Pharmacology, Toxicology and Environmental Health Commons^™

Promoting Healthier Treatment Outcomes In Obese Cancer Patients Taking High Dose Methotrexate, Carly Dell'ova

Walden Dissertations and Doctoral Studies

Cancer and obesity rates continue to rise, creating enormous public heath burdens to the individual and at the national and global levels, reducing quality of life, and increasing spending. Moreover, the relationships between cancer and obesity are not well understood. A commonly used chemotherapy for several types of cancer is high dose methotrexate (HDMTX). Along with chemotherapy, especially at high doses, comes toxicity to specific organs and the entire body. However, limited research has been conducted on obese cancer patients as they are often excluded from clinical studies. Practitioners need to better understand how to dose these patients to provide …

Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour

Electronic Theses and Dissertations

Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …

Vapourized Cannabis Extract Administration Impairs Memory And Alters Neural Activity In Laboratory Rats, Megan Chladny

Theses and Dissertations (Comprehensive)

Although people have smoked cannabis for millennia, administration of cannabis by heating the dried plant material or distilled extracts to a temperature just below the combustion point (i.e., vapourization or "vaping") has rapidly increased over the past few years (Javadi-Payder, Cole, and Taffe, 2018; Manwell, Charchoglyan, Brewer, Matthews, Heipel, and Mallet, 2014). Conversely, most of the cannabinoid research using rodent models has used parenteral routes of administration to examine the effects of purified cannabis extracts such as ∆⁹-tetrahydrocannabinol (THC), making it difficult to directly compare laboratory research to human drug use. Building on previous studies showing that THC …

Winter Dynamics Of Storm Water Management Ponds And Winter Tolerance In Three Aquatic Plant Species, Patrick Strzalkowski

Theses and Dissertations (Comprehensive)

The vast majority of the research into the performance of stormwater management ponds (SWMPs) has been performed in warm regions or during the warmer seasons in temperate regions. It is presumed that SWMPs are inactive in the winter as any potential stormwater is trapped in snow and ice. The main goal of this thesis was to test this presumption and to study the dynamics and performance of three SWMPs during the winter. Remote water level loggers were installed into the three SWMPs and daily grab samples from the influents and effluents were taken and analyzed for total phosphorus (TP), chloride, …

Hepatic Transcriptomic Assessment Of Sprague Dawley Rats In Response To Dietary Perfluorobutane Sulfonate (Pfbs) Ingestion, Isaac Appiah

College of Graduate Studies: Theses & Dissertations

Perfluorobutane sulfonate (PFBS) is a short-chain PFAS that is considered to be a less toxic replacement for the rather more toxic long-chain perfluorooctane sulfonate (PFOS). Its numerous industrial applications and widespread presence in the environment have raised environmental and health concerns because of growing evidence associating adverse health effects and certain liver diseases to PFBS exposure. The study goal was to investigate whether dietary ingestion of PFBS would induce liver injuries, damage, inflammations, and oxidative stress. To achieve these goals, Sprague-Dawley rats were assigned into three PFBS dietary treatment groups (0, 50, and 100 PPM) for 11 weeks. After this …

Novel Strategies In Head And Neck Tumor Therapy; Contribution Of Senescence In Therapy Response, And Resistance Development After Cisplatin Treatment, Fereshteh Ahmadinejad

Theses and Dissertations

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local, and distant metastasis and disease relapse as well as cisplatin-induced resistance are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild- type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further established a cisplatin-resistant cell line from HN30 parental cell line that underwent brief senescence …

Intrinsic Efficacy As A Determinant Of Opioid Effectiveness In Treatment Of Pain-Depressed Behavior, Edna Santos

Theses and Dissertations

Pain is a major public health concern that is commonly associated with behavioral depression, and a major goal in pain treatment is alleviation of pain-related behavioral depression. High-efficacy mu opioid receptor (MOR) agonists (e.g. fentanyl, morphine, oxycodone) are effective to treat pain, but their use is limited by side effects that not only endanger the patient but may also obscure analgesic rescue of pain-depressed behavior. The ongoing epidemic of opioid abuse and overdose deaths has stimulated research to discover non-opioid alternative analgesics; however, this search neglects the clinical potential of safer intermediate-efficacy MOR agonists (e.g. buprenorphine). The objective of the …

Modulation Of Opioid-Induced Respiratory Depression By Stimulants And Their Associated Monoaminergic Receptor Mechanisms In Mice Using Whole Body Plethysmography, Harrison J. Elder

Theses and Dissertations

Opioid overdose and associated deaths involving opioid-induced respiratory depression (OIRD) began to accelerate beginning in 2015 with the emergence of illicitly manufactured fentanyl and its analogs and currently represents one of the most significant public health challenges in the United States. The increases in overdose deaths have occurred despite the increased availability of the opioid overdose reversal agent, naloxone, to first responders and the public. This new phase of the opioid epidemic has been paralleled by substantial growth in the co-use of opioids with stimulants, particularly methamphetamine. The objective of this dissertation is to ascertain whether fentanyl is particularly resistant …

Epithelial Membrane Protein 3 (Emp3b) Is A Novel Regulator Of Sympathetic Nervous System Development In Zebrafish., Jessica M. White

Theses and Dissertations

Notable progress has been made in understanding the development of the neural crest (NC). Neural crest cells (NCCs) can be divided into 4-5 subpopulations. A major lineage among trunk NC derivatives are sympathoadrenal (SA) cells, which give rise to the sympathetic nervous system (SNS). Trunk NCCs follow a ventromedial migration pathway where signals derived from the dorsal aorta instruct migrating NCCs to a SA cell fate. Defects in NC development can result in syndromes known as neurocristopathies. Neuroblastoma is one of the most common forms of pediatric cancer affecting nearly 800 infants each year in the United States (Takita et …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Examining The Oxidative Stress Effects In Rats Exposed To 2-Aminoanthracene In Utero And High Fat Diet Three Months After, Brianna A. Lanoix

Honors College Theses

Polycyclic aromatic hydrocarbons are organic compounds that are created synthetically or found in partially burned oil, gasoline, and coal. 2-aminoanthracene (2AA) is a common example of a PAH and can affect lipid and carbohydrate metabolism and resulting in inflammatory problems and oxidative stress. The objective of the research project is to investigate oxidative stress in relation to diabetes in rats exposed to 2AA in utero and a high fat diet later in life. Pregnant dams were separated into treatment groups based on their dosages of 2AA; 0 mg/kg (control), 50 mg/kg (low), 100 mg/kg (high). During the gestation -postpartum period, …

Inferring Exposure To Harmful Pseudo-Nitzschia Blooms From Ocean-To-Estuary Gradients In Domoic Acid Concentrations In Humboldt Bay Bivalves, Natasha Hope Ficzycz Winnacott

Cal Poly Humboldt theses and projects

Harmful algal blooms (HABs) result from outbreaks of any of several different species of toxin-producing phytoplankton and that can have major detrimental effects on marine ecosystems and pose severe health and economic threats to human communities. Of particular concern along the United States West Coast are HABs of pennate diatom genus Pseudo-nitzschia that produce the potent neurotoxin domoic acid (DA). The coastal ocean between Cape Mendocino, CA, and Cape Blanco, OR is a hotspot for Pseudo-nitzschia spp. HABs. Such blooms impact coastal fisheries and pose a potential threat to aquaculture operations in Humboldt Bay, California’s second largest estuary and largest …

Clinical Vaccination Education Guideline For The African American Community, Margaret Chinedum Nwoji

Walden Dissertations and Doctoral Studies

AbstractVaccination hesitancy is high among African Americans and other people of color. The practice gap addressed in this project was the lack of a culturally sensitive clinical guideline for vaccination education relevant to the African American community. The practice-focused question was answered by developing an evidence-based Clinical Vaccination Education Guideline for the African American Community (CVEGAAC) that was validated by a group of four content experts using the Appraisal of Guidelines, Research, and Evaluation tool. The content experts scored each of the domains above 90%, implying that the CVEGAAC is of high quality and ready for implementation. The end users …

Assessment Of Spilled Toxic Bait By Wild Pigs And Potential Risk To Non-Target Species, John C. Kinsey, Justin A. Foster, Nathan P. Snow, Jason D. Wishart, Linton D. Staples, Janis K. Bush, Kurt V. Vercauteren

United States Department of Agriculture Wildlife Services: Staff Publications

Background

In 2018, a sodium nitrite (SN)-based toxic bait for invasive wild pigs (hereafter wild pigs; Sus scrofa), was evaluated to determine its effectiveness in reducing local wild pig populations in Texas. Localized population reductions of > 70% were achieved, but spillage of bait outside wild pig-specific feeders (bait stations) caused by feeding wild pigs resulted in the deaths of non-target animals. To evaluate risks to non-target animals, we tested whether bait presentation influenced the total amount of bait spilled by wild pigs and estimated the associated risk to non-target species.

Results

We found that bait spilled outside bait stations …

Acute Copper (Cu) Toxicity In Dragonfly Naiads (Insecta: Odonata), Jeff M. Simpson

Department of Entomology: Distance Master of Science Projects

The objective of this study was to examine the effects copper (Cu) on mortality within a pair of test groups of naiads in the order Odonata, and to replicate previous observations regarding their potential uses as indicators for water quality. Few past studies have examined toxicity within relation to the odonates. It has been suggested that this order may contain valuable model organisms (Tollett et al., 2008). Very little focus has been given to odonates as bioindicators, with the few studies done being performed on species that would typically inhabit lentic environments (Trevino, 1999). Similarly, the test subjects for this …

Wastewater Pandemic Preparedness: Toward An End-To-End Pathogen Monitoring Program, Justin R Clark, Austen Terwilliger, Vasanthi Avadhanula, Michael Tisza, Juwan Cormier, Sara Javornik-Cregeen, Matthew Clayton Ross, Kristi Louise Hoffman, Catherine Troisi, Blake Hanson, Joseph Petrosino, John Balliew, Pedro A Piedra, Janelle Rios, Jennifer Deegan, Cici Bauer, Fuqing Wu, Kristina D Mena, Eric Boerwinkle, Anthony W Maresso

Faculty, Staff and Student Publications

Molecular analysis of public wastewater has great potential as a harbinger for community health and health threats. Long-used to monitor the presence of enteric viruses, in particular polio, recent successes of wastewater as a reliable lead indicator for trends in SARS-CoV-2 levels and hospital admissions has generated optimism and emerging evidence that similar science can be applied to other pathogens of pandemic potential (PPPs), especially respiratory viruses and their variants of concern (VOC). However, there are substantial challenges associated with implementation of this ideal, namely that multiple and distinct fields of inquiry must be bridged and coordinated. These include engineering, …

Gut-Lung Axis Of The Microbiome Alterations After Ultrafine Particles And Ozone Inhalation, Md Habibul Hasan Mazumder

Graduate Theses, Dissertations, and Problem Reports (ETD)

Air pollution poses a significant threat to public health. It is a mixture of particulate matter, gaseous substances, and other secondary substances. Despite epidemiological research indicating the interactive effects of various components of air pollution, existing studies and regulatory limits often focus on single-exposure scenarios. The emerging understanding of the microbiome’s role in regulating immune response, metabolism, and pathophysiology of various diseases points towards interactions between environmental exposures and microbial dysbiosis. In this dissertation, mice were exposed to relevant deposited doses of carbon black (CB) and ozone (O3), and lung inflammation as well as the lung-gut axis of the microbiome …

Antibacterial, Antioxidant, And Repellency Potential Of The Essential Oil From Spartium Junceum L. Grown In Lebanon, Hawraa Zahrddin, Mahmoud Khalil, Akram Hijazi

BAU Journal - Science and Technology

The goal of our present study is to assess the pharmacological potential of essential oil extracted from Spartium junceum cultivated in Lebanon. This oil was obtained by hydrodistillation using the Clevenger apparatus. Then, an organoleptic characterization and an evaluation of its antioxidant, repellent/insecticidal, and antibacterial activities have been evaluated. The obtained results showed that this oil had an antioxidant activity reaching 82 % dependent on the dilution used. In addition, it showed an insecticidal effect and an antibacterial effect.

Risk Factors For Emergency Medical Care Or Hospitalization Due To Heat-Related Illness Or Injury: A Systematic Review, Blair Litwiller, Amber N. Barnes

Florida Public Health Review

Background: Temperatures globally have been predicted to increase due to changes in the climate. As the earth gets warmer, it is expected that heat-related illness will also increase worldwide. An effective and appropriate public health response will be critical. Purpose: The aim of this review was to identify risk factors associated with heat-related illness and injury to provide target areas for future interventions. Methods: A review of existing literature was analyzed for risk factors that may increase the likelihood of being admitted to an emergency department for a heat related illness or injury. Results: Of the …