Pharmacology Commons^™

Novel Strategies To Overcome Carboplatin Resistance In Triple Negative Breast Cancer Using Patient Derived Xenografts, Mohammad A. Al Zubi

Theses and Dissertations

Triple-negative breast cancer (TNBC) patients have a poor prognosis and rely on chemotherapeutic treatment as standard of care. Often, they develop chemotherapy resistance, which leaves them without more therapeutic options, like targeted therapy. New models have been developed to test targeted inhibitors in human tumors, and they are known as patient-derived xenografts (PDX). These tumors are obtained from patients, then established and maintained in mice where they areused for tumor studies. In this work, we characterized 14 PDXs for their primary tumor growth rate and investigated metastatic propensity using spontaneous and experiment metastasis models. We utilized RNA-sequencing to characterize contributions …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

The Efficacy Of Ketamine In Adult Patients With Obsessive Compulsive Disorder With Symptoms Refractory To Standard Of Care Treatment., Brooke Thornton

Capstone Showcase

First line pharmacologic treatments for adult patients with Obsessive Compulsive Disorder (OCD) involve selective serotonin/norepinephrine reuptake inhibitors (SSRI/SNRIs). These drug classes often fail to deliver timely relief of symptoms as well as maintain longevity of symptom recurrence. This research analyzed the use of ketamine in adult patients suffering with OCD for the purposes of more efficacious management of symptoms. Although ketamine demonstrated a timelier relief of symptoms in some small clinical studies, its effects were ultimately unable to be sustained long term. Additionally, a wide range of adverse effects including dissociation, and rebound symptoms were observed. As a result, large …

The Effect Of Waterpipe/Hookah On Platelet Function And The Impact Of Inhibition Of Gβγ Subunits On Hemostasis And Thrombogenesis, Ahmed Alarabi

Open Access Theses & Dissertations

Abstract (Hookah)

Cardiovascular diseases (CVD’s) is a major public health problem. Among CVD’s risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of CVD’s mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipe/hookah has been rising, mainly due to the perception that they are “less harmful” than regular cigarettes. Strikingly, there are few studies on the negative effects of waterpipes on the cardiovascular system, and none regarding their direct contribution to thrombus formation. We employed a waterpipe whole-body exposure protocol that mimics real‐life human …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

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. …

An Electronic Medical Records-Based Approach To Identify Idiosyncratic Drug-Induced Liver Injury In Children., Tracy L. Sandritter, Jennifer Goldman, Clayton J Habiger, James F. Daniel, Jennifer Lowry, Ryan T. Fischer

Manuscripts, Articles, Book Chapters and Other Papers

Drug-induced liver injury (DILI) is the leading cause of liver failure in the United States and the most common cause of drug recall. As opposed to the recognized direct toxicity of super-therapeutic acetaminophen or chemotherapeutic agents in children, limited data exists for pediatric populations on the incidence of idiosyncratic DILI (iDILI) that may develop independently of drug dose or duration of administration. To improve the detection of adverse drug reactions at our hospital, we utilized electronic medical records-based automated trigger tools to alert providers of potential iDILI. Clinical criteria concerning for iDILI were defined as serum ALT > 5x or serum …

An Investigation Into The Relationships Between Bullying, Discrimination, Burnout And Patient Safety In Nurses And Midwives: Is Burnout A Mediator?, Judith Johnson, Lorraine Cameron, Lucy Mitchinson, Mayur Parmar, Gail Opio-Te, Gemma Louch, Angela Grange

HPD Articles

BACKGROUND: Bullying and discrimination may be indirectly associated with patient safety via their contribution to burnout, but research has yet to establish this. AIMS: The aims of this study were to investigate the relationships between workplace bullying, perceived discrimination, levels of burnout and patient safety perceptions in nurses and midwives and to assess whether bullying and discrimination were more frequently experienced by Black, Asian and minority ethnic than White nurses and midwives. METHODS: In total, 528 nurses and midwives were recruited from four hospitals in the United Kingdom to complete a cross-sectional survey between February and March 2017. The survey …

Sustainable Solutions, Fall/Winter 2020, Issue 41

Sustain Magazine

No abstract provided.

Acetaminophen Protein Adducts In Hospitalized Children Receiving Multiple Doses Of Acetaminophen., Sibo Jiang, Valvanera Vozmediano, Susan M. Abdel-Rahman, Stephan Schmidt, Laura P. James

Manuscripts, Articles, Book Chapters and Other Papers

Previous reports have questioned the safety of multiple doses of acetaminophen administered to ill children. Acetaminophen protein adducts (adducts) are a biomarker of acetaminophen-induced liver injury and reflect the oxidative metabolism of acetaminophen, a known mechanism in acetaminophen toxicity. In this prospective observational study, we analyzed adduct concentrations in 1034 blood samples obtained from 181 hospitalized children (1 to 18 years inclusive) who received 2 or more doses of acetaminophen. Linear regression analysis showed that serum adduct concentrations increased as a function of the cumulative acetaminophen dose, which could be attributed, in part, to a long half-life of adducts (2.17 …

Environmentally Responsible Land Use, Spring/Summer 2010, Issue 22

Sustain Magazine

No abstract provided.

Sustainable Communities, Fall/Winter 2010, Issue 21

Sustain Magazine

No abstract provided.

Sustainable Building, Spring/Summer 2009, Issue 20

Sustain Magazine

No abstract provided.

Environmental History, Fall/Winter 2009, Issue 19

Sustain Magazine

No abstract provided.

Student Research, Spring/Summer 2008, Issue 18

Sustain Magazine

No abstract provided.

Evolving Pollution Prevention, Fall/Winter 2008, Issue 17

Sustain Magazine

No abstract provided.

Climate Change, Spring/Summer 2007, Issue 16

Sustain Magazine

No abstract provided.

Our Energy Future, Fall/Winter 2007, Issue 15

Sustain Magazine

No abstract provided.

Land Conservation, Spring/Summer 2006, Issue 14

Sustain Magazine

No abstract provided.

Pollution And Heart Disease, Fall/Winter 2006, Issue 13

Sustain Magazine

No abstract provided.

Green Cities, Spring/Summer 2005, Issue 12

Sustain Magazine

No abstract provided.

Global Sustainability, Fall/Winter 2005, Issue 11

Sustain Magazine

No abstract provided.

Environmental Justice, Spring/Summer 2004, Issue 10

Sustain Magazine

No abstract provided.

Kentucky's Environmental Future, Fall/Winter 2004, Issue 9

Sustain Magazine

No abstract provided.

Urban Ecology, Spring/Summer 2003, Issue 8

Sustain Magazine

No abstract provided.

Urban Regeneration, Fall/Winter 2003, Issue 7

Sustain Magazine

No abstract provided.

Urban Air Quality, Spring/Summer 2002, Issue 6

Sustain Magazine

No abstract provided.