Medicine and Health Sciences Commons^™

Direct Nose To The Brain Nanomedicine Delivery Presents A Formidable Challenge, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular …

Novel Biomarkers Of Ciliary Extracellular Vesicles Interact With Ciliopathy And Alzheimer’S Associated Proteins, Ashraf M. Mohieldin, Amal Alachkar, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles …

Clinical Utility And Cost Effectiveness Of Long-Acting Lipoglycopeptides Used In Deep-Seated Infections Among Patients With Social And Economic Barriers To Care, Kayla Antosz, Majdi N. Al-Hasan, Z. Kevin Lu, Benjamin Tabor, Julie Ann Justo, Alexander Milgrom, Joseph Kohn, P. Brandon Bookstaver

Faculty Publications

The use of long-acting lipoglycopeptides (LaLGPs) in serious, deep-seated infections is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients were matched 1:1 to those who received standard of care (SOC). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics …

Evaluating The 0–10 Point Pain Scale On Adolescent Opioid Use In Us Emergency Departments, Michael T. Phan, Daniel M. Tomaszewski, Cody Arbuckle, Sun Yang, Brooke Jenkins, Michelle A. Fortier, Theodore Heyming, Erik Linstead, Candice Donaldson, Zeev N. Kain

Pharmacy Faculty Articles and Research

Objective: To evaluate trends in national emergency department (ED) adolescent opioid use in relation to reported pain scores. Methods: A retrospective, cross-sectional analysis on National Hospital Ambulatory Medical Care Survey (NHAMCS) data was conducted on ED visits involving patients aged 11–21 from 2008–2017. Crude observational counts were extrapolated to weighted estimates matching total population counts. Multivariate models were used to evaluate the role of a pain score in the reported use of opioids. Anchors for pain scores were 0 (no pain) and 10 (worst pain imaginable). Results: 31,355 observations were captured, which were extrapolated by the NHAMCS to represent 162,515,943 …

Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation Of Monocytes And Reduces Il-1Β Secretion By Urate Crystal Stimulated Gout Pbmcs, Sandy Elsayed, Gregory D. Jay, Ralph Cabezas, Marwa Qadri, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Objectives

To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.

Methods

Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU …

Symmetrical Drug-Related Intertriginous And Flexural Exanthema Induced By Cellulitis Prophylaxis, Tiffany Truong, Jonathan H. Ryder, Erica Lee, Clayton Mowrer, Ashley Wysong, Jasmine R. Marcelin

Graduate Medical Education Research Journal

Penicillin VK and hydroxyzine are typically well-tolerated antipruritic agents that are indicated in the prophylaxis of cellulitis. We herein report a case of a unique rash occurring during penicillin VK and hydroxyzine treatment in combination with the ingestion of cashews.

A 77-year-old male presented with new onset rash. Eleven days after the administration of penicillin VK and hydroxyzine for cellulitis prophylaxis, he developed a symmetric, erythematous, scaling rash on his buttocks and perineal region with associated pruritus and bleeding without fevers, chills, adenopathy, night sweats, or any other symptoms. He was diagnosed with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) …

Mansouramycins E–G, Cytotoxic Isoquinolinequinones From Marine Streptomycetes, Mohamed Shaaban, Khaled A. Shaaban, Gerhard Kelter, Heinz Herbert Fiebig, Hartmut Laatsch

Center for Pharmaceutical Research and Innovation Faculty Publications

Chemical investigation of the ethyl acetate extract from the marine-derived Streptomyces sp. isolate B1848 resulted in three new isoquinolinequinone derivatives, the mansouramycins E–G (1a–3a), in addition to the previously reported mansouramycins A (5) and D (6). Their structures were elucidated by computer-assisted interpretation of 1D and 2D NMR spectra, high-resolution mass spectrometry, and by comparison with related compounds. Cytotoxicity profiling of the mansouramycins in a panel of up to 36 tumor cell lines indicated a significant cytotoxicity and good tumor selectivity for mansouramycin F (2a), while the activity profile of E ( …

Design And Synthesis Of Fused Pyrimidines As Single Agents With Combination Chemotherapy Potential, As Tubulin Polymerization And One-Carbon Metabolism Inhibitors For Cancer, Tasdique Quadery

Electronic Theses and Dissertations

This dissertation describes the design, synthesis, and biological evaluation of bicyclic fused pyrimidines as single agents with combination chemotherapy potential with both antiangiogenic and cytotoxic effects. The dissertation also discusses one-carbon metabolism inhibitors and tumor targeting proteolysis targeting chimeras (PROTACs).

In cancer chemotherapy, the two major limitations are the dose-limiting toxicities of clinically used agents and the development of resistance to the treatment. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with both antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid …

Ketamine As A Treatment Modality For Treatment-Resistant Depression, Tracy Wulff, Shen Cao

Physician Assistant Capstones, 2020-current

Many recent studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to produce antidepressant effects that may be effective in helping reduce treatment-resistant major depression. In particular, three double-blinded randomized control trials have been conducted to assess the viability and effectiveness of this medication for treatment. This systematic literature review will analyze these studies and determine if the overall research indicates that ketamine is useful in improving depression as measured by the Montgomery–Asberg Depression Rating Scale (MADRS)¹.

Objective: Assess the effectiveness of IV Ketamine in reducing treatment-resistant major depressive disorder as measured by the Montgomery–Asberg …

Delivery Of Sirna With Drugs Targeting Polyamine Metabolism As Combinational Cancer Treatment, Ao Yu

Theses & Dissertations

Cancer has been a major public health issue worldwide for years and is the second leading cause of death in the United States. Important barrier must be broken to extend the life expectancy in every country. The standard care for cancer causes severe side effects which affects patients’ physical health and quality of life. Polyamines are highly related with the cell proliferation and apoptosis. Dysregulated polyamine metabolism in cancer leads to increased polyamine concentration in neoplastic cells. Thus, polyamine metabolism for cancer therapy can be an intriguing target. However, the heterogeneity affecting key cancer pathways poses significant challenges for effective …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

A New Criterion For Fluoroquinolone-Associated Disability Diagnosis: Functional Gastrointestinal Disorders, Deanna N. Cannizzaro, Lydia F. Naughton, Maya Z. Freeman, Linda Martin, Charles L. Bennett M.D., Ph.D., Cecilia Bove

Faculty Publications

Background and Objectives: Fluoroquinolones (FQs) are a broad-spectrum class of antibiotics routinely prescribed for common bacterial infections despite recent recommendations to use them only for life-threatening cases. In addition to their antimicrobial properties, FQs act in the central nervous system as GABAA receptor inhibitors, which could potentially affect functionality of the vagus nerve at the forefront of gastrointestinal (GI) tract function. Alterations in neural control of digestion have been shown to be linked to Functional Gastrointestinal Disorders (FGIDs), which are usually diagnosed based on self-reported symptoms. The aim of this study was to assess the incidence of FGIDs following FQ …

“Holistic Risk-Based Site Surveillance – A Data-Based Approach To Site Quality Risk Identification And Assessment In The Pharmaceutical Industry”, Matteo Bernasconi, Thomas Friedli, Nuala Calnan (Editor)

Level 3

Effective quality risk management is fundamental in guaranteeing the development and manufacture of high-quality drugs, reducing drug shortages, and avoiding harm to patients’ health. The ability to accurately assess the actual risk environment, predict potential product quality or supply disruption issues and act to eliminate, prevent, reduce or mitigate them is key to improvements in quality management maturity. This paper illustrates a just-launched research project aimed at developing a comprehensive framework for how to assess and predict risks by leveraging a range of diverse factors.

“Gaining Organisational Acceptance Of A Data Analytics Programme In Eli Lilly”, Anthony Maguire, Marcus O'Mahony

Level 3

This paper describes how Eli Lilly overcame barriers to enable new use of data. This was achieved by adopting a deep understanding of end-user needs and the support of site leaders and end-users to standardise process monitoring. A standard approach of ‘Contexting’, ‘Data-Extraction’, ‘Model build’, ‘On-line Config’, ‘Deploy’, was utilised, using a commercial off-the-shelf software. The paper describes proof of concept demonstrations undertaken and discusses the ingredients to make the journey a success.

Total Synthesis Of Decahydroquinoline Poison Frog Alkaloids Ent-Cis-195a And Cis-211a, Takuya Okada, Naizhen Wu, Katsuki Takashima, Jungoh Ishimura, Hiroyuki Morita, Takuya Ito, Takeshi Kodama, Yuhei Yamasaki, Shin-Ichi Akanuma, Yoshiyuki Kubo, Ken-Ichi Hosoya, Hiroshi Tsuneki, Tsutomu Wada, Toshiyasu Sasaoka, Takahiro Shimizu, Hideki Sakai, Linda P. Dwoskin, Syed R. Hussaini, Ralph A. Saporito, Naoki Toyooka

Pharmaceutical Sciences Faculty Publications

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that …

Pharmacist Avoidance Or Reductions In Medical Costs In Critically Ill Adults: Pharm-Crit Study, Megan A. Rech, Payal K. Gurnani, William J. Peppard, Keaton S. Smetana, Megan A. Van Berkel, Drayton A. Hammond, Alexander H. Flannery

Pharmacy Practice and Science Faculty Publications

OBJECTIVES: To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions.

DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019.

SETTING: Community hospitals and academic medical centers in the United States.

PARTICIPANTS: ICU clinical pharmacists.

INTERVENTIONS: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance.

MEASUREMENTS AND MAIN RESULTS: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of …

Optimizing Empiric Vancomycin Use In Febrile Neutropenia Patients, Nicole Tadros, Erika Dittmar, Radhan B. Gopalani

Nursing & Health Sciences Research Journal

Introduction: National guidelines do not support routine empiric vancomycin use in the initial management of febrile neutropenia (FN) and only recommend it in patients with specific clinical indications. This bi-phasic quality improvement project aimed to evaluate current vancomycin use in FN and improve compliance with a guideline-driven algorithm (GDA) to ensure appropriate prescribing and therapy duration in a community hospital.

Methods: Phase I was a retrospective review of charts of adults receiving empiric vancomycin therapy for FN at a community hospital. Phase II was a prospective review of charts of patients with FN, who received pharmacist-led interventions, to improve de-escalation …

Major Publications In The Critical Care Pharmacotherapy Literature: 2020, Brittany D. Bissell, Jeannee Campbell, Reagan Collins, Charles Cook, Dharati Desai, Jessica Dewitt, Ifeoma Mary Eche, Ijeoma Julie Eche, Pansy Elsamadisi, Janelle Juul, Soyoung Kim, Courtney T. Makowski, Ruben J Mylvaganam, Adam Smith, Jennifer Stancati, Katherine Stonesifer, Justin Tawil, Melanie Smith Condeni

Pharmacy Practice and Science Faculty Publications

OBJECTIVES: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2020.

DATA SOURCES: The Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update group screened 36 journals monthly for impactful publications.

STUDY SELECTION: The group reviewed a total of 119 articles during 2020 according to relevance for practice.

DATA EXTRACTION: Articles were selected with consensus and importance to clinical practice from those included in the monthly Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. The group reviewed articles according to Grading of Recommendations, Assessment, Development, and Evaluations criteria. Articles with a 1A grade were selected.

DATA SYNTHESIS: Several trials …

Characterization Of Lithium Toxicity At A Large Academic Medical Institution, Melissa R. Vesey, Marian Matalka, Sarah Goldsborough, Mark F. Lutz, John Zaccardelli

Conference Presentation Abstracts

No abstract provided.

Evaluation Of A Pharmacist-To-Dose Voriconazole Protocol On Adverse Drug Reactions, Darius A. Savickas, Chad L Richardson, Christine Yost

Conference Presentation Abstracts

No abstract provided.

Keratin 1 As A Cell-Surface Receptor In Cancer, Oluseye Ogunnigbagbe, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Keratins are fibrous proteins that take part in several important cellular functions, including the formation of intermediate filaments. In addition, keratins serve as epithelial cell markers, which has made their role in cancer progression, diagnosis, and treatment an important focus of research. Keratin 1 (K1) is a type II keratin whose structure is comprised of a coiled-coil central domain flanked by flexible, glycine-rich loops in the N- and C-termini. While the structure of cytoplasmic K1 is established, the structure of cell-surface K1 is not known. Several transformed cells, such as cancerous cells and cells that have undergone oxidative stress, display …

The Global Burden Of Adolescent And Young Adult Cancer In 2019: A Systematic Analysis For The Global Burden Of Disease Study 2019, Elysia M. Alvarez, Lisa M. Force, Rixing Xu, Kelly Compton, Dan Lu, Ismaeel Yunusa Ph. D., Et Al.

Faculty Publications

Background

Methods

Early Multicenter Experience With Imipenem-Cilastatin-Relebactam For Multidrug-Resistant Gram-Negative Infections, Nicholas Rebold, Taylor Morrisette, Abdalhamid M. Lagnf, Sara Alosaimy

Faculty and Student Publications

A multicenter case series of 21 patients were treated with imipenem-cilastatin-relebactam. There were mixed infection sources, with pulmonary infections (11/21,52%) composing the majority. The primary pathogen was Pseudomonas aeruginosa (16/21, 76%), and 15/16 (94%) isolates were multidrug-resistant. Thirty-day survival occurred in 14/21 (67%) patients. Two patients experienced adverse effects.

Cryo-Em Reveals The Architecture Of Placental Malaria Var2csa And Provides Molecular Insight Into Chondroitin Sulfate Binding, Kaituo Wang, Robert Dagil, Thomas Lavstsen, Sandeep K. Misra

Faculty and Student Publications

Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of …

Identification Of A Solo Acylhomoserine Lactone Synthase From The Myxobacterium Archangium Gephyra, Hanan Albataineh, Maya Duke, Sandeep K. Misra, Joshua S. Sharp

Faculty and Student Publications

Considered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized metabolites to facilitate predation of microbes. This capacity to produce specialized metabolites and the associated abundance of biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all myxobacterial biosynthetic gene clusters deposited in the antiSMASH database, only one putative acylhomoserine lactone (AHL) synthase, agpI, was observed, in genome data from Archangium gephyra. Without an AHL receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI …

Characterization And In Vitro And In Vivo Evaluation Of Tacrolimus-Loaded Poly(Ε-Caprolactone) Nanocapsules For The Management Of Atopic Dermatitis, Guilherme Dos Anjos Camargo, Leandro Ferreira, Diego José Schebelski, Amanda Martinez Lyra

Faculty and Student Publications

Background: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. Methods: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. Results: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticu-late systems presented a spherical shape with a smooth and regular surface, …

Extracts From Pulsatilla Patens Target Cancer-Related Signaling Pathways In Hela Cells, Grażyna Łaska, Magdalena Maciejewska-Turska, Elwira Sieniawska, Łukasz Świątek

Faculty and Student Publications

The purpose of this study was to determine if a methanolic extract of the Pulsatilla patens (L.) Mill. can inhibit the progression of cancer through the modulation of cancer-related metabolic signaling pathways. We analyzed a panel of 13 inducible luciferase reporter gene vectors which expression is driven by enhancer elements that bind to specific transcription factors for the evaluation of the activity of cancer signaling pathways. The root extract of P. patens exhibited strong inhibition of several signaling pathways in HeLa cells, a cervical cancer cell line, and was found to be the most potent in inhibiting the activation of …

Functional Genomics Study Of Pseudomonas Putida To Determine Traits Associated With Avoidance Of A Myxobacterial Predator, Shukria Akbar, D. Cole Stevens

Faculty and Student Publications

Predation contributes to the structure and diversity of microbial communities. Predatory myxobacteria are ubiquitous to a variety of microbial habitats and capably consume a broad diversity of microbial prey. Predator–prey experiments utilizing myxobacteria have provided details into predatory mechanisms and features that facilitate consumption of prey. However, prey resistance to myxobacterial predation remains underexplored, and prey resistances have been observed exclusively from predator–prey experiments that included the model myxobacterium Myxococcus xanthus. Utilizing a predator–prey pairing that instead included the myxobacterium, Cystobacter ferrugineus, with Pseudomonas putida as prey, we observed surviving phenotypes capable of eluding predation. Comparative transcriptomics between P. putida …

Transmission Studies And The Composition Of Prokaryotic Communities Associated With Healthy And Diseased Aplysina Cauliformis Sponges Suggest That Aplysina Red Band Syndrome Is A Prokaryotic Polymicrobial Disease, Matteo Monti, Aurora Giorgi, Cole G. Easson, Deborah J. Gochfeld

Faculty and Student Publications

Aplysina cauliformis, the Caribbean purple rope sponge, is commonly affected by Aplysina Red Band Syndrome (ARBS). This transmissible disease manifests as circular lesions with red margins and results in bare spongin fibers. Leptolyngbya spp. appear to be responsible for the characteristic red coloration but transmission studies with a sponge-derived isolate failed to establish disease, leaving the etiology of ARBS unknown. To investigate the cause of ARBS, contact transmission experiments were performed between healthy and diseased sponges separated by filters with varying pore sizes. Transmission occurred when sponges were separated by filters with pore sizes ≥ 2.5 μm, suggesting a prokaryotic …

An Investigation Into The Use Of An Herbal Labor Induction Tincture Containing Black Cohosh, Cramp Bark, Partridgeberry, And Motherwort On Contractile Responses Produced From Isolated Strips Of Mouse Uterine Tissues, Clayton Neuenschwander, Katrina Wu, Teresa F. Degolier

Biological Sciences Faculty Publications

Introduction: Alternative solutions in the form of herbal remedies meant to ease or expedite the process of labor have often been pursued and administered but have seldom been quantitatively tested for efficacy. Published research has shown some validation for some commonly used herbs such as blue cohosh (Caulophyllum thalictroides), red raspberry (Rubus idaeus), castor bean (Ricinus communis) and evening primrose (Oenothera biennis) on isolated mouse uterine strips. Methods: This study tested an array of herbs used by midwives in a labor induction tincture, which included black cohosh (Actaea racemosa), cramp bark (Viburnum opulus), partridgeberry (Mitchella repens), and motherwort (Leonurus cardiaca). …