Pharmacy and Pharmaceutical Sciences Commons^™

Efficacy And Safety Of Mulberry Leaves On Glycemic Control In Patients With Obesity And Patients With Type 2 Diabetes, Thanchanit Thaipitakwong

Chulalongkorn University Theses and Dissertations (Chula ETD)

This work was divided into three study phases: the two-phase randomized controlled clinical trials and proteomics study. First, the phase I clinical trial aimed to determine efficacy and safety of mulberry leaves on postprandial glucose following the 50-g sucrose ingestion in healthy nondiabetic adults and to explore the optimal administered dose of 1-deoxynojirimycin (DNJ), the major antihyperglycemic compound of mulberry leaves. The results showed the alleviation of postprandial hyperglycemia by mulberry leaves in a dose-dependent fashion. Adverse effects of mulberry leaves included bloating and flatulence, loose stool, and nausea. In addition, 12 mg of DNJ was considered the optimal dose …

Phytochemical Screening, In Vitro Antimalarial Activity And Genetic Diversity Of Selected Asteraceae Medicinal Plants Indigenous To Thailand, Desy Liana

Chulalongkorn University Theses and Dissertations (Chula ETD)

The emergence of artemisinin resistance leaded the effort to find the new antimalarial drug or artemisinin activity booster. Due to the chance that secondary metabolites can be evolutionary conserved, combining phylogeny with ethnobotanical data for screening antimalarial activity may be helpful to predict bioactivity and minimize the expenditure and time for laboratory research. The aimed of this study is screening the antimalarial activity, phytochemicals and genetic diversity of selected Asteraceae medicinal plants generated by combinatorial phylogeny and ethnobotanical data. 733 medicinal plants were obtained from literature search however only 340 taxa were met the inclusion and exclusion criteria hence these …

Pharmacognostic Specification And Rotenone Content In Derris Elliptica Stems, Macroscopic, Microscopic And Molecular Identification Of Selected Derris Species In Thailand, Krittapat Phairoh

Chulalongkorn University Theses and Dissertations (Chula ETD)

The genus Derris belonging to Fabaceae family are distributed along the equatorial zone in Africa and Asia. In Thailand, 16 species of Derris species can be found throughout the country. Derris elliptica (Hanglai-Dang), is well-known among fishermen and gardeners as fish poison and insecticide, especially the stem and root which contain isoflavonoid compound named rotenone. This study established the pharmacognostic specification of Derris elliptica dried stem crude drug and developed the quantitative analysis of rotenone content in D. elliptica stem using TLC-densitometry and image analysis. The physico-chemical parameters of D. elliptica stem included total ash, acid-insoluble ash, loss on drying …

Strategies And Devices For Improving Respiratory Drug Delivery To Infants And Children With Cystic Fibrosis, Karl Bass

Theses and Dissertations

Cystic Fibrosis (CF) is a degenerative disease, which causes thickening of the airway surface liquid and reduced mucociliary clearance, which provides an ideal habitat for bacterial infections. Early treatment of CF in children can prevent chronic infection, improve quality of life, and increase life expectancy. The most predominant bacteria found in CF-diseased lungs is Pseudomonas aeruginosa (Pa), which can be treated with inhaled tobramycin. Excipient enhanced growth (EEG) powder formulations are well suited for administering tobramycin to children, as the EEG approach provides minimal upper airway loss and targeted drug delivery. This method uses an initially small aerosol for high …

Development Of Dexamethsone Sodium Phosphate Loaded Nanoparticles For Treating Corneal Allograft Rejection, Vineet R. Kulkarni

Theses and Dissertations

Corneas are the most commonly transplanted tissue worldwide, with approximately 80,000 transplantations performed in the United States in 2018 alone. Corneal transplantation is used to restore the vision due to opaque corneas in various diseases such as fungal keratitis, keratoconus, Fuchs’s dystrophy, corneal ulceration, traumatic injury, abrasions or scarring, inflammation, and infection. Corneal transplant surgery could involve replacing the entire cornea (penetrating keratoplasty) or selective replacement of the corneal layers (e.g. Descemet’s membrane endothelial keratoplasty and deep anterior lamellar keratoplasty). Immunologic graft rejection is one of the main causes of graft failure in these corneal transplantations. The 2-year rejection rate …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

3-D Homology Modeling Of Organic Anion Transporters (Oats): Defining The Biochemical Basis For Oat-Substrate Interactions, Christopher Jay

Theses and Dissertations

A goal in the drug development process, as indicated by the FDA, is to evaluate a drug’s ADME profile, as potential drug interactions could exist, leading to adverse drug reactions or loss of efficacy. Transport proteins, specifically organic anion transporters (OATs) are involved in the absorption, distribution, and elimination of small, negatively charged compounds. Although there is an exhaustive list of structurally diverse organic anions which interact with OATs, interactions at a molecular level are still shrouded in mystery particularly due to the lack of a solved crystal structure. Therefore, in silico homology models (hOAT1, 2, 3) were generated using …

New Persistent And Chronic Opioid Use In Cancer Survivors After Curative Intent Radiation, Elena V. Fernández

Theses and Dissertations

Background: Emerging evidence suggests that as more patients are surviving cancer, new persistent opioid use (no prior exposure to opioids before cancer therapy but requiring opioid prescriptions after curative intent treatment; NPOU) is of greater concern. In patients receiving curative intent radiation (definitive radiation therapy and as treatment for cure; CIR), the extent to which patients develop NPOU or continue opioid use (COU) following CIR is not known. Neither are factors associated with NPOU or COU, opioid doses, or time to discontinuation (TTD) of opioids in 5CS known. Objectives: Describe longitudinal trends opioid use in cancer survivors who received CIR, …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

The Impact Of The Fda Warning On Post-Tonsillectomy Opioid Prescribing In Publicly And Privately Insured Children, Dianna J. Soelberg

Theses and Dissertations

Due to reports of significant adverse events, the U.S. FDA placed a Boxed Warning on the opioid codeine in February 2013 – contraindicating its use in pediatric patients undergoing tonsillectomy and/or adenoidectomy. Studies conducted in privately insured children showed a reduction in codeine prescribing and a slight increase in alterative opioid prescribing following the FDA warning, yet the extent to which the FDA warning impacted prescribing in publicly insured children is unknown. Using a quasi-experimental interrupted time series design, this study evaluated codeine and alternative opioid prescribing before and after the FDA warning in both publicly and privately insured children …

Development And Validation Of Predictive Risk And Multiple Criteria Decision Analysis Models To Evaluate Cardiovascular Outcomes Among Cancer Patients, Purva N. Parab

Theses and Dissertations

Objective: The objectives of our study were to characterize the study population with cancer and cardiovascular diseases (CVD) both as compared to those without and to build a predictive model using machine learning (ML) algorithms that can predict the risk of CVD in cancer patients. In addition, our objective was also to evaluate characteristics associated with cardiotoxic adverse events of breast cancer therapies and develop a multiple criteria decision analysis (MCDA) model to conduct benefit-risk assessment of breast cancer therapy regimens. Methods: We used Medical Expenditure Panel Survey (MEPS) and FDA Adverse Events Reporting System (FAERS) 2005-2015 files along with …

Development Of A Screening Assay For Type Iii Secretion System Inhibitors And High Throughput Screening Campaign Of Inhibitors Of Prp Of Staphylococcus Aureus, Heather A. Pendergrass

Theses and Dissertations

Antibiotics inhibit the growth or survival of bacteria by targeting their essential functions.¹ Due to weaknesses in traditional antibiotics and the increasing prevalence of antibiotic resistance genes, virulence factors are being targeted for therapeutic treatment of bacterial infection.² We have developed an assay to quantify and observe type III secretion system (T3SS) activity. The type III secretion system (T3SS) is a virulence factor present in some Gram-negative pathogens including enteropathogenic and enterohemorrhagic E. coli (EPEC and EHEC, respectively),³ and others.^4–9 The T3SS between EPEC and EHEC are highly conserved and share over 90% sequence identity with …

Vaccine Hesitancy: Experimentalism As Regulatory Opportunity, Ana Santos Rutschman, Timothy L. Wiemken

All Faculty Scholarship

This symposium on patient innovation has prompted us to explore problems related to departures from official vaccination schedules. At a time in which vaccine confidence has been plummeting across the world, we argue that a more granular understanding—and ultimately a more finely tuned regulatory framework—is needed to reflect the current behavioral heterogeneity among indicated patients who choose to forego or delay administration of recommended vaccines. In particular, we focus on a phenomenon we term “vaccine staggering:” a departure from vaccination schedules in the form of delays in receiving one or more vaccines, which is motivated by the desire to boost …

Multimorbidity, Immune Checkpoint Inhibitor Use, And Healthcare Expenditures Among Older Patients With Late-Stage Melanoma, Pragya Rai

Graduate Theses, Dissertations, and Problem Reports (ETD)

With decades of unchanged cancer care with no added survival benefit, immune checkpoint inhibitors (ICI) changed the treatment landscape of late-stage melanoma in 2011. A key factor in determining the use of ICIs is the presence of pre-existing chronic conditions, which can influence the outcome. However, the prevalence of multimorbidity (defined as presence of two or more chronic conditions) among older patients with late-stage melanoma remains unknown. It also remains unknown if the presence of multimorbidity factors into the use of ICIs. Hospital-related factors associated with ICI use have been studied. Yet, patient-level factors, such as age, sex, marital status, …

Applications Of Machine Learning Methods In Health Outcomes Research: Heart Failure In Women, Khalid Abdullah Alhussain

Graduate Theses, Dissertations, and Problem Reports (ETD)

There is robust evidence that heart failure (HF) is associated with substantial mortality, morbidity, poor health-related quality of life, healthcare utilization, and economic burden. Previous research has revealed that there are sex differences in the epidemiology, etiology, and disease burden of HF. However, research on HF among women, especially postmenopausal women, is limited. To fill the knowledge gap, the three related aims of this dissertation were to: (1) identify knowledge gaps in HF research among women, especially postmenopausal women, using unsupervised machine learning methods and big data (i.e., articles published in PubMed); (2) identify emerging predictors (i.e., polypharmacy and some …

Development Of An R Script For Simple Lipidomic And Metabolomic Data Analysis, Suad Alshammari, Joshua M. Morriss, Daniel Contaifer, Dayanjan S. Wijesinghe, Monther Alsultan

Graduate Research Posters

Background: Metabolomic and lipidomic studies generate vast quantities of data that are often analysed in a closed software environment with little to no access to the underlying algorithms. As a result, data processed via different software pipelines yield different results thus leading to a widespread problem of low reproducibility within these fields. To address this problem, we are developing LipidAnalyst; an R based lipidomics software pipeline. As a part of this project, we are creating a simple statistical analysis and graphing module in R to generate accurate, reproducible, high-resolution figures.

Methods: R scripts were developed under version 3.5.3 with the …

Molecular Predictors Of Anakinra Treatment Success In Heart Failure Patients With Reduced Ejection Fraction, Joshua Morriss, Daniel Contaifer Jr, Leo F. Buckley, George Wohlford, Monther Alsultan, Suad Alshammari, Asanga D. Ranasinghe, Salvatore Carbone, Justin M. Canada, Cory Trankle, Elvin T. Price, Antonio Abbate, Benjamin W. Van Tassell, Dayanjan S. Wijesinghe

Graduate Research Posters

Background. Kineret (Anakinra) is an interleukin-1 antagonist that is under investigation for its novel clinical application treating patients that have heart failure with reduced (<50%) ejection fraction (HFrEF). A prior study from our group indicated that Anakinra may restore heart function by addressing dysregulations in HFrEF metabolic pathways. Herein, we attempt to elicit Anakinra’s effects on both metabolome and lipidome.

Methods. Lipids and metabolites that had previously been quantified by mass spectrometry (MS) from patients (n=49) who had ≥2 mg/L of high-sensitivity C-reactive protein (hs-CRP) were mTIC normalized and transformed. We conducted a stepwise Linear Discriminant Analysis (r- LDA) to test Anakinra (2 and 12 weeks) vs placebo for separation from combined baseline. Metabolic pathway analysis was performed with Fisher’s exact test algorithm for detection of over-represented and enriched analytes. Univariate analysis (one tailed t-test …

Local Lung Targeting Of Tumor Associated Macrophages Combined With Cytoreductive Therapy Decrease Tumor Burden In A Secondary Lung Cancer Model, Sulaiman Alhudaithi, Hanming Zhang, Rashed Almuqbil, Wei Du, Fatemah Sunbul, Paula Bos, Sandro Da Rocha

Graduate Research Posters

Backgrounds. The efficacy of a locally administered small molecule colony stimulating factor 1 receptor inhibitor (CSF-1Ri), PLX3397, alone or in combination with cytoreductive therapy (paclitaxel) in reducing the tumor burden of an in vivo model of secondary lung cancer was investigated in this work. Local administration of immunotherapy to the lungs may enhance lung biodistribution of such therapies and reduce potential unwanted off-target toxicity. In addition, combination of such therapy with low dose standard of care chemotherapy may offer improved anti-tumor effects.

Methods. Murine breast cancer cells (4T1, known to be highly metastasized to the lungs) were transduced to …

Naming Convention, Interchangeability, And Patient Interest In Biosimilars, Mariana P. Socal, Jace B. Garrett, William B. Tayler, Ge Bai, Gerard F. Anderson

Faculty Publications

Although biosimilars may offer cost savings over their comparable biologics, use of biosimilars in the United States remains relatively low. This study investigates two barriers to uptake of biosimilars in the United States. First, the U.S. Food and Drug Administration requires that four-letter suffixes be added to the nonproprietary names of all biosimilars, as well as to the nonproprietary names of all biologics approved after March 2020. Second, biosimilars are not interchangeable with their reference biologic product at the pharmacy counter; a new prescription is needed for the biosimilar to be dispensed in place of the biologic. We conducted two …

Introducing A Model And A Framework To Unify The Pharmaceutical Quality System Enablers Quality Risk Management & Knowledge Management, Martin J. Lipa, Kevin O'Donnell, Anne Greene

Articles

An organization that effectively manages knowledge should be able to recognize and proactively apply new learnings to better anticipate risks. This is particularly important in the manufacture of medicinal products. Since the publication of ICH Q10 in 2010, Quality Risk Management (QRM) and Knowledge Management (KM) have been positioned as co-enablers to the Pharmaceutical Quality System. The authors of this paper present a Knowledge Management process model to foster greater practical understanding of the practice of knowledge management. This model when joined with the familiar ICH Q9 process model for QRM, should enable a company to better manage their knowledge …

An Exploration Of Pharmacy Education Researchers' Perceptions And Experiences Conducting Qualitative Research, Antonio A. Bush, Mauriell Amechi, Adam Persky

Educational Leadership & Workforce Development Faculty Publications

Objective. To investigate pharmacy education researchers' experiences in conducting qualitative research and their perceptions of qualitative research in pharmacy education

Methods. A phenomenological approach was used to conduct one-time, in-depth interviews with 19 participants from 12 schools and colleges of pharmacy. Interview transcripts were coded and themes were identified using a modified form of the Sort and Sift, Think and Shift method of data analysis.

Results. Faculty members were the largest subgroup in the sample, followed by graduate students, postdoctoral fellows/scholars, and residents. Pharmacy education researchers had varying levels of training in conducting qualitative research and some had none at …

Predictors Of Cardiovascular And Gastrointestinal Disorders, Inappropriate Nonsteroidal Anti-Inflammatory Drug Use, And Alzheimer’S Disease And Related Dementia In Older Adults With Osteoarthritis, Jayeshkumar Patel

Graduate Theses, Dissertations, and Problem Reports (ETD)

Osteoarthritis (OA) is a degenerative arthritis affecting over 30 million Americans most of whom are over 65 years or older. Its clinical management is complicated by several disease- and treatment-specific factors. These include the co-occurrence of cardiovascular and gastrointestinal disorders (CV-GID), the inappropriate use of non-steroidal anti-inflammatory drugs (NSAID) to manage pain, and the risk of certain age-related chronic conditions like Alzheimer’s disease and related dementia (ADRD). Moreover, older adults with OA are at a higher risk of CV-GID, inappropriate NSAID use, and ADRD. Additionally, these factors can also affect one another in both a positive and a negative way. …

Bioactive Indanes: Development And Validation Of An Lc-Ms/Ms Bioanalytical Method For The Determination Of Ph46a, A New Potential Anti-Inflammatory Agent, In Dog And Rat Plasma And Its Application To A Pharmacokinetic Study In Dog, Gaia Scalabrino, Tao Zhang, Neil Frankish, Helen Sheridan

Articles

A new chemical entity, which is a chiral indane dimer, PH46A, has been developed by our research group. As a clinical candidate. PH46A has recently completed Phase I clinical studies in man. Previously, during its pre-clinical development, in in vivo pre-clinical studies PH46A showed potent anti-inflammatory properties, which can be targeted at a range of diseases, including inflammatory bowel disease (IBD). To support the pre-clinical development of this drug candidate, we developed a LC MS/MS method for determining PH46 (the acid form of PH46A salt) in both dog and rat plasma using Compound 1 as internal standard (IS). Those species …

Design, Synthesis, And Biological Evaluation Of Aryl Piperazines With Potential As Antidiabetic Agents Via The Stimulation Of Glucose Uptake And Inhibition Of Nadh:Ubiquinone Oxidoreductase, R. Devine, M. Kelada, S. Leonard, D.S.D. Martin, J.M.D. Walsh, C.J. Breen, R.B. Driver, Gemma K. Kinsella, J.B.C Findlay, J.C. Stephens

Articles

The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose …

Tannic Acid Inhibits Lipid Metabolism And Induce Ros In Prostate Cancer Cells, Prashanth K.B. Nagesh, Elham Hatami, Pallabita Chowdhury, Shashi Jaun, Nirnoy Dan, Vivek Kumar Kashyap, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely …

Clinical Risk Assessment In Early Pregnancy For Preeclampsia In Nulliparous Women: A Population Based Cohort Study, Anna Sandstrom, Jonathan Snowden, Jonas Höijer, Matteo Bottai, Anna-Karin Wikström

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective

To evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women.

Design and setting

A population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008–13 in the Stockholm-Gotland Counties in Sweden.

Methods

Maternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine …