Medicine and Health Sciences Commons^™

Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf

Dissertations & Theses (Open Access)

Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 …

The Role Of Antioxidant Rich Berries In The Prevention Of Postmenopausal Bone Loss, Lydia Karimi Kaume

Graduate Theses and Dissertations

Postmenopausal osteoporosis is the most prevalent form of osteoporosis and results in fragility fractures. Smoking is one of the major risk factors for osteoporosis and is known to aggravate bone loss in postmenopausal women due to increased oxidative stress and inflammation. Diet-based interventions using berries have shown bone protective affects in animal studies partially due to antioxidant and anti-inflammatory properties of their phenolic compounds. The goal of this research was to determine the effects of antioxidant-rich fruits in the prevention of postmenopausal bone loss. Our first study examined the dose dependent effects of blackberries in preventing bone loss in an …

The Effects Of Phytosterols On Lipoprotein Particle Size, Laura J. Kunces

Master's Theses

Phytosterols (PS) have become a recent popular medication alternative for treatment of hypercholesterolemia and have proven effective. Whether PS decrease risk of cardiovascular disease through other mechanisms, such as lipoprotein particle size and inflammatory markers, remains unclear. PURPOSE: The primary aim of this study was to examine the effects of two forms of PS in milk on lipoprotein particle size, inflammatory markers and fat-soluble vitamins. METHODS: Twenty subjects (13 males, 7 females; age; 55±6.1 years, height; 169±10 cm, weight; 77.9±16.9 kg, BMI; 27.3) consumed 16oz of cow’s milk daily for 12 weeks. The three sequential four-week phases consisted of 2% …

Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin

Dissertations & Theses (Open Access)

Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.

P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated, thus …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …

An Examination Of Bacterial Communities In The Upper Respiratory Tracts Of Asthmatics And Non-Asthmatics, Kelly O'Brien

Senior Theses and Projects

The human body is colonized with commensal microbes that attach to the skin and mucosal membranes and function to protect the host as part of the innate immune response. These indigenous microbiota are able to prevent infections by blocking attachment sites and outcompeting invading pathogens for necessary nutrients. Disturbance of the host-microbe symbiotic balance may increase a host’s susceptibility to disease. In addition, proper colonization of the normal flora has been implicated in playing a vital role in shaping the immune response. It has been hypothesized that reduced exposure to infectious microorganisms early in life can disrupt the development of …

Statin-Mediated Attenuation Of Chemokine Expression In Peripheral Nerve Vascular Endothelial Cells, Kelly Ann Langert

Dissertations

Pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), play a pivotal role in the pathogenesis of Guillain-Barré Syndrome (GBS), a debilitating autoimmune disorder that affects the peripheral nervous system. By up-regulating endothelial expression of chemokines and cell adhesion molecules (CAMs), TNF-α facilitates the recruitment and trafficking of autoreactive leukocytes across the blood-nerve barrier and into peripheral nerves, an early pathological hallmark of GBS. Literature indicates that TNF-α, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) are locally increased in patients with GBS, correlating with disease severity. Similar findings have been demonstrated in an animal model of GBS, experimental autoimmune neuritis …

Evaluation Of The Role Of Oxidative Stress, Inflammation And Apoptosis In The Pulmonary And The Hepatic Toxicity Induced By Cerium Oxide Nanoparticles Following Intratracheal Instillation In Male Sprague-Dawley Rats, Siva Krishna Nalabotu

Theses, Dissertations and Capstones

The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data …

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …

Neuron To Microglia Communication; A Study Of Cx3cl1 Signaling Implications In Cognitive Function, Inflammation, And Neurodegeneration, Joshua M. Morganti

USF Tampa Graduate Theses and Dissertations

As a consequence of aging, the brain is subject to chronic neuroinflammatory conditions. The resident immune cells of the brain, microglia, act similarly to peripheral macrophages to protect the brain from insults, infection, and physical trauma. However, without proper regulation of their respective host defense mechanisms, these actions can become neurotoxic. In the healthy brain neurons have several signaling systems that directly interact with microglia in order to maintain a calming influence upon their actions, one of particular interest is the chemokine CX3CL1. This chemokine is found predominantly on neurons, while its cognate receptor CX3CR1 is found exclusively on microglia. …

Maternal Immune Dysregulation In The Pathogenesis Of Neurodevelopmental Disorders: Interleukin-6 As A Central Mechanism And Therapeutic Target Of Flavonoids, Ellisa Carla Parker-Athill

USF Tampa Graduate Theses and Dissertations

Activation of the maternal immune system and resultant maternal cytokine expression due to prenatal infection has been implicated as a significant contributor to the pathology of neuropsychiatric and neurodevelopmental disorders such as schizophrenia and Autism Spectrum Disorder (ASD). Increased maternal interleukin-6 (IL-6) expression, observed clinically and in animal models of prenatal infection, and resultant activation of key signaling pathways, has been shown to be a biological indicator of pathology, and a central component of the pathological mechanism. In animal models of prenatal infection and clinically in pregnancy disorders hallmarked by immunological irregularities and increased IL-6 expression, inhibition of IL-6 has …

Apolipoprotein E Mimetic Peptide Improves Hdl Functionality And Inhibits Atherosclerosis Progression In Mouse Models Of Atherosclerosis, Gaurav Nayyar

All ETDs from UAB

Despite major advances in diagnosis and treatment, coronary artery disease (CAD) is still the number one cause of morbidity and mortality in United States. An ideal treatment for lipid-mediated inflammatory disorders would not only reduce plasma cholesterol dramatically but also improve high density lipoproteins (HDL) function. Apolipoprotein E (apo E), a protein component of HDL and very low density lipoprotein (VLDL), is necessary for the receptor mediated hepatic uptake of apolipoprotein-B (apo B) containing remnant lipoproteins and also possesses strong anti-inflammatory properties. We hypothesized that a synthetic dual domain apo E mimetic peptide, Ac-hE18A-NH2 (a 28-residue peptide) containing receptor binding …