Medicine and Health Sciences Commons^™

Preclinical Study Of Potential Antiglioma Novel Tetrahydroisoquinoline Analogs: Pharmacokinetics And Mechanism Of Action, Fei Ma

Theses and Dissertations (ETD)

Gliomas, the tumors of glial cells, account for 80% of primary malignant brain tumors. In 2011, there were about 18,300 new cases of maligant gliomas in the United States alone. Patients with glioblastoma multiforme or anaplastic astrocytoma, the two major types of malignant gliomas, have a median survival of 14 months or 2 to 3 years, respectively. Therefore novel treatments for malignant glioma are urgently needed.

A novel series of tetrahydroisoquinoline derivatives with antiglioma activity has been undergoing drug metabolism/pharmacokinetics (DMPK)-guided lead optimization. EDL-291 was result from structure modification of last generation compound EDL-155. Its preclinical pharmacokinetics were characterized in …

The Traditional Roles Of Caring For Elders: Views From First Nations Elders Regarding Health, Violence, And Elder Abuse, Eileen A. Owen-Williams

Theses and Dissertations (ETD)

This study sought to respectfully understand Northern British Columbia First Nations Elders' views regarding health of communities, intergenerational relationships, Elder roles, and violence towards Elders. Injuries, both intentional and unintentional, are a leading cause of death for First Nations Peoples. Information regarding Elder abuse in First Nations communities is lacking, though family violence has been identified as a problem within First Nations communities. The goal of this research was to understand the point of view and Elders' reality through the creation of a dialogue with Elders, and to discern the interface between Traditional First Nations' belief systems, healing methods, and …

A Secular Increase In The Tempos Of Tooth Formation: 1980-2010, Kevan Michael O'Neill

Theses and Dissertations (ETD)

Introduction: Improved environments in the U.S. have resulted in taller, larger, and heavier children and adults compared to past generations. Studies of other skeletal-dental dimensions have shown increases across generations, and our perception is that teeth now are forming faster. The purpose of this study is to test for a secular trend towards faster tempos of tooth mineralization in a sample of U.S. white adolescents over the past quarter century (1980-85 to 2005-10).

Materials: Two cohorts of 200 children each were identified, each with an age range of 10-to- 15 years, one group from 1980-85 and the more recent group …

Phenotypic And Electrophysiologic Characterization Of A Mouse Model Of Fragile X Syndrome, Snigdha Roy

Theses and Dissertations (ETD)

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. It is caused by a mutation in the fragile X mental retardation (FMR1) gene on the X chromosome. Many children with FXS exhibit autistic behaviors and deficits in motor coordination including speech articulation deficits. The development of the FMR1 knockout (Fmr1 KO) mouse, in which the Fmr1 gene is inactivated, has provided an animal model that can be used to investigate underlying neuro-physiological mechanisms associated with FXS as well as to evaluate potential therapeutic treatments. In this study, quantitative behavioral assays were used, such as long term …

Oropharyngeal Airway Volume Following Orthodontic Treatment: Premolar Extraction Versus Non-Extraction, Thomas Patrick Shannon

Theses and Dissertations (ETD)

Orthodontic correction of tooth size versus arch size discrepancy (TSASD) can be achieved with two distinct methods of treatment. The first involves the extraction of teeth to gain the space needed for tooth alignment. The second relies on arch expansion to gain the space needed for correction. In recent decades, arguments for and against the extraction of teeth for orthodontic purposes have become increasingly important, particularly in regards to oropharyngeal airway size. Purpose: The purpose of this study is to determine whether there is a decrease in oropharyngeal dimensions following the extraction of four premolars and subsequent orthodontic therapy. Methods: …

Cns Penetration Of Tyrosine Kinase Inhibitors In Mouse Models, Mohamed Elmeliegy

Theses and Dissertations (ETD)

For the past three decades, advances in the treatment of central nervous system (CNS) tumors such as malignant glioma have only been modest. One particular challenge facing treatment of brain tumors is the delivery of therapeutically effective concentrations of anti-cancer agents to the target site in the brain. The sanctuary of the brain is protected by several barrier systems such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). These barriers restrict the passage of anti-cancer drugs into the brain via several protective mechanisms.

In the present study, we used cerebral microdialysis sampling, a technique for sampling unbound …

Rankl And Osteoprotegerin Levels In Response To Orthodontic Forces, Katherine Ann Hart D.D.S.

Theses and Dissertations (ETD)

Orthodontic tooth movement is mediated by interactions between PDL cells and those of the alveolus. One protein—the receptor activator nuclear factor kappa B ligand (RANKL)—is critical for osteoclastogenesis, and osteoprotegerin (OPG) is a decoy ligand that competitively inhibits RANKL. A higher RANKL/OPG ratio is associated with areas of bone resorption, while a lower ratio occurs in areas of bone deposition and homeostasis. There have been almost no clinical studies of RANKL and OPG expression in human subjects undergoing orthodontic tooth movement. The purpose of this study was to quantify changes in the levels of RANKL and of OPG expression in …

Contribution Of The Unfolded Protein Response To Vegf Expression, Ethel Rose Pereira

Theses and Dissertations (ETD)

Tumor cells experience a limiting microenvironment due to inadequate vascularization that can affect the normal functioning of intracellular organelles. In the case of the endoplasmic reticulum, the limiting environment is further exacerbated by the high metabolic demands of the tumor cells, which together interfere with the proper maturation of nascent proteins synthesized there. The resultant accumulation of unfolded proteins activates a signal transduction pathway known as the Unfolded Protein Response, which serves primarily to protect the cell during stress and helps restore homeostasis to this organelle. As tumors expand resulting in regions that are a greater distance from functional blood …

Oropharyngeal Airway Volume Following Orthodontic Treatment: Premolar Extraction Versus Non-Extraction, Thomas Patrick Shannon

Theses and Dissertations (ETD)

Orthodontic correction of tooth size versus arch size discrepancy (TSASD) can be achieved with two distinct methods of treatment. The first involves the extraction of teeth to gain the space needed for tooth alignment. The second relies on arch expansion to gain the space needed for correction. In recent decades, arguments for and against the extraction of teeth for orthodontic purposes have become increasingly important, particularly in regards to oropharyngeal airway size. Purpose: The purpose of this study is to determine whether there is a decrease in oropharyngeal dimensions following the extraction of four premolars and subsequent orthodontic therapy. Methods: …

Pronthocyanidin-Rich Cranberry-Fractioninduced Alteration Of Periodontal Pathogen Lipopolysaccharide Functions, Vreiti Sangha

Theses and Dissertations (ETD)

The cranberry (species: Vaccinium macrocarpon, family: Ericaceae) is a polyphenolicrich berry fruit native to North America and exhibits numerous beneficial properties for human health, such as inhibition of human cancer cell line proliferation and prevention of urinary tract colonization by bacterial pathogens. The proanthocyanidin rich cranberry fraction has long been speculated to possess the capacity to reduce the production of inflammatory mediators by LPSstimulated macrophages and gingival fibroblasts and to inhibit host extracellular matrix destructive enzyme production and activity.

The purpose of this investigation was to examine the effect of cranberry non dialyzable material (NDM), which was shown to be …

Acetaldehyde And Epithelial Junctions: Role Of Pp2a And Occludin Phosphorylation, Mitzi Dunagan

Theses and Dissertations (ETD)

Chronic alcohol consumption causes health problems including cancers, liver damage, and cirrhosis.These problems are exacerbated by endotoxins from the bacterial population of the colon, which can enter the bloodstream when gastrointestinal tight junctions, protein complexes that prevent paracellular passage of molecules, are compromised. The mechanisms of this barrier disruption are the subject of current study.

Acetaldehyde, produced as a result of ethanol breakdown by intestinal microflora as well as intestinal epithelia, is a known carcinogen. It compromises the barrier function of intestinal epithelial cells by causing irregularities in the phosphorylation of tight junction proteins. It also reacts with proteins, lipids, …

The Delivery System Design Of A Community Mental Health Center And Provision Of Quality: Cardiometabolic Screening For Persons With A Severe Mental Illness Prescribed Atypical Antipsychotic Medication, Dawn Marie Vanderhoef

Theses and Dissertations (ETD)

Background: Persons with a severe mental illness (SMI) prematurely lose up to 25 years of life when compared to the general population. This patient population has increased morbidity and mortality due to higher than normal rates of obesity, hypertension, diabetes, and cardiovascular disease. Treatment of SMI often includes the use of atypical antipsychotic (AA) medication which has been associated with the development of cardiometabolic illnesses. In response to the higher rates of co-morbid, chronic physical illness, monitoring guidelines for cardiometabolic illness have been published. Despite these guidelines, screening rates for cardiometabolic illness in this population remain low. Neither community mental …

Investigations Of Pharmacokinetic Challenges In Premature Infants, Yi Zhang

Theses and Dissertations (ETD)

Premature infants (gestational age less than 37 weeks) are considered a vulnerable patient population due to their immaturity at birth. Currently, off-label prescribing is common in younger pediatric populations, especially in premature neonates and infants, which is a primary group receiving intensive care. Unique pharmacokinetic (PK) challenges—such as limited blood volume and frequency of blood sample collections, rapid growth and continuous developmental changes, complexity of pediatric studies as well as scientific, practical, and ethical concerns— lead to the current lack of PK information and empirical dosing in premature neonates and infants. In this research, several approaches were investigated to overcome …