Other Pharmacy and Pharmaceutical Sciences Commons^™

Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. …

Assessing The Effect Of Chronic Dopamine Receptor 2 Blockade As A Potential Model Of Secondary Negative Symptoms In Rats Using The Fr5/Chow Feeding Choice Task, Cyrene Nicholas

Honors Scholar Theses

Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic …

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or …

Smart Delivery Of Genes And Drugs For Treatment Of Cancer, Feng Lin

Theses & Dissertations

The ineffective delivery of genes and drugs have become a big obstacle for the treatment of cancer, due to either poor stability or low aqueous solubility. In the first part, A ROS responsive polymer named poly(ethylene glycol)–poly[aspartamidoethyl(p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA) was developed for codelivery miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) for the treatment of pancreatic ductal adenocarcinoma (PDAC), since tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion is significant downregulated while Polo-like kinase 1 (PLK1) closely associated with short survival rates of pancreatic cancer patients is remarkably upregulated . In part 2, …

Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash

Theses & Dissertations

Purpose The aim of this study was to determine whether coadministration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonategraft- dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice.

Methods P-DTX and P-CYP were synthesized from mPEGb- PCC through carbodiimide coupling reaction and characterized by 1H–NMR. The micelles were prepared by film hydration and particle size was measured by dynamic light scattering (DLS). Cytotoxicity, apoptosis and cell cycle analysis of P-DTX and P-CYP were evaluated in MIA PaCa-2 cells. In vivo efficacy …

Ocular, Neural, And Cellular Biodistribution Of Multifunctional Antioxidants, Damian Daszynski

Theses & Dissertations

Aging is a complex biological process which stems from a growing imbalance between the regenerative capacity of an organism and endogenous as well as exogenous damaging factors. This imbalance leads to the slow deterioration of individual cells, organs, and eventually the entire organism. The free radical theory of aging combines the evolutionary and mechanistic aspects of aging, postulating that the innate process is caused by deleterious, irreversible, and inevitable changes in biological systems caused by oxidative damage that accumulates over the lifespan. Evidence of this phenomenon is supported by the pathogenesis of age-related diseases, such as age-related macular degeneration and …

Regulating Neuronal Growth With Structurally Defined Glycans, Gabriella D. Hartman

Honors Theses

Chondroitin sulfate proteoglycans (CSPGs) and keratan sulfate proteoglycans (KSPGs) play an important role in neural development. Aggrecan, a CSPG, operates in the neural extracellular matrix where it negatively regulates neurite outgrowth to prevent aberrant process formation. Unfortunately, this aggrecan or CSPG-rich/KSPG-rich barrier can also prevent neuronal regeneration, which contributes to the inability to repair brain and spinal cord injuries. Removal of CSPGs and KSPGs has been shown to increase neurite outgrowth. We extend these findings by testing the ability of structurally-defined glycans to outcompete aggrecan and allow neurite outgrowth. Our overall goal is to determine if there is a particular …

Studies Of Salvinorin-Based Antagonists To Elucidate Pertinent Interactions For Kappa Opioid Receptor Antagonism, Madeline Keane

Honors Theses

Opioid abuse, leading to addiction and related deaths, has created a chronic epidemic in the United States for the past 30 years. This crisis has sprung from reliance on the prescription of opioid analgesics as the primary method for the management of pain in the 1990s. At that time, these drugs, specifically Purdue Pharma’s OxyContin, were marketed as non-addictive. Due to this systemic minimization of the addictive properties of opioid analgesics, as prescription rates increased, opioid-related mortality rates climbed. This epidemic continues to be pervasive, as opioid-related overdose resulted in 47,600 deaths in 2017. In addition to the opioid epidemic, …

In-Vitro Assessment Of Cb1/Cb2 Receptor Binding And Function, Joey M. Davis

Honors Theses

Cannabinoid receptors CB1 and CB2 are G protein-coupled receptors that have a variety of physiological effects on the human body. Many natural product agonists and antagonists are presumed to interact with the cannabinoid receptors and are therefore heavily studied in drug discovery. Assays are used to study the binding of compounds to these receptors. However, a limited number of these assays are efficient in determining the functional activity of ligands associated with CB1 and CB2. Of those, many use radioactivity which is both expensive and potentially dangerous to the researcher. In this study, we first validated the assays already found …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …

Effect Of Diabetes Mellitus On Ocular Surface Tight Junctions And Glycocalyx, Saleh M. Alfuraih

Pharmaceutical Sciences (MS) Theses

Introduction: Diabetes mellitus is the disease of the century that affects many body organs. In the eye, diabetes mellitus causes retinopathy, cataract, glaucoma, papillopathy, and ocular surface disease. Ocular surface abnormalities in patients of diabetes mullites include impairment of corneal epithelial barrier function, conjunctival defects, increased incidence of corneal and conjunctival infections and higher prevalence of dry eye disease. Impairment of tight junctions and glycocalyx, which are critical for ocular surface barrier function, may underlie these diabetes-associated ocular surface defects. Therefore, the present study was designed to investigate the effect of high glucose exposure and type I diabetes mellitus on …

Role Of Protein Phosphatase-2a In Regulating Monocyte Activation By Soluble And Crystalline Uric Acid In Gout, Sandy Elsayed

Pharmaceutical Sciences (MS) Theses

Gout is a chronic inflammatory disease caused by the phagocytosis of monosodium urate monohydrate (MSU) crystals by monocytes/macrophages resulting in downstream expression and production of interleukin-1 beta (IL-1β) and chemokines. The activation of monocytes by MSU crystals involves the priming of monocytes with danger signals e.g. lipopolysaccharide (LPS) or soluble uric acid (UA), crystal phagocytosis and subsequent NLRP3 inflammasome activation and conversion of pro-IL-1β to active IL-1β. Protein-phosphatase-2A (PP2A) is a serine/threonine phosphatase that plays an important role in cell growth and inflammation. The prodrug Fingolimod (FTY720) and its phosphorylated active metabolite (p-FTY720) activate intracellular PP2A. We hypothesized that monocyte …

Effects Of Lisdexamfetamine And Haloperidol On A Binge-Like Eating Model & Preliminary Investigations Of The Dopaminergic Mechanism Underlying Binge Eating Disorder (Bed), Maxime Braun

Honors Scholar Theses

Binge eating disorder (BED) is a psychophysiological disorder defined as the excessive intake of high-caloric, palatable foods within a short span of time, accompanied by feelings of distress. Animal models of binge-like eating behavior have been developed that give intermittent, limited access to a highly palatable food. Presby et al. (2020) used chocolate as the highly palatable food to induce binge-like eating behavior in rats. Lisdexamfetamine (LDX), a d-amphetamine prodrug and dopamine (DA) uptake inhibitor, is currently used to treat BED in humand. In rats, binge-like eating of chocolate was induced by exposure to unpredictable and limited chocolate access over …

Sulforaphane Protects Against Ethanol-Induced Apoptosis And Teratogenesis Through Epigenetic Modulation Of Anti-Apoptotic Genes., Yihong Li

Electronic Theses and Dissertations

Background. Ethanol-induced excessive apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is one of the major mechanisms underlying the pathogenesis of Fetal Alcohol Spectrum Disorders (FASD). However, the molecular mechanisms underlying FASD that results from maternal alcohol exposure during pregnancy are poorly understood. The overall goals of this study are to examine the mechanisms by which ethanol induces apoptosis and malformations in vitro and in vivo, and to develop a nutritional-based approach by using SFN and SFN-rich BSE to prevent FASD through epigenetic modulation. Results. This study demonstrates that ethanol exposure resulted in a significant increase …

Evaluation Of Potential Drug Interaction Of Analgesic In Cancer Patient Receiving Palliative Care In Dharmais Cancer Hospital, Eme Stepani Sitepu, Atika Wahyu Puspitasari, Nuriza Ulul Azmi, Lila Nilam Sari

Pharmaceutical Sciences and Research

Analgesics are mostly used in cancer patients receiving palliative care to improve the quality of life of patients. Besides analgesics, cancer patients receiving palliative care were also given other drugs in combination to overcome other symptoms of cancer, and this combination could potentially cause drug interactions. This study was aimed to analyze the potential of drug interactions with analgesics in cancer patients. The study design was cross-sectional with a retrospective method and descriptive study. The sample of this study was cancer palliative care patient’s prescription at Dharmais Cancer Hospital in the period of January – December 2017. The sample analyzed …

Anti-Proliferative Effects Of A Coumarin Benjaminin On Four Human Cancer Cell Lines, Siau Hui Mah, Soek Sin Teh, Ahmad Azri Fitri Ismail, Gwendoline Cheng Lian Ee

Pharmaceutical Sciences and Research

Cancer is a major health issue around the globe. Chemotherapy and radiation therapy are no longer the standard treatments for patients as these remedies lead to many adverse effects. Thus, the development of alternative effective drugs from lead compounds, especially natural products is necessary. This study aimed to isolate cytotoxic phytochemical constituents from a plant Calophyllum inophyllum, which has been used as traditional medicine since ancient time. The root of C. inophyllum was extracted and subjected for phytochemical constituent isolation. A coumarin, benjaminin (1) was isolated successfully from the chloroform extract and its structural elucidation was performed by spectroscopy analyses …

Ace Inhibitory Activity And Functional Group Analysis Of Solvent- Partitioned Fractions Of Eleusine Indica, Jade Celon Cometa, Liahona Faith Roldan Mancol, Anthony Nalzaro Yen, Joanne Katherine Talens Manlusoc

Pharmaceutical Sciences and Research

Eleusine indica Linn. Gaerth or Indian goose grass has been widely used as an alternative natural anti-hypertensive agent. However, the rationale behind this mechanism is still unknown. The purpose of this study is to confirm the presence of functional groups that may be responsible for its ACE inhibitory activity and its possible synergism. Each solvent-portioned fraction was analyzed by FTIR, individual ACE inhibitory activity, and combination of fractions. FTIR results of solvent- partitioned fractions revealed that O-H and C-H stretches were present in all fractions. In addition to this, C-O and C=O groups were also present in all fractions except …

Assessment Of Depression Among Older Adults Staying In Old Home Care In Klang, Malaysia, Muhammad Qamar, Nurul Zahirah, Sohail Ahmad

Pharmaceutical Sciences and Research

Mental disorders such as depression are widespread, often underdiagnosed, and usually inappropriately treated. The early recognition of factors that may promote depression with the help of depression screening aid can help to plan better care for the patient. Therefore, this study aimed to determine the depression prevalence among the older adults staying in old home care, to explore any association and differences of depression across various socio-demographic variables, and to study the predictors of depression among study subjects. A cross-sectional study was conducted with a convenience sample of 141 elderly by using the validated tool. The study instrument was divided …

An Exploration Of Electrospun Fibers Containing Drug-Cyclodextrin Inclusion Complexes, Fatimah Fatimah, Zeynep Aytac, Tamer Uyar, George Pasparakis, Gareth R. Williams

Pharmaceutical Sciences and Research

A series of new core-shell fibers were developed containing anticancer drugs (5-fluorouracil or ferulic acid) and their cyclodextrin inclusion complexes, with a gadolinium-based magnetic resonance imaging (MRI) contrast agent. These were prepared by electrospinning, a simple method for producing ultra-fine fibers through the application of a strong electrostatic force on a polymer solution. The shell of the fibers was formed from Eudragit S100, and the drugs were loaded in the core. Scanning electron microscopy images showed the formation of smooth ribbon-like fibers, with diameters ranging from 1.4 to 5.1 μm, and transmission electron microscopy reveals a transparent interface between the …