Pharmacy and Pharmaceutical Sciences Commons^™

Pharmacists On The Front Lines Of Polypharmacy: The Individualized Medication Assessment And Planning (Imap) Project To Improve Medication Use In Senior Adults With Cancer, Ginah Nightingale Pharmd, Bcop, Laura T. Pizzi Pharmd, Mph, Emily Hajjar Pharmd, Bcps, Bcacp, Cgp, Elizabeth Pigott, Margaret Wang, Shannon Doherty, Kristine Swartz Md, Andrew Chapman Do, Facp

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

A Phase I Study Of Ad5-Gucy2c-Padre In Stage I And Ii Colon Cancer Patients, Adam E. Snook, Trevor R. Baybutt, Michael J. Mastrangelo, Nancy L. Lewis, Scott D. Goldstein, Walter K. Kraft, Yaa D. Oppong, Terry Hyslop, Ronald E. Myers, Vitali Alexeev, Laurence C. Eisenlohr, Takami Sato, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Posters

Background

Ad5-GUCY2C-PADRE is a replication-deficient human type 5 recombinant adenovirus (Ad5) vaccine encoding guanylyl cyclase C (GUCY2C) fused to the PAn DR Epitope (PADRE). GUCY2C, a paracrine hormone receptor producing the second messenger cyclic GMP (cGMP), is selectively expressed by intestinal epithelial cells and a subset of hypothalamic neurons, but not other tissues. Importantly, GUCY2C is over-expressed in nearly all primary and metastatic human colorectal tumors. Preclinical studies in mice demonstrated selective tolerance of GUCY2C-specific CD4+ T cells, but not CD8+ T or B cells, necessitating inclusion of the exogenous CD4+ T helper cell epitope PADRE to maximize GUCY2C-specific CD8+ …

Regulating Drug Promotion To Promote The Public Health: A Response To Bennett, Et Al., Patricia J. Zettler

Faculty Publications By Year

No abstract provided.

Compatibility Of Vancomycin And Oxacillin During Simulated Y-Site Delivery, Chad A. Knoderer, Hilary M. Teibel, Kristen R. Nichols

Scholarship and Professional Work – COPHS

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) …

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Pharmaceutical Science and Research

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation …

2014 Brings New Drugs, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Predicting Aqueous Solubility Of Pharmaceutical Agents By Solid Dispersion Prepared By Solvent Evaporation Method, Karthik Reddy Patlolla

University of the Pacific Theses and Dissertations

Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research objective was to determine the descriptors which significantly influence the solubility enhancement by solid dispersions. After enhancing the solubility of selected poorly-soluble …

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy And Minimal Toxicity, Ngoc T. Vo

UROP Posters

Cancer is the second leading cause of death in the U.S. and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations …

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Pharmaceutical Science and Research

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. …

3,4,5-Trichloroaniline Nephrotoxicity In Vitro: Potential Role Of Free Radicals And Renal Biotransformation, Christopher Racine, Dakota Ward, Dianne K. Anestis, Travis Ferguson, Deborah Preston, Gary O. Rankin

Pharmaceutical Science and Research

Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a …

Analysis Of Ligand Bias In Functional Studies Involving The Allosteric Modulation Of G Protein- Coupled Receptors, Frederick J. Ehlert, Michael T. Griffin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Introduction

The affinity constants of a ligand for active and inactive states of a receptor ultimately determine its capacity to activate downstream signaling events. In this report, we describe a reverse-engineering strategy for estimating these microscopic constants.

Methods

Our approach involves analyzing responses measured downstream in the signaling pathway of a G protein-coupled receptor under conditions of allosteric modulation and reduced receptor expression or partial receptor inactivation. The analysis also yields estimates of the isomerization constant of the unoccupied receptor, the sensitivity constant of the signaling pathway, and the more empirical parameters of the receptor population including the observed affinities …

Lrh1 As A Driving Factor For Cancer Development, Alissa M. Margraf

Senior Honors Projects

LRH1 as a driving factor for cancer development

Alissa Margraf, Qi Tang, Qiushi Lin, Xiaoqun Dong

Department of Biomedical and Pharmaceutical Science, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881 USA

Cancer is a major public health problem worldwide. Colon cancer ranks as the third most common causes of cancer mortality in the United States, with an estimated 96,830 new cases and 50,310 deaths in 2014. Colon cancer develops in the digestive tract where benign growths called polyps transform into malignant tumors. Colon cancer cells invade and destroy nearby tissue and can …

Nudging The Fda, W. Nicholson Price Ii, I. Glenn Cohen

Law Faculty Scholarship

[Excerpt] "The FDA’s regulation of drugs is frequently the subject of policy debate, with arguments falling into two camps. On the one hand, a libertarian view of patients and the health care system holds high the value of consumer choice. Patients should get all the information and the drugs they want; the FDA should do what it can to enforce some basic standards but should otherwise get out of the way. On the other hand, a paternalist view values the FDA’s role as an expert agency standing between patients and a set of potentially dangerous drugs and potentially unscrupulous or …

Facile, Regio-And Diastereoselective Synthesis Of Spiro-Pyrrolidine And Pyrrolizine Derivatives And Evaluation Of Their Antiproliferative Activities, Abdulrahman I. Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Chen, Brian Sullivan, Kellen Mccaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali

Pharmacy Faculty Articles and Research

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 M) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-alpha-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Meta-Analysis Of Herbal Cannabis Therapy For Chronic Pain, Michael J. Seneca

UNF Graduate Theses and Dissertations

Since the first so-called “medical marijuana” legislation was passed in California in 1996, a total of twenty states and the District of Columbia have passed laws permitting limited use of cannabis. Despite the changes in state laws, cannabis remains illegal for any purpose under federal law. Changes in state laws have coincided with a renewed interest in the substance for the treatment of a variety of conditions. There has been a significant increase in published data over the past twenty years examining the efficacy of cannabis as an appetite stimulant, antiemetic agent, and analgesic adjuvant. The purpose of this meta-analysis …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Mk-0448, A Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics And Pharmacodynamic Electrophysiology In Experimental Animal Models And In Humans., Behzad B. Pavri, Howard E Greenberg, Walter K. Kraft, Nicole Lazarus, Joseph J Lynch, Joseph J Salata, Mark T Bilodeau, Christopher P Regan, Gary Stump, Li Fan, Anish Mehta, John A Wagner, David E Gutstein, Daniel Bloomfield

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led …

Pharmacologic Management Of The Opioid Neonatal Abstinence Syndrome., Walter K. Kraft, John N Van Den Anker

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Opioid use in pregnant women has increased over the last decade. Following birth, infants with in utero exposure demonstrate signs and symptoms of withdrawal known as the neonatal abstinence syndrome (NAS). Infants express a spectrum of disease, with most requiring the administration of pharmacologic therapy to ensure proper growth and development. Treatment often involves prolonged hospitalization. There is a general lack of high-quality clinical trial data to guide optimal therapy, and significant heterogeneity in treatment approaches. Emerging trends in the treatment of infants with NAS include the use of sublingual buprenorphine, transition to outpatient therapy, and pharmacogenetic risk stratification.

Effect Of Concomitant Medications Affecting Gastric Ph And Motility On Posaconazole Tablet Pharmacokinetics, Walter K. Kraft, P. Chang, Mlps Van Iersel, H. Waskin, G. Krishna, W. Kersemaekers

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Poster presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (52^nd ICAAC) held in San Francisco 9/9-9/12

Background: Posaconazole (POS) oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new POS tablet formulation has demonstrated improved bioavailability over oral suspension in healthy adults in the fasting state. This study evaluated the effect of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and motility (metoclopramide) on the pharmacokinetics of POS tablet.

Methods: This was a prospective, open-label, 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg (100 …

Phosphorylation Of Vasodilator-Stimulated Phosphoprotein Ser239 Suppresses Filopodia And Invadopodia In Colon Cancer., David S Zuzga, Joshua Pelta-Heller, Peng Li, Alessandro Bombonati, Scott A Waldman, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

In colorectal cancer, the antitumorigenic guanylyl cyclase C (GCC) signalome is defective reflecting ligand deprivation from downregulation of endogenous hormone expression. Although the proximal intracellular mediators of that signal transduction system, including cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), are well characterized, the functional significance of its distal effectors remain vague. Dysregulation of ligand-dependent GCC signaling through vasodilator-stimulated phosphoprotein (VASP), an actin-binding protein implicated in membrane protrusion dynamics, drastically reduced cGMP-dependent VASP phosphorylation levels in colorectal tumors from patients. Restoration of cGMP-dependent VASP phosphorylation by GCC agonists suppressed the number and length of locomotory (filopodia) and invasive (invadopodia) …

Molecular Staging Individualizing Cancer Management, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Although the most important prognostic and predictive marker in colorectal cancer is tumor cells in lymph nodes, ∼30% of patients who are node-negative die from occult metastases. Molecular staging employing specific markers and sensitive detection technologies has emerged as a powerful platform to assess prognosis in node-negative colon cancer. Integrating molecular staging into algorithms that individualize patient management will require validation and the definition of relationships between occult tumor cells, prognosis, and responses to chemotherapy. J. Surg. Oncol. 2012; 105:468-474. © 2012 Wiley Periodicals, Inc.

Copyright © 2012 Wiley Periodicals, Inc.

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …

Retrospective Comparison Of The Incidence Of Acute Kidney Injury In Patients Treated With Intravenous Polymyxin B Or Intravenous Colistimethate Sodium, Rebecca A. Sumner Pharmd, Jarrod W. Kile Rph, Bcps

Department of Pharmacy

No abstract provided.

Retrospective Evaluation Of Admissions For Chemotherapy-Inducednausea, Vomiting, And Dehydration, Katelin Van Leer Pharmad, Janine Barnaby Rph, Bcop

Department of Pharmacy

No abstract provided.

The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, Prajyot Kumta, Joy C. Macdermid, Saurabh Mehta, Paul W. Stratford

Physical Therapy Faculty Research

Study

DesignPsychometric study design.

Objectives

To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.

Background

Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.

Methods

Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. …

Novel Amino Acid Transporter-Targeted Radiotracers For Breast Cancer Imaging, Fanlin Kong

Dissertations and Theses (Open Access)

Breast cancer is the most common malignancy among women in the world. Its 5-year survival rate ranges from 23.4% in patients with stage IV to 98% in stage I disease, highlighting the importance of early detection and diagnosis. ¹⁸F-2-Fluoro-2-deoxy-glucose (¹⁸F-FDG), using positron emission tomography (PET), is the most common functional imaging tool for breast cancer diagnosis currently. Unfortunately, ¹⁸F-FDG-PET has several limitations such as poorly differentiating tumor tissues from inflammatory and normal brain tissues. Therefore, ¹⁸F-labeled amino acid-based radiotracers have been reported as an alternative, which is based on the fact that tumor cells uptake …

Formulation Of Buprenorphine For Sublingual Use In Neonates., Ellena A Anagnostis, Rania E Sadaka, Linda A Sailor, David E Moody, Kevin C Dysart, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVES: The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration.

METHODS: Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each …

The Incidence Of Deep Vein Thrombosis Detected By Routine Surveillance Ultrasound In Neurosurgery Patients Receiving Dual Modality Prophylaxis., Patricia C Henwood, Thomas M Kennedy, Lynda Thomson, Taki Galanis, George L Tzanis, Geno J Merli, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The optimal method of thromboprophylaxis and the value of screening ultrasonography for detection of deep venous thrombosis (DVT) in neurosurgery patients remains unclear. The goal of this study was to determine the incidence of DVT in neurosurgical patients who, by hospital protocol, receive surveillance ultrasonography of the lower extremities twice weekly, in addition to prophylaxis with unfractionated heparin and external pneumatic compression sleeves. A retrospective review of 7,298 ultrasound studies carried out on 2,593 patients over 4 years at a university neurosurgical hospital was conducted. There was a 7.4% incidence of proximal lower extremity DVT and a 9.7% total incidence …