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
-
Serum chemotactic activity is important in regulating neutrophil migration. The ability of neutrophils to migrate to infectious site is crucial for host effective pathogen control, but unregulated neutrophil activation can also cause tissue damage. During bacterial sepsis, the complement alternative pathway (AP) is massively activated in blood and tissues and reportedly contributes to sepsis pathogenesis. ⋯ To delineate the contribution of these downstream effectors, we incubated AP-active sera (AP activated by zymosan/CVF) or sera from sham and septic mice with anti-C5a or mAb1379 (anti-Ba) neutralizing antibody. We found that anti-C5a, but not mAb1379, markedly attenuated the neutrophil chemotactic effect of the AP-activated sera and that of septic sera. Taking together, these data suggest that the complement AP activation during bacterial sepsis plays a pivotal role in promoting blood chemotactic activity through a C5a-dependent mechanism.
-
Fluid overload is associated with increased morbidity and mortality in critically ill patients. However, researches rarely study the precise start or end point of fluid removal and no protocol was developed to control the fluid removal process. We hypothesized that individualized fluid removal with ultrasound-guided protocol could improve the efficacy and safety of fluid removal in post-resuscitated critically ill patients. ⋯ The time of lung B-lines to reduce to zero was shorter and B-line at the end point was less (49.5 ± 36.6 h vs. 75.6 ± 58.8 h, 0[1] vs. 0[0], P < 0.05) in Ultrasound group. The length of intensive care unit stay in shock subgroup had a tendency to shorten (96.1 ± 61.5 h vs. 174.6 ± 132.0 h, P > 0.05) in Ultrasound group. We concluded that fluid removal with individualized ultrasound-guided protocol improves the efficacy and safety of dehydration in critically ill patients.
-
Autophagy plays an important role in cell survival, sequestering, and degrading a wide variety of substrates. Although an increase of autophagosomes in liver has been reported in sepsis patients as well as in septic mice, the influence of autophagy on liver injury, the interaction between autophagy, and other types of cell death in sepsis remain unclear. The aim of this study was to elucidate the contribution of liver autophagy to the pathophysiology of sepsis. ⋯ Serum aspartate transaminase levels (P = 0.005) and serum interleukin-6 levels (P = 0.020) were significantly increased in the KO mice compared with controls. Deficiency of autophagy in liver significantly decreased survival in the murine sepsis model (P = 0.025). In conclusion, blocking liver autophagy accelerates time to mortality in the murine sepsis model, suggesting that liver autophagy plays a protective role for organ failure through degradation of damaged mitochondria, as well as prevention of apoptosis.
-
Heat shock factor 1 (HSF1), an important transcriptional molecule in the heat shock process, can regulate the expression of a lot of inflammatory mediators in addition to heat shock proteins. This study evaluated the inhibitive function of HSF1 on the expression of suppressor of cytokine signaling 3 in cerulein-induced acute pancreatitis. ⋯ HSF1 can protect AR42J cells from cerulein-induced pancreatitis through inhibiting the expression of SOCS3.