Medical Sciences Commons^™

Understanding Pseudomonas Aeruginosa Alginate Regulation And Its Link To Chronic Lung Infections In Cystic Fibrosis Patients, Roy Al Ahmar

Theses, Dissertations and Capstones

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). This disorder results in thick lung secretions which compromise the patient’s immune system. Chronic lung infections with Pseudomonas aeruginosa biofilms is a major factor that contributes to poor outcome for clinical treatment. The overall hypothesis of this dissertation is that small colony variant and pyrimidine biosynthesis are linked with biofilm formation, alginate production is dependent on MucA proteolysis, rifaximin can be repurposed to treat biofilm infection and multiplex PCR can be used to rapidly measure the bacterial cell density in …

Cardiovascular Aging In The Female F344xbn Rat Model, Jacqueline C. Fannin

Theses, Dissertations and Capstones

Despite continued advances in medical care, cardiovascular disease (CVD) remains the leading cause of death for American women [1]. Although humans and non-human primates are the only mammals to experience menses, rodent models are commonly used to study age-associated cardiovascular alterations due to similar ovarian aging, low expense, and short lifetime to investigate cardiovascular aging. Previous studies have found that aging in the female rodent is characterized by increased ventricular apoptosis, elevations in oxidative-nitrosative stress, ventricular remodeling, increased collagen content, mild systolic and diastolic dysfunction, and reduced occurrence of arrhythmias compared to males [2-7]. Similarly, age-associated alterations in the female …

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 …

Age-Associated Alterations In The F344xbn Rat Heart And The Efficacy Of Chronic Acetaminophen Ingestion As A Therapeutic Approach, Sunil K. Kakarla

Theses, Dissertations and Capstones

Despite advances in therapeutic and diagnostic strategies cardiovascular disease still remains the leading cause of death in older people. Recent studies suggest that age- related elevations in oxidative stress are associated with increases in cardiac apoptosis and compensatory hypertrophy of the remaining cardiomyocytes. Acetaminophen has been shown to exhibit cardioprotective effects following ischemia-reperfusion injury by acting as an antioxidant. Here, we investigate the molecular mechanisms underlying aging associated cardiac remodeling in male F344XBN rats and examine the efficacy of chronic acetaminophen ingestion as a therapeutic approach.

Aging in male F344XBN rats is characterized by a significant increase in heart size, …

Regulation Of Alginate Production Of Pseudomonas Aeruginosa Pseudomonas Aeruginosa, Fredrick Heath Damron

Theses, Dissertations and Capstones

Pseudomonas aeruginosa (P.a.) is a major threat to the health and well being of a person living with cystic fibrosis (CF). P.a. is capable of conversion to mucoidy or alginate overproducing phenotype. Mucoidy facilitates the chronic infection of P.a. infection in the CF lung. Mutations in the anti-sigma factor mucA, result in activation of the sigma factor AlgU which promotes expression of alginate through the alginate biosynthetic operon. However, P.a. can produce alginate independent of mucA mutation via a mechanism known as regulated proteolysis. Proteases AlgW and MucP can degrade MucA to liberate and activate AlgU. In this dissertation, two …

The Effect Of A Nurse-Respiratory Therapist Weaning Protocol On The Duration Of Mechanical Ventilation And The Incidence Of Ventilator-Associated Pneumonia, Andrea Lucas

Theses, Dissertations and Capstones

The purpose of this research study was to show the effectiveness of implementing a standardized nurse-respiratory driven weaning protocol in decreasing the time spent on mechanical ventilation and the incidence of ventilator-associated pneumonia in mechanically ventilated patients compared to using individual physician methods. Chart reviews were performed to compare the incidence of ventilator-associated pneumonia (VAP) prior to the initiation of the nurse-respiratory driven weaning protocol. Sister Callista Roy’s Adaptation theory was used as a framework for this study to show that nurses could promote adaption by using a standardized ventilator weaning protocol. The study did not show statistical significance that …

Age-Related Dgc Structure And Function In The F344/N X Bn Rat Heart, Sunil K. Kakarla

Theses, Dissertations and Capstones

Recent data has suggested that disruption of the dystrophin-glycoprotein complex (DGC) may be involved in mediating the progression of cardiac hypertrophy and failure. Here we examined the regulation of DGC proteins in the hearts of adult (6 months), aged (30 months), and very aged (36 months) F344/N X BN rats . Compared to adult animals, the content of α- and β-dystroglycan were 6.93 ± 5.16% and 58.36 ± 3.64% higher, respectively (P < 0.05) in very aged animals. Immunoblotting and immunhistochemical analysis suggested that aging appeared to diminish alpha-sarcoglycan, beta-sarcoglycan and delta-sarcoglycan content by 13.89 ± 3.1%,15.8 ± 2.8% and 18.63 ± 3.04%, respectively (P < 0.05). These alterations in the DGC occurred coincident with age- associated alterations in cytoplasmic anti-rat IgG immunoreactivity, TUNEL positive nuclei, alpha-fodrin cleavage, indices of caspase-3 activation and diminished AKT phosphoryation (Ser 308). Taken together, these data suggest that aging alters cardiac DGC structure and function.

Aging Influences Multiple Indices Of Oxidative Stress In The Heart Of The Fischer 344/Nnia X Brown Norway/Binia Rat, Shinichi Asano

Theses, Dissertations and Capstones

Here we report the influence of aging on multiple markers of oxidativenitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36- month) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Compared to 6 month old rat hearts, indices of oxidative (superoxide anion (–O2 ·), 4-hyrdoxy-2- nonenal (4-HNE)) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r>0.669; r>0.710 and p<0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.

Regulation Of Biofilm Formation Of Pseudomonas Aeruginosa, Nathaniel Edwards Head

Theses, Dissertations and Capstones

Cystic fibrosis (CF) is the most common, autosomal recessive lethal genetic disease in the Caucasian population, resulting from a malfunctioned cystic fibrosis transmembrane conductance regulator (CFTR) and leading to bacterial lung infections. P. aeruginosa, an opportunistic pathogen, establishes a chronic infection in CF with a phenotype of overproduction of an exopolysaccharide (alginate) due to host-directed mutagenesis. While free-floating planktonic bacteria can be properly cleared from the CF lung, P. aeruginosa, along with alginate production, establishes an infection in the form of a biofilm which supports its survival in nature and in vivo. As a result, genomic structure, …

Discovering The Barriers To Health-Promoting Lifestyles Among Appalachian Veterans With Uncontrolled Hypertension, Tara L. Porter

Theses, Dissertations and Capstones

Introduction: The purpose of this study was to discover the barriers to health promoting lifestyles among the Appalachian veteran population with uncontrolled hypertension.

Design: A quantitative research study was conducted over five months using a non-experimental, descriptive research design. Pender’s Health Promotion Model served as the study’s framework. Subjects were recruited from a primary care setting through advertisement within the hospital. A convenience sample of thirty-two subjects was obtained.

Method: The Health Promotion Lifestyle Profile (HPLP) II survey assessed for barriers to controlled hypertension in the following areas: health-promoting lifestyle, health responsibility, stress management, spiritual growth, interpersonal relationships, nutrition, and …

The Cardiovascular And Metabolic Adaptations To Iso-Caloric Moderate Intensity And High Intensity Exercise, Summerson Desmond

Theses, Dissertations and Capstones

Cardiovascular disease is the leading cause of death in the industrialized nations, and accounts for 1 million deaths in the United States each year (McArdle, Katch & Katch, 1991). One of the major risk factors for cardiovascular disease is physical inactivity, which is a behavioral modified risk factor. Physical inactivity plagues 59% of the people in the United States (ACSM Resource Manual, 1998). Physical inactivity often leads to obesity, diabetes, hypertension and hypercholemia, and places sedentary individuals at more risk for cardiovascular disease (CVD), or coronary heart disease (CHD). The question which remains unclear is the quantity and quality of …