Medicine and Health 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 …

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.

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 …

The Impact Of The Sentinel Initiative And Faers Surveillance System On Consumer Safety, Sonia Batra

Walden Dissertations and Doctoral Studies

The U.S. Food and Drug Administration (FDA) uses the FDA Adverse Event Reporting System (FAERS) to monitor adverse events resulting from pharmaceutical drug use. However, this system has limitations such as not allowing real-time data collection. To address these limitations, the FDA launched the Sentinel Initiative in 2008. This comparative case study was conducted to describe perceptions of investigating the efficacy of the Sentinel Initiative compared with the FAERS. The study was based on the theory of preemption as it emphasized the need for efficient means for providing unquestionable proof that consumers suffered adverse drug effects. The sample included interivews …

Redox-Sensitive Block Copolymer Nanoparticle Preparation And Characterization, Mary Virginia Portera

Honors Theses

The purpose of the research conducted in this project was to add to a wealth of knowledge concerning chemotherapy. Although chemotherapy has been used since Paul Ehrlich's discover of Salvarsan's ability to kill Treponema pallidum (the bacterium that causes syphilis), today the term chemotherapy is mostly used in conjunction with cancer treatment. There have been many successful chemotherapy drugs produced throughout the years, but a constant problem with chemotherapy is the fact that it also affects noncancerous cells. The topic of this research investigated targeted drug delivery systems that incorporate paclitaxel, a hydrophobic chemotherapy drug. This research mainly focused on …

Students' And Pharmacists' Perspectives On The Issue Of Adhd Prescription Medication Abuse At The University Of Mississippi, Meghan Wagner

Honors Theses

No abstract provided.

Patient Experiences With Small-Scale Pharmacy Compounding, Morgan Cawthon

Honors Theses

Investigators examined patients' use, knowledge and perceptions of pharmacy compounding at an independent compounding pharmacy in Mandeville, Louisiana. Data were collected using a self-administered survey that patients could complete in hard-copy in the pharmacy or at home, or online using Qualtrics. Investigators found that, in some instances, patients who use compounded medications, or have a member of their household who uses compounded medications, may be more knowledgeable or have more positive perceptions of compounded medications. However, patients who did not have experience with compounds were not unknowledgeable about the practice and did not report any negative perceptions of compounding. These …

Evaluation And Enhancement Of Physical Stability Of Amorphous Solid Dispersions, Xin Feng

Electronic Theses and Dissertations

A major concern during formulation development has been to enhance the dissolution rate and bioavailability of poorly water-soluble drugs.[1],[2] The amorphous forms of APIs have attracted considerable attention as the amorphous forms tend to exhibit significantly higher levels of supersaturation in aqueous media when compared to the crystalline forms.[3],[4] For drugs which bioavailability is limited by aqueous solubility (biopharmaceutical classification system (BCS) class II drugs), which is a significant number of recently discovered drug candidates, the improved solubility may lead to enhanced bioavailability.[5-7] Oral absorption of APIs depends on two broad, but crucial, events, namely drug solubilization and gastrointestinal permeation.[8] …

Exploring New Chemical Entities From Traditional Medicine: Docking, Synthesis And Specific Bioactivities, Chinni Yalamanchili

Electronic Theses and Dissertations

Traditional medical systems contributed significantly to medicine with a number of their phytochemicals found to possess good biological properties. Recently, Dr. Youyou Tu was awarded the Nobel Prize (2015) for her discovery/isolation of Artemisinin from the TCM plant Artemisia annua. Our first aim is to identify active phytochemicals against botulinum neurotoxin A (BoNT/A), and diabetes from Ayurveda and TCM, respectively, by using in silico, in vitro and in vivo approaches. In our second aim, we wanted to enantioselectively synthesize scalable quantities of phytoestrogenic isoflavans such as equol and sativan. The following three chapters summarize results of the three research goals. …

Novel Approaches For Ungual And Trans-Ungual Delivery Of Drugs, Avadhesh Singh Kushwaha

Electronic Theses and Dissertations

Topical therapy is commonly used for the treatment of nail diseases such as onychomycosis and nail psoriasis due to less severe side effects, non-invasiveness, direct drug delivery at the site of infection, patient compliance and lower cost of treatment. However, topical treatment is limited due to poor permeability and hard nature of nail plate. The main objective of first project was to investigate the penetrability of apremilast into and across the nail plate, folloby the preparation of a novel nail lacquer formulation to improve its ungual and trans-ungual permeation for the treatment of nail psoriasis. Dexpanthenol and salicylic acid were …

Critical Quality Attributes Of Topical Semi-Solid Dosage Forms: Solvent Activity, Muralikrishnan Angamuthu

Electronic Theses and Dissertations

Critical quality attribute has been defined as “a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality”. Deviations from preset quality metrics may potentially result in drug products with inferior therapeutic efficacy and unacceptable clinical safety profile. Topical cream formulations may possess numerous quality attributes that can affect the permeation of the drug through skin and consequently therapeutic efficacy. CQAs of topical formulations are often aimed at characterizing either the physicochemical properties of APIs or bulk characteristics of the formulation itself. Solvent systems constitute a …

Hot-Melt Extrusion: A Versatile Pharmaceutical Technology, Hemlata Patil

Electronic Theses and Dissertations

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. The first objective of this research work was to describe a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME) using Quality by Design (QbD) principles. Fenofibrate SLN were prepared by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Varying the process parameters enabled the production of SLN below 200 nm. At the end of a 5-h in-vitro dissolution study, …

Characterization And Economic Burden Associated With Pediatric Opioid Exposures And Poisonings, Anisha M. Patel

Theses and Dissertations

Introduction

The main objectives of this study were: 1) to examine the prevalence and characteristics of opioid exposures, 2) to estimate the economic costs associated with opioid poisonings, and 3) to examine the characteristics associated with opioid poisoning-related health care resource use (HCRU) and costs in children.

Methods

Data from the National Poison Data System from January 1, 2010 to December 31, 2014 were utilized to examine the prevalence and characteristics of opioid exposures and poisonings in children <18 years. Economic costs were estimated using the 2012 Nationwide Emergency Department Sample, Kids’ Inpatient Database, Multiple Cause-of-Death file and other published sources, applying a societal perspective. Direct costs included costs associated with ED visits, hospitalizations and ambulance transports. Indirect cost included productivity costs due to caregivers’ absenteeism and premature mortality among children.

Results

There were a total of 83,418 pediatric opioid exposures and nearly half of them resulted in poisoning. The epidemiology of opioid …

Exploration Of The Srx-Prx Axis As A Small-Molecule Target, Murli Mishra

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a leading cause of cancer-related mortality irrespective of gender. The Sulfiredoxin (Srx) and Peroxiredoxin (Prx) are a group of thiol-based antioxidant proteins that plays an essential role in non-small cell lung cancer. Understanding the molecular characteristics of the Srx-Prx interaction may help design the strategies for future development of therapeutic tools. Based on existing literature and preliminary data from our lab, we hypothesized that the Srx plays a critical role in lung carcinogenesis and targeting the Srx-Prx axis or Srx alone may facilitate future development of targeted therapeutics for prevention and treatment of lung cancer. First, …

The Synthesis And Applications Of [2.2]Paracyclophane Derivatives, Craig Hicks

Doctoral

This work concerns the preparation of novel [2.2]paracyclophane derivatives intended for use as asymmetric ligands and investigations into surface coatings prepared from [2.2]paracylophanes. This begins with a general introduction to enantioselective synthesis, followed by a review of relevant reported ligands based on the [2.2]paracyclophane framework and their applications. Next is described the preparation of novel ligands based on the [2.2]paracyclophane structure. Starting with the preparation of a range of mono and disubstituted [2.2]paracyclophanes, including several novel analogues, this moves on to investigating resolution procedures where a novel method for the preparation of enantiopure 4-bromo[2.2]paracyclophane is described. The coupling of prepared …

Anode Catalysts For The Direct Ethanol Fuel Cell, Daryl Fox

Doctoral

The anodic reaction of the Direct Ethanol Fuel Cell has been studied with various catalysts such as electrodeposited platinum, palladium, nickel and gold electrodes. The mechanism of bimetallic catalysts was used to reduce the platinum content needed for ethanol oxidation. The effects of increased temperature, ethanol concentration, electrolyte pH and scan rate have been examined. The impact of different carbon surfaces such as carbon ink, carbon paper and commonly used Vulcan XC72 have also been analysed in order to determine the optimum conditions for the EOR in a fuel cell.

Electrochemical methods were used to analyse catalyst performance such as …