Pharmacology Commons^™

Validating A Genetic Knockout Of Ninein In A Mouse Model, Jessikah M. Buys, E R. Gnatowski, L Vermuri, A Safeer, L Holmes, M. F. Miles

IRBEH/Spit for Science Publications and Presentations

Ninein (Nin) is a microtubule associated protein that has been previously characterized by the Miles Lab for regulating the anxiety-reducing (anxiolytic) effects of alcohol, which is thought to contribute to development of Alcohol Use Disorder (AUD). Previous studies in the lab have investigated the role of Nin deletion on anxiety and ethanol-related behaviors in a conditional knockout model. The following set of studies seek to validate this genetic model. The model was validated using three main methods: immunofluorescence, qRT-PCR, and gel electrophoresis. In PCR studies, Ninein was significantly reduced in cre-expressing animals compared to controls. Gel Electrophoresis confirmed this reduction …

Effects Of Psychedelics On Acute Nicotine Pharmacological Responses, Aleny Oros, Belle Buzzi, Julian Vaughn, Burhan Buttar, Javier Gonzalez-Maeso, M Imad Damaj

IRBEH/Spit for Science Publications and Presentations

Smoking is a major risk factor for illnesses, such as cancers, cardiovascular diseases and respiratory conditions. In smoking, nicotine activates nicotinic acetylcholine receptors in the brain region. Prolonged use of nicotine will desensitize these specific receptors and cause nicotine dependence, resulting in smokers to experience withdrawal symptoms, such as anhedonia, depression, stress, and craving, leading to relapse.2 As the rate cigarette smoking has declined over the years, it is not significantly entitled by the tremendous increase rate of e-cigarette use. In a previous study being published, life-time use of psychedelics is associated with lower nicotine dependence.1

Psychedelics, specifically psilocybin, which …

Developing Stiripentol Analogs As Potential Ldh Inhibitors For The Treatment Of Glioblastoma, Anshika Y. Jain

Theses and Dissertations

Glioblastoma multiforme (GBM) is a highly proliferative brain tumor that has a 5-year survival rate of ~7 %. Temozolomide (TMZ) is the current standard of care therapeutic for GBM. However, 50% of patients develop resistance to TMZ. Therefore, further investigation for new GBM therapeutics is necessary to overcome this issue of drug resistance. GBM patients are known to overexpress lactate dehydrogenase (LDH), which is inversely correlated with their survival. This key glycolytic enzyme catalyzes the interconversion of pyruvate and lactate and plays an important role in cancer proliferation and invasion. Therefore, we aimed to inhibit LDH for developing therapeutics for …

Metformin In Overcoming Enzalutamide Resistance In Castration-Resistant Prostate Cancer, Kendall Simpson, Derek B. Allison, Daheng He, Jinpeng Liu, Chi Wang, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Androgen deprivation is the standard treatment for patients with prostate cancer. However, the disease eventually progresses as castration-resistant prostate cancer (CRPC). Enzalutamide, an androgen receptor inhibitor, is a typical drug for treating CRPC and with continuous reliance on the drug, can lead to enzalutamide resistance. This highlights the necessity for developing novel therapeutic targets to combat the gain of resistance. Metformin has been recently investigated for its potential antitumorigenic effects in many cancer types. In this study, we used enzalutamide and metformin in combination to explore the possible rescued efficacy of enzalutamide in the treatment of enzalutamide-resistant CRPC. We first …

Identification Of Pharmacophore Modifications That Enhance Bmp-Receptor Agonism, An Investigation To Understand The Development Of Potential Therapeutic Interventions, Maleka T. Stewart

Theses and Dissertations

Bone morphogenetic proteins (BMPs) are the largest subfamily of the Transforming Growth Factor (TGF)-ß superfamily. BMPs are renowned for their pivotal role in cellular functions such as cell growth, apoptosis, and differentiation. Yet, BMPs have also been attributed to the maintenance of adult tissue homeostasis. BMPs elicit physiological function at the cell membrane via a heterotetrameric complex composed of two Type I and two Type II serine-threonine kinase BMP receptors. Activation of BMP transmembrane receptors results in activation of either canonical (Smad-dependent) and/or non-canonical (Smad-independent) signaling. Given the physiological importance of this intricate communication between receptor activation and induction of …

Effect Of Paxlovid On Neurodevelopmental Disorder Diagnosis Outcomes In Offspring Of Mothers Infected With Sars-Cov-2 During Pregnancy, Simone Rogers

CMC Senior Theses

The onset of the 2020 COVID-19 pandemic brought concern over the effects that this virus would have on pregnancy and fetal outcomes, specifically neurodevelopmental outcomes. Maternal immune activation (MIA), caused by infection during pregnancy, is known to result in neurodevelopmental disorder (NDD) diagnosis in offspring, typically autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). This effect has already been observed in mothers who were infected with COVID-19 during pregnancy. However, in 2023, Paxlovid, the COVID-19 antiviral drug, became available to patients experiencing symptoms of the virus, including pregnant women. Consequently, this study seeks to determine whether the risk of …

Investigating The Role Of Dynamic Signaling Of Nrg3-Erbb4 In The Prefrontal Cortex In Mediating Nicotine Withdrawal Phenotypes, Emily Prantzalos

Theses and Dissertations--Pharmacy

While several pharmacotherapies are currently available for nicotine use disorder (NUD), smoking cessation success rates remain below 10% each year. The molecular mechanisms underlying failed quit attempts continue to represent a critical gap in our knowledge. However, recent advances in understanding the genetic contributions to nicotine dependence offer a promising avenue for developing more effective cessation therapies. Prior research has identified genetic variation in Neuregulin 3 (Nrg3) and its cognate receptor ErbB4 as potential contributors to affective nicotine withdrawal (WD) phenotypes and cessation outcomes. Therefore, this dissertation aims to systematically investigate the region-specific, functional role of the Neuregulin Signaling Pathway …

Unleashing Serine Palmitoyltransferase In Test Tubes And Mice, Matthew W. Peart

Theses and Dissertations

Canonically known both for structural contributions to lipid bilayers and roles in cell signaling, the sphingolipids comprise a dynamic, multifaceted class of molecules which are studied to understand homeostatic cell biology as well as pathophysiology. Sphingolipids contribute to tissue-specific structures such as myelin, a multilayer membrane that allows for rapid conduction of action potentials along neuronal axons. All sphingolipids are downstream products of the rate-limiting and initiating enzyme in the de novo sphingolipid synthesis pathway, Serine palmitoyltransferase (SPT). Demonstrative of its status as the enzyme that catalyzes a crucial step in a biochemical pathway, SPT activity is strictly regulated. This …

Scopolamine-Induced Modulation Of Serotonin And Dopamine Transporters Activity: Behavioral And Molecular Insights Into Rapid Antidepressant Action, Deepak Karunakaran

Theses and Dissertations

Major depressive disorder (MDD) affects over 350 million individuals worldwide and is characterized by profound dysregulation of serotonin (5-HT) and dopamine (DA) systems that govern mood, reward processing, and motivation. The serotonin transporter (SERT) and dopamine transporter (DAT), both dynamically regulated through phosphorylation, serve as critical determinants of synaptic monoamine signaling. Despite decades of therapeutic development, current antidepressants require 4-6 weeks to achieve efficacy, and approximately one-third to half of patients develop treatment-resistant depression. The emergence of rapid-acting antidepressants like ketamine represents a paradigmatic shift, demonstrating symptom relief within hours; however, ketamine's therapeutic potential remains constrained by abuse liability, dissociative …

Phytochemical And Nutritional Composition Of Vernonia Amygdalina: Antioxidant, Antidiabetic Efficacy, And Hematological Benefits, Hassan A. Adewuyi, Messiah Atapia, Emmanuel Ochonung, Sakariyau A. Waheed, Adebimpe H. Oluwatoyin, Chizoba V. Obunadike, Adeleye A. Edema, Samad Hussein, Usman A. Mohammed, Kevin L. Sebastine, Tolulope O. Jaiyeola

Chemistry & Biochemistry Faculty Publications

Vernonia amygdalina, a traditionally used medicinal plant, has been purported to possess health-promoting properties. The aim of this study is to investigate the phytochemical and nutritional composition of V. amygdalina, evaluate its antioxidant and antidiabetic efficacy, and assess its hematological benefits. Phytochemical screening, proximate analysis, antioxidant assays (DPPH, ABTS), antidiabetic evaluations in treptozotocin induced diabetic rats, and hematological assessments were conducted according to standard protocol. V. amygdalina exhibited a rich phytochemical profile, comprising flavonoids, phenolic acids, and terpenoids, alongside significant antioxidant activity (IC50 = 12.5 μg/mL) and complete source of protein. Proximate analysis revealed high protein (21.1%) and …

Tick Responses To Diverse Chemical Attractants To Enhance Tick Surveillance Methods' Efficacy, Pamela Kelman, Tyler Chavers, Emily Owens Pickle, Daniel Sonenshine, Melissa S. Nolan, Holly Gaff

Biological Sciences Faculty Publications

Amblyomma maculatum Koch (Acari: Ixodidae), Ixodes scapularis Say, and Dermacentor variabilis Say are three hard-bodied ticks responsible for vectoring pathogens that cause most human tick-borne diseases in the United States of America (USA). Tick surveillance is critical to elucidate high-risk areas for targeted vector control and public health interventions. Despite tick-borne diseases having a higher annual incidence compared to mosquito-borne diseases in the USA, tick traps used for surveillance are grossly under-developed compared to the suite of sophisticated mosquito traps available on the commercial market. This study sought to identify potential prospective tick trap improvements by evaluating the relative attraction …

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 …

Biodistribution And Method Validation Of Xylazine In A Mouse Model Using Liquid-Chromatography-Quadrupole-Time Of Flight Mass Spectrometry, Julia E. Perschbacher

Master of Science in Forensic Science Directed Research Projects

Xylazine is a nonopioid veterinary sedative and an α2 adrenergic receptor agonist. It emerged in the opioid epidemic as an adulterant of illicit fentanyl. As xylazine becomes more involved in fatal overdoses, it is relevant to elucidate its biodistribution post-exposure due to its exacerbation of adverse events, namely respiratory depression, as xylazine’s contributions to existing adverse effects of synthetic opioids is understudied. A bioanalytical method to quantify xylazine and select metabolites in tissue using LC-QToF was validated and applied to a preclinical mouse model in order to characterize xylazine’s biodistribution in whole blood and six tissues at a dose known …

Identification Of Fentanyl And Fentanyl Analogs Found In Human Urine Using Gas Chromatography-Mass Spectrometry, Adam M. Fisher

Electronic Theses & Dissertations (2024 - present)

Identification of fentanyl and its analogs in unknown samples is a frequent practice completed in forensic crime labs, as the fentanyl epidemic continues. With the continued increase in illicit drug use, crime labs are not able to keep up with the flooding of new fentanyl analogs being developed, resulting in new analogs slipping past the crime labs’ authority. This research is to start to develop a database of commonly found fentanyl analogs in New York State. Gas Chromatography-Mass Spectrometry (GC-MS) is a widely used method for the detection and identification of illicit drugs in forensic crime labs. A database that …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

The Effects Of Plx 3397 On Fentanyl Escalation In Male And Female Sprague-Dawley Rats, Jakob Shaykin

Theses and Dissertations--Psychology

Purpose: A hallmark characteristic of opioid use disorder (OUD) is a persons’ ‘loss of control’, which leads to the compulsion to seek and obtain opioids, resulting in increased consumption. This phenomenon is known as ‘escalation of drug intake’. Chronic opioid use causes microglial reactivity and subsequent release of proinflammatory cytokines leading to neuroinflammation, weakening one’s executive control over drug taking and ultimately leading to greater use. Previous research in our laboratory has explored heterogeneity of fentanyl intake in extended access (6-hr) sessions and identified distinct endophenotypes of fentanyl intake. Moreover, we have observed a positive correlation between Treml1 expression …

Investigating Whether Txnrd2 Is A Therapeutic Target Against Triple Negative Breast Cancer Using African American-Derived Models, Keacha Chang

Dissertations

Despite similar breast cancer incidence rates, African American (AA) women experience a 40% higher mortality rate compared to Caucasian American (CA) women. This disparity is multifactorial and particularly pronounced in the Chicago area. AA women are twice as likely to be diagnosed with triple-negative breast cancer (TNBC), often at a younger age and with more aggressive disease. TNBC is a heterogeneous subtype lacking targeted therapies and is associated with the poorest prognosis among breast cancer types. Therefore, there is an urgent need for novel therapeutic strategies for TNBC, especially those tailored to AA patients. The thioredoxin pathway is essential for …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Pediatric Flecainide Pharmacogenomics: A Roadmap To Delivering Precision-Based Care To Pediatrics Arrhythmias., Ronald Palmen, Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Flecainide acetate is a Class 1c anti-arrhythmic with a potent sodium voltage gated channel blockade which is utilized for the second-line treatment of tachyarrhythmias in children and adults. Given its narrow therapeutic index, the individualization of drug therapy is of utmost importance for clinicians. Despite efforts to improve anti-arrhythmic drug therapy, there remain knowledge gaps regarding the impact of variation in the genes relevant to flecainide's disposition and response. This variability is compounded in developing children whose drug disposition and response pathways may remain immature. The purpose of this comprehensive review is to outline flecainide's disposition and response pathways while …

Acknowledgment Of Reviewers_2024

Journal of Food and Drug Analysis

No abstract provided.