Browsing by Author "Tomašević, Ratko (6603547250)"

Disorders of haemostasis are frequent in the diseases of the liver, and are in correlation with the degree of liver insufficiency. As a result, bleeding occurs, which, at long end, affects prognosis and life duration in these patients. The aim of this study is to evaluate mean values of some factors of coagulation (factor II, V, VII) and coagulation inhibitors (Anti-thrombin, AT-III) in 69 patients with decompensated alcoholic liver cirrhosis (Child C) and to determine the influence of coagulation disorders on the onset of bleeding and survival rate. We came to conclusion that there was no significant difference in level of coagulation factors and inhibitors between bleeding and non-bleeding patients, although the mean values of investigated parameters were 50% lower for coagulation factors and 60% for coagulation inhibitors in bleeders. The reason for this result we found in positive correlation in decreasing both factors and inhibitors, which agrees with hypothesis that in these cases haemostasis is regulated on new, lower level. Patients with final lethal outcome had significantly low level of AT-III what we considered as an important predictive factor. This results show complex interrelation between haemostasis factors, bleeding, quality of life and survival rate in patients with decompensated liver cirrhosis.

Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease. © Copyright © 2021 Tomić, Đokić, Stevanović, Ilić, Gruden-Movsesijan, Dinić, Radojević, Bekić, Mitrović, Tomašević, Mikić, Stojanović and Čolić.

Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease. © Copyright © 2021 Tomić, Đokić, Stevanović, Ilić, Gruden-Movsesijan, Dinić, Radojević, Bekić, Mitrović, Tomašević, Mikić, Stojanović and Čolić.