Chemicals and Drugs Commons^™

Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, …

Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper

Honors College Theses

After its discovery back in the 1900s, photosensitizers became a critical study for potential treatments and cures for medical issues, including cancer. It was discovered that porphyrins appeared to target and accumulate in proliferating cells, and to reach the cells, a certain wavelength of light with maximum absorbance associated with the porphyrin was necessary to achieve cell death. Photodynamic therapy involves making use of porphyrins or metalloporphyrins as activators when exposed to such light. When activated, these compounds generate reactive oxygen species (ROS), such as HO- or O2-, which can react with nucleic acids found in DNA and RNA. In …

An Examination Of The Legal Responses By United States To Technological Advances In Organized Drug Smuggling, Abdulwahab Aldossary

University Honors Program

Recent advances in technology have aided terrorists in their ability to smuggle drugs in order to finance their operations. Drug trading routes have changed and so have methods of transportation and financial transaction. This study investigates the improved technology utilized by transnational organized crime groups and how the present laws and policies address the use of the improved technology for drug smuggling. The study will first look into the current models, such as the Counter-Terrorist Funding and Money Laundering model, and understand its weaknesses regarding drug smuggling within the United States. Moreover, the paper will focus on the current laws …

The Efficacy Of Neuroleptics On Mental Health Disorders, Rathea Hersi

Honor’s College Freeman Research Journal

Mental health disorders affect a lot of people in the world and can be triggered by a wide variety of reasons. The treatment of mental health disorders varies based on the type of disorder one is dealing with, as well as the symptoms that each portrays. While history has changed how people view mental health disorders, it also shows that the models of treatment used have not always been beneficial to the wellness of human beings. Research shows that there are different ways in which mental health disorders affect the brain, which means that a study of the different parts …

Cyclic And Linear Peptides Containing Tryptophan And Arginine Residues As Cell-Penetrating Peptides And Antifungal Agents, Khushbu Bhakta

Pharmaceutical Sciences (MS) Theses

Here, we synthesized a novel group of linear and cyclic amphiphilic peptides containing different sequences of arginine (R) and tryptophan (W) residues. The peptides included a class of cyclic peptides, [R3W3]2, [R3WRW]2, [RWW]4, [WRR]4, [RWRW3]2, and the corresponding linear peptides, (R3WRW)2, (RWW)4, (WRR)4, (RWRW3)2. The peptides were examined as potential molecular transporters and cell-penetrating peptides (CPPs), and their efficiency in delivering cell-impermeable compounds was compared with [WR]5. The peptides showed no significant cytotoxicity in different cell lines (MDA-MB-231, SK-OV-3, and HEK-293) at a concentration of 1 µM and after 3 h of incubation time. The uptake of fluorescence-labeled cargo molecules …

Fragment Based Drug Development Based On 6,7-Dimethoxyquinazoline As A Core Scaffold, Cody M. Orahoske

ETD Archive

The work entitled “Fragment Based Drug Design based on 6,7- Dimethoxyquinazoline core structure” presents a unique approach to drug discovery, specifically focusing on the pharmacophore 6,7-dimethoxyquinazoline. This study explores the structural diversity of 6,7-Dimethoxyquinazoline derivatives to identify other pharmacologically relevant targets, with evidence indicating that this core structure possesses intrinsic properties that make it suitable as a base structure of small molecule drugs. Furthermore, this pharmacophore has been observed in various approved therapeutics or drug candidates under investigation, highlighting its importance in drug discovery. My research showcases of 6,7-dimethoxyquinazoline core structure been derivatized to generate an anti-trypanosomiasis drug candidates and …

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

Renal Toxicity Warnings And Precautions Of Drugs Marketed In The Us, Mohammad Al Ghamdi

Pharmaceutical Sciences (MS) Theses

INTRODUCTION: The use of drugs can lead to renal adverse effects prompting the need to include warnings and precautions on medication labels. Studies evaluating renal warnings and precautions need to be improved. This study assessed the characteristics of FDA renal toxicity warnings and precautions included in the labels of drugs approved by the FDA and marked in the US. The study also evaluated the potential factors of including a boxed warning on a drug label.

METHODS: We extracted the labels of human prescription drugs with renal toxicity boxed warnings and warnings and precautions from the “FDA Label: Full-Text Search of …

The Developing Effects Of Potassium Ferricyanide On Tetrahymena, Katelyn Coronell

Whittier Scholars Program

Potassium Cyanide is a highly toxic chemical asphyxiant that interferes with the body's ability to use oxygen, typically by directly affecting the body by ingestion, inhalation, skin contact, or eye contact(CDC, 2011). Due to its high toxicity, the main effect that leads to the downfall of the organism begins with the cessation of aerobic metabolism; it does this by cyanide binding to the ferric ions and inhibiting cytochrome oxidase within the mitochondria (Zhang, 2015). There are no physical dangers the substance causes. Although, there are many chemical dangers. If used at temperatures higher than 70℉ The substance may produce toxic …

Characterization Of Differential Rearing And Sex On 5-Ht2ar Receptor Activation, Kelsey Lowe

Theses/Capstones/Creative Projects

The prevalence of substance use disorders (SUDs) continues to rise while the number of medications to combat this deadly disorder remains stagnant. Entirely new thinking about what exemplifies a possible therapeutic is needed. Hallucinogens are continually being studied more as possible treatments for many psychological conditions, including SUDs. Classic hallucinogens engage many serotonin and monoamine systems, but the hallucinogenic effects are driven by serotonin 5-HT_2A receptor (5-HT_2AR) activation. Forced social isolation induces chronic stress, increases 5-HT_2AR expression in the cortex and have been suggested to play a role in the comorbidity between stress, maladaptive coping, …

Self-Confidence And Hormonal Contraceptive Use, Abigail Doran

Biological Sciences Undergraduate Honors Theses

Hormonal contraceptives are widely used to regulate menstrual cycles, alleviate certain symptoms linked to reproductive hormones, and prevent pregnancy. However, women who take hormonal contraceptives may experience significant physical and psychological side effects such as increased rates of depression and changes in self-image. The current study examined self-confidence in women before beginning hormonal contraceptives and two months after using them. These participants were compared to a control group of naturally cycling women who were also assessed twice. I hypothesized that women would experience decreased feelings of self-confidence in several domains of their lives, compared to the naturally cycling women. Results …

Study On The Effect Of Lipoic Acid Presence In Heptamethine Cyanine Dyes For Near-Infrared Surface-Enhanced Raman Scattering (Nir-Sers), George Pollinger

Forensic Science Master's Projects

The use of Near-Infrared (NIR) Surface-Enhanced Raman Spectroscopy (SERS) has recently served as a strong candidate for highly sensitive bioimaging without the use of ionizing radiation and strong magnetic fields. Given the potential of heptamethine cyanine dyes to absorb in the NIR region while retaining stability and sensitivity, recent research has focused on altering the chemical moiety at the heptamethine displacing the meso-chloride to discover novel reporter molecules with enhanced SERS signaling. Such research has determined that lipoic acidcontaining N-acetyl amino tri-carbocyanine can produce a strong SERS intensity, given the affinity of sulfur for AuNPs. Such discoveries have utilized improper …

Qualitative And Quantitative Analysis Of Cannabinoids In Commercially Available Hemp-Infused Oils By Hplc And Complementary Analytical Methods, Gina Delmonache

Forensic Science Master's Projects

For decades, cannabis consumption has remained one of the most controversial topics of discussion in both science and law. However, Cannabis sativa, from which both hemp and marijuana are derived, has served as an essential component of medicine, industry, and recreation for centuries. Approximately 500 compounds have been identified from cannabis alone, and only around 66 are termed cannabinoids which account for the majority of research on the substance. The major cannabinoid constituents include delta 9-tetrahydrocannabinol (delta 9-THC), responsible for the psychoactive effects of cannabis, in addition to, cannabidiol (CBD), tetrahydrocannbinolic acid (THCA), cannbidolic acid (CBDA), cannbigerol (CBG), …

Cytotoxic Effects Of Bpa And Dehp On Human Epithelial Cells, Noah Stickrod

Theses/Capstones/Creative Projects

Endocrine disrupting chemicals (EDCs) are substances in the environment, food sources, personal care products, and manufactured products that interfere with the normal function of the body’s endocrine system. Most humans are exposed to some amount of these chemicals from many different sources, such as the air we breathe, food we eat, and the water we drink. EDCs can also permeate through the skin. The endocrine system is important because it works with other systems in the body to ensure healthy development and function throughout life. EDCs interfere with the way our body’s hormones work. Some EDCs can mimic natural hormones …

Exploration Of Salivary-Omics Analyses For Stress Biomarker Monitoring, Ashanthi Snell

Honors Scholar Theses

BACKGROUND/PURPOSE: To support long-term study into the salivary -omics responses to stress that may be used in biomonitoring during exercise and environmental stress, we pursued a focused study to establish optimized protocols and demonstrate that stress-specific markers are expressed to sufficient detectable limits and responsive to rest, exercise-heat stress, and to multi-day acclimation. Exosomes are extracellular vesicles, >150 nm in diameter secreted by multiple cell types and contain potentially stress-, disease-, or cell-damage-specific proteins, mRNAs, and miRNAs. Exosomes can be fractionated by their solubility and density from a variety of biofluids and probed for vesicular biomarkers (vs. freely circulating or …

Assessing Knowledge, Attitude, And Practice Among College Students Regarding Second-Hand And Third-Hand Smoke, Laura Y. Rebolledo

Electronic Theses, Projects, and Dissertations

Background: The tobacco epidemic has been a constant since the popularization of tobacco products. However, with the introduction of non-combustible products that include e-cigarettes and vapes, the usage of tobacco products has continued to increase. Tobacco exposure can stem from first-hand (FHS), second-hand (SHS), and third-hand smoke (THS), with the last two impacting even non-smokers. The health effects from all types of tobacco exposure can be detrimental. These effects include the risk of cancer in any organ of the body, cardiovascular disease, and respiratory diseases.

Methods: The study utilized a cross-sectional design through an anonymous web-based survey given …

Design And Synthesis Of Peripherally Selective Endocannabinoid Enzyme Inhibitors For Ocular Indications, Kezia Reji Thomas

Senior Honors Theses

Peripherally selective compounds have been found to stimulate endocannabinoid receptor activity, which has been observed to have positive physiological effects such as ocular wound healing and inflammation control. The activation of the cannabinoid 1 receptor via binding of the endogenous ligands, anandamide and 2-arachidonoylglycerol, has been indicated to elicit these effects. Both ligands are controlled by two hydrolase enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which can be targeted for therapeutic inhibition. Sulfonamide derivatives of JZL195 containing carbamate functionalities in the southern region of the inhibitor compounds were produced using novel carbamate exchange reactions. Polar functionalities were …

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

The Impact Of Treatment With Palynziq® On Quality Of Life For Individuals With Pku, Teresa Heller

Dissertations and Theses (Open Access)

Management for phenylketonuria (PKU) has traditionally involved adhering to a strict low-protein diet to maintain phenylalanine (Phe) levels within the recommended range (μmol/L). The time commitment and financial, emotional, and social burdens of adhering to a restrictive diet, as well as the neurocognitive symptoms associated with elevated Phe levels, make it challenging to manage PKU and lead to reductions in quality of life. Palynziq^® is an enzyme substitution therapy used to lower blood Phe levels and liberate individuals with PKU from their restrictive diets. Previous studies have demonstrated the safety and efficacy of Palynziq^®, but our study …

An Investigation On The Effect Of Conserved Hinge Histidine On Influenza Hemagglutinin(Ha2) Protein Conformation Using Md Simulations, Nada Tolba

Chemistry & Biochemistry Undergraduate Honors Theses

Hemagglutinin is a protein on the surface of Human Influenza Viruses.¹ It is composed of two glycopolypeptide domains, the HA1 and HA2 domains. Previous studies have found that across different strains of Influenza viruses, HIS435 residues remain conserved.⁴ In studies where mutations occurred in hinge-site histadine residues, the Influenza virus was inactive.⁴ These investigations indicated a significant role of HIS435 (hinge-site histadines) in virulence. Four systems were created using Molecular dynamics (MD) simulations. Each system was composed of an Isolated HA2 trimer solvated in a 150 mM NaCl rectangular water box at 310 K under isobaric and …

Expression And Characterization Of Gcmaf In Pichia Pastoris, Rajan Amit Patel

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Death Due To Drug Reaction With Eosinophilia And Systemic Symptoms (Dress) Syndrome: A Case Report, Samantha P. Sternad, Jane Pangburn, Chad Johnston, David Rowe

HCA Healthcare Journal of Medicine

Background

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening, multi-organ adverse drug reaction with an incidence of 1 in 1000 to 1 in 10 000 highrisk drug exposures.

Case Presentation

An elderly female presented to the hospital with progressive weakness and a diffuse erythematous macular rash covering most of her body that started 3 days prior. Over the next 3 days, the patient quickly deteriorated, developing disorientation with acute onset left-sided weakness, leukocytosis, thrombocytopenia, eosinophilia, liver and kidney failure, and hypoxia. Clinical and histological changes supported the diagnosis of DRESS syndrome caused by intravenous (IV) ampicillin …

Reducing Unnecessary Acid Suppression Use In Hospitalized Patients: A Description Of Targeted Strategies Implemented Across A Large Health System, Elizabeth H. Wiggins, L. Hayley Burgess, Joan Kramer

HCA Healthcare Journal of Medicine

Background

Ensuring the appropriate use of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) is an important hospital patient safety and quality initiative because therapy may be inappropriately continued during transitions of care. In this article, we aim to describe the impact of targeted quality improvement strategies to reduce unnecessary acid suppression use in hospitalized patients across a large health system.

Methods

Beginning January 1, 2018, focused quality improvement strategies to prevent unnecessary initiation and continuation of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) were implemented throughout a large health system. Targeted strategies were initially …

The Intersection Of Herbicide Policy, Exposure, And Health At The University Of Connecticut, Katherine Hayward

Honors Scholar Theses

Pesticides play an extremely complicated role in our everyday lives. From the water you use to make your coffee, to the breastmilk your neighbor provides for their child, to the lake your dog swims in, chemical pesticides or their byproducts have been found in nearly every corner of our lives. The chemicals used in synthetic herbicides, a subcategory of pesticides, have far reaching negative impacts on human health, biodiversity, and water quality. Despite there being numerous published studies on the relationships between pesticide exposures and health, there is still ongoing discord and controversy surrounding their role in our lives. After …

Protective Effect Of Betulinic Acid Administration On Kidney Damage In Acetaminophen-Induced Nephrotoxicity Model, Eda Dokumacioglu, Hatice İskender, Armagan Hayirli, Guler Yenice, Kubra Asena Terim Kapakin, Ismail Bolat, Esra Manavoglu Kirman

Makara Journal of Health Research

Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP.

Methods: Sprague–Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot …

Older Adults And Opioids, Elba L. Scherer

Morehead State Theses and Dissertations

A thesis presented to the faculty of the Caudill College of Arts, Humanities and Social Sciences at Morehead State University in partial fulfillment of the requirements for the Degree Master of Arts by Elba L. Scherer on April 27, 2023.

Testing Of Indazole Inhibitors Of Kasa, A Vital Enzyme Of M. Tuberculosis, Karissa Highlander

Departmental Honors & Graduate Capstone Projects

Tuberculosis is a disease that affects the lungs caused by Mycobacterium tuberculosis (M. tuberculosis). Although drug treatment options exist, increased rates of antibiotic resistant strains have become more prevalent in recent years, driving a need for new treatment approaches. KasA, a β-ketoacyl synthase, has been found to synthesize parts of the cell wall and been identified as an attractive drug target. Previous medicinal chemistry research has been completed to synthesize six effective competitive inhibitors of KasA that would potentially block the enzyme from binding the substrate, preventing elongation of the backbone and creation of the mycolic fatty acids that …

The Synergistic Effect Of Loganetin And 5-Fluorouracil On The Carcinogenesis Of Glioblastoma Cancer Cells, Jonathan Wollenberg

ATU Scholars Symposium

Chemoresistance is a discouraging trend that affects chemotherapeutic agents like 5-fluorouracil (5-FU) and leads to decreased efficacy of treatment. This has led to numerous studies into compound synergism. Glioblastomas are a type of lethal cancer that has shown chemoresistance to therapeutic agents such as 5-fluorouracil. Being the most common and lethal primary brain tumor, research on mechanisms of growth inhibition is vastly important (Lustig, 2018). The purpose of this study was to analyze whether 5-fluorouracil and a compound named Loganetin could synergistically inhibit glioblastoma cancer cells. This specific study utilized an extract created from the Lonicera etrusca plant. It was …

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Departmental Honors & Graduate Capstone Projects

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H⁺ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …

Splenic Asssessment Of The Toxicological Effects Of Dietary Consumption Of Pfbs (Perfluorobutane Sulfonic Acid), Janelene Sanders

Honors College Theses

Perfluoroalkyl and polyfluoroalkyl substances (PFAs) are synthetic chemicals that can pose adverse health effects such as kidney cancer, thyroid disease, pregnancy complications and liver damage due to human exposure in food and drinking water. In this study, the class of PFAs that will be investigated is Perfluorobutane sulfonic acid (PFBS), which is commonly found in the environment and consumer products such as wastewater, dust, and floor cleaners, and consists of 4 carbon chain bonded with fluorine and a sulfonic acid functional group. To accomplish study goals, PFBS, a shorter carbon chain length was ingested by Sprague Dawley rats. Serum LDH …