Chemicals and Drugs Commons^™

Epidural Hematoma Risks Associated With Ceasing Vs. Maintaining Anticoagulant And/Or Antiplatelet Medications For Cervical And Thoracic Interlaminar Epidural Steroid Injections, Michael Furman, Jesse Bernstein, Lelia Gilhool, Christopher Bednarek, Holden Caplan, Ajay Kurup, Byron Schneider

SKMC Student Presentations and Publications

Background: There is a lack of substantiated evidence to support or refute the risks of ceasing vs maintaining anticoagulant and/or antiplatelet medications (ACAP) prior to cervical and thoracic interlaminar epidural steroid injections. The ACAP medication is frequently stopped pre-procedure due to concerns for potential bleeding complications, particularly epidural hematomas (EH). This article provides evidence regarding EH incidence in this population. Methods: Data for this study was collected retrospectively on all patients from September 19, 2009–Jun 16, 2017 who were scheduled for an Interlaminar Cervical and/or Thoracic Epidural Steroid Injections (IL-CTESI) and were on an ACAP medication at the time a …

Effect Of Caffeine In Pattern Memory And Reaction Time Test Among College Students, William T. Clark, Micheal Lawson, Garrett Garnto, Evan Smith, Kelly Massey

International Undergraduate Journal of Health Sciences

Caffeine is commonly used by college students to aid in staying alert throughout the day. The purpose of this study was to determine the effects of caffeine on visual memory and reaction time performance on college students aged 18-25 years old. The Human Benchmark (https://humanbenchmark.com) Visual Memory (VM) and Reaction Time (RT) tests were used to assess participant’s baseline scores and scores 15min post treatment. Five male (19.0y ± 1.26) and four female (20.3y ± 0.43) college students volunteered to be participants in a three-week long cross-over, counterbalanced study. Blood pressure (BP) and heart rate (HR) were assessed before each …

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …

Isatin-Pyrimidine Hybrid Derivatives As Enoyl Acyl Carrier Protein Reductase (Inha) Inhibitors Against Mycobacterium Tuberculosis, Amira Khalil, Samy Mohamady, Amgad Albohy, Marwa M. Abdel-Aziz, Abdalrahman Khalifa

Pharmacy

Tuberculosis is a worldwide problem that impose a burden on the economy due to continuous development of resistant strains. The development of new antitubercular drugs is a need and can be achieved through inhibition of druggable targets. Mycobacterium tuberculosis enoyl acyl carrier protein (ACP) reductase (InhA) is an important enzyme for Mycobacterium tuberculosis survival. In this study, we report the synthesis of isatin derivatives that could treat TB through inhibition of this enzyme. Compound 4l showed IC50 value (0.6 ± 0.94 µM) similar to isoniazid but is also effective against MDR and XDR Mycobacterium tuberculosis strains (MIC of 0.48 and …

Computational And Experimental Investigation Of Elemental Sulfur And Polysulfide, Jyoti Sharma

Dissertations

Petroleum processing results in the generation of significant quantities of elemental sulfur (S₈), leading to a surplus of sulfur worldwide. Despite its abundance and low cost, the use of sulfur in value-added organic compound synthesis is limited due to its unpredictable and misunderstood reactivity. This dissertation aims to address this issue by tackling it from two angles. Firstly, by utilizing Density Functional Theory (DFT) calculations, the reactivity of sulfur in the presence of nucleophiles is studied. This facilitates the identification of organic polysulfide intermediates that can be generated under different conditions, as well as the corresponding reactivity for …

Environmental Isolate Developing Antibiotic Resistance By Complementation, Mary Ridgeway, Ashley Fink, David Mitchell

Biology Faculty Publications

Antibiotic resistance is a growing concern within the scientific community. With few new antibiotics being introduced and an increasing number of resistant microbes, routine bacterial infections are becoming more difficult to treat in clinics and hospitals. The purpose of this study is to compare the ability of two environmental isolates – Staphylococcus aureus (S. aureus) and Exiguobacterium undae (E. undae) to grow in solutions of increasing concentrations of tetracycline and ciprofloxacin. After the bacteria showed grow in the solutions, antibiotic susceptibility was tested by examining zones of inhibition on Trypticase Soy Agar (TSA) plates. Our results …

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Medicine Faculty Publications

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …

Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, …

Nanodiscs: A Novel Approach To The Study Of The Methionine Abc Transporter System, Michael T. Winslow

Master's Theses

Membrane transporter proteins play the vital role of moving compounds in and out of the cell and are essential for all living organisms. ATP Binding Cassette (ABC) family transporters function both as importers and exporters in prokaryotes. MetNI is an E. coli Type I ABC transporter responsible for the uptake of methionine into the cytosol from the cell periplasmic space through the cell membrane to maintain intracellular methionine pools. ABC transporters, like other membrane proteins, are most often mechanistically and structurally studied in vitro, solubilized by detergents. However, detergent micelles may affect the conformational changes of membrane proteins relative to …

The Noloco Strategy For Essential Hypertension, F. Matthew Mihelic Md

Faculty Publications

Ninety-nine percent of all “essential” hypertension can be controlled by using the NoLoCo strategy, without causing any significant side-effects and without an increase in insulin resistance. NoLoCo stands for Norvasc (amlodipine), Lozol (indapamide), and Cozaar (losartan), but the medicines are considered and used in reverse order.

Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero

School of Medicine Faculty Publications

Purpose: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Methods: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Comparing Antimicrobial Resistant Genes And Phenotypes Across Multiple Sequencing Platforms And Assays For Enterobacterales Clinical Isolates, Rebecca Rose, David J. Nolan, Deborah Ashcraft, Amy K. Feehan, Leonor Velez-Climent, Christopher Huston, Benjamin Lain, Simon Rosenthal, Lucio Miele, Gary B. Fogel, George Pankey, Julia Garcia-Diaz, Susanna L. Lamers

School of Medicine Faculty Publications

Introduction: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, …

Reminiscence Therapy For Prevention Of Post-Stroke Anxiety And Depression In Adults, Carly Porter

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

Anxiety and depression are prevalent after a stroke.^1,2 Peer support is a non-pharmacologic intervention utilized to manage post-stroke anxiety and depression with inconsistent results.³ Reminiscence therapy is an intervention that has been studied in the dementia population but is a relatively new intervention for the stroke population and has the potential to impact the psychological care provided to stroke patients.⁴

Stimulant Medication Use In Children/Adolescent Athletes With Adhd Reduce The Recovery Time Of Concussions And Traumatic Brain Injury, Matthew Lee

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

• Concussions and TBIs are well-known injuries occurring 30-50 million times a year worldwide and are commonly seen in sports.¹ The majority of TBIs are mild yet still have the potential to cause lifelong detrimental effects.
• Short- and long-term complications include difficulty thinking, difficulty concentrating, changes in emotions and personality, decreased memory and sensation, and may lead to depression and dementia.²
• Especially in children and adolescents who are undergoing brain development.
• There are no known prophylactic medications, however, some studies have indicated that sympathomimetic drugs, MPH, may be neuroprotective in the setting of TBIs.
• The purpose of this …

Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino

Theses & Dissertations

Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …

Overcoming Resistance Mechanisms To Cdk4/6 Inhibitor Treatment Using Cdk6-Selective Protac, Sarah Truong

Theses & Dissertations

Hormone receptor-positive (HR+) breast cancer (BC) constitutes approximately 75% of all breast cancer patients. These tumors rely on hormones, estrogen and progesterone, for their proliferation. The interaction between the hormones and their respective receptors enhances cyclin D expression, which results in the persistent activation of CDK4 and CDK6. The CDK4/6-cyclin D complex engages in a phosphorylation cascade that ultimately allows the cells to proceed past the G1/S checkpoint of the cell cycle. Inhibition of CDK4/6 has been shown to trigger cell cycle arrest, inhibit tumor growth, and induce apoptosis. Currently, there are three FDA-approved CDK4/6 inhibitors (CDK4/6i). A limitation of …

Exploiting Vulnerabilities In The Ras-Rac Signaling Pathway For The Selective Targeting Of Pancreatic Cancer Cells, Neha Chaudhary

Theses & Dissertations

Deregulation of the KRas (Kirsten rat sarcoma virus) GTPase is one of the early hallmarks of Pancreatic Cancer (PC). The most common genetic alteration found in PC are mutations in the KRas protein that block its ability to hydrolyze GTP to GDP and resulting in higher levels of GTP-bound KRas, its active form. Pancreatic tumors driven by oncogenic mutants of KRas tend to be addicted to the oncogene, to the extent that its repression leads to the induction of cell death. This addiction to the KRAS oncogene makes the KRas protein an ideal target for cancer therapy. However, the globular …

Unlocking The Potential Of Kinase Targets In Cancer: Insights From Canceromicsnet, An Ai-Driven Approach To Drug Response Prediction In Cancer, Manali Singha, Limeng Pu, Gopal Srivastava, Xialong Ni, Brent A. Stanfield, Ifeanyi K. Uche, Paul J.F. Rider, Konstantin G. Kousoulas, J. Ramanujam, Michal Brylinski

School of Medicine Faculty Publications

Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …