Digital Commons Network^™

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

The Role And Regulation Of Inhibitor Of Kappa B Kinase In The Impaired Monocyte Response., Norman James Galbraith

Electronic Theses and Dissertations

Trauma, major surgery and systemic infection can lead to a subsequent immunosuppressed state which can predispose patients to nosocomial infection and death. Approximately a sixth of patients will have impaired monocyte function, as determined by decreased HLA-DR expression or decreased TNF-α production in response to ex-vivo lipopolysaccharide (LPS) stimulation. This project aimed to develop an in-vitro model of impaired monocyte function using isolated monocytes from healthy volunteers, to study the effect of monocyte impairment on IκK signaling, and determine the role of IκK in the impaired monocyte response. These studies have provided the following results:

1. Monocytes treated with low dose …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Effect Of Genipin On Cisplatin- Induced Nephrotoxicity, Eglal Orner Mahgoub

Theses

Cisplatin (CSP) is a potent and widely used chemotherapeutic agent. However, clinical efficacy of CSP is compromised due to the elicitation of nephrotoxicity and ototoxicity. In this study, I have investigated the nephroprotective effects of a phytochemical – genipin (GP) isolated from gardenia flower (Gardenia jasminoides), on a murine model of cisplatin-induced nephropathy. CSP-induced renal tissue injury was characterized by elevated levels of serum blood urea nitrogen (BUN), creatinine (Cr) and cystatin-C. In addition, levels of kidney injury molecule-1 (KIM-1) were increased in the renal tissues of CSP administered animals. CSP also induced renal oxidative stress, evidenced by increased NADPH …

The Effect Of Mechanical Vibration On Human Pdl Cell Differentiation And Response To Inflammation, Megan Desroches

Master's Theses (2009 -)

Low magnitude mechanical vibration is a therapeutic adjunct being investigated to alter bone remodeling and inflammation in areas such as osteoporosis, bone fracture healing, and muscle soreness after exercise. In orthodontics a device named AcceleDent has been marketed that claims to increase the rate of tooth movement and decrease pain. However evidence for these claims is lacking. In this study we looked at two potential cellular mechanisms for these claims: periodontal ligament (PDL) cell differentiation and inflammation under an orthodontic model of strain (IL-1β). Increased PDL cell differentiation into osteogenic cells could be an avenue of increasing orthodontic tooth movement. …

Sleep Duration Patterns From Adolescence To Young Adulthood And Their Impact On Asthma And Inflammation, Chighaf Bakour

USF Tampa Graduate Theses and Dissertations

This dissertation includes three studies that examined the impact of inadequate sleep duration in adolescents and young adults on asthma and systemic inflammation. We used data from the Florida Youth Risk Behavior Survey (YRBS), years 2009-2013, and from the National Longitudinal Study of Adolescent to Adult Health (Add health), which was conducted between 1994 and 2008.

The first study used data from 16,738 high school students participating in the Florida YRBS. We examined the cross-sectional association between sleep duration and asthma, and the interactive effects of sleep duration and BMI. We found that short and long sleep durations were associated …

Legacy Mining Metal Exposures Contribute To Circulating Oxidized Low Density Lipoprotein And Serum Inflammatory Potential In A Native Community, Molly Harmon

Biomedical Sciences ETDs

Numerous abandoned uranium mines (AUM) within the Navajo Nation contribute uranium (U), arsenic (As) and other metals to the soil, air and groundwater that continue to pose potential health risks to Navajo residents. The prevalence of inflammatory-related cardiovascular disease (CVD) and type 2 diabetes (T2D) has increased among the Navajo community in recent decades. Environmental exposure to metal contaminants may alter the circulation in ways that are associated with the inflammation-driven process of atherosclerotic plaque formation. Thus, we hypothesize that exposures to AUM metal contaminants are associated with pro-atherogenic changes in the circulation as evidenced by increased low-density lipoprotein (LDL) …

Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim

Dissertations & Theses (Open Access)

Preeclampsia (PE) is a severe, acute disease of pregnancy affecting approximately 8% of pregnant women after week 20 of gestation. PE is characterized by hypertension and renal damage reflected by proteinuria and has significant morbidity to both mother and fetus. Maternal symptoms range from headaches, nausea, edema, to visual changes, but once maternal symptoms present, damage to the fetus has begun. Mothers who progress untreated through the disease can also experience a condition called eclampsia characterized by seizure, coma, and, ultimately, death. PE-affected newborns experience features similar to prematurity—abnormal lung and renal development, intrauterine growth retardation (IUGR), and, possibly, fetal …

Abin1 In The Pathogenesis Of Glomerulonephritis And The Novel Polocyte-Neutrophil Proinflammatory Axis., Erik Anderson Korte

Electronic Theses and Dissertations

Glomerulonephritis (GN) is the most common cause of end-stage renal disease worldwide and is characterized by deposition of immune complex, inflammation, proteinuria and podocyte damage. Immunosuppressive therapy is effective in less than 50% of patients, indicating that immunological activity is not the only relevant cause of kidney injury. While methods have been described for neutrophil-mediated immune activation, specific glomerular mechanisms for recruitment of neutrophils and development of GN have not been determined. Here I present a pathogenic mechanism for the development of GN involving a novel podocyte-neutrophil axis and reveal the importance of glomerular NF-κB inhibition by the ubiquitin binding …

Role Of Microrna-21 In Atherogenesis., Rihab Hamed-Berair

Electronic Theses and Dissertations

MicroRNA-21 (miR-21) is an evolutionarily conserved microRNA, abundant in most cardiovascular tissues. It has been implicated in the pathogenesis of several cardiovascular diseases including restenosis, myocardial infarction, and heart failure. However, little is known about the contribution of miR-21 in atherosclerosis. My data show that expression of miR-21 is increased by >1.5-fold in murine atherosclerotic lesions and by 1.5-2.0-fold in the macrophages of Western diet (WD)-fed LDLR-KO mice (for 12-20 weeks). In vitro, LDL, oxidized LDL, acetylated LDL and LPS induced miR-21 by 2-4-fold and down-regulated its target protein, PDCD4, in bone marrow-derived macrophages. Basally, macrophages isolated from miR-21-KO …

The Relationship Of Chlamydia Antigen, Ad-Like Pathology, And Inflammation In The Brains Of Intranasally Infected Balb/C Mice, Brittany L. Kane

PCOM Biomedical Studies Student Scholarship

Alzheimer's' Disease (AD) is a progressive neurodegenerative disease that affects millions of elderly individuals in the western world. There are two forms of AD, sporadic late-onset AD and Familial AD. The neuropathy seen in both cases of AD is the same; neurofibrillary tangles (NFTs) that are composed of modified tau protein, and neuritic senile plaques (NSPs) composed of deposited beta amyloid peptide. The objective of this study is to continue to investigate the role of infection as a possible risk factor for sporadic AD. Previous mouse models using Chlamydia pneumoniae demonstrated that intranasal inoculation with this organism induced AD-like pathology …

The Effects Of Super-Fruits Including Montmorency Tart Cherries And Pomegranate On The Human Body: A Literature Review, Keeley D. Forrester

Senior Honors Theses and Projects

This literature review explores several published articles that report results related to health benefits of super-fruits including Montmorency tart cherries and pomegranate. Research suggests that Montmorency tart cherry supplementation may have the ability to relieve pain by decreasing inflammation, prevent gout flare ups by reducing uric acid levels in the bloodstream, relieve insomnia with natural exogenous melatonin, and lessen symptoms of muscle damage from physical exertion by decreasing oxidative stress. Studies have also shown that pomegranate supplementation may have the ability to help prevent obesity by helping to decrease body weight and fat production and improving insulin sensitivity as well …

Ppap2b Expression Limits Lesion Formation In Murine Models Of Atherosclerosis, Paul A. Mueller

Theses and Dissertations--Physiology

Coronary artery disease (CAD) is the leading cause of death in both men and women worldwide and is defined as a narrowing of the coronary arteries due to accumulation of atherosclerotic plaques. Genome-wide association studies have identified risk loci within the gene PPAP2B that confers increased risk of developing CAD. Evidence suggests these aforementioned SNPs are regulating PPAP2B expression in a cis-manner through the interruption of transcription factor binding sites. PPAP2B encodes the lipid phosphate phosphatase 3 enzyme that plays a key role in degrading bioactive lysophosphatidic acid (LPA). LPA has a plethora of effects on vascular tissue and is …

The Role Of Enteric Glia In Opioid-Induced Constipation, Sukhada Bhave

Theses and Dissertations

Morphine is one of the most widely used drugs for the treatment of pain but its clinical efficacy is limited by adverse effects including persistent constipation and colonic inflammation. Morphine-induced colonic inflammation is facilitated by microbial dysbiosis and bacterial translocation. In this study, we demonstrate that secondary inflammation and persistent constipation are modulated by enteric glia. In chronic morphine treated mice (75 mg morphine pellet/5 days), ATP-induced currents were significantly enhanced in enteric glia isolated from the mouse colon myenteric plexus. Chronic morphine resulted in significant disruption of the colonic epithelium and increased Il-1β in the myenteric plexus. The increase …

Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel

Theses and Dissertations

Traumatic brain injury (TBI) leads to short-term and long-term consequences that can cause many different life-long disorders. Studies of TBI have generally focused on the acute stage; however, it is now becoming important to investigate chronic responses following TBI as clinical reports of dementia and cognitive impairments have been linked to a history of TBI. Recent data have established that cognitive function is associated with hippocampal neurogenesis. Chronic injury induced changes in the brain may affect this endogenous process. Chronic responses following TBI include cell death pathways and inflammatory responses that are persistent in the brain for months to years …

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

The Role Of Mammalian Tribbles Homolog 3 (Trb3) In Macrophage Biology; Evidence For Reciprocal Regulation Of Macrophage Function In Foam Cell Formation, Dennis Steverson

All ETDs from UAB

Atherosclerosis is disease characterized by dysregulated lipid metabolism and chronic inflammation. Macrophages are critical to the progression of the disease and are involved in the pathophysiology at all stages of the disease. In the early stages, macrophages are responsible for fatty streak formation by becoming foam cells through lipid uptake. In the later stages, macrophages contribute to the degradation of the fibrous cap and are largely responsible for chronic inflammation in atherosclerotic plaques. Tribbles homolog 3 (TRB3) is a pseudokinase that inhibits Akt activation by blocking its phosphorylation site. TRB3 is expressed on numerous cell types in the body (pancreatic …

Examining Hiv-Associated Symptom Burden And Microbial Translocation In The Veterans Aging Cohort Study: A Secondary Data Analysis, Natalie Lynn Wilson

All ETDs from UAB

The pathophysiological effects of HIV infection, including inflammation, contribute to symptom burden and poor clinical outcomes. Within the gut associated lymph tissue, immune activation leads to dysfunction of the gastrointestinal epithelial barrier and subsequent movement of microbial products from the gut into the blood. The translocation of microbial products from the gut into the blood circulation has been identified as a key contributor to HIV disease progression and chronic inflammation. Chronic inflammation has been associated with various symptoms including symptoms commonly reported in HIV disease. However, it is unknown if these symptoms are associated with inflammation related to microbial translocation. …

The Effect Of Arsenic On Type 2 Diabetes And Inflammation, Kayla Penta

Theses and Dissertations

Arsenic, a ubiquitous environmental contaminant, has been shown to cause a number of health effects. At high concentrations the inorganic form is a well-known toxin, but at lower concentrations the effects range from various cancers, to cardiovascular disease and type 2 diabetes. At higher concentrations of arsenic (500- 1000μg/L) there have been epidemiological studies conducted demonstrating an increased risk in the development of type 2 diabetes with this exposure. At lower levels of arsenic exposure (<500 μg/L) the epidemiological results are inconclusive. Arsenic is also an immunotoxicant, meaning that it will cause changes in the immune response. The changes in the immune response will vary depending on a number of variables, including amount of arsenic exposure, forms of exposure and route of exposure. We wanted to determine if arsenic could modulate the immune system, and if this change could lead to an increase in susceptibility to type 2 diabetes development. We chose to examine this in C57BL/6 and db/+ mice – two non-susceptible strains. After 8 weeks (4 weeks old to 12 weeks old) of low dose inorganic arsenic exposure (50 μg/kg or 500 μg/kg) we evaluated changes in body composition, glucose tolerance and immune response. We saw that there were differences based on sex, genotype and treatment group present after the 8-week treatment period in body composition, while there were minimal changes in glucose tolerance. Finally, the immune response showed great variability depending on sex, genotype and treatment group. This project has demonstrated that while we are trying to compare differences in in vivo and epidemiological studies to find a link between arsenic and type 2 diabetes, there may be deeper levels of complications based on individual variability to arsenic exposure.

A Role For Transforming Growth Factor-Beta In Urinary Bladder Dysfunction With Cyclophosphamide-Induced Cystitis, Eric James Gonzalez

Graduate College Dissertations and Theses

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain disorder characterized by at least six weeks of lower urinary tract symptoms and unpleasant sensations (pain, pressure and discomfort) thought to be related to the urinary bladder and not meeting exclusion criteria. While the etiology is not known, BPS/IC may involve a "vicious circle" of uroepithelial dysfunction, inflammation and peripheral and central sensitization. We propose that the urinary bladder inflammatory insult partly mediates voiding dysfunction and visceral neurogenic pain characteristic of BPS/IC. Several studies from our laboratory have already demonstrated the role(s) of cytokines and their downstream targets in the …