Chemicals and Drugs Commons^™

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

Reducing Polypharmacy In Older Adults At End Of Life: The Outcome On Quality Of Life, Melissa Jenson

All Graduate Theses, Dissertations, and Other Capstone Projects

Background: Older adults at the end of life are commonly prescribed multiple medications which can lead to polypharmacy. Research has shown that optimizing medications through targeted deprescribing reduces inappropriate medications, reduces adverse effects and improves select outcomes. However, the impact of deprescribing remains uncertain--specifically whether this intervention improves quality of life (QOL). Objective: Explore polypharmacy in older adults at the end of life examining outcomes of deprescribing on the QOL. Methods: A systematic literature search using Academic Search Premier, CINAHL, Medline, JSTOR and Nursing and Allied Health Database was conducted between October 2020 to November 2020. Select articles …

Cannabis Treatment Of Autism In Children: A Literature Review, Mai Xiong

All Graduate Theses, Dissertations, and Other Capstone Projects

Objectives: This literature review aims to summarize the effects of medical cannabis use in children on Autism Spectrum Disorder (ASD) symptoms, side effects and provide recommendations for practice, education, and research. Background: ASD is characterized by core behaviors of significant impairment in social communication and interaction and restricted and repetitive patterns of behavior, interests, or activities (APA, 2013). In addition to these core behaviors, individuals with ASD often have noncore behavioral disorders and several medical comorbidities. Treatment for ASD symptoms includes Cognitive Behavioral Therapy (CBT), aripiprazole (Abilify) and/or risperidone (Risperdal). As of this review, 14 states have added ASD …

A Multivariable Model Of Parent Satisfaction, Pain, And Opioid Administration In A Pediatric Emergency Department, Candice D. Donaldson, Thomas W. Heyming, Louis Ehwerhemuepha, Brooke N. Jenkins, Michelle A. Fortier, William Feaster, Zeev N. Kain

Psychology Faculty Articles and Research

Introduction: Children and adolescents are not impervious to the unprecedented epidemic of opioid misuse in the United States. In 2016 more than 88,000 adolescents between the ages of 12–17 reported misusing opioid medication, and evidence suggests that there has been a rise in opioid-related mortality for pediatric patients. A major source of prescribed opioids for the treatment of pain is the emergency department (ED). The current study sought to assess the complex relationship between opioid administration, pain severity, and parent satisfaction with children’s care in a pediatric ED.

Methods: We examined data from a tertiary pediatric care facility. A health …

Continuous Manufacturing Of Pharmaceuticals Using Novel Platforms, Sarah S. Aboelela

Theses and Dissertations

Pharmaceuticals have been synonymously manufactured in a centralized, batch mode with less attention to process and formulation understanding. However, due to rising drug costs, shortages, and robustness issues, in addition to the alarming lack of flexibility and agility, regulatory agencies have pushed towards switching to continuous processes. They believed in continuous manufacturing, providing cleaner, flexible, and more efficient processes. Hence, it was foreseen to reduce development and manufacturing costs, time, and environmental impact and ensured drug product quality. Over the last two decades, continuous manufacturing quality, environmental, and economic advantages have been evident through many case studies and approved products …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Synthesis Of Glycopharmaceuticals For The Treatment Of Microbial Sepsis, Nicholas Forsythe, Alexei Demchenko, Catherine Alex

Undergraduate Research Symposium

Carbohydrates (glycans) form the basis of all living organisms and, consequently, are ubiquitous both in nature as biologically active compounds and in medicine as pharmaceuticals. One important application of carbohydrate-based drugs (glycopharmaceuticals) is the treatment of microbial sepsis, an acute illness that causes 100,000+ human deaths annually in the US alone. Exposure of the patient’s blood system to E. coli bacteria causes a massive, and often fatal, immune response. One important cellular receptor that senses the bacterium and is critically involved in triggering the immune response is CD14. Significant efforts by our team and others have been made to develop …

Quadruple Convergence – Rising Cannabis Prevalence, Intensity, Concentration And Use Disorder Treatment, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

In collating and synthesizing several data sources on cannabis exposure, Manthey and colleagues have elegantly compiled a foundational resource for subsequent epidemiological studies on cannabis use [1]. The study includes an impressive body of evidence on cannabis use prevalence (in the month and year prior to interview), high risk cannabis use (daily or near daily), tetrahydrocannabinol (THC—the principal psychoactive constituent of cannabis) concentration in European cannabis herb and processed resin (cannabis concentrates), and treatment demand for Cannabis Use Disorder (CUD). All four domains studied show a modest to dramatic increases across 2010-2019.

Cannabinoid Exposure As A Major Driver Of Pediatric Acute Lymphoid Leukaemia Rates Across The Usa: Combined Geospatial, Multiple Imputation And Causal Inference Study, Albert Stuart Reece, Gary K. Hulse

Research outputs 2014 to 2021

Background: Acute lymphoid leukaemia (ALL) is the commonest childhood cancer whose incidence is rising in many nations. In the USA, between 1975 and 2016, ALL rates (ALLRs) rose 93.51% from 1.91 to 3.70/100,000 < 20 years. ALL is more common in Caucasian-Americans than amongst minorities. The cause of both the rise and the ethnic differential is unclear, however, prenatal cannabis exposure was previously linked with elevated childhood leukaemia rates. We investigated epidemiologically if cannabis use impacted nationally on ALLRs, its ethnic effects, and if the relationship was causal. Methods: State data on overall, and ethnic ALLR from the Surveillance Epidemiology and End Results databank of the Centre for Disease Control (CDC) and National Cancer Institute (NCI) were combined with drug (cigarettes, alcoholism, cannabis, analgesics, cocaine) use data from the National Survey of Drug Use and Health; 74.1% response rate. Income and ethnicity data was from the US Census bureau. Cannabinoid concentration was from the Drug Enforcement Agency Data. Data was analyzed in R by robust and spatiotemporal regression. Results: In bivariate analyses a dose-response relationship was demonstrated between ALLR and Alcohol Use Disorder (AUD), cocaine and cannabis exposure, with the effect of cannabis being strongest (β-estimate = 3.33(95%C.I. 1.97, 4.68), P = 1.92 × 10− 6). A strong effect of cannabis use quintile on ALLR was noted (Chi.Sq. = 613.79, P = 3.04 × 10− 70). In inverse probability weighted robust regression adjusted for other substances, income and ethnicity, cannabis was independently significant (β-estimate = 4.75(0.48, 9.02), P = 0.0389). In a spatiotemporal model adjusted for all drugs, income, and ethnicity, cannabigerol exposure was significant (β-estimate = 0.26(0.01, 0.52), P = 0.0444), an effect increased by spatial lagging (THC: β-estimate = 0.47(0.12, 0.82), P = 0.0083). After missing data imputation ethnic cannabis exposure was significant (β-estimate = 0.64(0.55, 0.72), P = 3.1 × 10− 40). 33/35 minimum e-Values ranged from 1.25 to 3.94 × 1036 indicative of a causal relationship. Relaxation of cannabis legal paradigms had higher ALLR (Chi.Squ.Trend = 775.12, P = 2.14 × 10− 112). Cannabis legal states had higher ALLR (2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000, P = 5.05 × 10− 10). Conclusions: Data show that ALLR is associated with cannabis consumption across space-time, is associated with the cannabinoids, THC, cannabigerol, cannabinol, cannabichromene, and cannabidiol, contributes to ethnic differentials, demonstrates prominent quintile effects, satisfies criteria for causality and is exacerbated by cannabis legalization.

Identification And Characterisation Of Putative Drug Binding Sites In Human Atp-Binding Cassette B5 (Abcb5) Transporter, Lokeswari P. Tangella, Mahreen Arooj, Evelyne Deplazes, Elin S. Gray, Ricardo L. Mancera

Research outputs 2014 to 2021

© 2020 The Author(s) The human ATP-binding cassette B5 (ABCB5) transporter, a member of the ABC transporter superfamily, is linked to chemoresistance in tumour cells by drug effluxion. However, little is known about its structure and drug-binding sites. In this study, we generated an atomistic model of the full-length human ABCB5 transporter with the highest quality using the X-ray crystal structure of mouse ABCB1 (Pgp1), a close homologue of ABCB5 and a well-studied member of the ABC family. Molecular dynamics simulations were used to validate the atomistic model of ABCB5 and characterise its structural properties in model cell membranes. Molecular …

Positive Drug Stories: Possibilities For Agency And Positive Subjectivity For Harm Reduction, Liam B. Engel, Stephen J. Bright, Monica J. Barratt, Matthew M. Allen

Research outputs 2014 to 2021

People who use drugs understand drugs and drug use in ways that are often different to the way knowledge of drug use is constructed within the dominant medico-legal discourse. Their experiences are, more often than not, represented in negative ways within dominant discourse, a disconnect that can create adverse consequences for people who use drugs, through the production of stigma and shame leading to poor health and social outcomes. A key difference in how drugs are understood by people who use drugs is the capacity of the former to recognize positive aspects of drug use and create more agentic subjectivities …

Effect Of Goji Berry On The Formation Of Extracellular Senile Plaques Of Alzheimer's Disease, Warnakulasuriya M. A. D. B. Fernando, Ke Dong, Rosalie Durham, Regine Stockmann, Vijay Jayasena

Research outputs 2014 to 2021

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and a major source of morbidity and mortality. Currently, no therapy nor drug can cure or modify AD progression, but recent studies suggest that nutritional compounds in certain foods can delay or prevent the onset of AD. Diets with high antioxidants is one of the examples which is believed to influence AD pathogenesis through direct effect on amyloid beta levels. Compared to other fruits and vegetables, goji berry (GB) has high levels of polyphenolic substances with antioxidant activities which have shown some positive effects on cognitive function while its mechanism …

Causal Inference Multiple Imputation Investigation Of The Impact Of Cannabinoids And Other Substances On Ethnic Differentials In Us Testicular Cancer Incidence, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

Background: Ethnic differences in testicular cancer rates (TCRs) are recognized internationally. Cannabis is a known risk factor for testicular cancer (TC) in multiple studies with dose-response effects demonstrated, however the interaction between ancestral and environmental mutagenic effects has not been characterized. We examined the effects of this presumed gene-environment interaction across US states. Methods: State based TCR was downloaded from the Surveillance Epidemiology and End Results (SEER) website via SEERStat. Drug use data for cigarettes, alcohol use disorder, analgesics, cannabis and cocaine was taken from the National Survey of Drug Use and Health a nationally representative study conducted annually by …

Impact Of 17-Beta Estradiol And Moderate-Intensity Exercise On Mesenteric Arterial Function Of Uc Davis Type-2 Diabetes Mellitus Rats, Md Rahatullah Razan

University of the Pacific Theses and Dissertations

The studies in this dissertation were designed to investigate the impacts of estrogen (17-β estradiol/E2) and moderate-intensity exercise (MIE) on the mesenteric arterial (MA) function of the University of California Davis type-2 diabetes mellitus (UCD-T2DM) Rat model. Our recent report suggests that diabetes impairs MA vasorelaxation in both sexes of the UCD-T2DM model. Particularly, we reported that MA from prediabetic male rats showed a greater impairment compared to that in prediabetic females. However, when females become diabetic, they exhibit a greater vascular dysfunction than males. Therefore, the aim of the first study was to investigate whether female sex hormone, specifically …

Vaccine Clinical Trials And Data Infrastructure, Ana Santos Rutschman

All Faculty Scholarship

We find ourselves at a momentous turn in the history of vaccines. The COVID-19 pandemic triggered a quasi-global vaccine race that not only compressed vaccine research and development (R&D) timelines, but also paved the way for the administration of a new type of vaccine technology – mRNA vaccines, which work in substantially different ways from the vaccines in use before the pandemic.

While the process of bringing emerging COVID-19 vaccines to market has taken place in an unusually short timeframe, it was largely predicated on the same scientific and regulatory processes that govern the development, approval and deployment of new …

Combining Cryo-Em Density Map And Residue Contact For Protein Secondary Structure Topologies, Maytha Alshammari, Jing He

Computer Science Faculty Publications

Although atomic structures have been determined directly from cryo-EM density maps with high resolutions, current structure determination methods for medium resolution (5 to 10 Å) cryo-EM maps are limited by the availability of structure templates. Secondary structure traces are lines detected from a cryo-EM density map for α-helices and β-strands of a protein. A topology of secondary structures defines the mapping between a set of sequence segments and a set of traces of secondary structures in three-dimensional space. In order to enhance accuracy in ranking secondary structure topologies, we explored a method that combines three sources of information: a set …

Impact Of Targeting Glycosylated Ceramides On Tumorigenic Properties, And Characterization Of Sphingolipids In Head And Neck Tumors, Katherine E. Hylton

Theses and Dissertations

Sphingolipids play a crucial role in signaling, membrane structure, and migration, making them important molecules in cancer development, metastasis, and drug resistance. While some sphingolipids have been associated with pro-apoptotic or pro-survival behaviors, the role of many sphingolipids in cancer remains poorly defined. Chapter 1 of this study investigated the impact of three enzymes that compose most of the ceramide to Lc3 ceramide pathway – UGCG, GBA, and B3GNT5 – and how their alteration impacts chemoresistance and basal membrane invasion in vitro. It was found that the CΒE-induced inhibition of GBA, which converts glucosylceramide to ceramide, has no effects on …

Developing A Vector For Expressing Serratiopeptidase In Lactococcus Lactis, Taylor C. Mauzy

EWU Masters Thesis Collection

Chronic inflammation stems from the inability of the body to resolve acute inflammation. Chronic inflammation is a growing health concern, as nearly 60% of Americans reported coping with at least one chronic condition (as of 2014). On a world scale, three fifths of deaths result from a chronic inflammation disease. Treatments for chronic inflammation include lifestyle changes (diet and exercise) and a variety of conventional drugs. Beyond these treatments, supplementing the body with systemic enzymes may attenuate inflammation. One promising enzyme is serratiopeptidase. Serratiopeptidase is a serine protease expressed by Serratia marcescens which has demonstrated anti-inflammatory, anti-edemic, and analgesic activity …

Molecular Basis Of Arrested Liver Stage Development Of The Gamma Irradiated Plasmodium Yoelii Sporozoite, George A. Ndeta, J. M. Porter-Kelly

Health & Biomedical Sciences Faculty Publications

Worldwide, about 270 million people are diagnosed with malaria annually and about a million deaths occur from this disease mostly in children and pregnant women in Africa. Despite enormous effort and resources directed towards malaria control and eradication, problems of resistance to chloroquine by the malaria parasite and resistance to insecticide by the mosquito vector have only contributed to worsening of the spread of the disease. These problems have led to the search for alternate and efficacious mode of treatments with one being vaccine. Previously, sporozoites isolated from mosquitoes exposed to 12,000 rads of radiation from a 137Cesium source and …

Molecular Basis Of Cross-Sensitization In Colonic Inflammation-Induced Somatic Hypersensitivity, Parshva K. Mehta

Theses and Dissertations

A major portion of pain experienced by patients with an Irritable Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS) can be attributed to visceral hypersensitivity. Visceral stimuli transmitted through primary afferent neurons in the dorsal root ganglia (DRG) induce a nociceptive response. Notably, a subset of patients has also experienced the development of somatic pain, such as leg pain, after diagnosis of a bowel disorder. The aim of this investigation is to ascertain which biochemical mediators are involved in the development of such viscerosomatic cross-sensitization. Initially, the Von Frey Test was used to find behavioral evidence of somatic referred pain; …