Medicine and Health Sciences Commons^™

Strategies For The Management Of Postoperative Anemia In Elective Orthopedic Surgery, Taylor D. Steuber, Meredith L. Howard, Sarah A. Nisly

Scholarship and Professional Work – COPHS

Objective: To assess the use of oral iron, intravenous (IV) iron, and erythropoiesis-stimulating agents (ESAs) for the prevention and management of perioperative anemia in elective orthopedic surgery patients, and to provide a clinical algorithm for use. Data Sources: A PubMed and MEDLINE search was conducted from 1964 through March 2016 using the following search terms alone or in combination: orthopedic, surgery, elective, anemia, blood transfusion, iron, erythropoiesisstimulating agents, and erythropoietin. Study Selection and Data Extraction: All English-language prospective and retrospective human studies and meta-analyses evaluating oral iron, IV iron, or ESA alone or in combination in elective orthopedic surgery …

Glp-1 Agonists In Type 1 Diabetes Mellitus: A Review Of The Literature, Kristin M. Janzen, Taylor D. Steuber, Sarah A. Nisly

Scholarship and Professional Work – COPHS

Objective: To review the use of GLP-1 agonists in patients with type 1 diabetes mellitus (T1DM). Data Sources: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed through March 2016 using the search terms glucagon-like peptide 1 (GLP-1) agonists, incretin, liraglutide, exenatide, albiglutide, dulaglutide, type 1 diabetes mellitus. Study Selection and Data Extraction: All English-language trials that examined glycemic end points using GLP- 1 agonists in humans with T1DM were included. Data Synthesis: A total of 9 clinical trials examining the use of GLP-1 agonists in T1DM were identified. On average, hemoglobin A1C (A1C) was lower than …

Ascorbic Acid For The Treatment Of Rasburicase Induced Methemoglobinemia In The Setting Of Acute Renal Failure, David J. Reeves, Lindsay Saum, Ruemu Birhiray

Scholarship and Professional Work – COPHS

Purpose A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported.

Summary A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. …

Development And Implementation Of A Pharmacist-Managed Outpatient Parenteral Antimicrobial Therapy Program, Eun Kyoung Chung, Cole B. Beeler, Eva W. Muloma, Danielle Osterholzer, Kendra M. Damer, Sharon M. Erdman

Scholarship and Professional Work – COPHS

Purpose The development and implementation of a pharmacist-managed outpatient parenteral antimicrobial therapy (OPAT) program in a county teaching hospital are described.

Summary A pharmacist-managed OPAT program was developed and implemented at a county teaching hospital to provide consistent evaluation, approval, and monitoring of patients requiring OPAT for the treatment of infection. The developmental and implementation stages of the OPAT program included (1) a needs assessment, (2) the identification of resources necessary for program operation, (3) delineation of general OPAT program operations and activities of individual OPAT clinicians, (4) the development of patient selection criteria, including a plan of care algorithm, …

Nucleosome Distortion As A Possible Mechanism Of Transcription Activation Domain Function, Tamara Y. Erkina, Alexandre M. Erkine

Scholarship and Professional Work – COPHS

After more than three decades since the discovery of transcription activation domains (ADs) in gene-specific activators, the mechanism of their function remains enigmatic. The widely accepted model of direct recruitment by ADs of co-activators and basal transcriptional machinery components, however, is not always compatible with the short size yet very high degree of sequence randomness and intrinsic structural disorder of natural and synthetic ADs. In this review, we formulate the basis for an alternative and complementary model, whereby sequence randomness and intrinsic structural disorder of ADs are necessary for transient distorting interactions with promoter nucleosomes, triggering promoter nucleosome translocation and …

Retrospective Analysis Of Methotrexate Elimination When Coadministered With Levetiracetam, David Reeves, Sarah Didominick, Suzanne Finn, Hyeon Jin Kim, Amanda Shake

Scholarship and Professional Work – COPHS

Background: Delayed elimination of methotrexate was previously reported in 2 patients receiving concomitant levetiracetam. Objective: To explore the potential interaction between methotrexate and levetiracetam in patients receiving high-dose methotrexate. Methods: This retrospective study reviewed the records of 81 adults receiving 280 cycles of methotrexate to determine the effects of levetiracetam on methotrexate elimination. Institutional review board approval was obtained. Results: Levetiracetam was administered in 33 (12%) cycles of methotrexate. Patients receiving levetiracetam had significantly lower 24-hour methotrexate concentrations compared with those not receiving levetiracetam (2.91 vs 7.37 µmol/L, P = 0.005). Despite this difference, concentrations at 48 and 72 hours …

Population Pharmacokinetics And Pharmacodynamics Of Extended-Infusion Piperacillin And Tazobactam In Critically Ill Children, Chad A. Knoderer, Kristen R. Nichols, Eun Kyoung Chung, Lauren E. Buenger, Daniel P. Healy, Jennifer Dees, Ashley S. Crumby, Michael B. Kays

Scholarship and Professional Work – COPHS

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillintazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) …

Doctor Of Pharmacy Overview, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Biochemistry and Microbiology

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes.

Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Ovarian Tumour Growth Is Characterized By Mevalonate Pathway Gene Signature In An Orthotopic, Syngeneic Model Of Epithelial Ovarian Cancer, Daniel B. Hardy

Physiology and Pharmacology Publications

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor …

Nicotine Directly Induces Endoplasmic Reticulum Stress Response In Rat Placental Trophoblast Giant Cells, Michael K. Wong, Alison Holloway C, Daniel B. Hardy

Physiology and Pharmacology Publications

Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats,nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency, however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblastgiant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (e.g., phosphorylated PERK, eIF2α, CHOP, BiP/GRP78) and trophoblast giant cell differentiation and function (e.g., Pl-1, Pgf, Hsd11b1, and Hsd11b2) were quantified via Western blot or …

Perceptions Of Licensed Pharmacist Managers Regarding Formally Versus Informally Trained Pharmacy Technicians, Shalonica Marie Cluse

Walden Dissertations and Doctoral Studies

Pharmacists rely on pharmacy technicians to assist with accurately dispensing prescriptions and providing information to clients. Texas does not have regulations for the education or training of pharmacy technicians, which may result in mistakes when dispensing prescriptions, causing significant harm to customers. The purpose of this qualitative phenomenological study was assessing formally and informally trained pharmacy technicians' job performance as perceived by licensed pharmacists/managers. Data were collected via face to face interviews with 9 pharmacy managers in Texas to gain insight into their lived experiences of supervising not formally and formally trained technicians. Audio recorded interview data were transcribed and …

Pharmacogenomic Management Of Familial Hypercholesterolemia: An Integrative Review Of The Literature, Brian V. Skibo

Honors Undergraduate Theses

The purpose of this thesis is to examine familial hypercholesterolemia (FH) and emerging pharmacogenomics therapies that propose to lower serum low density lipid (LDL) levels. The search of various data bases resulted in nine research articles being selected for review. Syntheses of the articles suggest emerging phamacogenomic drug therapy can improve treatment outcomes for individuals with a diagnosis of FH. The Human Genome Project (HGP) has had far reaching applications for genomic technologies and pharmacagenomic interventions, tailored to human conditions associated with select genomic traits. Synthesis of nine research articles demonstrate that little is known on the topic and reveals …

Harmful Or Helpful? Direct To Consumer Advertising, Sally A. Kiss

The Graduate Review

Policy change in 1997 by the Food and Drug Administration made the United States only one of two countries to allow direct-to-consumer advertising (DTCA). DTCA refers to the promotion of prescription medications through media directly to consumers as opposed to distribution of information only medical professionals. Supporters argue that DTCA educates consumers and helps them to make more informed decisions about their health care. On the other side, opponents argue that it leads to otherwise healthy people believing they are sick, thereby increasing profits for pharmaceutical companies. After reviewing the history of DTCA and literature demonstrating the pros and cons …

Phytopharmaceuticals In Mongolia: Past, Present, And Future, Disan Gunbilig, Ulziinyam Rentsendorj

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

Over the last two decades, the consumption of medicinal plants has increased in Mongolia. Once banned by the post-revolutionary government, it is now valued by the practitioners of orthodox medicine, government as well as by the society. Yet the scientific community has to give this major and crucial component of traditional Mongolian medicine the attention it deserves, scientific knowledge about biologically active principles within medicinal plants remain poorly unknown. At the same time, due to over exploitation of plants many species are becoming extinct together with invaluable traditional knowledge being lost. For these reasons, there is a certain urgency to …

Medication Therapy Management, Ayman M. Noreddin, Francis Ndemo, David Ombengi

Pharmacy Faculty Articles and Research

"According to the Institute of Medicine report medications are the most common medical intervention. However, drug-related morbidity and mortality now represents a major public health challenge due to the ineffective and unsafe consequences of medication use. Morbidity in this case relates to disease and illness associated with drug therapy whereas mortality relates to death associated with drug therapy. It is also estimated in the US that drug-related morbidity and mortality cost about $200 billion annually in health care expenditure.

This is clearly a failure in our healthcare systems."

Capillary Endothelia From Two Adpkd Patients Are Polyploidy, Sarmed H. Kathem, Wissam A. Aboualaiwi, Xiaolin Zi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Bilateral renal cyst formation is the main feature of autosomal dominant polycystic kidney disease (ADPKD). We and other laboratories have previously shown that cystlining epithelia of kidneys from ADPKD patients are characterized by polyploidy. In this report, we show that endothelia from the renal capillary beds of two ADPKD patients are also polyploidy. Spectral karyotyping study further confirms our flow cytometry analyses. We suggest that polyploidy may be used as a potential cellular marker in ADPKD.

Improving The Renal Profile Of A Hiv Drug Combination Through Prodrug Alteration, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

"Human immunodeficiency virus (HIV) continues to alter the lives of countless individuals, who once infected, live on a continuum between viral suppression and acquired immunodeficiency syndrome. The former being achieved via the use of various antiretrovirals beginning with the release of zidovudine over a quarter-century ago; whereas the latter may result from treatment failure or lack of treatment such as in the absence of diagnosis or the inaccessibility of medication. As no cure is yet available, regimens must be continued lifelong. Thus, contemporary treatment is given as a combination of agents from various antiretroviral drug classes in an effort to …

Manufacturing Barriers To Biologics Competition And Innovation, W. Nicholson Price Ii, Arti K. Rai

Faculty Scholarship

As finding breakthrough small-molecule drugs gets harder, drug companies are increasingly turning to “large molecule” biologics. Although biologics represent many of the most promising new therapies for previously intractable diseases, they are extremely expensive. Moreover, the pathway for generic-type competition set up by Congress in 2010 is unlikely to yield significant cost savings.

In this Article, we provide a fresh diagnosis of, and prescription for, this major public policy problem. We argue that the key cause is pervasive trade secrecy in the complex area of biologics manufacturing. Under the current regime, this trade secrecy, combined with certain features of FDA …

Rnd3 As A Novel Target To Ameliorate Microvascular Leakage, Jerome W. Breslin, Dayle A. Daines, Travis M. Doggett, Kristine H. Kurtz, Flavia M. Souza-Smith, Xun E. Zhang, Mack H. Wu, Sarah Y. Yuan

Molecular Pharmacology & Physiology Faculty Publications

Background: Microvascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.

Methods and Results: Using immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate–albumin and transendothelial electrical resistance of human umbilical vein endothelial …

Intra-Articular Interleukin-1 Receptor Antagonist (Il1-Ra) Microspheres For Posttraumatic Osteoarthritis: In Vitro Biological Activity And In Vivo Disease Modifying Effect, Khaled A. Elsaid, Anand Ubhe, Ziyad Shaman, Gerard D'Souza

Pharmacy Faculty Articles and Research

Background: Interleukin-1 receptor antagonist (IL-1 ra) can be disease-modifying in posttraumatic osteoarthritis (PTOA). One limitation is its short joint residence time. We hypothesized that IL-1 ra encapsulation in poly (lactide-co-glycolide) (PLGA) microspheres reduces IL-1 ra systemic absorption and provides an enhanced anti-PTOA effect.

Methods: IL-1 ra release kinetics and biological activity: IL-1 ra encapsulation into PLGA microsphere was performed using double emulsion solvent extraction. Lyophilized PLGA IL-1 ra microspheres were resuspended in PBS and supernatant IL-1 ra concentrations were assayed. The biological activity of IL-1 ra from PLGA IL-1 ra microspheres was performed using IL-1 induced lymphocyte proliferation …

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Synthesis, Characterization, And In Vitro Anti-Tumor Studies Of Bis Imidazolium Salts With Alkyl Chain Linkers And Naphthylmethyl Substituents, Steven R. Crabtree

Williams Honors College, Honors Research Projects

Bis imidazolium salts, with alkyl chain linkers ranging from methylene to dodecyl, were synthesized with naphthylmethyl substituents at the N¹ and N^1’ positions for a structure-activity relationship (SAR) study. All compounds were characterized by ¹H and ¹³C NMR spectroscopy. The cationic portion of 2 as the PF₆ salt, 3, 4, and 5 were also characterized by single-crystal X-ray crystallography. Compounds 1-8, 10, and 12 were tested for their in vitro anti-cancer activity against four NSCLC cell lines via the MTT assay (NCI–H460, NCI–H1975, HCC827, and A549). Compounds 10 and 12 which …

Using Semiphysiologically-Based Pharmacokinetic (Semi-Pbpk) Modeling To Explore The Impact Of Differences Between The Intravenous (Iv) And Oral (Po) Route Of Administration On The Magnitude And Time Course Of Cyp3a-Mediated Metabolic Drug-Drug Interactions (Ddi) Using Midazolam (Mdz) As Prototypical Substrate And Fluconazole (Flz) And Erythromycin (Ery) As Prototypical Inhibitors, Mengyao Li

Theses and Dissertations

The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI.

Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on hepatic and gut wall (GW) CYP3A metabolism of MDZ, using available in-vitro/in-vivo information. Model-simulated MDZ …

Role Of T Lymphocyte Trafficking In Diabetic Cardiomyopathy, Chowdhury Sayef Abdullah

Electronic Theses and Dissertations

Diabetic cardiomyopathy is a distinct pathological condition characterized by myocardial fibrosis and cardiac dysfunction in diabetic patients. The resolution of myocardial fibrosis to improve cardiac function in diabetes is an active area of research. Notably, increased T lymphocyte infiltration into myocardium has been attributed to increased cardiac fibrosis and dysfunction in diabetes. However, the experimental data on the role of T lymphocyte modulation in diabetic myocardial fibrosis is scarce. To this end, sphingosine 1-phosphate receptor 1 (S1P1) regulates the egress of mature T lymphocytes from lymphoid organs to blood and peripheral organs. Thus, the inhibition of T cells trafficking through …

Novel Cellular Targets Of Aspirin In Chemoprevention Studies On P53, G6pd And C-Myc, Guoqiang Ai

Electronic Theses and Dissertations

Background

Aspirin has generated a significant interest in recent years as a potential chemopreventive agent supported by strong evidence from epidemiological data; however, the mechanisms are not well understood. The objective of this dissertation is to identify novel cyclooxygenase (COX)-independent pathways by which aspirin exerts its anticancer effects in epithelial cancer cell lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Neuroinflammatory Pain Models In Mice, Muzaffar Abbas

Electronic Theses and Dissertations

Neuroinflammatory pain affects about 1.5% of the United States population. Around 20-40% patients having neurological disorders are affected with neuroinflammatory pain. As a part of the limbic system, hippocampus is known to play a critical role in pain perception and processing, and is densely populated with microglial cells and α7 nicotinic acetylcholine receptors (nAChRs). Given the role of microglial α7 nAChRs in neuroinflammation, the α7 nAChRs have emerged as potential target for neuroinflammatory pain treatment. We hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary …

Global Reach, Local Markets: The Challenges Of Leading Global Innovation, Sarah Higgins

Honors Theses

This Global Studies honors thesis addresses how managers and leaders of global firms manage innovation across multiple markets. Current research on multinational corporations provides an understanding of different kinds of innovation and the ways to attend to multiple markets. However, there is less documentation of how these innovation strategies are actually implemented on the ground and the tensions that these efforts might produce. Therefore, my research focuses in particular on the challenges and tensions faced by leaders of global firms as they implement transnational innovation strategies. This study is based upon in-depth interviews with 20 participants who held positions in …

The Effects Of Amixicile, A Pyruvate Ferredoxin Oxidoreductase Inhibitor, On Oral Treponemes, Lucas A. Reed

Theses and Dissertations

Periodontal disease (PD) is a polymicrobial infection characterized by inflammation of the gingiva, alveolar bone resorption, and tooth loss (edentulism). Treponema denticola along with Porphyromonas gingivalis and Tannerella forsythia are among the “Red Complex” and are main etiological agents in PD. Treponemes are a member of the Spirochaeta phylum and are obligate anaerobes, that express pyruvate ferredoxin oxidoreductase (PFOR). The enzyme catalyzes the oxidation of pyruvate to acetyl-CoA and reduced ferredoxin. Amixicile is a novel bacteriostatic derivative of nitazoxanide and an inhibitor of PFOR. In light of the fact that Treponemes express PFOR, this study was conducted to investigate the …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …