaCl) to 20% (Imipenem) and 33% (L-257), whereas the combination of Imipenem and L-257 significantly improved survival to 50%. Imipenem and L-257 together prevented cardiovascular collapse and improved both organ function and bacterial killing, but did not reduce lung inflammatory cell numbers and actually increased lung cytokine levels. These data suggest that conventional management in combination with selective inhibition of DDAH1 may have therapeutic potential in the management of sepsis in pregnancy.
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Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. ⋯ The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.