Pharmacy and Pharmaceutical Sciences Commons^™

Development Of Tools To Assess The Effects Of Lunasin On Normal Development And Tumor Progression In Drosophila Melanogaster, Gillian E. Jones

Masters Theses & Specialist Projects

Soy contains many bioactive molecules known to elicit anti-cancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells while having no cytotoxic effect on non-tumorigenic or established cancer cell lines. In this study we attempt to understand the developmental effects of Lunasin overexpression in vivo and create reagents that will help us understand Lunasin’s anti tumorigenic effects in an intact organism. cDNA encoding lunasin and EGFP-lunasin were cloned into pUAST and microinjected into Drosophila embryos. Tissue-specific overexpression of EGFP-Lun in the resulting transgenic lines was accomplished by crossing transgenics to various GAL4 driver lines. …

Isolation And Structural Elucidation Of Phytochemicals Present In Red Maple Flowers, Holly Tran

Senior Honors Projects

Natural medicines and the use of botanical extracts in the prevention and treatment of ailments is globally gaining interest (Mazzio and Soliman, 2009). Detrimental side effects may be reduced using natural therapies (Desai et al., 2008). Worldwide, there are about 120 different maple species. Of those, thirteen are native to eastern North America (Maple Field Guide, 2002). Maple syrup is a natural sweetener derived from collected and concentrated maple tree sap. It takes about 40 liters of sap to make one liter of syrup. Maple plant parts have been used by Native Americans for medicinal purposes. The University of Rhode …

Conflicts Of Interest And The Quality Of Recommendations In Clinical Guidelines, Lisa Cosgrove, Allen F. Shaughnessy, Deborah R. Erlich, Emily E. Wheeler, Harold J. Bursztajn

Counseling, School Psychology & Sport Faculty Publication Series

Background: There is increasing concern that conflicts of interest affect the development process of clinical practice guidelines. We evaluated The American Psychiatric Association's Practice Guideline for the Treatment of Patients with Major Depressive Disorder to determine the existence of financial and intellectual conflicts of interest and examine their possible effects. We selected this guideline because of its influence on clinical practice and because this guideline recommends pharmacotherapy for all levels of depression, despite controversies over the evidence base.

Methods and Findings: We determined the number and type of financial conflicts of interest for members of the guideline development group as …

Development Of Hif-1Α/Hif-1Β Heterodimerization Inhibitors Using A Novel Bioluminescence Reporter Assay System For In Vitro High Throughput Screening And In Vivo Imaging, Yun-Chen Chiang

Dissertations and Theses (Open Access)

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study …

Design, Development, And Characterization Of Novel Antimicrobial Peptides For Pharmaceutical Applications, Yazan H. Akkam

Graduate Theses and Dissertations

Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs. Histatin 5 is a naturally occurring human salivary antifungal peptide and the first line of defense against infections of the oral cavity. This research has focused on understanding the activity of histatin 5, and subsequently designing novel peptides that may serve as models for the further development of therapeutics to treat fungal infection.

This objective has been achieved in three steps: studying the structural requirement of histatin 5 involved in antifungal activity, the identification of …

Polysaccharide-Based Nanocarriers For Improved Drug Delivery, Nan Zhang

Dissertations - ALL

The field of drug delivery has provided a solution to the limited efficacy and high toxicity of many drugs. Nano-sized drug carriers are popular because their size allows for selective accumulation in the diseased area. Polysaccharides are non-toxic and biodegradable natural polymers that can serve as the basis for these nano-sized carriers. Polysialic acid (PSA) is such a polysaccharide with strong hydrophilicity that may reduce uptake by the reticuloendothelial system and prolong drug circulation. In this study, we developed PSA-based nanocarriers, specifically micelles and nanoparticles, for improved drug delivery with improved efficacy and minimized toxicity. PSA-based micelle systems were developed …

Rupture Test And Bioavailability Of Oil-Soluble Vitamins, Lipika Chablani

Pharmacy Faculty/Staff Publications

In lieu of an abstract, here is the article's first paragraph:

Bioavailability of multi-vitamins as dietary supplements has always been a concern. Dissolution studies have been successfully used to predict drug release of bioactive molecules, but with vitamins there are some exceptions. United State Pharmacopoeia (USP) defines the dissolution requirements of multi-vitamin supplements based on the composition and type of dosage form. As oil-soluble vitamins do not meet the criterion of “dissolution”, the performance of dosage forms containing such vitamins is evaluated by disintegration studies primarily. Dissolution studies are not applicable for such dosage forms [1].

Combination Of Sirna-Directed Gene Silencing With Cisplatin Reverses Drug Resistance In Human Non-Small Cell Lung Cancer, Shanthi Ganesh, Arun K. Iyer, Jan Weller, David V. Morrissey, Mansoor M. Amiji

Pharmaceutical Sciences Faculty Publications

One of the most challenging aspects of lung cancer therapy is the rapid acquisition of multidrug-resistant (MDR) phenotype. One effective approach would be to identify and downregulate resistance-causing genes in tumors using small interfering RNAs (siRNAs) to increase the sensitivity of tumor cells to chemotherapeutic challenge. After identifying the overexpressed resistance-related antiapoptotic genes (survivin and bcl-2) in cisplatin-resistant cells, the siRNA sequences were designed and screened to select the most efficacious candidates. Modifications were introduced in them to minimize off-target effects. Subsequently, the combination of siRNA and cisplatin that gave the maximum synergy was identified in resistant cells. We then …

A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia

Theses and Dissertations

In vitro dissolution, release and permeation testing is a common practice during drug product research and development. These in vitro tests, if predictive, are referred to as biorelevant tests and can play diverse roles to facilitate and expedite product development in a cost effective manner. Oral transmucosal products (OTPs) are currently tested using compendial and modified in vitro tests which may or may not be good predictors of in vivo performance due to a lack of biorelevance. A critical need for a broadly applicable and biorelevant in vitro system for OTPs has been expressed in the literature and the goal …

Computational And Experimental Insights Into The Mechanism Of Substrate Recognition And Feedback Inhibition Of Protoporphyrinogen Oxidase, Ge-Fei Hao, Ying Tan, Sheng-Gang Yang, Zhi-Fang Wang, Chang-Guo Zhan, Zhen Xi, Guang-Fu Yang

Pharmaceutical Sciences Faculty Publications

Protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) is an essential enzyme catalyzing the last common step in the pathway leading to heme and chlorophyll biosynthesis. Great interest in PPO inhibitors arises from both its significance to agriculture and medicine. However, the discovery of PPO inhibitors with ultrahigh potency and selectivity is hampered due to lack of structural and mechanistic understanding about the substrate recognition, which remains a longstanding question central in porphyrin biology. To understand the mechanism, a novel binding model of protogen (protoporphyrinogen IX, the substrate) was developed through extensive computational simulations. Subsequently, amino acid residues that are critical for …

Dose Ratios Between High Dose Oral Morphine Or Equivalents And Oral Methadone, Megan S. Chatham, Elizabeth S. Dodds Ashley, Jefferson S. Svengsouk, Katherine Juba

Pharmacy Faculty/Staff Publications

Background: Methadone is a commonly used opioid in hospice and palliative care for patients with refractory pain. Various methadone dose conversion methods utilize progressively higher morphine equivalent dose (MED) to methadone dose ratios to compensate for increased methadone potency with escalating opioid doses.

Objective: The purpose of this study was to determine the dose ratio between equianalgesic doses of high dose oral morphine (daily doses >1200 mg morphine or MED) and oral methadone.

Methods: This study was a retrospective chart review of 324 patients who received methadone at Strong Memorial Hospital or the associated outpatient clinic during a nine-month period …

Random Mutagenesis Of The Aspergillus Oryzae Genome Results In Fungal Antibacterial Activity, Cory A. Leonard, Stacy D. Brown, James Russell Hayman

ETSU Faculty Works

Multidrug-resistant bacteria cause severe infections in hospitals and communities. Development of new drugs to combat resistant microorganisms is needed. Natural products of microbial origin are the source of most currently available antibiotics. We hypothesized that random mutagenesis of Aspergillus oryzae would result in secretion of antibacterial compounds. To address this hypothesis, we developed a screen to identify individual A. oryzae mutants that inhibit the growth of Methicillin-resistant Staphylococcus aureus (MRSA) in vitro. To randomly generate A. oryzae mutant strains, spores were treated with ethyl methanesulfonate (EMS). Over 3000 EMS-treated A. oryzae cultures were tested in the screen, and one isolate, …

Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande

Theses and Dissertations

The major physiological function of hemoglobin (Hb) is to bind, transport and deliver oxygen to tissues; made efficient by endogenous effectors, such as protons and 2,3-diphosphoglycerate. Synthetic allosteric effectors of Hb (AEHs) are also known to modulate Hb oxygen affinity, showing potential for the treatment of sickle cell disease (SCD) and ischemic-related diseases. In this project, AEHs which increase Hb affinity for oxygen, including derivatives of the anti-sickling compounds, 5HMF and benzaldehydes, as well as an AEH that decreases Hb affinity for oxygen, RSR-13, were synthesized for their effects on Hb oxygen binding property and their capability to release NO …

Analgesic Effect Of A Mixed T-Type Channel Inhibitor/Cb2 Receptor Agonist, Vinicius M. Gadotti, Haitao You, Ravil R. Petrov, N. Daniel Berger, Philippe Diaz, Gerald W. Zamponi

Biomedical and Pharmaceutical Sciences Faculty Publications

Background: Cannabinoid receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181. Results: NMP-181 action on CB1 and CB2 receptors was characterized in radioligand binding and in vitro GTP gamma[S-35] functional assays, and block of transiently expressed human Cav3.2 T-type channels by NMP-181 was analyzed by patch clamp. The analgesic effects and in vivo mechanism of action of NMP-181 delivered spinally or systemically were analyzed in formalin and CFA mouse models of pain. NMP-181 inhibited peak Ca(V)3.2 currents with IC50 values …

The College Of Pharmacy, South Dakota State University

Jackrabbits Script and Scope (Formerly called College of Pharmacy and Allied Health Professions Magazine)

[Page] 2 Endowed professorship created A trust created by a pharmacist who never attended college is providing the funds for the college’s first endowed professorship.
[Page] 3 Berry power The inaugural speaker at the Francis Miller Lecture extols the value of blueberries in fighting cancer — and he’s got the research to prove it. [Page] 4 Medication safety Deidra Van Gilder and Tasha Rausch are part of a national effort to curb medication mistakes through the Patient and Clinical Pharmacy Service Collaborative.
[Page] 6 Ashley Potter The P3 student took a rather indirect route to leadership in a student pharmaceutical …

Teaching Residents To Teach: Preparing Faculty And Clinical Educators, Sarah Nisly, Tracy Sprunger, Alison Walton, Tracy Costello, Jane M. Gervasio, Mary H. Andritz

Scholarship and Professional Work – COPHS

Abstract from the 114th Annual Meeting of the American Association of Colleges of Pharmacy, Chicago, IL, July 13-17, 2013.

Tigecycline Induction Of Phenol-Soluble Modulins By Invasive Methicillin-Resistant Staphylococcus Aureus Strains, Jason Yamaki, Timothy Synold, Annie Wong-Beringer

Pharmacy Faculty Articles and Research

We examined the effects of tigecycline on three types of exoproteins, α-type phenol-soluble modulins (PSMα1 to PSMα4), α-hemolysin, and protein A, in 13 methicillin-resistant Staphylococcus aureus isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSMαs occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSMα₁ to PSMα₄, as protein A and α-hemolysin production was decreased under the same conditions by all of the antibiotics used.

Metal-Based Nanoparticle Interactions With The Nervous System: The Challenge Of Brain Entry And The Risk Of Retention In The Organism, Robert A. Yokel, Eric A. Grulke, Robert C. Macphail

Pharmaceutical Sciences Faculty Publications

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical–chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in …

Pharmacy Law Brief: Exclusion Of Practitioners From Federally Funded Health Programs, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Gene Transfer Of Mutant Mouse Cholinesterase Provides High Lifetime Expression And Reduced Cocaine Responses With No Evident Toxicity, Liyi Geng, Yang Gao, Xiabin Chen, Shurong Hou, Chang-Guo Zhan, Zoran Radic, Robin J. Parks, Stephen J. Russell, Linh Pham, Stephen Brimijoin

Pharmaceutical Sciences Faculty Publications

Gene transfer of a human cocaine hydrolase (hCocH) derived from butyrylcholinesterase (BChE) by 5 mutations (A199S/F227A/S287G/A328W/Y332G) has shown promise in animal studies for treatment of cocaine addiction. To predict the physiological fate and immunogenicity of this enzyme in humans, a comparable enzyme was created and tested in a conspecific host. Thus, similar mutations (A199S/S227A/S287G/A328W/Y332G) were introduced into mouse BChE to obtain a mouse CocH (mCocH). The cDNA was incorporated into viral vectors based on: a) serotype-5 helper-dependent adenovirus (hdAD) with ApoE promoter, and b) serotype-8 adeno-associated virus with CMV promoter (AAV-CMV) or multiple promoter and enhancer elements (AAV-VIP). Experiments on …