Medicine and Health Sciences Commons^™

A Holistic Investigation Of Acidosis In Breast Cancer, Bryce Ordway

USF Tampa Graduate Theses and Dissertations

In the early 20th century, Nobel laureate Otto Warburg made the observation that cells of a carcinoma had considerably higher glycolytic metabolism and considerably lower oxidative metabolism compared to cells of a normal tissue. He postulated that within this observation was the key to deciphering the differences between malignant and normal tissue. It is now well established that tumors of the breast are unequivocally acidic, caused by an abnormal amount of aerobic glycolysis, colloquially known as the Warburg effect. Over the last decades, our group, led by Dr. Robert J. Gillies, has set out to characterize the causes and consequences …

Role Of Bmi1 In Acute Lung Injury, María Helena Hernández-Cuervo

USF Tampa Graduate Theses and Dissertations

Acute Lung Injury (ALI) is a set of signs and symptoms that lead to acute hypoxemic respiratory failure characterized by bilateral pulmonary infiltrates not attributed to cardiogenic origin. It is caused by a massive innate immune response, with the migration of white blood cells (neutrophils and macrophages principally) and a cytokine storm, followed by alterations in mitochondrial function, increase in reactive oxygen species production, and oxidative stress that in turn induces more mitochondrial damage. Several studies have shown that mitochondrial alterations are key events in the mechanism of ALI and reducing mitochondrial dysfunction could be a possible target in the …

Moving In Fluid: Exploring How Fishes Manipulate Water To Swim Efficiently, Nils B. Tack

USF Tampa Graduate Theses and Dissertations

Moving through a dense fluid such as water presents some unique challenges to minimizing energy use and maximizing performance (i.e., speed). Due to animal-fluid interactions during swimming (drag and thrust production) fish have evolved a variety of morphological structures and locomotor mechanisms. For instance, fish rely on body bending and/or fins to interact with the surrounding water such that energy can be transferred to generate thrust. Typically, this synergy promotes morphologies and behaviors aimed at enhancing propulsive efficiency and/or minimizing metabolic activity to lessen the cost of transport (COT). This work focuses on quantifying the energetic and hydromechanical benefits of …

Targeting Cancer-Anorexia Cachexia Syndrome And Septic Inflammatory-Based Atrophy With R/S 1,3 Butanediol Acetoacetate Diester, Andrew P. Koutnik

USF Tampa Graduate Theses and Dissertations

Cancer anorexia cachexia syndrome (CACS) is a distinct atrophy disease negatively influencing multiple aspects of clinical care and patient quality of life. Although it directly causes 20% of all cancer-related deaths, there are currently no model systems that encompass the entire multifaceted syndrome, nor are there any effective therapeutic treatments. Here, we show that the VM-M3 mouse model of systemic metastasis demonstrates a novel, immunocompetent, logistically feasible, repeatable phenotype with progressive tumor growth, spontaneous metastatic spread, and the full multifaceted CACS with expected sex dimorphisms across tissue wasting. We also demonstrate that the ubiquitin proteasomal degradation pathway was significantly upregulated …

Functional Significance Of Endothelial Sigma-1 Receptors In Vascular Reactivity And Barrier Function, Zeinab Y. Motawe

USF Tampa Graduate Theses and Dissertations

The sigma-1 receptor (σ1) is a single 25 kD polypeptide that acts as a chaperone protein residing primarily in the endoplasmic reticulum Its interaction with mitochondria at the mitochondria-associated ER membrane domain is well-documented. Following activation, σ1 binds to the inositol trisphosphate receptor (Hayashi & Su), and modulates intracellular calcium homeostasis. Also, the activated σ1 modulates plasma membrane receptors and ion channel functions, and may regulate cellular excitability. Further, σ1 affects trafficking of lipids and proteins essential for neurotransmission, cell growth and motility. Activation of σ1 provides neuroprotection and cardio-protection in various models. Examples of neuroprotection include but not limited …

Evaluation Of Novel Hemocompatible Surface Coatings For Extracorporeal Life Support: A Biocompatible Alternative To Systemic Anticoagulation, Teryn Rose Roberts

USF Tampa Graduate Theses and Dissertations

Extracorporeal life support (ECLS) is a class of technologies used to support or replace the function of failing organs. During ECLS, blood is withdrawn from systemic circulation and circulated through an artificial organ or “treatment membrane” that performs the function of the failing organ, prior to return to systemic circulation. While ECLS provides life-saving therapy to wide patient populations from pre-term infants to combat-wounded soldiers, this therapy is limited due to secondary thrombotic and bleeding complications that result from: 1) exposure of blood to the foreign surfaces in the device circuit and 2) administration of anticoagulant drugs to prevent clot …

Hypercapnic Hyperoxia Increases Free Radical Production And Cellular Excitability In Rat Caudal Solitary Complex Brain Slice Neurons, Geoffrey Edward Ciarlone

USF Tampa Graduate Theses and Dissertations

The caudal solitary complex (cSC) is a cardiorespiratory integrative center in the dorsal medulla oblongata that plays a vital role in the central CO₂-chemoreceptive network. Neurons in this area respond to hypercapnic acidosis (HA) by a depolarization of the membrane potential and increase in firing rate, however a definitive mechanism for this response remains unknown. Likewise, CO₂-chemoreceptive neurons in the cSC respond to hyperoxia in a similar fashion, but via a free radical mediated mechanism. It remains unknown if the response to increased pO₂ is merely an increase in redox signaling, or if it’s the …

Sialylation And Cardiomyocyte Complex N -Glycosylation Protect Against Dilated Cardiomyopathy And Heart Failure, Wei Deng

USF Tampa Graduate Theses and Dissertations

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure, often associated with arrhythmias and sudden cardiac death if not controlled. Metabolic and/or environmental factors, such as alcohol abuse, obesity, diabetes and Chagas disease, alter glycoprotein glycosylation, can lead to DCM. Inherited genetic disease, such as the human congenital disorders of glycosylation (CDG), causes multi-system manifestations including DCM. Non-congenital changes in glycosylation are also occurred in humans with and in animal models of DCM and heart failure. However, mechanisms responsible for glyco-dependent DCM are not understood. Here we sought to investigate the impact of sialylation and N-glycosylation …

Modulation Of Whole Cell Currents In Human Neuroblastoma Cells Via The Hormone Aldosterone: An In Vitro Study, Harish Kumar Chittam

USF Tampa Graduate Theses and Dissertations

Ion channels play a critical role in maintaining homeostasis by moving various ions in and out of cells. The Na⁺-K⁺-2Cl^- or NKCC1 ion channel is involved in the regulation of Na⁺, K⁺, and Cl^- across cell membranes, and plays a key role in many forms of cellular physiology. In the cochlea, NKCC1 is involved in endolymph production and maintenance of the endocochlear potential. Our hypothesis is that blocking NKCC1 channels should directly impact auditory sensitivity causing hearing loss. Our lab has also shown that the hormone aldosterone (ALD) can upregulate …

Minocycline Treatment And The Necessity To Develop A Novel Outcome Measure For Children With Angelman Syndrome, Joseph Christopher Grieco

USF Tampa Graduate Theses and Dissertations

Angelman syndrome (AS) is a rare genetic disorder affecting 1/10,000 to 1/20,000 births. This disorder arises through the genetic disruption of the maternal UBE3A allele, which when coupled with epigenetic silencing of the paternal allele UBE3A allele, gives rise to an absence of UBE3A protein in the central nervous system. Clinical manifestations of the syndrome vary in severity and include poor motor function, deficits in language and severe intellectual impairments. Previous research in the Angelman syndrome mouse model revealed abnormalities in dendritic spine density and morphology of hippocampal pyramidal cells. As seen in humans with AS, mice show abnormal behavioral …

Assessment Of The Impact Of Attention Deficit Hyperactivity Disorder On Type 1 Diabetes, Kellee Miller

USF Tampa Graduate Theses and Dissertations

Individual day-to-day management and effective control of type 1 diabetes (T1D) is ultimately driven by decisions made by the individual. Individuals with attention deficit hyperactivity disorder (ADHD) have a higher tendency to be inattentive, impulsive, and hyperactive. Attention deficits and impulsivity among adolescents and adults with T1D could result in poor diabetes management through infrequent self-monitoring of blood glucose and inadequate insulin dosing – key components of achieving optimal glycemic control.

This study included 7,380 adolescents and young adults, ages 13-25 years, participating in the T1D Exchange clinic registry (median age 17.4 years, duration 7.7 yrs, 50% female, 81% white). …

Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky

USF Tampa Graduate Theses and Dissertations

Stroke is the fifth leading cause of death in the United States and a major cause of long-term disability in industrialized countries. The core region of an ischemic stroke dies within minutes due to activation of necrotic pathways. Outside of this core region is the penumbral zone, where some perfusion is maintained via collateral arteries. Delayed cell death occurs in this area due to the triggering of apoptotic mechanisms, which expands the ischemic injury over time. The cellular and molecular events that produce the expansion of the ischemic core continue to be poorly understood. The increases in the amyloid precursor …

Systematic Review Of Core Muscle Electromyographic Activity During Physical Fitness Exercises, Jason Martuscello

USF Tampa Graduate Theses and Dissertations

Activating the core muscles through exercise training programs is believed to be important for athletic performance. Considerable attention has been credited to the lumbar multifidus, transverse abdominis, and quadratus lumborum in designing exercise training programs. Numerous core exercise claims and recommendations abound in the fitness and physical therapy communities touting a superior core challenge for these muscles. The plethora of core activation literature with conflicting outcomes has convoluted the process of choosing exercises for an optimal core training approach. Although an abundance of research studies have quantified the muscle activity, collectively, a consensus on the type of exercise that elicits …

The Effects Of Oxygen On The Electrophysiology Of Co2/H+-Chemosensitive And -Insensitive Neurons Of The Solitary Complex Of The Rat, Michael Patrick Matott

USF Tampa Graduate Theses and Dissertations

This study tested the hypothesis that decreasing the control O₂ level from 95% to 40% (5% CO₂ + 55% N₂) maintains viability in caudal solitary complex (cSC) neurons in transverse slices (~300-400ꝳ) prepared from neonatal rat (P2-22) maintained at 32-34°C. The underlying rationale is to reduce exposure to redox and nitrosative stimuli generated during several hours of exposure to 95% O₂ that produces a tissue O₂ tension throughout the slice which is in excess of 203 kPa (2.0 atmospheres absolute,ATA) oxygen. Whole cell recordings of cSC neurons maintained in 40% O₂ exhibited spontaneous …

Aberrant Sialylation Alters Cardiac Electrical Signaling, Andrew Ednie

USF Tampa Graduate Theses and Dissertations

In the heart, electrical signaling is responsible for its rhythmicity and is necessary to initiate muscle contraction. The net electrical activity in a cardiac myocyte during a contraction cycle is observed as the action potential (AP), which describes a change in membrane potential as a function of time. In ventricular cardiac myocytes, voltage-gated sodium channels (Nav) and voltage-gated potassium channels (Kv) play antagonistic roles in shaping the AP with the former initiating membrane depolarization and the latter repolarizing it. Functional changes in the primary cardiac Nav isoform, Nav 1.5, or any one of the many Kv isoforms expressed in the …

Store-Operated Calcium Channels In The Function Of Intracardiac Neurons, Timetria Bonds

USF Tampa Graduate Theses and Dissertations

Proper autonomic regulation of mammalian cardiac function is dependent upon very complex and precise communication among the intracardiac ganglia and individual neurons within the ganglia. An array of neuromodulators is found within the ganglia that direct neuronal activity by modulating the movement of calcium. The current study determines that opioidergic agonists, which have been found to contribute to severe cardiac disease states and intracellular calcium mobilization, are also responsible for changes in the function of the intracardiac neuron via their effects on store-operated calcium channels (SOCs).

Previous studies suggest that phosphorylation plays a role in SOC regulation. Using Fura-2 calcium …

Secreted Factors From Human Umbilical Cord Blood Cells Protect Oligodendrocytes From Ischemic Insult, Derrick Rowe

USF Tampa Graduate Theses and Dissertations

Oligodendrocytes (OL)s are the dominant cell type in the white matter and are integral for synaptic transmission essential for proper neuronal communication between brain areas. Previous studies have shown that intravenous administration of the mononuclear fraction of human umbilical cord blood (HUCB) cells in rat models of stroke reduced white matter injury, gray matter injury and behavioral deficits. Yet the mechanisms used by HUCB cells remain unknown in ischemic injury. These studies will investigate both in vitro and in vivo approaches to elucidate this mechanism in OLs. When mature primary OLs were coincubated with HUCB cells, HUCB cells secreted soluble …