Medicine and Health Sciences Commons^™

Potential Natural Product Phosphodiesterase Inhibitors, Michael John Cunningham

Electronic Theses and Dissertations

Three different studies set forth to investigate the role of phosphodiesterase (PDE) enzyme inhibitors in sexual dysfunction and mood regulation. First, naturalproducts were screened by computer modeling of PDE5A1. Second, compounds were isolated from a plant traditionally used as an aphrodisiac. Third, a new synthesis of psychoactive PDE4 inhibitor was attempted. An in silico screen was performed using chemical structures of isolated compounds thought to have some PDE inhibitory activity based on traditional use of the plants. A collection of compounds with structures similar to known natural product inhibitors was also included in the docking library. Glide docking software (Schrödinger) …

Structural Characterization And Bioactivity Of Cranberry Oligosaccharides, Kimberly M. Auker

Electronic Theses and Dissertations

Complex carbohydrates from plant sources, such as the fruits of cranberry (Vaccinium macrocarpon Aiton), promote human health in a variety of ways. However, complete studies of carbohydrate function often hinge on a detailed understanding and thorough elucidation of the chemical structure. Several methods have been used in the structure elucidation of cranberry oligosaccharides, such as derivatization folloby analysis using gas chromatography-mass spectrometry (GC-MS). In this manner, the identity and quantity of glycosyl units within two cranberry oligosaccharides were investigated through hydrolysis of the oligomers and subsequent synthesis of trimethylsilyl and alditol acetate derivatives. Further analysis using partially methylated alditol acetate …

Pharmacy Law Brief: Contemporary Legal Issues For Leadership In Non-Profits - Iii, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Community Pharmacists' Attitudes Toward An Expanded Class Of Nonprescription Drugs, Ruchitbhai Mukesh Shah

Electronic Theses and Dissertations

Objectives: there has been considerable discussion about creating a third class of drugs which would not require a prescription, but require a pharmacist's consultation upon purchase. Very recently the Food and Drug Administration (FDA) held a hearing which repositioned a third class as an expanded nonprescription drug class termed as the "new paradigm" using certain innovative technologies. The specific objectives of this study were to: 1) measure community pharmacists' attitudes toward an expanded nonprescription drug class under the FDA’s proposed "new paradigm"; 2) determine if attitudes of community pharmacists toward an expanded nonprescription drug class under the FDA’s proposed "new …

Concurrent Adherence To Multiple Chronic Disease Medications: Examining The Behavior And Issues Concerning Its Measurement, Ram Sankar Basak

Electronic Theses and Dissertations

Objectives the objectives were to 1) examine adherence to multiple medications prescribed for a chronic disease (intra-disease multiple medication adherence) and that of multiple chronic diseases (inter-disease multiple medication adherence); 2) determine appropriate measurement paradigm from different intra-disease multiple medication adherence measurement approaches; 3) identify optimal cut-point for a dichotomized composite measure. Methods a retrospective study design was used. The subjects came from the marketscanâ® commercial claims and encounters data 2002-2003 and filled both sulfonylurea (su) and thiazolidinedione (tzd). Adherence was measured by proportion of days covered (pdc) over each period of 30 or 90 days and cumulatively. Random components …

Relationship Between Clandestine Methamphetamine Laboratory Seizures And Burns In Kentucky, David A. Wittmer

MPA/MPP/MPFM Capstone Projects

Methamphetamine is a highly addictive stimulant that is synthetically produced using equipment and chemicals available in the community. Its burden to society may be determined through a number of mechanisms, including the imposed strain on healthcare systems. The evolution of methamphetamine use and production methods has led to reports of increased methamphetamine related burn admissions among hospital burn units[1-3] . Current literature identifies an increase in injury severity, comorbid complications, and cost of care associated with methamphetamine related burn injuries[1-5]. The intent of this study is to identify burn injuries in Kentucky and assess whether a statistically significant association exists …

Molecular Modeling And Sar Studies Of Cdk5/P25 Selective Inhibitors, Arindam Chatterjee

Electronic Theses and Dissertations

Alzheimer's disease (AD) is one of the most dreaded forms of progressive neurodegenerative diseases. The two main hallmarks of AD are the formation of amyloid senile plaques and neurofibrillary tangles. Cyclin dependent kinase 5 (CDK5) is a proline directed serine/threonine kinase, which expressed primarily in the central nervous system. In the biochemical process the CDK5-natural activator, p35 is cleaved by calpain to a shorter protein p25, which in turn hyperphosphorylates Tau, forms neurofibrillary tangles and causes AD. CDK5 deregulation is also indicated in other neurodegenerative diseases, such as Huntington's chorea, stroke, Parkinson's disease, amyotrophic lateral sclerosis, major depression and substance …

Scaffold Perception, Compharmacophore Model Development, And Quantitative Structure-Affinity Relationships Of Sigma Site Ligands, David Enos Watson

Electronic Theses and Dissertations

Sigma receptors are endogenous proteins with potential utility in treating psychological disorders, ischemia, the psychological and convulsive effects of drugs of abuse, and as an imaging agent for cancerous tissues, among others. Drug design efforts targeting these receptors have been hindered by a lack of structural information of the receptors themselves. Traditional ligand-based approaches have succeeded in generating many compounds with high affinity, and quite a few with selectivity for σ-1 receptors. There are few selective ligands for use as pharmacological probes for the σ-2 receptor. Much effort has gone into exploring the structure activity relationships of ligands targeting these …

Menthol Binding And Inhibition Of A7-Nicotinic Acetylcholine Receptors, Abrar Ashoor, Jacob C. Nordman, Daniel Veltri, Keun-Hang Susan Yang, Lina T. Al Kury, Yaroslav M. Shuba, Mohamed Magoub, Frank Christopher Howarth, Bassem Sadek, Amarda Shehu, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca2+-dependent Cl− channels, since menthol inhibition remained unchanged by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing …

Oral Mucositis And Stomatitis Associated With Conventional And Targeted Anticancer Therapy, Amy Parkhill

Pharmacy Faculty/Staff Publications

Oral mucositis and stomatitis are characterized by pain, inflammation, and redness in the oral cavity. In the case of mucositis, ulceration also occurs. Despite being understudied, these symptoms are some of the most troubling, and yet common, adverse effects associated with cancer treatment. The incidence of these toxicities is highly variable depending on treatment-related and patient-related risk factors. However, most cancer treatment regimens carry some risk of this toxicity. The presence of mucositis or stomatitis can result in a significant decrease in the patient?s quality of life due to severe pain and the inability to eat or drink. These toxicities …

Association Between Concomitant Use Of Bisphosphonates And Serotonin Reuptake Inhibitors And Increased Risk Of Osteoporotic-Related Fractures: Among Community-Dwelling Postmenopausal Women, Abner Nyandege

Theses and Dissertations

Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs …

Medicare Part D Roulette: Potential Implications Of Random Assignment And Plan Restrictions, Rajul A. Patel, Mark P. Walberg, Joseph A. Woelfel, Michelle M. Amaral, Paresh Varu

School of Pharmacy Faculty Articles

Background: Dual-eligible (Medicare/Medicaid) beneficiaries are randomly assigned to a benchmark plan, which provides prescription drug coverage under the Part D benefit without consideration of their prescription drug profile. To date, the potential for beneficiary assignment to a plan with poor formulary coverage has been minimally studied and the resultant financial impact to beneficiaries unknown.

Objective: We sought to determine cost variability and drug use restrictions under each available 2010 California benchmark plan.

Methods: Dual-eligible beneficiaries were provided Part D plan assistance during the 2010 annual election period. The Medicare Web site was used to determine benchmark plan costs and prescription …

Identification Of Distant Drug Off-Targets By Direct Superposition Of Binding Pocket Surfaces., Marcel Schumann, Roger S Armen

College of Pharmacy Faculty Papers

Correctly predicting off-targets for a given molecular structure, which would have the ability to bind a large range of ligands, is both particularly difficult and important if they share no significant sequence or fold similarity with the respective molecular target ("distant off-targets"). A novel approach for identification of off-targets by direct superposition of protein binding pocket surfaces is presented and applied to a set of well-studied and highly relevant drug targets, including representative kinases and nuclear hormone receptors. The entire Protein Data Bank is searched for similar binding pockets and convincing distant off-target candidates were identified that share no significant …

Fibroblast Growth Factor-2 (Fgf2) And Syndecan-1 (Sdc1) Are Potential Biomarkers For Putative Circulating Cd15+/Cd30+ Cells In Poor Outcome Hodgkin Lymphoma Patients., Rajendra Gharbaran, Andre Goy, Takemi Tanaka, Jongwhan Park, Chris Kim, Nafis Hasan, Swathi Vemulapalli, Sreeja Sarojini, Madalina Tuluc, Kip Nalley, Pritish Bhattacharyya, Andrew Pecora, K Stephen Suh

College of Pharmacy Faculty Papers

BACKGROUND: High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment.

METHODS AND MATERIALS: Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Bioassay Guided Fractionation Of American Ginseng. A Hexane Fraction Of American Ginseng Suppresses Colitis And Associated Colon Cancer. Mechanism Of Action., Deepak Poudyal

Theses and Dissertations

Inflammatory Bowel Disease (IBD) [Ulcerative colitis (UC) and Crohn's Disease (CD)] is a group of chronic disorders of unknown etiology characterized by inflammation in the gastrointestinal tract associated with a high colon cancer risk. UC is characterized by periods of active disease ("flare-ups"), followed by periods when the disease is inactive ("remission"). The end result is an abnormal immune response with repeated episodes of colonic inflammation. Conventional treatment of UC by aminosalicylates, TNFα inhibitors, and steroids have modest effects, and come with a high risk of side effects including dyspeptic symptoms, gastric ulceration and sometimes hospitalization and deaths. Because of …

Effects Of Dna Damage And Cdk Inhibitors On The Nucleoli, Vineet Garg

Theses and Dissertations

The nucleolus is the primary site of ribogenesis and consists of three compartments, namely, fibrillar center (FC), dense fibrillar component (DFC) and granular component (GC). Recent studies have observed a novel structure distinct from these three compartments which forms in the nucleolus upon DNA damage called Intranucleolar body (INoB). Previous studies in our laboratory have found INoBs forming in HT1080 fibrosarcoma cell lines after ectopic overexpression of damage-inducible cell cycle inhibitor p21. This INoB formation has been observed to be decreased by Senexin A which is an inhibitor of transcription regulating kinases CDK8/CDK19.

Here we show that INoB formation correlates …

K+ Channels And Beta3 Adrenergic Receptors As New Pharmacological Targets For Overactive Bladder Treatment, Serge Amani Yao Afeli

Theses and Dissertations

Overactive bladder (OAB) is a pathophysiological condition which is characterized by the urinary bladder's failure to achieve proper storage of urine. OAB has a tremendous impact on the patient's quality of life by disturbing his sleep, work, and sexual activity. About 17% of Americans are affected with this disease and most patients experience symptoms of urgency, frequent urination, and abnormally elevated detrusor smooth muscle (DSM) contractility. Despite, numerous attempts to treat the disorder in the past with antimuscarinics and now with beta3 adrenergic receptors (beta3-AR agonists), OAB still remains a serious public health issue because the long term efficacy of …

A Novel Approach To The Design Of Selective Inhibitors For Cell Cycle Cyclin Dependent Kinases, Tracy Perkins

Theses and Dissertations

CDK2/cyclin A and CDK4/cyclin D1 are proven targets for cancer drug discovery. The development of novel CDK inhibitors, with high selectivity, are being investigated by targeting the cyclin binding groove (CBG) located on the cyclin, the regulatory subunit of CDK. The CBG is a shallow area that is involved in signaling and the inhibition of cell cycle CDKs via endogenous tumor suppressors. Currently, non-peptidic inhibitors are being developed based on the recognition amino acid sequence, HAKRRLIF, of the C-terminal peptide sequence of the CDK inhibitor p21WAF1. Computational design and the utilization of non-natural amino acids are being proposed to identify …

Snail Induces Mesenchymal Transition And Promotes Egfr Tki Resistance In Nsclc Cells Harboring Efgr Kinase Domain Mutations, Rutu Gandhi

Master's Theses

Lung cancer is the leading cause of cancer related death, accounting for one third of all deaths from cancer worldwide. About 85-90% of lung cancers are non-small cell lung cancers (NSCLCs). Molecular targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) provide an effective treatment option for oncogene addicted NSCLC. However, the development of resistance to EGFR TKIs continues to be the major limitation in the treatment of NSCLC. Resistance to EGFR TKIs has been associated with the loss of canonical epithelial protein E-cadherin, suggesting involvement of epithelial to mesenchymal transition (EMT) in conferring EGFR TKI …

Development Of Cell Based Reporter Assay To Measure Pkc-Delta Promoter Activity, Kushal Prajapati

Master's Theses

Protein kinase C- δ (PKC-δ) acts as a tumor suppressor in skin cancer and is lost in 30% of human Squamous Cell Carcinoma (SCC). This loss is at the transcriptional level and involves the pathway leading to PKC-δ promoter repression after activation of Ras,PI3K,Fyn, and NF-κB. We proposed development of a high throughput, cell-based luciferase reporter assay on Ras transformed keratinocyte cell line, HaCaT-Ras to screen compounds having potential to inhibit this pathway and re-induce PKC-δ expression. First we developed a stable, PKC-δ promoter-reporter transfected HaCaT-Ras cell line. Next, we tested 13 compounds for their abilities to induce PKC-δ …

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Prevalence Of Anti-Diabetic And Antilipidemic Medications In Children And Adolescents Treated With Atypical Antipsychotics In A Virginia Medicaid Population, Della Varghese

Theses and Dissertations

Objective: To determine if the prevalence of anti-diabetic and antilipidemic medication use among children treated with atypical antipsychotics is higher than those not treated with antipsychotics. Methods: Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010 to July 31, 2011 with at least two prescription claims for atypical antipsychotics were the exposed group. All other subjects during the study period were the non-exposed group. Prevalence of anti-diabetic and antilipidemic medication use in both groups were computed and compared using Chi-square test (α=0.05). Results: A total of 299,593 and 4,922 subjects were identified as the non-exposed and exposed groups, …

Kinetics And Mechanisms Of Accumulation For Liposomal Ciprofloxacin Into Rat Alveolar Macrophages, Sayeed Mossadeq

Theses and Dissertations

The kinetics and mechanism of accumulation for liposomal ciprofloxacin (Lipo-CPFX) into the rat alveolar macrophage NR8383 cells were studied in vitro, in comparison to unformulated ciprofloxacin (CPFX). Upon incubation with CPFX or Lipo-CPFX, cellular drug accumulation was determined from the cell lysates or efflux was from the extracellular media by fluorescence-HPLC. The accumulation for Lipo-CPFX reached the asymptotic values at ≥ 2 hours, which was a result of uptake and efflux. The uptake appeared to be due to liposomes, mediated via cellular energy-independent mechanism like lipid fusion. In contrast, the efflux appeared to be due to ciprofloxacin, partly cellular energy-dependent, …

In Vitro Lung Epithelial Cell Transport And Anti-Inflammatory Activity For Liposomal Ciprofloxacin, Ruba Darweesh

Theses and Dissertations

Liposomal ciprofloxacin (Lipo-CPFX) is being developed for inhalation, with a goal of sustaining the therapeutic activity, compared to unformulated ciprofloxacin (CPFX). However, the kinetics and mechanism of its sustained local lung retention and pharmacological activity are yet to be fully characterized. This project hypothesized that Lipo-CPFX enables slower and sustained lung epithelial transport and uptake, compared to CPFX, thereby producing prolonged local pharmacological actions. The human bronchial epithelial Calu-3 cells were used as monolayers to characterize the kinetics and mechanism of transport and/or uptake, and to assess the effects of such slow kinetics for Lipo-CPFX on its inhibition against lipopolysaccharide …

Precision And Accuracy: Omnipod Pdm® (O-Pdm) Versus Freestyle Lite Meter® (Fsl Meter) Utilizing Freestyle Lite (Fsl)® Test Strips In Multiple Patient Situations, Christine M. Hayden

Honors Theses

Today, diabetes mellitus affects 8.3% of the people in the United States and is having detrimental effects on patient populations as well as health care. To this date, there are numerous monitors that all meet specific requirements and industry standards in order to aid patients in self-monitoring of blood glucose (SMBG). There is currently a large market for these monitors and efforts have been made to devise the monitors to be accurate and precise. Through this study, accuracy and precision were studied by evaluating the difference between the O-PDM and FSL meter monitoring systems. It was hypothesized that a difference …

Novel Therapy For Nicotine Addiction In Alcohol Dependent Rats, Bethany Ann Stennett

UNF Graduate Theses and Dissertations

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process …

Regulation Of Over-The-Counter Derivatives: A Comparative Study Of Proposals In Singapore And Hong Kong, Chao-Hung Christopher Chen

Research Collection Yong Pung How School Of Law

This chapter identifies some of the potential legal and policy issues involved in the future regulation of over-the-counter (OTC) derivatives. First, regulators must be cautious in the regulation and solvency of some mammoth clearing- houses. Second, Singapore and Hong Kong both face challenges in the areas of global regulatory cooperation and extra-territorial regulatory effects. Third, the exact scope of a clearing obligation determines whether there is any regulatory competition or room for regulatory arbitrage in the future. Fourth, there are legal definition problems with the term ‘derivative’ and its sub-categories that must be addressed. Fifth, there are potential privacy and …

Research News: 2012, No. 2, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants and contracts recently awarded

Preparasi, Karakterisasi Dan Evaluasi Pelepasan Obat Dari Beads Kalsium Alginat Deksametason Dengan Metode Gelasi Ionik, Christye Aulia, Joshita Djajadisastra

Majalah Ilmu Kefarmasian

Inflammatory Bowel Disease (IBD) is a disease of inflammation in the colon. Targeted delivery systems for the treatment of IBD is designed to increase the drug concentration in the local tissue. Dexamethasone is a drug having anti-inflammatory and antifibrosis effects which is used to repair scar tissue arising from postoperative IBD. This research purpose to create calciumalginate beads dexamethasone to be released only in the colon. Beads were made by using sodium-alginate and Ca2+ as crosslinker by ionic gelation method, with ratio between sodium alginate-dexamethasone (3:1). A concentration of solution sodium alginate 3 % b/v with variation concentration of crosslinker …