Life Sciences Commons^™

Cardioprotective Role Of The Cholinergic System, Mouhamed Dakroub

Electronic Thesis and Dissertation Repository

The process of aging is an irreversible continuum experienced by all individuals. A large number of physiological transformations occur to the cardiovascular system as one ages. These changes result in increased risk of developing cardiovascular diseases, many of which are frequently seen in geriatric populations. While the exact mechanisms of age-related cardiac dysfunction have not been established, abnormal cholinergic dysfunction has been implicated in the pathology of other age related diseases; therefore, we have hypothesized that age induced cholinergic dysfunction is detrimental to cardiac function and health. This study seeks to identify whether increased cholinergic signaling, either by transgenic overexpression …

Regulation Of Hepatic Drug Metabolizing Enzymes In Chronic Kidney Disease, Thomas J. Velenosi

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD) occurs as a result of declining renal function for 3 or more months. CKD effects 1 in 10 Canadians and is associated with a number of co-morbidities including diabetes and cardiovascular disease. To manage CKD and associated co-morbidities, patients take an average of 12 medications with a median pill burden of 19. Indeed, renal drug elimination is compromised in CKD, as declining glomerular filtration reduces drug excretion into urine. More recently, studies have provided evidence of altered non-renal drug clearance in CKD. The majority of drug clearance occurs in the liver by CYP2C and CYP3A drug …

Cytochrome P450 3a4 Expression And Regulation In Non-Alcoholic Fatty Liver Disease, Sarah J. Woolsey

Electronic Thesis and Dissertation Repository

Non-alcoholic fatty liver disease (NAFLD) is defined as lipid accumulation within hepatocytes (steatosis) in the absence of excess alcohol consumption. It is the most common liver disease in the western world, affecting one third of the general adult population with particularly high prevalence in obesity and type 2 diabetes. NAFLD is a disease continuum originating with simple hepatic steatosis that can progress to non-alcoholic steatohepatitis (NASH) with fibrosis and potentially cirrhosis, which places patients at risk for hepatocellular carcinoma. Unfortunately, there are not yet specific pharmacologic agents to treat NAFLD and so its management involves treatment of comorbidities, but there …

Clinical And Mechanistic Insights Into Novel Probiotic Functions And Formulations, Jordan Bisanz

Electronic Thesis and Dissertation Repository

Using a combination of hypothesis and discovery based approaches, the goal of this thesis was to better describe novel probiotic functions and their mechanisms while striving to better understand the effect of formulation on Bifidobacterium animalis subsp. lactis, Lactobacillus paracasei and L. rhamnosus.

Using RNA-Seq, a bacterial metatranscriptome analysis of a commonly consumed probiotic yogurt showed that the organisms adapted to storage time and flavor additions. This led to the discovery that in addition to the probiotic health benefits, members of the L. casei group (L. rhamnosus and L. paracasei) produce volatile sulfur compounds mediated by a novel …

Quantitative Estimation Of P-Glycorptein-Mediated Drug Transport By Mechanistically Modeled Intrinsic Clearance, Alex D. Morgan

Electronic Thesis and Dissertation Repository

P-glycoprotein (P-gp/ABCB1) is an important efflux drug transporter affecting the disposition of 50% of marketed drugs. Cell monolayer permeability assays are the gold standard for assessing P-gp-drug interactions in vitro, but inter-laboratory assay differences produce heterogeneous results. We compared the validity and sensitivity of traditional assay metrics of efflux transport (unidirectional apparent permeability and efflux ratio) with a modeled clearance metric, CL_P-gp and hypothesized that CL_P-gp would be superior. Cell monolayers heterologously transfected with ABCB1, and 1,25(OH)₂D₃-modulated ABCB1 in cells served as experimental models. P-gp expression was quantified by western …