Pharmacy and Pharmaceutical Sciences Commons^™

Response Of Dopaminergic System To Cocaine Exposure, Recovery After Cocaine Abstinence, And Impact Of A Long-Acting Cocaine Hydrolase, Jing Deng

Theses and Dissertations--Pharmacy

Cocaine produces its physiological effects by targeting multiple proteins in the central nervous system, particularly by binding with dopamine transporter (DAT) to block the normal dopamine (DA) recycling process. This process along with the pleasure feeling would wear off shortly after the abstinence from the drug. However, chronic cocaine use is associated with neuroadaptations in the dopaminergic system, including increases in the density of DAT on plasma membrane of dopaminergic neurons. Given the critical role of DAT in neurotransmission, various studies have been carried out on animal models to learn its structure, function, and distribution. Long-standing evidence supports that DAT …

Liposomal Technologies To Improve Gene Delivery, David Nardo Padron

Theses and Dissertations--Pharmacy

Lipid based nanoparticles (LBNs) are used in myriad applications in medicine from small molecule drug delivery to mRNA vaccines. A major contributing factor to the development of the field has been the ongoing development of novel compounds that retain the functionality of natural lipids but expand upon them through inclusion of functional moieties that can be applied to specific scientific and biomedical questions. In the body of this dissertation, an extensive overview of LBNs is provided, focusing primarily on their use in immune modulation. The research presented herein begins with the synthesis of a novel class of lipids based on …

The Relative Contribution Of Liver And Intestine In Reverse Cholesterol Transport, Rupinder Kaur

Theses and Dissertations--Pharmacy

Despite decades of advances in research, death due to cardiometabolic disease remains the largest contributor to mortality in the US. While present therapies oppose “forward cholesterol transport,” and atherosclerotic plaque progression, they do not remove cholesterol from established atherosclerotic plaques. Reverse cholesterol transport (RCT) is the active process of mobilizing peripheral cholesterol for excretion through the hepatobiliary (transhepatic cholesterol elimination, THCE) or intestinal (transintestinal cholesterol elimination, TICE) pathways. Currently, there are no clinically approved therapeutics that target RCT. Elucidation of the mechanisms that govern RCT and TICE, and the subsequent identification of novel targets is of importance. The present work …

Development Of Accurate And Efficient Computational Methodologies For Predicting Protein-Ligand And Protein-Protein Binding Free Energies, Alexander Hamilton Williams

Theses and Dissertations--Pharmacy

Computational modeling is an invaluable tool in the drug discovery process either for small ligand or protein therapeutics. The widespread availability of protein X-Ray Crystal and Cryo-Electron Microscopy (Cryo-EM) structures has allowed for more accurate molecular dynamics (MD) simulations that are not reliant on methods such as homology modeling, which may produce structures that require significant computational time to demonstrate their stability. In this thesis we describe several novel methodologies for the computationally efficient modeling of protein/ligand and protein/protein complexes that may be employed within both large-scale virtual screenings and lead compound optimization. These methodologies may also be utilized in …

Development Of Zafirlukast Derivatives Active Against Porphyromonas Gingivalis, Kaitlind C. Howard

Theses and Dissertations--Pharmacy

Periodontal diseases are inflammatory diseases that can lead to damage of the soft tissue and bone supporting the teeth. Gingivitis is the reversible early stage of gum disease, which consist of gums that bleed when brushing or flossing teeth. When left untreated, the preventable but irreversible late stage of periodontal disease, periodontitis, can lead teeth to loosen or even fall out. Oral bacterial species, such as the Gram-negative anaerobic pathogen Porphyromonas gingivalis trigger these inflammatory diseases through oral dysbiosis. P. gingivalis is a keystone pathogen, meaning that the damage caused by P. gingivalis is not proportional to its abundance. Treatment …

Polymeric Nanovaccine Delivery System For Influenza Vaccine, Chaitanya K. Valiveti

Electronic Theses and Dissertations

Vaccines are the most efficient and cost-effective method for preventing illnesses caused by infectious pathogens. Even though the great success of vaccines over decades, the development of safe and robust vaccines is still essential for emerging new pathogens, re-evolving old pathogens, and improving the insufficient protection given by existing vaccines. One of the most critical strategies for developing effective new vaccines is selecting and using a suitable adjuvant or immune stimulant. Immunologic adjuvants are essential for improving vaccine potency by enhancing the immune response of vaccine antigens. The amount of antigen could be spared with improved potency, especially during mass …

Nh125 Sensitizes Staphylococcus Aureus To Cell Wall-Targeting Antibiotics Through The Inhibition Of The Vras Sensor Histidine Kinase, Shrijan Bhattarai, Lane Marsh, Kelsey Knight, Liaqat Ali, Antonio Gomez, Allison Sunderhaus, May H. Abdelaziz

Pharmacy Faculty Publications and Presentations

Staphylococcus aureus utilizes the two-component regulatory system VraSR to receive and relay environmental stress signals, and it is implicated in the development of bacterial resistance to several antibiotics through the upregulation of cell wall synthesis. VraS inhibition was shown to extend or restore the efficacy of several clinically used antibiotics. In this work, we study the enzymatic activity of the VraS intracellular domain (GST-VraS) to determine the kinetic parameters of the ATPase reaction and characterize the inhibition of NH125 under in vitro and microbiological settings. The rate of the autophosphorylation reaction was determined at different GST-VraS concentrations (0.95 to 9.49 …

Modulation Of Ptz-Induced Convulsions In Rats Using Topiramate Alone Or Combined With Low Dose Gamma Irradiation: Involving Akt/M-Tor Pathway, Marwa Safar

Pharmacy

The current study evaluates the anticonvulsant effect low dose whole body gamma irradiation (LDR) alone or combined with topiramate against pentylenetetrazole (PTZ)-induced convulsions. Male Wister rats received either saline or PTZ (75mg/kg i.p.). The other three groups were pretreated with single low dose radiation (0.5Gy), topiramate (50mg/kg, p.o., seven days) and TPM with LDR respectively before PTZ injection. Racine’ score, latency, and duration of the convulsions were assessed. Glutamate and GABA were measured. AKT/m-TOR signaling pathway including AKT (protein kinase B), mammalian target of rapamycin (m-TOR), protein S6, and caspase 3 were also assessed. Measurements of markers of oxidative stress …

The Combinatory Effects Of Pediatric Obesity And Ontogeny On Monocarboxylate Transporter Expression In Tissues Of Drug Disposition, Michael Ng

University of the Pacific Theses and Dissertations

Proton-coupled and sodium-dependent monocarboxylate transporters are encoded by the SLC16A and SLC5A gene family of solute carriers, and are responsible for the transport of essential nutrients such as L-lactate, pyruvate, and ketone bodies. Basigin, or CD147, acts as an ancillary protein for MCT1 and MCT4, and is involved in membrane surface expression of transporters. MCT's are also involved in the shuttling of monocarboxylic xenobiotics across cell membranes, including the drugs valproate and gamma hydroxybutyrate. MCT’s are also important for normal mammalian development, particularly during embryogenesis and early neonatal life. Previous studies have shown that ketogenic diets increase MCT expression in …

Photochemical Reaction Of Renieramycins And Evaluation Of Cytotoxicity Against Lung Cancer Cells, Suwimon Sinsook

Chulalongkorn University Theses and Dissertations (Chula ETD)

Lung cancer causes more deaths than any other type of cancers, with the majority of patients diagnosed with non-small cell lung cancer (NSCLC). Lung cancer is a difficult disease to treat because of the drug resistant problem. Therefore, there is an immediate need for effective, safe, and easily accessible anti-lung cancer drug. Ecteinascidin 743 (Trabectedin or Yondelis®), a marine-derived tetrahydroisoquinoline alkaloid, is an approved drug for treating human lung cancer. This research was studied on the semi-syntheses of new renieramycins derivatives with similar structures to above drug for discovery and development of potent NSCLC cytotoxic agents. Renieramycins was extracted from …

Anti-Inflammatory Compounds In Human Peripheral Blood Mononuclear Cells From Dendrobium Species, Virunh Kongkatitham

Chulalongkorn University Theses and Dissertations (Chula ETD)

In these studies, four new compounds including three phenanthrene derivatives (dendrocrumenols A, B and D) and one fluorenone (dendrocrumenol C) and four known compounds including gigantol, 3,7-dihydroxy-2,4,8-trimethoxyphenanthrene, densiflorol B and cypripedin were isolated from Dendrobium crumenatum Sw. Each structure of isolated compounds from D. crumenatum was elucidated by spectroscopic data. These isolated compounds were then evaluated for anti-inflammatory effects in human peripheral blood mononuclear cells (PBMCs). Among the tested compounds, dendrocrumenols B and D showed the most promising anti-inflammatory effects through inhibition of tumor necrosis factor tumor (TNF) and interleukin-2 (IL-2) in monocytes and T cells. The deep immune profiling …

Titania Nanosheets Induce Anticancer Activityin Human Non-Small Cell Lung Cancer Cells, Rapeepun Soonnarong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Metal nanomaterials can enhance the efficacy of current cancer therapies. Here, we show that Ti0.8O2 nanosheets cause cytotoxicity in several lung cancer cells but not in normal cells. The nanosheet-treated cells showed certain apoptosis characteristics. Protein analysis further indicated the activation of the p53-dependent death mechanism. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses revealed the cellular uptake of the nanosheets and the induction of cell morphological change. Ti0.8O2 nanosheets induce apoptosis through a molecular mechanism involving peroxynitrite (ONOO−) generation. As peroxynitrite is known to be a potent inducer of S-nitrosylation, we further found that the nanosheets mediated …

Chemical Constituents And Nitric Oxide Inhibitory Activity Of Capparis Micracantha And Maerua Siamensis, Sasiwimon Nukulkit

Chulalongkorn University Theses and Dissertations (Chula ETD)

The chemical investigation of two plants in Capparaceae family, which are Capparis micracantha and Maerua siamensis, leads to the isolation of 13 compounds. The structures of the isolates were elucidated using spectroscopy techniques and comparison of the previous reports. Of five known compounds from the stems of C. micracantha were an indole alkaloid (methyl 6-methoxy-3-indolecarbonate), a benzoic acid derivative (vanillic acid), a lignan [(−)-syringaresinol], and two stilbene dimers [(+)-ampelopsin A and (−)-pauciflorol E]. In addition, eight new indole alkaloids named (+)-maeruanitrile A, maeruanitrile B, maeroximes A-C and maeruabisindoles A-C were isolated from the roots of M. siamensis,. All isolates were …

Neuroprotective Effect Of Intranasal Delivery Of Asiatic Acid Against Amyloid Beta1-42-Induced Alzheimer's Disease In Mice, Ridho Islamie

Chulalongkorn University Theses and Dissertations (Chula ETD)

Asiatic acid (AA) is an active natural compound that can be derived from Centella asiatica extract. Several pharmacological studies were reported that AA has potential as neuroprotector in the central nervous system disorders. AA penetration in the brain was limited due to its low bioavailability. Nasal delivery system of solid lipid nanoparticles (SLNs) loaded-AA was developed to increase AA penetration in the brain. The current study aimed to investigate neuroprotective effect and protective mechanisms of AA in SLNs by nasal-to-brain delivery technique against Aβ1–42 induced memory impairment by in vivo study. Male ICR mice were divided into six groups (n=11-12/group); …

Medication Usage In Independent Living: A Continuing Care Retirement Community Aging In Place Initiative, Aarti Deshpande, Carrie B Rubenstein, Ruth Benfield, Lee Burnside

All Poster Presentations

Purpose: The purpose of the study was to identify medication use concerns in this community.

Background: In this study, Swedish Geriatric Medicine Fellow partnered with this community to identify medication use concerns in this population.

Continuing Care Retirement Communities (CCRCs) are intended to support residents as they age in place. These communities tend to be well resourced but less studied. This survey attempts to identify medication use concerns in this population. Mirabella CCRC has 324 Independent living (IL) residents, 82 of which are couples. The average age is 85 years. The current cost of an IL unit is from $4673- …

Trajectories Of Medication Non-Adherence With Time-Varying Predictors And Association With Health Outcomes: A Comparison Of Classical Statistical Methods With Machine Learning Algorithms, Vasco Pontinha

Theses and Dissertations

Background: Medication adherence is a major obstacle to improving health care outcomes in long-term therapies for chronic diseases. According to the World Health Organization, interventions for improving medication adherence can have a higher impact on the health of the population than any other advance in medical treatments. Approximately 125,000 individuals die every year in the U.S. because of non-adherence to medication, representing societal costs of $100-289 billion. Previous research has successfully used group-based trajectories methods to identify similar longitudinal medication adherence trajectories. However, medication adherence is not an isolated behavior and is influenced by many factors that current interventions fail …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

Incidence Of Cancer, Depression, And Economic Burden Of Prescription Nsaids Among Older Adults With Osteoarthritis: Statistical And Machine Learning Approaches, Nazneen Fatima Mohammed Umer Shaikh

Graduate Theses, Dissertations, and Problem Reports (ETD)

Understanding the role of chronic inflammation among older adults is critical because of its implications on chronic inflammatory conditions as well as its interaction with anti-inflammatory medications. Osteoarthritis (OA) is a heterogeneous multi-faceted joint disease with multi-tissue involvement of varying severity, and increasing evidence demonstrates a key role of chronic inflammation in its pathogenesis. Approximately 30 million adults in the United States have OA, and it is reported that a large proportion (43%) of them are older than 65 years. OA is typically treated using non-steroidal anti-inflammatory drugs (NSAIDs) for minimizing pain and reducing inflammation. NSAIDs have consistently shown clinically …

Formulation Development Of Drug Loaded Cyclodextrin-Based Nanoparticles For Ocular Delivery, Hay Man Saung Hnin Soe

Chulalongkorn University Theses and Dissertations (Chula ETD)

The development of topical eye drops for treatment of glaucoma and fungal keratitis is still challenging. Due to low aqueous solubility of drugs and the presence of ocular barriers, it is difficult to achieve effective therapeutic drug levels in targeted ocular tissues. In this present study, cyclodextrin (CD)-based nanoparticles (NPs) and synthetic CD-polymers were introduced to overcome these drawbacks and evaluated for their safety and efficacy. γ-Cyclodextrin (γCD) was able to increase the solubility of intraocular pressure lowering drugs, i.e., irbesartan (IRB) and candesartan cilexetil (CAC). The addition of Soluplus® significantly enhanced the complexation efficiencies of IRB/γCD and CAC/γCD complexes. …

Development Of An Extraction Method Of Mucuna Pruriens Seeds For A Chemically And Physically Stable Extract, Chayarit Vilairat

Chulalongkorn University Theses and Dissertations (Chula ETD)

Levodopa (L-DOPA) is a drug for the treatment of Parkinson's disease (PD). Currently, it derives from chemical synthesis and plants, especially Mucuna Pruriens (MP) seeds. The results of clinical studies found using the L-DOPA-containing MP for the treatment of PD could reduce side effects more than the synthetic one but patients must take MP powder in high amounts per a single dose which may cause inconvenience. Therefore, using the extract can help in the reduction of the dose. Unfortunately, the water extract from the MP seeds can be easily degraded physically and chemically; especially the physical appearance e.g., darkening color, …

Anti-Adipogenic Activity Of 4,5,4'-Trihydroxy-3,3'-Dimethoxybibenzyl From Dendrobium Ellipsophyllum In 3t3-L1 Preadipocytes, Hnin Ei Ei Khine

Chulalongkorn University Theses and Dissertations (Chula ETD)

Obesity and its global prevalence have become a threat to human health due to not only the abnormal lipid accumulation in the body as a result of aberrant expression levels in adipocyte differentiation and lipogenesis but also the underdeveloped pharmacotherapy. Recently, the bioactive compounds from the natural products have gained a lot of attention due to undertaking prophylactic and therapeutic effects on obesity. Here, we probed how 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB) extracted from an Thai orchid (Dendrobium ellipsophyllum) could exert its roles on the differentiation and function of murine (3T3-L1) and human (PCS-210-010) preadipocytes and offer some implications to modulate obesity. Cytotoxic …

Clinical Skills Development In The Virtual Learning Environment: Adapting To A New World, Erini S. Serag-Bolos, Liza Barbarello Andrews, Jennifer Beall, Kelly A. Lempicki, Aimon C. Miranda, Carol Motycka, Chelsea Phillips Renfro, Brittany L. Riley, Chasity M. Shelton, Deepti Vyas, Kimberly Won

Pharmacy Faculty Books and Book Chapters

The rapid transition to distance learning in response to the unexpected SARS-CoV-2/COVID-19 pandemic led to disruption of clinical skills development, which are typically conducted face-to-face. Consequently, faculty adapted their courses, using a multitude of active learning modalities, to meet student learning objectives in the didactic and experiential settings. Strategies and considerations to implement innovative delivery methods and address potential challenges are elucidated. Furthermore, integration of a layered learning approach may allow for more broad perspectives and allow additional interactions and feedback, which is especially necessary in the virtual environment.

Phytochemical Constituents Of Aquilaria Malaccensis Leaf Extract And Their Anti-Inflammatory Activity Against Lps/Ifn-Γ-Stimulated Raw 264.7 Cell Line, Eman Ramadan, Manar A. Eissa, Yumi Z. H-Y Hashim, Dina M. El-Kersh

Pharmacy

This study aims to identify the major phytochemical constituents in Aquilaria malaccensis (Thymelaeaceae) ethanolic leaf extract (ALEX-M) and elucidate their ability to suppress nitric oxide (NO) production from a murine macrophage-like cell line (RAW 264.7) stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Dichloromethane (DCM) and ethyl acetate (EtOAc) fractions of ALEX-M were subjected to column chromatography. Eight known compounds were isolated for the first time from this species. Compounds were identified using spectroscopic techniques (IR, UV, HRESIMS, and 1D and 2D NMR). Anti-inflammatory activity of both extract and isolated compounds were investigated in vitro. The fractions offered the isolation of …

Neuroprotective Effect Of Liraglutide In An Experimental Mouse Model Of Multiple Sclerosis: Role Of Ampk/Sirt1 Signaling And Nlrp3 Infammasome, Marwa Safar

Pharmacy

The heterogeneous nature of multiple sclerosis (MS) and the unavailability of treatments addressing its intricate network and reversing the disease state is yet an area that needs to be elucidated. Liraglutide, a glucagon-like peptide-1 analogue, recently exhibited intriguing potential neuroprotective effects. The currents study investigated its potential effect against mouse model of MS and the possible underlying mechanisms. Demyelination was induced in C57Bl/6 mice by cuprizone (400 mg/kg/day p.o.) for 5 weeks. Animals received either liraglutide (25 nmol/kg/day i.p.) or dorsomorphin, an AMPK inhibitor, (2.5 mg/ Kg i.p.) 30 min before the liraglutide dose, for 4 weeks (starting from the …

Research News, Publications, 2022, Volume 2, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period of April 1 through June 30, 2022.

Research News, Publications, 2022, Volume 1, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period of January 1 through March 31, 2022.

Research News, Publications, 2022, Volume 3, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period of July 1 through September 30, 2022

Research News, Grants, 2022, Volume 2, Soumyajit Majumdar

Grants (2015-)

Grants and contracts awarded during April - June 2022.

Research News, Grants, 2022, Volume 3, Soumyajit Majumdar

Grants (2015-)

Grants and contracts awarded during July - September 2022

Will Covid-19 Be Eradicated?, Matthew Kieke

Williams Honors College, Honors Research Projects

In this paper I want to define the meaning of “eradication”, explain the history of various diseases that have been eradicated, and compare and contrast them to covid-19, to answer the question of “Will covid-19 be eradicated”?