Medicine and Health Sciences Commons^™

August 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Bioinformatic Analysis Of Endogenous And Exogenous Small Rnas On Lipoproteins, Ryan M. Allen, Shilin Zhao, Marisol A. Ramirez Solano, Wanying Zhu, Danielle L. Michell, Yuhuan Wang, Yu Shyr, Praveen Sethupathy, Macrae F. Linton, Gregory A. Graf, Quanhu Sheng, Kasey C. Vickers

Pharmaceutical Sciences Faculty Publications

To comprehensively study extracellular small RNAs (sRNA) by sequencing (sRNA-seq), we developed a novel pipeline to overcome current limitations in analysis entitled, “Tools for Integrative Genome analysis of Extracellular sRNAs (TIGER)”. To demonstrate the power of this tool, sRNA-seq was performed on mouse lipoproteins, bile, urine and livers. A key advance for the TIGER pipeline is the ability to analyse both host and non-host sRNAs at genomic, parent RNA and individual fragment levels. TIGER was able to identify approximately 60% of sRNAs on lipoproteins and >85% of sRNAs in liver, bile and urine, a significant advance compared to existing software. …

Self-Assembling Bioaffinity Hydrogels For Localized Antibody Delivery, Wen Liu

Electronic Theses and Dissertations

The scope of illnesses that are being treated using monoclonal antibodies (mAbs) has been expanding from cancers to autoimmune diseases due to their high specificity to their molecular target. Because many of the new mAbs are aimed to modulate the immune system, an emerging concern is that patients with chronic illnesses are subjected to immune-related Adverse Events (irAEs). Loss of immunological tolerance to self-antigens or increased susceptibility to infections have been documented in some mAb treatments. Localized sustained release of mAb at disease sites might mitigate the risk of such toxicities. Antibody drugs are formulated typically for parenteral delivery because …

Effects Of Natural Antioxidants On Motor And Cognitive Deficits In An Animal Model Of Aging And Obesity And Dopaminergic-Like Sh-Sy5y Cell Line, Sneha Potdar

Electronic Theses and Dissertations

Aging is a universal phenomenon. One of the greatest challenges faced by the elderly population is to sustain a healthy standard of living. Advancing age is associated with increased motor and cognitive deficits. Loss of balance, falls, hip fractures, and poor memory all contribute to a decline in the quality of life of the aging population. While ongoing research is making advances to find therapeutic interventions for neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases, there is a pressing need to address deficits associated with normal aging.

Increase in oxidative stress and a decline of antioxidant mechanisms with aging have been …

Research News. Grants, 2018. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Grants (2015-)

Grants and contracts awarded during January-June 2018

Medication Exposure Patterns In Primary Care Patients Prescribed Pharmacogenetically Actionable Opioids, Mitchell R. Knisely, Janet S. Carpenter, Marion E. Broome, Ann M. Holmes, Diane Von Ah, Todd Skaar, Claire Burke Draucker

The Qualitative Report

Current approaches to assessing medication exposure fail to capture the complexity of the phenomenon and the context in which it occurs. This study’s purpose was to develop a typology of subgroups of patients who share common patterns of medication exposure. To create the typology, we used an exemplar sample of 30 patients in a large public healthcare system who had been prescribed the pharmacogenetically actionable opioids codeine or tramadol. Data related to medication exposure were drawn from large data repositories. Using a person-oriented qualitative approach, eight subgroups of patients who shared common patterns of medication exposure were identified. The subgroups …

Targeting Neuropeptides To Bone Fractures For Accelerated Healing, Nicholas A. Young, Jeffery J. Nielsen, Philip S. Low

The Summer Undergraduate Research Fellowship (SURF) Symposium

In patients over the age of 65 especially, bone fractures represent a significant disease burden. Non-invasive drug therapies are not available for bone fractures which represents a problem for this population. Vasoactive intestinal peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), two neuromodulator peptides in the glucagon superfamily, have demonstrated positive regulation of osteoblast proliferation and activity. Using acidic oligopeptides, we have developed ligands that target to and accumulate at fracture sites. These targeting ligands can be synthesized in sequence with bone anabolic peptides to minimize off target effects and increase potency at the fracture site to create safer and …

Research News. Publications, 2018. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period January 1 through June 30, 2018

Dietary Inclusion Of Enriched Chicken Bone Broth Prevents Trigeminal Sensitization Meditated By Early Life Stress, Orion Peterson

Graduate Theses/Dissertations

Early life stress is considered a risk factor for development of migraine, which is a prevalent painful neurological disorder involving sensitization and activation of trigeminal neurons, and irritable bowel syndrome, a condition often comorbid with chronic migraine. The focus of my study was to determine the effects of early life stress and dietary inclusion of enriched chicken bone broth on trigeminal nociceptor sensitization and the gut microbiota. Adult Sprague-Dawley male “sender” rats subjected to primary traumatic stress were placed next to breeding or pregnant female rats that served as “receiver” rats (secondary traumatic stress) and in proximity to the offspring …

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory …

A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …

Pharmaceutical Care Management Association V. Rutledge, John J. Crean, Karl Williams

Doctoral External Publications

On June 8, 2018 the federal Eighth Circuit Court of Appeals announced its decision concerning Arkansas' attempt to regulate perceived unfair payment practices of pharmacy benefit managers (PBMs) in the case Pharmaceutical Care Management Association v. Rutledge.¹ Because pharmacies across the country face similar problems, and this ruling may influence other federal appellate courts, review and discussion is useful for the purpose of making strategic decisions.

An Opportunity For Pharmacists To Help Improve Coordination And Continuity Of Patient Health Care, Jon C. Schommer, Lawrence M. Brown, Ryan (Alyssa) Bortz, Alina Cernasev, Basma T. Gomaa, Keri D. Hager, Lisa Hillman, Olihe Okoro, Serguei V. S. Pakhomov, Paul L. Ranelli

Pharmacy Faculty Articles and Research

Pharmacist workforce researchers are predicting a potential surplus of pharmacists in the United States that might result in pharmacists being available for engagement in new roles. The objective for this study was to describe consumer opinions regarding medication use, the health care system, and pharmacists to help identify new roles for pharmacists from the consumer perspective. Data were obtained from the 2015 and 2016 National Consumer Surveys on the Medication Experience and Pharmacist Roles. Out of the representative sample of 36,673 respondents living in the United States, 80% (29,426) submitted written comments at the end of the survey. Of these, …

Aminoflavone Inhibits Α6-Integrin And Growth Of Tamoxifen Resistant Breast Cancer, Petreena S. Campbell

Loma Linda University Electronic Theses, Dissertations & Projects

Approximately 40% of estrogen receptor positive (ER+) breast cancer patients develop resistance to standard of care agent tamoxifen, while ER negative (ER-) breast cancer patients are intrinsically resistant to tamoxifen. Resistance often promotes metastasis, recurrence and death. Tumor-initiating cells (TICs) represent key contributors to resistance and adhesion protein α6-integrin is a putative TIC biomarker. Investigational agent Aminoflavone (AF) demonstrates efficacy against breast cancer cells irrespective of ER status. Interestingly, we found tamoxifen resistant (TamR) cells and tumors exhibited elevated α6-integrin expression in comparison to their tamoxifen sensitive counterparts. AF effectively disrupted mammospheres enriched for TICs and reduced α6-integrin levels in …

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 …

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 …

“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 …