Medicine and Health Sciences Commons^™

Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni

Theses and Dissertations

Selective Mu Opioid Receptor (MOR) antagonists possess immense potential in the treatment of opioid abuse/addiction. Utilizing the “message-address” concept, our laboratory reported a novel, reversible, non-peptide MOR selective antagonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4՛-pyridyl)carboxamido]morphinan (NAP). Molecular modeling studies revealed that the selectivity of NAP for the MOR is because of a π-π stacking interaction of its pyridine ring with the Trp318residue in theMOR. Pharmacological characterization showed that NAP is a P-glycoprotein substrate, thereby limiting its use in the treatment of opioid abuse/addiction. Thus, to modify NAP, we replaced the pyridine ring with its isosteric counterpart thiophene. Isosteric replacement …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Impact Of A Primary Care Pharmacist Utilizing A Team-Based Model Of Care, Priya Verma Pharmd, Rachel Steele Pharmd, Bcacp, Ashley Parrott Pharmd, Mba, Bcps, Bcacp

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster 11-134

Objective: To characterize the impact of a primary care pharmacist working in a team-based care model, by determining: • The acceptance rate for all recommendations • The total number of each recommendation type • The number of referrals to the primary care pharmacist, if the patient was an appropriate candidate for comprehensive medication management

Assessing Appropriateness Of Inpatient Rifaximin Use In A Community Health System, Alissa Keillor Pharmd, Sarah Pfaehler Pharmd, Mba, Bcps, Lorin Yolch Pharmd, Bcgp, Bcac

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster # 11-135

Objective: To evaluate the appropriateness of inpatient rifaximin use and healthcare resource utilization best-practices within a community health-system.

Impact Of Atypical Antipsychotics On Sedation Requirements In Mechanically Ventilated, Critically Ill Patients, Michael Genday Pharmd, Dustin D Linn Pharmd, Bcps, Bcccp, Jim Roy Pharmd, Bcps, Bcccp

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada

Objective: To determine if atypical antipsychotics lower continuous infusion sedation requirements while also assessing risk

Standardized Approach To Implementation Of Infusion Pump Interoperability, Tara Jellison Pharmd, Mba, Fashp, Rebecca S. Mahuren Bsn, Rn

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster #708041 08-105

Purpose: Describe the process to implement smart pump–electronic health record (EHR) interoperability technology throughout a multi-facility community health system to improve intravenous (IV) medication safety and efficiency with auto-programming, reducing keystroke errors and edits from 17 step manual process to 7 steps.

The Role Of Aryl Hydrocarbon Receptor (Ahr) In Drug-Drug Interaction And The Expression Of Ahr In Pichia Pastoris, Yujuan Zheng

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor is a ligand-activated transcription factor that is involved in many important functions in the body. To study the role and function of AHR, an abundant amount of in vitro expressed and purified protein is needed. A baculovirus insect expression system is commonly employed to express AHR, however, there are several drawbacks with this method, such as mutation potential and high cost. A better in overexpression system is needed and we hypothesize that Pichia pastoris, a yeast expression system, could stably express AHR and ARNT (aryl hydrocarbon receptor nuclear translocator) in sufficient amount with reasonable cost. Codon …

The Potency Of Ag10 In Stabilizing Transthyretin Is Driven By Interactions Mimicking The Disease-Suppressing T119m Variant, Dengpan Liang

University of the Pacific Theses and Dissertations

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While destabilizing TTR mutations increase the risk of developing ATTR-CM, the naturally occurring Thr119Met (T119M) variant stabilizes TTR and prevent disease. The two Serine 117 and Serine 117’ (S117/S117’) side chain hydroxyl groups of monomers A and B in T119M variant TTR form direct hydrogen bonds with each other. AG10 is an orally available, small molecule TTR stabilizer in Phase 3 clinical development for ATTR-CM. Structural features that infer high potency of AG10 for stabilizing TTR remains incompletely characterized.

In order to investigate the contribution of …

Development And Characterization Of Ldv Peptide Targeted Nanocarriers For Paclitaxel Delivery: A Comparative Study Of Micelles, Liposomes And Solid Lipid Nanoparticles, Poonam Dattani

University of the Pacific Theses and Dissertations

Nanocarriers have been established as delivery vehicles to target cancer tumors. However, premature drug leakage is one of the major reasons for inefficient drug delivery of nanocarriers to the tumor. Drug diffusion out of the nanocarriers or destabilization of drug loaded nanocarriers by physiological interactions with blood cells, serum proteins, and cell membranes upon systemic administration contribute to premature drug release. In this study, targeted micelles, liposomes and solid lipid nanoparticles (SLNs) of similar composition were prepared and characterized to compare physicochemical characteristics, in vitro stability, in vitro release rates in release media and in vivo performance. Peptide Amphiphiles (PAs) …

Lipid-Coated Magnesium Phosphate Nanoparticles For Intrapulmonary Protein Delivery In Mice, Mallika Vadlamudi

University of the Pacific Theses and Dissertations

Proteins are a diverse category of biomolecules with great therapeutic potential. Intracellular delivery of proteins can augment the deficient activities of dysfunctional or poorly expressed innate proteins and therefore represents a promising strategy to treat the associated diseases. One major barrier to intracellular protein delivery is the translocation of the protein across the cellular membrane. Endocytosis provides an important pathway for protein nanocarriers to enter cells across the plasma membrane. However, the cargo protein must then promptly escape from the endosomes to avoid degradation in the lysosome and to exert its cellular function.

Previously, we reported a cationic lipid-coated magnesium …

The Effect Of Energy Drinks On Cardiovascular Variables: A Randomized Controlled Trial, Cynthia Lee

University of the Pacific Theses and Dissertations

Many studies have investigated the effects of energy drinks on cardiovascular parameters. These studies were typically conducted with high volume (32 ounces) energy drinks and have demonstrated association with QT prolongation and blood pressure elevation after consumption. Currently, there is inconclusive evidence with lower volume energy drinks. This study intends to evaluate the effects of the largest commercially available energy drink can (24 ounces) in the United States on cardiovascular parameters compared with placebo arm. A randomized, double-blinded, placebo-controlled, crossover trial was conducted over 2 separate days with a minimum of 6-day wash out period. Healthy volunteers between the age …

Development Of A New Class Of Ligand-Targeted Chemotherapeutics With Enhanced Safety And Efficacy Profile, Arindom Pal

University of the Pacific Theses and Dissertations

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of …

Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li

University of the Pacific Theses and Dissertations

Benzo[a]pyrene (BaP), is one of the most potent mutagens and carcinogens known. It requires metabolic activation through cytochrome P450 (CYP)1A1 to yield the ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to DNA and form predominantly covalent (+) trans adducts at the N2 position of guanine causing DNA damage. Rutaecarpine (RTC) is an herbal medicine that has been used to treat several diseases such as headache, hypertension, gastrointestinal disorders, amenorrhea, and anti-inflammation. It has also been reported as a potent inducer of CYP enzymes, including CYP1A1, and CYP1A2. The mechanisms underlying up-regulation of CYP1A1 by RTC is dependent on aryl …

A Cost Control Model For Inpatient Medications Among Adults With Mental And Behavioral Health Disorders, Huanan Li

University of the Pacific Theses and Dissertations

Pharmaceutical expenditures are an important part of the entire hospital operating budget, and inpatient pharmaceuticals denote one of the highest costs in hospital care. Predictions for medication budgets based on the types of patients have been largely undertaken in medical hospitals and not psychiatric facilities. According to several previous studies, gender, age, diagnosis, comorbidity and length of stay (LOS) affect the general inpatient treatment expenditures. However, whether or not the impact of these factors differs in psychiatric hospitals remains to be investigated. To that end, the current study examines medication costs for mental and behavioral health disorder as well as …

State And Regional Comparisons Of Breastfeeding Policies And Rates: A National Study, Erin Johnson

Honors Theses

State legislation focused on promoting and supporting breastfeeding is relatively new, beginning in the 1990s. The purpose of this study is to determine if there is an association between state breastfeeding rates and state breastfeeding legislation and other institutional policies. The Centers for Disease Control and Prevention releases breastfeeding report cards with the most up-to-date state breastfeeding rates. These reports are used to examine the relationship between state breastfeeding rates and number of breastfeeding policies passed by a state. Government initiatives, such as Healthy People Initiative, and organizational practices, such as Baby-Friendly USA Inc., are also studied to determine their …

Geographical Variability In Antibacterial Chemical Defenses Of The Caribbean Sponge Xestospongia Muta, Coleman Sisson

Honors Theses

Coral reefs are important and diverse marine ecosystems, and sponges represent the majority of species in Caribbean reefs. Xestospongia muta is a giant barrel sponge that is one of the most abundant and visible sponges on Caribbean reefs, and has been the subject of many studies. Xestospongia muta produces a diversity of secondary metabolites that have various ecological functions including allelopathy, anti-fouling, predation deterrence, and antibacterial activity. The chemical defenses produced by a sponge can change in response to various biotic and abiotic stressors, including water temperature, sedimentation, nutrient runoff, and predation. This study compared the antibacterial activity of X. …

The Protective Role Of Estrogen On Hiv-1 Mediated Neurotoxicity, Macklin Licamied

Honors Theses

The prevalence of HIV among men have been in a steady inclination over the last several decades, yet the accelerated infection rate among older women is considerably concerning. Not only does the HIV virus affect the immune system but it also affects the central nervous system. One of its viral proteins, Tat, acts as an excitotoxin and disrupts the cell’s membrane potential by increasing the concentration of Ca2+ inside the cell. This influx of calcium ions leads to apoptosis and secretion of the cell’s contents into the surrounding area. Macrophages, along with other innate immune components, gather and induce the …

Sexual Dimorphism In Aortic Function Of Uc Davis Type 2 Diabetes Mellitus Rat Model: Estrogen Specific Responses, Farjana Akther

University of the Pacific Theses and Dissertations

Little is known about the interaction between diabetes and sex in vasculature. This study was designed to investigate the effects of estrogen as well as type 2 diabetes (T2D) on aortic function in rats with respect to sex. To test the effects of T2D and sex, UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model was used. To study the effects of estrogen, ovariectomized Sprague- Dawley female rats and UCD-T2DM rats at pre-diabetic stage were used and the rats were implanted subcutaneously either with placebo or 17 β-estradiol pellets (60 days release, 1.5mg/pellets). The plasma analytes for metabolic parameters and …

Angiogenic Effect Of Salt-Leached Thai Silk Fibroin Scaffolds With Human Adipose-Derived Stem Cells, Tanapong Watchararot

Chulalongkorn University Theses and Dissertations (Chula ETD)

Angiogenesis plays important role in tissue regeneration. Biomaterials that allow and promote angiogenesis are thus beneficial. Silk fibroin (SF) scaffolds are good candidates for angiogenesis activation because of the biodegradability, biocompatibility, and interaction of extracellular matrices. Human adipose-derived stem cells (ADSCs) are also promising for tissue regeneration. This study thus aims to investigate the angiogenic potential of SF scaffolds with/without ADSCs on chick chorioallantoic membrane (CAM). Firstly, the SF scaffolds were fabricated with a porosity of 77.34 ± 16.96% and a pore diameter of 513.95 µm. Then, ADSCs were seeded on SF scaffolds (SF-ADSC scaffolds) and placed on CAM on …

Population Pharmacokinetics Of Nicotine In Thai Smokers, Kathy Moe San

Chulalongkorn University Theses and Dissertations (Chula ETD)

Despite the popularity of nicotine gum in Thailand, population pharmacokinetics of nicotine gum in Thai population has not been investigated yet. This study aimed to develop a population pharmacokinetic model to quantify the effects of genetic and nongenetic factors to nicotine pharmacokinetics after administration of nicotine gum to adult Thai smokers. A population pharmacokinetic analysis was performed using secondary data collected from a previous clinical trial assessing cytochrome P450 2A6 (CYP2A6) genotypes in Thai smokers. Eighteen healthy adult smokers were included in the study. Blood samples were collected at pre-dose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, and …

In Vitro Safety And Permeation Assessments Of Lidocaine Loaded In Dissolving Microneedle Patch For Ocular Administration, Sirikool Thamnium

Chulalongkorn University Theses and Dissertations (Chula ETD)

The challenge in ocular drug delivery have brought much attention in pharmaceutical research. Efforts have been made to improve the low bioavailability causing by physiological limitations of ophthalmic drug administration. Topical lidocaine solution is a popular choice for ocular treatment, but less than 5% of topically applied dose reached to the target site. Lidocaine loaded in dissolving microneedle patch was considered a good alternative approach to treating eyes. The study aimed to investigate the cytotoxicity of the lidocaine loaded in dissolving microneedle administration against human corneal epithelial cells (HCECs) as well as ex vivo drug target localization with tissue penetration. …

Effect Of Extraction Solvents On Biological Activities Of Murraya Paniculata Leaves In Cosmetic Application, Siriruethai Ruanmai

Chulalongkorn University Theses and Dissertations (Chula ETD)

The objective of this study was to evaluate and compare the antioxidant activity and tyrosinase inhibition activity of Murraya paniculata (Linn.) Jack leaves extract (MPE) obtained from different extraction solvents for the use of cosmetic purposes. The result showed that 75 % ethanolic extract presented the highest antioxidant activity (IC50 = 1.43 mg/mL), the total phenolic content of 66.12 mg GAE/g and the total flavonoids content of 7.83 mg QE/g. All of the obtained extracts had low tyrosinase inhibitory activity. The final MPE lotion contained 1 %w/w of 75 % ethanolic extract dissolved in 50 %w/w of propylene glycol, 20 …

Development Of Niosome Containing Ace Inhibitor/Cyclodextrin Complexes As An Ophthalmic Delivery For Lowering Intraocular Pressure, Hay Marn Hnin

Chulalongkorn University Theses and Dissertations (Chula ETD)

The purpose of this study was to develop a stable niosomal eye drop containing angiotensin converting enzyme (ACE) inhibitor for lowering intraocular pressure. Three ACE inhibitors i.e., captopril, quinapril and fosinopril (FOS) were used in this study. Their inclusion complexes formation with parent CDs i.e., alphaCD, betaCD and gammaCD were determined. All drugs represented 1:1 stoichiometry inclusion complex with each CD. Of these, FOS/gammaCD complex showed the highest stability constant. Kinetic degradation study confirmed that FOS showed the lowest degradation in the presence of gammaCD. The obtained results of solution- and solid-state characterizations including molecular docking supported the true inclusion …

Development And Optimization Of Self-Microemulsifying Astaxanthin Delivery System Using The Design Of Experiment (Doe) Approach, Mo Mo Ko Zin

Chulalongkorn University Theses and Dissertations (Chula ETD)

The purpose of this research was to develop and optimize a self-microemulsifying delivery system (SMEDS) to improve dissolution rate of poor soluble compound AST by mixture experimental design. The solubility of AST was analyzed with various excipients so that the appropriate oil, surfactant, and cosurfactant were figured out. Through the findings about the microemulsion existence area, the pseudoternary phase diagrams were constructed for selecting the optimum combination of excipients in a formulation of SMEDS. The optimized LCT-SMEDS obtained from the design space was composed of 19.59% castor oil (oil; X1), 62.34% Cremophor® RH 40 (surfactant; X2), and 18.03% Tween® 80 …

Chemical Modifications Of Α-Mangostin For Cytotoxic Study On Lung Cancer Cell Lines, Nan Yadanar Lin Pyae

Chulalongkorn University Theses and Dissertations (Chula ETD)

α-Mangostin is a natural oxygenated and prenylated xanthone, which is mainly isolated from the pericarps of Garcinia mangostana. It possesses numerous pharmacological properties and promising therapeutic effects. However, the limitations of α-mangostin such as highly hydrophobicity and poor bioavailability hider its therapeutic applications. To overcome these drawbacks of α-mangostin, chemical modifications have been performed to discover the improved analogs. Herein, two semi-synthetic approaches to obtain new α-mangostin derivatives were investigated by the modifications of the phenolic hydroxy groups at C-3 and C-6 positions involving Smiles rearrangement to install amine functional groups and the addition reaction of isocyanate to form the …

Prostate Cancer Screening In Thailand: Cost-Effectiveness Analysis And Budget Impact Evaluation, Chavalit Romyen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Objectives: As public health insurance schemes in Thailand did not included prostate cancer screening in their benefits package, this study aimed to systematically gather the effectiveness and explore the cost effectiveness of difference prostate cancer screening programs for the Thai population and find the financial impact for adapting prostate cancer strategy. Method: We perform systematic and network meta-analysis, health economic evaluation using Markov’s model to compare four prostate cancer screening strategies with no screening options. And we perform budget impact analysis to assess the potential burden for adopting selected strategy. Result: The result from systematic review and network meta-analysis suggest …

Drug Classification Scheme Review And The Economic Impact Analysis Of Abandoning Non-Prescription Drug Reimbursement In Thailand, Doungporn Leelavanich

Chulalongkorn University Theses and Dissertations (Chula ETD)

In Thailand, controversies regarding the drug classification system persist; it was believed that the number of schemes should be changed, and most drugs classified into improper schemes. The system is not also fully used to allocate healthcare budgets, while several other countries cease non-prescription (OTC) drugs reimbursement to allocate this expenditure to catastrophic diseases instead. This study thus aims to (i) review drug classification system in Thailand by comparing to other countries, (ii) evaluate the economic impact of delisting OTC drugs from drug reimbursement list using non-sedating antihistamines (AH) in patients suffering from intermittent allergic rhinitis as a case study, …

Exploring Alcohol Withdrawal Syndrome And Predicting Alcohol Consumption Change In Patients Admitted To A Genenral Hospitals In Vietnam, Loan Thi Mai Nguyen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Risky alcohol drinking is common in hospitalized patients. Early detecting risky alcohol drinkers in hospital is important to provide appropriate management of Alcohol withdrawal syndrome (AWS). This first aim of this study was to identify the extent to which patients admitted to a general hospital in Vietnam meet the criteria for risky alcohol drinker (RAD), alcohol use disorder (AUD), and alcohol withdrawal syndrome (AWS). The second aim was to identify predictors of intension to change and changing alcohol consumption using the Integrated Behavior Model as a conceptual framework. Design: A prospective survey was conducted in Kien An - a general …

Study Of Pharmacist Workforce In Public Sector, Of Republic Of The Union Of Myanmar, Lwin Nyein Aye

Chulalongkorn University Theses and Dissertations (Chula ETD)

Health workforce shortage was common across the world including Myanmar. However, there was not previous study about the pharmacist workforce to ascertain the shortage problem in Myanmar. This study was aimed to analyze the current situation of pharmacist workforce in Myanmar especially in public sector and to construct a simulation model to suggest the appropriate policy options to the policymakers in improving the pharmacist workforce situations in the public hospitals.For the first objective, the study design was a cross-sectional survey using a mixed method which consisted of the secondary data analysis and semi-structured face-to-face interviews. The government registry data related …

Precision Medicine Reimbursement Policy Landscape, Nisita Jirawutkornkul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Access to precision medicine is limited due to many factors such as precision medicine technology of each country, high-cost technology that requires high finance, limitations on knowledge and competency of personnel and access to precision medicine. Each country manages access to precision medicine differently. The existing evidences of precision medicine reimbursement policy were limited. Objective: To explore reimbursement decision of precision medicine focusing on diagnostic tests and factors associated with reimbursement decision among high-income and upper-middle-income countries. Methods: A targeted review of literatures was conducted through PubMed, MEDLINE, Embase, Cochrane Library, and hand-searching. The study included 13 selected precision …