Medicine and Health Sciences Commons^™

Examination Of The Pharmacodynamics And Pharmacokinetics Of A Diclofenac Poly(Lactic-Co-Glycolic) Acid Nanoparticle Formulation In The Rat, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory.

MATERIALS AND METHODS: Rats were administered a single dose of methylcellulose (VEH), blank NP, DICLO (10 mg/kg), or a DICLO-NP suspension equivalent to the DICLO dose. Urinary and blood parameters were measured …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

The Influence Of Safety, Efficacy, And Medical Condition Severity On Natural V. Synthetic Drug Preference, Brian P. Meier, Courtney M. Lappas

Psychology Faculty Publications

Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as …

Biological And Chemical Investigation Of Panamanian Plants For Potential Utility Against Metabolic Syndrome, Yelkaira Vasquez

Electronic Theses and Dissertations

Metabolic syndrome (MetS) affects approximately 25% of the adult population of the world and represents a public health concern with high socioeconomic impact worldwide. Latin American populations exhibit a high prevalence of MetS, similar or even higher than developed countries. This complex and progressive disorder can develop over many years as a cluster of conditions characterized by a constellation of metabolic abnormalities. Specific guidelines have not yet been established for the treatment of MetS per se. The increased prevalence of MetS has been associated with a greater risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In …

Food/Drug Interactions: Assessing Student Knowledge Before And After Viewing An Interactive Educational Website, Cole Smith

Undergraduate Honors Thesis Collection

Background: Knowledge of food and drug interactions is important and may greatly impact compliance and success of drug therapy. Patients are required to be educated about food and drug interactions at the point of care by the Joint Commission on Accreditation of Healthcare Organizations’ standards; and, in both the institutional and community settings, quality of patient care is improved if the patient understands the importance of food and drug interactions. Methods: This study was conducted online via a web-based survey using Survey Monkey. Students in their second year of pre-pharmacy classes were asked to complete a pre-survey, review a website …

The Efficacy Of Antidepressants In Alleviating Anhedonia In Depressed Patients, Paras Patel

Undergraduate Honors Thesis Collection

Background: Anhedonia, or the inability to feel pleasure, is an important symptom of depression because it may be involved in preventing complete recovery and facilitating depression relapse. The relationship between depression severity and anhedonia in patients being treated with antidepressants has not been widely studied. The objective of this study was to characterize the alleviation of anhedonia in patients taking antidepressants for depression.

Methods: This was a prospective survey distributed at three outpatient psychiatric settings. Subjects above the age of twenty who indicated a depression diagnosis were included. Subjects with schizophrenia, bipolar disorder, or substance abuse disorder were excluded. A …

The Use Of Podcast As A Teaching Tool For A Pharmacy Compounding Pre-Laboratory Lecture: A Survey Based Study, Lara Kratochwill, Elise Almagambetova, Anthony Corigliano, Christine R. Birnie Phd, Lipika Chablani

Pharmacy Faculty/Staff Publications

Objective: To determine the opinions of pharmacy students towards use of podcast as a replacement to a traditional pre-laboratory lecture for a compounding course.

Methods: Second year pharmacy students were asked to view a podcast prior to their laboratory section as a replacement to an in-class pre-laboratory lecture. A voluntary survey was administered to obtain student feedback regarding the usefulness of podcasts and preferences for its use in future.

Results: A total of 192 out of 232 students responded to the survey conducted during 2011, 2012 and 2013. Of these, 94% of respondents reported viewing entire/ parts of the podcast. …

Use Of Continuous Renal Replacement Therapy For Removal Of Dabigatran In A Patient In Need Of Emergent Surgery, Sara E. Parli, Melissa L. Thompson Bastin, Daniel A. Lewis

Pharmacy Practice and Science Faculty Publications

Purpose. To report the ability to remove serum dabigatran using continuous renal replacement therapy (CRRT) in a patient with life-threatening bleeding. Summary. A 77-year-old female with history of atrial fibrillation who takes dabigatran for stroke prevention presented with abdominal pain. Patient was found to have bleeding and possible mesenteric ischemia and was taken to the operating room and had continued bleeding postoperatively. CRRT was initiated for the removal of any remaining dabigatran, with serum dabigatran levels collected to evaluate removal of dabigatran with CRRT. This patient had an increased dabigatran level prior to intervention, which decreased to an …

A Branch Point Of Streptomyces Sulfur Amino Acid Metabolism Controls The Production Of Albomycin, Aditya Kulkarni, Yu Zeng, Wei Zhou, Steven Van Lanen, Weiwen Zhang, Shawn Chen

Pharmaceutical Sciences Faculty Publications

Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century. Although the productivity of S. griseus can be increased with random mutagenesis methods, understanding of Streptomyces sulfur amino acid (SAA) metabolism, which supplies a precursor for ABM biosynthesis, could lead to improved and stable production. We previously characterized the …

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 …

Multifunctional Nanocarriers For Cancer Therapy, Bei Cheng

Theses and Dissertations

Cancer is one of the leading causes of human mortality and mortality in all diseases. There has been a boost in developing nanocarrier-based therapies for treating cancer or other diseases during the past decade. One of the major advantages about nanocarrier (with the size range from 1-1000 nm) lies in its ability to specifically target tumor and maximize drug accumulation in tumor foci through the enhanced permeability and retention effect. Advancement in nanotechnology has opened a new paradigm in pharmaceutical field. But new challenges have to be overcome in order to fully exploit the technology and improve safety in clinical …

Selectivity Targeting Polo-Like Kinase 1 (Plk1) Using Novel Inhibitors Of The Polo-Box Domain, Merissa Lynnea Baxter

Theses and Dissertations

Polo-like Kinse 1 (PLK1) is a serine/threonine protein kinase that is expressed in dividing cells. It is a widely studied protein that plays an important role in regulating mitotic progression. PLK1 is over-expressed in several tumor types, and studies have shown that down-regulating PLK1 expression inhibits cancer cell proliferation, validating PLK1 as an oncotarget. Efforts to target this protein therapeutically has led to the development of several ATP-based inhibitors, although these are not exclusively specific. Because other PLK family members are tumor suppressors, it is important that PLK1 inhibitors selectively bind to PLK1 and not the other PLKs, particularly PLK3. …

Stimuli Responsive Nanoparticle For Cancer Targeted Therapy, Huacheng He

Theses and Dissertations

Nanoparticle is the particle with a size in the range from several nanometers to hundreds of nanometers. It has been extensively used for cancer diagnosis and therapy. However, it is still a great challenge to fabricate nanoparticles with spatiotemporally controllable delivery of anticancer drugs to tumors and with high therapeutic efficacy. This thesis mainly focuses on the development of stimuli responsive nanoparticles for cancer targeted therapy. These nanoparticles either response to internal stimuli such as pH and redox potential or external stimuli like temperature and light could effectively target tumors and control the release of anticancer drugs there to improve …

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 …

Two Sudden And Unexpected Deaths Of Patients With Schizophrenia Associated With Intramuscular Injections Of Antipsychotics And Practice Guidelines To Limit The Use Of High Doses Of Intramuscular Antipsychotics, Nasratullah Wahidi, Katie M. Johnson, Allen Brenzel, Jose De Leon

Psychiatry Faculty Publications

Intravenous haloperidol has been associated with torsades de pointes (TdP). These two sudden deaths were probable adverse drug reactions (ADRs) following intramuscular (IM) antipsychotics. The autopsies described lack of heart pathology and were highly compatible with the possibility of TdP in the absence of risk factors other than the accumulation of antipsychotics with a high serum peak after the last injection, leading to death within hours. The first case was a 27-year-old African-American male with schizophrenia but no medical issues. His death was probably caused by repeated IM haloperidol injections of 10 mg (totaling 35 mg in 2 days). The …

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 …

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 …