Digital Commons Network^™

Does Better A1c Control Worsen Osteoarthritis? An Electronic Health Record Cross-Sectional Study, Sarah C. Cattaneo

USF Tampa Graduate Theses and Dissertations

Obesity is a major risk factor for osteoarthritis (OA). There is evidence that diabetes also increases risk. Our hypothesis is that A1C is a predictor of OA severity. The aim is to investigate the association between A1C, BMI, and knee and hip OA severity. This is a cross-sectional study within the Veterans Health Administration (VHA) database containing 818 patients with diagnosed diabetes. Patients at one VHA facility with recorded diabetes in fiscal year 2020 were identified. A1C and BMI data was obtained from the electronic health record. Chart reviews were performed to collect data on imaging reports of weight-bearing joints …

Role Of Ceramide-1 Phosphate In Regulation Of Sphingolipid And Eicosanoid Metabolism In Lung Epithelial Cells, Brittany A. Dudley

USF Tampa Graduate Theses and Dissertations

Ceramide 1-Phosphate (C1P) is a sphingolipid metabolite which plays a large role in inflammation, cell survival and proliferation¹. C1P is known to have both pro- and anti-apoptotic roles in lung cancer cells, governed by ceramide kinase (CERK), upstream of precursor ceramide (Cer)². Previous work reveals C1P serves as the liaison between sphingolipid and eicosanoid synthesis, by decreasing the dissociation rate of group IVA cytosolic PLA₂ (cPLA_2α) from the Golgi membrane, C1P directly activates this phospholipase for downstream eicosanoid synthesis and subsequent inflammatory response³. CERK has been discovered to modulate eicosanoid synthesis, …

Mass Spectrometry Discovery-Based Proteomics To Examine Anti-Aging Effects Of The Nutraceutical Nt-020 In Rat Serum, Samantha M. Portis

USF Tampa Graduate Theses and Dissertations

Aging is a complex physiological process that leads to the deterioration of all cells and tissues throughout the body. Aging is a major risk factor for the onset of many degenerative diseases in both the central nervous system (CNS) and the periphery, but even nonpathological aging (“normal” aging) is associated with chronic inflammation, oxidative stress, and decreased stem cell proliferation and regenerative capacity. This decreased regenerative capacity in stem cell niches is thought to be a key component underlying the aging process and many disease states associated with aging.

While the exact biological mechanisms underlying impaired stem cell proliferation and …

Role Of Serum Amyloid P Component In The Pathogenesis Of Chronic Traumatic Encephalopathy, Brittany Urban

USF Tampa Graduate Theses and Dissertations

Serum amyloid P (SAP) component is a glycoprotein that is a major constituent of human serum. SAP has been recognized to stimulate amyloid fibrillogenesis. One way that SAP can be transported to the brain is by passing through the blood brain barrier (BBB). Traumatic brain injury (TBI) and repeated or severe non-penetrating head injury, can escalate the exposure of the brain to SAP, which in turn can contribute to neurodegeneration. TBI can lead to chronic traumatic encephalopathy (CTE) which is a neuropathological condition that has been found in people who have been exposed to repeated head injuries or impacts. In …

Neutrophil Extracellular Traps And Vascular Barrier Injury, Jamie E. Meegan

USF Tampa Graduate Theses and Dissertations

Sepsis is a life-threatening inflammatory condition with high morbidity and mortality rates. Though improvements to diagnosis and management of sepsis have been made, the complexity of the disease process and an incomplete understanding of its endpoint mechanisms have prevented major breakthroughs for early diagnosis and treatment. Representing a common endpoint in a number of inflammatory injuries including sepsis, endothelial barrier dysfunction causes fluid leakage and leukocyte infiltration that leads to tissue damage and multiple organ failure. Therefore, elucidating mechanisms of endothelial barrier regulation is needed to further develop targeted therapies in inflammatory disease.

Sepsis is characterized by a hyperinflammatory response …

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 …

Aspirin Triggered Resolution Phase Interaction Product D1: A Novel Treatment For Hyperoxic Acute Lung Injury, Ruan Rollin Cox, Jr.

USF Tampa Graduate Theses and Dissertations

Acute Lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are respiratory maladies that present immense clinical challenges. ALI affects 200,000 individuals annually and features a 40% mortality rate. ALI can be initiated by both pathogenic and sterile insults originating locally in the lungs or systemically. While immense research has been poured into this disease in an effort to find a therapeutic strategy, the heterogeneously diffuse nature of the disease has not yielded a cure for the disease. Death from this disease is strongly attributed to reduced gas exchange from a severely compromised alveolar-capillary barrier. The only …

Neuroinflammatory Alterations Via Cd-36 In Traumatic Brain Injury, Diana G. Hernandez-Ontiveros

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) has become an increasingly unmet clinical need due to intense military conflicts worldwide. Directly impacted brain cells suffer massive death, with neighboring cells succumbing to progressive neurodegeneration accompanied by inflammatory and other secondary cell death events. Subsequent neurodegenerative events may extend to normal areas beyond the core of injury, thereby exacerbating the central nervous system’s inflammatory response to TBI. Recently CD-36 (cluster of differentiation 36/fatty acid translocase (FAT), a class B scavenger receptor of modified low-density lipoproteins (mLDLs) in macrophages, has been implicated in lipid metabolism, atherosclerosis, oxidative stress, and tissue injury in cerebral ischemia, and …

The Interrelationship Of Brca1 185delag, Interleukin-1Β, And Ovarian Oncogenesis, Kamisha Woolery

USF Tampa Graduate Theses and Dissertations

While the etiology of ovarian cancer (OC) is not completely understood, evidence suggests that chronic inflammation may promote malignant transformation. However, familial history remains the strongest risk factor for developing OC and is associated with germline BRCA1 mutations, such as the 185delAG mutation. Normal human ovarian surface epithelial cells expressing the 185delAG mutant, BRAT, exhibit molecular and pathological changes that may contribute to OC oncogenesis. In the current study, I sought to determine whether BRAT could promote an inflammatory phenotype by investigating BRAT's impact on the expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Using a culture model system of normal …

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are …

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 …

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 …

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. …

The Role Of Hiv-1 Proteins In Alzheimer's Disease Pathology, Brian Nelson Giunta

USF Tampa Graduate Theses and Dissertations

Prevalence of HIV-associated cognitive impairment is rising, the worst form of which is HIV-associated dementia (HAD). The disease is fuiled by a chronic innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia. We first created an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. This activation, as measured by TNF-alpha and NO release, is synergistically attenuated through the alpha7nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA …

The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline

USF Tampa Graduate Theses and Dissertations

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C’ (

FAM5C) gene have been associated with myocardial infarction (MI), and one single-nucleotide polymorphism (SNP) has partially accounted for linkage in an acute coronary syndrome subset. The linkage peak on FAM5C corresponds directly with a quantitative trait locus for the inflammatory biomarker monocyte chemoattractant protein 1, as well as a linkage peak to metabolic syndrome (MetS). Metabolic syndrome increases the risk of developing CHD, and MI has been positively …

The Relationship Between Fam5c Snp (Rs10920501) Variability, Metabolic Syndrome, And Inflammation, In Women With Coronary Heart Disease, Jennifer L. Cline

USF Tampa Graduate Theses and Dissertations

The leading cause of death among women is coronary heart disease (CHD), a multifactorial disease with polygenic heritability estimated at 50%. Polymorphisms in the family with sequence similarity 5, member C' (FAM5C) gene have been associated with myocardial infarction (MI), and one single-nucleotide polymorphism (SNP) has partially accounted for linkage in an acute coronary syndrome subset. The linkage peak on FAM5C corresponds directly with a quantitative trait locus for the inflammatory biomarker monocyte chemoattractant protein 1, as well as a linkage peak to metabolic syndrome (MetS). Metabolic syndrome increases the risk of developing CHD, and MI has been …

Pegylation Of Niosomes, John A. Elliott

USF Tampa Graduate Theses and Dissertations

The research presented in this dissertation describes the creation and characterization of a novel antibody-vesicle conjugate modified with polyethylene glycol (PEG) that possesses enhanced binding to and uptake by inflammation-activated endothelial cells with improved storage stability and longer shelf-life and potential reduction in immunogenic potential compared to previous designs.

Targeted drug delivery provides an effective means of delivering therapeutic concentrations of a drug to the site or organ of action. The drug is delivered using a niosome, a vesicle with an aqueous core and a bilayer membrane composed of non-ionic surfactants and cholesterol. Antibodies that recognize specific cell antigens are …

Molecular Intervention In Mouse Models Of Amyotrophic Lateral Sclerosis And Alzheimer’S Disease – Neuropathology And Behavior, Steven Prescott Bennett

USF Tampa Graduate Theses and Dissertations

Neurodegeneration describes the progressive loss of structure and function of neurons, leading ultimately to cell and organism death. Although the initiating factors of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic Lateral Sclerosis may be different, they share common pathophysiologies. Proteinopathies, as these diseases are now termed, are characterized by atypical deposits of proteins, often due to misfolding. Associated with these deposits are dysfunctional mitochondria, oxidative stress, disrupted axonal transport, inflammation, and apoptotic cell death. If this occurs in motor neurons, as in ALS, ataxia precedes death with little or no change in cognition. On the other hand, if …

Immunomodulatory Effects Of Novel Therapies For Stroke, Aaron A. Hall

USF Tampa Graduate Theses and Dissertations

Each year, approximately 795,000 people suffer a new or recurrent stroke. About 610,000 of these are first attacks, and 185,000 are recurrent attacks (Carandang et al. 2006). Currently the only FDA approved treatment for ischemic stroke is recombinant tissue plasminogen activator (Alteplase) (Marler and Goldstein 2003). Unfortunately its use is restricted to a short, 4.5 hour, time window. Two promising therapies in the treatment of stroke at delayed timepoints are human umbilical cord blood cells (HUCBC) and the sigma receptor agonist DTG

The first series of experiments were conducted to characterize the effects of sigma receptors on various aspects of …

The Role Of Curcumin In Human Dendritic Cell Maturation And Function, Shawna A. Shirley

USF Tampa Graduate Theses and Dissertations

Curcumin is the yellow pigment found in the Indian spice curry. It has anti-inflammatory, ant-oxidant, anti-cancer, anti-viral, anti-bacterial and wound healing properties. It is widely used in industry for its flavor as a spice and as a coloring agent because of its brilliant yellow color. It is also used as a dye for textiles and as an additive to cosmetics. Dendritic cells (DCs) are the sentinels of the immune system and functions as the bridge between the innate and adaptive immune response. The effect of curcumin on DCs is poorly understood. A study shows curcumin prevents the immuno-stimulatory function of …

Immunomodulation As A Potential Therapeutic Approach For Alzheimer’S Disease, William Veljko Nikolic

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease (AD) is the most prevalent form of progressive dementia and is characterized by the accumulation of amyloid beta (Aß) peptide in the brain and in the cerebral vessels forming cerebral amyloid angiopathy (CAA). As previously reported, an active immunization strategy of mice with Aß_1-42 peptide results in decreased Th1 and increased Th2 cytokine responses as well as an effectively clearance of CNS Aß. This approach has also yielded favorable results for many patients, unfortunately, a small percentage of these study participants developed severe aseptic meningoencephalitis likely secondary to CNS invasion of activated T-cells. We have previously demonstrated …

The Role Of Extracellular Matrix And Matrix-Degrading Proteases In Neonatal Hypoxic-Ischemic Injury, Christopher C. Leonardo

USF Tampa Graduate Theses and Dissertations

Improvements in medical care over recent decades have increased the number of premature and low birth weight infants that survive hypoxic-ischemic (H-I) insults. Because there is a rising incidence in diseases associated with these events, it is critical to develop effective therapies to treat the various resulting neuropathies. Extracellular matrix constitutes the majority of brain parenchyma. Lecticans and matrix-degrading proteases including ADAMTSs (a disintegrin and metalloproteinase with thrombospondin repeats) and matrix metalloproteinases (MMPs) exert effects on cell viability and may be associated with either protective or destructive processes after H-I. Both ADAMTSs (Cross et al. 2006; Tian et al. 2007) …

Alternative Targets For The Treatment Of Stroke, Craig T. Ajmo Jr.

USF Tampa Graduate Theses and Dissertations

Stroke is cerebrovascular injury that has been reported to be the third leading cause of death and the first leading cause of disability in the world (W. H.O. 2007). Currently, there is only one FDA approved treatment for stroke which is recombinant tissue plasminogen activator. This treatment has a narrow therapeutic window of three hours after ischemic stroke and can adversely cause the production of oxygen free radicals and intracranial hemorrhage. These limitations result in only 2-3% of all stroke victims as being candidates for this therapy as many patients do not arrive at the hospital in time to receive …

Mechanisms Of Ss-Amyloid Clearance By Anti-Aß Antibody Therapy, Donna Marie Wilcock

USF Tampa Graduate Theses and Dissertations

Alzheimers disease (AD) is defined as a progressive neurodegenerative disorder that gradually destroys a persons memory and ability to learn. There are three pathological hallmarks of the disease which are necessary for diagnosis of AD, these are; extracellular amyloid plaques composed of [beta]-amyloid (A[beta]) protein, intracellular neurofibrillary tangles and neuronal loss. Amyloid plaques exist as both compact deposits which stain with Congo red and more numerous diffuse deposits. Active immunization against A[beta] 1-42 or passive immunization with monoclonal anti-A[beta] antibodies reduces amyloid deposition and improves cognition in APP transgenic mice.

Over several studies of active immunization in APP+PS1 transgenic mice …