Medicine and Health Sciences Commons^™

Pharmacological Characterization Of Novel Serotonin Transporter Inhibitors Identified Through Computational Structure-Based Virtual Screening, Michael Wasko

Electronic Theses and Dissertations

Depression is a mental health disorder affecting greater than 350 million people worldwide with roughly 7% of the United States population diagnosed as of 2017. The selective serotonin reuptake inhibitors (SSRIs) have been the mainstay of pharmacotherapies for depression for the last 40 years. The SSRIs target the serotonin transporter (SERT), a monoamine transporter (MAT) responsible for terminating serotonergic neurotransmission. The SSRIs are not perfect therapeutics and suffer from delayed response times, inconsistent efficacy among patients, and often produce intolerable side effects. Therefore, a strong need exists to develop new antidepressants that are more efficacious and have fewer adverse effects. …

Retrospective Cohort Study Of Patients With Chronic Low Back Pain In An Outpatient Pain Specialist Clinic, Gauri Desai

Electronic Theses and Dissertations

Background: Chronic low back pain (LBP) is a back pain that lasts for three or more than three months in the lumbar region of the spinal cord. A nerve injury or damage in the spinal cord region (neuropathic pain) requires multimodal treatment approach for pain reduction. With various treatment options utilized in the pain management of these patients, identifying demographical and clinical characteristics of patients with chronic LBP utilizing interventional procedures and pharmacologic treatments is imperative.

Objective: (i) To describe the demographics (age, gender, race, ethnicity, smoking status, alcohol consumption status, drug use status) and clinical characteristics (procedures, medications) …

Design And Synthesis Of Pyrimidine Based Fused Heterocyclics In The Potential Treatment Of Cancer And Opportunistic Infection, Farhana Islam

Electronic Theses and Dissertations

Dose-limiting toxicities of clinically used agents and development of resistance are two significant limitations in cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with dual antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid drug-drug interactions, lower the drug dose, decrease overlapping toxicities, and delay or prevent tumor cell resistance. The work in this dissertation reflects the progress of fused …

Health Insurance Plan Design And Chronic Disease Management, Daniel E. Feldman

Electronic Theses and Dissertations

Each year, Americans spend more money on health care than any other industrialized nation, despite comparable mortality rates for people with risk factors for heart disease. The reasons for this lack of health care value in the US are numerous and complex – including market distortions like supplier-inflated pricing and regulatory structures that enable consumers to utilize ubiquitous, high-cost medical technologies that yield uncertain benefits. Health insurance, once thought to be an insignificant contributor to rising health spending, has changed considerably in the past few decades in ways that make it more accessible and more generous in coverage. Health insurance …

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapies In Cystic Fibrosis: A Retrospective Evaluation Of A Nationwide Specialty Pharmacy Database, Zumi Mehta

Electronic Theses and Dissertations

Background: Cystic fibrosis (CF) is a progressive, genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CF experience excessive mucus build up and infections leading to complications in the pancreas, lungs, and other organs. There has been a paradigm shift in the treatment of CF with the introduction of CFTR modulator therapies and given their high acquisition cost, assessing their economic burden along with the adherence rate of patients is imperative. Objective: (i) To assess the utilization of CFTR modulator therapies in a specialty pharmacy CF patient population and (ii) to calculate …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Sulforaphane Protects Against Ethanol-Induced Apoptosis And Teratogenesis Through Epigenetic Modulation Of Anti-Apoptotic Genes., Yihong Li

Electronic Theses and Dissertations

Background. Ethanol-induced excessive apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is one of the major mechanisms underlying the pathogenesis of Fetal Alcohol Spectrum Disorders (FASD). However, the molecular mechanisms underlying FASD that results from maternal alcohol exposure during pregnancy are poorly understood. The overall goals of this study are to examine the mechanisms by which ethanol induces apoptosis and malformations in vitro and in vivo, and to develop a nutritional-based approach by using SFN and SFN-rich BSE to prevent FASD through epigenetic modulation. Results. This study demonstrates that ethanol exposure resulted in a significant increase …

Profiling Transcription And Retrotransposition Of Mouse L1 Subfamilies, Lingqi Kong

Electronic Theses and Dissertations

Transposable elements, also called jumping genes, comprise almost 45% of the human genome. In contrast, only 1% of the human genome is protein-coding sequences. The function and advantages of maintaining such massive copies of transposable elements in the human genome are still unclear. Long interspersed element 1 (L1), the most substantial group and the only active autonomous transposable element in the human genome, has revealed its unique roles in many diseases. The insertional mutagenesis induced by L1 retrotransposition events could threaten human genomic stability and generate unexpected mutations. L1 overexpression has been documented in both somatic and germline cells and, …