Medicine and Health Sciences Commons^™

Proteinase 3 Contributes To Endothelial Dysfunction In An Experimental Model Of Sepsis, Eric K. Patterson, Carolina Gillio-Meina, Claudio M. Martin, Douglas D. Fraser, Logan R. Van Nynatten, Marat Slessarev, Gediminas Cepinskas

Paediatrics Publications

In sepsis-induced inflammation, polymorphonuclear neutrophils (PMNs) contribute to vascular dysfunction. The serine proteases proteinase 3 (PR3) and human leukocyte elastase (HLE) are abundant in PMNs and are released upon degranulation. While HLE’s role in inflammation-induced endothelial dysfunction is well studied, PR3’s role is largely uninvestigated. We hypothesized that PR3, similarly to HLE, contributes to vascular barrier dysfunction in sepsis. Plasma PR3 and HLE concentrations and their leukocyte mRNA levels were measured by ELISA and qPCR, respectively, in sepsis patients and controls. Exogenous PR3 or HLE was applied to human umbilical vein endothelial cells (HUVECs) and HUVEC dysfunction was assessed by …

Impact Of Graded Passive Cycling On Hemodynamics, Cerebral Blood Flow, And Heart Function In Healthy Adults And Septic Icu Patients, Jennifer Chen

Electronic Thesis and Dissertation Repository

Sepsis is a life-threatening dysregulation of host response to an infectious insult, which often leads to multi-organ failure. Sepsis survivors suffer from post-intensive care syndrome in part due to their prolonged bed rest and lack of mobility. Although early mobilization has been championed as a mechanism to counter the adverse effects associated with ICU immobility, due to sedation and mechanical ventilation, active early mobilization is not often administered in septic patients due to worries of hemodynamic instability and potential for inducing adverse events. Passive exercise is a mobilization modality that circumvents the need for patients to be conscious and participatory …

Epilepsy Risk Among Survivors Of Intensive Care Unit Hospitalization For Sepsis, Tresah C. Antaya, Britney N. Allen, Lucie Richard, Salimah Z. Shariff, Gustavo Saposnik, Jorge Burneo

Neuroepidemiology Research Unit Project Summaries

Research Summary: Key Findings

• 407 (0.28%) patients developed epilepsy within 2 years of their ICU discharge, 103 (25.3%) of whom were exposed to sepsis.
• Sepsis survivors were significantly more likely to develop epilepsy, relative to non-septic ICU survivors.
• Among sepsis survivors, epilepsy risk increased with age and was higher among those with chronic kidney disease.

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Mitogen-Activated Protein Kinase Phosphatase-1 Inhibits Myocardial Tnf-Α Expression And Improves Cardiac Function During Endotoxemia, Ting Zhang, Xiangru Lu, Paul Arnold, Yin Liu, Reshma Baliga, Hong Huang, John Anthony Bauer, Yusen Liu, Qingping Feng

Paediatrics Publications

Aims: Myocardial tumour necrosis factor-α (TNF-α) expression induces cardiac dysfunction in endotoxemia. The aim of this study was to investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP1) pathway in myocardial TNF-α expression and cardiac function during endotoxemia. Methods and results: Lipopolysaccharide (LPS) increased MKP1 expression in the myocardium in vivo and in cultured neonatal cardiomyocytes in vitro. LPS-induced extracellular signal-regulated kinase (ERK) 1/2 and p38 phosphorylation in the myocardium was prolonged in MKP1 -/- mice. Myocardial TNF-α mRNA and protein levels were enhanced in MKP1 -/- compared with wild-type (WT) mice in endotoxemia, leading to a further decrease in …

Rac1 Activation Induces Tumour Necrosis Factor-Α Expression And Cardiac Dysfunction In Endotoxemia, Ting Zhang, Xiangru Lu, Frank Beier, Qingping Feng

Paediatrics Publications

Induction of tumour necrosis factor-α (TNF-α) expression leads to myocardial depression during sepsis. However, the underlying molecular mechanisms are not fully understood. The aim of this study was to investigate the role of Rac1 in TNF-α expression and cardiac dysfunction during endotoxemia and to determine the involvement of phosphoinositide-3 kinase (PI3K) in lipopolysaccharide (LPS)-induced Rac1 activation. Our results showed that LPS-induced Rac1 activation and TNF-α expression in cultured neonatal mouse cardiomyocytes. The response was inhibited in Rac1 deficient cardiomyocytes or by a dominant-negative Rac1 (Rac1N17). To determine whether PI3K regulates Rac1 activation, cardiomyocytes were treated with LY294002, a PI3K selective …