Chemicals and Drugs Commons^™

Benzofuran Derivatives Substitute For The Discriminative Stimulus Effects Of 3,4methylenedioxymethamphetamine (Mdma) In Male Sprague-Dawley Rats, Candace Johnson

Masters Theses

4-Methylenedioxymethamphetamine (MDMA) is currently under evaluation in phase III clinical trials as medication-assisted therapy for post-traumatic stress disorder (PTSD) and is expected to be approved by the FDA for clinical use in the near future. MDMA is also a popular abused substance with risks for cardiovascular toxicity and neurotoxicity, particularly when misused at higher doses. Characterization of the behavioral and neurochemical effects of novel psychoactive substances is an essential step in the development of safer alternative therapeutic agents. Drug discrimination is a preclinical behavioral assay with pharmacological specificity for characterizing in vivo drug actions in the central nervous system. This …

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …

Data-Driven Analysis Of Drug And Substance Abuse Rates Across The Varying Regions In The United States Of America, Reem Saleh

University Honors Theses

Drugs and substance abuse is one of the leading causes of death for adolescents in the United States. The consequences of using these drugs are profound and can cause both damage to one's physical and psychological health. The rates of drug abuse in the United States continue to increase over the years. This paper analyzes the trends in rates of drug abuse in the four regions in the United States. It looks at the rates in cocaine, cigarettes, marijuana, and tobacco. A preliminary analysis was done to look at the trend in rates followed by an ARIMA time series model …

Omarigliptin Attenuates Rotenone-Induced Parkinson's Disease In Rats: Possible Role Of Oxidative Stress, Endoplasmic Reticulum Stress And Immune Modulation, Shereen Mowaka, Haidy E. Michel, Mariam M. Tadros, Moataz S. Hendy, Bassam M. Ayoub

Pharmacy

The current study aimed to explore the potential neuroprotective effect of omarigliptin (OG), an antidiabetic drug that crosses the blood-brain barrier (BBB), in a Parkinson's disease (PD) rotenone-based rat-model. Results showed that OG attenuated motor impairment, histological aberrations, α-synuclein accumulation, and rescued the dopaminergic neurons in rotenone-administered rats. Furthermore, OG halted rotenone-induced oxidative stress; as shown by reduced lipid peroxidation, decline in the oxidative stress sensor (nuclear factor erythroid 2-related factor 2) and its downstream heme oxygenase-1. In addition, OG abrogated neuroinflammation and apoptosis in rotenone-treated rats. Moreover, OG ameliorated endoplasmic reticulum (ER) stress in rotenone-administered rats; as evidenced by …

Early Th2 Inflammation In The Upper Respiratory Mucosa As A Predictor Of Severe Covid-19 And Modulation By Early Treatment With Inhaled Corticosteroids: A Mechanistic Analysis, Jonathan R. Baker, Mahdi Mahdi, Dan V. Nicolau, Sanjay Ramakrishnan, Peter J. Barnes, Jodie L. Simpson, Steven P. Cass, Richard E. K. Russell, Louise E. Donnelly, Mona Bafadhel

Research outputs 2022 to 2026

Background: Community-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19. Methods: The STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in …

Elisa Validation Method For The Detection Of Ketamine In Hair, Daria A. Centonza

Student Theses

An ELISA method was developed and validated to detect ketamine in human hair samples. Ketamine is an anesthetic drug that causes memory loss, dissociative sensations, and hallucinations. Due to these adverse effects, ketamine is a common drug used in drug facilitated sexual assaults (DFSAs). It is very important to be able to detect the substances used in DFSAs over a longer period of time due to the delayed reporting of these crimes. Victims, often out of fear and from the sedative/memory loss effects of the drugs, tend to report these crimes when it is too late to use urine and …

Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan

School of Medicine Faculty Publications

Abstract: Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

Synthesis, Characterization, And Bioactivity Of 3-Substituted Coumarins As An Undergraduate Project, Karsen King, Nicholas Campbell, Ronald Okoth, Wathsala Medawala

Georgia Journal of Science

Coumarins are an important class of phytochemicals, a chemical defense presumed to be secreted by plants. More recently, Coumarins have gathered popularity for their basis in anti-cancer agents. This paper dives into the organic synthesis of two 3-substituted coumarins from o-vanillin using the Knoevenagel condensation reaction. The 3-substituted coumarin were characterized using melting point analysis, ¹H-NMR, and UV-Vis spectroscopy. In addition, the anticancer activity of synthesized 3-substituted coumarin compounds were assayed against topoisomeraseIIα, which is the target enzyme of FDA approved anti-cancer drug etoposide since it is an active enzyme in cancer cell replication. The demonstrated procedures can be …

Updates In The Pharmacologic Prophylaxis And Treatment Of Invasive Candidiasis In The Pediatric And Neonatal Intensive Care Units, James Hunter Fly, Seerat Kapoor, Kelly Bobo, Jeremy S. Stultz

Faculty Publications

Purpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).

Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United …

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …

The Use Of Silica Nanoparticles For Controlled Drug Delivery Of Nicotine, Jennifer C. Iwenofu

Honors College Theses

Drug molecules can be administered in different ways to the human body. Nanotechnology stands out over other alternatives by delivering drugs to specific locations and reducing reactivity time. In this research, the hydrogen bond between silica nanoparticles and the drug molecule, nicotine, were studied to controllably deliver nicotine by varying pH values.

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …

Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani

Mathematics, Physics, and Computer Science Faculty Articles and Research

At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection …

Synthetic Investigations In Chemical Probe Development Part 1: Design And Synthesis Of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis Of 2,8-Dihydroxychrysene, Rachel Irene Hammond

Honors Theses

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired …

Lectin-Glycan Complexes: A Comprehensive Analysis Of Docking Calculations, Ashton Custer

Honors Theses

Lectins are a type of glycan-binding protein that noncovalently bind glycans. Carbohydrates are molecules consisting of sugar units joined together. Glycans are carbohydrates. Hence, glycans are also sugars. Lectins and lectin-glycan complexes have a range of biological roles and can be found in animals (including humans), plants, bacteria, viruses, and yeasts and fungi.¹ Many scientists focus on the computational study of these complexes due to their intricate roles in many living organisms. Computational study is important in furthering our knowledge of lectin-glycan complexes and other such protein complexes. However, computational study is not perfect. There are many challenges in …

A Study Of Dextran As A Macromolecular Crowding Agent, Katherine Morgan

Honors Theses

Deoxyribonucleic acid (DNA) is the hereditary material in all living organisms. According to the Watson and Crick model, DNA exists as two long strands coiled into a double helix. However, DNA has been found to have the potential to exist in secondary forms known as G-Quadruplexes and i-motifs. I-motifs (intercalated-motif or iM) are formed under acidic conditions when sets of cytosines pair with protonated cytosines and are looped around each other. The pKa value for iMs in dilute solutions is approximately 6.5, but iMs can potentially exist at a higher, physiological pH value under crowded conditions. Within the interior of …

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs in enhancing transdermal …

The Effects Of Thc On Hiv Tat Protein-Mediated Neuroinflammation, Camille Martin

Honors Theses

Although antiretroviral therapies have allowed people living with human immunodeficiency virus (HIV) to achieve normal life expectancies, they cannot cure HIV nor the neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological disorders including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition. The mechanisms by which HIV promotes neurological impairment are not known, but may involve actions of its neurotoxic proteins. One such protein that has been well-characterized is the HIV trans-activator of transcription (Tat). Tat exerts neurotoxic effects via various means, one of which is to activate microglia, the macrophages of …

Lc-Ms Identification Of Serum Proteins Adsorbed Onto Ionic Liquid-Coated Nanoparticles, Anh M. Hoang

Honors Theses

Nanocarriers are promising candidates for drug delivery due to their size and tunable surface characteristics. However, when they are intravenously injected, few particles make it to their designated location. This is because upon entering the bloodstream, the serum in the blood, which is rich with a diversity of proteins, adsorbs onto the particles’ surfaces forming a protein corona. Many of the attached proteins trigger the mobile immune system and are removed by macrophages, and many particles are then filtered out by the liver and kidneys. Ionic Liquids (ILs), which consist of asymmetric, bulky components that are liquid

The Development Of Polymeric Dexamethasone Prodrug Nanomedicines For The Treatment Of Lupus Nephritis, Zhifeng Zhao

Theses & Dissertations

Lupus nephritis (LN) is a significant cause of morbidity and mortality among lupus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GCs’ adverse effects while maintaining their potent therapeutic efficacy, we have developed a micelle-forming polyethylene glycol (PEG)-conjugated dexamethasone prodrug (ZSJ-0228), which could passively target the inflamed kidney in NZB/W F1 lupus-prone mice. It was found that monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. Unlike the dose equivalent daily dexamethasone treatment, long-term …

Characterization Of 1,1-Diarylethylene Foxm1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells, Cassie Liu

Theses & Dissertations

Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases, and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell …

Effects Of Waterborne Benzo[A]Pyrene Embryonic Exposure On Development, Behavior, Reproduction, And Mitochondrial Bioenergetics In Zebrafish, Megha Patel

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen leading to adverse effects in the development of both humans and animals. BaP is also continuously present in the environment leading to regular exposure via inhalation or ingestion. Because organisms’ early life stages can be more susceptible to contaminant exposure, our focus was on BaP’s adverse impacts on survival, length, weight, behavior, bioenergetic state, and fecundity following developmental exposures. To study BaP’s impacts, zebrafish (Danio rerio) were used as a model organism. BaP is a ligand for the aryl hydrocarbon receptor (AHR in humans; Ahr in …

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most …

The Role Of Age Ligand And Rap1a In Myofibroblast Signaling Cascade In Type 2 Diabetes Mellitus-Induced Cardiomyopathic Conditions, Camilla Puglia

Honors Theses

Diabetes is one of the leading causes of death in the United States, taking more than 90,000 lives annually. Type 2 diabetes mellitus-induced cardiac fibrosis is a common condition seen in diabetic patients. The AGE/RAGE signaling cascade has been strongly associated with this supposed cardiac fibrosis along with hyperactive myofibroblasts which excessively remodel extracellular matrix tissue, leading to damaged and enlarged heart muscle tissue. In diabetic patients, Advanced Glycation End Products (AGEs) are produced in abundance and accumulate in the extracellular matrix of heart tissue. To investigate the role of of the AGE ligand on fibroblast behavior, increasing amounts of …

Investigation Into The Detection Of Drug Metabolites In Latent Fingerprints, Paige Oden

Honors Theses

Fingerprinting has proved a useful mode of identification for thousands of years. Following numerous technological advancements, it has become a technique for categorizing and keeping track of people over large geographical spaces for almost half of a century. Those living in the beginnings of fingerprinting used them as a form of signature as it was something completely unique to each individual that could not be replicated. Although they are no longer used as the primary form of signature, it certainly remains a biomarker of identity. Over the past century the practice has been heavily refined in order to identify people …

Migratory Dermatographic Urticaria Following Covid-19 Vaccine Booster In Young Adult Male, Richard A. Maiella, Kelly Staples, Ashok Veldanda

Rowan-Virtua Research Day

With the recent approval of booster vaccinations in the United States for adults who already received their primary vaccinations, millions of adults have been administered the Pfizer-BioNTech or Moderna booster vaccines.

Adverse events related to these vaccines continue to be reported and are majority self-limited. In this case report, we present a young male who acquired chronic, migratory dermatographic urticaria two weeks after administration of the Moderna mRNA-1273 COVID-19 vaccine booster.

Safety And Efficacy Of Silver-Coated Biomaterials In Vivo, Megan Klem, Darien L. Seidman, Rahyan Mahmoud, Manuella Adu, Lei Yu, Jeffrey Hettinger, Renee M Demarest

Rowan-Virtua Research Day

Overtreatment and overuse of antibiotics in healthcare and agricultural settings have contributed to the selective pressure on bacterial strains to develop resistance. Resistance can develop as a result of mutations and subsequent resistance genes that allow bacteria to survive against antibiotics. Novel silver-oxide coatings were developed and were previously demonstrated to prevent adhesion of gram-negative bacteria (Escherichia Coli and Pseudomonas Aeruginosa) to the disc, but did not prevent gram-positive bacterial adherence (Streptococcus Aureus). In order to determine whether the silver-oxide coatings are bacterial static and may be preventing progression to biofilm formation, in vivo analysis of S. Aureus attached to …

Stroke In Hfref Without Atrial Fibrillation And Concurrent Protein S Deficiency: What Is The Best Treatment?, Rohan Umrani, Trinava Roy, Bhavana Kadiyala, Yvette Wang

Rowan-Virtua Research Day

Hypercoagulable disorders are often the culprit for repeated strokes in young patients, with or without other comorbidities

Medications typically used for stroke prophylaxis:

• Warfarin
• Aspirin
• Direct Oral Anticoagulants (DOACs)

Warfarin is the preferred method of anticoagulation for stroke prophylaxis in patients with hypercoagulable disorders

A deficiency of protein S increases the risk of pro coagulation due to a relative deficiency of anticoagulants.

Patients with protein S deficiency tend to have recurrent venous thromboses and pulmonary emboli