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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Inflammatory responses can induce microvascular and endothelial dysfunction, which is associated with the development of sepsis. This study is aimed at examining the concentrations of plasma tissue factor (TF), von Willebrand factor (vWF), and tumor necrosis factor-α (TNF-α) in patients with sepsis and at determining how septic plasma (SP) regulates TF and vWF expression and p38 mitogen activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB) pathways in human endothelial cells. The concentrations of plasma TF, vWF, and TNF-α in 22 septic patients and eight healthy controls (HCs) were examined by enzyme-linked immunosorbent assay, and their potential association with disease severity was analyzed. ⋯ Furthermore, treatment with SP, but not NP, induced TF and vWF production in HUVECs in a dose- and time-dependent manner, which was associated with sequential activation of the p38 MAPK and NF-κB pathways. Septic plasma induced HUVEC apoptosis, which was inhibited by activating the NF-κB pathway. The sepsis-related inflammatory factors promoted endothelial cell activation, dysfunction, and apoptosis through activation of the p38 MAPK pathway that was regulated by NF-κB signaling.
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The renin-angiotensin (Ang) system is involved in maintaining cardiovascular function by regulating blood pressure and electrolyte homeostasis. More recently, alternative pathways within the renin-angiotensin system have been described, such as the ACE-2/Ang-(1-7)/Mas axis, with opposite effects to the ones of the ACE/Ang-II/AT1 axis. Correspondingly, our previous work reported that Ang-(1-7) via its receptor Mas inhibits the mRNA expression of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α increased by lipopolysaccharide (LPS) in mouse peritoneal macrophages. ⋯ Mas mice were less resistant to LPS-induced endotoxemia, their survival rate being 50% compared with 95% in wild-type mice. Telemetric analyses showed that Mas mice presented more pronounced LPS-induced hypothermia with a 3°C lower body temperature compared with wild-type mice. Altogether, our findings suggest that Ang-(1-7) and Mas inhibit LPS-induced cytokine production and hypothermia and thereby protect mice from the fatal consequences of endotoxemia.
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Decreased serum and increased hepatic iron uptake is the hallmark of acute-phase (AP) response. Iron uptake is controlled by iron transport proteins such as transferrin receptors (TfRs) and lipocalin 2 (LCN-2). The current study aimed to understand the regulation of iron uptake in primary culture hepatocytes in the presence/absence of AP mediators. ⋯ This increase in secretion was further enhanced by combination of IL-6 + iron. In conclusion, iron uptake is tightly controlled by already present iron concentration in the culture. This uptake can be further enhanced by AP cytokines, mainly by IL-6.
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There are very few data regarding the effects of norepinephrine uptitration on global and regional hemodynamics in cardiogenic shock. We studied 25 patients with shock secondary to myocardial infarction successfully treated with percutaneous coronary intervention. Before the inclusion, 16 of 25 patients presented a cardiac arrest in the presence of medical staff. ⋯ The StO2 recovery slope and delta StO2, respectively, increased from 3.0% ± 1.3%/s to 3.6% ± 1.3%/s and 10% ± 3% to 14% ± 4%, whereas StO2 did not change (83% ± 6% to 83% ± 7%). After H1, norepinephrine was decreased to basal values, and all variables returned to baseline. In conclusion, a short-term increase in MAP with norepinephrine in resuscitated cardiogenic shock complicated by postreperfusion disease is associated with better cardiac performance and improved microcirculatory variables.