H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Modification Of Hyaluronic Acid To Enable Click Chemistry Photo-Crosslinking Of Hydrogels With Tailorable Degradation Profiles, Ciara Buckley

Articles

Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that, due to its inherent bioactivity and extracellular matrix-like structure, has the potential to be utilised extensively in tissue engineering. However, this glycosaminoglycan lacks the properties required for cellular adhesion and photo-crosslinking by UV light, which significantly hinders this polymers applicability. This research presents a method for modifying hyaluronic acid via thiolation and methacrylation to generate a novel photo-crosslinkable polymer with improved physicochemical properties, biocompatibility and the potential to customize biodegradability according to the ratio of monomers used. A decrease in stiffness proportional to increasing thiol concentration was observed when testing the …

Investigation Into The Potential For Acquired Cross Tolerances Of Amphetamines, Benjamin Weldon

CMC Senior Theses

In the United States, the treatment of ADHD through use of psychostimulants in adolescents is a growing reality that many people know today and many more will know in the coming years. Although the effectiveness of psychostimulants is a known asset, the benefits of these medications may not be a permanent solution, suggesting not only the presence of a tolerance build up, but as many stimulants are prescribed in a joint effort to combat ADHD, a possible cross tolerance between two prescribed medications. There are minimal studies published that have addressed the topic of cross stimulation tolerance buildup between prescription …

Integration Of Medicinal Fungi Into The Heber W. Youngken Jr. Medicinal Garden, Anthony Makashov

Senior Honors Projects

The Heber W. Youngken Jr. Medicinal Garden is a one-of-a-kind resource that houses close to 300 medicinal plants and is filled to the brim with educational opportunities. For the College of Pharmacy, this garden has been the centerpiece of many classes taught here at the University of Rhode Island and has roots as a physical teaching space. While the garden contains a plethora of plant species, medicinal fungi have yet to have been included in the garden, despite their relevance as both sources of pharmaceutical drug discovery and as natural products with inherent physiological benefits themselves. The purpose of my …

Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman

Chemical Engineering Undergraduate Honors Theses

This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that the programming does …

Antibacterial Activity, Structure-Activity Relationships, And Scale-Up Reaction Of 1,3,4-Oxadiazoles, Olivia Marie Smith

Undergraduate Honors Thesis Projects

Oxadiazoles are compounds in the field of organic chemistry that have been gathering interest in the medicinal chemistry and microbiology communities for their biological properties, which range from anti-inflammatory agents, to chemotherapy drugs, to antibiotics. The synthesis of oxadiazoles can be difficult due to the expensive and complex nature of the techniques used as well as the volatile reagents and elevated temperatures that are often required in organic synthesis. The Grote lab has recently developed a new method for the synthesis of 1,3,4-oxadiazoles under mild conditions. The goals of this thesis were thus twofold: to develop a viable scale-up procedure …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London

Mathematics & Statistics Faculty Publications

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA …

Mechanism For Selective Binding Of Aromatic Compounds On Oxygen-Rich Graphene Nanosheets Based On Molecule Size/Polarity Matching, Heyun Fu, Bingyu Wang, Dongqiang Zhu, Zhicheng Zhou, Shidong Bao, Xiaolei Qu, Yong Guo, Lan Ling, Shourong Zheng, Pu Duan, Jingdong Mao, Klaus Schmidt-Rohr, Shu Tao, Pedro J.J. Alvarez

Chemistry & Biochemistry Faculty Publications

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match–based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding …

Colchicine, Covid-19 And Hematological Parameters: A Meta-Analysis, Musharraf Sarwar, Zahid Ali, Mahnoor Fatima, Zouina Sarfraz, Azza Sarfraz, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Introduction: Colchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients.
Methods: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, …

Pharmacologic And Clinical Considerations Of Nalmefene, A Long Duration Opioid Antagonist, In Opioid Overdose., Amber N. Edinoff, Catherine A. Nix, Tanner D. Reed, Elizabeth M. Bozner, Mark R. Alvarez, Mitchell C. Fuller, Fatimah Anwar, Elyse M. Cornett, Adam M. Kaye, Alan D. Kaye

School of Medicine Faculty Publications

No abstract provided.

Molecular Analysis Of Mchm Toxicity In Zebrafish, Cassandra Pelton

Honors College Theses

In early 2014 Freedom Industries, located in Charleston, WV, leaked approximately 10,000 gallons of 4-methylcyclohexane methanol into the Elk River. This river serviced approximately 300,000 people as a source of municipal water. Its effects on the people and surrounding wildlife is largely unknown.

Chemicals in surface runoff have the potential to induce aquatic animal trait changes, such as altered movement and feeding, that can ultimately alter predator-prey dynamics in aquatic systems. However, chemicals with high potential to enter aquatic systems, like 4-methylcyclohexane methanol (MCHM) used to clean coal, were tested using only short-term, single-species studies prior to use. Data from …

Research Of Properties Of Polycondensation Type Phosphoric Acid Cationic Exchange Resins, Khasan Makhmudov, M Egamberdiyeva, A Yuldashev, T Tursunov, R Nazirova, S Turabjanov Dsc, B Kedelbaev

Technical science and innovation

One of the main properties of ion exchangers is their exchange capacity. Static exchange capacity of the new phosphorus acid cationic exchange resins obtained by phospholysis of polymer based on cube waste of the Shurtan gas chemical complex and a secondary product of hydrolysis industry - furfural was determined by alkalometric titration using 0.1 N solution of NaOH and NaCl, capacity by phosphorus content in ionite and capacity by curves of potentiometric titration. The values of exchange capacity found by the above methods are almost indistinguishable from each other. The cationite belongs to moderately acidic ions, the found values of …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Formulation Of Coffee Extract As Polymeric Nanoparticles And Studying Their Potential Biological Activities, Nouran Sharaf

Theses and Dissertations

Coffee extract was prepared and optimized (by solvent extraction) and subsequently entrapped into PLGA nanoparticles using single emulsion-solvent evaporation method (using Design Expert software). Dynamic Light Scattering, Scanning Electron Microscope, Fourier Transform-Infrared Spectroscopy and Folin Ciocalteau assay were used to characterize the NPs and to aid in selecting the optimum formulation conditions. The optimized NPs were in-vitro evaluated for their antimicrobial (by agar-well diffusion method), antioxidant (by DPPH assay) and anticancer (by MTT assay) activities. Finally, the release rate study was conducted for the NP sample showing the highly promising results.

The succeeded NP sample, in terms of the most …

Identifying The Cardiovascular Effects Of Multiple Pollutants., Katlyn Elizabeth Mcgraw

Electronic Theses and Dissertations

Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to PM_2.5 is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD is less clear. Overall, this work aimed to examine the effect of pollutants with lesser documented effects on cardiovascular disease using a multi-pronged approach to exposure assessment. The three aims were to examine the relationship between county-level toxic chemical releases and CVD mortality in the contiguous United States between 2002 and 2012, to assess the relationship between individual-level VOC metabolites and vascular function, and to build multipollutant …

Mediation Of The Uncoupled Enos Pathway Following Oxidative Stress Using Tetrahydrobiopterin And Nitric Oxide Donor Drugs To Restore Tetrahydrobiopterin Concentration, Brianna Munnich

Scholar Week 2016 - present

Presentation Location: Warming House, Olivet Nazarene University

Abstract

The eNOS pathway, found in the endothelium of blood vessels, is a key regulator of nitric oxide levels in the circulatory system. The pathway is controlled through several positive and negative feedback loops [2]. The cofactor tetrahydrobiopterin (BH4) is a major control point in this pathway and under conditions of stress can be reduced into the dihydrobiopterin (BH2) [2,6,7,8,9]. When the reduced form is predominant, the pathway produces reactive oxygen species (ROS) rather than nitric oxide, causing stress and damage to the vessels [6,7,8,9]. In this study, different treatments were studied …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Retrospective Review Of Anticoagulation Regimens Used For The Prevention Of Venous Thromboembolisms In Critically Ill Patients Infected With Sars-Cov-2, Tony Nguyen, Heidi Clarke

All Publications

No abstract provided.

A Comparison Of 4-Year Total Medical Care Costs, Adverse Outcomes, And Opioid/Prescription Analgesic Use For 3 Knee Osteoarthritis Pain Treatments: Intra-Articular Hyaluronic Acid, Intra-Articular Corticosteroids, And Knee Arthroplasty., John Mackowiak, John T Jones, Vinod Dasa

School of Medicine Faculty Publications

To compare the medical costs associated with treatments for knee osteoarthritis (OA): intra-articular corticosteroids (ICS) and intra-articular hyaluronic acid (IHA) primarily, and ICS/IHA vs knee arthroplasty (TKA) secondarily. This was a retrospective analysis of an insurance claims database. Eligible members had diagnosed OA and no claims for ICS, IHA, or TKA during the 6–18-month look-back period. Cohorts of interest over the 4-year observation period were: patients who received ICS only, those who received IHA only, and those who received TKA only. Outcomes assessed included: (1) total allowed medical costs, (2) claims for pre-specified, treatment-related adverse outcomes and costs, and (3) …