Medicine and Health Sciences Commons^™

Phytochemicals With Α-Glucosidase Inhibitory Activity From Cissus Javana, Dendrobium Christyanum, Gastrochilus Bellinus And Huberantha Jenkinsii, Htoo Tint San

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemical investigations of Cissus javana DC., Dendrobium christyanum Rchb. f., Gastrochilus bellinus Rchb. f. Kuntze and Huberantha jenkinsii (Hook. f. & Thomson) Chaowasku led to the isolation of twenty-seven compounds, six of which were new naturally occurring compounds. From Cissus javana, three known compounds were isolated, including bergenin, stigmast-4-en-3-one, and β-sitosterol. From Dendrobium christyanum, thirteen known compounds were identified, namely, n-eicosyl trans-ferulate, n-docosyl 4-hydroxy-trans-cinnamate, 4,5-dihydroxy-2-methoxy-9,10-dihydrophenanthrene, moscatilin, aloifol I, gigantol, batatasin III, dendrosinen B, coniferyl aldehyde, methyl haematommate, atraric acid, vanillin and diorcinolic acid. From Gastrochilus bellinus, four new compounds, comprising three phenanthropyrans and a phenanthrene derivative, were isolated and structurally …

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 …

Bioengineered Regenerative Therapy For Diabetes Mellitus: Establishment Of Canine Mesenchymal Stem Cell-Derived Insulin Producing Cells, Watchareewan Rodprasert

Chulalongkorn University Theses and Dissertations (Chula ETD)

Trend of regenerative therapy for diabetes in human and veterinary practice has conceptually been proven according to Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource is a challenge task for further clinical application. In this study, IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs), was of interest. The results illustrated that cBM-MSCs and cAD-MSCs contained distinct pancreatic differentiation potential and required the tailor-made induction protocols. Generation of functional cBM-MSC-derived IPCs needed an integration of genetic and microenvironment manipulation using hanging-drop culture of PDX-1-transfected cBM-MSCs …

Association Between Nat2 Polymorphisms And Anti-Tuberculosis Drug-Induced Liver Injury In Myanmar Patients In Thailand, Khin Sandi Thaw

Chulalongkorn University Theses and Dissertations (Chula ETD)

The aims of this study were to determine the N-acetyl transferase 2 (NAT2) genetic distribution of Myanmar tuberculosis (TB) patients and evaluate the association of NAT2 polymorphisms and antituberculosis drug-induced liver injury (AT-DILI) in Myanmar patients. A case-control study was conducted in adult Myanmar TB patients at Samut Sakorn Hospital. Fifty-four patients who completed anti-TB treatment without liver injury (controls) and five patients with AT-DILI during their anti-TB treatment (cases) were enrolled. Patients’ baseline characteristics, anti-TB doses, and liver enzyme levels were collected from the hospital’s record. Blood samples were collected and four NAT2 SNPs, rs1041983, rs1799929, rs1799930, and rs1799931, …

Effect Of Gigantol On Tumorigenicity Of Non-Small Cell Lung Cancer Cells Via Cancer Stem Cell Signal Suppression, Nattanan Losuwannarak

Chulalongkorn University Theses and Dissertations (Chula ETD)

Lung cancer is a major cause of cancer-related death. Tumor growth is a fundamental process of cancer progression. Vital characteristics that potentiate tumor growth are cancer stem cell (CSC) and enhance cell proliferation. Previous studies reported that targeting on CSC-promoting pathways or proliferative signals was a promising strategy in cancer treatment. Gigantol, a bibenzyl compound from Dendrobium draconis, was reported to have a suppressive activity on CSC phenotypes, in vitro. However, the effects of gigantol on tumorigenicity in vivo, cancer cell proliferation and related CSC-promoting and proliferation regulatory mechanisms have not been explored. In this study, ectopic tumor xenograft in …

N, N-Bis (5-Ethyl-2-Hydroxybenzyl) Methylamine Induces Apoptosis Of Non-Small Cell Lung Cancer Cells Via C-Myc Protein Degradation, Nicharat Sriratanasak

Chulalongkorn University Theses and Dissertations (Chula ETD)

Lung cancer is a common cancer disease that contributes as a major cause of cancer related death. The oncoprotein, c-Myc plays a major role in oncogenic malignancies. It has been shown that the up—regulated c-Myc relates with aggressiveness of cancers and treatment failure. In this study, we purposed N, N-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD), a benzoxazine dimer to be a novel c-Myc targeting compound and displayed evidence presenting the potential effect of EMD on c-Myc degradation in human lung cancer cells. EMD exhibited cytotoxicity to lung cancer cells through apoptosis induction. EMD dramatically eliminated c-Myc in the cells and initiated caspase-dependent …

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

National And Local Antibiotic Prescribing Trends And Prescribing Appropriateness In Older Adults, Fawaz M. Alotaibi

Theses and Dissertations

Background: Antibiotic overuse/misuse has been documented in several reports to increase the risk of Clostridioides difficile (C.diff) infection and antibiotic resistance. The older adult population is more prone to use antibiotic medications than any other age group due to decreased immune function, use of urinary catheters, ventilation during hospitalization and other factors. Antibiotic resistance and C.diff are major public health problems. However, studies examining the trends of antibiotic use and the association between the antibiotic use and negative health outcomes among older adults in the outpatient and emergency department settings are limited.

Objectives: The main objectives of this …

Understanding Medication Self-Management Capacity Among Older Adults Living In Low-Income Housing Communities, Amal M. Badawoud

Theses and Dissertations

Understanding Medication Self-Management Capacity among Older Adults Living in Low-Income Housing Communities

ABSTRACT

Background: Medication self-management capacity (MMC) is an individual’s cognitive and functional ability to self-administer a medication regimen as prescribed. Poor MMC is an issue in older adults often resulting in negative health outcomes and loss of independence. Therefore, understanding low-income older adults’ capacity to manage their medications may help identify individuals who are at risk for developing medication mismanagement and guide future intervention strategies based on an individual need to promote safe medication use and healthy aging in place in the community.

Objectives: 1) To determine the …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

A Hybrid Molecule Of Melatonin And Curcumin For Therpeutic Use In Pulmonary Fibrosis, Varsha V. Nair

Theses and Dissertations

Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms …

Molecular Pharmacology Of Non-Phyto-Cannabinoid Approaches For Treatment Of Neuropathic Pain, Nadejda A. Blajkevich

Theses and Dissertations

Approximately twenty million people in United States have some form of peripheral neuropathy. It has been shown that the CB₂ cannabinoid receptor is upregulated when there is peripheral nerve injury and activating the CB₂ receptor produces anti-inflammatory effects that translate to a reduction in signs of “neuropathic pain” in animal models. Elevating endogenous cannabinoids by inhibiting degradative enzymes has also been used to reduce neuropathic pain signs in laboratory animal models of pain. We hypothesize that the molecular pharmacology of these two approaches can be leveraged to optimize CB₁/CB₂ activation to improve non-phyto-cannabinoid treatments for …

Predictors And Health Outcomes Of Treatment-Resistant Depression Among Adults With Chronic Non-Cancer Pain Conditions And Major Depressive Disorder, Drishti Shah

Graduate Theses, Dissertations, and Problem Reports (ETD)

Understanding major depressive disorder (MDD) as a comorbidity in patients with chronic non-cancer pain conditions (CNPC) is of importance because of the high prevalence and well documented bi-directional relationship between MDD and pain. Furthermore, presence of CNPC among adults with MDD often reduces benefits of antidepressant therapy, thereby increasing the possibility of treatment resistance. Treatment-resistant depression (TRD) commonly defined as insufficient response to multiple antidepressant trials, often worsens depression and pain symptoms and can amplify the clinical and economic burden among adults with CNPC and MDD. Additionally, long-term opioid therapy (LTOT) may be prescribed at a higher rate to adults …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Platelet Biology And Thrombosis: Juul E-Cigarette Exposure And 5ht2a Receptor Drug Discovery, Jean Emmanuel Montes Ramirez

Open Access Theses & Dissertations

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Development Of Ligand-Kinase Binding Affinity Predictive Model, Govinda Kc

Open Access Theses & Dissertations

Prediction of interaction between drugs or drug like compounds and targets, is of high importance in drug discovery process as it provides important insights into therapeutic potential and possible adverse effects. As the experimental testing would be highly expensive, laborious and time consuming, screening the molecules computationally before performing experiments would be cost effective, faster and convenient as a method of approach. In this study, I have developed computational models, leveraging machine learning techniques, to predict drug-kinase binding affinities. The predictive model is mainly built using the Random Forest (RF) machine learning method. This study is focused on kinases because …

Cost Effectiveness Analysis Of Enzalutamide, Abiraterone Plus Prednisone And Cabazitaxel Plus Predinsone For The Treatment Of Visceral Metastatic Castration Resistant Prostate Cancer (Mcrpc) After Docetaxel Therapy, Yazan K. Barqawi

Pharmaceutical Sciences ETDs

Background: Prostate cancer is the second leading cause of death after lung cancer among men in the US. The America Cancer Society predicts 164,690 new cases and 29,430 prostate cancer deaths in 2018. Of those diagnosed with prostate cancer, about 10-20 % will develop castration-resistant prostate cancer (CRPC) within 5 years of diagnosis and 70 % of those cases will metastasize to mCRPC. In 2014, nearly US $13.4 billion was spent on prostate cancer in the US and expected to reach US $15.4 billion by 2020; making prostate cancer the fifth most costly cancer.

Objective: To conduct a cost-effective analysis …

Fwer Controlling Procedures In Simultaneous And Selective Inference, Li Yu

Dissertations

With increasing complexity of research objectives in clinical trials, a variety of relatively complex and less intuitive multiple testing procedures (MTPs) have been developed and applied in clinical data analysis. In order to make testing strategies more explicit and intuitive to communicate with non-statisticians, several flexible and powerful graphical approaches have recently been introduced in the literature for developing and visualizing newer MTPs. Nevertheless, some theoretical as well as methodological issues still remain to be fully addressed. This dissertation addresses several important issues arising in graphical approaches and related selective inference problems. It consists of three parts.

In the first …

Functionalized Carbon Nanotubes In Hydrophobic Drug Delivery, Kun Chen

Dissertations

The direct incorporation of carboxylated carbon nanotubes (f-CNTs) into hydrophobic drug particles during their formation via anti-solvent precipitation is presented. The approach is tested using two drugs namely antifungal agent Griseofulvin (GF) and antibiotic Sulfamethoxazole (SMZ) that have very different aqueous solubility. It is observed that the f-CNTs dispersed in the water serve as nucleating sites for crystallization and are readily incorporated into the drug particles without altering crystal structure or other properties. The results show that the hydrophilic f-CNTs dramatically enhance dissolution rate for both drugs. The increased degree of functionalization leads to higher hydrophilicity and therefore faster dissolution …

Research News. Publications, 2018. Volume 2, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period July 1 through December 31, 2018

Development And Ex Vivo Characterization Of Enteric Coated Chitosan Beads For Crohn’S Disease Management, Craig Mendonca

University Scholar Projects

Drug delivery is the process of transporting a drug to its site of action. It includes controlled delivery, where the drug is released at the tissue in a regulated manner. Additionally, it includes targeted delivery, where the drug is aimed at a specific tissue or region to avoid unwanted side effects (that would occur if the drug were distributed throughout the body). A cellulose acetate phthalate coated chitosan bead was developed as a formulation for controlled and targeted release of dexamethasone to the ilium and colon. This formulation was determined to be effective in delaying dexamethasone release until the formulation …

Pharmacy-Based Travel Health Services In The United States, Keri Hurley-Kim, Jeffery Goad, Sheila Seed, Karl M. Hess

Pharmacy Faculty Articles and Research

The aim of this paper is to review pharmacy laws and regulations, pharmacist training, clinic considerations, and patient care outcomes regarding pharmacy-based travel health services in the United States. Pharmacists and pharmacies in the United States are highly visible and accessible to the public, and have long been regarded as a source for immunization services. As international travel continues to increase and grow in popularity in this country, there is a pressing need for expanded access to preventative health services, including routine and travel vaccinations, as well as medications for prophylaxis or self-treatment of conditions that may be acquired overseas. …

A Review Of Beneficial Low-Intensity Exercises In Diabetic Peripheral Neuropathy Patients, Carley Johnson, Jody K. Takemoto

Pharmacy Faculty Publications and Presentations

The American Diabetic Association standards of medical care for diabetic patients recommends moderate intensity exercise to help manage diabetes; however, this recommendation may be unmanageable for patients who have become inactive or unable to reach this intensity. The purpose of this review is to determine if low-intensity exercises demonstrate improvement in diabetic peripheral neuropathy symptoms in order to utilize these exercises as a starting point for inactive patients. Studies in low-intensity exercises from 2013 to May 2018 were systematically searched in PubMed, SCOPUS, and Cochrane Library databases. The studies in this research have shown that low-intensity resistance exercises have promising …

Mutants Of Cocaine Esterase, Donald Landry, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Patents

Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

Community Pharmacists And Substance Use Disorders: Attitudes, Knowledge And Practices, Deepika Rao

Electronic Theses and Dissertations

Background: Substance use disorder (SUD) is a serious health concern affecting a large proportion of the US population. Community pharmacists are well-positioned to prevent, screen, and provide appropriate treatment for SUD. Stigma towards these patients and SUD results in reduced quality of care as well as poor treatment outcomes. It is imperative that pharmacists have the appropriate knowledge of and attitude towards prevention, harm reduction and treatment to develop therapeutic relationships and improve their delivery of pharmacy services

Objective: To assess knowledge, practices (with an emphasis upon screening), stigma and general attitudes of community pharmacists towards SUD and evaluate the …

Using An In Vitro-In Vivo Correlation For The ‘Bioequivalence By Design’ Development Of An Immediate Release Carbamazepine Product, Douglas Steinbach

Electronic Theses and Dissertations

The quality of a drug product may be characterized by the consistency with which its indicated clinical effect, and safety profile, is experienced by the patient. The concept that such quality should be built into a product is at the core of the United States Food and Drug Administration’s (FDA) quality by design (QbD) initiative. This vision for pharmaceutical product development emphasizes the risk-based identification of critical quality attributes (CQA) which summarize a product’s performance, the efficient refinement of critical product/process parameters (CPP) that can affect such attributes, and the systematic development of CPP limits, which assure appropriate performance of …

The Association Between Depression, Anxiety And Clinical Outcomes For Type 2 Diabetes Mellitus, Elham Heidari

Electronic Theses and Dissertations

Objective: To evaluate the impact of depression and/or anxiety on clinical outcomes of diabetes, including glycosylated hemoglobin (HgA1c), blood glucose, blood pressure, total cholesterol, weight and LDL among patients with incident type 2 diabetes mellitus (T2DM).

Method: A retrospective cohort study utilizing electronic medical record (EMR) data from a primary care physician (PCP) group practice was conducted to identify patients newly diagnosed with T2DM with at least 6 months pre-diagnosis and 12 months post-diagnosis of EMR data using International Classification of Disease 9th edition Clinical Modification (ICD-9-CM) coding. The presence of comorbid depression and anxiety was identified to identify four …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

Synthesis Of Novel 6-Substituted And 5-Substituted Pyrrolo[2,3-D] Pyrimidine Antifolates As Targeted Anticancer Therapies, Xinxin Li

Electronic Theses and Dissertations

The dissertation will give an introduction, background and current research progress in the areas of antifolates and chemotherapy of anticancer. The design and synthesis of classical 6- substituted pyrrolo[2,3-d]pyrimidines and 5-substituted pyrrolo[2,3-d]pyrimidines as potential antifolates have been described. The design variations include: methylated thiophene regioisomers, fluorinated phenyl regioisomers, thionyl regioisomers on the side chain of pyrrolo[2,3-d]pyrimidines. As a part of this study, a series of new compounds have been synthesized and characterized. Of these, ten final compounds were submitted for biological evaluation.

The Influence Of Age, Gender, And Thiol Repletion In An In Vivo Model Of Lewy Body Disorders, Daniel Mason

Electronic Theses and Dissertations

Lewy body disorders are a family of neurological brain disorders associated with olfactory, motor, and cognitive deficits and are collectively defined as α-synucleinopathies, as they are characterized by hallmark “Lewy bodies” composed of aggregated, fibrillar α-synuclein. It is not certain but often posited that fibrillar α-synuclein seeds the progressive, self-propagating spread of Lewy pathology through neuroanatomical circuitry. Furthermore, the site of disease induction is still debated. In Aim I, we developed a novel protocol for generating reproducible and robust α-synucleinopathy in the limbic temporal lobe following infusions of preformed α-synuclein iv fibrils into the mouse olfactory bulb, which is frequently …