Chemical and Pharmacologic Phenomena Commons^™

Design And Investigation Of Small Molecule Drugs For Potential Treatment Of Cns Disorders, Flaviviral Infections, And Cancers, Viktoriya Mashinson

Theses & Dissertations

Chapter 1 discusses the development of antagonists against the dopamine 4 receptor (D4R) that is expressed in the motor, associative, and limbic subdivisions of the basal ganglia network and is involved in Parkinson’s disease (PD). Levodopa is the firstline drug for the management of PD symptoms but its long-term use often leads to development of levodopa-induced dyskinesia (LID). D4R antagonists have been shown to decrease the abnormal involuntary movement scores in mouse models of LID. Chapter 1 outlines the development and optimization of selective D4R antagonists for potential treatment of LID. During the investigation of our D4R antagonists we discovered …

Uncontrolled Hypertension Or A Bad Medication Interaction? The Importance Of Reviewing Over-The-Counter Medications During Medication Reconciliation, Shefali Amin Do, Caitlyn R. Moss Md

Transformative Medicine

Introduction: In the management of chronic conditions, review of the complete medication list for potential drug-drug interactions is crucial. This case involves a patient taking activated charcoal for unclear reasons, leading to misdiagnosed uncontrolled hypertension.

Case Description: We present the case of an elderly male with uncontrolled hypertension who had been placed on multiple chronic antihypertensives for years. On further review, he was found to be taking activated charcoal twice daily thereby inactivating his five oral antihypertensive medications and making his blood pressure difficult to control. Discontinuation of the activated charcoal led to significant improvement in his blood …

Autoimmunity And The Epigenome, Jeffrey S. Miller Jr

The Cardinal Edge

No abstract provided.

Effects Of Sex And Estrous Cycle On Extended-Access Oxycodone Self-Administration And Cue-Induced Drug Seeking Behavior, Bhumiben P Patel, Jessica A Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Increasing evidence indicates that sex is a factor that impacts the abuse liability and relapse vulnerability of prescription opioids like oxycodone. However, while women are more likely than men to be prescribed and to use these drugs, the impact of sex and ovarian hormones on prescription opioid use and relapse vulnerability remains unclear. Accurately assessing these measures is complicated by the fact that chronic opioid exposure can lower ovarian hormone levels and cause cycle irregularities.

METHODS: Adult male and female Sprague-Dawley rats self-administered oxycodone (0.1 mg/kg/infusion) under extended-access conditions (6 h/day, 10 days) followed by forced abstinence. Separate groups …

Meca In Streptococcus Mutans Is A Multi-Functional Protein, Kassapa Ellepola, Robert C. Shields, Jessica K. Kajfasz, Hua Zhang, Jose A. Lemos, Hui Wu, Zezhang T. Wen

School of Dentistry Faculty Publications

UNLABELLED: Our recent studies have shown that deficiency of MecA in Streptococcus mutans significantly affects cell division, growth, and biofilm formation. In this study, an in vitro mixed-species model, proteomics, and affinity pull-down assays were used to further characterize the MecA-mediated regulation in S. mutans. The results showed that compared with the wild type, UA159, the mecA mutant significantly reduced its production of glucans and weakened its ability to facilitate mixed-species biofilm formation. Relative to the wild type, the mecA mutant also displayed unique characteristics, including colony morphology, growth rate, and biofilm formation that did not fully resemble any of …

Diverse Pathways In Gpcr-Mediated Activation Of Ca2+ Mobilization In Hek293 Cells, Francesco De Pascali, Asuka Inoue, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

G protein-coupled receptors transduce extracellular stimuli into intracellular signaling. Ca²⁺ is a well-known second messenger that can be induced by G protein-coupled receptor activation through the primary canonical pathways involving Gα_q- and Gβγ-mediated activation of phospholipase C-β (PLCβ). While some G_s-coupled receptors are shown to trigger Ca²⁺ mobilization, underlying mechanisms remain elusive. Here, we evaluated whether G_s-coupled receptors including the β₂-adrenergic receptor (β₂AR) and the prostaglandin EP₂ and EP₄ receptors (EP₂R and EP₄R) that are endogenously expressed in human embryonic kidney 293 …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

An Interesting Case Of Wunderlich Syndrome And Page Kidney, Megan Worthington, Nicholaus Monsma, Raj Pyne

Advances in Clinical Medical Research and Healthcare Delivery

We present a case of Wunderlich Syndrome and Page Kidney, a rarely reported combination. Wunderlich Syndrome, characterized by spontaneous renal hemorrhage without a history of trauma, is typically associated with Lenk’s triad of flank pain, mass, and hypovolemia. Page Kidney induced hypertension, a rare condition resulting from external renal compression associated with renin-mediated mechanisms. Our case demonstrates the importance in quick recognition and treatment as blood pressure changes can be fast and dramatic. Our case also has the added dimension of renin measurements. After the patients hypertension developed, his initial renin levels were within normal range, but they later showed …

Intrinsically Disordered Membrane Anchors Of Rheb, Rhoa, And Diras3 Small Gtpases: Molecular Dynamics, Membrane Organization, And Interactions, Chase M Hutchins, Alemayehu A Gorfe

Faculty, Staff and Student Publications

Protein structure has been well established to play a key role in determining function; however, intrinsically disordered proteins and regions (IDPs and IDRs) defy this paradigm. IDPs and IDRs exist as an ensemble of structures rather than a stable 3D structure yet play essential roles in many cell-signaling processes. Nearly all Ras superfamily GTPases are tethered to membranes by a lipid tail at the end of a flexible IDR. The sequence of the IDR is a key determinant of membrane localization, and interaction between the IDR and the membrane has been shown to affect signaling in RAS proteins through the …

Uses Of Herbal Extracts In Endodontology: A Literature Review, Reem Chamseddine, Roula S. Abiad

BAU Journal - Science and Technology

The use of natural herbal extracts in the field of dentistry, and specifically in endodontology had gained a high popularity in the past few years. The main objective of endodontic treatment is to prevent and eliminate the infection from the root canal, seize the invasion of microorganisms to periradicular tissues and preserve the natural dentition. Studies had shown that some herbs are better alternatives to traditional chemical irrigants or medicaments used in root canal treatment, based on their potential antimicrobial effect, smear layer removal capabilities, tissue dissolution effect, antioxidant, anti-inflammatory and regenerative properties. Aim: The purpose of this literature review …

Identifying Targetable Vulnerabilities To Circumvent Or Overcome Venetoclax Resistance In Diffuse Large B-Cell Lymphoma, Clare M. Adams, Amanda Mcbride, Peter Michener, Irina Shkundina, Ramkrishna Mitra, Hyun Hwan An, Pierluigi Porcu, Christine M. Eischen

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Clinical trials with single-agent venetoclax/ABT-199 (anti-apoptotic BCL2 inhibitor) revealed that diffuse large B-cell lymphoma (DLBCL) is not solely dependent on BCL2 for survival. Gaining insight into pathways/proteins that increase venetoclax sensitivity or unique vulnerabilities in venetoclax-resistant DLBCL would provide new potential treatment avenues. Therefore, we generated acquired venetoclax-resistant DLBCL cells and evaluated these together with intrinsically venetoclax-resistant and -sensitive DLBCL lines. We identified resistance mechanisms, including alterations in BCL2 family members that differed between intrinsic and acquired venetoclax resistance and increased dependencies on specific pathways. Although combination treatments with BCL2 family member inhibitors may overcome venetoclax resistance, RNA-sequencing and drug/compound …

The Role Of Skeletal Muscle Ampk/Mtorc1 Signaling In Disrupted Metabolism During Chemotherapy Treatment And Recovery, Jessica L. Halle

Alternative Theses and Dissertations (AETDs)

Colorectal cancer patient survival rate has increased over the past decade due to improved screening and treatment options. The clinically relevant FOLFOX (5-fluorouracil [5-FU], oxaliplatin, leucovorin) chemotherapy regimen is a mainstay treatment option, despite the development of severe side-effects that can occur acutely or develop as a late effect after treatment cessation. Cancer and chemotherapy can promote systemic metabolic dysfunction; consequently, patients will likely experience debilitating weakness and fatigue, and these symptoms are often accompanied by excessive fat and muscle loss. Although studies have established chemotherapy effects on the tumor, few have investigated mechanisms underlying the metabolic complications associated with …

An Integrative Review Of The Absorption Of Fda-Approved Chemical Sunscreen Filters Into The Blood, Srinidhi Banala, Samrat Gollapudi, Abhiram Gollapudi, Bhaumik Patel

Rowan-Virtua Research Day

Introduction: This integrative review examines the absorption of FDA-approved chemical sunscreen filters, specifically avobenzone and oxybenzone, into the bloodstream. The study aims to compare the levels of absorption and potential health effects of systemic exposure to these sunscreen ingredients in the United States.

Methods: The researchers conducted a literature search of 57 articles, of which 15 were used for the review. Inclusion criteria focused on studies discussing absorption levels of avobenzone and oxybenzone, as well as methods of absorption into the bloodstream. Exclusion criteria included sunscreen ingredients not approved in the United States, non-English studies, and studies on methods to …

Soluble Antimicrobial Peptide (Amp) Screening To Rationally Design Amp-Hydrogels That Selectively Prevent Biofilm Formation, Matthias Recktenwald, Muskanjot Kaur, Mohammed M. Benmassaoud, Aryanna Copling, Tulika Khanna, Michael Curry, Denise Cortes, Gilbert Fleischer, Valerie J. Carabetta, Sebastián L. Vega

Rowan-Virtua Research Day

Staphylococcus aureus is an opportunistic pathogen that lives on surfaces and skin and can cause serious infections once inside the body. While antibiotics effectively kill bacteria, there are a growing number of infections with antibiotic-resistant strains. Antimicrobial peptides (AMPs) are part of the innate immune system and can eliminate pathogens including bacteria, fungi, and viruses, and are a promising alternative to antibiotics. Although studies have reported that AMP-functionalized hydrogels can prevent bacterial adhesion and biofilm formation, these materials generally consist of one AMP at an arbitrary concentration, and AMP dosing and the combined effects of multiple AMPs are not well …

Selective Serotonin Reuptake Inhibitors And Pharmacological Resetting Of The Mind, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

Mental activity is capable of processing analytical data (mathematics, physics, socio-political science, philosophy, etc.) similar to computer software. At the same time, mental activity largely depends on the brain, which works like a hard component of a computer. While the computer stores data on a physical medium, mental activity and data are supported by physiological mechanisms that are constantly operating (both in wakefulness and sleep). For this reason, the lack of brain oxygenation even for short periods of time (5-10 minutes) causes the loss of all data, including the disappearance of the individual's existence as a mental entity. This means …

An Exploration Of The Effectiveness Of Xanthorrhiza Simplicissima And Its Secondary Alkaloids As Antibiotics Against Staphylococcus Aureus With The Use Of Reserpine, Donald Bothe, Savita Chaurasia

Undergraduate Theses

Xanthorhiza simplicissima is a plant that is steeped in medical history. It has been used for hundreds of years by the Native Americans, and later by the Europeans, of Appalachia for its medicinal properties. One of the most useful medical applications of this plant are its antibiotic properties, as typified by its use as a tea that was consumed to treat mouth sores. These antibiotic properties can be attributed to some of its secondary alkaloids such as berberine, liriodenine, oxyacanthine, and magnoflorine. These compounds have been studied in other systems; however, oxyacanthine and magnoflorine have not been researched in tandem …

Non-St Elevation Myocardial Infarction Presentation In Severe Aortic Stenotic Patient, Margi Desai, Daniel Maysonet

The Journal of Integrated Primary Care

This case report demonstrates a patient who presents with typical findings for a diagnosis of NSTEMI. Upon further evaluation, this diagnosis was able to be ruled out. Presentations and labs consistent with NSTEMI masked the true diagnosis of aortic stenosis due to oxygen supply/demand mismatch.

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: Scholarly Activities

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …

Exploring The Developmental Effects Of Antidepressants In Caenorhabditis Elegans, Alexandra Van Stone

Annual Research Symposium

It is so important to explore the potential side effects of antidepressants especially if these side effects could lead to a future detriment to an individual’s financial and social well-being. A better understanding of these side effects in regards to human developmental issues is imperative considering issues related to mental health and depression affect a large percentage of the population. In this study, we tested if Caenorhabditis (C.) elegans could be a potential model organism to predict possible side effects associated with select antidepressants. Their developmental problems potentially encountered upon drug treatment may be encountered in humans.

Synthesis And Biological Evaluation Of New Nicotinic Acid Derivatives As Potential Anti-Inflammatory Agents With Enhanced Gastric Safety Profile, Eman Ramadan, Zeinab Mahmoud, Nadia Khalil

Pharmacy

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 …

Hardness Removal By A Continuous Flow Electrochemical Reactor From Different Types Of Water, Shahad Fadhil Alrubaye, Naseer A. Al Haboubi, Hussein A. Al-Amili, Aiman H. Al-Allaq, Dhuha Ahmed Mohammed

Mechanical & Aerospace Engineering Faculty Publications

The present study focuses on the technique of hardness removal by using a novel reactor performing an electrocoagulation (EC) process. The variation of alkalinity is also recorded. Continuous flow experiments were conducted for Total Hardness (TH) removal using a transparent plastic reactor using aluminum plate electrodes that have holes so that the water flows through the plates in a zigzag way. The influence of various operating parameters such as the number of plates (two and four), flow rate (600, 1000 L/h), and water type (Tigris River & rejected water from Reverse Osmosis system RO) was investigated. The results showed that …

Synthetic Neuroactive Steroids Targeting Gaba-A Receptors As A Potential Therapy For Contraceptive-Associated Mood Disorders, Alexandria A. Davis

Scripps Senior Theses

4-10% of women who use hormonal oral contraceptives (HOCs) discontinue use after experiencing symptoms of anxiety, irritability, and depression in the first 3 months of administration. Previous studies have acknowledged a relationship between HOCs and emotional dysregulation but have not identified mechanisms by which HOCs have this effect. As a result, effective treatment options for HOC-induced mood disorders are lacking. Current theories implicate combined-HOCs, particularly those containing ethinyl estradiol and levonorgestrel (EE-LNG), in reducing neuroactive steroid levels. Specifically, HOC users show decreases in allopregnanolone, a positive allosteric modulator associated with neuronal inhibition and emotional regulation. The objective of this study …

The Impact Of Prenatal Paternal Cigarette Smoke On Male Urogenital Disorders: A Systematic Review, Raphaelia V. Mcdonald

Honors Undergraduate Theses

Urogenital disorders, including cryptorchidism, hypospadias, and reduced semen quality, represent significant congenital and developmental challenges in male reproductive health. While maternal smoking during pregnancy is a well-established risk factor, emerging evidence indicates that paternal smoking may also have adverse effects on male offspring’s reproductive development. This systematic review assessed the impact of paternal cigarette smoke exposure before and during pregnancy on the incidence of various urogenital disorders.

By synthesizing data from five critical studies, we found that paternal smoking was associated with a 3.8-fold increased risk of cryptorchidism and hypospadias, a 1.26-fold reduction in semen quality, and potential epigenetic changes …

Cellular Metabolism Is A Viable Therapeutic Target For Radiation-Induced Pulmonary Fibrosis, Josly Pierre-Louis Odoom

Theses and Dissertations

Herein, we provide evidence for cellular metabolic reprogramming as a driver of radiation-induced pulmonary fibrosis (RIPF). We are the first to identify a distinct metabolic signature for RIPF in a cohort of patients with radiographic sequela. We also used a RIPF mouse model to detect the metabolic pathways that enrich during pathogenesis. Our previous work highlighted the importance of lactate, a derivative of the glycolysis end-product pyruvate. Consequently, we took a special interest in the effects of radiation on the glycolysis pathway. We learned that radiation accelerates and reprograms glycolysis to an anabolic state in a pyruvate kinase M2 (PKM2)-dependent …

Exploration Of Dopaminergic And Serotonergic Pathways Utilizing Pleiotropic Agents, Charles B. Jones Iii

Theses and Dissertations

2-(Benzoyl)piperidines (BPs) are at a crossroads of therapy and abuse. These compounds are a hybrid between the ADHD medication methylphenidate and abused stimulant cathinones. Here we use computational molecular modeling, synthesis, mutagenesis, and epifluorescence microscopy to further improve the understanding of and potential treatments for several neuropsychiatric disorders. Utilizing the BP scaffold and controlling chirality and aryl substitution, these agents were examined at DAT and SERT. From these investigations it has now been established that R isomer BPs are favored for DAT while S isomer BPs are favored for SERT. Aryl-substitution can greatly affect the selectivity of these agents with …