Chemicals and Drugs Commons^™

Design, Synthesis, Biological And Computational Studies Of Flavonoid Acetamide Derivatives, Daniel Kasungi Isika

Dissertations

Flavonoid compounds (FC) have extensive biological applications through potent antimicrobial, anti-inflammatory, anticancer, antidiabetic, and antioxidant properties. These applications are nevertheless limited by low bioavailability, poor aqueous solubility, enzymatic degradation, rapid metabolism, and fast body clearance. FC show unique structure-activity relationships (SARs) essential in assessing and mitigating the prevalent challenges impeding their applications. These challenges can be addressed by structural modification of the FC through functionalization of the phenolic rings, modification of the ketone group, and modification of the phenolic hydroxyl groups with bioisosteres.

The objectives of this work are to (i) design and synthesize novel flavonoid acetamide derivatives (FADs) and …

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …

Acceptability Of Fully Guided Virtual Implant Planning Software Among Dental Undergraduate Students, Shishir Ram Shetty, Colin Murray, Sausan Al Kawas, Sara Jaser, Wael Talaat, Medhini Madi, Vinayak Kamath, Nisha Manila, Raghavendra Shetty, Vidya Ajila

School of Dentistry Faculty Publications

Background: Fully guided implant surgery as a technique is gaining popularity. It has been observed that use of surgical guides improves precision and predictability for dental implant placement. However, like any other newer technology, the acceptance of fully guided dental implant technology among users is based upon its perceived usability. This study aimed at evaluating the perception about using Virtual Implant Planning Software (VIPS) among undergraduate dental students at the university of Sharjah. Methods: Ninety-Six dental surgery students from the University of Sharjah were included in the study. One week after the Virtual Implant Planning Software (Planmeca Romexis version 6.2 …

Ethical Issues And Standards Of Responsible Research Conduct And Monitoring In An Adventist Institution Of Higher Learning - The Babcock Experience, Kayode O. Ogunwenmo, Godswill N. Anyasor, Grace O. Tayo

Adventist Human-Subject Researchers Association

Ethical issues and standards of responsible research conduct involving human participants are important considerations in any institution of higher learning and in particular Adventist institutions. Research conduct and ethics are reviewed and approved before they begin by the Babcock University Health Research Ethics Committee (BUHREC)

Driving Under The Influence Of Cannabis: Impact Of Combining Toxicology Testing With Field Sobriety Tests, Robert L. Fitzgerald, Anya Umlauf, Jacqueline A. Hubbard, Melissa A. Hoffman, Philip M. Sobolesky, Shannon E. Ellis, David J. Grelotti, Raymond T. Suhandynata, Marilyn A. Huestis, Igor Grant, Thomas D. Marcotte

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers.

METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) 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 …

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

Photoisomerizable Membrane Active Peptides, Cristina Ventura

Seton Hall University Dissertations and Theses (ETDs)

Membrane active peptides (MAPs) bind and partition into the cell membrane thus causing permeabilization. Many α-helical membrane active peptides contain central proline residues that distinguish the hydrophobic and hydrophilic faces of the helix. The proline induces a bend that produces a helix-hinge-helix motif. Mutation of these proline residues has a significant effect on the activity of the MAP. Azobenzene is a photoisomerizable molecule that switches from its trans to cis isomer upon excitation with ultraviolet (UV) light and from its cis to trans isomer upon excitation with visible light (VL). In this work it is hypothesized that the hinge function …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Novel Allosteric Effectors Targeting Human Transcription Factor Tead, Mayar Terek Ibrahim, Gennady M. Verkhivker, Jyoti Misra, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The Hippo pathway is an evolutionary conserved signaling network involved in several cellular regulatory processes. Dephosphorylation and overexpression of Yes-associated proteins (YAPs) in the Hippo-off state are common in several types of solid tumors. YAP overexpression results in its nuclear translocation and interaction with transcriptional enhanced associate domain 1-4 (TEAD1-4) transcription factors. Covalent and non-covalent inhibitors have been developed to target several interaction sites between TEAD and YAP. The most targeted and effective site for these developed inhibitors is the palmitate-binding pocket in the TEAD1-4 proteins. Screening of a DNA-encoded library against the TEAD central pocket was performed experimentally to …

Improved Synthesis And Anticancer Activity Of A Potent Neuronal Nitric Oxide Synthase Inhibitor, Dhananjayan Vasu, Cory T. Reidl, Eric Wang, Sun Yang, Richard B. Silverman

Pharmacy Faculty Articles and Research

An improved synthesis of 4-methyl-7-(3-((methylamino)methyl)phenethyl)quinolin-2-amine (1) is reported. A scalable, rapid, and efficient methodology was developed to access this compound with an overall yield of 35%, which is 5.9-fold higher than the previous report. The key differences in the improved synthesis are a high yielding quinoline synthesis by a Knorr reaction, a copper-mediated Sonogashira coupling to the internal alkyne in excellent yield, and a crucial deprotection of the N-acetyl and N-Boc groups achieved under acidic conditions in a single step rather than a poor yielding quinoline N-oxide strategy, basic deprotection conditions, and low yielding copper-free conditions that …

Diffusion Of Ionic Liquid-Modified Polymer Nanoparticles Through Nasal Mucus, Mary Vanlandingham

Honors Theses

Mucosal barriers are a natural defense system for preventing the entry of foreign objects into the body; however, they pose as obstacles for effective drug delivery. Coated polymer nanoparticles have been proven to possess improved rates of diffusion across mucus compared to their uncoated, or bare, counterparts. When choline-based ionic liquids (ILs) are introduced to an aqueous system, their dissociation leads to an increase in solution conductivity which ultimately reduces the viscosity of mucus without significantly affecting its structure. Additionally, ILs are highly tunable, so they work well in a range of pHs and conductivities, making ILs an ideal choice …

Botulinum Toxin For Abductor Type Spasmodic Dysphonia: A Systematic Review, Keyona Sutton

Honors Theses

A systematic review was conducted to show that BTX (Botulinum Toxin) is the most effective treatment for Abductor Spasmodic Dysphonia (ABSD). There were a total of 117 records screened for inclusion in this review. After the initial screening, there were seven successive rounds of screening for eligibility. This process produced a total of three eligible records that met the following conditions: patients presented with spastic abduction, electromyography BTX type A injection into the posterior cricoarytenoid muscle, and measurement of results with acoustic dimensions. After surveying all eligible studies, it was concluded that BTX is an effective treatment for ABSD. Every …

Dextromethorphan/Quinidine For The Pseudobulbar Affect In Neurological Disorders And Injuries: Systematic Review And Meta-Analysis, Magnolia Livingston

Honors Theses

AVP-923, commonly known as Nuedexta or Zenvia, is a drug that has recently been suggested as a potential treatment for Pseudobulbar Affect in patients affected by different neurological disorders and injuries. Studies have been done to examine the effectiveness of AVP-923 on PBA, but the results of these studies don’t seem to be comparable. The goal of this meta-analysis is to assess the efficacy and safety of AVP-923. 781 individuals from six trials were included in the analysis. The analysis's findings revealed that AVP-923 considerably lowered the Center for Neurological Study Lability Scale (CNS-LS) scores and the frequency and severity …

Eco-Interoception: What Plants, Fungi And Protista Have Taught My Body, Sara Riley Dotterer

Art Theses and Dissertations

To me, ecology is the relational, full-body awareness that I am made up of and deeply connected to everything around me; and for better or worse, this is reciprocal. I form ecotones, an ecological transitional zone between two ecosystems, with the world around me. I use this ecotonal lens to blur binaries and dissolve boundaries between me and the world “outside my body.” During my Masters of Fine Arts at Southern Methodist University, I have continuously explored and represented the lives of various more-than-human species outside of my body, including plants, fungi and protista through an ecotonal lens. Although these …

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …

Comparison Between Honey Produced By Bees, Aphids And Wasps In Kurdistan Region - Iraq Based On Biochemical Parameters, Jian Lateif Hussein

Al-Bahir

Honey is a sweet substance that has been valued by humans for its taste and health benefits. It is produced by honey bees from the sugary secretions of plants. However, other insects, such as aphids and wasps, also produce honey-like substances. This study aimed to compare the physical and biochemical properties of honey produced by honey bees, aphids, and wasps in the Kurdistan Region of Iraq. To achieve this, samples of honey, bitter honey, honeydew, and wasp honey were collected and examined. The samples were analyzed for total sugar, sucrose, water, Hydroxymethylfurfural (HMF), acidity, total acidity, diastase activity, total phenolic …

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 …

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Intramuscular Administration Of The Host-Derived Immunostimulant Cpdi-02 Increases Protection Of Outbred Mice And Piglets Against Dermal Mrsa Infection In A Curative Setting And Is Well Tolerated After Repeated Administration, Jason P. Stewart

Theses & Dissertations

Staphylococcus aureus is the most common cause of bacterial skin and soft tissue infections (SSTIs) and the leading cause of hospital-associated infections in the United States. The abundance of S. aureus infections is due, in part, to its virulence factors that suppress host immune system and the development of antibiotic resistance strains such as methicillin-resistant S. aureus (MRSA). In contrast to antibiotics, Host-Directed Therapeutics (HDTs), avoid the pitfalls of antibiotics by targeting the host for immune system rather than targeting the pathogen. This mechanism of action avoids selective evolutionary pressure, which leads to antibiotic resistance and helps the host immune …

Detection Of Sars-Cov-2 Mutations In Vermillion, Sd, Wastewater Utilizing Probe-Based Rt-Qpcr, Matthew J. Schmitz

Honors Thesis

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the subgenus Sarbecovirus, has presented numerous public health challenges for communities across the globe. As demonstrated by the Delta variant (B.1.617.2) and the recent Omicron variants, the virus can mutate and pose new risks for communities, such as reinfection, increased transmissibility, and variable mortality. As such, accurately monitoring the spread of specific variants has become a priority for public health agencies. However, clinical testing faces various limitations, and the increased use of at-home test kits inhibits surveillance. Wastewater-based epidemiology (WBE) can monitor infection rates of entire …

The Threat Of Hospital Wastewater: An Evidence-Based Call To Action, Ann P. Nguyen

DNP Qualifying Manuscripts

Introduction: Hospital wastewater carries a unique composition of pollutants, a burden that includes high chemical and biological residuals. These pollutants are discharged into sewage treatment plants and natural environments where they contaminate human water sources and larger ecosystems. Water treatment plants are not designed to treat the high loads of biomedical waste and persistent organic compounds found in hospital wastewater and therefore pollutants survive in conventionally treated water. Evidence of contaminated soil, municipal wastewater, surface water, ground water, and even drinking water have been demonstrated in studies conducted around the world highlighting the ubiquity of the problem. Hospital effluent as …

The Effects Of Prenatal Buprenorphine Exposure On The Neurobehavioral Development Of The Child, Zaineb Zubair, Maryam Zubair, Juan Alonso, Abdullah Zubair

Rowan-Virtua Research Day

Background: Current guidelines for pregnant women with substance use disorder advise prenatal maintenance of opioid agonist therapy with either buprenorphine or methadone. Despite this rise in prenatal opioid agonist therapy, little is known about the effect of prenatal buprenorphine on the neurobehavioral development of the child. This poses the question: does buprenorphine have a long-lasting effect on the central and peripheral nervous system development and behavior of children who were exposed prenatally?

Methods: A comprehensive literature review identified articles relating to prenatal buprenorphine and neurobehavioral outcomes. Article searches were conducted on PubMed and Dynamed. Publications from 2002 through November 2021 …

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 …

Characterization Of Antibiotic Susceptibility Profiles Of Extensively- And Pan-Drug Resistant Acinetobacter Baumannii Clinical Isolates, Rachel Carr, Justin Halim, Rebecca Fliorent, Henry Fraimow, Dejan Nikolic, Valerie Carabetta

Rowan-Virtua Research Day

Acinetobacter baumannii is an opportunistic pathogen common in intensive care units (ICUs), particularly among immunocompromised individuals. Nosocomial A. baumannii infections have become increasingly problematic in recent years, as these bacteria rapidly acquire antibiotic resistance, leading to the emergence of multidrug, extensively drug and pan drug-resistant (MDR, XDR, and PDR, respectively) isolates. Recently, Cooper University Hospital (CUH) experienced a large increase in highly drug-resistant A. baumannii infections, which had a mortality rate of 60%. Oftentimes, physicians had to turn to combinations of drugs with no experimental verification or historically shelved antibiotics, such as the polymyxins, in a desperate attempt to save …

Chemical Restraints In The Emergency Department, Nicholas Noffsinger

Rowan-Virtua Research Day

Chemical restraint is a critical intervention used in emergency departments to manage acutely agitated or violent patients. It involves the administration of medication to induce sedation and control behavior, with the goal of ensuring patient and staff safety while allowing necessary medical interventions to be performed. However, the use of chemical restraints necessitates close observation of vital signs and any potential side effects, as well as careful consideration of patient-specific considerations.

Brash Syndrome Case Report And Brief Review, Kelly Schuitema

Rowan-Virtua Research Day

BRASH syndrome is an acronym that stands for bradycardia, renal failure, AV node blocker, shock and hyperkalemia. The syndrome is precipitated by synergism from AV nodal blocking agents and hyperkalemia. The combination of the AV nodal blockade and renal failure leads to a cycle of severe bradycardia and hyperkalemia. We will discuss a case of BRASH syndrome with a 68 year old female who presented with generalized weakness and was found to be hypotensive, bradycardia, in acute renal failure with hyperkalemia likely related to metoprolol and amlodipine use.

Release The Kratom: Post-Acute Withdrawal Syndrome In A 70 Year Old Male, Nardin El-Shammaa, Kyle Street, Narsimha Pinninti

Rowan-Virtua Research Day

Centuries in Eastern medicine.. Kratom has been commonly used for chronic pain and opiate withdrawal symptoms with first reported cases in the United States in the early 2000s. It is a plant that consists of psychoactive alkaloids that target opioid receptors with different affinity. Effects from Kratom are dose-dependent, at lower doses, it acts as a stimulant, while at higher doses produces analgesia and euphoria. Although Kratom is legal and easily accessible over the counter, there have been increasing reports of potential for addiction and toxicity. Cessation of Kratom can result in withdrawal symptoms similar to opiate withdrawal. Here we …