Pharmacy and Pharmaceutical Sciences Commons^™

Data-Driven Design Of An Ebola Therapeutic, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

Formulation is very important in drug delivery. The wrong formulation can render a drug product useless. The amount of preclinical (animal and in vitro) work that must be done before a new drug candidate can be tested in humans can be a problem. The cost of these cGxP studies is typically $3-$5 million. If the wrong drug product formulation is tested, new iterations of the formulation must be tested with additional costs.

Data-driven computational science can help reduce this cost. In the absence of existing human exposure, a battery of preclinical tests must be performed in at least two species …

Towards A Better Understanding Of On And Off Target Effects Of The Lymphocyte-Specific Kinase Lck For The Development Of Novel And Safer Pharmaceuticals, Xiaofei Zhang, Amir Kucharski, Wibe A. De Jong, Sally R. Ellingson

Markey Cancer Center Faculty Publications

In this work we have developed a multi-tiered computational platform to study protein-drug interactions. At the beginning of the workflow more efficient and less accurate methods are used to enable large libraries of proteins in many conformations and massive chemical libraries to be screened. At each subsequent step in the workflow a subset of input data is investigated with increased accuracy and more computationally expensive methods. We demonstrate the developed workflow with the investigation of the lymphocyte-specific kinase LCK, which is implicated as a drug target in many cancers and also known to have toxic effects when unintentionally targeted. Several …

Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 g/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of …

Pharmacological Approaches For The Management Of Patients With Moderately Elevated Triglycerides (150-499 Mg/Dl), Michael S. Kelly, Craig Beavers, John D. Bucheit, Evan M. Sisson, Dave L. Dixon

Pharmacy Faculty Articles and Research

Hypertriglyceridemia, defined as serum triglyceride (TG) levels > 150 mg/dL, now affects over one-quarter of the U.S. adult population and is associated with an increased risk of atherosclerotic cardiovascular disease. Available guidelines for managing hypertriglyceridemia vary with respect to triglyceride thresholds and severity of disease. Lifestyle modifications and management of secondary causes (e.g., diabetes) remain the first step in managing hypertriglyceridemia, with pharmacotherapy reserved to reduce the risk of pancreatitis and/or further reduce TG levels. Several classes of lipid-lowering agents are available with variable TG-lowering efficacy. While there is no consensus regarding the choice of initial TG-lowering pharmacotherapy, there is general …

Effects Of Phosphodiesterase 3a Modulation On Murine Cerebral Microhemorrhages, Rachita K. Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.

Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and …

Prevalence And Predictors Of Herbal Medicine Use Among Adults In The United States, Mohamed Rashrash, Jon C. Schommer, Lawrence M. Brown

Pharmacy Faculty Articles and Research

Objective: To describe the prevalence of herbal medicine use among US adults and to assess factors associated with and predictors of herbal use. Design: The data for herbal products use were collected from the 2015 National Consumer Survey on the Medication Experience and Pharmacists’ Roles. Chi-square test was used to analyz factors associated with herbal use, and predictors of herbal use were assessed with logistic regression analysis. Results: Factors associated with herbal supplement use include age older than 70, having a higher than high school education, using prescription medications or over-thecounter (OTC) medications, and using a mail-order …

Commencement Program 2017, Loma Linda University

Commencement Programs

CONTENTS

1 | Message from the President

3 | 2017 Events of Commencement

5 | The Academic Procession

7 | Significance of Academic Regalia

9 | The Good Samaritan

10 | University History Highlights

12 | Loma Linda University Song - "Healing Love"

13 | The University Honorees

26 | The Programs, The School Honorees, and The Speakers

• School of Medicine, 27
• School of Pharmacy, 52
• School of Dentistry, 64
• School of Allied Health Professions - Allied Health Studies, Cardiopulmonary Sciences, Clinical Laboratory Science, Communication Sciences and Disorders, Health Informatics and Information Management, Nutrition and Dietetics, Physician Assistant Sciences, Radiation …

Loss Of Resistance To Angiotensin Ii-Induced Hypertension In The Jackson Laboratory Recombination-Activating Gene Null Mouse On The C57bl/6j Background, Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert Charles Speth, Kathryn Sandberg

Faculty Articles

Resistance to angiotensin II (Ang II)–induced hypertension in T-cell–deficient male mice with a targeted mutation in the recombination-activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1^−/−-M), which was reported by 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per minute was identical between B6.Rag1^−/−-M and male wild-type littermates. Moreover, there were no differences in the time course or magnitude increase …

Immune Checkpoint Inhibition And The Prevalence Of Autoimmune Disorders Among Patients With Lung And Renal Cancer, Sherif M. El-Refai

Pharmaceutical Sciences Faculty Publications

PURPOSE: Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation. We sought to identify, among patients with lung and renal cancer, how many harbor a comorbid autoimmune condition and may be at risk of worsening their condition while on immune checkpoint inhibitors such as nivolumab and pembrolizumab.

METHODS: An administrative health care claims database, Truven MarketScan, was used to identify patients diagnosed with lung and renal cancer from 2010 to 2013. We assessed patients …

Identification Of A Nucleoside Analog Active Against Adenosine Kinase-Expressing Plasma Cell Malignancies, Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J. Barelli, Michelle A. Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H. Shoemaker, J. David Warren, Olivier Elemento, Kenneth M. Kaye, Ethel Cesarman

Pharmacy Faculty Articles and Research

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we …

Power Dissipation And Power Correlations For A Retreatblade Impeller Under Different Baffling Conditions, Chadakarn Sirasitthichoke

Theses

Glass-lined stirred reactors and tanks are commonly used in the pharmaceutical industry because of their corrosion resistance, ease of cleanliness and minimization of product contamination. Most industrial glass-lined tank reactors are provided with a torispherical tank bottom and a retreat curve impeller with low impeller clearance from the vessel bottom. The power, P, dissipated by the impeller is a critical process parameter to mixing processes to achieve the desired mixing effect, especially since the power per unit volume, P/V, directly controls mass transfer processes and other mixing phenomena. However, little information has been published about the power dissipation and the …

Introduction To Systematic Reviews And Meta Analysis Php ###, Joanna Burkhardt

Library Impact Statements

No abstract provided.

May 2017, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Nano-Assembly Of Amyloid Β Peptide: Role Of The Hairpin Fold., Sibaprasad Maity, Mohtadin Hashemi, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14-23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14-23) monomers form fibrils. Additionally, an equimolar mixture of the monomer and the hairpin assembles into non-fibrillar aggregates, demonstrating that the hairpin fold dramatically changes the …

Optimizing Medication Appropriateness In Older Adults: A Randomized Clinical Interventional Trial To Decrease Anticholinergic Burden, Daniela C. Moga, Erin L. Abner, Dorinda N. Rigsby, Lynne Eckmann, Mark Huffmyer, Richard R. Murphy, Beth B. Coy, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

Background

The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined.

Methods

We conducted an 8-week, parallel-arm, randomized trial to evaluate whether a targeted patient-centered pharmacist–physician team MTM …

Phase Iii Prospective Randomized Comparison Trial Of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab In Patients With Advanced Carcinoid Tumors: Swog S0518, James C. Yao, Katherine A. Guthrie, Cesar Moran, Jonathan R. Strosberg, Matthew H. Kulke, Jennifer A. Chan, Noelle Loconte, Robert R. Mcwilliams, Edward M. Wolin, Bassam Mattar, Shannon Mcdonough, Helen Chen, Charles D. Blanke, Howard S. Hochster

Markey Cancer Center Faculty Publications

Purpose

Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs.

Patients and Methods

Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary …

Applied Drug Development And Combinatorial Strategies For Antimicrobial Treatment, Steven K. Lai Hing

Andrews Research Conference

Streptococcus mutans JH1140 is a strain of bacteria which produces a lantibiotic product, named mutacin 1140. Mutacin 1140 has been shown to be effective at inhibiting Gram-positive bacterial infections caused by Staphylococcus aureus and Streptococcus pneumoniae. Mutacin 1140 is a ribosomally synthesized peptide antibiotic that undergoes extensive posttranslational modifications (PTM). We have found that Mutacin 1140 and an aminoglycoside, Kanamycin, when combined together, act synergistically against Staphylococcus aureus. This was determined by performing serial kill curve dilution overlays on solid media, followed up with kill curve by microdilution plate, and most recently confirmed with kill curve CFU count plates …

Bis-Quaternary Ammonium Cyclophane Compounds That Interact With Neuronal Nicotinic Acetylcholine Receptors, Peter A. Crooks, Linda P. Dwoskin, Guangrong Zheng, Sangeetha Sumithran, David Allen, Zhenfa Zheng, Paul Lockman

Pharmaceutical Sciences Faculty Patents

Provided are bis-quaternary ammonium cyclophane compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders.

Evaluation Of An Unfractioned Heparin Pharmacy Dosing Protocol For The Treatment Of Venous Thromboembolism In Nonobese, Obese, And Severely Obese Patients, Chad A. Knoderer, Lindsey M. Hosch, Emily Y. Breedlove, Lauren E. Scono

Scholarship and Professional Work – COPHS

Background: Despite large interpatient variability in dose response, heparin is utilized for treatment of venous thromboembolism (VTE). Current data on the optimal heparin dosing in obese patients are conflicting. Objective: The objective was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol. Methods: This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese …

A Consensus Definitive Classification Of Scavenger Receptors And Their Roles In Health And Disease, Mercy R Prabhudas, Cynthia L Baldwin, Paul L Bollyky, Dawn M E Bowdish, Kurt Drickamer, Maria Febbraio, Joachim Herz, Lester Kobzik, Monty Krieger, John Loike, Benita Mcvicker, Terry K Means, Soren K Moestrup, Steven R Post, Tatsuya Sawamura, Samuel Silverstein, Robert Charles Speth, Janice C Telfer, Geoffrey M Thiele, Xiang-Yang Wang, Samuel D Wright, Joseph El Khoury

Faculty Articles

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and …