The aim of this study was to monitor the development of coagulation abnormalities in patients with severe sepsis using thromboelastometry and to assess whether increased endotoxin activity was associated with a change in coagulation. Data collected on ICU admission, day 2, 3, and 4 were analysed in 61 patients. Thromboelastometry made it possible to identify patients with a normal (group 1), hypercoagulable (group 2), or hypocoagulable (group 3) pattern. The best accuracy of thromboelastometry parameters as potential indices of coagulation abnormalities was yielded by the clot formation time and maximum clot firmness. The mortality rate was low in group 1(16%) and the presence of abnormalities, indicating either a hyper or hypocoagulation pattern, was associated with significantly higher mortality (42 and 39% respectively; P = 0.05). In group 1, baseline endotoxin activity was low [0.22 endotoxin activity units (EAU), 0.15-0.43] and did not change significantly during the observation period. In group 2, baseline endotoxin activity was elevated (0.52 EAU (0.39-0.62)) and remained high on day 2, 3, and 4. In group 3, baseline endotoxin activity was elevated (0.56 EAU (0.28-0.80)) and similarly to group 2, remained high on day 2, 3, and 4. The presence of coagulation disorders indicates a high-risk subpopulation of critically ill patients as reflected in significantly higher mortality rates and increased endotoxin activity.
To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU).A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay.One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46–0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17–0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16–29] and 19 [16–25]; Sequential Organ Failure Assessment [SOFA] = 10 [7–13] and 11 [8–12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P < 0.001). There was a strong correlation between EA and serum PCT (P < 0.001, R = 0.5). The presence of endotoxemia on admission to the ICU was associated with an increased mortality rate: 52% in the group of patients with endotoxemia and 25% in the group without endotoxemia. EA in survivors was 0.39 EAU (0.26–0.57) and 0.53 EAU (0.4–0.61) in nonsurvivors (P = 0.004). The median PCT level in survivors was 6.7 ng/mL (2.3–28.0), compared with 16.7 ng/mL (5.3–31.0) in nonsurvivors (P = 0.04).This observational study revealed that endotoxemia in patients with septic shock on admission to the ICU was frequently found and was associated with an elevated PCT level and a high mortality rate. Endotoxemia was a common occurrence in patients with septic shock, regardless of the infecting microorganism.
Ageing is accompanied by the inevitable changes in the function of the immune system. It provides increased susceptibility to chronic infections that have a negative impact on the quality of life of older people. Therefore, rejuvenating the aged immunity has become an important research and therapeutic goal. Yolkin, a polypeptide complex isolated from hen egg yolks, possesses immunoregulatory and neuroprotective activity. Considering that macrophages play a key role in pathogen recognition and antigen presentation, we evaluated the impact of yolkin on the phenotype and function of mouse bone marrow-derived macrophages of the BMDM cell line. We determined yolkin bioavailability and the surface co-expression of CD80/CD86 using flow cytometry and IL-6, IL-10, TGF-β and iNOS mRNA expression via real-time PCR. Additionally, the impact of yolkin on the regulation of cytokine expression by MAPK and PI3K/Akt kinases was determined. The stimulation of cells with yolkin induced significant changes in cell morphology and an increase in CD80/CD86 expression. Using pharmaceutical inhibitors of ERK, JNK and PI3K/Akt, we have shown that yolkin is able to activate these kinases to control cytokine mRNA expression. Our results suggest that yolkin is a good regulator of macrophage activity, priming mainly the M1 phenotype. Therefore, it is believed that yolkin possesses significant therapeutic potential and represents a promising possibility for the development of novel immunomodulatory medicine.
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