Chemicals and Drugs Commons^™

Structural Biology Of The Enterovirus Replication-Linked 5'-Cloverleaf Rna And Associated Virus Proteins, Steven M. Pascal, Ravindranath Garimella, Meghan S. Warden, Komala Ponniah

Chemistry & Biochemistry Faculty Publications

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5′ end of the strand is an approximately 90-nucleotide self-complementary region called the 5′ cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Efficacy Of Onabotulinumtoxina (Botox) Injections Compared To Oral Topiramate In Reduction Of Migraines Suffered In Adults, Stephanie Blaha

Capstone Showcase

Abstract

Introduction: Migraines are a leading cause of disability in many people worldwide. There are numerous postulations as to their etiology and various medications that treat them. As crippling as migraines are, it is critical that there are therapies to prevent them rather than just treat them acutely. Both OnabotulinumtoxinA (Botox) and Topiramate have been shown to be beneficial as prophylaxis for migraines. This review aims to determine if, in adults who suffer from chronic migraines [P], OnabotulinumtoxinA injections [I] are more effective than oral Topiramate [C] in reduction of the amount of migraines suffered [O].

Methods: A literature search …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Does Enhancing Epidermal Barrier Function With Moisturizing Topical Products Improve Acne Vulgaris In Adult Patients Compared To Non-Moisturizing Products Or Non-Intervention?, Aziza Jadallah

Capstone Showcase

Introduction: Acne is a common skin disorder with multifactorial causes that can persist beyond adolescence or appear for the first time in adulthood. Treatments of varying potency exist, ranging from over-the-counter face washes and creams to prescription topical and oral treatments. Current treatment guidelines target sebum production, exfoliation of excess skin cells, and the bacteria Propionibacterium acnes. Research as early as 1995 suggests dysfunctions of the skin barrier, such as abnormal ceramide levels and increased water loss, play a role in the pathophysiology of acne and are not addressed by current treatments. This review analyzes the role of moisturizing …

The Comparative Efficacy Of Amantadine Vs. Lcig Therapy For The Treatment Of Levodopa-Induced Dyskinesia In Patients With Advanced Parkinson's Disease, Katelynn Timony

Capstone Showcase

Introduction: Though levodopa-carbidopa therapy remains the gold standard of Parkinson’s disease (PD) treatment to this day, patients often experience increased dyskinetic activity as a result of long-term treatment; known as levodopa-induced dyskinesia (LID); the mechanism of which is not completely understood. In this review, the efficacy of two adjunct treatments for LID are compared: 1) the concomitant administration of amantadine, an antiviral medication with antidyskinetic properties; and 2) a new form of levodopa administration in the form of an intestinal gel delivered straight via a device much like an insulin pump.

Methods: Two systematic literature searches of primary, peer-reviewed articles …

The Effectiveness Of Cannabidiol In Rheumatic Disease Pain: A Systematic Review, Mary C. Wiczek

All Graduate Theses, Dissertations, and Other Capstone Projects

Cannabinoids have long been a part of human culture and medicine, and more recently have been rediscovered for their potential use in the management of rheumatic disease pain. The objective of this review was to evaluate the known clinical effectiveness of cannabidiol treatment for rheumatic disease related pain. The legality and current regulation of these products was also reviewed to establish the current status of federal and state rules regarding their clinical use. Basic definitions of the terms used to differentiate cannabidiol from other cannabinoid products was also outlined. A systematic literature search was then conducted to explore the current …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Reply To Lipworth Et Al., Angela M. Moran, Sanjay Ramakrishnan, Catherine A. Borg, Clare M. Connolly, Simon Couillard, Christine M. Mwasuku, Ian D. Pavord, Timothy S.C. Hinks, Lauri Lehtimӓki

Research outputs 2014 to 2021

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that …

Organic Compound Farnesol Reduces Disease Severity And Onset In Mouse Model Of Multiple Sclerosis, Lacey B. Sell

EWU Masters Thesis Collection

No abstract provided.

Evaluation Of A Remote Symptom Assessment And Management (Sam) System For People Receiving Adjuvant Chemotherapy For Breast Or Colorectal Cancer: Mixed Methods Study, Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar

Research outputs 2014 to 2021

©Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar. Background: The Symptom Assessment and Management (SAM) program is a structured, online, nurse-supported intervention to support symptom self-management in people receiving adjuvant chemotherapy post surgery for breast or colorectal cancer. Objective: The objective of this study was to describe the development, implementation strategy, and evaluation of the SAM system. Methods: The development of the SAM program involved 3 phases. In phase 1, the web app was developed through consultation with consumers and clinicians and of the literature to ensure that the system was evidence-based and reflected the realities …

Chemical Composition And Behavioural Responses Of Male And Female Bactrocera Dorsalis To Their Volatile Emissions, Fikira Kimbokota

Journal of Humanities and Social Sciences

Bactrocera dorsalis, (Tephritidae) presented a grave threat to a broad range of fruit and vegetables in the tropics, including Tanzania. Bactrocera dorsalis is among the most destructive tephritid fruit fly, causing devastating loss of fruits especially mango. Insects use olfactory cues to locate hosts, oviposition sites and mating, in which pheromones are believed to be a strong cue used by insect to locate their mates. However, due to their high ability to adapt and occupy different ecological niches into various agroecological zones, there is a need to evaluate pheromonal composition from time to time to improve their control strategies. Therefore, …

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Targeted Inhibition Of Histone Deacetyltransferases For Pancreatic Cancer Therapy, Richard Laschanzky

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a dismal five-year survival rate of less than 10%. One major obstacle in PDAC treatment is acquired drug resistance. Pan-histone deacetylase inhibitors (pan-HDACi) are a relatively new class of anti-cancer drugs, with demonstrated ability to overcome drug resistance and re-sensitize PDAC tumors to Gemcitabine (Gem). These agents target HDACs, a family of 18 enzymes (divided into four classes, I-IV) that catalyze the deacetylation of histones and other cellular proteins and have multiple effects on cell growth, differentiation, survival, and tumorigenesis. Although pan-HDACi have shown significant efficacy in preclinical analysis, and some …

Subanesthetic Iv Ketamine Reduces Acute Suicidal Ideation In Patients With Mood Disorders, Kimberly Jenko, Jack Anzilotti

Physician Assistant Capstones, 2016 to 2019

Background. Depression and suicide are common in the United States and present a significant problem in the healthcare landscape. Currently, there are few options that can rapidly reduce suicidal ideation in patients with depression. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to reduce acute suicidality in patients with depression. Previous studies have a reduction of suicidal ideation compared to saline placebo, but few studies have shown a significant effect compared to a similar psychoactive drug such as midazolam.

Method. A search of PubMed and PsychNET was performed in September 2018 using the terms “ketamine,” “suicide,” …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Optical Detection Of The Structural Properties Of Tumor Tissue Generated By Xenografting Of Drug-Sensitive And Drug-Resistant Cancer Cells Using Partial Wave Spectroscopy (Pws), Prakash A. Adhikari, Prashanth K.B. Nagesh, Fatemah Alharthi, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu, Prabhakar Pradhan

School of Medicine Publications

A mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and …

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β₂ agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E₂ (PGE₂), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE₂, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …

Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study Of Plasmodium Falciparum Hsp70s, Arnold Amusengeri, Lindy Astl, Kevin Lobb, Gennady M. Verkhivker, Özlem Tastan Bishop

Mathematics, Physics, and Computer Science Faculty Articles and Research

Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malaria cases. To prevent catastrophic results, we need to find non-conventional approaches. Allosteric drug targeting sites and modulators might be a new hope for malarial treatments. Heat shock proteins (HSPs) are potential malarial drug targets and have complex allosteric control mechanisms. Yet, studies on designing allosteric modulators against them are limited. Here, we identified allosteric …

Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali Yallapu, Subhash C. Chauhan

School of Medicine Publications

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely …

Doxycycline-Induced Acute Pancreatitis: A Likely Source Rarely Seen, Paul Hoffman Do, Wilco Civil Sr, Jung Yoon Do, Gurjeet Kang Do, Christopher Lozano Orpiano Do, Michael Quinn Do, Joseph Staffetti Md, Dilip Ghanekar Md, Lakshminarasimhan Venu Md, Lily N. Jones Do, Ji Kwon Do, Shaival Thakore Md

Gastroenterology

No abstract provided.

P-19 Anticancer Activity Of Heteroaromatic Cyanostilbenes, Joshua Rotich

Celebration of Research and Creative Scholarship

Cancer is currently the second leading killer disease. There are many different kinds of cancer that are associated with almost every organ in the human body (e.g., brain cancer, colon cancer, breast cancer, prostate cancer, blood cancer, lung cancer, etc.).

In the Biology Department, Dr. Smith and Dr. Murray are researching glioblastoma brain cancer cells. Glioblastoma is a very invasive cancer that is highly lethal. Chances of not surviving when its at stage four is more than 98%. Detecting this cancer while it is developing is difficult because symptoms are mild headache, fatigue, nausea and slight loss of weight. By …

Optimizing Antibiotic Management Of Pediatric Acute Otitis Media In An Emergency Department, Alicia Daggett, Alaina N. Burns, Brian R. Lee, Nirav Shastri, Patricia Phillips, Rana E. El Feghaly

Posters

Problem

Children diagnosed with acute otitis media (AOM) at the Children's Mercy Hospital Kansas Emergency Department routinely get antibiotic prescriptions. There is rarely discussion with families about watchful waiting (defined as discussion of observation with parents and providing a safety-net antibiotic prescription that parents can ill if the patient is not improving or is worsening over the next 48 hours).

The aim of this quality improvement project is to increase watchful waiting for AOM at the CMK ED by 20% by March 2020, with an overall goal of decreasing antibiotic use for AOM.

Effects Of Dabigatran In Mouse Models Of Aging And Cerebral Amyloid Angiopathy, Neethu Michael, Mher Mahoney Grigoryan, Kelley Kilday, Rachita K. Sumbria, Vitaly Vasilevko, Joanne Van Ryn, David H. Cribbs, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) …

A Population Pharmacokinetic Model For Simvastatin And Its Metabolites In Children And Adolescents., Kayode Ogungbenro, Jonathan B. Wagner, Susan M. Abdel-Rahman, J Steven Leeder, Aleksandra Galetin

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Poor adherence to dietary/behaviour modifications as interventions for hypercholesterolemia in paediatric patients often necessitates the initiation of statin therapy. The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status.

METHODS: Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg < 17 years and 20 mg ≥ 18 years) pharmacokinetic dataset of 32 children and adolescents.

RESULTS: The population PK model included …

Observing Growth Effects Of Pigment Epithelium-Derived Factor On Human Retinal Pericytes In Vitro, Anjalee Choudhury, Andrew Tsin, Zachary Perez, Fransisco Elisarraras

School of Medicine Publications

The purpose of this study is to investigate and determine the role of PEDF in the pathogenesis of diabetic retinopathy as induced by advanced glycation end-products (AGEs). Human retinal pericytes were isolated from donors and will be measured for cell proliferation under the influence of PEDF both in the presence and absence of AGEs. Expected outcomes involve both the maintenance and increased survival of HRPs after treatment with PEDF under stimulated hyperglycemic conditions.