Chemicals and Drugs Commons^™

Lessons From Canada’S Notice Of Compliance With Conditions Policy For The Life-Cycle Regulation Of Drugs, Melanie Mcphail, Howard Zhang, Zohra Bhimani, Tania M. Bubela

Office of the Provost

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada's regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market …

Contrast-Enhanced Cardiac Magnetic Resonance Imaging With A Manganese-Based Alternative To Gadolinium For Tissue Characterization Of Acute Myocardial Infarction, Benjamin P. Bonner, Salva R. Yurista, Jaume Coll-Font, Shi Chen, Robert A. Eder, Anna N. Foster, Khoi D. Nguyen, Peter Caravan, Eric M. Gale, Christopher Nguyen

School of Medicine Faculty Publications

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance imaging is an effective and reproducible method for characterizing myocardial infarction. However, gadolinium-based contrast agents are contraindicated in patients with acute and chronic renal insufficiency. In addition, several recent studies have noted tissue deposition of free gadolinium in patients who have undergone serial contrast-enhanced magnetic resonance imaging. There is a clinical need for alternative forms of magnetic resonance imaging contrast agents that are acceptable in the setting of renal insufficiency. METHODS AND RESULTS: Three days after 80 minutes of ischemia/reperfusion of the left anterior descending coronary artery, cardiac magnetic resonance imaging was performed …

Moderate-Intensity Exercise Improves Mesenteric Arterial Function In Male Uc Davis Type-2 Diabetes Mellitus (Ucd-T2dm) Rats: A Shift In The Relative Importance Of Endothelium-Derived Relaxing Factors (Edrf), Md Rahatullah Razan, Said Amissi, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric …

Pyrazole-Sulfonamide Scaffold Featuring Dual-Tail Strategy As Apoptosis Inducers In Colon Cancer, Amira Khalil, Reham M. M. El Hazek, Nashwa H. Zaher, Hagar E. S. Emam, Marwa G. Elgazzar

Pharmacy

Dual-tail strategy has been successfully utilized in the development of novel carbonic anhydrase IX (CA IX) inhibitors. Herein we adopted this approach in the design and synthesis of a series of novel pyridine sulfonamide-pyrazole hybrid scaffold mimicking dual-tail inhibitors of CA IX. A library of 15 compounds was synthesized and assessed for their potential cytotoxic effects against colorectal cancer cells. Compounds 3, and 11 induced potential cytotoxic effects against the three cancer cell lines (HCT-116, HT-29, and SW-620) with IC₅₀s’ of 45.88, 28.27, and 16.57 uM, 25.01, 8.99, and 3.27 µM, respectively. Both compounds induced cellular apoptosis …

A Scoping Review Of Risk And Protective Factors For Negative Cannabis Use Consequences, Timothy J. Grigsby, Andrea Lopez, Larisa Albers, Christopher J. Rogers, Myriam Forster

Social and Behavioral Health Faculty Research

Objective:

Numerous reviews have examined risk and protective factors for alcohol-related negative consequences, but no equivalent review of risk and protective factors exists for cannabis-related negative consequences (CRNCs)-a gap filled by the present study. This scoping review examined survey-based research of risk and protective factors for CRNCs such as neglecting responsibilities, blacking out, or needing more cannabis.

Methods:

Three databases (PubMed, PsycINFO, and Google Scholar) were searched for peer-reviewed manuscripts published between January 1, 1990, and December 31, 2021. A qualitative synthesis was performed using the matrix method and the results were organized using the socioecological model as a framework. …

Upregulation Of Cell Surface Glycoproteins In Correlation With Kshv Lana In The Kaposi Sarcoma Tumor Microenvironment, Sara R. Privatt, Owen Ngalamika, Jianshui Zhang, Qinsheng Li, Charles Wood, John T. West

School of Medicine Faculty Publications

HIV-associated epidemic Kaposi sarcoma (EpKS) remains one of the most prevalent cancers in sub-Saharan Africa despite the widespread uptake of anti-retroviral therapy and HIV-1 suppression. In an effort to define potential therapeutic targets against KS tumors, we analyzed previously published KS bulk tumor transcriptomics to identify cell surface biomarkers. In addition to upregulated gene expression (>6-fold) in the EpKS tumor microenvironment, biomarkers were selected for correlation with KSHV latency-associated nuclear antigen (LANA) expression. The cell surface glycoprotein genes identified were KDR, FLT4, ADAM12, UNC5A, ZP2, and OX40, as well as the endothelial lineage determinants Prox-1 and CD34. Each protein …

Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Lorealaus: Lorlatinib Real-World Australian Experience In Advanced Alk-Rearranged Nsclc, Marliese Alexander, Joe Wei, Sagun Parakh, Thomas John, Steven Kao, Adnan Nagrial, Samantha Bowyer, Lydia Warburton, Melissa Moore, Brett G. M. Hughes, Timothy D. Clay, Nick Pavlakis, Benjamin J. Solomon, Malinda Itchins

Research outputs 2022 to 2026

Introduction: Over the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with ALK-positive (ALK+) lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival. Methods: Multicenter real-world study of individuals with pretreated advanced ALK+ lung cancers managed on a lorlatinib access program between 2016 and 2020. Key outcomes were lorlatinib efficacy, tolerability, and treatment sequencing. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method among all individuals (PFSa and OSa), with at least 30 days (one-cycle) lorlatinib exposure (PFSb and OSb), and with good performance status (PFSc …

Phase Ib Study Of Talimogene Laherparepvec In Combination With Atezolizumab In Patients With Triple Negative Breast Cancer And Colorectal Cancer With Liver Metastases, J. R. Hecht, S. S. Raman, A. Chan, K. Kalinsky, J. F. Baurain, M. M. Jimenez, M. M. Garcia, M. D. Berger, U. M. Lauer, Adnan Khattak, A. Carrato, Y. Zhang, K. Liu, E. Cha, A. Keegan, S. Bhatta, C. P. Strassburg, A. Roohullah

Research outputs 2022 to 2026

Background: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases.ncidence, and secondary endpoints included efficacy and AEs. Methods: In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤ 4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg …

March / April 2023, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the March & April 2023 issue of Rural Rocks from the SWOSU College of Pharmacy.

Synthesis And Characterization Of Some Disubstituted Cyclopentadienyl Rhenium Complexes As Potential Candidates In Semiconductive Materials, Chloe Vernon

Senior Honors Theses

Since 2000, when the Nobel Prize in Chemistry as awarded for conductive polymer research few studies have been performed concerning the conductive capabilities of discrete organometallic compounds. For this project, organometallic compounds were formed specifically with a transition metal included in the structure. Through oxidation and reduction reactions, the variation in the electrical conductivity could allow for an analysis of whether this unique structure would allow for tunability. The goal of this research was to begin with aromatic substituted fulvenes and perform various multistep synthesis processes, utilizing thallium salt intermediates, to produce several disubstituted cyclopentadienyl rhenium complexes. In this project, …

Mandates, Mistrust, And Misconceptions: An Overview Of Vaccine Hesitancy, Evelyn Ryan

Senior Honors Theses

Vaccines are one of the most successful ways to prevent diseases and are considered one of the most influential achievements in the history of public health. While vaccines have many benefits, the number of parents that refuse vaccinations for their children is increasing. People are concerned about potential risks and health problems that are thought to result from vaccination. There are risks and contraindications involved with vaccines, but many reasons for vaccine hesitancy that are cited by the public are not founded on evidence-based data. When making vaccine decisions, it is essential that the public has accurate information and that …

Efficacy Of Kidney Reperfusion Treatments Relative To Function And Survival Rates After Transplantation, Mitchell Rohr

Senior Honors Theses

Donor kidneys are damaged upon circulatory death before being preserved with machine perfusion until transplantation. During machine perfusion, blood is pumped back into the vasculature of the kidney, causing damage called ischemic reperfusion injury. The two forms of machine perfusion are hypothermic machine perfusion and normothermic machine perfusion. Different methods of treatment can be used during either hypothermic machine perfusion or normothermic machine perfusion to prevent ischemic reperfusion injury. Each of the treatment methods that were reviewed showed potential for preventing ischemic reperfusion injury, with hypothermic treatments having higher average levels of feasibility than normothermic treatments. The effect of the …

Triazole Compounds – Potentials In The Treatment Of Cystic Fibrosis, Maggie Taylor

Undergraduate Research Conference

Cystic Fibrosis (CF) is a genetic disease that affects the respiratory and digestive system and is most common among Caucasians of Northern European origin. CF is caused by mutations in a membrane protein CFTR (Cystic Fibrosis Transmembrane-conductance Regulator). This mutation impairs the membrane protein’s chloride ion channel function. One of the most common CFTR mutations is the DF508 mutation that affects over 70% of CF cases. Our research has shown that the DF508-CFTR mutation can be partially reversed by physical and chemical means [Heda & Marino, BBRC, 271:659-664, 2000]. In cell lines expressing DF508-CFTR, synthetic anion carriers have shown to …

Gh-05 Exploring Drug Efficacy In The Pediatric Population: Determining The Differences Among Various Drug Classes, William F. Gardner Ii, Brooks T. Mcphail

SC Upstate Research Symposium

Exploring Drug Efficacy in the Pediatric Population: Determining the Differences Among Various Drug Classes

William F. Gardner II¹, M. Jacob Wurst¹, Brooks McPhail, PhD^1,2

¹University of South Carolina School of Medicine Greenville, Greenville, SC,

²Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Introduction: Pharmacodynamics is commonly defined as what the drug does to the body. The pharmacodynamic effects of a drug are required to determine its efficacy and safety. Due to the unique nature of pediatric development, and the challenges in doing research on children, the efficacy and safety of many drugs are …

Xylazine In The Opioid Epidemic: A Systematic Review Of Case Reports And Clinical Implications, Shahana Ayub, Shanli Parnia, Karuna Poddar, Anil K. Bachu, Amanda Sullivan, Ali M. Khan, Saeed Ahmed, Lakshit Jain

School of Medicine Publications

Introduction and objectives: The opioid overdose epidemic is exacerbated by the emergence of Xylazine as an illicit drug adulterant. Xylazine, a veterinary sedative, can potentiate opioid effects while also causing toxic and potentially fatal side effects. This systematic review aims to assess the impact of Xylazine use and overdoses within the opioid epidemic context.

Method: A systematic search was conducted following PRISMA guidelines to identify relevant case reports, and case series related to Xylazine use. A comprehensive literature search included databases like Web of Science, PubMed, Embase, and Google Scholar, utilizing keywords and Medical Subject Headings (MeSH) terms related to …

Potential Of Dietary Flavonoids In The Prevention And Therapy Of Covid-19 : Focusing In Mast Cell - Calcium Ion Channel Axis, Aryo Tedjo

Indonesian Journal of Medical Chemistry and Bioinformatics

Syndrome Acute Respiratory Syndrome Corona Virus-2 (SARS COV2) is the virus that causes the COVID19 disease and has caused more than 4 million deaths worldwide. This virus infects the host cell through the interaction between the virus’s glycoprotein S molecule with the ACE2 which is the virus receptor, binding, undergoes membrane fusion and enters the cell and replicates in it. Currently, several strategies used in developing anti-viral compounds are targeting compounds that play a role in the process of entering the virus into host cells such as ACE2, S glycoprotein, and TMPRSS2, while some target main proteases such as RNA …

Accelerometry-Based Analysis Of Postural Sway In Parkinson's Disease Patients With Levodopa-Induced Dyskinesia, Chandler Brock

UNO Student Research and Creative Activity Fair

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, with patient numbers projected to double to 12 million in the next 20 years. Levodopa-induced dyskinesia (LID) is a major problem associated with the long-term use of levodopa for symptomatic treatment of PD. These involuntary movements can become disabling and may interfere with quality of life. Our prior research showed that PD w/ LID were less stable while standing (i.e., increased postural sway) and had a higher incidence of falls. The aim of this study is to determine if postural sway properties are altered by LID via decomposing the sway signal. We …