Chemicals and Drugs Commons^™

Cenobamate Use In Pregnancy: A Case Report, Tiara Paul, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.

Elv-N34, Rvd6-Isomer, Or Npd1 Halt Replication Of Sars-Cov-2 Omicron Ba.5 Virus In Human Lung And Nasal Cells, Jorgelina M. Calandria, Haydee E. Bazan, Surjyadipta Bhattacharjee, Marie-Audrey I. Kautzmann, Nicholas J. Maness, Nicolas G. Bazan

School of Medicine Faculty Publications

Current vaccines rely on the sequence of Spike (S) protein to induce immunity against the severe acute respiratory coronavirus-2 (SARS-CoV-2) virus. Because of the high mutation rate of the viral S protein, new mutant strains are developed to generate new infectivity profiles. Bioactive lipid mediators (LMs) derived from docosahexaenoic acid (DHA) are synthesized on demand to sustain homeostasis. The purpose of this study was to determine the action of selected LMs in the viral replication of SARS-CoV-2 Omicron BA.5 variant in human lung and nasal epithelial cells. Cells from healthy donors were infected with Omicron BA.5 for one hour and …

Integrative Computational Modeling Of Distinct Binding Mechanisms For Broadly Neutralizing Antibodies Targeting Sars-Cov-2 Spike Omicron Variants: Balance Of Evolutionary And Dynamic Adaptability In Shaping Molecular Determinants Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we conducted a comprehensive analysis of the interactions between the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and four neutralizing antibodies—S309, S304, CYFN1006, and VIR-7229. Using integrative computational modeling that combined all-atom molecular dynamics (MD) simulations, mutational scanning, and MM-GBSA binding free energy calculations, we elucidated the structural, energetic, and dynamic determinants of antibody binding. Our findings reveal distinct dynamic binding mechanisms and evolutionary adaptation driving the broad neutralization effect of these antibodies. We show that S309 targets conserved residues near the ACE2 interface, leveraging synergistic van der Waals and electrostatic interactions, while S304 focuses on …

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

The Effect Of Nonsteroidal Anti-Inflammatory Drugs On Union Rates Following Operative Repair Of Distal Radius Fractures, Michael Chang, Alexis Kasper, Juliet Chung, Justin Wright, Margaret Pennington, Asif M. Ilyas

Student Papers, Posters & Projects

Purpose

Methods

Methylprednisolone After Shoulder Arthroplasty Leads To Decreased Opioid Prescriptions Without An Increased Risk Of Infection: A Matched Cohort Analysis, Tej Joshi, Tuckerman Jones, Akhil Katakam, Daniella Ogilvie, Amanda Azer, Sefy Paulose, Balazs Galdi

Jefferson Hospital Staff Papers and Presentations

Background

Methods

Fear And Oxytocin: Effects Of Intraperitoneal Pretreatment In Rats, Daniel Yeromenko, Kelsie German, Eros Fuentes, Jenna Meade, Ben Bustos

2025 Symposium

INTRODUCTION: Oxytocin is a neuropeptide widely known for its role in social bonding and emotional regulation. Recent studies have suggested its involvement in modulating fear, stress, and anxiety responses, potentially offering therapeutic applications for trauma-related disorders such as PTSD. This study investigated whether pretreatment with oxytocin reduces behavioral and physiological fear responses in male and female Sprague-Dawley rats using a classical fear conditioning model. METHODS : Twenty-four Sprague-Dawley rats (12 males, 12 females) were assigned to one of four groups: control (no shock, no oxytocin), shock only, shock + low-dose oxytocin (0.5 mg/kg), and shock + high-dose oxytocin (1.0 mg/kg). …

Preparation And In-Vitro Evaluation Of Dompridone Oral Thin Film, Fatima Mohammed Hussein Wais

Maaen Journal for Medical Sciences

The aim of the current study was to formulate and evaluatedompridone nanoparticles and loaded in oral fast dissolve film, for enhance the solubility of poor water soluble dompridone by nanoparticles and fasten the action by prepared as oral thin film and also to improve patient compliance. Domperidone is the recommended medication for nausea and vomiting brought on by viral infections, chemotherapy, migraines, and food poisoning.Domperidonenanoparticles were made using two type of polymers (hydroxypropyl methylcellulose HPMC-K15 and methylcellulose MC-A4C) in a range of ratios (1:1, 1:2, and 1:3) drug:polymer ratio by solvent antisolvent technique. In nanoparticle formulation, HPMC-K15 and MC-A4C were …

Spravato® Fda-Approved As Monotherapy For Adults With Treatment-Resistant Depression, Rileigh Rahrig, Kennedy Kosikowski, Haylee Whyde, Kiley Devoll, Allie Honigford, Macy Davis, Joshua Honaker, Samantha Mccord, Manoranjan D'Souza

Pharmacy and Wellness Review

Treatment-resistant depression (TRD) is a challenging and possibly life-threatening condition that affects millions of people worldwide. Patients with major depressive disorder (MDD) are diagnosed with TRD once they have tried and failed to respond to two antidepressant treatments at the maximum dose for a full trial of six to eight weeks. Most traditional antidepressant therapies work by increasing the levels of monoamine neurotransmitters such as dopamine, serotonin, and norepinephrine in the brain. These medications have a delayed onset of action, ranging from two to eight weeks, and often fail to relieve depressive symptoms in a patient with TRD. Therefore, targeting …

Tacrolimus Dosing In Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial, Jeffrey Khong, Megan Lee, Curtis Warren, Un Kim, Sergio Duarte, Kenneth Andreoni, Sunaina Shrestha, Mark Johnson, Narendra Battula, Danielle Mckimmy, Thiago Beduschi, Ji-Hyun Lee, Derek Li, Chih-Ming Ho, Ali Zarrinpar

Department of Surgery Faculty Papers

Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large …

Reducing Premedication Use With Intravenous Iron In The Outpatient Setting, Tara Rakiewicz, Liam Heneghan, Mark Attilio, Ruben Rhoades, Michael Zimmerman, Matthew Tucker, Brianna Costello, Adam Binder, Tanya Thomas

Health Equity and Quality Improvement (HEQI) Summit

Background

• Intravenous (IV) formulations of iron are safe, quick, easy to administer, and are indicated in patients with Iron Deficiency.
• Prior formulations of IV iron were associated with anaphylaxis and have since been removed from the market -- healthcare workers remain anxious about their potential for reactions
• Rate of anaphylactic reactions are about 1 in 200,000 infusions
• Current IV formulations available can be associated with a complement mediated, pseudo-allergy, that presents with flushing, myalgia/arthralgia, and chest pressure. Reactions are dependent on infusion rate and improve after stopping the infusion.
• Premedication with acetaminophen and diphenhydramine are often ordered for IV iron …

Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton

School of Medicine Faculty Publications

In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically …

Physiologically Based And Population Pharmacokinetic Modeling Of Midazolam In Children With Obesity Using Real-World Data, Sean Mccann, Victória E. Helfer, Stephen J. Balevic, William J. Muller, John N. Van Den Anker, Amira Al-Uzri, Marisa L. Meyer, Sarah G. Anderson, Sitora Turdalieva, Andrea N. Edginton, Daniel Gonzalez, Best Pharmaceuticals For Children Act Pediatric Trials Network Steering Committee

Department of Pediatrics Faculty Papers

Children represent a highly complex and variable population for treatment, including interindividual differences in drug dose-exposure. Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity. Population pharmacokinetic modeling assessed whether measures of …

Chronic Inflammation: The Link Between A High Added Sugar Diet And Disease, Anna Collins

Senior Honors Theses

The modern diet includes many processed foods that contain added sugars, resulting in a significant increase in daily glucose and fructose consumption. Considering this, there is an increased effort to uncover the effects of excess sugar intake on the body’s health and metabolism. Strong evidence supports the connection between a high added sugar diet and the presence of chronic, low-grade inflammation due to cellular distress and metabolic dysfunction. Prolonged inflammatory responses are linked to tissue damage and the development of various metabolic diseases that are prevalent in modern society, such as obesity, fatty liver disease, cardiovascular disease, and type 2 …

Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-Contractile Effect Of Benzodiazepines On Airway Smooth Muscle, Dominic R. Villalba, Arun K. Jannu, Elham Javed, Isha Dandekar, Ruping Wang, Deepak A. Deshpande, Steven S. An, Reynold A. Panettieri, Dale D. Tang, Raymond B. Penn, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

BACKGROUND: We recently reported that the ovarian cancer G protein-coupled receptor-1 (OGR1) can be pharmacologically biased with specific benzodiazepines to couple with distinct heterotrimeric G proteins in human airway smooth muscle (ASM) cells. Lorazepam stimulated both G

METHODS: Models of histamine (His) -stimulated contraction included imaging of ex vivo human precision cut lung slices (hPCLS) and Magnetic Twisting Cytometry (MTC) analysis of human ASM cell stiffness. To explore mechanisms of regulation, we examined effects on myosin light chain (pMLC) phosphorylation and PKA activity in primary human ASM cultures, as well as actin cytoskeleton integrity as defined by changes in the …

Probing Binding And Allosteric Mechanisms Of The Kras Interactions With Monobodies And Affimer Proteins : Ensemble-Based Mutational Profiling And Thermodynamic Analysis Of Binding Energetics And Allostery Reveal Diversity Of Functional Hotspots And Cryptic Pockets Linked By Conserved Communication Network, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Guang Hu, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

KRAS, a historically "undruggable" oncogenic driver, has eluded targeted therapies due to its lack of accessible binding pockets in its active state. This study investigates the conformational dynamics, binding mechanisms, and allosteric communication networks of KRAS in complexes with monobodies (12D1, 12D5) and affimer proteins (K6, K3, K69) to characterize the binding and allosteric mechanisms and hotspots of KRAS binding. Through molecular dynamics simulations, mutational scanning, binding free energy analysis and network-based analyses, we identified conserved allosteric hotspots that serve as critical nodes for long-range communication in KRAS. Key residues in β-strand 4 (F78, L80, F82), α-helix 3 (I93, H95, …

A Chemical Investigation: Monitoring Cannabidiol Concentration In The Presence Of Ionic Liquids, Hannah E. Mabie

Honors Theses

Cannabidiol (CBD) is a non-psychoactive cannabinoid from the plant, Cannabis sativa. CBD’s structure degrades over time and other minor cannabinoids are formed when in contact with organic solvents. This is a growing area of interest due to the Agriculture Improvement Act (The Farm Bill) in 2018, which led to growing marijuana consumption and increased CBD markets. Monitoring the concentration of CBD can be used by forensic investigators and researchers to determine how CBD interacts with solvents, like ionic liquids. In this study, different ionic liquids were used to determine the best route of solubility and if choline based ionic liquids …

Menthalactone From Mentha Piperita L., A Monocot-Selective Bioherbicide, Adam Soltani

Honors Theses

The challenge of managing invasive weed species continues to affect the agricultural industry, presenting ecological, economic, and agronomic hurdles that lead to over 100 billion USD in annual crop losses globally. One such concern is the management of Agrostis stolonifera L., commonly known as creeping bentgrass, particularly due to its ability to form hybrids. This scenario underscores the urgent need for innovative, effective, and environmentally sustainable herbicides, steering the focus toward natural substances as potential candidates. We report here a promising natural lactone, commonly known as menthalactone, which is derived from Mentha piperita L. Its phytotoxic activity was assessed against …

Investigating The Cytotoxic Effects Of Amino Acid-Based Ionic Liquids And Peg-Pla Nanoparticles On Mcf10a Human Breast Epithelial Cells For Drug Delivery Applications, Ella C. Mertins

Honors Theses

This study investigates the cytotoxic effects of polyethylene glycol-polylactic acid (PEG-PLA) nanoparticles (NPs) both bare and coated with choline-based ionic liquids (ILs) on MCF10A human breast epithelial cells. The goal was to evaluate how IL-modified NPs influence cell viability at varying concentrations and to assess their potential as drug delivery systems. Three choline-based ILs, Choline-L-Asparagine 1:1, Choline-DL-Isoleucinate 1:1, and Choline-L-Leucinate 1:1, were used as surface coatings for PEG-PLA NPs. Additionally, the ILs were tested independently to establish a baseline for their cytotoxicity. Using a luminescent ATP-based viability assay following the treatment of MCF10A cells, the ILs were found to be …

Validating The Ability Of Iag933 To Block The Interaction Of Yap1 And Tead In Ovarian Cancer Cells, Alex Sage

Theses & Dissertations

Ovarian cancer is the most common and deadliest gynecologic malignancy. Approximately 40% of ovarian cancer patients exhibit chemoresistance after receiving initial treatment in the form of neoadjuvant chemotherapy or interval debulking surgery, of which YAP1 (Yes-associated protein 1) has been implicated in enhancing the resistance of ovarian cancer to Cisplatin and Taxol.^1,2. This highlights the need to develop new therapeutic strategies that target the Hippo pathway to overcome resistance to traditional therapies.

YAP1 is a protein that acts as a transcription coregulator, promoting the transcription of genes involved in cellular proliferation and suppressing apoptotic genes. It is a …