Medicine and Health Sciences Commons^™

The Lived Experience Of Self-Intermittent Catheterisation In People With Spinal Cord Injury, Brendan J. Bakes

Theses: Doctorates and Masters

Self-intermittent catheterisation (SIMC) is one of the most common and safest methods of bladder emptying in people with spinal cord injury (SCI). There is a large amount of literature relating to the biomedical aspects of SIMC, such as infection rates and renal complications. There is however, very little information about how people actually experience SIMC and its effect on their daily lives. Through a series of semi-structured interviews this study describes the lived experience of eight men with spinal cord injuries who perform self-intermittent catheterisation to empty their bladder. The study uses Husserlian phenomenology and Colaizzi's method to analyse data …

Determining Standard Criteria For Endotracheal Suctioning In The Paediatric Intensive Care Patient: An Exploratory Study [Thesis], Kylie Davies

Theses: Doctorates and Masters

Endotracheal tube (ETT) suction is a common nursing procedure within the paediatric intensive care (PIC) setting. Significant side effects associated with this procedure can dramatically affect the stability of the critically ill ventilated paediatric patient. A comprehensive literature review failed to establish clear standards for determining when the procedure is warranted, especially in the paediatric population. This can present difficulty for the inexperienced paediatric intensive care nurse when assessing a patient's need for ETT suction. The aim of the research was to design an evidence based endotracheal suction assessment tool (ESAT) for use by nurses caring for paediatric patients. The …

Does Training With Powercranks™ Affect Economy Of Motion, Cycling Efficiency, Oxygen Uptake And Muscle Activation Patterns In Trained Cyclists?, Jack Burns

Theses: Doctorates and Masters

PowerCranks™ are claimed to increase economy of motion and cycling efficiency by reducing the muscular recruitment patterns that contribute to the resistive forces occurring during the recovery phase of the pedal stroke. However, scientific research examining the efficacy of training with PowerCranks™ is lacking. Therefore, the purpose of this study was to determine if five weeks of training with PowerCranks™ improves economy of motion (EOM), gross efficiency (GE), oxygen uptake (V.O2) and muscle activation patterns in trained cyclists. Sixteen trained cyclists were matched and paired into either a PowerCranks™ (PC) or Normal Cranks (NC) training group. Prior to training, all …

Neuromuscular Fatigue And Endocrine Responses In Elite Australian Rules Football Players, Stuart J. Cormack

Theses: Doctorates and Masters

The first purpose of this research was to establish the reliability of numerous measures obtained from a single and short duration repeated countermovement jump (CMJ) utilising a portable forceplate (Experimental Studies 1 and 2). Secondly, the response of reliable CMJ variables and T, C and T:C to a single elite level ARF match was assessed to identify the pattern of response and highlight those measures with the greatest potential for usefulness as monitoring tools across longer periods (Experimental Study 3). Finally, those variables identified as most valuable in Experimental Study 3 in addition to T, C and T:C; were measured …

The Relationship Between Training Load And Incidence Of Injury And Illness Over A Pre-Season At An Australian Football League Club, Benjamin Piggott

Theses: Doctorates and Masters

In any competitive sporting environment, it is crucial to a team's success to have the maximum number of their players free from injury and illness and available for selection in as many games as possible throughout the season. The training programme of the club, and therefore training load, can have an impact on the incidence of injury and illness amongst the players. The purpose of this study was to investigate the relationship between the training load and the incidence of injury and illness over an entire pre-season at an Australian Football League (AFL) club. Sixteen players were subjects; all full …

The Effect Of Nurse Initiated Paracetamol On Emergency Department Patients With Pain From Low Acuity Injury, Joanne G. Wilson

Theses: Doctorates and Masters

Early identification and management of pain was identified at the commencement of this study as a key area requiring research in emergency departments. Prolonged waiting times for analgesia especially, was highlighted in the National Institute of Clinical Studies emergency department collaborative in 2003. Many barriers exist for a patient to receive analgesia. In Western Australia this is compounded by the legislation which restricts prescribing rights for nurses. Three considerations guided the development of the research project. Firstly, the patient has initial contact with the emergency department from the nurse at triage. Secondly, paracetamol was recognised as a potentially effective analgesic …

Beliefs, Perceptions, And Preferences For Treatment In Latinas With Breast Cancer, Barbara Ann Kreling

Walden Dissertations and Doctoral Studies

Research documents that breast cancer is the leading cause of death in Latina females. The exact numbers are unknown, but studies reveal that Latinas with breast cancer underuse recommended follow-up chemotherapy, decreasing their rates of survival. Although several factors may be responsible, cultural influences are a possible barrier. However, there is a gap in the literature about how culture affects decisions about breast cancer treatment. This focused ethnographic study examined the role of cultural beliefs and perceptions in the decision-making process for Latina women about whether or not to receive chemotherapy following a breast cancer diagnosis. Drawing from Douglas' cultural …

The Effects Of In Utero Environmental Tobacco Smoke Exposure On Immune Responses To Allergen In Adult Offspring, Rodney Lamar Rouse

LSU Doctoral Dissertations

Fetal stress has been linked to adult atherosclerosis, obesity, and diabetes. Epidemiology studies have associated fetal exposure to maternal smoking and post-natal exposure to environmental tobacco smoke (ETS) with increased asthma risk. We tested the hypothesis, in a mouse model of asthma, that ETS exposure in utero alters airway function and respiratory immune responses in adult offspring. Pregnant BALB/c mice were exposed daily to ETS or filtered air (AIR). Neonatal gene expression was assessed. Offspring inhaled aerosolized ovalbumin (OVA) or saline in weeks 7-8. Regardless of whether they inhaled OVA or saline, mice were sensitized by OVA injections in weeks …

The Relationship Between Pro-Inflammatory Cytokines, Prostaglandins, And Fetal Hypothalamic-Pituitary-Adrenal Axis Activation In Mares With Infective Pre-Term Delivery, Sara K. Lyle

LSU Doctoral Dissertations

Ascending placentitis is a significant cause of abortions, stillbirths, and perinatal loss in horses. A technique for laparoscopic-guided catheterization of the allantoic space was developed and utilized in an experimental model of streptococcal infective pre-term delivery in pony mares. Mares received either 1 x 107 CFU live S. zooepidemicus (n=3), 5.1 x 108 CFU live S. zooepidemicus (n=1), 1 x 107 heat-killed S. zooepidemicus (n=3), 1 mL sterile PBS (n=3). Sham control mares did not receive a transcervical inoculation (n=3). One mare not instrumented with an allantoic catheter received 5.1 x 108 CFU live S. zooepidemicus. Mares with spontaneous abortion …

The Role Of Pax7 In The Formation Of The Superior Colliculus And The Vertebrate Visual System, Jennifer A. Thompson

Theses: Doctorates and Masters

This thesis has explored the role of Pax7 in formation and maturation of the mouse superior colliculus, an important brain region associated with topographic visual input and the capacity to evoke appropriate visuomotor responses to environmental stimuli. The research performed was explicitly targeted at understanding the relationship between Pax7 expression and the formation of the topography of the superior colliculus, including neuron specification and differentiation, boundary formation, polarisation and retinocollicular mapping. By employing histochemical, immunohistochemical and immunofluorescent techniques, together with quantification utilising Optimas Digital Image Analysis, this project assessed Pax7 expression in diverse mutant and wildtype mice …

Design, Synthesis, And Pharmacological Evaluation Of A Series Of Novel, Guanidine And Amidine-Containing Neonicotinoid-Like Analogs Of Nicotine: Subtype-Selective Interactions At Neuronal Nicotinic-Acetylcholine Receptor., Aaron Joseph Haubner

University of Kentucky Doctoral Dissertations

The current project examined the ability of a novel series of guandine and amidine-containing nicotine analogs to interact with several native and recombinantlyexpressed mammalian neuronal nicotinic-acetylcholine receptor (nAChR) subtypes. Rational drug design methods and parallel organic synthesis was used to generate a library of guanidine-containing nicotine (NIC) analogs (AH compounds). A smaller series of amidine-containing nicotine analogs (JC compounds) were also synthesized. In total, >150 compounds were examined. Compounds were first assayed for affinity in a high-throughput [³H]epibatidine radioligand-binding screen. Lead compounds were evaluated in subtype-selective binding experiments to probe for affinity at the α₄β_{2 …}

Translational Regulatory Mechanisms Of The Rat And Human Multidrug Resistance Protein 2, Yuanyuan Zhang

University of Kentucky Doctoral Dissertations

Multidrug resistance protein 2 (MRP2) is the second member the C subfamily in the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) efflux transporters. MRP2 is a critical player for generation of bile acidindependent bile flow and biliary excretion of glutathione, glucuronate and sulfate conjugates of endo- and xenobiotics. Dysfunctional expression of MRP2 is associated with Dubin-Johnson Syndrome.

Pathological and physiological states or xenobiotics change the MRP2 expression level. Under some conditions, expression of the human MRP2 and rat Mrp2 proteins are regulated at the translation level. There are several transcription initiation sites in MRP2/Mrp2 gene. The 5’ untranslated regions (5’UTRs) …

Role Of The Reactive Oxygen Species Peroxynitrite In Traumatic Brain Injury, Ying Deng

University of Kentucky Doctoral Dissertations

Reactive oxygen species (ROS) is cytotoxic to the cell and is known to contribute to secondary cell death following primary traumatic brain injury (TBI). We described in our study that PN is the main mediator for both lipid peroxidation and protein nitration, and occurred almost immediately after injury. As a downstream factor to oxidative damage, the peak of Ca2+-dependent, calpainmediated cytoskeletal proteolysis preceded that of neurodegeneration, suggesting that calpain-mediated proteolysis is the common pathway leading to neuronal cell death. The time course study clearly elucidated the interrelationship of these cellular changes following TBI, provided window of opportunity for pharmacological intervention. …

Endothelial Cell Dysfunction By Environmental Contaminants, Elizabeth Grace Oesterling

University of Kentucky Doctoral Dissertations

Within the last few decades, epidemiological evidence has linked exposure to air pollution, both its particles and its organic components, with cardiovascular disease (CVD) progression. CVD is a life long disease with the disruption of the endothelium being the inaugural event in this inflammatory process. The vascular endothelium is extremely susceptible to environmental insults given its tremendous surface area and that it is in constant contact with blood and components circulating within the blood, including xenobiotics. The endothelium is important as a barrier from blood constituents however, dysfunction of this barrier leads to the influx of lymphocytes and granulocytes that …

Implications For The Hsf2/Prc1 Interaction And Regulation Of Condensin By Phosphorylation During Mitosis, Lynea Alene Murphy

University of Kentucky Doctoral Dissertations

At the beginning of mitosis, chromosomes are condensed and segregated to facilitate correct alignment later in cytokinesis. Condensin is the pentameric enzyme responsible for this DNA compaction and is composed of two structural maintenance of chromosomes (SMC) subunits and three non-SMC subunits. Condensin mutations generate chromosomal abnormalities due to improper segregation, leading to genome instability and eventual malignant transformation of the cell. Cdc2 phosphorylation of the non-SMC subunits, CAP-G, CAP-D2, and CAP-H, has been demonstrated to be important for condensin supercoiling activity and function. While these subunits are thought to be phosphorylated by Cdc2, the exact sites have not yet …

Application Of Linear Free Energy Relationships In The Prediction Of Triglyceride/Water Partition Coefficients And Lipid Bilayer Permeability Coefficients Of Small Organic Molecules And Peptides, Yichen Cao

University of Kentucky Doctoral Dissertations

Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the …

Thermal Sensitivity Of Vagal Pulmonary Sensory Neurons: Role Of Transient Receptor Potential Vanilloid Channels, Dan Ni

University of Kentucky Doctoral Dissertations

Hyperthermia can occur in lungs and airways during both physiological and pathophysiological conditions. A previous study carried out in our laboratory showed that hyperthermia activates and sensitizes vagal bronchopulmonary Cfiber afferents, whether this effect is through a direct action of hyperthermia on sensory nerves is not known. This dissertation study was aimed to investigate the thermal-sensitivity of pulmonary sensory neurons, and the roles of thermalsensitive transient receptor potential vanilloid (TRPV) channels. Whole-cell patch-clamp recordings of neurons isolated from nodose/jugular ganglia were applied in the study. Results of this study showed that hyperthermia directly activates pulmonary sensory neurons, and this effect …

Regulation Of L-Type Voltage-Dependnet Calcium Channels By The Rem Gtpase, Chunyan Pang

University of Kentucky Doctoral Dissertations

The Rem, Rem2, Rad, and Gem/Kir GTPases, comprise a novel subfamily of the small Ras-related GTP-binding proteins known as the RGK GTPases, and have been shown to function as potent negative regulators of high voltage-activated (HVA) Ca²⁺ channels upon overexpression. HVA Ca²⁺ channels modulate Ca²⁺ influx in response to membrane depolarization to regulate a wide variety of cellular functions and they minimally consist of a pore-forming α1 subunit, an intracellular β subunit, and a transmembrane complex α₂/δ subunit. While the mechanisms underlying RGK-mediated Ca²⁺ channel regulation remain poorly defined, it appears that both membrane …

Genetic Regulation Of Hematopoietic Stem Cell Aging, Erin J. Oakley

University of Kentucky Doctoral Dissertations

It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. In C57BL/6 (B6) mice, the HSC population steadily increases with age, whereas in DBA/2 (D2) mice, this population declines. Our lab has previously mapped a quantitative trait locus (QTL) to murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In these dissertation studies, I first aim to …

Role Of Reactive Oxygen Species Peroxynitrite In Traumatic Spinal Cord Injury, Yiqin Xiong

University of Kentucky Doctoral Dissertations

Peroxynitrite (PN, ONOO-), formed by nitric oxide radical (^•NO) and superoxide radical (O2^•-), plays an important role in post-traumatic oxidative damage. In the early work, we determined the temporal characteristics of PN-derived oxidative damage in a rat spinal cord injury (SCI) model. Our results showed 3-nitrotyrosine (3-NT), a specific marker for PN, rapidly accumulated at early time points (1 hr, 3 hrs), after when it plateaued and the high level was sustained to 1 week post injury. The co-localization of 3-NT and lipid peroxidation derived-4-HNE observed in immunohistochemistry indicates PN is involved in lipid peroxidative as …

Nitration And Inactivation Of Manganese Superoxide Dismutase Plays A Critical Role In Metabolic Switch, Muthuswamy Anantharaman

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD) is a multifactorial, progressive, age-related neurodegenerative disease. Oxidative stress hypothesis is most prevalent and is gaining significant support. Inspite of the progress achieved on oxidative stress related damages in AD brain; the modification occurring on the various cellular antioxidant enzymes antioxidant has not been identified. Tyrosine nitration, a marker for peroxynitrite induced oxidative damage to protein is widespread in AD brain and Manganese superoxide dismutase (MnSOD), primary mitochondrial antioxidant enzyme is prone to peroxynitrite induced nitration and inactivation. Nitration of proteins involved in energy metabolism has been demonstrated in AD brain, which may explain the altered glucose …

Reciprocal Regulation Of Par-4 And Caspase-8 In The Trail Signaling Pathway, Padhma Ranganathan

University of Kentucky Doctoral Dissertations

Par‐4 is a pro‐apoptotic tumor suppressor that is mutated, suppressed or inactivated in cancer. Par‐4 exploits components of the extrinsic pathway to cause apoptosis selectively of cancer cells. This study identified Par‐4 as an essential component of the apoptotic pathway induced by TRAIL, which selectively targets cancer cells. RNA interference‐mediated knockdown of Par‐4 rendered cancer cells unresponsive to TRAIL‐induced apoptosis. Cells with knocked‐down levels of Par‐4 were deficient in the activation of the apoptosis‐initiator caspase‐8 and the apoptosis‐effector caspase‐3 in response to TRAIL. Par‐4 was identified as a critical mediator of membrane translocation of caspase‐8 and the adapter protein FADD. …

A Novel Class Of Immunoproteasome Catalytic Subunit Lmp2 Inhibitor And Its Therapeutic Potentials In Cancer, Yik Khuan (Abby) Ho

University of Kentucky Doctoral Dissertations

The immunoproteasome, known to play an important role in MHC class I antigen processing and presentation, have been linked to neurodegenerative diseases and hematological cancers. However, the pathophysiological functions of the immunoproteasome in these diseases are still not very well established. This can be attributed mainly to the lack of appropriate molecular probes that selectively target the immunoproteasome catalytic subunits. Herein, we report the development of a small molecular inhibitor (AM) that selectively targets the major catalytic subunit, LMP2, of the immunoproteasome. We show that the compound covalently modifies the LMP2 subunit with high specificity in human prostate …

Effect Of Chronic Airway Inflammation Induced By Allergen Sensitization On Vagal Bronchopulmonary Sensory Nerves In Rats, Guangfan Zhang

University of Kentucky Doctoral Dissertations

Airway hyperresponsivness (AHR) is one of most prominent pathophysiological features of asthma. Increasing evidence suggests that vagal bronchopulmonary afferents may be involved in the development of AHR. However, the underlying mechanisms are not clear. Therefore, the purpose of this dissertation was to investigate the effect of chronic airway inflammation induced by allergen sensitization on vagal bronchopulmonary afferents. The study was carried out in an animal model of allergic asthma. Brown-Norway rats were sensitized by intraperitoneal Ovalbumin (Ova) and exposed to aerosolized Ova 3 times/week for three weeks. Control rats received the vehicle. In vivo single-fiber recording technique was applied in …

Zinc Deficiency And Mechanisms Of Endothelial Cell Dysfunction, Huiyun Shen

University of Kentucky Doctoral Dissertations

Atherosclerosis is a chronic inflammatory disease thought to be initiated by endothelial cell dysfunction. Research described in this dissertation is focused on the role of zinc deficiency in endothelial cell activation with an emphasis on the function of the transcription factors nuclear factor-κB (NF-κB), peroxisome proliferator activated receptor (PPAR), and the aryl hydrocarbon receptor (AhR), which all play critical roles in the early pathology of atherosclerosis. Cultured porcine aortic vascular endothelial cells were deprived of zinc by the zinc chelator TPEN and/or treated with the NF-κB inhibitor CAPE or the PPARγ agonist rosiglitazone, followed by measurements of PPARα expression, cellular …

The Effect Of Pparγ Activation By Pioglitazone On The Lipopolysaccharide-Induced Pge2 And No Production: Potentialunderlying Alteration Of Signaling Transduction, Bin Xing

University of Kentucky Doctoral Dissertations

Microglia-mediated neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Uncontrolled microglia activation produces major proinflammatory factors including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) that may cause dopaminergic neurodegeneration. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone has potent antiinflammatory property. We hypothesize pioglitazone protects dopaminergic neuron from lipopolysaccharide (LPS)-induced neurotoxicity by interacting with relevant signal pathways, inhibiting microglial activation and decreasing inflammatory mediators.

First, the neuroprotection of pioglitazone was explored. Second, the signaling transductions such as jun N-terminal kinase (JNK) and the interference with these pathways by pioglitazone were investigated. Third, the effect of …

Selective Regulation Of Cardiomyocyte Signaling By Rgl2, Leah M. Allen

University of Kentucky Doctoral Dissertations

A key cardiovascular signaling molecule involved in both physiologic and pathologic regulation of cardiomyocytes is the small molecular weight G-protein, Ras. Differential effects of Ras are mediated by multiple effector molecules, including the RalGEFs which activate Ral. Studies performed in cardiomyocytes have indicated a role for Ral in cardiac hypertrophic signaling and the RalGEF family member, Rgl2, was shown to specifically interact with Ras in the heart. Therefore, I hypothesized that Rgl2 was an important Ras effector that would regulate cardiomyocyte signaling.

To elucidate the potential importance of Rgl2 in regulating cardiomyocyte signaling, a gain-of-function approach was utilized in which …

Induction Of The Heat Shock Response To Protect Against Polyglutamine Diseases And The Role Of Protein Sumoylation In Laminopathies And Alzheimer's Disease, Yu-Qian Zhang

University of Kentucky Doctoral Dissertations

Heat shock proteins function as molecular chaperones which help protein folding and prevent protein aggregation. My study shows that celastrol, a pharmacological compound capable of up-regulating the levels of heat shock proteins, inhibits cell death and protein aggregation caused by expanded polyglutamine containing protein, and the protective effects of celastrol are dependent on heat shock factor 1. These results suggest the potential of celastrol as a therapeutic agent in the treatment of polyglutamine diseases.

Sumoylation is a protein modification which plays diverse roles in regulating the target proteins. My study shows that lamin A is a target of protein sumoylation, …

Effects Of Fescue Herbicides Plateau® And Cimarron® On Pregnancy Maintenance In Broodmares And On Alkaloid Concentrations In Endophyte Infected Tall Fescue, Kathleen Scarlett Black

University of Kentucky Master's Theses

Ingestion of endophyte infected (E+) fescue by pregnant mares can cause significant reproductive problems. Plateau® and Cimarron® herbicides suppress fescue while leaving desired forages unharmed. To determine if these herbicides are harmful to pregnant mares, they were allowed to graze pastures treated with Plateau®, Cimarron®, or vehicle carrier. Pregnancies were monitored via ultrasonography, blood chemistry, and hematology. Of the components measured only creatinine differed among treatments over time (P=0.0003) and that increase was only significant in one of four studies.

Two additional experiments were conducted to determine the effect of the herbicides on alkaloids within E+ fescue. A greenhouse experiment …

Academic Incentives Impact On Increasing Seventh -Graders Physical Activity During Leisure Time, Jeffrey Scott Brinker

Walden Dissertations and Doctoral Studies

Recent research clearly demonstrates that a decrease of physical activity has occurred among young people. Hence, the purpose of this study was to examine the impact of external motivation on physical activity. Drawn from self-determination theory, the specific research question examined if academic incentives effectively motivated 7th grade students to participate in a 3-week fitness program. A quasi-experimental pre-post design examined treatment and control groups drawn from a sample of 24 students from three physical education classes. The treatment group received academic incentives whereas the control group received no external incentives but were asked to complete the same fitness Program. …