Organic Chemicals Commons^™

Detailing The Effects Of Cannabidiol On Exosome Release In Ewing’S Sarcoma, Bennett Hasley

Theses

Ewing’s sarcoma (ES) is a highly aggressive pediatric cancer found within bone that carries a low five-year survival rate within its patients. This is due, in part, to the cancer’s high malignancy properties as well as the development of resistance to the chemotherapies used to combat this cancer. This project aims to determine if cannabidiol (CBD) has an effect on either exosome release or the protein, signal transducer and activator of transcription 3 (STAT3) within ES cells. Exosomes are vesicles that can carry proteins and other signaling molecules which are released by the cell and allow for cell-to-cell communication. Within …

Purification And Isolation Of Α-Chloro-Β-Lactone Precursor Molecules, Matthew Ellis

ASPIRE 2024

This research investigates the synthesis of α-chloro-β-lactone molecules, focusing on the production, isolation, and purification of two precursor compounds from chloroacetic acid and substituted benzaldehydes. While multiple methods were explored, including EDC, DIC, and DCC catalysis, DCC proved to be most effective in producing higher yields. However, challenges in purification arose due to the formation of byproducts, particularly with DCC, prompting further investigation for efficient extraction and purification techniques. DCC, however, shows a promising route for α-chloro-β-lactone synthesis, despite purification complexities.

Etiology Of Drug-Induced Edema: A Review Of Dihydropyridine, Thiazolidinedione, And Other Medications Causing Edema, Evan S. Sinnathamby, Bretton T. Urban, Robert A. Clark, Logan T. Roberts, Audrey J. De Witt, Danielle M. Wenger, Aya Mouhaffel, Olga Willett, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

Edema is an accumulation of fluid in the body's tissues that affects millions of Americans yearly. It can affect multiple body parts, for example, the brain or eyes, but often occurs in the periphery, including the feet and legs. Medications, such as dihydropyridine and thiazolidinediones (TZDs), can be the etiology of edema. Edema can develop in association with problems in the vasculature or lymphatic flow. In recent years, a better understanding of these drug-induced mechanisms has been appreciated. Specifically, dihydropyridines can increase hydrostatic pressure and cause selective pre-capillary vessel vasodilation. TZDs can cause edema through increased vascular permeability and increased …

Nanoparticles For Applications In Specific Diagnostics And Precision Medicine, Naxhije Berisha

Dissertations, Theses, and Capstone Projects

Heterogeneity is common in the expression of cancer and treatment response. Precision medicine enables healthcare providers to tailor medical care to an individual's distinct genetic and environmental makeup. This customization has the potential to result in more efficient treatments while minimizing side effects. We believe that by studying the interface of nanotechnology and cancer medicine we can elucidate innovative solutions that address the challenges of disease heterogeneity. This includes advancements in drug delivery, formulations development, and diagnostic sensing. We highlight three studies that use nanotechnology for applications in precision medicine. In Chapter 2, we highlight design optimization of drug formulations …

Hyperkalemia: Pharmacotherapies And Clinical Considerations, Evan S. Sinnathamby, Kelly T. Banh, William T. Barham, Tyler D. Hernandez, Audrey J. De Witt, Danielle M. Wenger, Vincent G. Klapper, David Mcgregor, Antonella Paladini, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

Hyperkalemia has been defined as a condition where a serum potassium level is > 5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain medical conditions, such as chronic kidney disease (CKD), diabetes mellitus, and others, can lead to hyperkalemia. Many of the signs of hyperkalemia are nonspecific. A history and physical examination can be beneficial in the diagnosis of the condition. In this regard, certain characteristic electrocardiogram findings are associated with hyperkalemia along with laboratory potassium levels. In acute and potentially lethal conditions, hyperkalemia treatments include glucose and insulin, bicarbonate, calcium gluconate, beta-2 agonists, hyperventilation, and dialysis. There …

Design, Synthesis, And Anti-Mcf-7 Activity Of New Thieno[2,3-D]Pyrimidinone Derivatives As Potential Breast Cancer Treatment, Bassem H. Naguib, Amgad Albohy, Mostafa A. Abdelaziz, Hanan H. Kadry

Pharmacy

Breast cancer is one of the top leading causes of death and the most aggressive type of cancer in women. Resistance to chemotherapy is one of the challenges associated with the development of strategies for the treatment of breast cancer. One way to overcome this issue is to design new agents that target breast cancer cell lines such as MCF-7. In this study, a new series of S-alkylated thieno[2,3-d]pyrimidin-4-ones bearing carboxamide or ketonic scaffolds was synthesized and screened for their cytotoxicity against MCF-7 breast cell lines. Among synthesized candidates, 6d exhibited more potent cytotoxicity against MCF-7 cell lines with IC50 …

Advancing Small Molecule Therapies For Myotonic Dystrophy Type 1, Sawyer M. Hicks

Electronic Theses & Dissertations (2024 - present)

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expression of expanded CUG (CUG^exp) repeat RNA from the myotonic dystrophy protein kinase (DMPK) gene. This CUG^exp repeat RNA’s gain-of-function mechanism leads to the sequestration of muscleblind-like (MBNL) proteins, resulting in widespread alternative splicing dysregulation across tissues. Despite significant research, there are currently no approved therapeutics targeting the underlying causes of DM1. This dissertation explores the development and optimization of a novel class of small molecules, Modified Polycyclic Compounds (MPCs), designed to address splicing dysregulation in DM1. MPCs were designed from previously published …

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

First-Generation Cephalosporins For Treatment Of Acute Hematogenous Osteomyelitis In Children: A Study Of Efficacy And Adverse Effects, Lisa Hiskey, Hiba Saifuddin, Emily R. Levy, Roland Hentz, Nipunie S. Rajapakse, Laura M. Dinnes, Elizabeth H. Ristagno

School of Medicine Faculty Publications

BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule. METHODS: We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and …

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …

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 …

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 …

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 …

Exogenous Exposure To Dihydroxyacetone Mimics High Fructose Induced Oxidative Stress And Mitochondrial Dysfunction, Raj Mehta

Honors Theses

Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette) combustion. Increased use of sunless tanning products and e-cigarettes has elevated exposures to DHA through inhalation and absorption. Studies have confirmed that DHA is rapidly absorbed into cells and can enter into metabolic pathways following phosphorylation to dihydroxyacetone phosphate (DHAP), a product of fructose metabolism. Recent reports have suggested metabolic imbalance and cellular stress results from DHA exposures. However, the impact of elevated exposure to DHA on human health is currently under-investigated. We propose that exogenous exposures to …

The Role Of Alpha-2 Agonists For Attention Deficit Hyperactivity Disorder In Children: A Review, Elisa E. Neuchat, Brooke E. Bocklud, Kali Kingsley, William T. Barham, Patrick M. Luther, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications’ long-term safety and efficacy remain uncertain, with a lack …

Study Of The Potential Toxicity Of Adrenaline To Neurons, Using The Sh-Sy5y Human Cellular Model, Vera Marisa Costa, João Paulo Capela, Maria Lourdes Bastos, Fernando Remião, Kurt James Varner, José Alberto Duarte, Félix Carvalho

School of Graduate Studies Faculty Publications

Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration-and time-dependent in both assays, since the lowest concentration …

Management And Considerations In The Usage Of Txa In Hemorrhagic Trauma Patients, Matthew Petterson, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Tranexamic acid is a synthetic reversible competitive inhibitor that exerts its action on plasminogen, preventing plasmin formation and deterring fibrinolysis.1 Current FDA-approved indications of TXA include heavy menstrual bleeding and short-term blood loss prevention in patients with hemophilia following tooth extraction.1 TXA has more recently been utilized in the management of massive hemorrhagic trauma patients despite this being an off-label use. While TXA has shown promise as a hemostatic agent for this patient population, considerations in the pre-hospital and hospital settings must be examined for its integration into massive hemorrhage protocols.

Case Report: Epinephrine-Containing Topical Anesthetic Gel Inducing Systemic Epinephrine Toxicity, Md Fateha, Philip Willsie

Rowan-Virtua Research Day

Systemic epinephrine toxicity is a rare complication following inadvertent or excessively large or rapid subcutaneous, intramuscular or intravenous administration. Signs and symptoms of epinephrine toxicity include rapid onset of transient agitation, hypertension, tachycardia, lactic acidosis, and dysrhythmias with potentially fatal consequences. In this case report, we present a 33-year-old female who experienced epinephrine toxicity following the use of a topical anesthetic cream containing lidocaine and epinephrine. The patient had multiple applications to her chest before and during tattoo placement which led to tachycardia, elevated blood pressure, headache, chest pain, nausea, vomiting, and anxiety. The patient was brought into the ED …

Case Report: Nosocomial Digital Eczema From Surface Cleansing Bleach, James Espinosa, Umar Sannoh, Alan Lucerna

Rowan-Virtua Research Day

We report the case of a healthcare provider who developed hand eczema, predominantly on the first digit and thumb of the right hand, in association with contact with the surface of a desk and mouse pad at work. The eczema abated on days off and was exacerbated within hours of work. The diagnosis was made of hand eczema from surface cleaning bleach. It was noted that several other healthcare providers had developed similar symptoms. The patient's eczema was confirmed by a dermatologist and was successfully treated with topical triamcinolone and emollient cream to the affected areas. Prevention by adhesive strip …

Case Report And Review: Hawthorne Root Toxicity, James Espinosa, Darren Finn, Alan Lucerna

Rowan-Virtua Research Day

Here we present the case of a patient who purchased a hawthorn root product, Raiz de Tejocote, for weight loss purposes. The side effect profile seen, including a positive digoxin level, are consistent with hawthorn root. This case reinforces the importance of asking a patient about all medications, including over the internet medications.