ACTIVE GENERAL SURGERY RESEARCH STUDIES: ABSTRACTS
PI: Endean, Eric
SPONSOR: Blue Grass Community Foundation
GRANT NUMBER:
TITLE: Jane Keeble Resident Education Fund 2012-13
ABSTRACT: Surgical resident education, which may include educational materials and equipment, travel expenses for surgical meetings, board exams and licensing, and seed money, for surgical residents with financial need.
PI: Roth, John
CO-PI: Bower, Curtis
GRANT NUMBER:
TITLE: Foundation for Surgical Fellowship 2012-2013
ABSTRACT: Dr. Roth will mentor Dr. Curtis Bower on various research projects.
PI: Saito, Hiroshi
SPONSOR: National Institute on Aging
GRANT NUMBER: R01 AG039732
TITLE: The Role of Adipose Tissue in Age-dependent Sensitivity to Critical Illiness
ABSTRACT: Aging is characterized by an altered stress response that underlies a compromised resistance to disease or injury. Activation of inflammatory and coagulant pathways is a frequent consequence of severe critical illnesses and results in the progression of systemic inflammatory response syndrome (SIRS). Recent evidence suggests that adipose tissue-derived signaling proteins, including cytokines, coagulation factors and hormones, may play an important role in the inflammatory response. Our long-term goals are to identify the mechanisms by which adipose tissue contributes to age-dependent severity of SIRS and to develop therapeutic strategies for decreasing vulnerability to critical illnesses in the aged. For these studies we will use two widely accepted mouse models of SIRS — acute endotoxemia induced by injection with bacterial endotoxin lipopolysaccharide and an intra-abdominal sepsis model induced by cecal ligation and puncture. The objective of this project is to identify and evaluate the expression of adipose-derived inflammatory and coagulant factors that differ by aging upon inflammatory stress. Our central hypothesis is that expression patterns of inflammatory/coagulant factors in the adipose tissue during SIRS are significantly altered by aging and that this alteration contributes to age-dependent severity of critical illnesses. To achieve the above goals, we will pursue the following three specific aims: (1) To define the role of adipose tissue in age-related alterations of coagulation during critical illness; (2) To understand the mechanisms of age-related inflammatory cytokine production in the adipose tissue during critical illness; (3) To evaluate methods of body fat loss as potential therapies and preventative measures for reducing severity of critical illness in the aged. These studies will provide significant insight into the association of the previously neglected adipose organ in aging and critical illness.
PI: Saito, Hiroshi
SPONSOR: National Institute on Aging
GRANT NUMBER: R01 AG025908
TITLE: Vulnerability to Sepsis in Old Age
ABSTRACT: Sepsis is an infection-initiated manifestation of the systemic inflammatory response syndrome that often progresses to septic shock, multiple organ failure with high risks of death. Sepsis is a particularly serious problem in the geriatric population, as the elderly patients with sepsis suffer much higher morbidity and mortality than younger patients. In fact, sepsis is a major cause of death in elderly patients at intensive care units in the US. Although this problem is increasingly recognized, the underlying mechanism(s) responsible for this age-associated vulnerability remain largely unknown. The long-term goal of our research is to determine the mechanisms responsible for the increased septic vulnerability in the aged, and to use this information to develop new treatment strategies for sepsis. The age-associated vulnerability to sepsis is also seen in animal models. We have shown that aged mice suffer significantly higher mortality than young mice in two commonly used models for sepsis: endotoxemia induced by bacterial lipopolysaccharide injection and an intra-abdominal sepsis induced by cecal ligation and puncture. We have also found that the elevated mortality in aged mice is associated with altered inflammatory and coagulation responses and increased oxidative damages. Our central hypothesis is that loss of homeostasis in old age leads to excessive inflammation, oxidative damage, and coagulation, contributing to the age-associated vulnerability to sepsis. Our objective in this project is to define the age-associated alterations in pathophysiology and gene expression in the mouse model of sepsis, and to develop strategies to improve the survival of the old mice with sepsis. To achieve these goals, we pursue the following three specific aims: (1) To determine the effects of aging on the pathophysiology of sepsis, (2) To identify the age-associated alterations in gene expression that affect mortality in sepsis, and (3) To test likely strategies for their ability to decrease age-associated mortality in sepsis. The information obtained from this project should provide the basis for new therapeutic strategies to substantially decrease the mortality in elderly patients with sepsis.
