Pharmacy and Pharmaceutical Sciences Commons^™

Effects Of Slco1b3, Abcb1 And Cyp3a5 Polymorphisms On Clinical Response And Adverse Events Of Paclitaxel-Based Chemotherapy In Advanced Non-Small-Cell Lung Cancer Patients, Pawienar Mueangprom

Chulalongkorn University Theses and Dissertations (Chula ETD)

Paclitaxel is recommended first-line therapy for patients with advanced non-small cell lung cancer. Genetic polymorphisms of Paclitaxel’s metabolic pathway may affect treatment outcomes and adverse events. The purpose of this study was to determine the association of genetic polymorphisms and clinical outcomes. A total of 58 Thai NSCLC patients with Paclitaxel-based chemotherapy were enrolled for this cohort study. The prevalence of variant allele of SLCO1B3 (rs7311358), ABCB1 (rs2032582) and CYP3A5 (rs776746) were 72.4%, 40.5% and 67.5%, respectively. This study found that SLCO1B3, ABCB1 and CYP3A5 polymorphisms were not associated with clinical response and clinical benefit in paclitaxel-based chemotherapy among Thai …

Genome, Physicochemical Properties And Esterase Gene Cloning Of Novel Lentibacillus And Halobacillus Species, Auttaporn Booncharoen

Chulalongkorn University Theses and Dissertations (Chula ETD)

A total of 831 moderately halophilic bacteria isolated from various samples in Thailand were screened for their lipolytic activity. Three hundred and forty-nine isolates showed activity on agar plate while 322 isolates exhibited in broth. The grouping and identification of 322 isolates based on DNA-fingerprinting using (GTG)5+ERIC2 primer and 16S rRNA gene sequence, 180 DNA patterns could be generated. The result indicated that the representative isolates belonged to genera Bacillus, Halobacillus, Lentibacillus, Marinobacter, Thallossobacillus, and Virgibacillus. On the basis of polyphasic taxonomic study and genome analysis, a selected moderately halophilic strain SSKP1-9T, Gram-staining-positive, aerobic, endospore-forming, rod-shaped was closely related to …

In Vitro Antiplatelet Activity Of Lusianthridin In Human Platelets, Hla Nu Swe

Chulalongkorn University Theses and Dissertations (Chula ETD)

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. The objective of this study is to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. Turbidometric aggregometry method was used to measure the extent of platelet aggregation, then cyclic adenosine monophosphate (cAMP) levels were measured by ELISA kit. Inhibitory effect of lusianthridin on cyclooxygenase enzymes was analyzed by COX fluorescent inhibitor screening assay kit. The results indicated that Lusianthridin most potently inhibited arachidonic acid -induced platelet aggregation by maximum percent inhibition of aggregation of 89.7 ± 1.2 …

Cytotoxic Constituents Of Cymbidium Finlaysonianum And Paphiopedilum Dianthum, Nonthalert Lertnitikul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chemical investigation of two orchids native to Thailand led to the isolation of eighteen compounds. From the whole plants of Cymbidium finlaysonianum Wall. ex Lindl, a new dihydrophenanthrene, 1-(4-hydroxybenzyl)-2,7-dihydroxy-4,6-dimethoxy-9,10-dihydrophenan-threne, and nine known stilbenoids, including a phenanthrenequinone, cymbinodin-A, a dihydrophenanthrenequinone, ephemeranthoquinone B, a bibenzyl, batatasin III, two phenanthrenes, 2,4-dimethoxy-3,7-dihydroxyphenanthrene and 3,7-dihydroxy-2,4,6-trimethoxyphenanthrene, and four dihydrophenanthrenes i.e. coelonin, 6-methoxycoelonin, flavanthridin and lusianthridin, were obtained. From the roots and leaves of Paphiopedilum dianthum Tang & Wang, two new stilbene dimers, paphiodianthins A and B, were isolated along with three known stilbenes i.e. pinosylvin monomethyl ether, 2,3'-dihydroxy-5'-methoxystilbene and (E)-2,5'-dihydroxy-2'-(4-hydroxybenzyl)-3'-methoxystilbene, and three known flavonoids i.e. isalpinin, …

Protective Mechanisms Of Polyphenols Against Nsaids-Induced Intestinal Cell Death In Caco-2 Cells, Cherdsak Boonyong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Indomethacin (INDO) and diclofenac (DIC) cause intestinal cell death through reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and mitochondrial dysfunction. This study investigated the cytoprotective effects of certain natural polyphenolic antioxidants against INDO- and DIC-mediated Caco-2 cell death as well as underlying mechanisms. In this study, caffeic acid (CAF), curcumin (CUR), epigallocatechin gallate (EGCG), gallic acid (GAL), hypophyllanthin (HYPO), naringenin (NAR), phyllanthin (PHY), piperine (PIP), quercetin (QUE), rutin (RUT) and silymarin (SLY) were able to decrease ROS production in Caco-2 cells treated with INDO and DIC. However, only EGCG, QUE and RUT (100 µM) could prevent INDO- and …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Development Of Bivalent Ligands Targeting The Putative Mu Opioid Receptor And Chemokine Receptor Cxcr4 Heterodimer, Bethany A. Reinecke

Theses and Dissertations

Human immunodeficiency virus (HIV) and opioid abuse have been described as synergistic epidemics. Pharmacologically, it has been found that opioids have the capacity to enhance HIV infection and replication. Research has shown that activation of the mu-opioid receptor (MOR) elevates the expression of the HIV-1 entry co-receptor CXCR4 on T-lymphocytes in the peripheral nervous system, thus allowing for enhanced viral entry and invasion. Although the exact mechanism for opioid modulation of CXCR4 expression and subsequent exacerbation of HIV is unknown, several hypotheses exist. One hypothesis is that MOR and CXCR4 are functionally interacting through the formation of a heterodimer. This …

Effects Of Rhinacanthin-C In Multidrug-Resistance Breast Cancer Cells, Suwichak Chaisit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Rhinacanthin-C (RN-C) is a major bioactive naphthoquinone ester found in Rhinacanthus nasutus Kurz (Acanthaceae). This compound has potential therapeutic value as an anticancer agent. Rhinacanthin-C was reported to enhance doxorubicin cytotoxicity in breast cancer cells through direct inhibition of P-gp activity. However, its ability in reversing multidrug resistance (MDR) in cancer cells through the down-regulation of P-gp expression, alteration of detoxification system, and increase in apoptosis proteins remains unreported. Thus, this study was to investigate the potential MDR reversal effect of rhinacanthin-C and its underlying mechanisms in MCF-7/DOX. In this study, rhinacanthin-C (1 µM, 48 h) significantly enhanced cytotoxicity of …

Effect Of Sulfobutyl Ether Β-Cyclodextrins On Oral And Dermal Pharmacokinetics Of Drugs, Vijay Kumar Shankar

Electronic Theses and Dissertations

Silymarin is an extract of Milk Thistle, major constituents are taxifolin, silychristin, silydianin, silybin A, silybin B, isosilybin A and isosilybin B. The in vitro, preclinical and clinical studies have demonstrated silymarin possesses hepatoprotective, anticancer, hypocholesterolemic, cardioprotective effect and dermatological beneficial effect (treatment of UV induced erythema, melanoma, non-melanoma skin cancer, rosacea, melasma, vitiligo and psoriasis) both individually and collectively. Solubility enhancement of silymarin constituent is utmost important to increase bioavailability and to improve drug developability property. The solubility of silymarin in water was enhanced by SBE-β-CD by conventional and heating method, heating method was found to be more efficient …

Pegylated Nanostructured Lipid Carries For Amphotericin B Ocular Delivery, Prit Manish Lakhani

Electronic Theses and Dissertations

The Chapter II focuses on formulation of an optimized and robust amphotericin B ocular formulation with prolonged precorneal residence and ocular tissue concentration at par or superior to the marketed preparations. Additionally, demonstrating stability of amphotericin B formulations in presence of preservative in comparison to marketed preparation, making it an ideal choice of formulation for multi-dosing. As mentioned earlier, we optimized PEGylated nanostructured lipid carriers (PEG-NLC-AmB) for ocular delivery of amphotericin B. The formulations could be autoclaved with at least one-month stability and in vivo ocular biodistribution was statistically insignificantly different compared to AmBisome®. To accomplish the aim, strategies such …

Effect Of Solvent Interaction & Soluble Microneedles On Skin Permeability To Drug Molecules, Abhijeet Maurya

Electronic Theses and Dissertations

Skin forms a formidable barrier protecting the human body from external environmental rigors and excessive loss of water; maintaining equilibrium. The barrier properties of the skin can be attributed to its unique macromolecular organization and morphology. As a route for drug administration, skin presents a large surface area and can be used for both systemic and localized targeted drug delivery applications offering several advantages over conventional drug therapy; avoidance of first pass metabolism, patient compliance, sustained or controlled delivery for an extended period, to name a few. However, the organized structure of the skin, since intended to prevent entry of …

Novel Applications Of Hot-Melt Extrusion Technology In Trans-Buccal And Topical Drug Delivery Systems, Nicole Mendonsa

Electronic Theses and Dissertations

As the buccal route of administration can avoid the first pass effect, the bioavailability of drugs that are metabolized in the liver can be increased through this route. Few studies have been conducted using oleic acid as a permeation enhancer in any trans-buccal dosage form. The objective of this study was to develop a buccal tablet using two concentrations of oleic acid for a model drug (Ondansetron) via melt extrusion technology and investigate the effects of oleic acid on the physicochemical properties of the tablet. Formulations consisting of the active drug (ondansetron hydrochloride), polymers and oleic acid were prepared by …

Testing A Modified Model Of Stress Process For Understanding Quality Of Life Among Informal Caregivers And Assessing Their Formal Service Use, Nilesh V. Gangan

Electronic Theses and Dissertations

Informal caregivers provide timely care to family members who are disabled or have a chronic condition that requires close monitoring or constant assistance. To provide adequate support to informal caregivers there is a need to assess ways to improve their quality of life (QOL) and understand how formal services can be improved. This dissertation strives to extend the knowledge available for policy makers by examining the factors that can be targeted by policy makers to improve QOL of informal caregivers as well as the factors that enable the use of formal services provided to support informal caregivers. The psychometric properties …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Animal Model Of Major Depressive Disorder, Sami Alzarea

Electronic Theses and Dissertations

Major depressive disorder (MDD) is the most prevalent psychiatric disorder, affecting about 10% of the global population and is the leading cause of disability in USA. Nearly one-third of depressed patients fail to respond to conventional antidepressant therapies. Therefore, novel therapies are needed, and require a new target and molecular mechanisms underlying MDD. Brain glial mechanisms, specifically, microglial α7 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important target for MDD associated with neuroinflammation. We hypothesized that microglial α7 nAChRs positive allosteric modulator (PAM) has an important role in the regulation of behavioral, cellular, biochemical and molecular mechanisms underlying …

Evaluation Of The Effect Of Carvedilol On The Thioredoxin Pathway In H9c2 Rat Cardiomyocytes, Metab Alharbi

Electronic Theses and Dissertations

The thioredoxin (Trx) system is an endogenous antioxidant system that affects cell function and survival through controlling cellular redox status. Trx and TrxR are the main enzymes in this system while thioredoxin interacting protein (TXNIP) is a negative regulator. This study’s goal was to better understand the Trx system’s involvement in the cardiovascular disease and modulate the pathway through drug treatment. Carvedilol is a non-selective β-blocker that also exhibits antioxidant properties, but the exact mechanism of the antioxidant effect is still unclear. H9c2 rat cardiomyocytes were used to examine the effect of carvedilol on the Trx system under normal conditions. …

Development Of Tissue-Derived Biomaterial ‘Cornea-Ecmix’: Its Utility In The Management Of Corneal Diseases, Somshuvra Bhattacharya

Electronic Theses and Dissertations

Transparent cornea, at the front of the eye, mediates vision by refracting incoming light. Due to its anatomical position, cornea is susceptible to a variety of physical and chemical insults. Severe damage caused to cornea due to trauma or disease conditions can impair vision. While the cornea’s inherent repair mechanism restores partial vision loss, transplantation is the only viable treatment option if its transparency is completely lost. A global shortage of transplantable donor tissues necessitates the need for the development of functional corneal prosthetics. As cornea mostly is made up of extracellular matrix (ECM), several studies have explored the utility …

Thiol Specific Fluorogenic Agents For Live Cell Subcellular Organelle Thiol Imaging, Yahya Alqahtani

Electronic Theses and Dissertations

Thiols or sulfhydryl groups (-SH) play a significant role in protein structures and functions. The unique properties of a thiol group are the basis for its roles in cellular functions. Structurally, thiols are divided into protein thiols (PSH) and non-protein thiols (NPSH). NPSH include glutathione, cysteine, and homocysteine. Thiols are distributed in an uneven manner in the cell and subcellular organelles. Disturbance of thiol levels has been associated with serious diseases such as cancer, aging, cardiovascular diseases, Alzheimer disease, liver damage, and edema. The significant roles of thiols in the biological system have stimulated the development of various approaches to …

Long-Acting Intraductal Drug Delivery Systems For The Breast, Mibin Joseph

Electronic Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer in women in the US. Ductal carcinoma in situ (DCIS) is a premalignant lesion that has not metastasized through the regional lymph nodes to other organs. Currently, all breast cancers including localized breast cancers are treated with the same aggressive therapy. Localized drug delivery by direct intraductal injections into the mammary ducts can achieve high drug concentration at the target site. However, poor retention of drugs in the ducts limits the successful translation of this approach to the clinic. To this end, the main goal of this dissertation is to develop …

Effect Of Rurality On Diabetes-Related Hospitalizations In A Small Acute Care Hospital In Jackson County, Indiana, Lindsey Ridlen

Undergraduate Honors Thesis Collection

Patient access to healthcare can be a potentially significant barrier to overall health outcomes, especially when paired with a costly and complex disease state such as diabetes. The purpose of this study was to determine if patients with Type 2 diabetes mellitus living in rural areas of Jackson County experience greater health disparity and more diabetes-related hospitalizations than those living in non-rural areas. The study was conducted at Schneck Medical Center in Seymour, Indiana. A total of 164 patients were included in the final analysis based on the presence of a diabetes-related diagnosis code in the patient’s chart; of these, …

Comparison Of Patient Outcomes In A Pharmacist-Led Outpatient Parenteral Antimicrobial Therapy Program, Zachary Howe

Undergraduate Honors Thesis Collection

Purpose: Outpatient parenteral antimicrobial therapy (OPAT) is a therapeutic option meant to conserve healthcare resources when treating infections requiring the administration of IV antibiotics over a prolonged treatment course. In November 2016 at Franciscan Alliance Indianapolis, a dedicated pharmacist was hired to build a formal OPAT program for all patients discharged on IV antimicrobials under the care of the infectious disease physician group. The number of “good catch” events observed since the program’s formal inception has encouraged the creation of this study designed to examine the impact of this program on patient outcomes and antimicrobial stewardship.

Methods: This was a …

Preparation And Characterization Of Multimodal Hybrid Organic And Inorganic Nanocrystals Of Camptothecin And Gold, Christin P. Hollis, Alan K. Dozier, Barbara L. Knutson, Tonglei Li

Pharmaceutical Sciences Faculty Publications

We demonstrate a novel inorganic-organic crystalline nanoconstruct, where gold atoms were imbedded in the crystal lattices as defects of camptothecin nanocrystals, suggesting its potential use as simultaneous agents for cancer therapy and bioimaging. The incorporation of gold, a potential computed tomography (CT) contrast agent, in the nanocrystals of camptothecin was detected by transmission electron microscope (TEM) and further quantified by energy dispersive X-ray spectrometry (EDS) and inductively coupled plasma-optical emission spectrometers (ICP-OES). Due to gold's high attenuation coefficient, only a relatively small amount needs to be present in order to create a good noise-to-contrast ratio in CT imaging. The imbedded …

Methods To Quantify Nanomaterial Association With, And Distribution Across, The Blood-Brain Barrier In Vivo, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. …

Actionable Patient Safety Solutions (Apss) #6: Hand-Off Communications, Steven Barker, Nick Adams, Misti B. Baskett, Victoria Baskett, Michael Becker, Michel Bennett, Laressa Bethishou, Mike Ramsay, Jeff Dunn, Hisham El-Bayar, William Floyd, Frank Gencorelli, Christina Hazekamp, Kristy Blomquist, Edwin Loftin, Ariana Longley, Jacob Lopez, David Lubarsky, Pete Melrose, Brent Nibarger, Karen Rehling, Patricia Roth, Kris Stegner, Laura Townsend

Pharmacy Faculty Articles and Research

Hand-off communications, or hand-off processes, involve the transition of care as well as the transfer of patient-specific information by one healthcare professional to another with the purpose of providing a patient with safe, continuous care. A successful hand-off can only be achieved by effective communication.

Drug Repositioning Based On Bounded Nuclear Norm Regularization, Mengyun Yang, Huimin Lao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Computational drug repositioning is a cost-effective strategy to identify novel indications for existing drugs. Drug repositioning is often modeled as a recommendation system problem. Taking advantage of the known drug–disease associations, the objective of the recommendation system is to identify new treatments by filling out the unknown entries in the drug–disease association matrix, which is known as matrix completion. Underpinned by the fact that common molecular pathways contribute to many different diseases, the recommendation system assumes that the underlying latent factors determining drug–disease associations are highly correlated. In other words, the drug–disease matrix to be completed is low-rank. Accordingly, …

At Risk Alcohol Consumption With Smoking By National Background: Results From The Hispanic Community Health Study/Study Of Latinos, Frank C. Bandiera, Eliseo J. Pérez-Stable, Folefac Atem, Raul Caetano, Denise C. Vidot, Marc D. Gellman, Elena L. Navas-Nacher, Jianwen Cai, Gregory Talavera, Neil Schneiderman, Robert Kaplan

United States Food and Drug Administration: Publications

Introduction: Tobacco smoking and binge or excess drinking are unhealthy behaviors that frequently co-occur. Studies of Hispanics/Latinos have mostly been of Mexican Americans although there are substantial differences in smoking and drinking by heritage background. Associated with co-use by 5 subpopulations.

Methods: Cross-sectional data of 16,412 Hispanics/Latinos from Miami, the Bronx, Chicago and San Diego collected between 2008 and 2011 as part of the HCHS/SOL were analyzed. Smoking and alcohol consumption and demographic data were measured by self-report. Prevalence of smoking and alcohol consumption and co-use were reported. Logistic regression models examined the odds of co-use of smoking and binge …

Comparing Methods For Clinical Investigator Site Inspection Selection: A Comparison Of Site Selection Methods Of Investigators In Clinical Trials, Nicholas Hein, Elena Rantou, Paul Schuette

United States Food and Drug Administration: Publications

Background During the past two decades, the number and complexity of clinical trials have risen dramatically increasing the difficulty of choosing sites for inspection. FDA’s resources are limited and so sites should be chosen with care.

Purpose To determine if data mining techniques and/or unsupervised statistical monitoring can assist with the process of identifying potential clinical sites for inspection.

Methods Five summary-level clinical site datasets from four new drug applications (NDA) and one biologics license application (BLA), where the FDA had performed or had planned site inspections, were used. The num- ber of sites inspected and the results of the …

Phytochemical Investigation And Drug Interaction Potential Of Cyanotis Vaga, Ibrahim Almarabi

Electronic Theses and Dissertations

Cyanotis. vaga (Lour.) Schult, & Schult. f. (C. vaga) previously called Tradescantia vaga and Cyanotis barbata, is a perennial herb. It is native to Eastern Asia and Tropical Africa. It has been reported that its decoction reduces fever and enhances well-being. Recently, C. vaga has been used widely for its anabolic effects, due to its richness of ecdysteroids. Even though C. vaga is a commedicinal plant (dietary supplement), there are no reports about its effect on the drug metabolizing enzyme Cytochromes P450 to predict its interaction with concomitantly used medications. In this study, eight ecdysteroids were isolated …

Cheminformatic Approach For Deconvolution Of Active Compounds In A Complex Mixture - Phytoserms In Licorice, Manal Mohammad Alhusban

Electronic Theses and Dissertations

ABSTRACT After the validation of our in silico models by using the previous knowledge in this area the alerting phytochemicals from two Glycyrrhiza species (G. glabra and G. uralensis) were clustered. Exhaustive computational mining of licorice metabolome against selected endocrinal and metabolic targets led to the discovery of a unique class of compounds which belong to the dihydrostilbenoids (DHS) class appended with prenyl groups at various positions. To the best of our knowledge this interesting group of compounds has not been studied for their estrogenic activities or PXR activation. In addition some of the bis-prenylated DHS have been reported to …

Comparative Characteristics Of Antibacterial Activity Of Plants Growing In The Central Part Of The Republic Of Tajikistan., Saidbeg Satorov, F. Mirzoeva, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: To evaluate the spectrum of antibacterial activity of plants growing in the central part of the Republic of Tajikistan.
Methods: The antibacterial properties of 18 plant species from the 14 families were studied. The extract samples on dry filter discs were prepared according to the method developed at Rutgers University. Screens-to-Nature (STN) and disc diffusion (DD) methods were used to assess antimicrobial properties of the extracts. The antimicrobial activity of plant extracts was determined against four types of pathogenic standard museum strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, as well as …

Localized Transdermal Delivery Of Chemopreventive Agents To The Breast, Abdulsalam Alqahtani

Electronic Theses and Dissertations

Breast cancer is the second leading cause of cancer death in women. About 1 in 8 women will develop breast cancer in their lifetime. The current systemic approaches are associated with significant side effects including some life-threatening toxicity, leading to poor patient compliance. To overcome this limitation, localized transdermal drug delivery system was investigated in the current study. In addition, majority of breast cancers originate from the ducts and lobules in the breast. Therefore, localized transdermal drug delivery system can maximize drug concentration in the breast and minimize systemic adverse effects, resulting in a potential approach for preventing and/or treating …