Pharmacy and Pharmaceutical Sciences Commons^™

Ovarian Tumour Growth Is Characterized By Mevalonate Pathway Gene Signature In An Orthotopic, Syngeneic Model Of Epithelial Ovarian Cancer, Daniel B. Hardy

Physiology and Pharmacology Publications

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor …

Nicotine Directly Induces Endoplasmic Reticulum Stress Response In Rat Placental Trophoblast Giant Cells, Michael K. Wong, Alison Holloway C, Daniel B. Hardy

Physiology and Pharmacology Publications

Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats,nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency, however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblastgiant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (e.g., phosphorylated PERK, eIF2α, CHOP, BiP/GRP78) and trophoblast giant cell differentiation and function (e.g., Pl-1, Pgf, Hsd11b1, and Hsd11b2) were quantified via Western blot or …

Perceptions Of Licensed Pharmacist Managers Regarding Formally Versus Informally Trained Pharmacy Technicians, Shalonica Marie Cluse

Walden Dissertations and Doctoral Studies

Pharmacists rely on pharmacy technicians to assist with accurately dispensing prescriptions and providing information to clients. Texas does not have regulations for the education or training of pharmacy technicians, which may result in mistakes when dispensing prescriptions, causing significant harm to customers. The purpose of this qualitative phenomenological study was assessing formally and informally trained pharmacy technicians' job performance as perceived by licensed pharmacists/managers. Data were collected via face to face interviews with 9 pharmacy managers in Texas to gain insight into their lived experiences of supervising not formally and formally trained technicians. Audio recorded interview data were transcribed and …

Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo

Honors Undergraduate Theses

The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals …

Harmful Or Helpful? Direct To Consumer Advertising, Sally A. Kiss

The Graduate Review

Policy change in 1997 by the Food and Drug Administration made the United States only one of two countries to allow direct-to-consumer advertising (DTCA). DTCA refers to the promotion of prescription medications through media directly to consumers as opposed to distribution of information only medical professionals. Supporters argue that DTCA educates consumers and helps them to make more informed decisions about their health care. On the other side, opponents argue that it leads to otherwise healthy people believing they are sick, thereby increasing profits for pharmaceutical companies. After reviewing the history of DTCA and literature demonstrating the pros and cons …

Phytopharmaceuticals In Mongolia: Past, Present, And Future, Disan Gunbilig, Ulziinyam Rentsendorj

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

Over the last two decades, the consumption of medicinal plants has increased in Mongolia. Once banned by the post-revolutionary government, it is now valued by the practitioners of orthodox medicine, government as well as by the society. Yet the scientific community has to give this major and crucial component of traditional Mongolian medicine the attention it deserves, scientific knowledge about biologically active principles within medicinal plants remain poorly unknown. At the same time, due to over exploitation of plants many species are becoming extinct together with invaluable traditional knowledge being lost. For these reasons, there is a certain urgency to …

Medication Therapy Management, Ayman M. Noreddin, Francis Ndemo, David Ombengi

Pharmacy Faculty Articles and Research

"According to the Institute of Medicine report medications are the most common medical intervention. However, drug-related morbidity and mortality now represents a major public health challenge due to the ineffective and unsafe consequences of medication use. Morbidity in this case relates to disease and illness associated with drug therapy whereas mortality relates to death associated with drug therapy. It is also estimated in the US that drug-related morbidity and mortality cost about $200 billion annually in health care expenditure.

This is clearly a failure in our healthcare systems."

Capillary Endothelia From Two Adpkd Patients Are Polyploidy, Sarmed H. Kathem, Wissam A. Aboualaiwi, Xiaolin Zi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Bilateral renal cyst formation is the main feature of autosomal dominant polycystic kidney disease (ADPKD). We and other laboratories have previously shown that cystlining epithelia of kidneys from ADPKD patients are characterized by polyploidy. In this report, we show that endothelia from the renal capillary beds of two ADPKD patients are also polyploidy. Spectral karyotyping study further confirms our flow cytometry analyses. We suggest that polyploidy may be used as a potential cellular marker in ADPKD.

Improving The Renal Profile Of A Hiv Drug Combination Through Prodrug Alteration, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

"Human immunodeficiency virus (HIV) continues to alter the lives of countless individuals, who once infected, live on a continuum between viral suppression and acquired immunodeficiency syndrome. The former being achieved via the use of various antiretrovirals beginning with the release of zidovudine over a quarter-century ago; whereas the latter may result from treatment failure or lack of treatment such as in the absence of diagnosis or the inaccessibility of medication. As no cure is yet available, regimens must be continued lifelong. Thus, contemporary treatment is given as a combination of agents from various antiretroviral drug classes in an effort to …

Rnd3 As A Novel Target To Ameliorate Microvascular Leakage, Jerome W. Breslin, Dayle A. Daines, Travis M. Doggett, Kristine H. Kurtz, Flavia M. Souza-Smith, Xun E. Zhang, Mack H. Wu, Sarah Y. Yuan

Molecular Pharmacology & Physiology Faculty Publications

Background: Microvascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.

Methods and Results: Using immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate–albumin and transendothelial electrical resistance of human umbilical vein endothelial …

Intra-Articular Interleukin-1 Receptor Antagonist (Il1-Ra) Microspheres For Posttraumatic Osteoarthritis: In Vitro Biological Activity And In Vivo Disease Modifying Effect, Khaled A. Elsaid, Anand Ubhe, Ziyad Shaman, Gerard D'Souza

Pharmacy Faculty Articles and Research

Background: Interleukin-1 receptor antagonist (IL-1 ra) can be disease-modifying in posttraumatic osteoarthritis (PTOA). One limitation is its short joint residence time. We hypothesized that IL-1 ra encapsulation in poly (lactide-co-glycolide) (PLGA) microspheres reduces IL-1 ra systemic absorption and provides an enhanced anti-PTOA effect.

Methods: IL-1 ra release kinetics and biological activity: IL-1 ra encapsulation into PLGA microsphere was performed using double emulsion solvent extraction. Lyophilized PLGA IL-1 ra microspheres were resuspended in PBS and supernatant IL-1 ra concentrations were assayed. The biological activity of IL-1 ra from PLGA IL-1 ra microspheres was performed using IL-1 induced lymphocyte proliferation …

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Synthesis, Characterization, And In Vitro Anti-Tumor Studies Of Bis Imidazolium Salts With Alkyl Chain Linkers And Naphthylmethyl Substituents, Steven R. Crabtree

Williams Honors College, Honors Research Projects

Bis imidazolium salts, with alkyl chain linkers ranging from methylene to dodecyl, were synthesized with naphthylmethyl substituents at the N¹ and N^1’ positions for a structure-activity relationship (SAR) study. All compounds were characterized by ¹H and ¹³C NMR spectroscopy. The cationic portion of 2 as the PF₆ salt, 3, 4, and 5 were also characterized by single-crystal X-ray crystallography. Compounds 1-8, 10, and 12 were tested for their in vitro anti-cancer activity against four NSCLC cell lines via the MTT assay (NCI–H460, NCI–H1975, HCC827, and A549). Compounds 10 and 12 which …

Using Semiphysiologically-Based Pharmacokinetic (Semi-Pbpk) Modeling To Explore The Impact Of Differences Between The Intravenous (Iv) And Oral (Po) Route Of Administration On The Magnitude And Time Course Of Cyp3a-Mediated Metabolic Drug-Drug Interactions (Ddi) Using Midazolam (Mdz) As Prototypical Substrate And Fluconazole (Flz) And Erythromycin (Ery) As Prototypical Inhibitors, Mengyao Li

Theses and Dissertations

The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI.

Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on hepatic and gut wall (GW) CYP3A metabolism of MDZ, using available in-vitro/in-vivo information. Model-simulated MDZ …

Role Of T Lymphocyte Trafficking In Diabetic Cardiomyopathy, Chowdhury Sayef Abdullah

Electronic Theses and Dissertations

Diabetic cardiomyopathy is a distinct pathological condition characterized by myocardial fibrosis and cardiac dysfunction in diabetic patients. The resolution of myocardial fibrosis to improve cardiac function in diabetes is an active area of research. Notably, increased T lymphocyte infiltration into myocardium has been attributed to increased cardiac fibrosis and dysfunction in diabetes. However, the experimental data on the role of T lymphocyte modulation in diabetic myocardial fibrosis is scarce. To this end, sphingosine 1-phosphate receptor 1 (S1P1) regulates the egress of mature T lymphocytes from lymphoid organs to blood and peripheral organs. Thus, the inhibition of T cells trafficking through …

Novel Cellular Targets Of Aspirin In Chemoprevention Studies On P53, G6pd And C-Myc, Guoqiang Ai

Electronic Theses and Dissertations

Background

Aspirin has generated a significant interest in recent years as a potential chemopreventive agent supported by strong evidence from epidemiological data; however, the mechanisms are not well understood. The objective of this dissertation is to identify novel cyclooxygenase (COX)-independent pathways by which aspirin exerts its anticancer effects in epithelial cancer cell lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Neuroinflammatory Pain Models In Mice, Muzaffar Abbas

Electronic Theses and Dissertations

Neuroinflammatory pain affects about 1.5% of the United States population. Around 20-40% patients having neurological disorders are affected with neuroinflammatory pain. As a part of the limbic system, hippocampus is known to play a critical role in pain perception and processing, and is densely populated with microglial cells and α7 nicotinic acetylcholine receptors (nAChRs). Given the role of microglial α7 nAChRs in neuroinflammation, the α7 nAChRs have emerged as potential target for neuroinflammatory pain treatment. We hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary …

Global Reach, Local Markets: The Challenges Of Leading Global Innovation, Sarah Higgins

Honors Theses

This Global Studies honors thesis addresses how managers and leaders of global firms manage innovation across multiple markets. Current research on multinational corporations provides an understanding of different kinds of innovation and the ways to attend to multiple markets. However, there is less documentation of how these innovation strategies are actually implemented on the ground and the tensions that these efforts might produce. Therefore, my research focuses in particular on the challenges and tensions faced by leaders of global firms as they implement transnational innovation strategies. This study is based upon in-depth interviews with 20 participants who held positions in …

The Effects Of Amixicile, A Pyruvate Ferredoxin Oxidoreductase Inhibitor, On Oral Treponemes, Lucas A. Reed

Theses and Dissertations

Periodontal disease (PD) is a polymicrobial infection characterized by inflammation of the gingiva, alveolar bone resorption, and tooth loss (edentulism). Treponema denticola along with Porphyromonas gingivalis and Tannerella forsythia are among the “Red Complex” and are main etiological agents in PD. Treponemes are a member of the Spirochaeta phylum and are obligate anaerobes, that express pyruvate ferredoxin oxidoreductase (PFOR). The enzyme catalyzes the oxidation of pyruvate to acetyl-CoA and reduced ferredoxin. Amixicile is a novel bacteriostatic derivative of nitazoxanide and an inhibitor of PFOR. In light of the fact that Treponemes express PFOR, this study was conducted to investigate the …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Examination Of The Pharmacodynamics And Pharmacokinetics Of A Diclofenac Poly(Lactic-Co-Glycolic) Acid Nanoparticle Formulation In The Rat, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory.

MATERIALS AND METHODS: Rats were administered a single dose of methylcellulose (VEH), blank NP, DICLO (10 mg/kg), or a DICLO-NP suspension equivalent to the DICLO dose. Urinary and blood parameters were measured …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

The Influence Of Safety, Efficacy, And Medical Condition Severity On Natural V. Synthetic Drug Preference, Brian P. Meier, Courtney M. Lappas

Psychology Faculty Publications

Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as …

Biological And Chemical Investigation Of Panamanian Plants For Potential Utility Against Metabolic Syndrome, Yelkaira Vasquez

Electronic Theses and Dissertations

Metabolic syndrome (MetS) affects approximately 25% of the adult population of the world and represents a public health concern with high socioeconomic impact worldwide. Latin American populations exhibit a high prevalence of MetS, similar or even higher than developed countries. This complex and progressive disorder can develop over many years as a cluster of conditions characterized by a constellation of metabolic abnormalities. Specific guidelines have not yet been established for the treatment of MetS per se. The increased prevalence of MetS has been associated with a greater risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In …

Food/Drug Interactions: Assessing Student Knowledge Before And After Viewing An Interactive Educational Website, Cole Smith

Undergraduate Honors Thesis Collection

Background: Knowledge of food and drug interactions is important and may greatly impact compliance and success of drug therapy. Patients are required to be educated about food and drug interactions at the point of care by the Joint Commission on Accreditation of Healthcare Organizations’ standards; and, in both the institutional and community settings, quality of patient care is improved if the patient understands the importance of food and drug interactions. Methods: This study was conducted online via a web-based survey using Survey Monkey. Students in their second year of pre-pharmacy classes were asked to complete a pre-survey, review a website …

The Efficacy Of Antidepressants In Alleviating Anhedonia In Depressed Patients, Paras Patel

Undergraduate Honors Thesis Collection

Background: Anhedonia, or the inability to feel pleasure, is an important symptom of depression because it may be involved in preventing complete recovery and facilitating depression relapse. The relationship between depression severity and anhedonia in patients being treated with antidepressants has not been widely studied. The objective of this study was to characterize the alleviation of anhedonia in patients taking antidepressants for depression.

Methods: This was a prospective survey distributed at three outpatient psychiatric settings. Subjects above the age of twenty who indicated a depression diagnosis were included. Subjects with schizophrenia, bipolar disorder, or substance abuse disorder were excluded. A …

The Use Of Podcast As A Teaching Tool For A Pharmacy Compounding Pre-Laboratory Lecture: A Survey Based Study, Lara Kratochwill, Elise Almagambetova, Anthony Corigliano, Christine R. Birnie Phd, Lipika Chablani

Pharmacy Faculty/Staff Publications

Objective: To determine the opinions of pharmacy students towards use of podcast as a replacement to a traditional pre-laboratory lecture for a compounding course.

Methods: Second year pharmacy students were asked to view a podcast prior to their laboratory section as a replacement to an in-class pre-laboratory lecture. A voluntary survey was administered to obtain student feedback regarding the usefulness of podcasts and preferences for its use in future.

Results: A total of 192 out of 232 students responded to the survey conducted during 2011, 2012 and 2013. Of these, 94% of respondents reported viewing entire/ parts of the podcast. …

Use Of Continuous Renal Replacement Therapy For Removal Of Dabigatran In A Patient In Need Of Emergent Surgery, Sara E. Parli, Melissa L. Thompson Bastin, Daniel A. Lewis

Pharmacy Practice and Science Faculty Publications

Purpose. To report the ability to remove serum dabigatran using continuous renal replacement therapy (CRRT) in a patient with life-threatening bleeding. Summary. A 77-year-old female with history of atrial fibrillation who takes dabigatran for stroke prevention presented with abdominal pain. Patient was found to have bleeding and possible mesenteric ischemia and was taken to the operating room and had continued bleeding postoperatively. CRRT was initiated for the removal of any remaining dabigatran, with serum dabigatran levels collected to evaluate removal of dabigatran with CRRT. This patient had an increased dabigatran level prior to intervention, which decreased to an …

A Branch Point Of Streptomyces Sulfur Amino Acid Metabolism Controls The Production Of Albomycin, Aditya Kulkarni, Yu Zeng, Wei Zhou, Steven Van Lanen, Weiwen Zhang, Shawn Chen

Pharmaceutical Sciences Faculty Publications

Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century. Although the productivity of S. griseus can be increased with random mutagenesis methods, understanding of Streptomyces sulfur amino acid (SAA) metabolism, which supplies a precursor for ABM biosynthesis, could lead to improved and stable production. We previously characterized the …

Purin-6-One Derivatives As Phosphodiesterase-2 Inhibitors, Wei Yuan, Xin-Yun Zhao, Xi Chen, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

A series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC₅₀ values of 1.73, 0.18, and 3.43 μM, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds 2j, 2p, and 2q were further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of …