Medicine and Health Sciences Commons^™

Antidepressants Versus Placebo For Generalized Anxiety Disorder: A Systematic Review And Meta-Analysis, Katarina Kopcalic

Electronic Thesis and Dissertation Repository

Objectives: To assess the efficacy and acceptability of antidepressants compared to placebo among adults with a primary diagnosis of generalized anxiety disorder (GAD). Methods: Five electronic databases and 2 trial registries were searched to identify studies for inclusion. The risk of bias version 1 tool was used to assess the risk of bias. A random-effects meta-analysis was conducted using RevMan web. Results were presented using forest plots. Results: 38 studies (12,570 participants) were included. Very low-quality evidence showed a benefit for antidepressants over placebo in the rate of treatment response (RR, 1.39: 95% CI: 1.27, 1.52) and no differences in …

Investigating A Novel Receptor That Mediates Vasoconstriction In Mouse Femoral Arteries, Joselia Carlos

Electronic Thesis and Dissertation Repository

The synthetic peptide trans-cinnamoyl-leucine-isoleucine-glycine-arginine-leucine-ornithine-amide (tcLIGRLO) causes smooth muscle contraction in mouse femoral arteries. The identity of the receptor that mediates this response is undetermined. We hypothesize that the novel mechanism for tcLIGRLO-induced contractions involves a G-protein coupled receptor (GPCR) and a G_q-Ca²⁺ signalling pathway. Chapter 2 describes experiments using femoral arteries isolated from male and female systemic protease-activated receptor 2 (PAR2KO) mice (n=31; 21 – 39 weeks of age) using tcLIGRLO and the G_q-inhibitor, YM-254890 (YM). Contractions produced by tcLIGRLO did not differ by sex but decreased as age increased. YM inhibited tcLIGRLO-induced contractions. Chapter …

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …

Pregestational Diabetes Induced Congenital Heart Defects And Coronary Artery Malformations; Mechanisms And Preventative Therapies, Anish Engineer

Electronic Thesis and Dissertation Repository

Congenital heart defects (CHDs) arise from perturbations in complex molecular and cellular processes underlying normal embryonic heart development. CHDs are the most common congenital malformation, occurring in 1 to 5% of live births, and are the leading cause of pediatric mortality. Adverse genetic and environmental factors can impede normal cardiogenesis and increase the likelihood of CHDs. Pregestational maternal diabetes increases the risk of CHDs in children by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. The aim of …

Maternal Nicotine Exposure Induces Congenital Heart Defects In The Offspring Of Mice, Elizabeth Greco

Electronic Thesis and Dissertation Repository

Congenital heart defects are the most prevalent birth defect, and maternal cigarette smoking is a known risk factor. Nicotine replacement therapies are recommended to pregnant women who smoke to aid in smoking cessation, as this alternative is thought to be much safer compared to cigarette smoking. However, these products contain nicotine, and the safety of nicotine on the developing heart is not well known. In this thesis, a mouse model was used to test the hypothesis that maternal nicotine exposure (MNE) during pregnancy leads to congenital heart defects and coronary artery defects in the offspring of mice. MNE resulted in …

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the best …

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration are …

Beta Blocker Dialyzability And Effectiveness In Chronic Hemodialysis Patients, Alvin Tieu

Electronic Thesis and Dissertation Repository

Of the minimal information describing drug dialyzability, the majority was obtained prior to modern hemodialysis membranes. This study characterized the dialyzability of the most commonly prescribed beta blockers in patients undergoing high-flux hemodialysis. Eight subjects were recruited to a pharmacokinetic, 4-way crossover trial. Drug concentrations were measured using mass spectrometry and dialyzability determined by the arterial-venous difference and recovery clearance methods. A provincial-wide retrospective cohort study was designed to determine the effect of dialyzability on adverse clinical outcomes. Beta blocker efficacy can be hindered if substantial clearance occurs during dialysis. Our results demonstrate atenolol and metoprolol are extensively cleared during …

Evaluating The Role Of Intestinal Transporters In Fruit Juice-Drug Interactions, Mandy Mj Li

Electronic Thesis and Dissertation Repository

Fruit juice-drug interactions (FJDIs) involving non-metabolized oral medications result in decreased drug exposure that may lead to reduced therapeutic efficacy. The effect is thought to be mediated by inhibition of the intestinal drug transporters organic anion transporting polypeptide 1A2 and 2B1 (OATP1A2 and OATP2B1) by fruit juice constituents, however the exact mechanisms remain controversial. We tested the hypothesis that fruit juices limit the absorption of fexofenadine through interactions with specific intestinal transporters. In vitro transport and fruit juice inhibition studies using fexofenadine, a medication involved in FJDIs, revealed that in addition to previously implicated transporters, organic cation transporter 1 (OCT1) …

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 …

Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka

Electronic Thesis and Dissertation Repository

Pharmaceutical residues can reach agricultural land through amendment with animal or human waste. Since 2010, a series of replicated plots received annual applications of ivermectin, monensin and zinc bacitracin, either singly or in a mixture, at 0.1 mg/kg and 10 mg/kg concentrations. I collected soil samples before and after the fourth annual application of pharmaceuticals and assayed them for functional changes and amoA gene abundance, a gene needed for ammonia oxidation. In 2013, I exposed the soils to 100 mg/kg in a laboratory experiment which resulted in acceleration of nitrification. Under 10 mg/kg treatments in the field the abundance of …

Effect Of Ascorbate On Coagulation And Fibrinolytic Factors In The Septic Microvasculature, Scott Swarbreck

Electronic Thesis and Dissertation Repository

Sepsis, a systemic inflammatory response to an infection, is a significant cause of morbidity and mortality worldwide. The microcirculation during sepsis fails, in part, due to microthrombosis and the resulting plugging of capillaries, precipitating organ failure. Intravenous injection of ascorbate has been shown to reduce capillary plugging, however the mechanism of this protective effect is unclear. We hypothesized that ascorbate-mediated destabilization of the microthrombi through promoting fibrinolysis could contribute to this protection.

We showed that streptokinase, a pro-fibrinolytic agent, reduced the capillary plugging to a similar degree as ascorbate. This similarity provided the impetus for studying the effect of ascorbate …