Pharmacy and Pharmaceutical Sciences Commons^™

Beyond Peroxisome: Abcd2 Modifies Pparα Signaling And Identifies A Subclass Of Peroxisomes In Mouse Adipose Tissue, Xiaoxi Liu

Theses and Dissertations--Pharmacy

ABCD2 (D2) has been proposed as a peroxisomal long-chain acyl-CoA transporter that is essential for very long chain fatty acid metabolism. In the livers of mice, D2 is highly induced by fenofibrate, a PPARα ligand that has been widely used as a lipid lowering agent in the treatment of hypertriglyceridemia. To determine if D2 is a modifier of fibrate responses, wild-type and D2 deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARα signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Synthesis And Biological Evaluation Of Novel Resveratrol And Combretastatin A4 Derivatives As Potent Anti-Cancer Agents, Nikhil Reddy Madadi

Theses and Dissertations--Pharmacy

Resveratrol has been reported as a potential anticancer agent but cannot be used as an antitumor drug due to its chemical and metabolic instability. We have designed and synthesized 184 novel compounds related to resveratrol in an attempt to produce more potent and drug-like molecules. We have identified a tetrazole analog of resveratrol, ST-145(a) as a lead anticancer agent from the resveratrol analog series of compounds with a GI₅₀ value of less than 10nM against almost all the human cancer cell lines in the National Cancer Institute’s screening panel.

In a separate study, we tested the hypothesis that the …

Multi-Component Microparticulate/Nanoparticulate Dry Powder Inhalation Aerosols For Targeted Pulmonary Delivery, Xiaojian Li

Theses and Dissertations--Pharmacy

The aim of the work was to design, manufacture, and characterize targeted multi-component dry powder aerosols of (non-destructive) mucolytic agent (mannitol), antimicrobial drug (tobramycin or azithromycin), and lung surfactant mimic phospholipids (DPPC:DPPG=4:1 in molar ratio). The targeted dry powder for inhalation formulation for deep lung delivery with a built-in rationale of specifically interfering several disease factors of chronic infection diseases in deep lungs such as cystic fibrosis, pneumonia, chronic bronchitis, and etc. The dry powder aerosols consisting of selected chemical agents in one single formulation was generated by using spray drying from organic solution.

The physicochemical properties of multi-component dry …

Human Butyrylcholinesterase Mutants For Cocaine Detoxification, Shurong Hou

Theses and Dissertations--Pharmacy

Cocaine is one of the most reinforcing drugs of abuse and has caused serious medical and social problems. There is no FDA-approved medication specific for cocaine. It is of a high priority to develop an effective therapeutic treatment for cocaine abuse. Human butyrylcholinesterase (BChE) has been recognized as a promising candidate of enzyme therapy to metabolize cocaine into biologically inactive metabolites and prevent it from reaching central nervous system (CNS). However, the catalytic activity of wide-type human BChE against cocaine is not sufficiently high for treatment of cocaine abuse. Dr. Zhan’s lab has successfully designed and discovered a series of …

Lobelane Analogs With Various Methylene Linker Lengths And Acyclic Lobelane Analogs As Potential Pharmacotherapies To Treat Methamphetamine Abuse, Zheng Cao

Theses and Dissertations--Pharmacy

Methamphetamine interacts with vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine (DA) uptake and promotes DA release from presynaptic vesicles, increasing cytosolic DA available for methamphetamine-induced reverse transport by DA transporters. By inhibiting VMAT2, lobelane, a defunctionalized, saturated lobeline analog, decreases methamphetamine-evoked DA release and methamphetamine self-administration in rats. In this dissertation structure-activity relationships around the lobelane structure were investigated on racemic lobelane analogs with varying methylene linker lengths at central piperidine ring. Affinity for dihydrotetrabenazine (DTBZ) sites on VMAT2 and for inhibition of VMAT2 function was determined to be 0.88-63 and 0.024-4.6 µM, respectively, and positively correlated. The most potent …

Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey

Theses and Dissertations--Pharmacy

Type II polyketide synthase (PKS) produced natural products have proven to be an excellent source of pharmacologically relevant molecules due to their rich biological activities and chemical scaffolds. Type II-PKS manufactured polyketides share similar polycyclic aromatic backbones leaving their diversity to stem from various chemical additions and alterations facilitated by post-PKS tailoring enzymes. Evidence suggests that post-PKS tailoring enzymes form complexes in order to facilitate the highly orchestrated process of biosynthesis. Thus, protein-protein interactions between these enzymes must play crucial roles in their structures and functions. Despite the importance of these interactions little has been done to study them. In …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

A Review Of Common Drug-Drug And Food-Drug Interactions Associated With Cardiovascular Medications, Raymond Kho, Sarah Kim, Stacy Lee, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on the common drug-drug and food-drug interactions associated with cardiovascular medications.

Simultaneous Bactericidal And Osteogenic Effect Of Nanoparticulate Calcium Phosphate Powders Loaded With Clindamycin On Osteoblasts Infected With Staphylococcus Aureus, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

S aureus internalized by bone cells and shielded from the immune system provides a reservoir of bacteria in recurring osteomyelitis. Its targeting by the antibiotic therapy may thus be more relevant for treating chronic bone infection than eliminating only the pathogens colonizing the bone matrix. Assessed was the combined osteogenic and antibacterial effect of clindamycinloaded calcium phosphate nanoparticles of different monophasic compositions on co-cultures comprising osteoblasts infected with S aureus. Antibiotic-carrying particles were internalized by osteoblasts and minimized the concentration of intracellular bacteria. In vitro treatments of the infected cells, however, could not prevent cell necrosis due to the …

Nanoparticulate Drug Delivery Platforms For Advancing Bone Infection Therapies, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Introduction—The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition.

Areas covered—Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is …

Programmable Folding Of Fusion Rna In Vivo And In Vitro Driven By Prna 3wj Motif Of Phi29 Dna Packaging Motor, Dan Shu, Emil F. Khisamutdinov, Le Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

Misfolding and associated loss of function are common problems in constructing fusion RNA complexes due to changes in energy landscape and the nearest-neighbor principle. Here we report the incorporation and application of the pRNA-3WJ motif of the phi29 DNA packaging motor into fusion RNA with controllable and predictable folding. The motif included three discontinuous ∼18 nucleotide (nt) fragments, displayed a distinct low folding energy (Shu D et al., Nature Nanotechnology, 2011, 6:658–667), and folded spontaneously into a leading core that enabled the correct folding of other functionalities fused to the RNA complex. Three individual fragments dispersed at any …

Knowledge And Provision Practices Of Misoprostol Among Pharmacies In Senegal, Ramatoulaye Ndao, Babacar Mane, Eva Burke, Nafissatou Diop, Kate Reiss, Thoai Ngo, Katharine Footman, Maaike Van Min

Reproductive Health

In developing countries, postpartum hemorrhage and complications related to unsafe abortions are direct causes of maternal death. In Senegal, actions have been undertaken by the government to reduce this burden and significant advances have been made in these areas in recent years. However, progress is still necessary to achieve the Millennium Development Goals for the reduction of the maternal mortality rate to the target numbers by 2015. The objective of the study was to understand the knowledge about, availability of, and practices in the provision of misoprostol at pharmacies in Dakar, Senegal, to ensure correct delivery of the product. Pharmacists …

Understanding Ligand Binding, Selectivity And Functions On The G Protein-Coupled Receptors: A Molecular Modeling Approach, Saheem Zaidi

Theses and Dissertations

The assessment of target protein molecular structure provides a distinct advantage in the rational drug design process. The increasing number of available G protein-coupled receptor crystal structures has enabled utilization of a varied number of computational approaches for understanding the ligand-receptor interactions, ligand selectivity and even receptor response upon ligand binding. The following dissertation examines the results from three different projects with varied objectives – i) structural modeling of human C-C chemokine receptor type 5 (CCR5) and assessment of the ligand binding pocket of the receptor, ii) assessment of the selectivity profile of naltrexone derivatives on the three opioid receptors …

Dereplication And Prioritization Of Natural Product Extracts For Antifungal Drug Discovery, Kara Fowler

Honors Theses

The prevalence of opportunistic fungal infections in hospital settings are at alarming rates. Through technological advances in natural product research, plants have become a useful source for antifungal drug discovery. More samples can be screened at once, fractionated in less time, and biologically tested at smaller quantities. However, isolating antifungal compounds from these plant extracts and determining their specific chemical makeup can still take up a significant amount of time. Therefore, this thesis presents a prioritization technique to prevent the need to isolate every compound within an active fraction. With the guidance of literature research on the genus and species …

Mississippi Pharmacists' Knowledge And Attitudes About Pharmacy Compounding Safety And Regulation, Kimberly Allen

Honors Theses

Introduction: Pharmacy compounding, which is defined by The Food and Drug Administration (FDA) as a practice in which a licensed pharmacist combines, mixes, or alters ingredients in response to a prescription to create a medication tailored to the medical needs of an individual patient,1 has gained recent attention at both national and state levels. Outbreaks of adverse events associated with pharmacy compounding have led to many proposed and enacted changes in how to appropriately and best regulate traditional compounding pharmacies and those that act as manufacturers. Given such recent controversies and potential confusion as to exactly how compounding is regulated, …

Reproductive And Multigenerational Effects Of Dietary Benzo[A]Pyrene Exposure In Zebrafish, Mallory White

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen that also acts as an endocrine disruptor. Multigenerational impacts of PAH exposure are suggested in human cohort studies. To investigate mechanisms and developmental phenotypes associated with a dietary BaP exposure, zebrafish (Danio rerio) were used. We hypothesized that BaP exposure would cause: 1) phenotypic malformations in the gonad that would affect reproductive success; 2) developmental deformities in the offspring that would lead to decreased survival and ability to reproduce without additional BaP exposure; and 3) changes in gene expression that would be conserved across generations and related …

Pharmacists' Preparedness For Acute Medical Emergencies, James W. Parrett

Electronic Theses and Dissertations

Purpose/Objectives: This project studied how prepared community pharmacists are to respond to acute medical emergencies, as well as their perceived efficacy in addressing these situations. Specifically, it considered what training pharmacists have for responding to medical emergencies, what emergency medical equipment pharmacies have on-hand, the frequency that medical emergencies occur within pharmacies, and the types of emergencies encountered. It also measured self and collective efficacy of pharmacists in responding to medical emergencies within their pharmacy to determine if differences in self-efficacy or collective efficacy exist. Methods: This study utilized a cross-sectional, non-experimental, descriptive design via a self-administered, Internet-based survey distributed …

Management Of Breast Cancer In The Medicaid Population, Rohan Mahabaleshwarkar

Electronic Theses and Dissertations

Breast cancer is the second most comcancer and the second leading cause of cancer-related death among women. The current project examined some key issues important for effective breast cancer management in the Medicaid population. Medicaid is one the largest healthcare insurance systems in the US providing coverage to more than 60 million low-income individuals. As a part of this project, three studies were conducted. The first study determined the healthcare burden associated with breast cancer in the form of healthcare use (inpatient, outpatient, and emergency room [ER] visits) and costs associated with the condition in the Medicaid population. Significant healthcare …

Cranberry Metabolites With Urinary Anti-Adhesion Activity, Christina M. Coleman

Electronic Theses and Dissertations

The fruit of the American cranberry (Vaccinium macrocarpon Aiton, Ericaceae) is a comfood and a top selling dietary supplement in the U.S. Cranberry juice is traditionally used for the prevention of urinary tract infections (UTIs), many of which are caused by P-fimbriated Escherichia coli. Human urine produced after cranberry juice consumption can prevent E. coli adhesion, but the urinary metabolites responsible for this activity are currently not known. High-molecular weight components of cranberry juice, specifically proanthocyanidin oligomers (PACs), are currently believed to be responsible for the ability of cranberry juice to prevent UTIs. Cranberry PACs can prevent the adherence of …

Structure, Synthesis And Biological Activity Of Harmful Algal Bloom Toxins From Karlodinium Sp. And Exploration Of Microbial Derived Natural Products, Amanda Leigh Waters

Electronic Theses and Dissertations

This work features natural products isolated from both the marine and microbial environments. Part I focuses on the elucidation of toxins from harmful algal blooms (HAB). The HAB dinoflagellate Karlodinium veneficum produces a harmful suite of molecules identified as the karlotoxins (KmTx) that have been implicated in massive fish kills pan-globally. Nine new karlotoxin congeners were isolated from various Karlodinium blooms around the world and utilizing the structure of KmTx2 were characterized using overlaid 2D NMR techniques. Due to the contrasting conformational differences between KmTx and the closely related amphidinols, the absolute configuration of KmTx was further evaluated by extensive …

Intranasal Delivery Of Therapeutics Targeted To Csf And Brain, Prashanth Manda

Electronic Theses and Dissertations

Blood-brain barrier and blood-cerebrospinal fluid barrier limit the systemic delivery of therapeutics to the brain and cerebrospinal fluid (CSF) respectively. Therapeutic agents targeting CNS are currently being administered by invasive routes which are not patient compliant and do not allow frequent administration. Intranasal delivery of therapeutics to target CSF and brain is a noninvasive route of administration which is patient compliant and allows frequent administration. In the current study, the plausibility of delivering ziconotide and cefotaxime to CSF and brain respectively via intranasal pathway using barrier modulating agents like chitosan was investigated. The ability of chitosan to enhance the permeation …

Secondary Metabolite Production By An Endophytic Bacillus Sp. From Platanus Occidentalis, Michael C. James

Electronic Theses and Dissertations

Endophytes are bacterial and fungal microbes that live inside of plant tissue without causing disease. Endophytes have applications in many industries including the pharmaceutical and food industries as producers of natural products. This potential was demonstrated by investigating the natural product production from a Bacillus amyloliquefaciens endophyte of Platanus occidentalis using a combination of MALDI-IMS, LC-MS, MS-MS, and NMR methods, by purifying nicotianamine from soy flour, and by reviewing natural product inhibitors of the hepatitis C virus (HCV). The secondary metabolite production of the endophytic B. amyloliquefaciens was investigated under a variety of fermentation conditions. It was discovered that the …

A Collaborative Approach To Combining Service, Teaching, And Research, Suzanne M. Galal, Sian M. Carr-Lopez, Seth Gomez, Van Duong, Caitlin Mizoshiri, Lauren Ujihara, Tina H. Tran, Rajul A. Patel, Joseph A. Woelfel

School of Pharmacy Faculty Articles

Objective. To describe a faculty-student collaborative model and its outcomes on teaching, service, and scholarship.

Design. A Medicare Part D elective course was offered that consisted of classroom and experiential learning where pharmacy students participated in community outreach events to assist Medicare beneficiaries with Part D plan selection. The course training was expanded to include medication therapy management (MTM) and the administration of immunizations. At the completion of the course, students collaborated with faculty members on research endeavors.

Evaluation. During the first 6 years of this course, the class size more than doubled from 20 to 42 students, and all …

Cost Variability Of Suggested Generic Treatment Alternatives Under The Medicare Part D Benefit, Rajul A. Patel, Mark P. Walberg, Emily Tong, Florence Tan, Ashley E. Rummel, Joseph A. Woelfel, Sian M. Carr-Lopez, Suzanne M. Galal

School of Pharmacy Faculty Articles

BACKGROUND: The substitution of generic treatment alternatives for brand-name drugs is a strategy that can help lower Medicare beneficiary out-of-pocket costs. Beginning in 2011, Medicare beneficiaries reaching the coverage gap received a 50% discount on the full drug cost of brand-name medications and a 7% discount on generic medications filled during the gap. This discount will increase until 2020, when beneficiaries will be responsible for 25% of total drug costs during the coverage gap.

OBJECTIVE: To examine the cost variability of brand and generic drugs within 4 therapeutic classes before and during the coverage gap for each 2011 California stand-alone …

Role Of Micro Rna 148/152 Family In Cancer Progression, Anusha Chaparala

Theses and Dissertations

Micro RNA are small single stranded RNA that regulate the expression of various genes. MiRNA guide the mRNA disintegrating RISC complex to the complimentary sequence in the target mRNA. Each micro RNA has multiple targets and can play a different biological role depending on the population of targets at the particular stage of the cell or a physiological state. Several miRNA show elevated or decreased levels of expression in various cancers because of their role in tumor initiation and progression. MiRNA belonging to mir148/152 family are examples of such MicroRNA. This family includes miR148a, miR148b and miR152. MiR148a and miR152 …

Rat Hippocampal Responses Up To 90 Days After A Single Nanoceria Dose Extends A Hierarchical Oxidative Stress Model For Nanoparticle Toxicity, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

Ceria engineered nanomaterials (ENMs) have very promising commercial and therapeutic applications. Few reports address the effects of nanoceria in intact mammals, let alone long term exposure. This knowledge is essential to understand potential therapeutic applications of nanoceria in relation to its hazard assessment. The current study elucidates oxidative stress responses in the rat hippocampus 1 and 20 h, and 1, 7, 30 and 90 days following a single systemic infusion of 30 nm nanoceria. The results are incorporated into a previously described hierarchical oxidative stress (HOS) model. During the 1-20 h period, increases of the GSSG: GSH ratio and cytoprotective …

Beta-Blockers Act Through Clathrin-Dependent Internalization And Egfr Transactivation To Promote Erk Phosphorylation, Taiwo Ajumobi

Graduate Thesis Collection

For cardiovascular diseases such as high blood pressure, angina pectoris, and left ventricle hypertrophy; long-term activation of beta-adrenergic receptors is strongly linked to the progression of these diseases. A class of antagonistic drugs that target betaadrenergic receptors are collectively called beta-blockers. These drugs are commonly used to reduce the inotropic and chronotropic effects of beta-adrenergic receptor activation. This past decade has revealed that beta-blockers and other ligands are capable of functional selectivity at receptors. Functional selectivity describes the ability of ligands acting at 0 protein-coupled receptors (OPCRs) to preferentially activate or inhibit different signal transduction pathways. The studies on beta-adrenergic …

Evaluation Of The Allometric Exponents In Prediction Of Human Drug Clearance, Da Zhang

Theses and Dissertations

Background. Allometric scaling (AS) is widely used in predicting human clearance (CL) based on animal data. Substantial prediction errors have been commonly observed and various modifications to AS have not provided a broad reliable improvement. In this study, an extensive data set was assembled including animal and human systemic CL and physiochemical properties. The allometric exponents were calculated based on multiple species AS and single-species AS methods. The correlations between the allometic exponents and physiochemical properties were evaluated in an attempt to find covariates that may explain the inter-compound variability in the allometric exponents. Lastly, the statistical approaches in analyzing …