Pharmacy and Pharmaceutical Sciences Commons^™

Elucidating Proteasome Catalytic Subunit Composition And Its Role In Proteasome Inhibitor Resistance, Kimberly C. Carmony

Theses and Dissertations--Pharmacy

Proteasome inhibitors bortezomib and carfilzomib are FDA-approved anticancer agents that have contributed to significant improvements in treatment outcomes. However, the eventual onset of acquired resistance continues to limit their clinical utility, yet a clear consensus regarding the underlying mechanisms has not been reached.

Bortezomib and carfilzomib are known to target both the constitutive proteasome and the immunoproteasome, two conventional proteasome subtypes comprising distinctive sets of catalytic subunits. While it has become increasingly evident that additional, ‘intermediate’ proteasome subtypes, which harbor non-standard mixtures of constitutive proteasome and immunoproteasome catalytic subunits, represent a considerable proportion of the proteasome population in many cell …

Development Of Cocaine Hydrolase For Therapeutic Treatment Of Cocaine Abuse, Xiabin Chen

Theses and Dissertations--Pharmacy

Cocaine abuse is a world-wide public health and social problem without a U.S. Food and Drug Administration (FDA)-approved medication. An ideal anti-cocaine medication would accelerate cocaine metabolism producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Recent studies in our lab have led to discovery of the desirable, highly efficient human cocaine hydrolases (hCocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of central nervous system (CNS). Preclinical and clinical data have demonstrated that these hCocHs are safe for use in humans and effective for accelerating cocaine metabolism. However, the actual therapeutic use of …

Acute Kidney Injury In Patients Treated With Vancomycin And Piperacillin-Tazobactam: A Retrospective Cohort Analysis, Wilbur Cliff Rutter

Theses and Dissertations--Pharmacy

Empiric antimicrobial therapy often consists of the combination of Gram-positive coverage with vancomycin (VAN) and Gram-negative coverage, specifically an anti-pseudomonal beta-lactam, such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports demonstrate increasing nephrotoxicity rates among patients treated with the combination of VAN and PTZ. This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI), as defined by the RIFLE criteria, compared to VAN and PTZ monotherapies.

Overall, 11,650 patients were analyzed, with 1,647 (14.1%) AKI cases occurring. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy …

Clinical Outcomes Associated With Time To Antimicrobial Therapy Change From Vancomycin To Daptomycin In Staphylococcal Bacteremia, Sarah J. Tennant

Theses and Dissertations--Pharmacy

Background: Staphylococcus aureus is an aerobic, Gram positive commensal organism that is capable of causing a wide spectrum of disease. This study contributes to previously published literature regarding daptomycin versus vancomycin use in S. aureus bacteremia (SAB).

Methods: Adult patients admitted between 2010 and 2014, billed for ICD-9 code V09.0, 038.11, 038.12, 041.11, or 041.12, and received vancomycin and daptomycin were included in this retrospective analysis. Patients were stratified by time to change in antibiotics from vancomycin to daptomycin to the early switch (1-3 days), intermediate switch (4-7 days), or late switch (8 days or later) group. The primary outcome …

Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi

Theses and Dissertations--Pharmacy

The emerging field of RNA nanotechnology is developing into a promising platform for therapeutically application. Utilizing the state-of-art RNA nanotechnology, RNA nanoparticles can be designed and constructed with controllable shape, size for both RNA therapeutics and chemical drug delivery. The high homogeneity in particle size and ease for RNA therapeutic module conjugation, made it feasible to explore versatile RNA nanoparticle designs for preclinical studies.

One vital module for therapeutic RNA nanoparticle design is RNA aptamer, which can enable the RNA nanoparticles find its specific target for targeted drug delivery. A system of screening divalent RNA aptamers for cancer cell targeting …

Investigating Mechanisms Determining Cancer Cell Sensitivity To Carfilzomib And Novel Strategies To Overcome Resistance, Lin Ao

Theses and Dissertations--Pharmacy

Proteasome inhibitors (PIs) are a class of FDA-approved anti-cancer agents which includes the first-generation PI bortezomib (BTZ) and second-generation carfilzomib (CFZ). Drug resistance is a major challenge in PI therapy with no solution currently available. While a few resistance mechanisms had been proposed for BTZ, little was known about CFZ resistance before the start of our studies. In this dissertation work, we investigated multiple mechanisms contributing to CFZ resistance—alterations in the drug transporter activity, metabolic stability, and proteasome activity profiles—and evaluated potential strategies to overcome CFZ resistance.

We observed marked upregulation of the drug efflux transporter P-glycoprotein (P-gp) in our …

Rna As A Unique Polymer To Build Controllable Nanostructures For Nanomedicine And Nanotechnology, Hui Li

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that involves the design, construction and functionalization of nanostructures composed mainly of RNA for applications in biomedical and material sciences. RNA is a unique polymer with structural simplicity like DNA and functional diversity like proteins. A variety of RNA nanostructures have been reported with different geometrical structures and functionalities. This dissertation describes the design and construction of novel two-dimensional and three-dimensional self-assembled RNA nanostructures with applications in therapeutics delivery, cancer targeting and immunomodulation. Firstly, by using the ultra-stable pRNA three-way junction motif with controllable angles and arm lengths, tetrahedral architectures composed purely of RNA …

Online Self-Testing Resources Prepared By Peer Tutors As A Formative Assessment Tool In Pharmacology Courses, Melinda E. Lull, Jennifer Mathews

Pharmacy Faculty/Staff Publications

Objective. To assess the effectiveness of optional online quizzes written by peer tutors in a pharmacology course for doctor of pharmacy students.

Methods. Online quizzes were written by peer tutors for second-year pharmacy students. Quizzes reflected the material taught during lecture and were in a format similar to that of the examinations. Data related to performance on each quiz and each examination were collected throughout the semester. At the end of the semester, students and peer tutors were surveyed to gather information on the utility and success of the quizzes.

Results. Students taking online quizzes performed significantly better on examinations …

An Analysis Of Psychologist Postdoctoral Psychopharmacology Training Materials For Critiques Of Neurobiological Hypotheses Of Depression's Etiology, Critical Analyses Of The Dsm's Rigor, And For Consumer/Survivor/Ex-Patient Content., Chris William Nicholas Rowe

Antioch University Dissertations & Theses

There is widespread agreement that neurobiology plays a role in psychological distress and that psychiatric diagnosis and associated psychopharmacological interventions can be helpful. However, there are also unresolved issues surrounding the limits of empirical support for current diagnostic criteria, shortcomings in neurobiological explanations of psychopathology, and unanswered questions about the mechanism, safety, and efficacy of psychiatric medications. This has implications for treatment errors which can precipitate negative socio-economic and health consequences, particularly for vulnerable groups like the Consumer/Survivor/Ex-Patient (c/s/x) population. It is for these reasons that the training psychologists receive to prescribe should, in addition to integrating the critiques of …

Assessment Of Celecoxib Poly(Lactic-Co-Glycolic) Acid Nanoformulation On Drug Pharmacodynamics And Pharmacokinetics In Rats, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP).

MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma …

Cytotoxicity And Chemical Investigation Of The Aerial Parts Of Markhamia Zanzibarica (Bojer Ex Dc.) K. Schum. (Bignoniaceae), Dina M. El-Kersh, Riham S. El Dine, Dina R. Abou-Hussein, Fatma S. El-Sakhawy, Mohamed M. Elmazar

Pharmacy

The ethanolic extract of the aerial parts of Markhamia zanzibarica (Bignoniaceae) was tested for its cytotoxic activity against human cervical adenocarcinoma cell line (HeLa). It showed a potent effect with an IC50 of 9.68 μg/ml compared to Doxorubicin (7.28 μg/ml). The fractions obtained from the successive partitioning of the total extract, were tested against the same cell line; the results revealed that n-hexane extract was the most potent 9.23 μg/ml, followed by ethyl acetate, butanol and chloroform fractions with IC50 of 21.2, 22.4 and 49.6 μg/ml, respectively. Column chromatography led to the isolation of oleanolic acid (1), ursolic acid (2) …

Senegal: The Impact Of A Study On Misoprostol Use And Knowledge Among Pharmacists, Eva Burke, E. Robinson, Nafissatou Diop, Kate Reiss, Katharine Footman, Maaike Van Min, Barbara Reichwein, Ian Askew

Reproductive Health

The availability of misoprostol is a key part of improving maternal health in low- and middle-income countries. In Senegal, where the drug is not widely available, pharmacies are one of the few places women can access it. STEP UP conducted a study to understand misoprostol knowledge and provision in these pharmacies. The Ministry of Health’s (MoH) commitment to training public providers and pharmacists on all products on the essential medicines list is a promising step toward bettering the health of women in Senegal. Marie Stopes International (MSI) Senegal continues to work to build the capacity of healthcare providers in the …

Motivations And Predictors Of Cheating In Pharmacy School, Eric J. Ip, Kathy Nguyen, Bijal M. Shah, Shadi Doroudgar, Monica K. Bidwal

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To assess the prevalence, methods, and motivations for didactic cheating among pharmacy students and to determine predictive factors for cheating in pharmacy colleges and schools.

Methods. A 45-item cross-sectional survey was conducted at all four doctor of pharmacy programs in Northern California. For data analysis, t test, Fisher exact test, and logistic regression were used.

Results. Overall, 11.8% of students admitted to cheating in pharmacy school. Primary motivations for cheating included fear of failure, procrastination, and stress. In multivariate analysis, the only predictor for cheating in pharmacy school was a history of cheating in undergraduate studies.

Conclusion. Cheating occurs …

A Single Dose Tmv-Ha Vaccine Protects Mice From H5n1 Influenza Challenge, Jyothi K. Mallajosyula, Trushar Jeevan, Rachel Chikwamba, Richard J. Webby, Alison A. Mccormick

Faculty Publications & Research of the TUC College of Pharmacy

Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant Hemagglutinin (HA) subunit protein are often of low potency, requiring repeated boosting to generate a sustained immune response. Previously, we demonstrated improved immunogenicity of a plant-made H1 Hemagglutinin (HA) vaccine by chemical conjugation to the surface of the Tobacco Mosaic Virus (TMV) which is non infectious in mammals. Antigen coated TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier for subunit protein vaccines. In this work, we …

Perspectives On Transdermal Electroporation, Kevin B. Ita

Faculty Publications & Research of the TUC College of Pharmacy

Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary …

The Influence Of Solid Microneedles On The Transdermal Delivery Of Selected Antiepileptic Drugs, Julia Nguyen, Kevin B. Ita, Matthew J. Morra, Inna E. Popova

Faculty Publications & Research of the TUC College of Pharmacy

The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm²/h) compared to passive delivery (12.83 ± 6.30 µg/cm …

Wake Me When It's Over- Bacterial Toxin-Antitoxin Proteins And Induced Dormancy, Nathan P. Coussens, Dayle A. Daines

Biological Sciences Faculty Publications

Toxin-antitoxin systems are encoded by bacteria and archaea to enable an immediate response to environmental stresses, including antibiotics and the host immune response. During normal conditions, the antitoxin components prevent toxins from interfering with metabolism and arresting growth; however, toxin activation enables microbes to remain dormant through unfavorable conditions that might continue over millions of years. Intense investigations have revealed a multitude of mechanisms for both regulation and activation of toxin-antitoxin systems, which are abundant in pathogenic microorganisms. This minireview provides an overview of the current knowledge regarding type II toxin-antitoxin systems along with their clinical and environmental implications.

Selectivity Targeting Polo-Like Kinase 1 (Plk1) Using Novel Inhibitors Of The Polo-Box Domain, Merissa Lynnea Baxter

Theses and Dissertations

Polo-like Kinse 1 (PLK1) is a serine/threonine protein kinase that is expressed in dividing cells. It is a widely studied protein that plays an important role in regulating mitotic progression. PLK1 is over-expressed in several tumor types, and studies have shown that down-regulating PLK1 expression inhibits cancer cell proliferation, validating PLK1 as an oncotarget. Efforts to target this protein therapeutically has led to the development of several ATP-based inhibitors, although these are not exclusively specific. Because other PLK family members are tumor suppressors, it is important that PLK1 inhibitors selectively bind to PLK1 and not the other PLKs, particularly PLK3. …

Effects Of Hiv And Drugs Of Abuse On The Blood-Brain Barrier, Gopika Hari

Undergraduate Research Posters

Despite effective systemic therapy, HIV-1 infection within the brain results in neuronal degradation and neurocognitive dysfunction. This neurocognitive dysfunction is worsened in the setting of opiate abuse. The central nervous system (CNS) is protected by the blood-brain barrier (BBB), a selective barrier regulating the passage of substances from peripheral circulation into the CNS. The BBB is composed of microvascular endothelial cells encased by basal lamina, pericytes, and perivascular astrocyte endfeet. Intracellular junctional complexes comprising of adherens and tight junctions are located between the endothelial cells and form tight barrier, preventing traffic of compounds between cells (paracellular flux). Clinical and in …

Evaluation Of Current Heparin Weight Based Protocol In Obese Patients, Marie Lafosse, Simon Leung, Carla Hawkins, Madeline Camejo

Internet Journal of Allied Health Sciences and Practice

Purpose: To evaluate the difference in achieving goal activated partial thromboplastin time (aPTT) within 24 hours utilizing the institutional heparin weight based protocol between obese and non-obese patients. Methods: Retrospective, non-randomized, open label chart review in a community based hospital. Patients age 18 years or older receiving heparin therapy for greater than or equal to 24 hours identified. Patients were excluded if the protocol was utilized for acute coronary syndrome or interrupted within the initial 24 hours of therapy. Patients were also excluded if any deviations from the protocol were identified. The primary endpoint evaluated the difference in achieving goal …