Pharmacy and Pharmaceutical Sciences Commons^™

Understanding The Impact Of Bcrp And Pgp Efflux Transporters On The Disposition Of Their Endogenous, Xenobiotic And Dietary Substrates, Samit Ganguly

Theses and Dissertations (ETD)

Breast Cancer Resistant Protein (BCRP) and P-glycoprotein (PGP) are membrane-bound efflux transporters that transport multiple chemical classes of compounds and act as barriers to tissue permeability, thereby regulating tissue exposure of their substrates. The role of these transporters in therapeutic resistance of their xenobiotic substrates due to their expression and efflux function at target organs/tissues, especially in brain and intestine, is well established, which has fueled investigation toward identification of their inhibitors. Multiple clinically used drugs and dietary chemicals have been reported to inhibit these transporters and potentially increase the exposure of concomitantly administered BCRP and/or PGP substrates, which might …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

Determining The Effect Of Locally Delivered Bioactive Modulators On Macrophage Activation At The Implantation Site Of Different Biomaterials In Rats, Kamel Alkhatib

Graduate Theses and Dissertations

Altering the foreign body reaction by targeting macrophages has been of interest in the biomaterials field to improve the integration of longevity of implanted biomedical devices. The objective of this dissertation was to study the effect of locally delivered bioactive modulators on macrophage activation at the implantation site of different biomaterials in rats. Iloprost, a prostacyclin analog, was tested for its ability to direct macrophages to their pro-wound healing phenotype after the implantation of microdialysis probe in the subcutaneous space of male Sprague Dawley rats. This study showed that iloprost can shift macrophage activation states in vivo to the pro-wound …

Glutathione: A Small Molecule With Big Sense, Cristina E. Raya, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Glutathione, a peptide found in microbes, plants and animals including human plays a key role in maintaining healthy cells. The peptide exists in both reduced and oxidized forms. Synthesis of GSH occurs in the cytosol of cells, and the extent of glutathione synthesis relies on various factors, such as amino acid availability, protein activity etc. Once synthesized, glutathione exists in both forms: oxidized (GSSG) and reduced (GSH). Oxidized glutathione characterized by its disulfide linkage. On the other hand, presence of a thiol group characterizes the reduced glutathione. This thiol makes the tripeptide an essential component of health; it makes glutathione …

“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on the …

Limiting Antibiotic Use In Acute Sinusitis: Partly A Matter Of Vocabulary?, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

In his issue introduction, the editor-in-chief of Journal of Patient-Centered Research and Reviews comments on an included article that describes the successful use of an electronic medical record best practice alert to reduce the rate of antibiotic prescription for acute sinusitis. Various methods previously tried to improve antibiotic stewardship in this illness are briefly reviewed. Borrowing on the model of acute bronchitis, it is suggested that a change in conveyed diagnostic vocabulary to “sinus cold” when describing acute sinusitis may help limit antibiotics for this predominantly viral infection.

Impact Of An Academic Pharmacy Elective On Student Interest In A Career In Academia, Gina Bellottie, Pharmd, Bcacp, Lindsay Fitzpatrick, Bs, Pharmd, Elena Umland, Pharmd

College of Pharmacy Posters

Objective

To determine the impact of an academic pharmacy elective on student interest in pursuing academic careers.

Evaluating Feasibility Of Blockchain Application For Dscsa Compliance, Tracie Scott, Armand L. Post, Johnny Quick, Sohail Rafiqi

SMU Data Science Review

Abstract. We evaluated the feasibility of using a blockchain technology to create a traceability solution for pharmaceutical drugs that would promote compliance with recent legislation. Counterfeit and other illegitimate pharmaceutical drugs threaten patient safety, drug efficacy, and patient trust. The purpose of the Drug Supply Chain Security Act (DSCSA) is to greatly reduce distribution of illegitimate drugs by requiring all pharmaceuticals to be serialized and traceable from the manufacturer through the supply chain to the dispenser. A software application to serialize and track pharmaceuticals must overcome numerous obstacles. In particular, the solution must provide a high degree of trust while …

Antimalarial Proteasome Inhibitor Reveals Collateral Sensitivity From Intersubunit Interactions And Fitness Cost Of Resistance., Laura A. Kirkman, Wenhu Zhan, Joseph Visone, Alexis Dziedziech, Pradeep K. Singh, Hao Fan, Xinran Tong, Igor Bruzual, Ryoma Hara, Masanori Kawasaki, Toshihiro Imaeda, Rei Okamoto, Kenjiro Sato, Mayako Michino, Elena Fernandez Alvaro, Liselle F. Guiang, Laura M. Sanz, Daniel J. Mota, Kavitha Govindasamy, Rong Wang, Yan Ling, Patrick K. Tumwebaze, George Sukenick, Lei Shi, Jeremie Vendome, Purnima Bhanot, Philip J. Rosenthal, Kazuyoshi Aso, Michael A. Foley, Roland A. Cooper, Bjorn Kafsack, J Stone Doggett, Carl F. Nathan, Gang Lin

Natural Sciences and Mathematics | Faculty Scholarship

We describe noncovalent, reversible asparagine ethylenediamine (AsnEDA) inhibitors of the Plasmodium falciparum proteasome (Pf20S) β5 subunit that spare all active subunits of human constitutive and immuno-proteasomes. The compounds are active against erythrocytic, sexual, and liver-stage parasites, against parasites resistant to current antimalarials, and against P. falciparum strains from patients in Africa. The β5 inhibitors synergize with a β2 inhibitor in vitro and in mice and with artemisinin. P. falciparum selected for resistance to an AsnEDA β5 inhibitor surprisingly harbored a point mutation in the noncatalytic β6 subunit. The β6 mutant was resistant to the species-selective Pf20S β5 inhibitor but remained …

Jörg Langowski: His Scientific Legacy And The Future It Promises, Giuseppe Chirico, Alexander Gansen, Sanford H. Leuba, Ada L. Olins, Donald E. Olins, Jeremy C. Smith, Katalin Tóth

Pharmaceutical Sciences Faculty Publications

Background: With the passing of Jörg Langowski 6 May 2017 in a sailplane accident, the scientific community was deprived of a strident and effective voice for DNA and chromatin molecular and computational biophysics, for open access publishing and for the creation of effective scientific research networks. Methods: Here, after reviewing some of Jörg’s key research contributions and ideas, we offer through the personal remembrance of his closest collaborators, a deep analysis of the major results of his research and the future directions they have engendered. Conclusions: The legacy of Jörg Langowski has been to propel a way of viewing biological …

A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …

July 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Salts Of Therapeutic Agents: Chemical, Physicochemical, And Biological Considerations, Deepak Gupta, Deepak Bhatia, Vivek S. Dave, Vijaykumar B. Sutariya, Sheeba Varghese Gupta

Pharmacy Faculty/Staff Publications

The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a …

Enzyme Replacement Therapies: What Is The Best Option?, Azam Safary, Mostafa Akbarzadeh Khiavi, Rahimeh Mousavi, Jaleh Barar, Mohammad Rafi

Department of Neurology Faculty Papers

Despite many beneficial outcomes of the conventional enzyme replacement therapy (ERT), several limitations such as the high-cost of the treatment and various inadvertent side effects including the occurrence of an immunological response against the infused enzyme and development of resistance to enzymes persist. These issues may limit the desired therapeutic outcomes of a majority of the lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the recombinant enzymes into the target cells within the central nervous system (CNS), bone, cartilage, cornea, and heart still remain unresolved. All these shortcomings necessitate the development of more effective diagnosis and treatment modalities against LSDs. …

Cysteine Modifiers Suggest An Allosteric Inhibitory Site On The Cal Pdz Domain, Yu Zhao, Patrick R. Cushing, David C. Smithson, Maria Pellegrini, Alexandre A. Pletnev, Sahar Al-Ayyoubi, Andrew V. Grassetti, Scott A. Gerber, R. Kiplin Guy, Dean R. Madden

Pharmaceutical Sciences Faculty Publications

Protein–protein interactions have become attractive targets for both experimental and therapeutic interventions. The PSD-95/Dlg1/ZO-1 (PDZ) domain is found in a large family of eukaryotic scaffold proteins that plays important roles in intracellular trafficking and localization of many target proteins. Here, we seek inhibitors of the PDZ protein that facilitates post-endocytic degradation of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR): the CFTR-associated ligand (CAL). We develop and validate biochemical screens and identify methyl-3,4-dephostatin (MD) and its analog ethyl-3,4-dephostatin (ED) as CAL PDZ inhibitors. Depending on conditions, MD can bind either covalently or non-covalently. Crystallographic and NMR data confirm that MD …

A Novel Hplc Method For Determination Of Phenytoin In Human Plasma, Jesse Flores, Sheril Alexander, Mariana Babayeva

Touro College of Pharmacy (New York) Publications and Research

Aim: Aim of this research was to develop and validate a simple, efficient and reproducible high performance liquid chromatography method to measure phenytoin concentrations in human plasma

Study Design: Linearity, selectivity, sensitivity, accuracy and precision of the analytical methods were validated according to ICH guidelines.

Methodology: The method employed a Phenomenex C18 column kept at 25ºC. The mobile phase consisted of a 0.05 M potassium dihydrogen phosphate buffer solution (pH 2.8) and methanol in a ratio of 60:40, respectively. The flow rate of the mobile phase was 0.7 mL/min. Phenytoin was detected at a wavelength of 250 …

#Drugfree: Using Social Media Advertisements To Spread Health On A College Campus, Amy M. Fanous, Benjamin D. Aronson, Jessica L. Hinson, Lindsey M. Peters, Breanna R. Meinzer, Zachary T. Woods, Michael J. Rush

Pharmacy Faculty Scholarship

No abstract provided.

Jackrabbits Script & Scope, College Of Pharmacy And Allied Health Professions

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

[Page] 4 Mort Takes the Lead
[Page] 8 International Rotation
[Page] 11 Hedge Honored
[Page] 12 Convocation
[Page] 14 White Coat Ceremony
[Page] 16 Distinguished Graduate
[Page] 18 Pharm.D. Class of 2018
[Page] 21 Preceptor of the Year
[Page] 24 Precision Medicine
[Page] 25 Phonathon Changes
[Page] 26 Pharmaogenomics
[Page] 27 Schaefer Joins
[Page] 28 Faculty Honors
[Page] 31 Huether Liked the Lab
[Page] 32 Academic Assessment -Curriculum Report
[Page] 34 Department of Pharmaceutical Sciences
[Page] 35 Department of Pharmacy Practice
[Page] 36 Donors
[Page] 38 Development Director's Report

Stability Of Extemporaneously Prepared Sodium Benzoate Oral Suspension, Julia Atkins, Melinda E. Lull, Andrew S. Decker, David Hutchinson

Doctoral External Publications

The stability of extemporaneously prepared sodium benzoate oral suspension in cherry syrup and Ora-Sweet was studied. Oral solutions of 250-mg/mL sodium benzoate were prepared in either cherry syrup or Ora-Sweet. To a beaker, 50 grams of Sodium Benzoate Powder USP was dissolved and filtered, the solution was divided equally into two parts, and each aliquot was added into two separate calibrated 100-mL amber vials. In the first vial, cherry syrup was added to make a final volume of 100 mL. In the second vial, Ora-Sweet was added to give a final volume of 100 mL. This process was repeated to …

Analysis Of Student Performance Outcomes Using Virtual Dispensing Exercises, Sophia Brown, Clark D. Kebodeaux, Keith Sewell, Aric Schadler, Keenan Beaumont

Pharmacy Practice and Science Presentations

The objective of this study was to compare performance outcomes between PY1 and PY2 students on an identical exercise required during their final objective structured clinical exam (OSCE).

Incidence Of Acute Kidney Injury Among Patients Treated With Piperacillin-Tazobactam Or Meropenem In Combination With Vancomycin, Wilbur Cliff Rutter, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at least 2 days were …

Self-Resistance During Muraymycin Biosynthesis: A Complementary Nucleotidyltransferase And Phosphotransferase With Identical Modification Sites And Distinct Temporal Order, Zheng Cui, Xia-Chang Wang, Xiaodong Liu, Anke Lemke, Stefan Koppermann, Christian Ducho, Jürgen Rohr, Jon S. Thorson, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Muraymycins are antibacterial natural products from Streptomyces spp. that inhibit translocase I (MraY), which is involved in cell wall biosynthesis. Structurally, muraymycins consist of a 5′-C-glycyluridine (GlyU) appended to a 5″-amino-5″-deoxyribose (ADR), forming a disaccharide core that is found in several peptidyl nucleoside inhibitors of MraY. For muraymycins, the GlyU-ADR disaccharide is further modified with an aminopropyl-linked peptide to generate the simplest structures, annotated as the muraymycin D series. Two enzymes encoded in the muraymycin biosynthetic gene cluster, Mur29 and Mur28, were functionally assigned in vitro as a Mg·ATP-dependent nucleotidyltransferase and a Mg·ATP-dependent phosphotransferase, respectively, both modifying the …

Worsening Choreoathetosis In Huntington's Disease With Fluoxetine, Lisdexamfetamine, And Melatonin: A Case Report., Clayton J Hamilton, Tysen K Timmer, Robert C Munjal, Fernando Cardozo-Pelaez, Ian R Mcgrane

Articles, Abstracts, and Reports

Cognitive, affective, and sleep disturbances can be found in patients with Huntington's disease (HD), and medications used to treat these HD-related sequela can also impact HD-related movement disorders. We present the case of a 52-year-old Caucasian man with previously undiagnosed HD who exhibited significant choreoathetoid movements that improved with discontinuation of fluoxetine and lisdexamfetamine upon hospital admission. Following diagnosis of HD through genetic testing, he was administered 5mg of oral melatonin on two consecutive evenings, which resulted in worsening choreoathetosis. We calculated Naranjo adverse event scores of 5, 5, and 2 for fluoxetine, lisdexamfetamine, and melatonin, respectively, based on our …

Impact Of Outpatient Vs Inpatient Absssi Treatment On Outcomes: A Retrospective Observational Analysis Of Medical Charts Across Us Emergency Departments, P Brandon Bookstaver, Timothy C. Jenkins, Edward Stenehjem, Shira Doron, Jack Brown, Shannon H. Goldwater, Carlos Lopes, Angela Haynes, Chuka Udeze, Yifan Mo, Patrick Gillard, Yan Liu, Katelyn Keyloun

Faculty Publications

Background: The objective of this study was to characterize treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) and describe the association between hospital admission and emergency department (ED) visits or readmissions within 30 days after initial episode of care (IEC). Methods: This was a retrospective, observational, cohort study of adults with ABSSSI who presented to an ED between July 1, 2012, and June 30, 2013. Patient, health care facility, and treatment characteristics, including unplanned ED visits or readmissions, were obtained through manual chart review and abstraction. Adjusted logistic regression analysis examined likelihood of all-cause unplanned ED …

Nsu Sharks Rx-Summer, 2018, Nova Southeastern University

NSU Sharks Rx

No abstract provided.

What Predicts Medication Therapy Management Completion Rates? The Role Of Community Pharmacy Staff Characteristics And Beliefs About Medication Therapy Management, Omolola A. Adeoye-Olatunde, Leslie M. Lake, Spencer G. Lourens, Rachel E. Morris, Margie E. Snyder

Department of Pharmacy Practice Faculty Publications

Objectives: To model the association between pharmacy technicians' attitudes and planned behaviors toward participating in medication therapy management (MTM) and MTM completion rates. Secondary objectives included 1) to compare pharmacy technician and pharmacist attitudes and planned behaviors toward participating in MTM and 2) to identify respondent and pharmacy demographic factors associated with MTM completion rates.

Design: A 27-item survey, adapted from a previously published survey tool based on the Theory of Planned Behavior (TPB), was used to collect respondent perceptions of MTM. Study procedures were approved by the institutional review board.

Setting and participants: Pharmacy technicians and pharmacists representing 116 …

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the …

Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant toxicity up …

Drug-Phospholipid Complex-Loaded Matrix Film Formulation For The Enhanced Transdermal Delivery Of Quercetin, Darshan R. Telange, Kuldeep D. Wavare, Arun T. Patil, Milind J. Umekar, Sridhar Anand, Vivek S. Dave

Pharmacy Faculty/Staff Publications

A novel quercetin-phospholipid-complex(QPLC)-loaded matrix film for improved transdermal delivery of quercetin was developed. The QPLC formulation, prepared using a solvent-evaporation method, was optimized using a central-composite design. The optimized QPLC formulation was characterized by particle size and zeta potential analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). QPLC formulation was functionally evaluated for solubility and in vitro dissolution of quercetin. Matrix films of pure quercetin (Q-MF)or QPLC QPLC-MF) were prepared using a solvent casting method. The prepared Q-MF and QPLC-MF were characterized for weight uniformity, folding endurance, moisture content, and moisture uptake. The …

Guide To Popular Diets, Food Choices, And Their Health Outcome, Ronald D. Hills Jr., Emily Erpenbeck

Pharmaceutical Sciences Faculty Publications

Integrative medicine is becoming increasingly important for a patient population afflicted with preventable illnesses such as cardiometabolic disease. Diet and nutrition are an under-tapped opportunity in health care for improving wellness and patient-centered health outcomes. Key nutritional principles are reviewed for alternate dietary strategies patients choose from in pursuit of healthy living or to alleviate chronic illness. Whole food eating plans are discussed including plant-based, Mediterranean, Paleo, and ketogenic diets as well as the specific carbohydrate and low FODMAP diets for colitis and irritable bowel syndrome. Opposed to the traditional categorization of diets by macronutrient composition, it is more useful …