Diseases Commons^™

Effects Of Annexin A5 On Endothelial Inflammation Induced By Lipopolysaccharide-Activated Platelets And Extracellular Vesicles, Brent Jeffrey Tschirhart

Electronic Thesis and Dissertation Repository

Sepsis is a dysregulated immune response to infection and the leading cause of mortality globally, accounting for 11 million deaths in 2017. To date, no therapeutics are available to treat the underlying septic response. Previous research from our laboratory has shown that annexin A5 (Anx5) treatment increased survival by 40% in mice with endotoxemia, a model of sepsis. During sepsis, activated platelets release membrane fragments called extracellular vesicles (EVs) with externalization of phosphatidylserine to which annexin A5 binds with a high affinity. We hypothesized that annexin A5 will block the pro-inflammatory response induced by activated platelets and EVs in vascular …

Analysis Of Invariant Natural Killer T Cells In Intra-Abdominal Sepsis, Ram Venkatesh Anantha

Electronic Thesis and Dissertation Repository

Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of circulating iNKT cells in their peripheral blood, as compared to non-septic patients. We therefore investigated iNKT cells in mice with intra-abdominal sepsis (IAS). Our data show that iNKT cells are …

Effect Of Ascorbate On Coagulation And Fibrinolytic Factors In The Septic Microvasculature, Scott Swarbreck

Electronic Thesis and Dissertation Repository

Sepsis, a systemic inflammatory response to an infection, is a significant cause of morbidity and mortality worldwide. The microcirculation during sepsis fails, in part, due to microthrombosis and the resulting plugging of capillaries, precipitating organ failure. Intravenous injection of ascorbate has been shown to reduce capillary plugging, however the mechanism of this protective effect is unclear. We hypothesized that ascorbate-mediated destabilization of the microthrombi through promoting fibrinolysis could contribute to this protection.

We showed that streptokinase, a pro-fibrinolytic agent, reduced the capillary plugging to a similar degree as ascorbate. This similarity provided the impetus for studying the effect of ascorbate …

Involvement Of Interleukin-33/St2 In Myocardial Dysfunction In Murine Model Of Sepsis, Yoonmi Choe

Electronic Thesis and Dissertation Repository

The disruption of myocardial extracellular matrix (ECM) has been implicated in myocardial dysfunction during sepsis. However, the underlying mechanism(s) are not clear. Interleukin-33 (IL-33) is a cytokine which regulates collagen synthesis in various cardiac pathologies. The purpose of the present study is to test whether IL-33 contributes to sepsis-induced myocardial dysfunction through regulation of matrix metalloproteinase-9 (MMP-9). The in vivo, feces-induced peritonitis (FIP) in mice and in vitro lipopolysaccharide (LPS) treatments to isolated cardiomyocytes were used. In FIP mice, myocardial IL-33 and MMP-9 expression were increased and myocardial contractility was decreased. Myocardial function in FIP mice was improved when treated …