Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations

2021 ◽  
Vol 149 ◽  
pp. 111317
Author(s):  
Maria Cybularz ◽  
Sandy Wydra ◽  
Katharina Berndt ◽  
David M. Poitz ◽  
Peggy Barthel ◽  
...  
2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Cybularz ◽  
S Wydra ◽  
K Berndt ◽  
D Poitz ◽  
P Barthel ◽  
...  

Abstract Introduction Patients with frailty represent an increasing patient group in the intensive care medicine. A connection between frailty and inflammation has been suggested. An increased mortality rate in patients with high grade aortic valve stenosis (AS) and frailty, who underwent Transcatheter Aortic Valve Implantation (TAVI) has been observed. A systemic inflammatory reaction in the intensive care unit in the first days after TAVI is a positive predictive factor for an unfavorable outcome. Exact mechanisms are still not fully explained. Monocyte subpopulations are associated with both cardiovascular diseases and a high APACHE II score in critically ill patients. Purpose This study investigates the correlation between frailty and cellular and systemic inflammatory mechanisms and mortality after TAVI. Methods We examined 120 patients with symptomatic AS who underwent TAVI. Before the implantation, frailty status has been assessed. In all patients a flow cytometry analysis has been performed. Monocyte subpopulations were defined as follows: Mon1 (CD14++CD16–), Mon2 (CD14++CD16+) and Mon3 (CD14+CD16++). Expression of CD11b has been measured as a marker for monocyte activation. Pro-inflammatory cytokines such as interleukin IL-8, as well as CRP have been measured with Cytometric Bead Array or standard laboratory methods. Results After 3 months 15 of 120 patients died, primarily without relevant dysfunction of the implanted aortic valve. In 8 of 15 (53%) of the deceased patients and 20 of 100 (19%) of the surviving patients, frailty could be diagnozed before TAVI (p=0.003). Patients with frailty showed prior to TAVI signs of chronic inflammation: elevated CRP (3.7 vs. 5.9 mg/l, p=0.001) and elevated levels of considered as pro-inflammatory Mon2 monocytes (37 vs. 53, p=0.001). Expression of CD11b and IL-8 showed an increasing trend in patients with frailty. Frailty, the monocyte markers, IL-8 and CRP prior to TAVI correlated with increased early mortality after TAVI. Conclusion A considerable number of elderly patients with high grade aortic valve stenosis can be described as frail. This syndrome is associated with increased mortality and with signs of chronic systemic inflammation and pro-inflammatory monocytes. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Heart Center Dresden


Author(s):  
S.S. Poolsawat ◽  
C.A. Huerta ◽  
S.TY. Lae ◽  
G.A. Miranda

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.


2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.


2009 ◽  
Author(s):  
Virginia E. Ferent ◽  
Celestina Barbosa-Leiker ◽  
Bruce Wright

1985 ◽  
Vol 54 (02) ◽  
pp. 485-489 ◽  
Author(s):  
Yukiyoshi Hamaguchi ◽  
Masuichi Ohi ◽  
Yasuo Sakakura ◽  
Yasuro Miyoshi

SummaryTissue-type plasminogen activator (TPA) was purified from maxillary mucosa with chronic inflammation and compared with urokinase. Purification procedure consisted of the extraction from delipidated mucosa with 0.3M potassium acetate buffer (pH 4.2), 66% saturation of ammonium sulfate, zinc chelate-Sepharose, concanavalin A-Sepharose and Sephadex G-100 gel filtration chromatographies.The molecular weight of the TPA was approximately 58,000 ± 3,000. Its activity was enhanced in the presence of fibrin and was quenched by placental urokinase inhibitor, but not quenched by anti-urokinase antibody. The TPA made no precipitin line against anti-urokinase antibody, while urokinase did.All these findings indicate that the TPA in maxillary mucosa with chronic inflammation is immunologically dissimilar to urokinase and in its affinity for fibrin.


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