Pharmacy and Pharmaceutical Sciences Commons^™

The Teaching Of Performance Enhancing Drugs In U.S. Schools And Colleges Of Pharmacy, Sara Dorothy Green

Honors Theses

The teaching of performance enhancing drugs in U.S. schools and colleges of pharmacy is necessary to better help patients who are athletes especially those who compete in high-level athletics such as the Olympics or the National Collegiate Athletic Association (NCAA). There is no master list for banned substances, they differ for each organization and have many exceptions. Pharmacists can play a key role in preventing unintentional disqualifications of athletes as there are many medications considered performance enhancing drugs including some supplements and stimulants. For example, commonly used cold medications may contain pseudoephedrine hydrochloride, a banned substance in the world of …

In-Vitro Assessment Of Cb1/Cb2 Receptor Binding And Function, Joey M. Davis

Honors Theses

Cannabinoid receptors CB1 and CB2 are G protein-coupled receptors that have a variety of physiological effects on the human body. Many natural product agonists and antagonists are presumed to interact with the cannabinoid receptors and are therefore heavily studied in drug discovery. Assays are used to study the binding of compounds to these receptors. However, a limited number of these assays are efficient in determining the functional activity of ligands associated with CB1 and CB2. Of those, many use radioactivity which is both expensive and potentially dangerous to the researcher. In this study, we first validated the assays already found …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Improving Diabetes Self-Management Developing A Patient Decision Aid To Improve Patient Education, Morgan Baker

Honors Theses

Type 2 diabetes is a complex disease that affects a large population of people. It is imperative that efforts are made to develop more effective and inclusive treatment strategies for patients with this condition. A promising approach being studied is the utilization of community pharmacists to individualize and implement diabetes self-management training and education. The objective of this study is to develop a preliminary version of a patient decision aid (PDA) designed to evaluate patient knowledge and behavior towards diabetes self-management for use in the community pharmacy setting. The study design used to achieve this objective was a cross-sectional survey …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

The Impact Of Multidrug-Resistant Organisms On Outcomes In Patients With Diabetic Foot Infections, Oryan Henig, Jason M. Pogue, Emily Martin, Umar Hayat, Mahmoud Ja'ara, Paul E. Kilgore, Raymond Cha, Sorab Dhar, Keith S. Kaye

Department of Pharmacy Practice

Background. Multidrug-resistant organisms (MDROs) are important diabetic foot infection (DFI) pathogens. This study evaluated the impact of DFIs associated with MDRO pathogens (DFI-MDRO) on clinical outcomes.

Methods. Adults admitted to Detroit Medical Center from January 2012 to December 2015 with culture-positive DFI were included. Associations between outcomes and DFI-MDRO (evaluated as a single group that included methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant enterococci, Enterobacteriaceae resistant to third-generation cephalosporin [3GCR-EC], Acinetobacter baumannii, and Pseudomonas aeruginosa) were analyzed. Outcomes included above- and below-knee lower extremity amputation (LEA), readmissions, and mortality within a year after DFI. A propensity score predicting the likelihood …

Ccne1 Amplification As A Predictive Biomarker Of Chemotherapy Resistance In Epithelial Ovarian Cancer, Justin W. Gorski, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is the most-deadly gynecologic malignancy, with greater than 14,000 women expected to succumb to the disease this year in the United States alone. In the front-line setting, patients are treated with a platinum and taxane doublet. Although 40-60% of patients achieve complete clinical response to first-line chemotherapy, 25% are inherently platinum-resistant or refractory with a median overall survival of about one year. More than 80% of women afflicted with ovarian cancer will recur. Many attempts have been made to understand the mechanism of platinum and taxane based chemotherapy resistance. However, despite decades of research, few predictive markers of …

Apc-Β-Catenin-Tcf Signaling Silences The Intestinal Guanylin-Gucy2c Tumor Suppressor Axis., Erik S Blomain, Jeffrey A Rappaport, Amanda M Pattison, Babar Bashir, Ellen Caparosa, Jonathan Stem, Adam E Snook, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …

What’S The Word? Defining Community Pharmacy Interventions, Elizabeth Laughlin, Bsps, Danielle C. Mayer, Pharmd, Bcacp, Sarah Lynch, Pharmd, Bcacp

College of Pharmacy Posters

Primary Objective: Determine whether student pharmacists & licensed pharmacists are consistently able to categorize interventions

Secondary Objective: Evaluate trends in themes for situations that are not easily categorized

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy For Bloodstream Infections Secondary To Enterobacter, Serratia, And Citrobacter Species, Caroline Derrick, P. Brandon Bookstaver, Zhiqiang K. Lu, Christopher M. Bland

Faculty and Student Publications

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of …

Pregnane Steroidogenesis Is Altered By Hiv-1 Tat And Morphine: Physiological Allopregnanolone Is Protective Against Neurotoxic And Psychomotor Effects, Jason Paris, Philippe Lière, Sarah Kim, Fakhri Mahdi, Meagen E. Buchanan, Sara R. Nass, Alaa N. Qrareya, Mohammed F. Salahuddin, Antoine Pianos, Neïké Fernandez, Zia Shariat-Madar, Pamela E. Knapp, Michaël Schumacher, Kurt F. Hauser

Faculty and Student Publications

Pregnane steroids, particularly allopregnanolone (AlloP), are neuroprotective in response to central insult. While unexplored in vivo, AlloP may confer protection against the neurological dysfunction associated with human immunodeficiency virus type 1 (HIV-1). The HIV-1 regulatory protein, trans-activator of transcription (Tat), is neurotoxic and its expression in mice increases anxiety-like behavior; an effect that can be ameliorated by progesterone, but not when 5α-reduction is blocked. Given that Tat's neurotoxic effects involve mitochondrial dysfunction and can be worsened with opioid exposure, we hypothesized that Tat and/or combined morphine would perturb steroidogenesis in mice, promoting neuronal death, and that exogenous AlloP would …

Feasibility And Acceptability Of A Proposed Pharmacy-Based Harm Reduction Intervention To Reduce Opioid Overdose, Hiv And Hepatitis C, Beth E. Meyerson, Jon D. Agley, Wasantha Parakrama Jayawardene, Lori Ann Eldridge, Prachi Arora, Carriann Smith, Nina Vadiei, Amy K. Kennedy, Taylor J. Moehling

Scholarship and Professional Work – COPHS

Background: Evidence-based harm reduction intervention components which might benefit pharmacy patients have not been integrated and studied.

Objective: To investigate the feasibility and acceptability of a proposed pharmacy-based harm reduction intervention to reduce opioid overdose, HIV and hepatitis C called PharmNet.

Methods: Indiana managing pharmacists were surveyed in 2018 to assess the feasibility and acceptability of an intervention for opioid misuse screening, brief intervention, syringe and naloxone dispensing, and referrals provision. The Consolidated Framework for Implementation Research informed the survey development and analysis.

Result: The sample included 303 (30.8%) pharmacists; 215 (70.9%) provided detailed written comments. Intervention Characteristics: 83.3% believed …

The Effects Of An Adenosine A(2a) Agonist As An Adjunctive Treatment To Alleviate Sensorimotor Gating Deficits In A Rodent Model Of Schizophrenia, Hannah Rauhuff

Undergraduate Honors Theses

The adenosine system has become a promising target for the treatment of schizophrenia due to its unique relationship with dopamine D₂ receptors. Dopamine D₂ receptors display heightened sensitivity in schizophrenia, and inhibition of these receptors has been shown to alleviate some of the psychotic symptoms of the disorder. Inhibition of adenosine A(2A) receptors has been shown to decrease dopamine D₂ receptor sensitivity, making this receptor a potential target for treatment of the disorder. This effect occurs because adenosine A(2A) receptors form a mutually inhibitory heterodimeric complex with dopamine D₂ receptors. The present study looked at the …

Effect Of Diabetes Mellitus On Ocular Surface Tight Junctions And Glycocalyx, Saleh M. Alfuraih

Pharmaceutical Sciences (MS) Theses

Introduction: Diabetes mellitus is the disease of the century that affects many body organs. In the eye, diabetes mellitus causes retinopathy, cataract, glaucoma, papillopathy, and ocular surface disease. Ocular surface abnormalities in patients of diabetes mullites include impairment of corneal epithelial barrier function, conjunctival defects, increased incidence of corneal and conjunctival infections and higher prevalence of dry eye disease. Impairment of tight junctions and glycocalyx, which are critical for ocular surface barrier function, may underlie these diabetes-associated ocular surface defects. Therefore, the present study was designed to investigate the effect of high glucose exposure and type I diabetes mellitus on …

Role Of Protein Phosphatase-2a In Regulating Monocyte Activation By Soluble And Crystalline Uric Acid In Gout, Sandy Elsayed

Pharmaceutical Sciences (MS) Theses

Gout is a chronic inflammatory disease caused by the phagocytosis of monosodium urate monohydrate (MSU) crystals by monocytes/macrophages resulting in downstream expression and production of interleukin-1 beta (IL-1β) and chemokines. The activation of monocytes by MSU crystals involves the priming of monocytes with danger signals e.g. lipopolysaccharide (LPS) or soluble uric acid (UA), crystal phagocytosis and subsequent NLRP3 inflammasome activation and conversion of pro-IL-1β to active IL-1β. Protein-phosphatase-2A (PP2A) is a serine/threonine phosphatase that plays an important role in cell growth and inflammation. The prodrug Fingolimod (FTY720) and its phosphorylated active metabolite (p-FTY720) activate intracellular PP2A. We hypothesized that monocyte …

Effects Of Lisdexamfetamine And Haloperidol On A Binge-Like Eating Model & Preliminary Investigations Of The Dopaminergic Mechanism Underlying Binge Eating Disorder (Bed), Maxime Braun

Honors Scholar Theses

Binge eating disorder (BED) is a psychophysiological disorder defined as the excessive intake of high-caloric, palatable foods within a short span of time, accompanied by feelings of distress. Animal models of binge-like eating behavior have been developed that give intermittent, limited access to a highly palatable food. Presby et al. (2020) used chocolate as the highly palatable food to induce binge-like eating behavior in rats. Lisdexamfetamine (LDX), a d-amphetamine prodrug and dopamine (DA) uptake inhibitor, is currently used to treat BED in humand. In rats, binge-like eating of chocolate was induced by exposure to unpredictable and limited chocolate access over …