Medicinal Chemistry and Pharmaceutics Commons^™

Results Of A Phase 1, Randomized, Placebocontrolled First-In-Human Trial Of Griffithsin Formulated In A Carrageenan Vaginal Gel, Natalia Teleshova, Maria J. Keller, José A. Fernández Romero, Barbara A. Friedland, George W. Creasy, Marlena G. Plagianos, Laurie Ray, Patrick Barnable, Larisa Kizima, Aixa Rodriguez, Nadjet Cornejal, Claudia Melo, Gearoff Cruz Rodriguez, Sampurna Mukhopadhyay, Giulia Calenda, Shweta U. Sinkar, Thierry Bonnaire, Asa Wesenberg, Shimin Zhang, Kyle Kleinbeck, Kenneth Palmer, Mohcine Alami, Barry R. O'Keefe, Patrick Gillevet, Hong Hur, Yupu Liang, Gabriela Santone, Raina N. Fichorova, Tamara Kalir, Thomas M. Zydowsky

Publications and Research

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n …

Creating A Pre-Illness Covid-19 Action Plan: A Web-Based Public Education Initiative, Brian S. Hustad

DNP Research Projects

Abstract

Background: The COVID-19 pandemic took the world by storm in the beginning stages of 2020. Public health agencies were overwhelmed, undermanned, and therefore slow to respond. Information began to flow at an unprecedented rate. Yet, very limited resources were put into place to present this information or to instruct the public on evidence-based prevention, treatment, or care at home during active infection.

Intervention: A project website was created and accessed through a QR code on the project flyer or by entering the URL into any browser. Participants were able to access three evidence- based video modules, which introduced the …

Small G- Protein Regulators Of Islet Beta Cell Function, Suhadinie Sameera Gamage

Wayne State University Dissertations

Defects in insulin secretion from pancreatic islet beta- cells leads to long term complications such as type 2 diabetes mellitus. The mechanism and regulation of glucose stimulated insulin secretion (GSIS) as well as factors contributing to pancreatic islet beta-cell demise are yet poorly understood. Previous work from our laboratory demonstrated that Ras-related C3 botulinum toxin substrate 1 (Rac1), a small G- protein is involved in GSIS as well as in culminating dysfunction under metabolic stress. Cycling of Rac1 between its inactive and active form is considered a vital event in glucose stimulated insulin secretion. This conversion is made possible by …

The Arsenic Induced Endoplasmic Reticulum Stress Response Via The Activating Transcription Factor 6 In Human Bronchial Epithelial Beas-2b Cells, Priya Wadgaonkar

Wayne State University Dissertations

Arsenic is a well-known human carcinogen associated with a number of cancers, including lung cancers. We have previously shown that long-term exposure to an environmentally relevantconcentration of inorganic arsenic (As3+) leads to the malignant transformation of the BEAS-2B cells, and some of the transformed cells show cancer stem-like features (CSCs) with a significant upregulation of glycolysis and downregulation of mitochondrial oxidative phosphorylation. In the present report, we investigate the short-term effect of As3+ on the endoplasmic reticulum (ER) stress response—the “unfolded protein response (UPR)” and metabolism in human bronchial epithelial cell line BEAS-2B cells. Treatment of the cells with inorganic …

Fair Resource Allocation To Reduce Inequalities In Criminal Justice & Healthcare, Alex Liu, Alexia Rodrigues

Discovery Undergraduate Interdisciplinary Research Internship

Together, we are working to identify discrepancies in the criminal justice system that put substance users at an unfair advantage for possible treatment and success in the future. This is done by modeling regressions involving the arrest-rates, developing charts to show the patterns of past arrests, and tracking the resources available for substance users. By doing this, we provide models to the local sheriff office that forecasts incoming inmates which allows the office to prepare accordingly. On the flip side, we are working to create a prediction model that exemplifies the risk of relapse for substance users. Ultimately, our goal …

The Effect Of Pioglitazone On Phosphoproteome And Interactome Of Protein Phosphatase 2a In Primary Human Skeletal Muscle Cells, Lana Alghanem

Wayne State University Dissertations

Skeletal muscle insulin resistance is one of the main contributors to Type 2 Diabetes (T2D), which is a chronic disease affecting 37.3 million people in United States (US), with an estimated annual cost exceeding $300 billion in the US. T2D is being treated with a variety of medications, including Pioglitazone (PIO), a potent insulin sensitizer for skeletal muscle. PIO is a synthetic ligand for the peroxisome proliferator-activated receptor (PPAR-γ), nuclear receptors regulating the expression of many genes involved in lipid and glucose metabolism. To date, the molecular action of PIO that sensitizes muscle to insulin is incompletely understood. Protein phosphorylation …

Using Molecularly Imprinted Polymers For The Selective Extraction Of Analytes, Haley A. Mulder

Theses and Dissertations

Sample preparation is a critical steps in bioanalysis. Traditional methods such as solid-phase extraction and liquid-liquid extraction are laborious and ultimately incapable of properly separating target analytes from matrix and interferents. The co-extraction of these components interferes with the analytical instrument’s ability to properly detect and quantitate analytes. Molecularly imprinted polymers (MIPs) are synthetic polymers that have been “imprinted” with a template analyte in a co-polymer system. MIPs are capable of selectively extracting analytes from complex biological matrices and can be employed in off-line, benchtop extractions or for on/in-line instrument extractions. MIPs offer faster and more selective sample preparation, leading …

Comparison Of Free Versus Encapsulated Drugs On 3t3 Differentiation, Simon H. Friedrich, Gabriel Volpe

Undergraduate Research Posters

The scope of this project was to design, synthesize and test targeted nanoparticles containing hydrophobic and hydrophilic drugs that promote browning in adipose tissue. For hydrophilic drugs the use of liposomes and their hydrophilic core is more useful than the PLGA nanoparticles which have hydrophobic cores. The inhibition of the FOXO1 pathway and modulation of autophagy in adipose tissue can promote browning of white adipose tissue, or an energy burning state where excess energy is burned as heat instead of stored in the cell. If successful, these drugs would offer an alternative treatment for obesity where changes to the patient's …