Medical Pharmacology Commons^™

Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon

Honors Undergraduate Theses

Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic …

Utilizing Probiotics To Reduce Diet Induced Dysbiosis And Inflammation In Myelodysplastic Syndromes Susceptible Mice, Tejaswee Bolloju

Theses, Dissertations and Capstones

Human gut microbiota is helpful in digestion by helping in breaking complex carbohydrates, proteins, fats and fibers and many other physiological functions. The Western diet which is high in fat and carbo hydrate percentage alters gut microbiota and leads to growth of pathogenic bacteria and altered gut flora referred to as dysbiosis, which in turn cause gut inflammation and increased permeability of gut and it causes translocation of Lipopolysaccharides (LPS) which causes low grade systemic inflammation. Disturbance in gut microbiota correlated with metabolic conditions like obesity and leads to progression of hematologic diseases like Myelodysplastic Syndromes (MDS). Myelodysplastic syndromes are …

Administration Of Anti-Gfap Antibodies Increases Cgrp Expression And Increases Pain Hypersensitivity In Spinal Cord Injured Animals, Georgene W Hergenroeder, Samuel T Molina, Juan J Herrera

Faculty, Staff and Student Publications

Background: Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.

Objective: Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined …

A Quality Improvement Initiative To Decrease Sugammadex Expenditures, Jordan Austin Gardo

Graduate Theses, Dissertations, and Problem Reports (ETD)

Abstract

A Quality Improvement Initiative to Decrease Sugammadex Expenditures

Jordan Gardo

Introduction/Background: The manufacturer’s suggestion in the dosing of the Sugammadex is

generally dosed at 2-4 mg/kg of total body weight (TBW) depending on the extent of

neuromuscular blockade. Evidence suggests that in the morbidly obese population, this

can lead to excessive dosing due to the drug's hydrophilic properties, making it less cost-

effective. Dosing based on adjusted body weight (ABW) leads to dose reductions while

achieving full reversal of neuromuscular blockade as measured by quantitative train-of-

four monitoring, resulting in lower costs from decreased vial usage.

Purpose: The purpose …

Clinical Pharmacology And Medication Safety: A Remote Learning Elective Designed For Senior Medical Students, Elizabeth B. Graham, William T. Wightkin, Curt R. Bay, Uzoma S. Ikonne

Department of Biomedical and Translational Sciences Faculty Publications

In the United States, medical educators have expressed concern that an integrated and condensed pre-clerkship curriculum risks leaving gaps in student pharmacology knowledge. This study evaluates a remote-learning clinical pharmacology elective that integrates fundamental pharmacology concepts and principles of medication safety and explores how the course impacts senior medical students' self-reported readiness for residency. Clinical Pharmacology and Medication Safety is a remote elective course for senior medical students. The course integrates a review of basic pharmacology with clinical pharmacology topics through case-based learning sessions led by clinical pharmacists and physicians. To evaluate the elective's effectiveness, students in the fall and …

Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms Of Occurrence, Abdulaziz M. Eshaq, Thomas W. Flanagan, Abdulqader A. Ba Abbad, Zain Alabden A. Makarem, Mohammed S. Bokir, Ahmed K. Alasheq, Sara A. Al Asheikh, Abdullah M. Almashhor, Faroq Binyamani, Waleed A. Al-Amoudi, Abdulaziz S. Bawzir, Youssef Haikel, Mossad Megahed, Mohamed Hassan

School of Medicine Faculty Publications

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as …

Uncontrolled Hypertension Or A Bad Medication Interaction? The Importance Of Reviewing Over-The-Counter Medications During Medication Reconciliation, Shefali Amin Do, Caitlyn R. Moss Md

Transformative Medicine

Introduction: In the management of chronic conditions, review of the complete medication list for potential drug-drug interactions is crucial. This case involves a patient taking activated charcoal for unclear reasons, leading to misdiagnosed uncontrolled hypertension.

Case Description: We present the case of an elderly male with uncontrolled hypertension who had been placed on multiple chronic antihypertensives for years. On further review, he was found to be taking activated charcoal twice daily thereby inactivating his five oral antihypertensive medications and making his blood pressure difficult to control. Discontinuation of the activated charcoal led to significant improvement in his blood …

Naloxone Prescribing At Hospital Discharge: A Quality Improvement Initiative, Timothy Ford

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Opioid overdose deaths remain one of the largest public health challenges in the United States. Naloxone allocation is an important tool to help combat opioid overdose deaths. The literature supports that hospitalized patients are generally receptive to receiving naloxone and opioid education and interdisciplinary teams working together can help facilitate identification of high-risk patients for naloxone allocation. This quality improvement change, guided by the IHI Triple Aims and Model for Healthcare Improvement frameworks, sought to increase the rate of patients leaving the Hospital Medicine Service with naloxone. To accomplish this, during the target units’ daily interdisciplinary rounds, providers were prompted …

Onycholysis In An Elderly Woman: Proposal For Treatment With Coix Seed Extract Administration, Yasuhiro Horiuchi

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: The exact etiology of onycholysis, which is characterized by the painless separation of the nail from the nail bed, remains unclear. Currently, there are no established effective treatments for this condition. Coix seed extract (C-S extract), a traditional Chinese medicine, is recognized for its various biological properties.

Case Illustration: This report describes a case of onycholysis affecting the left index finger of a 62-year-old female patient, with initial symptoms appearing three months prior. Despite ongoing internal administration of C-S extract, the patient experienced a recurrence of onycholysis on both the index finger and pinky finger of the left hand …

Single-Molecule Studies Reveal The Off-Pathway Early Paused State Intermediates As A Target Of Streptolydigin Inhibition Of Rna Polymerase And Its Dramatic Enhancement By Gre Factors, Anatolii Arseniev, Mikhail Panfilov, Georgii Pobegalov, Alina Potyseva, Polina Pavlinova, Maria Yakunina, Jookyung Lee, Sergei Borukhov, Konstantin Severinov, Mikhail Khodorkovskii

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Antibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes (ECs) of RNAP in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected. Stl enhances the short-lived pauses associated with an off-pathway early paused state intermediates of the RNAP nucleotide addition cycle. Unexpectedly, we found that transcript cleavage factors GreA and …

Evaluation Of Pain Control In Lobectomies: Before And After The Removal Of Liposomal Bupivacaine From Formulary At An Academic Health System, Kelly Cheng Pharmd, Michael Guerra Pharmd, Rebecca Pulk Pharmd, Ms, Bsp, Amber Zaniewski Pharmd, Mba, Bcps, Ryan Brown Pharmd, Bcps

Posters

• Liposomal bupivacaine is an extended-release formulation of the long-acting traditional local anesthetic, bupivacaine.
• Yale New Haven Health system (YNHHS) removed liposomal bupivacaine from formulary in March 2024.
• This decision was based on primary research and meta-analyses showing little to no clinical or statistical benefit of liposomal bupivacaine over traditional bupivacaine in morphine milligram equivalent use (MME) and median pain score in all surgeries including lobectomies.

Identifying Current Barriers And Optimization Opportunities Of Rapid Access Pathway To Outpatient Care For High-Cost Biologics In An Academic Health System, Avani Topiwala Pharmd, Vincent Do Pharmd, Bcps, Bctxp, Joseph Rosano Bs, Pharmd

Posters

• Inpatient administration of specialty biologic agents can have significant financial impacts on a healthcare system.
• The “Never Administer Inpatient List” (NAIL) is an established reference which contains biologic infusions that should be administered in an outpatient setting when clinically appropriate.
• While outpatient administration may be clinically appropriate, there are many barriers to coordinating outpatient infusions that result in unnecessary inpatient administration. This can result in a prolonged length of stay and increased medication cost.

Exercise Therapy Rescues Skeletal Muscle Dysfunction And Exercise Intolerance In Cardiometabolic Hfpef, Heather Quiriarte, Robert C. Noland, James E. Stampley, Gregory Davis, Zhen Li, Eunhan Cho, Youyoung Kim, Jake Doiron, Guillaume Spielmann, Sujoy Ghosh, Sanjiv J. Shah, Brian A. Irving, David J. Lefer, Timothy D. Allerton

School of Graduate Studies Faculty Publications

Exercise intolerance, a hallmark of heart failure with preserved ejection fraction (HFpEF) exacerbated by obesity, involves unclear mechanisms related to skeletal muscle metabolism. In a “2-hit” model of HFpEF, we investigated the ability of exercise therapy (voluntary wheel running) to reverse skeletal muscle dysfunction and exercise intolerance. Using state-of-the-art metabolic cages and a multiomic approach, we demonstrate exercise can rescue dysfunctional skeletal muscle lipid and branched-chain amino acid oxidation and restore exercise capacity in mice with cardiometabolic HFpEF. These results underscore the importance of skeletal muscle metabolism to improve exercise intolerance in HFpEF.

Recent Developments In Tirzepatide's Role In Reducing Cardiovascular Disease Risk Factors In Adults With Type 2 Diabetes, Talaya Jones, Zaneh Kahook, Carina Bryan, Mayur Parmar

HCA-NSU MD Research Day

Objective: This literature review aims to investigate recent developments in tirzepatide’s ability to lessen CVD risk factors for adults with increased risk of major adverse cardiovascular events. Background: Tirzepatide is an FDA - approved medication primarily used to treat adults with type 2 diabetes mellitus (T2DM) by reducing A1C and chronic weight management, however its efficacy for reducing CVD risk factors is under examination. Methods: This review synthesizes data from recent early findings published by the pharmaceutical company, which has not yet undergone peer review, alongside existing literature on tirzepatide. Additional sources were identified through a systematic search of PubMed, …

Impact Of Multifactorial Interventions With Medication And Lifestyle Optimization On Patients With Type 2 Diabetes: A Randomised Controlled Trial, Marwan M. El Deyarbi

Thesis/ Dissertation Defenses

The incidence of diabetes is increasing worldwide, consequently increasing mortality rates due to complications such as diabetic kidney disease. Clinical evidence on the protective effect of balanced diet, exercise and medication adherence with glucose-lowering intensification therapies on the progression of diabetes is insufficient, and interventions that are most effective in slowing cardiorenal metabolic complications in patients with type 2 diabetes mellitus (T2DM), especially in the UAE population diabetes remain to be elucidated. Several studies have shown that patient-related factors and limited medication adherence in patients with chronic diseases, are associated with poor clinical outcomes, long-term complications, and increased overall disease …

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

Riluzole Attenuates Acute Neural Injury And Reactive Gliosis, Hippocampal-Dependent Cognitive Impairments And Spontaneous Recurrent Generalized Seizures In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Dominic Allocco, Laine Vande Hei, Heike Wulff, Jeffrey D. Erickson

School of Medicine Faculty Publications

Background: Riluzole exhibits neuroprotective and therapeutic effects in several neurological disease models associated with excessive synaptic glutamate (Glu) release. We recently showed riluzole prevents acute excitotoxic hippocampal neural injury at 3 days in the kainic acid (KA) model of temporal lobe epilepsy (TLE). Currently, it is unknown if preventing acute neural injury and the neuroinflammatory response is sufficient to suppress epileptogenesis. Methods: The KA rat model of TLE was used to determine if riluzole attenuates acute hippocampal neural injury and reactive gliosis. KA was administered to adult male Sprague-Dawley (250 g) rats at 5 mg/kg/hr until status epilepticus (SE) was …

Identification Of The N-Terminal Residues Responsible For The Differential Microdomain Localization Of Cyp1a1 And Cyp1a2, Robert M. Fuchs, James R. Reed, J. Patrick Connick, Markéta Paloncýová, Martin Šrejber, Petra Čechová, Michal Otyepka, Marilyn K. Eyer, Wayne L. Backes

School of Graduate Studies Faculty Publications

The endoplasmic reticulum is organized into ordered regions enriched in cholesterol and sphingomyelin, and disordered microdomains characterized by more fluidity. Rabbit CYP1A1 and CYP1A2 localize into disordered and ordered microdomains, respectively. Previously, a CYP1A2 chimera containing the first 109 amino acids of CYP1A1 showed altered microdomain localization. The goal of this study was to identify specific residues responsible for CYP1A microdomain localization. Thus, CYP1A2 chimeras containing substitutions from homologous regions of CYP1A1 were expressed in HEK 293T/17 cells, and the localization was examined after solubilization with Brij 98. A CYP1A2 mutant with the three amino acids from CYP1A1 (VAG) at …

Prevalence And Prognostication Of Cd5+ Mature T-Cell Lymphomas, Omar Elghawy, Miao Cao, Jason Xu, Daniel J. Landsburg, Jakub Svoboda, Sunita D. Nasta, Elise A. Chong, Stephen J. Schuster, Colin J. Thomas, Jordan S. Carter, Montreh Tavakkoli, Marco Ruella, Stefan K. Barta

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Background: T-cell lymphomas (TCLs) are a group of heterogenous cancers with poor rates and duration of response. There remains a great challenge in risk stratification of these cancers. Cluster of differentiation (CD) 5 has shown prognostic implication in many subtypes of B-cell lymphoma; however, its role in TCLs is not known. Methods: We performed a single-institution retrospective analysis of newly diagnosed patients with TCL. CD5 positivity was determined based on positive results via immunohistochemistry and/or flow cytometry. We used univariate and multivariable analysis of biological factors to assess their association with survival outcomes. Results: A total of 194 patients with …

Risk Of Stroke In Patients With Left Ventricular Thrombosis Who Undergo Coronary Angiography: A System-Wide Retrospective Analysis, Ashraf Ahmed, Shaun Abid Md, Abhinav Aggarwal, Samdish Sethi, Ilia Ryzhkov, Nur Rahman Md, Assad Ur Rehman Md, Mohamed A. Badheeb, Isaac Opoku Md, Rasha Kaddoura, Rajvir Singh Md, Sandeep S. Nayak, Gilead Lancaster

Posters

Left ventricular thrombus (LVT) has been associated with an increased risk of cardioembolic stroke. However, it has not been established if coronary angiography (CAG) or percutaneous intervention (PCI) would enhance that risk. This study aims to determine the risk of cardioembolic stroke among patients with LVT who underwent CAG or PCI.