Pharmacy and Pharmaceutical Sciences Commons^™

Purin-6-One Derivatives As Phosphodiesterase-2 Inhibitors, Wei Yuan, Xin-Yun Zhao, Xi Chen, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

A series of purin-6-one derivatives were synthesized, and their in vitro inhibitory activity against phosphodiesterase-2 (PDE2) was evaluated by using a fluorescence polarization assay. Three compounds, that are, 2j, 2p, and 2q, showed significant inhibitory activity against PDE2 with IC₅₀ values of 1.73, 0.18, and 3.43 μM, respectively. Structure-activity relationship (SAR) analysis was performed to explore the relationship between the chemical structures of these compounds and their inhibitory activity. Compounds 2j, 2p, and 2q were further selected for molecular docking study. The docking results suggested that these ligands bind with hydrophobic pockets of …

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy With Minimal Toxicity, Andy Vo

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Cancer is the second leading cause of death in the U.S., and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations on …

Investigation Of Enzymatically Synthesized Glycogen As A Novel Nanodendrimer For Therapeutic Delivery, Sarah Ann Engelberth

Legacy Theses & Dissertations (2009 - 2024)

The field of medicinal chemistry is ever expanding, designing and discovering new therapeutic strategies. Oftentimes, it is challenging for these therapeutics to undergo clinical translation due to ineffective administration or unwanted toxicity in vivo. As such, drug delivery vehicles are designed to overcome these hurdles, allowing for delivery to the site of action by improving biodistribution, protecting therapeutic cargo, and decreasing toxicity. The work presented here aims to investigate a naturally-derived carbohydrate nanodendrimer, enzymatically synthesized glycogen (ESG) for drug delivery. This nontoxic, highly-branched, glucose-based structure has interior void volumes to allow for cargo encapsulation as well as a large density …

Gastrointestinal Safety, Chemotherapeutic Potential, And Classic Pharmacological Profile Of Nosh-Naproxen (Avt-219) A Dual No- And H2s-Releasing Hybrid, Mitali Chattopadhyay, Ravinder Kodela, Pascale L. Duvalsaint, Khosrow Kashfi

Publications and Research

Naproxen (NAP) is a potent nonsteroidal anti-inflammatory drug (NSAID) with a favorable cardiovascular profile. However, its long-term use may lead to serious gastrointestinal and renal side effects. NOSH- (nitric oxide and hydrogen sulfide) releasing naproxen (NOSH-NAP, AVT-219) belongs to a new class of anti-inflammatory agents designed to overcome these limitations. We compared the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, and antiplatelet properties of AVT-219 to that of NAP in preclinical animal models. We also evaluated its anticancer effects in 11 human cancer cell (HCC) lines of six different tissue origins and in a chemotherapeutic xenograft mouse model of colon cancer. AVT-219: …

Bupropion Hydrochloride, Cylie A. Couch

Natural Sciences Student Research Presentations

This is a poster presented at the Natural Sciences Poster Session at Parkland College, which provides the chemical makeup, dosage, and the body's response to r bupropion hydrochloride (Wellbutrin, Zyban), a medication used to treat depression, smoking cessation, and seasonal affective disorder.

Aprepitant, Genesis N. Pagan

Natural Sciences Student Research Presentations

This is a poster presented at the Natural Sciences Poster Session at Parkland College, which provides the chemical makeup, dosage, and the body's response to Aprepitant, also known as Emend, a medication used to prevent acute and delayed nausea and vomiting associated with emetogenic chemotherapy.

Pharmacokinetics And Distribution In Interstitial And Pulmonary Epithelial Lining Fluid Of Danofloxacin In Ruminant And Preruminant Calves, D. A. Mzyk, R. E. Baynes, K. M. Messenger, M. Martinez, G. W. Smith

United States Food and Drug Administration: Publications

The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3-week-old) and ruminating (6-month-old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high-pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the …

Measuring And Understanding Health-Related Quality Of Life Among Adult Patients With Hemophilia, Ruchit Mukesh Shah

Electronic Theses and Dissertations

Objectives: The objectives of this study are to: 1) examine the psychometric properties of the Medical Outcomes Study Short Form-12 Version 2 (SF-12v2); 2) assess the measurement invariance of the SF-12v2 with respect to age, disease severity, and treatment regimen; 3) identify psychosocial predictors of health-related quality (HRQOL) among adults with hemophilia in the United States. Methods: This cross-sectional study was conducted using both a web-based and paper-based self-administered survey. Adults with hemophilia were recruited using an online panel, a Facebook community of hemophilia patients, and at the University of Mississippi Medical Center hemophilia treatment clinic. Psychometric properties of the …

Saffron Extract And Its Active Constituents As Preventative And/Or Treatment Agents For Prostate Cancer Using In Vitro And In Vivo Models, Faisal Fayih Albaqami

Electronic Theses and Dissertations

Saffron extract and its active constituents were evaluated as chemopreventatives and/or treatments for prostate cancer. Different models of prostate cancer (in vitro and in vivo) were used for studying saffron and its constituents’ mechanisms. In normal prostate cells, saffron extract, crocetin, and safranal, in non-toxic concentrations, possessed antioxidant properties against the reactive oxygen species induced by H2O2 which further supports saffron constituents as chemopreventative agents. Moreover, saffron and its active constituents produced cytotoxicity in prostate cancer cells through intrinsic apoptosis pathways. Potential efficacy in minimizing prostate cancer metastasis was also examined. Saffron extract, crocetin, and safranal decreased the migration and …

Targeting Protein Kinases To Manage Or Prevent Alzheimer’S Disease, Manal A. Nael

Electronic Theses and Dissertations

Due to the pressing need for new disease-modifying drugs for Alzheimer’s disease (AD), new treatment strategies and alternative drug targets are currently being heavily researched. One such strategy is to modulate protein kinases such as cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 5 (CDK5), glycogen synthase kinase-3 (GSK-3α and GSK-3β), and the protein kinase RNA-like endoplasmic reticulum kinase (PERK). AD intervention by reduction of amyloid beta (Aβ) levels is also possible through development of protein kinase C-epsilon (PKC-ϵ) activators to recover α-secretase levels and decrease toxic Aβ levels, thereby restoring synaptogenesis and cognitive function. In this way, we aim to develop …

Multiple Sirna Delivery Against Cell Cycle And Anti-Apoptosis Proteins Using Lipid-Substituted Polyethylenimine In Triplenegative Breast Cancer And Non-Malignant Cells, Manoj B. Parmar, Bárbara E. Arteaga Ballesteros, Timothy Fu, Remant Bahadur Kc, Hamidreza Montazeri Aliabadi, Judith C. Hugh, Raimar Löbenberg, Hasan Uludag

Pharmacy Faculty Articles and Research

Conventional breast cancer therapies have significant limitations that warrant a search for alternative therapies. Short-interfering RNA (siRNA), delivered by polymeric biomaterials and capable of silencing specific genes critical for growth of cancer cells, holds great promise as an effective and more specific therapy. Here, we employed amphiphilic polymers and silenced the expression of two cell cycle proteins, TTK and CDC20, and the anti-apoptosis protein survivin to determine the efficacy of polymer-mediated siRNA treatment in breast cancer cells as well as side effects in non-malignant cells in vitro. We first identified effective siRNA carriers by screening a library of lipid-substituted polyethylenimines …

Development Of The Adherence Predictive Index (Api) For Medication Taking, Jon C. Schommer, Paul D. Tieger, Anthony W. Olson, Lawrence M. Brown, Daniel M. Tomaszewski

Pharmacy Faculty Articles and Research

The objective for this study was to explore if characteristics of personality type using the Preferred Communication Style Questionnaire, in concert with the demographic characteristics of age, education, and race/ethnicity, are associated with, and help predict, individuals’ medication adherence behavior.

Data were collected via an on-line survey, sent to a sample of adults residing in the United States, between April 28 and June 22, 2015. Out of 26,173 responses to the survey, 16,736 reported taking one or more medications and were eligible for inclusion in this study.

The development of the Adherence Predictive Index (API) used mean Morisky Medication Adherence …

Bioactive Compounds From Aquilalia Crassna, Garcinia Gracilis And Hydnocarpus Ilicifolia With Antioxidant, Dna Protective And Α-Glucosidase Inhibitory Activities, Chonlakan Supasuteekul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemical study of the leaves of Aquilaria crassna Pierre ex Lecomte (Thymelaeaceae) led to the isolation of three major constituents, namely, genkwanin 5-O-β-primeveroside, iriflophenone 3,5-C-β-D-diglucoside and iriflophenone 3-C-β-D-glucoside. The leaves of Garcinia gracilis Pierre (Clusiaceae) yielded 5-hydroxymethyl-2-furaldehyde, vanillic acid and apigenin-8-C-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside. The fruits of Hydnocarpus ilicifolia King (Achariaceae) afforded five compounds, namely, chrysoeriol, schweinfurthinol, luteolin, luteolin 5,3'-dimethyl ether and D-pinitol. Their structures were determined by an analysis of spectroscopic data (NMR and HR-ESI-MS) and comparison with previously reported data. Each of these compounds was evaluated for its antioxidant activity using DPPH and superoxide anion radical scavenging assays. Iriflophenone 3-C-β-D-glucoside from …

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …

Identification Of Inhibitors Of Fxii, Alexandra C. Bensel

Honors Theses

Hereditary angioedema is characterized by recurrent swelling of the extremities, larynx, and gastrointestinal tract. While type I and type II hereditary angioedema result from a C1-inhibitor deficiency, a new variant of the disease, type III hereditary angioedema, was recently discovered in individuals with functioning levels of the C1-inhibitor. Ongoing research has postulated that increased activity of factor XII is responsible for this new form of hereditary angioedema because it causes overproduction of bradykinin. The purpose of the experiment was to identify inhibitors of factor XII. One hundred and seventy six molecules were screened through a dose response using Human Factor …

Exploration In The Effectiveness Of Solid Lipid Nanoparticle Formulations In Enhancing Ocular Delivery Of Win 55, 212 In The Management Of Glaucoma, Emily Ann Nesbit

Honors Theses

Glaucoma is a progressive and degenerative ocular disease which, without proper treatment, can result in permanent blindness. Due to a complex organization of lipophilic and hydrophilic ocular membranes, topical delivery of therapeutic agents has also proved to be a challenging task. Cannabinoids, such as Δ9-Tetrahydrocannabinol (THC), have intraocular pressure (IOP) lowering and neuroprotective capabilities. Due to the unfavorable physiochemical characteristics of these molecules, delivery into the eye through a topical route is very difficult. Previous research has shown that prodrug derivatization and formulations such as solid lipid nanoparticles (SLNs) improve the physiochemical characteristics and ocular bioavailability of such molecules. WIN …

The Impact Of The Sentinel Initiative And Faers Surveillance System On Consumer Safety, Sonia Batra

Walden Dissertations and Doctoral Studies

The U.S. Food and Drug Administration (FDA) uses the FDA Adverse Event Reporting System (FAERS) to monitor adverse events resulting from pharmaceutical drug use. However, this system has limitations such as not allowing real-time data collection. To address these limitations, the FDA launched the Sentinel Initiative in 2008. This comparative case study was conducted to describe perceptions of investigating the efficacy of the Sentinel Initiative compared with the FAERS. The study was based on the theory of preemption as it emphasized the need for efficient means for providing unquestionable proof that consumers suffered adverse drug effects. The sample included interivews …

Application Of Organ Clearance To Estimation Of The In Vivo Hepatic Extraction Ratio, Reza Mehvar

Pharmacy Faculty Articles and Research

Organ clearance, which has been derived from the organ blood flow and extraction ratio (E), has been extensively used by clinical pharmacologists to explain the pharmacokinetics of many drugs in health and disease. For example, the extent of hepatic clearance or E (E_h) of drugs would determine their response to changes in the liver blood flow and/or activities of the metabolizing enzymes. Although E_h may be obtained directly by cannulating internal blood vessels, the method is invasive. Therefore, indirect methods have been used to estimate E_h from the peripheral blood concentration-time data after intravascular administration of …

Analysis Of Kentucky Medicaid Managed Care Versus Fee-For-Service Systems: Medication Adherence In Patients With Prevalent Chronic Diseases, Catherine K. Herren

Theses and Dissertations--Pharmacy

Objectives: Managed care organizations reduce healthcare costs and may improve patient health outcomes by encouraging better control of prevalent chronic diseases. The purpose of this study was to determine whether changing from a fee-for-service program to a capitated managed care program improved medication adherence for Medicaid patients in Kentucky with hypertension, hypercholesterolemia, or type 2 diabetes.

Methods: We conducted a quasi-experimental study of patients enrolled in Kentucky Medicaid to evaluate the impact of transitioning to capitated managed care in November 2011. Medication adherence was measured using the proportion of days covered (PDC) method. Multivariable analyses measured the adjusted …

The Effect Of Nicotine Co-Administration On Alcohol-Induced Reactive Hippocampal Cell Proliferation During Abstinence In An Adolescent Model Of An Alcohol Use Disorder, Megan Heath

Theses and Dissertations--Pharmacy

A significant consequence of alcohol use disorders (AUDs) is hippocampal neurodegeneration. The hippocampus is responsible for learning and memory, and neurodegeneration in this brain region has been shown to result in cognitive deficits. Interestingly, some alcoholics demonstrate improvements in hippocampus-dependent functions, potentially due the phenomenon termed adult neurogenesis. Adult neurogenesis, the process by which neural stem cells (NSCs) proliferate, differentiate into neurons, migrate into the granule cell layer, and survive, occurs in two brain regions; however, this study examines only neurogenesis occurring in the subgranular zone of the hippocampal dentate gyrus. Four-day binge ethanol exposure in an animal model causes …