Medical Pharmacology Commons^™

The Mitochondria As An Emerging Target Of Self- Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly, Evelyn Winter, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T- ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both in vitro and in vivo, with some currently in …

Real-World Satisfaction And Experience With Injection And Autoinjector Device For Ofatumumab Indicated For Multiple Sclerosis., Amy Perrin Ross, Jacqueline Nicholas, Ming-Hui Tai, Stephen Yeung, Nazneen Fatima Shaikh, Helen Chen, Mariana Fernandes, Aaron Cortright, Kevin Hawkins

Neuroscience Articles

BACKGROUND: To evaluate the overall satisfaction, device usability, and injection experience of MS patients self-administering ofatumumab using the Sensoready

METHODS: This US-based, cross-sectional survey study included patients with MS (≥ 18 years) who self-administered ofatumumab using the Sensoready device within the previous 12 months of the survey. Eligible patients were administered a 30-item de novo questionnaire that focused on overall device satisfaction, device usability, convenience/flexibility for travel with the device, user confidence, injection experience, and time to administer the injection. Ratings were measured on Likert and numeric rating scales, with higher scores indicating positive responses.

RESULTS: Overall, 105 patients with …

Class Iii Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 In Cardiovascular Health And Disease, Yuanjun Shen, Jason Gleghorn

Pharmacy Faculty Scholarship

Phosphatidylinositol-3 kinases (PI3Ks) play a critical role in maintaining cardiovascular health and the development of cardiovascular diseases (CVDs). Specifically, vacuolar Protein Sorting 34 (VPS34) or PIK3C3, the only member of Class III PI3K, plays an important role in CVD progression. The main function of VPS34 is inducing the production of phosphatidylinositol 3-phosphate, which, together with other essential structural and regulatory proteins in forming VPS34 complexes, further regulates the mammalian target of rapamycin activation, autophagy, and endocytosis. VPS34 is found to have crucial functions in the cardiovascular system, including dictating the proliferation and survival of vascular smooth muscle cells and cardiomyocytes …

Investigating The Potential Of Broccoli Seed Extract To Attenuate Morphine Tolerance, Atharv Ashwin Battu, Minho Kang, Hamid Akbarali

Pharmacology and Toxicology Publications

Opioids remain one of the most effective treatment strategies for managing severe and persistent pain. However, its long-term use leads to pharmacological tolerance, requiring progressively higher doses to achieve analgesia. This dose escalation increases the risk of life-threatening side effects and dependence, underscoring the urgent need for safe adjuncts to preserve opioid efficacy. Emerging evidence suggests that morphine tolerance is linked to intestinal inflammation and disruption of gut barrier integrity. Broccoli Seed Extract (BSE), rich in the bioactive compound sulforaphane, exhibits antioxidant and anti-inflammatory properties that may protect against these effects. We hypothesized that BSE could prevent the development of …

Impact Of Tranexamic Acid On Patient Outcomes In Intracranial Hemorrhage: A Review, William G. Johnson

The PA Department Journal of Medical Science

Introduction: Intracranial hemorrhage is a medical emergency that remains a significant source of death and disability for patients globally. Tranexamic acid has shown promise in treating trauma related bleeding loss in various settings. This study aims to evaluate its role in the management of intracranial hemorrhages.

Methods: A review of data in the PubMed National Library of Medicine was conducted to find relevant and reputable studies related to this topic. Using the search “tranexamic acid AND intracranial hemorrhage*” and the following filters: last 5 years, free full text, English language, including RCTs, meta-analyses, and systematic reviews, 13 results …

Alpha-2 Agonist And Fentanyl Reinforcement Interactions In Male And Female Sprague Dawley Rats, Angeline Lopez, Allison Ortiz, Matthew L. Banks

IRBEH/Spit for Science Publications and Presentations

In the two studies that I participated in, a behavioral economic demand curve and choice procedure, we assessed whether two alpha-2 adrenergic agonists (i.e., xylazine, clonidine, and lofexidine) altered fentanyl reinforcement in male and female sprague dawley rats. We hypothesized that xylazine and clonidine would enhance fentanyl reinforcement in a proportion-dependent manner. Lofexidine interactions with fentanyl were more difficult to predict. The data showed that xylazine did not enhance fentanyl reinforcement. Furthermore, these results were consistent with those of clonidine and lofexidine. In opposition to xylazine, clonidine and lofexidine are approved for human use for antinociception, reduction of blood pressure, …

Astrovascular Decoupling In Awake 5×Fad Mice Is Associated With Reduced Astrocytic Calcium, Ruei-Lung Lin, Sophiya L. Sims, Nicholas A. Wright, Léopoldine B. Galopin, Blaine Weiss, Susan D. Kraner, Jacquelyn E. Rhinehart, Ting-Hsuan Lu, Pradoldej Sompol, Christopher M. Norris, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

INTRODUCTION

Evidence points to dysregulated Ca²⁺ in neurons and astrocytes in models of amyloidosis. While most of these data were obtained in vitro or in vivo under anesthesia, less work has investigated these variables in awake ambulating mice.

METHODS

Astrocytic Ca²⁺ fluctuations (GCaMP8f) were imaged concomitantly with vasoreactivity in S1 on a two-photon microscope during rest and ambulation. Single-cell resolution variables were extracted using continuous wavelet transform and traditional ΔF/F measures.

RESULTS

Along with increases in amyloid beta (Aβ) accumulation, we found significant reductions in measures of astrocyte functional connectivity, pairwise correlations, and network synchronicity in older 5×FAD …

Advancing Clinical Trial Readiness In White Matter Disease And Related Dementias: Key Steps For Future Research Progress, Pradoldej Sompol, Gregory A. Jicha, Jason D. Hinman, Adam M. Brickman, Steven M. Greenberg, Konstantinos Arfanakis, Marion S. Buckwalter, Irene Lorenzo Llorente, Jeff D. Williamson, Michael S. Wolf, Eric E. Smith, Aditi Gupta, Margaret E. Flanagan, Miguel A. Vazquez, Jeffrey M. Burns, S. Thomas Carmichael, Frank C. Barone

Pharmacology and Nutritional Sciences Faculty Publications

White matter disease, a broad-spectrum term that covers various types of white matter lesions and degeneration, is strongly related to age-related neurodegenerative disorders including Alzheimer’s disease (AD), and vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s related dementias (ADRD). There is no specific treatment for white matter disease. Therefore, basic research and clinical studies are essential for future outcomes. Since its formation in 2020, the Albert Research Institute for White Matter and Cognition (ARIWMC) mission has been to support white matter research by providing a forum for communication where basic and clinical scientists meet to discuss and debate …

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

Targeting Prmt5 In Inflammation And Cancer: A Nexus Of Endotoxin Signaling, Antigen Presentation And Immune Evasion., Jimmy James Msemo

Theses and Dissertations--Medical Sciences

Protein Arginine Methyltransferase 5 (PRMT5) is a member of PRMT family that controls both intrinsic and extrinsic oncogenic processes [1]. Protein arginine methyltransferase 5 (PRMT5) is a type II methyltransferase that exerts widespread influence over gene expression, splicing, DNA repair, and immune regulation through symmetric dimethylation of arginine residues on histone and non-histone proteins [2]. The addition of methyl groups induces gene silencing through producing dictatorial histone marks like H2AR3ne2s, H3R8me2s and H4R3mes [3], which act as epigenetic repressive marks on gene promoters. In non-histone proteins, PRMT5 can methylate and regulate transcription factor proteins such as p53, E2F1, and p65, …

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 …

A Unique Inflammaging Profile Generated By T Cells From People With Obesity Is Metformin Resistant, S. Santacruz‑Calvo, S. Saraswat, Gabriella Kalantar, E. Zukowski, H. Marszalkowski, Aida Javidan, F. Gholamrezaeinejad, L. P. Bharath, P. A. Kern, X. D. Zhang, Barbara S. Nikolajczyk

Pharmacology and Nutritional Sciences Faculty Publications

The alarmingly high prevalence of obesity in older adults coupled with the negative health effects of chronic inflammation in both obesity and aging highlight the importance of studies investigating the impacts of obesity on age-related inflammation. Since shifts in peripheral T-cell metabolism and function drive systemic inflammation in both obesity and aging, we hypothesize that obesity impacts the Th17-dominated inflammaging profile we identified in lean subjects and thus modifies the anti-inflammatory effects of geroprotective drugs like metformin. New cytokine profiling data showed that CD4+ T cells from older people with obesity generate a profile that specifically excludes Th17 cytokines. Metformin …

Bilirubin Hepatic And Intestinal Transport And Catabolism: Physiology, Pathophysiology, And Benefits, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Terry D. Hinds, Jr., Wang-Hsin Lee

Pharmacology and Nutritional Sciences Faculty Publications

Bilirubin, a metabolite derived from heme degradation, has traditionally been regarded as a waste product and a marker of liver injury. However, increasing evidence suggests that bilirubin also functions as a hormone, and reduced levels are associated with metabolic dysfunction. Studies have shown a strong association between low circulating bilirubin levels and an increased risk of metabolic disorders and cardiovascular disease. To advance bilirubin-based treatment strategies, it is essential to elucidate the mechanisms underlying bilirubin transport and metabolism. Therefore, we provide an in-depth discussion of bilirubin production and its subsequent fates, with a particular focus on the transport between the …

Cd47: An Immunoregulatory Nexus In Liver And Gastrointestinal Disorders, Josephine Otuagomah, Alana Newcomb, Taesik Gwag, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Cluster of differentiation 47 (CD47) is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system. It interacts with signal regulatory protein alpha to send a ‘do not eat me’ signal, thereby preventing phagocytosis and shaping immune responses. Beyond immunity, CD47 also influences cell death, growth and metabolism through interactions with integrins and thrombospondin-1. Recent studies implicate CD47 as a central nexus in the pathogenesis of diverse liver and gastrointestinal disorders, including metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, inflammatory bowel disease, liver ischaemia-reperfusion injury, drug-induced liver …

Gut Microbiome, Neuroinflammation, And Fetal Alcohol Spectrum Disorders: Insights From Rodent Models, Abdulrahman M. Busayli, Wenhua Xu, Ghaidaa A. Raffah, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, …

Calcineurin/Nfat Inhibitors Maintain Cognition In A Preclinical Prevention Study In An Aging Canine Model Of Alzheimer Disease, Lorena Sordo, Margo F. Ubele, Kathy Boaz, Jennifer L. Mefford, Erin Dehnart Jones, Katie L. Mccarty, Hollie Y. Van Rooyen, Jeffrey R. Smiley, Stasia A. Bembenek Bailey, Jessica A. Perpich, Beverly Meacham, David K. Powell, Frederick Bresch, Jacob W. Crump, Michael J. Phelan, Jessica A. Noche, Craig E. Stark, László G. Puskás, Christopher M. Norris, Elizabeth Head

Pharmacology and Nutritional Sciences Faculty Publications

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the impact of FDA-approved CN inhibitor, tacrolimus, and experimental NFAT inhibitor, Q134R, on cognitive outcomes during a three-year prevention study in 37 middle-aged beagles. While beagles treated with CN/NFAT inhibitors showed differences in the pattern …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar

Honors Undergraduate Theses

Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound …

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 …