Pharmacy and Pharmaceutical Sciences Commons^™

Topoisomerase I Inhibitory Compounds From The Roots Of Paphiopedilum Callosum, San Yoon Nwe

Chulalongkorn University Theses and Dissertations (Chula ETD)

Paphiopedilum callosum (Rchb.f.) Stein belongs to the Orchidaceae family. The phytochemistry and bioactivity of this plant have not been previously reported. In this study, the chromatographic separation of methanolic extract of P. callosum roots was bioassay-guided by a yeast cell-based assay. One new compound, 3′-hydroxy-2,6,5′-trimethoxystilbene (PC1) and five known compounds including 3′-hydroxy-2,5′-dimethoxystilbene (PC2), 3-methylethergalangin (PC3), galangin (PC4), 2,3′-dihydroxy-5,5′-dimethoxystilbene (PC5) and 2,3′-dihydroxy-5′-methoxystilbene (PC6) were isolated. The chemical structures of these isolated compounds were elucidated and identified on the basis of analysis spectroscopic (ESI-MS, NMR and IR), as well as comparison with those reported in the literature. Their topoisomerase I poison activity …

Development Of Novel Phenanthroline And Thiazole Orange Derived G-Quadruplex Ligands And Telomerase Inhibitors, Siwen Wang

University of the Pacific Theses and Dissertations

The end of the human chromosome is protected by telomeres which contain a special tandem guanine-rich DNA sequence, 5’-TTAGGG. The length of telomeres is shortened during cell replications, and its length limits the replication capacity of cells. Telomerase is over-expressed in 85–90% of cancer cells, responsible for extending the telomere length in cancer cells. Guanine-rich DNA sequence can self-assemble into unique G-quadruplex structures that interfere with the extension of telomeres by telomerase. Therefore, DNA G-quadruplex has recently received much attention because of its important regulatory functions in telomerase-mediated cancerization. The formation of G-quadruplex requires monovalent cations (Na+ and K+) or …

Determining The Role Played By Aryl Hydrocarbon Receptor (Ahr) In The Colon Carcinoma Tumor Model, Poonam Yakkundi

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. Work from many researchers has suggested that AHR can act as a tumor promoter or a tumor suppressor depending on the tumor type. Our goal is to understand the role played by AHR in MC38 syngeneic colon carcinoma tumor model. In the absence of AHR, MC38 tumor …

Evaluation Of New Antimalarial Drug Combinations, Robert Tyrone Higginbotham

Honors Theses

Malaria is a disease that has affected people throughout the world for centuries and is still responsible for over 200 million clinical cases per year. While a number of developed countries have eradicated the disease, its prevalence in tropical regions poses a significant global health challenge. The disease is caused by the Plasmodium genus, an obligate, intracellular parasite that is carried by the female Anopheles mosquito. While there are effective antimalarial drugs in clinical use, Plasmodium's resilient nature has allowed it to develop resistance to multiple drugs. This fact makes it imperative to seek out novel drugs to combat resistant …

Evaluation Of Anthelmintic Properties And Toxicity Of Pure Compounds Isolated From Dalea Spp (Plantae, Fabaceae), Victoria Lh Mcpherson

All Master's Theses

Infecting upwards of a billion people worldwide, hookworm is one of the most prevalent parasitic infections affecting the world today. Those infected experience hookworm disease, characterized by severe anemia, which can lead to malnutrition, low birth weights, and physical and mental impairments. Currently, the benzimidazoles albendazole and mebendazole are used as the primary treatment; however, resistance to these drugs is emerging. Due to this resistance, finding new anthelmintic compounds active against hookworm is a priority. Previously, a pure compound isolated from Dalea ornata was identified as having strong anthelmintic activity when used against the hookworm Ancylostoma ceylanicum. This project …

Design And Analysis Of Curcumin Conjugated Poly(Beta-Amino Ester) Networks For Controlled Release In Oxidative Stress Environments, Carolyn T. Jordan

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress, the imbalance of free radical generation with antioxidant defenses, leads to cellular inflammation, apoptosis and cell death. This compromised environment results in debilitating diseases, such as oral mucositis (OM), atherosclerosis, and ischemia/reperfusion injury. Antioxidant therapeutics has been a proposed strategy to ameliorate these imbalances and maintain homeostatic environments. However, the success of these approaches, specifically curcumin, has been limited due to characteristics such as hydrophobicity and high reactivity when released as bolus doses to contest to oxidative stress induced diseases. The development of a controlled release system to aid in protection of the antioxidant capacity of curcumin, as …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

Effect Of Compliance Of Enhanced Recovery After Surgery Protocols On Pain Control At A Community Medical Center, Julia Dickman Pharmd, Stacy Clore Pharmd, Bcps, Jamie Gaul Pharmd, Bcps, Sarah Fitzpatrick Pharmd, Bcps

Parkview Pharmacy Department

2018 ASHP Midyear Clinical Meeting / Anaheim, California / Poster 11-307

Objective: Determine the utilization of the Enhanced Recovery After Surgery (ERAS) protocols at Parkview Regional Medical Center (PRMC) • Assess the impact of both preoperative (pre-op) and postoperative (post-op) ERAS protocols on post-op pain management and nausea and vomiting in comparison to utilization of only pre-op or only post-op ERAS protocols.

Adherence To Guideline Recommended Treatment Of Copd In Discharged Patients Following An Acute Exacerbation, Kalee N. Swanson, Alissa Keillor Pharmd, Dustin D Linn Pharmd, Bcps, Bcccp

Parkview Pharmacy Department

Poster Presentation

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, affecting more than 10 million Americans. Worldwide COPD is a disease of increasing public health importance as estimates suggest that COPD will rise from the fourth to the third most common cause of death by 2020. Increased exposure to risk factors and an aging population will attribute to even more patients with COPD. Adherence to guideline-recommended treatment regimens may decrease healthcare costs and improve patient outcomes. According to the GOLD guidelines, COPD pharmacotherapy recommendations are derived from the “ABCD” assessment tool, which …

Rational Design Of Peptides Binding Towards Human Pd-L1 Using Knob-Socket Model, Xingchen Zha

University of the Pacific Theses and Dissertations

Programmed death-ligand 1 (PD-L1) is a type 1 transmembrane protein that has been reported to play a vital role in mediating suppressed immunity. The interaction between PD-L1 and PD-1 delivers a negative signal that reduces the proliferation of these T cells and induces apoptosis at the same time. Antibodies that can block the Programmed death-ligand 1 (PD-L1) on tumor cells have been shown to alleviate cancer-induced immunosuppression. While antibodies have a great potential in various therapeutic uses, many drawbacks such as the high cost of production, huge molecular size, and poor permeability impose restrictions on the extensive use of full-length …

Bimetallic Complexes: The Fundamental Aspects Of Metal-Metal Interactions, Ligand Sterics And Application, Michael Bernard Pastor

University of the Pacific Theses and Dissertations

Metal containing complexes have been used to catalyze various organic transformations for the past few decades. The success of several mononuclear catalysts led to transition metal catalysts used in pharmaceuticals, environmental, and industrial processes. While mononuclear complexes have been used extensively, bimetallic systems have received far less attention. Bimetallic or polynuclear sites are commonly found in metalloenzymes that perform elegant transformation in biological systems, underlying their significance. Inorganic chemists take inspiration from nature and design model bimetallic complexes to further study this cooperativity effect. A bimetallic platform offers many structural and functional differences such as the identity of the metal …

Peptide-Drug Conjugate For Her2-Targeted Drug Delivery, Yan Wang

University of the Pacific Theses and Dissertations

Recent strategies for anticancer drug design have been focused on utilizing antibody as a drug or targeted moiety for targeted drug delivery. Antibody−drug conjugates (ADCs) have become a promising new class of targeted therapeutic agents for treatment of cancer. ADCs are designed to preferentially direct a cytotoxic drug to a cell-surface antigen recognized by an antibody. However, there are some challenges in developing ADCs, such as limited solid tumor penetration, high manufacturing costs and antibody-drug stoichiometry. Smaller molecules such as peptides have been shown to specifically bind to cancer related targets. These peptides can be used to form peptide-drug conjugates …

Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu

University of the Pacific Theses and Dissertations

Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling.

We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 …

Design And In Vitro Characterization Of Lipids With A Ph-Sensitive Conformational Switch And Their Liposomes For Anticancer Drug Delivery, Shen Zhao

University of the Pacific Theses and Dissertations

The traditional anticancer drugs are distributed in vivo through systemic blood circulation with a very small portion reaching the tumor site. Targeted drug delivery systems are developed in efforts to concentrate the drug molecules in the tissue of interest while reducing the drug distribution to healthy tissues to reduce the side effects. Liposomes are colloidal systems composed of amphiphilic molecules that assemble into vesicle structures in aqueous media. They are common carriers for targeted drug delivery with the advantages of low toxicity, low immunogenicity and the ability of encapsulating both lipophilic and hydrophilic drugs.

Prior research indicated the advantages of …

An Evaluation Of Mobile Apps For The Collation Of Materials To Propose An App For Type-2 Diabetes Self-Management, Sydney Watson

Honors Theses

This study is an evaluation of mobile application (apps) with the intention to collate materials appropriate for the proposal of a mobile app for type 2 diabetes self-management. In order to decipher the most vital aspects to be included in the app, an evaluation of mobile apps pertaining to nutrition and diabetes management were investigated. It was found that there is a lack of mobile apps that have all-encompassing features regarding the management of the disease. Future app developers looking to develop a mobile app that is efficient in type 2 diabetes self-management should include each feature as follows: blood …

Synthesis Of (2r,6r)-Hydroxy-Norketamine For Evaluation Of Antidepressant Effects, Savannah Fairley

Honors Theses

Major Depressive Disorder, colloquially known as depression, is a devastating mental illness that affects a large portion of today's population. Following a drug side-effect that caused depression, the monoamine theory of depression was created, stating that depressive symptoms were caused by a decrease in concentrations of vital monoamine neurotransmitters at the synaptic cleft. Pharmaceutical remedies to combat depression were first introduced in the 1950s and to this date, most available drugs follow the monoamine theory. These drugs have a large loading dose lag time, numerous negative side effects, and still many patients do not experience relief from symptoms. In 2000, …

Discovery Of Natural Product Analogs Against Ethanol-Induced Cytotoxicity In Hippocampal Slice Cultures, Meredith A. Saunders-Mattingly

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol (ethanol; EtOH) use disorder (AUD). While there are 4 medications approved by the Food and Drug Administration (FDA) to treat AUD, these treatments have demonstrated poor clinical efficacy. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about the mechanisms underlying EtOH-induced changes in neurobiology and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for AUD in a rodent organotypic hippocampal slice culture model. Initial screens of several natural product compounds identified …

Mechanisms Of Rad51d-Dependent Repair Of Dna And Telomere Damage Induced By Interstrand Crosslinking Agents And Thiopurines, Nicole M. Reilly

Theses and Dissertations

Mutations in homologous recombination (HR) genes increase genomic instability, an enabling characteristic of cancer. However, the status of these same genes can also determine chemotherapy outcomes. RAD51D is a breast and ovarian cancer susceptibility gene that is an important component of HR. Mammalian cells defective for RAD51D have extensive chromosomal aberrations and are more sensitive to the interstrand crosslink-inducing agent mitomycin C (MMC) and the thiopurine 6-thioguanine (6TG). Previously, the RNF138 E3 ubiquitin ligase was identified to promote RAD51D ubiquitination, and loss of RNF138 also increased cellular sensitivity to MMC. Ubiquitination assays were used to show that a 3-ubiquitin modification …

Mechanistic Study Of P23-Mediated Aryl Hydrocarbon Receptor Expression, Beverly Pappas

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which is involved in diverse biological functions ranging from cancer metastasis to immune regulation. This receptor forms a cytoplasmic complex with Hsp90, p23, and XAP2. We have previously reported that down-regulation of p23 triggers degradation of the AHR protein, uncovering a potentially dynamic event which controls the cellular AHR levels without ligand treatment. Here we investigate the underlying mechanisms for this p23 effect using wild-type HeLa and the p23 knockdown HeLa cells. Reduction of the Hsp90 and XAP2 contents, however, did not affect the AHR protein levels, implying that this …

The Molecular Pathophysiology Of Sepsis-Associated Disseminated Intravascular Coagulation And Its Pharmacologic Modulation, Amanda Temple Walborn

Dissertations

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection. Sepsis patients are at risk of disseminated intravascular coagulation (DIC), a severe blood coagulation disorder. In DIC, inappropriate coagulation leads to the deposition of fibrin in the microvasculature and subsequent organ failure. This consumes platelets and coagulation factors, leaving patients at risk of severe or fatal bleeding. No treatments are approved for DIC in the United States.

In order to test the hypothesis that DIC would be best described by a combination of biomarkers representative of multiple physiological processes, an array of biomarkers, representative of hemostasis, inflammation, …

Mechanistic Study Of Potential Herbal Extracts For Development Into Hair Growth-Promoting Product, Woraanong Prugsakij

Chulalongkorn University Theses and Dissertations (Chula ETD)

Androgenic alopecia (AGA) is a major type of hair loss found in both males and females, caused by the overproduction of 5 alpha-dihydrotestosterone (DHT) which is formed from testosterone (T) by the enzymes 5 alpha-reductase (5α-R). In this study, the main focus was on cytokine factors evaluation of Avicennia marina (AM extract) in primary dermal papilla cells (DPCs) from AGA patients and the efficacy in vivo. The present study has revealed that AM extract and its active constituent, avicequinone C (AC) significantly inhibit the enzyme activity of 5α-R on cell-based assay combined with a non-radioactive thin layer chromatography (TLC) using …

Chemosensitizing Effect Of Peptides From Lentinus Squarrosulus On Cisplatin-Induced Apoptosis In Human Lung Cancer Cells, Hnin Ei Ei Khine -

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cisplatin, platinum-based chemotherapy, is one of the standard chemotherapies for the treatment of lung cancer. However, its usefulness is limited due to the adverse effects and susceptibility to chemoresistance which lead to therapeutic failure. Nowadays, natural chemosensitizers, which can enhance the efficacy and decrease the effective dose of chemo-drugs, have been found to be interested in novel therapeutic. Recently, the anticancer activity of peptides extracted from Lentinus squarrosulus Mont. in human lung cancer cells has been reported. The novel potential of L. squarrosulus peptides as a chemotherapeutic adjuvant to increase cisplatin-induced apoptosis was uncovered in this study. Crude peptides extracted …

Effects Of 4,5,4'-Trihydroxy-3,3'-Dimethoxybibenzyl From Dendrobium Ellipsophyllum On Induction Of Apoptosis And Inhibition Of Cancer Stem-Like Cells In Human Lung Cancer H460 Cells, Anirut Hlosrichok

Chulalongkorn University Theses and Dissertations (Chula ETD)

Failure of current chemotherapeutic drugs leads to the recurrence of tumors and increased mortality in lung cancer patients. This study investigated 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang as a novel anticancer agent for lung cancer. Selective anticancer activity of TDB against human lung cancer cells was demonstrated with a high half maximal inhibitory concentration (IC50) approximately > 300 µM in dermal papilla cells, while IC50 in human lung cancer H460 cells was approximately 100 ± 5.18 µM. Flow cytometry confirmed that TDB (50 µM) treatment for 24 h, caused significant early and late apoptosis but not …

Effect Of Major Triterpenoids Of Centella Asiatica On Neurite Outgrowth In Neuro-2a Cells, Nonthaneth Nalinratana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Centella asiatica has been reported to demonstrate neuroprotection and memory improvement in various animal models. Triterpenoid glycosides, madecassoside (MS), asiaticoside (AS), and their aglycones, madecassic acid (MA) and asiatic acid (AA) are considered as major neuroactive constituents in C. asiatica. In this study we aimed to compared MS, AS, MA and AA for their neurite outgrowth activities and mechanisms in Neuro-2a cells. Immunofluorescent staining against ßIII-tubulin showed that MS and AS significantly increased the percentage of neurite-bearing cells and neurite length with higher potency than MA and AA. Our mechanistic studies revealed the differences in signal activation between glycosides and …

A Study On The In Vitro Stability And Metabolism Of Curcumin Diethyl Disuccinate In Plasma, Pahweenvaj Ratnatilaka Na Bhuket

Chulalongkorn University Theses and Dissertations (Chula ETD)

Stability in aqueous media such as buffers and plasma are the one of important properties of drug candidates. Curcumin diethyl disuccinate (CDD), an ester prodrug of curcumin, has been developed to improve the chemical stability of curcumin. In this study, the in vitro stability of CDD in HCl buffer (pH 1.2), acetate buffer (pH 4.5), phosphate buffer (pH 6.8, 7.4 and 8.0) and in vitro metabolism of CDD in rat, dog and human plasma were investigated at 4, 25 and 37 °C. HPLC and nonlinear regression analyses showed that the degradation of CDD in buffers was temperature-dependent and followed pseudo-1st …

Effect Of Ercc1, Xrcc1 And Gstp1 Polymorphisms On Clinical Response And Adverse Events Of Platinum-Based Chemotherapy In Epithelial Ovarian Cancer Patients, Salisa Liblab

Chulalongkorn University Theses and Dissertations (Chula ETD)

Platinum-based chemotherapy is the first line chemotherapy regimen for epithelial ovarian cancer (EOC). Pharmacogenomics is one factor that might affect its efficacy and toxicity. This cohort study was aimed to investigate the association between ERCC1, XRCC1 and GSTP1 polymorphisms on clinical responses and adverse events related to platinum-based chemotherapy in Thai EOC patients. Fifty-two patients with advanced EOC were enrolled in this cohort study. The mean age was 55.7 years old. Genotyping analysis of ERCC1 (C>A, rs3212986), XRCC1 (A>G, rs25487) and GSTP (A>G, rs1695) were performed which allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. …

Effect Of Bitter Gourd Extracts On The Mutagenicity Of 1-Aminopyrene Reacted With Nitrite Using Ames Test, Korkiat Panpasuk

Chulalongkorn University Theses and Dissertations (Chula ETD)

This study was conducted to investigate the mutagenic activity of raw and cooked bitter gourd (Momordica charantia) including raw fruit extract (RW), blanching water (BW), hot water extract from blanched fruit (HB), stir-fried fruit extract (SF), and stir-fried fruit (pre-squeezed with salt) extract (SS). In addition, the effects of extracts in modifying the mutagenic activity of mutagen freshly prepared by the reaction between 1-aminopyrene and sodium nitrite and the effects when adding each extract at the beginning of the same reaction using Ames test on Salmonella typhimurium strains TA98 and TA100 without enzymatic activation were also determined. The data for …

Antioxidant And Antimutagenic Activity Of Extracts From Pericarp And Seed Of Zanthoxylum Limonella Alston, Patamawan Wipoosanapan

Chulalongkorn University Theses and Dissertations (Chula ETD)

This study was conducted to investigate the antioxidant and antimutagenic activity of Zanthoxylum limonella seed extract and that of Z. limonella pericarp extract. The total phenolic contents and antioxidant activity assay including DPPH assay and FRAP assay were performed. The results showed that the antioxidant activity of pericarp extract was higher than that of the seed extract. The direct mutagenicity assay was determined, with and without nitrite treatment using the Ames test towards Salmonella typhimurium strains TA98 and TA100. The mutagenic modification assay was performed by measuring the interfering effect of the pericarp extract and the seed extract on the …

Preparation And Antimicrobial Activity Of Caprylic Acid Emulsion For Food Coating, Raweewan Bunyovimonnat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Antimicrobial food coating is the interesting method for food preservation, especially in fruits and vegetables. Previous studies have been reported that the caprylic acid had the antimicrobial activity against a variety of microorganisms. However, little research has been conducted on the use of caprylic acid in the form of food coatings. Therefore, this study aims to determine the optimum conditions for the caprylic acid emulsion preparation and to evaluate the antimicrobial activity of the emulsion, including the effect of food coatings with caprylic acid emulsion on physical properties and microbial growth inhibition. Emulsions containing 4% w/v caprylic acid (oil) and …

Carbohydrate Content Of The Medications For Epileptic Children Treated With Ketogenic Diet At King Chulalongkorn Memorial Hospital, Thanarat Sawangrit

Chulalongkorn University Theses and Dissertations (Chula ETD)

The purposes of this study were to establish a database of the carbohydrate content of medications and investigate carbohydrate content of medications in epileptic children treated with ketogenic diet (KD) at King Chulalongkorn Memorial Hospital. One hundred sixty-nine KD order forms in 3 events (KD initiation, follow-up visit, and hospital re-admission) for epileptic children whose aged younger than 18 years old during 2009-2017 were selected. Clinical and nutritional data were obtained from medical records and KD order forms from the pediatric nutrition unit. The study showed that oral liquid dosage forms had the highest carbohydrate content in the formulations as …