Medicine and Health Sciences Commons^™

Investigation Of Cytotoxic Activity Of Full-Length And Truncated Colicin N On Human Cancer Cells, Methawee Duangkaew

Chulalongkorn University Theses and Dissertations (Chula ETD)

Bacteria, exposed to stress from the environment or competition, release toxins called bacteriocins. Bacteriocins are classified by their mode of cytotoxicity such as pore former, endonuclease, etc. Colicins are the member of bacteriocins produced by Escherichia coli (E.coli). Among several types of colicins cytotoxicity, Pore-forming colicins has been reported in both bacteria and various type of cancer cells. Colicin N is also a pore-forming colicin and the anticancer activity of colicin N has not been extensively reported. Here we examined the cytotoxic effects of colicin N and its domain on cancer cells. The expression and purification of recombinant full-length and …

Chemical Constituents With Alpha-Glucosidase Inhibitory Activity From Dendrobium Braianense And Dendrobium Kentrophyllum, Mia Indria Permatasari

Chulalongkorn University Theses and Dissertations (Chula ETD)

To investigate the phytochemicals of the entire plants of Dendrobium braianense brought about in the isolation of three bibenzyls, which included chrysotoxin, moscatilin and gigantol. From the whole plant of D. kentrophyllum three flavonoids, namely, quercetin, kaempferol and rutin were isolated, the structures of which were decided by means of analysis of spectroscopic data to compare the values already reported. They were assessed for their alpha-glucosidase inhibitory activity. Gigantol, quercetin and kaempferolwere found to exhibit strong alpha-glucosidase inhibitory activity when compared with the positive control acarbose, while chrysotoxin, moscatilin and rutin were devoid of activity.

Analysis Of Pharmaceutical Inventory Management In A State Hospital In Myanmar, Mya Pann Thazin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Inventory management (IM) analysis in a state-level hospital pharmacy of Myanmar was done by using qualitative and quantitative analysis to classify the drug categories that require different levels of management control. Workflow analysis was qualitatively conducted using in-depth interviews of pharmacists. The annual expenditure consumed on each drug of pharmacy for the years 2016 and 2017 was analyzed and application of ABC, VEN, ABC-VEN matrix analysis was performed. The study showed a lack of classification for drug procurement, monitoring, and reporting. There was a lack of appropriate communication between hospital and central procurement, shortage of pharmacists, lack of training about …

Development Of Hyaluronic Acid-Based Nanogel Platform For Improved Stability And Polyvalent Ligand Display Of Poly(I:C) As An Effective Immunostimulatory Adjuvant In Cancer Immunotherapy, Nararat Kotcharat

Chulalongkorn University Theses and Dissertations (Chula ETD)

The aim of this research was to develop a nanogel formulation-based on modified natural polymer, hyaluronic acid (HA), as a biodegradable material for adjuvant delivery. Polyinosinic:polycytidylic acid (poly(I:C)) have been approved by FDA as a promising adjuvant candidate for the TLR3 (Toll-Like Receptor 3) activation. However, it suffers from being poor stability and is subjected to rapid enzymatic hydrolysis in serum, so that it requires high administered dose leading to adverse effects. To augment the adjuvant stability and protection from the degradation, the nano-particulate carriers were herein designed with self-assembly of HA scaffold grafted with poly (N-isopropylacrylamide), or pNIPAM. The …

Comparison Of Area Under The Curves For Vancomycin From One- And Two-Compartment Models Using Sparse Data, Nyein Hsu Maung

Chulalongkorn University Theses and Dissertations (Chula ETD)

Vancomycin pharmacokinetics has been described by 1- and 2-compartment models. One-compartment models built from routine monitoring data, which were mainly trough samples, are commonly used to predict area under the curves (AUC), the useful indicator for vancomycin efficacy. The question stands whether AUCs from 1-compartment models with sparse data can sufficiently represent the true AUC. This study aimed to compare AUCs from 1- and 2-compartment models using sparse data. A previously published model was used to simulate full individual profiles for 100 patients. From these data, the reference AUC (AUCref) was calculated and two depleted datasets (trough-only and peak-trough) were …

Development Of Recombinant Human Epidermal Growth Factor Production In Nicotiana Benthamiana, Oranicha Hanittinan

Chulalongkorn University Theses and Dissertations (Chula ETD)

Human epidermal growth factor (hEGF) is a short polypeptide that has gained clinical importance in the recent decade for wound healing. Currently, plant-based expression system is considered as an alternative viable platform for low-cost recombinant protein production. Hence, this study aims to produce hEGF in Nicotiana benthamiana plants via., transient expression using a geminiviral vector. The hEGF gene constructs were designed into six different constructs. The optimal expression was observed from the construct targeting the endoplasmic reticulum with C-terminal histidine tag at the yield level up to 15.695 µg/g LFW or 0.499% TSP. The plant-produced hEGF was purified by using …

Effect Of Dietary Advice On The Components Of Metabolic Syndrome In Hiv/Aids Patients With Metabolic Syndrome, Patcharee Ketchaleaw

Chulalongkorn University Theses and Dissertations (Chula ETD)

Metabolic syndrome is a complication found in HIV/AIDs patients. The patients with metabolic syndrome had increased risk of cardiovascular disease. An appropriate dietary advice may help ameliorate this problem. This study aimed to investigate the effect of dietary advice on components of metabolic syndrome including anthropometric parameters, lipid profiles, fasting blood sugar, and blood pressure in the HIV/AIDs with metabolic syndrome who were on highly active antiretroviral therapy. This study was a randomized controlled trial. Sixty participants were randomly assigned into an intervention group (n = 30) and a control group (n = 30). All patients received the advice with …

Pharmacokinetic And Metabolomic Studies Of Standardized Extract Of Centella Asiatica (Eca 233) Capsule In Thai Healthy Volunteers, Phanit Songvut

Chulalongkorn University Theses and Dissertations (Chula ETD)

A well-characterized standardized extract of Centella asiatica (ECa 233) being developed as a phytopharmaceutical product for human use was explored in this clinical study. The first objective of this research was to understand changes in disposition kinetics after oral administration of both the original-formula capsule and a newly-modified enhanced-dissolution capsule of ECa 233. Secondly, this study aimed to investigate alteration of human metabolomes following administration of the modified capsule of ECa 233, using an NMR-based metabolomics approach. For pharmacokinetics, the study involved a phase I clinical trial in twelve healthy Thai volunteers, who each received 250 and 500 mg of …

Development Of Nanoparticle-In-Microsphere(Nimos) System For Oral Delivery Of Vaccine And Antibody Against Ped Virus For Swine, Rachatapan Junchay

Chulalongkorn University Theses and Dissertations (Chula ETD)

PED virus is a major barrier to the animal farming industry, and it is the main cause of the mortality of suckling piglets up to 95% by enteric infection. The 2C10 monoclonal antibody (mAb) obtained from Nicotiana benthamiana produced by transient expression was indicated as one of the potential candidates is an antibody against PEDV by oral delivery. The biologics are a new wave of pharmaceuticals and have been continuously developing, which has various benefits of low toxicity and high specificity. However, it unsuitable for use with oral drug delivery owing to limitations of the strong acidity and protease of …

Factors Contributing To Pharmacists' Turnover Intention: A Systematic Review, Su Myat Thin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Pharmacist turnover could negatively impact not only work efficiency, organizational performance, work productivity, and customer satisfaction but also the quality of pharmaceutical services and patient safety. The turnover intention was a core antecedent of turnover, therefore, this study aimed to systematically review the extent of pharmacists' actual turnover and their intention to leave their jobs or the pharmacy profession, and to elaborate on the factors affecting the pharmacists' turnover intention and their associations. Studies related to any factors affecting pharmacists' turnover intention in all pharmacy settings were included. The QualSyst assessment tool was used for assessing the quality of the …

Protective Effects Of Lusianthridin On Hemin-Induced Low Density Lipoprotein Oxidation And Foam Cell Formation Of Raw 264.7 Macrophage Cells, Su Wutyi Thant

Chulalongkorn University Theses and Dissertations (Chula ETD)

Oxidation of low-density lipoprotein (LDL) take parts in a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin and cause oxidative stress-promoting vascular complications in thalassemia patients. Hemin was used as an oxidizing agent for LDL oxidation. Lusianthridin (LST) from Dendrobium venustum is a plant phenolic compound and possess antioxidant activity. The aim of this study is to evaluate the protective effect of lusianthridin on hemin-induced LDL oxidation (he-oxLDL) and foam cell formation in RAW 264.7 macrophage cell loaded with he-oxLDL treated with LST. Various concentrations of LST (0.25, 0.5, 1 and …

Production And Characterization Of Anti-Receptor Activator Of Nuclear Factor Kappa-B Ligand Monoclonal Antibody From Nicotiana Benthamiana, Wanuttha Boonyayothin

Chulalongkorn University Theses and Dissertations (Chula ETD)

Anti-RANKL monoclonal antibody is a fully human monoclonal antibody (mAb) available for treatment of osteoporosis. In this study, anti-RANKL mAb was transiently expressed using the Geminiviral expression system in Nicotiana benthamiana. Moreover, the structure of plant-produced mAb was characterized and functional activity was also determined. The result indicated that anti-RANKL mAb was produced with the maximum expression level on 8 days post infiltration and estimated to be 0.5 mg/g leaf fresh weight. The recombinant mAb from crude extracts was purified by using protein A affinity column chromatography. The plant-produced mAb provided in vitro affinity binding with human RANKL, determined by …

Anti-Migratory And Anti-Invasive Activities Of 22-O-(N-Boc-L-Glycine) Ester Of Renieramycin M Against Human Lung Cancer H460 Cells, Yamin Oo

Chulalongkorn University Theses and Dissertations (Chula ETD)

The incidence of metastasis stage crucially contributes to high recurrence and mortality rate in lung cancer patients. Unfortunately, no available treatment inhibits migration, a key metastasis process in lung cancer. In this study, the effect of 22-O-(N-Boc-L-glycine) ester of renieramycin M (22-Boc-Gly-RM), a semi-synthetic amino ester derivative of bistetrahydroisoquinolinequinone alkaloid isolated from Xestospongia sp., on migratory behavior of human lung cancer cells was investigated. Following 24 h of treatment, 22-Boc-Gly-RM at non-toxic concentrations (0.5-1 µM) effectively restrained motility of human lung cancer H460 cells assessed through wound healing, transwell migration and multicellular spheroid models. The capability to invade through matrix …

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 …

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 …

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 …