Pharmacology Commons^™

Improving Antibiotic Prescribing For Urinary Tract Infections In Urgent Care Centers, Alexis Alastanos

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: Urinary tract infections (UTIs) are one of the most common infections that require antibiotic therapy. Providers working in three urgent care clinics located in Eastern West Virginia diagnosis and treat UTIs based on their clinical judgement. Variability in clinical judgement results in inappropriate antibiotic use which has implications on antibiotic resistance and the financial burden of the patients as well as the entire organization.

Evidence Review: A total of 10 articles were evaluated to support the implementation of antibiotic stewardship initiatives that provide guidance in caring for this population. Interventions include electronic health record enhancements, provider education, and tracking …

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 …

Effects Of Combined Ethanol And Nicotine Administration On Delay Discounting In Male And Female Sprague-Dawley Rats, Rebecca Lillian Chalme

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ethanol (EtOH) and nicotine (NIC) are among the most commonly used and co-used drugs in the world. Co-use occurs in people who use one or both drugs chronically, but also in people who only consume one or both drugs acutely, often in a “bingeing and chipping” pattern. Given that each drug on its own has previously been shown to affect impulsive choice in delay-discounting procedures, with some indication that drug effects could vary by sex, the purpose of the present experiments was to investigate effects of combined EtOH and NIC at a range of dose combinations on delay discounting in …

Aging, A Pathological Factor In Neurological Injury, Aruvi Vijikumar

Graduate Theses, Dissertations, and Problem Reports (ETD)

One of the main reasons for CNS drugs to fail in clinical development is not considering age as a risk factor while studying chronic age-related neurological/neurodegenerative diseases in preclinical studies. We first set out to gain a comprehensive understanding of the impact of age on various aspects (anatomical, immunological, and biochemical) in rodents that play a key role in determining the onset, progression, and evolution of disease severity. With advancing age, the vascular structure and function are compromised which is hypothesized to accelerate cognitive decline. The initial step toward developing novel therapeutics is to characterize the age-related vascular modifications. Utilizing …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Effects Of Acute And Chronic Nicotine Administration On Choice Of Probabilistic Outcomes, Katya A. Nolder

Graduate Theses, Dissertations, and Problem Reports (ETD)

Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer. Research suggests smokers engage in more risky or maladaptive decisions when compared to nonsmokers. The relation between nicotine and risky choice could benefit from further investigation, since nicotine is the active substance of tobacco products that maintains tobacco addiction. Acute nicotine administration has shown to alter risky choice; however, since the everyday smoker uses nicotine repeatedly, more research on chronic administration is warranted and would allow for assessment of tolerance or sensitization of these effects. The present study investigated effects of …

Acute And Repeated Effects Of Synthetic Cannabinoid Agonism And Cannabinoid Receptor 1 Positive Allosteric Modulation, Kristen R. Trexler

Graduate Theses, Dissertations, and Problem Reports (ETD)

Recent years have seen a rise in the diversity and use of synthetic cannabinoids. Currently, there is little known about the effects of specific synthetic cannabinoid compounds. As such, little research has been done evaluating the acute and chronic effects of synthetic cannabinoid administration or the development of tolerance and withdrawal. The present study aimed, in part, to evaluate the acute and repeated effect of a third-generation synthetic cannabinoid, AB-FUBINACA. Mice were treated with AB-FUBINACA (0.1-3 mg/kg, i.p.) or vehicle and were tested repeatedly in the tetrad battery of assays, which included tests of catalepsy, antinociception, hypothermia, and locomotor activity. …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Dysregulation Of Daf-16/Foxo3a-Mediated Stress Responses Accelerates T Oxidative Dna Damage Induced Aging, Aditi U. Gurkar, Andria R. Robinson, Yuxiang Cui, Xuesen Li, Shailaja K. Allani, Amanda Webster, Mariya Muravia, Mohammad Fallahi, Herbert Weissbach, Paul D. Robbins, Yinsheng Wang, Eric E. Kelley, Claudette M. St. Croix, Laura J. Niedernhofer, Matthew S. Gill

Faculty & Staff Scholarship

DNA damage is presumed to be one type of stochastic macromolecular damage that contributes to aging, yet little is known about the precise mechanism by which DNA damage drives aging. Here, we attempt to address this gap in knowledge using DNA repair-deficient C. elegans and mice. ERCC1-XPF is a nuclear endonuclease required for genomic stability and loss of ERCC1 in humans and mice accelerates the incidence of age-related pathologies. Like mice, ercc-1 worms are UV sensitive, shorter lived, display premature functional decline and they accumulate spontaneous oxidative DNA lesions (cyclopurines) more rapidly than wild-type worms. We found that ercc-1 worms …

Delay Discounting And Cannabinoid Enzyme Inhibitors, Devin Andrew Galdieri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Delay discounting is a measure of impulsive choice that is correlated with maladaptive behavior and psychological disorders. Disruptions to serotonin and dopamine pathways can cause changes in delay discounting, as can lesions to the prefrontal cortex and nucleus accumbens. The endocannabinoid system modulates other neurotransmitter systems, including dopamine and serotonin pathways. Cannabinoid receptors type 1 are found in relatively high concentrations in the nucleus accumbens and the prefrontal cortex. These receptors are activated by endogenous cannabinoids, which are synthesized on demand and broken down by catabolic enzymes. The action of these enzymes can be inhibited by a class of drugs …