Chemicals and Drugs Commons^™

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 …

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 …

Potential Production Of Theranostic Boron Nitride Nanotubes (64cu-Bnnts) Radiolabeled By Neutron Capture, Wellington Marcos Silva, Helio Ribeiro, Jaime Taha-Tijerina

Manufacturing & Industrial Engineering Faculty Publications

In this work, the radioisotope 64Cu was obtained from copper (II) chloride dihydrate in a nuclear research reactor by neutron capture, (63Cu(n, )64Cu), and incorporated into boron nitride nanotubes (BNNTs) using a solvothermal process. The produced 64Cu-BNNTs were analyzed by TEM, MEV, FTIR, XDR, XPS and gamma spectrometry, with which it was possible to observe the formation of64Cu nanoparticles, with sizes of up to 16 nm, distributed through nanotubes. The synthesized of 64Cu nanostructures showed a pure photoemission peak of 511 keV, which is characteristic of gamma radiation. This type of emission is desirable for Photon Emission Tomography (PET scan) …

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 …

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 …

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; …

Targeting Calcium Homeostasis For The Treatment Of Multiple Myeloma, Osama M. Elzamzamy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multiple myeloma (MM) is a hematological malignancy characterized by the neoplastic proliferation of the plasma cells. MM is a relatively rare cancer that accounts for about 1.8% of all cancers and is the second most common hematologic malignancies, and despite the advancement from untreatable to treatable malignancy, it is yet incurable. Calcium ions (Ca²⁺) play an important role as second messengers in regulating a plethora of physiological and pathological processes, hence cytoplasmic Ca²⁺ is tightly regulated with strict spatial and temporal control to initiate, maintain, and terminate appropriate signaling pathways and phenotypes including cellular proliferation, cell cycle …

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 …

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 …

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.

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 …

Inducing Compliance With Postmarket Studies For Drugs Under Fda's Accelerated Approval Pathway, Liang Xu, Hui Zhao, Nicholas C. Petruzzi

Research Collection Lee Kong Chian School Of Business

Problem definition: In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval pathway (AP) to allow promising drugs to enter the market based on limited evidence of efficacy, thereby permitting manufacturers to verify true clinical benefits through postmarket studies. However, most postmarket studies have not been completed as promised. We address this noncompliance problem. Academic/practical relevance: The prevalence of this noncompliance problem poses considerable public health risk, thus compromising the original purpose of a well-intentioned AP initiative. We provide an internally consistent and implementable solution to the problem through a comprehensive analysis of the myriad complicating factors and …

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 …

Covid-19: Race For Vaccine, L. Hayley Burgess, Jason J. Braithwaite, Emily Singleton, Aaron M. Young, Mandelin K. Cooper

HCA Healthcare Journal of Medicine

The world is in the midst of a pandemic from COVID-19, a disease caused by the virus SARS-CoV-2. Despite broad mitigation efforts, new cases continue with 74 million cases and 1.6 million deaths worldwide. Regardless of previous research efforts, there is no commercially available vaccine for any coronavirus. Novel vaccine development has historically taken at least 10 years from discovery to availability with only a 6% market entry probability.

With the global impact, there is an urgency to expedite a vaccine to protect the population. The U.S. government launched Operation Warp Speed with the goal to produce and deliver 300 …

Importance Of Awareness Of Adverse Drug Reaction Reporting During The Covid-19 Pandemic, Heather Ellis, Hale Z. Toklu

HCA Healthcare Journal of Medicine

Health care professionals hold the responsibility of reporting any adverse drug reactions in order to learn about new therapy and how best to safely care for our patients. The information derived from case publications and FDA MedWatch reports are essential to accumulate information and increase awareness for the possible risks of new drugs.

Exercise Improves Endothelial Function Associated With Alleviated Inflammation And Oxidative Stress Of Perivascular Adipose Tissue In Type 2 Diabetic Mice, Jinju Wang, Venkata Polaki, Shuzhen Chen, Ji Chen Bihl, Pasquale Pagliaro

Pharmacology and Toxicology Faculty Publications

Perivascular adipose tissue (PVAT), a type of adipose tissue that surrounds the blood vessels, has been considered an active component of the blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important nonpharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to the PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of …

Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells

Honors Program Theses and Projects

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. …

Imaging The Tumor Microenvironment Using 1,2-Dioxetane Chemiluminescence Agents, Lucas Ryan

Chemistry Theses and Dissertations

As complex organisms, animals and humans rely on a delicate interplay between many connected systems to maintain proper cellular and whole-body function. Oxygen regulation and homeostasis are vital for proper function in healthy cells, as are core components of aerobic metabolism and efficient ATP generation to supply our energy needs. Maintaining pH homeostasis is also of primary importance; cells maintain pH homeostasis through a host of active and passive transporters to maintain pH balance both inside and outside of the cell.

Events of uncontrolled cellular proliferation, also known as cancer, survive and thrive under conditions that perturb the delicate balance …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

LSU New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff

DNP Qualifying Manuscripts

Background: According to the National Institute for Occupational Safety and Health (2016), oral anticancer agents (OAC) are hazardous drugs (HD) and require the same safe handling interventions in the home setting as in controlled health care environments. The use of a safe handling checklist for OAC administration is a way nurses can provide safe handling education to patients and caregivers and assess for understanding and competency for critical tasks. Effective home management strategies outlining caregiver protections, proper storage, administration of OACs, spill clean-up, and waste disposal could reduce exposure risks to toxic agents.

Objective: To present a safe-handling checklist …

Honey Vs. Silver Sulfadiazine In The Reepithelialization Of Partial-Thickness Burn Wounds, Andi Diamond, Monica Bowler

Physician Assistant Capstones, 2020-current

Objective: To determine whether silver sulfadiazine (SSD) should remain the gold standard of initial burn wound treatment or if it should be replaced with an alternative treatment that allows for faster skin cell regrowth. Methods: Database search of PubMed and Google Scholar were used to evaluate patient clinical trials with the search terms “burn”, “honey”, and “silver”. Results: Three trials met inclusion criteria. All three of the studies found significant improvement in their primary endpoint with the use of honey. The first study showed the honey group to have healing time of 13.47 ± 4.06 days and …

Illicit Substance Use In Acute Care Hospitals: Creating A Safe Environment, Christina Sanford

Doctor of Nursing Practice (DNP) Projects

Problem: In January 2019, a medium-sized acute care hospital in Northern California reported new safety concerns related to patients using illicit substances in the hospital.

Context: Leaving the hospital AMA is an increasing problem in acute care hospitals among patients who use illicit substances, with a rate of 25% to 30% (Ti & Ti, 2015). Grewal et al. (2015) conducted a study of over 1,000 illicit substance users who had experienced a hospitalization, where 43.9% reported use of illicit substances while in the hospital.

Intervention: The project was the creation, implementation, testing, and evaluation of multiple interventions to improve …

Maternal Prenatal Cortisol Programs The Infant Hypothalamic–Pituitary–Adrenal Axis, Jessica L. Irwin, Amy L. Meyering, Gage Peterson, Laura M. Glynn, Curt A. Sandman, Laurel M. Hicks, Elysia Poggi Davis

Psychology Faculty Articles and Research

One of the key proposed agents of fetal programming is exposure to maternal glucocorticoids. Experimental animal studies provide evidence that prenatal exposure to elevated maternal glucocorticoids has consequences for hypothalamic–pituitary–adrenal (HPA) axis functioning in the offspring. There are very few direct tests of maternal glucocorticoids, such as cortisol, during human pregnancy and associations with infant cortisol reactivity. The current study examined the link between maternal prenatal cortisol trajectories and infant cortisol reactivity to the pain of inoculation in a sample of 152 mother-infant (47.4% girls) pairs. The results from the current study provide insight into fetal programming of the infant …

Internet Transparency Of Local Men’S Health Clinics In Nebraska, Jinfeng Jiang, Jordan Stegman, Christopher M. Deibert

Graduate Medical Education Research Journal

An overview of Men’s Health Clinics offering Testosterone Therapy in a Midwest State.

Introduction/ Background – Since 2001, there has been a 300% increase in the use of Testosterone therapy. However, there remains limited published data on the demographics of facilities and providers that advertise this service. This study aims to look at such demographics of advertised Men’s health clinics in Nebraska.

Methods/ Materials – An internet search was conducted with the phrases “Nebraska Male health clinics, Nebraska Low T/testosterone, Nebraska Hormone Replacement Therapy”. All clinics that were found offering Testosterone therapy with Men’s health in their mission statement were …

Impact Of Ketorolac On Opioid Consumption After Open Heart Surgery, Laura Neubauer, Radhan Gopalani, Kristen De Almeida, Andrea Marr-Peralto

All Publications

No abstract provided.

Retrospective Review Of Anticoagulation Regimens Used For The Prevention Of Venous Thromboembolisms In Critically Ill Patients Infected With Sars-Cov-2, Tony Nguyen, Heidi Clarke

All Publications

No abstract provided.

A Comparison Of 4-Year Total Medical Care Costs, Adverse Outcomes, And Opioid/Prescription Analgesic Use For 3 Knee Osteoarthritis Pain Treatments: Intra-Articular Hyaluronic Acid, Intra-Articular Corticosteroids, And Knee Arthroplasty., John Mackowiak, John T Jones, Vinod Dasa

School of Medicine Faculty Publications

To compare the medical costs associated with treatments for knee osteoarthritis (OA): intra-articular corticosteroids (ICS) and intra-articular hyaluronic acid (IHA) primarily, and ICS/IHA vs knee arthroplasty (TKA) secondarily. This was a retrospective analysis of an insurance claims database. Eligible members had diagnosed OA and no claims for ICS, IHA, or TKA during the 6–18-month look-back period. Cohorts of interest over the 4-year observation period were: patients who received ICS only, those who received IHA only, and those who received TKA only. Outcomes assessed included: (1) total allowed medical costs, (2) claims for pre-specified, treatment-related adverse outcomes and costs, and (3) …