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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This study tested the hypothesis that CD44 is involved in the development of cardiac fibrosis via angiotensin II (Ang II) AT1 receptor-stimulated TNFα/NFκB/IκB signaling pathways. Study was conducted in C57BL/6 wild type and CD44 knockout mice subjected to Ang II infusion (1,000 ng/kg/min) using osmotic minipumps up to 4 weeks or with gastric gavage administration of the AT1 receptor blocker, telmisartan at a dose of 10 mg/kg/d. Results indicated that Ang II enhances expression of the AT1 receptor, TNFα, NFκB, and CD44 as well as downregulates IκB. ⋯ These results suggest that the AT1 receptor is involved in the development of cardiac fibrosis by stimulating TNFα/NFκB/IκB-triggered CD44 signaling pathways. Knockout of CD44 blocked Ang II-induced cell migration/proliferation and cardiac fibrosis. Therefore, selective inhibition of CD44 may be considered as a potential therapeutic target for attenuating Ang II-induced deleterious cardiovascular effects.
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During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis-cecal ligation and puncture (CLP). ⋯ AMIT treatment significantly decreased macrophage TNFα expression and blunted M1 polarization. Altogether, during polymicrobial sepsis, AMIT treatment suppressed macrophage TNFα expression and the M1 phenotype, mitigating an initial hypercoagulable state, and protecting septic mice from delayed hypocoagulability. We propose that AMIT treatment is a promising therapeutic approach in the treatment of sepsis-associated coagulopathy and prevention of acute thromboembolic events or delayed bleeding complications.
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Clinical Trial Observational Study
Association Between Muscle Wasting and Muscle Strength in Patients Who Developed Severe Sepsis And Septic Shock.
To evaluate the association between the rectus femoris cross-sectional area (RFCSA) and the muscular strength obtained at the bedside in patients forwarded to the intensive care unit (ICU) for severe sepsis and septic shock. ⋯ There was an association of RFCSA with clinical muscle strength tests. In addition, it has been shown that sepsis can lead to short-term muscle degradation, regardless of whether they are submitted to mechanical ventilation or not.
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Current management principles of hemorrhagic shock after trauma emphasize earlier transfusion therapy to prevent dilution of clotting factors and correct coagulopathy. London's Air Ambulance (LAA) was the first UK civilian prehospital service to routinely offer prehospital red blood cell (RBC) transfusion (phRTx). We investigated the effect of phRTx on mortality. ⋯ phRTx was associated with increased survival to hospital, but not overall survival. The "delay death" effect of phRTx carries an impetus to further develop inhospital strategies to improve survival in severely bleeding patients.