Pharmacy and Pharmaceutical Sciences Commons^™

Glioma: A Tale Of Corticosteroids, Thiopurines And Proposed Novel Antiglioma Small Molecules, Amira Ahmed

Theses and Dissertations (ETD)

Glioma is a brain tumor that arises from glial cells or glial progenitor cells, and represents 80% of malignant brain tumor incidence in the United States. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor malignancy with fewer than 8% of patients with GBM surviving for 3 years. Over the past 10 years, despite improvement in diagnosis and therapies for cancer, the survival rate for high-grade glioma patients remains unchanged. The main focus of this dissertation is to investigate two therapeutic agents that are related to increase tumor resistance or increase secondary tumor incidence, which might play a role …

Assessing The Relationship Between The Blood-Air Partition Coefficient And Fractional Uptake Of Inspired Halothane, Acetone, And Ethanol Vapors In The Airways Of The C57bl/6j Mouse, Joshua Baruch Baldino

Honors Scholar Theses

The following series of studies investigates the elimination and uptake trends of halothane, acetone, and ethanol vapors in the airways of C57BL/6J mice. These vapors were chosen because they span a wide range of solubilities, as indicated by their blood-air partition coefficients, and are not associated with any significant airway metabolism or reactivity with tissue substrates in vivo. Mice were exposed to a homogeneous vapor mixture containing a 1:1:1 ratio of halothane, acetone, and ethanol at relative concentrations of approximately 10 ppm. Exposure studies were performed with mice in two states, conscious and deceased, in order to provide control …

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 …

Investigations Of Novel Mechanisms Of Action For Anti-Bacterial And Anti-Cancer Agent Development, Jenson Verghese

Theses and Dissertations

The development of drugs and therapeutic agents for combating infections and human malignancies continues to be a forefront area in both academic and industrial research. This is driven by the rapid emergence of multi-drug resistant bacterial strains and accumulating mutations in cancer targets that is quickly rendering our current arsenal of drugs ineffective for these therapies. Unless new drugs with novel mechanisms of action are identified and developed at a faster pace, we face a losing battle in managing these diseases. The first part of this work concerns with the natural product Simocyclinone D8 (SD8). Simocyclinone D8 is an angucyclinone …

Respon Bioakumulator Eceng Gondok (Eichhornia Crassipes) Terhadap Logam Berat Pb Dan Cd Di Sungai Pegangsaan Dua, Sri Teguh Rahayu, Meutia Faradilla, Ester Yani Verawati, Muchrip Triana

Pharmaceutical Sciences and Research

Eichhornia crassipes is one of Indonesia’s wild plant that considered as weed. Its presence can disrupt ecosystems in the river. However, it is proven to absorb Pb and Fe. It is also believed that E.crassipes can absorb other metals such as Hg , Zn , Cu and Cd which were belong to the same group as Pb and Fe. In addition to heavy metal sequestration, Eichhornia crassipes can also absorb pesticide residues. This descriptive research was done to determine the bioaccumulator response to Pb and Cd in Pegangsaan Dua river using Inductively Coupled Plasma method. Bioaccumulator response of Eichhornia crassipes …

Formulasi Gel Pacar Air (Impatiens Balsamina Linn.) Terhadap Propionibacterium Acnes Dan Staphylococcus Epidermidis, Diah Ismarani, Liza Pratiwi, Indri Kusharyanti

Pharmaceutical Sciences and Research

Acnes vulgaris is a chronic inflammatory disease of sebaceous follicles caused by Propionibacterium acnes and Staphylococcus epidermidis. The antibacterial activity of Impatiens balsamina L. has been studied for many years. The aims of this study are to find out the antiacne effect from methanolic extract of stems and leaves of Impatiens balsamina L. that formulated in gel. Simplicia were extracted using soxhlet technique bu using methanol as solvent. Extracts were then formulated in gel in three variations of HPMC 4000 and Carbopol 934 as gel base with ratio of 70:30 (F1), 50:50 (F2) and 30:70 (F3). The determination of antiacne …

Uji Aktivitas Antibakteri 1-[(Kuinazolin-4-On-2-Il)Metil]Piridin-1-Ium Bromida Dan 2-Bromometilkuinazolin-4-On, Hayun Hayun, Arif Arrahman, Herman Suryadi, Arry Yanuar

Pharmaceutical Sciences and Research

Antibacterial activity tests of quinazolin-4-one derivates: 1-[(6-nitroquinazolin-4one-2-yl)methyl]piridin-1-ium bromide (1), 1-[(6-aminoquinazolin-4-on-2-yl)methyl] piridin-1-um bromide (2), 2-bromomethylquinazolin-4-one (3) and 2-bromomethyl-6nitroquinazolin-4-one(4) with trimethoprim (5) as a positive standard were conducted. The antibacterial activity tests were carried out using disc diffusion method againts E.coli, S.aureus and S.thyposa, and determination of minimum inhibitory concentration (MIC). The results showed that compounds 1 and 2 are inactive as antibacterial, whereas compounds 3 and 4 are active.The activities to E.coli were ¼ times the activity of trimethoprim (MIC : 5 x 102 µg/ml compared to 1.25 x 102 µg/ml ). The activity to S. typhosa were ½-1 times the …

Uji Toksisitas Fraksi Air Impatiens Balsamina Pada Tikus Betina Galur Sprague Dawley, Entang Nurqolbiah, Indri Kusharyanti, Siti Nani Nurbaeti

Pharmaceutical Sciences and Research

The present study was aimed to predict the level of toxicity of aqueous fraction of Impatiens balsamina by acute toxicity study using OECD guideline 425. Female Sprague Dawley 8-12 week and weight between 140-170 gram were used, the amount of experimental rats were 10 rats. Rats were sequentially administered all the fraction in single dosage (limit test) of 2000 mg/kg body weight and 5000 mg/kg of body weight. All the animals were individually studied for mortality, wellness parameters, food consumption,water consumption, body weight. Histopathological examination was done on the liver and kidney. The result of this study showed that no …

Pengaruh Natrium Hialuronat Terhadap Penetrasi Kofein Sebagai Antiselulit Dalam Sediaan Hidrogel, Hidroalkoholik Gel, Dan Emulsi Gel, Joshita Djajadisastra, Zuraida Syafara Dzuhro, Sutriyo Sutriyo

Pharmaceutical Sciences and Research

Anticellulite topical gel preparation with caffeine as active ingredient needs a penetration enhancer to reach subcutaneous layer. Sodium hyaluronate (NaHA), the sodium salt of hyaluronic acid, is a hydrophilic polysaccharide derivative polymer. It has ability to enhance percutaneous penetration by loosening the dense of the compact substance stratum corneum. The aim of this research was to observe the effects of NaHA on caffeine penetration as anticellulite active agent in three types of gel preparation: hydrogel, hydroalcoholic gel, and gel emulsion. Each gel type contained caffeine 1,5% and was varied into three formulas. Formula 1 contained HPMC 2% as gel basis; …

Opioid-Ketamine And Norketamine Codrug Combinations For Pain Management, Joseph R. Holtman, Peter A. Crooks, Ujjwal Chakraborty

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of pain management, and more particularly to synergistic codrugs comprising an opioid and ketamine or norketamine which have been combined to form a single chemical codrug entity. When the codrug is administered it produces a synergistic analgesic response to pain.

Opioid-Nornicotine Codrugs Combinations For Pain Management, Joseph R. Holtman, Peter A. Crooks, Ujjwal Chakraborty

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of pain management, and more particularly to synergistic codrugs comprising an opioid and nornicotine which have been combined to form a single chemical codrug entity. When the codrug is administered it produces a synergistic analgesic response to pain.

Studies On Rationally Designed, Allosteric, Coagulation Inhibitors, Rio Boothello

Theses and Dissertations

Heparin is a natural allosteric modulator, with numerous structural and conformational variations leading to many reports of bleeding complications and variations in anticoagulant effects. A flurry of research has been directed towards understanding this puzzle. This work entails the utilization of three unique strategies to further our understanding of this complex issue. Traditional synthetic, biosynthetic and biophysical approaches have failed to conquer the GAG-protein complexity. Computational analysis however could serve as a powerful approach to decipher this dilemma. A dual filter algorithm was incorporated to identify unique hexasaccharide sequences for HCII and AT. Our experimental studies exhibit a good correlation …

Honokiol Enhances Paclitaxel Efficacy In Multi-Drug Resistant Human Cancer Model Through The Induction Of Apoptosis, Xu Wang, Jonathan J. Beitler, Hong Wang, Michael J. Lee, Wen Huang, Lydia Koenig, Sreenivas Nannapaneni, Arm R. Amin, Michael Bonner, Hyung Ju C. Shin, Zhuo Georgia Chen, Jack L. Arbiser, Dong M. Shin

Pharmaceutical Science and Research

Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC₅₀ ranging 3.35±0.13 µg/ml to 2.77±0.22 µg/ml), despite their significant differences in response to paclitaxel (IC₅₀ ranging 1.66±0.09 ng/ml to 6560.9±439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in …

The Effect Of Size On Ag Nanosphere Toxicity In Macrophage Cell Models And Lung Epithelial Cell Lines Is Dependent On Particle Dissolution, Raymond F. Hamilton, Sarah Buckingham, Andrij Holian

Biomedical and Pharmaceutical Sciences Faculty Publications

Silver (Ag) nanomaterials are increasingly used in a variety of commercial applications. This study examined the effect of size (20 and 110 nm) and surface stabilization (citrate and PVP coatings) on toxicity, particle uptake and NLRP3 inflammasome activation in a variety of macrophage and epithelial cell lines. The results indicated that smaller Ag (20 nm), regardless of coating, were more toxic in both cell types and most active in the THP-1 macrophages. TEM imaging demonstrated that 20 nm Ag nanospheres dissolved more rapidly than 110 nm Ag nanospheres in acidic phagolysosomes consistent with Ag ion mediated toxicity. In addition, there …

Childhood Obesity And Familial Hypercholesterolemia: Genetic Diseases That Contribute To Cardiovascular Disease, Alyssa Caudle

Senior Honors Theses

Childhood obesity occurs as the result of an imbalance between caloric intake and energy expenditure. Genetic risk factors for obesity have become an area of research due to its permanency. Mutated genes such as Fat Mass and Obesity Associated (FTO), Leptin (LEP), Leptin Receptor (LEPR), Melanocortin 4 Receptor (MC4R), Adiponectin C1Q and Collagen Domain Containing (ADIPOQ), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) all contribute to the development of childhood obesity. In the presence of high cholesterol caused by obesity, the genetic condition known as familial hypercholesterolemia is exacerbated. Familial hypercholesterolemia is caused by a …

Pharmacy Elder Abuse Assessment Project, Alexandrea Ham

College of Health Sciences Presentations

Purpose: The purpose of this project is to evaluate the perceptions of students at the College of Pharmacy at Idaho State University on the topic of elder abuse. Methods: The study will be conducted by using a web-based survey developed by the researchers. A thirteen question survey will be administered to a convenience sample of students at the College of Pharmacy to assess their current understandings and perceptions on the topic of elder abuse. The survey is also intended to help as an educational component by helping students identify red flags of abuse and neglect and gives direction on how …

Analysis Of Compounded Pharmaceutical Products To Teach The Importance Of Quality In An Applied Pharmaceutics Laboratory Course, Alyssa M. Pignato, Christine R. Birnie

Doctoral External Publications

Objective. To assess the effectiveness of a product-analysis laboratory exercise in teaching students the importance of quality in pharmaceutical compounding.

Design. Second-year pharmacy students (N=77) participated in a pharmaceutical compounding laboratory exercise and subsequently analyzed their final product using ultraviolet (UV) spectrometry.

Assessment. Reflection, survey instruments, and quiz questions were used to measure how well students understood the importance of quality in their compounded products. Product analysis showed that preparations compounded by students had an error range of 0.6% to 140%, with an average error of 23.7%. Students’ reflections cited common sources of error, including inaccurate weighing, contamination, and product …

Education In Pediatrics In Us Colleges And Schools Of Pharmacy, William Allan Prescott, Elizabeth M. Dahl, David Hutchinson

Pharmacy Faculty/Staff Publications

Objective. To determine the extent to which pediatrics is taught at US doctor of pharmacy (PharmD) programs and to characterize what is being taught and how.

Methods. A 40-question online survey instrument was sent to accredited and candidate-status US PharmD programs.

Results. Of 86 participating programs (67.2% response rate), 81 (94.2%) indicated that pediatric topics were included in their required classroom curricula (mean, 21.9 contact hours). A pediatric elective course was offered by 61.0% of programs (mean, 25.9 contact hours). Advanced pharmacy practice experiences (APPEs) in pediatrics were offered by 97.4% of programs, with an average of 27 students per …

Selective Inhibition Of Angiotensin Receptor Signaling Through Erk1/2 Pathway By A Novel Peptide, Jun Liu, Gina L. Yosten, Hong Ji, Dan Zhang, Wei Zheng, Robert C. Speth, Willis K. Samson, Kathryn Sandberg

HPD Articles

A seven-amino acid peptide (PEP7) is encoded within a short open reading frame within exon 2 (E2) in the 5'-leader sequence (5'LS) upstream of the rat ANG 1a-receptor (rAT1aR) mRNA. A chemically synthesized PEP7 markedly inhibited ANG II-induced Erk1/2 activation in cell culture by 62% compared with a scrambled PEP7 (sPEP7) [pErk1/2/Erk1/2 (AU): ANG II, 1.000 ± 0.0, ANG II+PEP7, 0.3812 ± 0.086, ANG II+sPEP7, 1.069 ± 0.18; n = 3]. Under these same conditions, PEP7 had no effect on ANG II-stimulated inositol-trisphosphate production. PEP7 also had no effect on epidermal growth factor- and phorbol methyl ester-induced Erk1/2 activation, suggesting …

Advanced Screencasting With Embedded Assessments In Pathophysiology And Therapeutics Course Modules, Ashley Woodruff, Megan Jensen, William Loeffler, Lisa M. Avery

Pharmacy Faculty/Staff Publications

Objective. To implement and assess the effectiveness of a hybrid learning model using advanced screencasting with embedded assessments in pathophysiology and therapeutics modules.

Design. Two pathophysiology and therapeutics course modules on viral hepatitis and the clinical pharmacokinetics of aminoglycosides were chosen for study. The preclass portion of the hybrid model involved student completion of interactive e-lectures that were created with the use of advanced screencasting and included embedded assessments. Students viewed the e-lectures and completed the assessment questions prior to in-class lecture.

Assessment. Preimplementation and postimplementation test scores were compared and student survey data were analyzed. Test scores improved significantly …

The Effect Of Transdermal Scopolamine For The Prevention Of Postoperative Nausea And Vomiting., María A Antor, Alberto A Uribe, Natali Erminy-Falcon, Joseph G Werner, Keith A Candiotti, Joseph V Pergolizzi, Sergio D Bergese

Pharmacy Articles

Postoperative nausea and vomiting (PONV) is one of the most common and undesirable complaints recorded in as many as 70-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia (SAMBA) guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue …

A Random Sequential Mechanism Of Aminoglycoside Acetylation By Mycobacterium Tuberculosis Eis Protein, Oleg V. Tsodikov, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

An important cause of bacterial resistance to aminoglycoside antibiotics is the enzymatic acetylation of their amino groups by acetyltransferases, which abolishes their binding to and inhibition of the bacterial ribosome. Enhanced intracellular survival (Eis) protein from Mycobacterium tuberculosis (Mt) is one of such acetyltransferases, whose upregulation was recently established as a cause of resistance to aminoglycosides in clinical cases of drug-resistant tuberculosis. The mechanism of aminoglycoside acetylation by MtEis is not completely understood. A systematic analysis of steady-state kinetics of acetylation of kanamycin A and neomycin B by Eis as a function of concentrations of these aminoglycosides …

The Association Between Influenza Treatment And Hospitalization-Associated Outcomes Among Korean Children With Laboratory-Confirmed Influenza, Jacqueline K. Lim, Tae Hee Kim, Paul E. Kilgore, Allison E. Aiello, Byung Min Choi, Kwang Chul Lee, Kee Hwan Yoo, Young-Hwan Song, Yun-Kyung Kim

Department of Pharmacy Practice

There are limited data evaluating the relationship between influenza treatment and hospitalization duration. Our purpose assessed the association between different treatments and hospital stay among Korean pediatric influenza patients. Total 770 children ≤ 15 yr-of-age hospitalized with community-acquired laboratory-confirmed influenza at three large urban tertiary care hospitals were identified through a retrospective medical chart review. Demographic, clinical, and cost data were extracted and a multivariable linear regression model was used to assess the associations between influenza treatment types and hospital stay. Overall, there were 81% of the patients hospitalized with laboratory-confirmed influenza who received antibiotic monotherapy whereas only 4% of …

Glutamate Transporter Control Of Ambient Glutamate Levels, Weinan Sun, Denis M. Shchepakin, Leonid Kalachev, Michael P. Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Accurate knowledge of the ambient extracellular glutamate concentration in brain is required for understanding its potential impacts on tonic and phasic receptor signaling. Estimates of ambient glutamate based on microdialysis measurements are generally in the range of ∼2–10 μM, approximately 100-fold higher than estimates based on electrophysiological measurements of tonic NMDA receptor activity (∼25–90 nM). The latter estimates are closer to the low nanomolar estimated thermodynamic limit of glutamate transporters. The reasons for this discrepancy are not known, but it has been suggested that microdialysis measurements could overestimate ambient extracellular glutamate because of reduced glutamate transporter activity in a …

The Fda Funding Crisis, Judith Alphonse, Sireesha Bellam, Marlene Fernandez, Anishka Gilbert, Lauren Roper, Antonia Zapantis, Robert C. Speth

HPD Articles

The role of the Food and Drug Administration (FDA) is to ensure the safety of prescription and nonprescription drugs, dietary supplements, and the food supply, representing more than 20% of US consumer spending. The increased need to monitor imported drugs, drug products and foods, drug shortages, and compounding pharmacies bring the adequacy of FDA funding into question. Performing even at status quo cannot be accomplished if responsibilities increase without equitable funding increases: both from the federal government and fees imposed on FDA-regulated industries. Additionally, scientific advancement, new legislation, and new industries are continually increasing the FDA workload, necessitating commensurate budget …

Controlling Protein Release Using Biodegradable Microparticles, Benjamin Patrick Kline

Open Access Theses

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety …

Mechanism Underlying Ikk Activation Mediated By The Linear Ubiquitin Chain Assembly Complex (Lubac), Hiroaki Fujita, Simin Rahighi, Mariko Akita, Ryuichi Kato, Yoshiteru Sasaki, Soichi Wakatsuki, Kazuhiro Iwai

Pharmacy Faculty Articles and Research

The linear ubiquitin chain assembly complex (LUBAC) ligase, consisting of HOIL-1L, HOIP, and SHARPIN, specifically generates linear polyubiquitin chains. LUBAC-mediated linear polyubiquitination has been implicated in NF-κB activation. NEMO, a component of the IκB kinase (IKK) complex, is a substrate of LUBAC, but the precise molecular mechanism underlying linear chain-mediated NF-κB activation has not been fully elucidated. Here, we demonstrate that linearly polyubiquitinated NEMO activates IKK more potently than unanchored linear chains. In mutational analyses based on the crystal structure of the complex between the HOIP NZF1 and NEMO CC2-LZ domains, which are involved in the HOIP-NEMO interaction, NEMO mutations …

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses To The Colorectal Cancer Antigen Gucy2c., Matthew Witek, Erik S Blomain, Michael Sullivan Magee, Bo Xiang, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined.

METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses …

Development Of An Evidence‐Based Implementation Plan For A System‐Wide Anticoagulation Management Service, Sarah Varney

Muskie School Capstones and Dissertations

The Mercy Health System of Maine (MHSM) is a large healthcare system located in Southern Maine. It consists of three inpatient campuses, one level II Emergency Department, four Express Care centers, seven Primary Care locations and an array of specialist practices. The organization has identified a need for improved management of anticoagulation therapy within the system as a large number of patients are receiving anticoagulation therapy throughout all of the various healthcare access sites. In order to address this need, MHSM seeks to implement a system‐wide, standardized approach for managing patients receiving anticoagulation therapy.

Pharmacy Newsletter : April 2014, Pharmacy Department

Department of Pharmacy Archives

Content:

• Investiture of Clean Room Pharmacy, Epitomize USP Chapter
• 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults
• Anticoagulation Clinic - Enhancing Patient Care
• Clinical Quality and Patient Safety Indicators