Medicine and Health Sciences Commons^™

First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill

Sanders-Brown Center on Aging Faculty Publications

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes …

Imatinib-Induced Interstitial Pneumonitis – A Literature Review And Case Report, Olga Hilda Orasan, Andreea Maria Stefan, Iulia Minciuna, Adela Sitar-Taut, George Ciulei, Simina Tarmure, Ioana Para, Flaviu Muresan, Ovidiu Fabian, Sorina Cezara Coste, Vasile Negrean, Angela Cozma, Laura Urian

Journal of Mind and Medical Sciences

Imatinib is generally well tolerated, with mild common side effects such as nausea and vomiting, diarrhea, muscle cramps, fatigue, skin rash and edema; however, pulmonary complications are uncommon. A 73-year-old woman undergoing one month treatment with Imatinib for chronic myeloid neoplasm associated with eosinophilia was admitted for sudden alteration of her performance status, dyspnea at rest and productive cough. On clinical examination, the patient was hypoxic (oxygen saturation on room air was 87%), and auscultation of her lungs revealed diffuse bilateral fine crackles. Computed tomography showed bilateral pulmonary interstitial syndrome. Imatinib was discontinued and the patient received systemic corticosteroid therapy …

Risk Factors, Predictive Markers And Prevention Strategies For Intrauterine Fetal Death. An Integrative Review, Roxana Bohiltea, Natalia Turcan, Christina M. Cavinder, Ionită Ducu, Ioana Paunica, Liliana Florina Andronache, Monica Mihaela Cirstoiu

Journal of Mind and Medical Sciences

According to World Health Organization (WHO), fetal death is defined as the death of the fetus prior to its complete expulsion, independent of the duration of pregnancy, thus only ascribing the term stillbirth to fetal deaths in the case of pregnancies after 28 weeks of gestation. The great progress of perinatology care is reflected in a significant reduction in the rate of stillbirths, especially in well-developed countries, with approximately 98% of stillbirth cases now occurring in poor and developing countries. Stillbirth powerfully impacts both the patient and the practitioner. Because nearly half of stillbirth cases result from apparently uncomplicated pregnancies, …

Muc13 Modulated Nanomechanical And Biophysical Responses In Pancreatic Cancer Cells, Andrew E. Massey

Theses and Dissertations (ETD)

Pancreatic adenocarcinoma is one of the deadliest forms of cancer. Even with recent advances in diagnostic tools, chemotherapeutic regimens, and biomarkers for earlier detection, it still has dismal survival rates. Part of the reason for this is the inherent difficulty in detecting and treating this disease. Recent findings suggest that the altered expression of mucins, including MUC13, may be useful molecular signatures for early disease diagnosis, chemotherapy response and predicting patient survival. MUC13, a recently identified transmembrane glycoprotein, is normally associated with forming a protective barrier on epithelial tissues. However, its overexpression/aberrant subcellular localization has been associated with cancer, disease …

Coronavirus Disease 2019 (Covid-19), Matthew Dunbar

Pharmacy Student Scholarship

No abstract provided.

Identification Of Factors Affecting Clinical Management And The Outcomes In Patients With Guillain Barre Syndrome, Vijaynarayana Kunhikatta Dr

Manipal College of Pharmaceutical Sciences, Manipal Theses and Dissertations

Introduction: Guillain Barre syndrome (GBS) is a rare autoimmune neurological disorder in which the body’s immune system attacks part of its peripheral nervous system resulting in limb and cranial nerve weakness often with respiratory compromise and limitation on physical function. The worldwide incidence of GBS ranges from 0.81 to 1.89 cases per 100000 person-years. Various factors such as age, symptoms and disease form that influence the outcome of GBS have been previously studied. This study seeks the additional fundamental knowledge of the factors affecting clinical management and the outcome in patients with GBS. Objective: To identify factors affecting clinical management …

Cancer Stem Cell Chemotherapeutics Assay For Prospective Treatment Of Recurrent Glioblastoma And Progressive Anaplastic Glioma: A Single-Institution Case Series, Tulika Ranjan, Candace M. Howard, Alexander Yu, Linda Xu, Khaled Aziz, David Jho, Jodi Leonardo, Muhammad A. Hameed, Stephen M. Karlovits, Rodney E. Wegner, Russell Fuhrer, Seth T. Lirette, Krista L. Denning, Jagan Valluri, Pier Paolo Claudio

Faculty and Student Publications

© 2020 BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA …

Concordance Between Electronic Health Record Data And Medicare Part D Claims Data For Oral Anticancer Drug Use, Manvi Sharma, Michael L. Johnson, Hui Zhao, Sharon H. Giordano, Holly M. Holmes

Faculty and Student Publications

No abstract provided.

Promising Selective Mao-B Inhibition By Sesamin, A Lignan From Zanthoxylum Flavum Stems, Shaymaa M. Mohamed, Narayan D. Chaurasiya, Nesma M. Mohamed, Soad A.L. Bayoumi, Babu L. Tekwani, Samir A. Ross

Faculty and Student Publications

© 2020 The Author(s) Monoamine oxidase inhibition is an important therapeutic approach for various neurodegenerative disorders. Reversible MAO inhibitors selectively targeting only one isoform possess substantial merit in terms of safety, efficacy, and side effect profile. This study aimed to isolate the secondary metabolites of Zanthoxylum flavum stems and evaluate their recombinant human MAO inhibition, antimicrobial, and antiprotozoal activities. As a result, fourteen compounds were isolated and identified (nine of them were reported from Z. flavum for the first time). Compound 3 (sesamin) exhibited potent selective MAO-B inhibition (IC50 value of 1.45 ± 0.05 µM) which reported herein for the …

A Public Health Issue: Dietary Supplements Promoted For Brain Health And Cognitive Performance, Cindy Crawford, Courtney Boyd, Bharathi Avula, Yan Hong Wang, Ikhlas A. Khan, Patricia A. Deuster

Faculty and Student Publications

© Cindy Crawford, et al. 2020; Published by Mary Ann Liebert, Inc. 2020. Background: Dietary supplements targeting brain health have quickly emerged in the marketplace as cognitive performance becomes an important public health issue. While manufacturers are required to report the exact ingredients and formulations listed on the Supplement Facts labels of products, many reports have indicated such labels are not always truthful, and the content of some products is inconsistent with the ingredients listed on the Supplement Facts label. Objectives: To identify dietary supplement products and ingredients marketed for brain health and cognitive performance and perform analyses of select …

Phad 795: Section 1 Special Topics: Applied Longitudinal Modeling, John P. Bentley Ph.D.

GMAS Course Syllabi

No abstract provided.

Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44^−/− BMDMs showed reduced MSU …

Plk1 Pbd Selective Inhibition As A Potential Cancer Therapy, Lauren E. Wilder

Senior Theses

Polo-Like Kinase 1 (PLK1) is a protein that has been found to be overexpressed in a variety of cancers including prostate and colorectal cancers, and it is often an indicator of poor patient prognosis. It has functions in initiating, maintaining, and completing mitosis, so it has an important role in controlling the proliferation of cells. PLK1 contains a highly conserved catalytic kinase domain and a less-conserved Polo Box Domain (PBD). Inhibiting the phospho-ligand binding of the PBD is a potential cancer therapy because it would prevent the cell from properly completing the cell cycle, thus inducing apoptosis. In Dr. McInnes’ …

Influenza Vaccination Coverage In Pediatric Patients With Inflammatory Bowel Disease, Kelly Brown

Senior Theses

Background: Children with chronic health conditions, including inflammatory bowel disease (IBD), are at especially high risk for influenza infection and complications. The Crohn’s & Colitis Foundation and American College of Gastroenterology recommend that IBD patients should receive annual influenza vaccination. The aims of this study were to evaluate influenza vaccination coverage over time and identify predictors of flu vaccination in pediatric IBD and non-IBD patients.

Methods: We utilized longitudinal data (2000 to 2016) from South Carolina Medicaid to conduct a matched cohort study. The primary exposure of interest was IBD diagnosis based upon ICD-9/10 diagnosis codes. Children with IBD were …

Augmenting The Access And Involvement Of Student Pharmacists In Research Opportunities Through Engaging Programming At An Academic Institution, Samantha Gruber

Honors Capstone Enhancement Presentations

A research study completed by Kritikos et al. investigated student pharmacists and their characteristics in order to find a relationship with their views of research and attitudes towards pharmacy practice research. The study also recognized perceived barriers to pursuing or completing pharmacy practice research and identified ways that pharmacy educators could promote research interest in pharmacy practice. The research study concluded that student pharmacists perceive a lack of awareness of the needs, benefits, and career opportunities associated with pharmacy practice research. In addition, the Accreditation Council for Pharmacy Education (ACPE) mentions in section 6.3 of the 2016 Standards that PharmD …

Epi-Pens: Honors Capstone Enhancement, Chelsey Boecker

Honors Capstone Enhancement Presentations

No abstract provided.

Covid-19 Vaccination Clinical Trials Should Consider Multiple Doses Of Bcg, Bassam M. Ayoub

Pharmacy

Vaccine repositioning is a hot research topic as an alternative to the traditional vaccine approach, which is a costly and time-consuming process due to the availability of previous safety and toxicology data. Multiple-dose BCG vaccine repurposing for COVID-19 will be an uprising breakthrough of vaccine discovery with safer outcomes. BCG induces cross-protection that might not be related to the target disease as innate immune cells, including monocytes and natural killer cells, contribute to this immune protection as known as “trained immunity” (Covián et al. 2019). BCG had multifaceted protection against TB, leprosy, and heterogeneous pathogens (Yamazaki-Nakashimada et al. 2020). Moreover, …

Dementia: Types, What They Are And How They Differ, Jessica N. Schnetzer

Honors Thesis

Dementia: types, what they are and how they differ centers on the known and unknown complexities of dementia. Dementia is a very complex cognitive disease that consumes the brain, an organ of which we know very little about. Even so, this common disorder is actively being researched and is the topic of special interest of this thesis research. Described are Alzheimer’s disease, Creutzfeldt-Jakob disease, Frontotemporal dementia, Huntington’s disease, Korsakoff’s syndrome, Lewy body dementia, Parkinson’s dementia, and Vascular dementia, focusing on what they are, their specific risks, diagnosis, treatment, and their differing progressions. Guidance of this study provided by thesis director …

Treatment With Protease Inhibitor And Development Of Diabetes Among Medicare Beneficiaries With Human Immune Virus/Acquired Immune Deficiency Syndrome (Hiv/Aids), Eric Ejike Chinaeke

Theses and Dissertations

Background: The possibility of an association between the use of protease inhibitors (PI) by HIV/AIDS patients and the occurrence of T2DM mellitus (T2DM) is largely debated. Medicare recipients are disproportionally affected by T2DM. Unfortunately, evidence is unavailable from that particular segment of the population. Clinical management of HIV/AIDS is progressively expanding to include chronic/metabolic complications, which may pose a significant economic burden to both the patients and the Medicare system, which are disproportionally impacted. Objectives: The aims of this project were to (1) examine the association between the use of PIs and the odds of developing T2DM among Medicare beneficiaries …

Research News. Publications, 2020. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period January 1 through March 31, 2020

Discrepancies In Written Versus Calculated Durations In Opioid Prescriptions: Pre-Post Study., Benjamin H. Slovis, John Kairys, Bracken Babula, Melanie Girondo, Cara Martino, Lindsey M. Roke, Jeffrey Riggio

Department of Medicine Faculty Papers

BACKGROUND: The United States is in the midst of an opioid epidemic. Long-term use of opioid medications is associated with an increased risk of dependence. The US Centers for Disease Control and Prevention makes specific recommendations regarding opioid prescribing, including that prescription quantities should not exceed the intended duration of treatment.

OBJECTIVE: The purpose of this study was to determine if opioid prescription quantities written at our institution exceed intended duration of treatment and whether enhancements to our electronic health record system improved any discrepancies.

METHODS: We examined the opioid prescriptions written at our institution for a 22-month period. We …

Adolescents’ Perceptions Of Contraception Access Through Pharmacies, Ashley H. Meredith, Emily Vahary, Tracey A. Wilkinson, Carolyn G. Meagher, Thomas Vielott, Mary A. Ott

Department of Pharmacy Practice Faculty Publications

Adolescent pregnancy is an important public health issue, and pharmacist prescribing has the potential to expand contraceptive access and decrease unintended pregnancy. However, little is known about acceptability and uptake of pharmacist prescribing among adolescents, particularly among youth in socially and politically conservative regions of the country. The study objective was to identify how young women in Indiana perceive pharmacist contraceptive prescribing. Participants were recruited from clinics and completed a simulated pharmacist contraception-prescribing encounter; a demographic and behavioral questionnaire; and an in-depth qualitative interview focused on adolescent perspectives on pharmacist prescribing. Data were analyzed using thematic analysis. Sixty young women …

A Novel Elvitegravir Nanoformulation For Drug Delivery Across The Blood-Brain Barrier To Suppress Hiv-1 In Macrophages And Microglia, Yuqing Gong

Theses and Dissertations (ETD)

Over the last two decades, the use of antiretroviral therapy (ART) has remarkably decreased the morbidity associated with HIV-1 infection. However, the prevalence of HIV-1-associated neurocognitive disorders (HAND) is still increasing. The appearance and persistence of HAND are partially due to the entry of HIV-1-infected monocytes into the brain. Within the central nervous system (CNS), HIV-1-infected macrophages and microglia serve as the major viral reservoirs and provide active viral replication even when systemic viral suppression has been achieved by ART. Efficient viral suppression of CNS macrophages and microglia is important for an effective HIV-1 treatment in the brain. The primary …

Method And System For Diterpene Production Platforms In Yeast, Joseph Chappell, Xun Zhuang, Shuiqin Wu

Pharmaceutical Sciences Faculty Patents

A method is provided for modifying yeast to express mutant avian farnesyl disphospate synthase and the resulting modified yeast. The yeast advantageously includes additional mutants including but not limited to having ergosterol dependent growth and being erg-. The modified yeast are beneficial for the production of various terpenes including diterpenes.

Using Medical Claims Database To Develop A Population Disease Progression Model For Leuprorelin-Treated Subjects With Hormone-Sensitive Prostate Cancer, Yixuan Zou, Fei Tang, Jeffery C. Talbert, Chee M. Ng

Pharmacy Practice and Science Faculty Publications

Androgen deprivation therapy (ADT) is a widely used treatment for patients with hormone-sensitive prostate cancer (PCa). However, duration of treatment response varies, and most patients eventually experience disease progression despite treatment. Leuprorelin is a luteinizing hormone-releasing hormone (LHRH) agonist, a commonly used form of ADT. Prostate-specific antigen (PSA) is a biomarker for monitoring disease progression and predicting treatment response and survival in PCa. However, time-dependent profile of tumor regression and growth in patients with hormone-sensitive PCa on ADT has never been fully characterized. In this analysis, nationwide medical claims database provided by Humana from 2007 to 2011 was used to …

The Incidence And Severity Of Drug Interactions Before And After Switching Antiretroviral Therapy To Bictegravir/Emtricitabine/Tenofovir Alafenamide In Treatment Experienced Patients, Ciara Walshe, Pharmd Candidate, Jason J. Schafer, Pharmd, Mph, Bcps-Aq Id, Bcidp, Aahivp

College of Pharmacy Posters

Objective

• The primary outcome was to measure the proportion of patients experiencing DIs before and after the ART switch.
• The secondary outcome was to measure changes in DI scores before and after the ART switch.

How Do Pharmacies Evaluate Cleanroom Automation Systems?, Kenneth Maxik, Craig Kimble, Alberto Coustasse, Chris Booth

Pharmacy Practice & Administration

Many pharmacies have implemented or considered implementing cleanroom automation or compounding systems. Intravenous (IV) admixture automation is one of the newest areas of technology that has been applied to pharmacy workflow. Manufacturers tout systems for reducing errors reaching patients. Clinical literature supports that cleanroom technology can aid in patient safety.

Diabetes Debunked: What You Need To Know, Maggie Hutson

Honors Program: Senior Projects (Public)

The goal of this Honors creative project is to encourage health literacy in populations who are curious about Type 2 Diabetes or have Type 2 Diabetes. From personal experience, I have seen noncompliance in diabetics and wondered why since it is a serious, progressive disease. After researching, I found that some diabetics do not understand the scope of their disease, especially since many of the dangerous complications that arise from Type 2 Diabetes do not present until later in the disease when it is too late. For my senior project, I decided to write an educational paper as a supplement …

Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both …

The Use Of Urine Drug Testing For Risk Stratification And Efficacious Drug Monitoring In Pain Management Settings, Ahmad I. Hasan, Kareem Elhage, Brendan Farley, Khaled J. Saleh

Medical Student Research Symposium

Objective: To understand the current landscape of urine drug testing (UDT) guidelines as part of risk assessment for opioid abuse, and to offer recommendations towards adopting universal screening guidelines.

Background: There has been an opioid epidemic within the United States, and the role of prescription opioids has been well established. Despite proposed recommendations, there has yet to be a published universal screening guideline on the use of UDT in the setting of opioid abuse risk stratification as well as postoperative drug monitoring.

Methods: We explored current guidelines for UDT on two levels. First, we explore general indications for UDT within …