Medicine and Health Sciences Commons^™

New Synthetic Methodologies For The Construction And Optimization Of Natural Products, Amir E. Wahba

Electronic Theses and Dissertations

Toxicity associated with bioactive natural products is considered as a major obstacle in the process of drug discovery. Manzamine A (MA) is one such candidate that requires optimization to overcome the toxicity problem. The manzamine alkaloids represents a unique class of natural products that have shown a diverse range of bioactivities including antimicrobial, antiparasitic, cytotoxicity, anti-inflammatory, pesticidial, and was shown to possess activity against HIV-1 and AIDS opportunistic infections. The greatest potential for the manzamine alkaloids appears to be against malaria and neuroinflammation. Experimental and modeling studies suggested that the planer ?-carboline moiety can act as DNA intercalator and hence …

Factors Affecting Community Pharmacy Owners' Attitudes Toward And Likelihood To Adopt Rxsync Service(Sm), Namita Joshi

Electronic Theses and Dissertations

Factors affecting community pharmacy owners' attitudes toward and likelihood to adopt RxSync ServiceSM. Objective. There is an increased recognition of the role of pharmacists in the provision of patient care services. Therefore, understanding factors that affect pharmacists' attitudes and likelihood to implement pharmacy services is warranted. The objective of this study is to examine how community pharmacy owners' entrepreneurial and demographic characteristics, perceptions of pharmacy service characteristics (perceived benefit, perceived compatibility, and perceived complexity), workload perceptions, and the number of pharmacy services they already offer, affect their attitude toward and likelihood to adopt RxSync ServiceSM, a newly developed prescription management …

Pharmacy-Level Quality Measures And The Consumer: Preferences And Attitudes, Zainab S. Shahpurwala

Electronic Theses and Dissertations

Objectives. To determine the perceptions of consumers toward community pharmacy quality measures and compare their perceptions regarding their pharmacy's overall quality before and after exposure to these measures. To explore the use of evaluative criteria applied by consumers to determine their preference for information related to these measures. Methods. Focus groups were used to refine attributes and levels used in the quantitative phase of the study. An Internet-based survey was administered to a national, online, consumer panel of community pharmacy patrons using maintenance medications. Descriptive statistics, MANOVA and t-tests were used to determine and compare perceptions related to the community …

Design, Synthesis, Biological Evaluation And Metabolic Stability Studies Of Sigma Receptor Ligands, Rohit Bhat

Electronic Theses and Dissertations

Sigma receptors represent a unique family of proteins that includes two subtypes: sigma-1 and sigma-2. Sigma-1 receptors have been implicated in the behavioral and motivational effects of psychostimulants as well as in the pathophysiology of depression and Alzheimer's disease. Sigma-2 receptors are widely expressed on many tumor cells and they are believed to play an important role in tumor cell proliferation. Therefore, sigma receptors are attractive targets for developing pharmaceutical agents directed to the treatment of psychostimulant abuse, cancer, Alzheimer's disease as well as diagnostic agents for cancer and brain imaging. A derivatized 2(3H)-benzothiazolone, (3-(2-(azepan-1-yl)ethyl)-6-propylbenzo[ d]thiazol-2(3H)-one) was reported to have …

Case-Mix Adjustment Of Adherence Based Pharmacy Quality Indicator Scores, Sai Hurrish Dharmarajan

Electronic Theses and Dissertations

Medication adherence has been shown to be influenced by demographics, health status and socio-economic status of the patient. Thus, adherence-based measures of pharmacy quality may be influenced by patient-related risk factors outside of the healthcare provider's control. This study examines the performance of a classical logistic regression model containing only patient characteristics and a random-effect model including patient characteristics and a pharmacy-specific effect in predicting medication adherence. These models were used to compute three different risk-adjusted scores on adherence-based pharmacy quality indicators: based on the classical logistic regression model (Method 1), the random effects model (Method 2) and the shrinkage …

Factors That Physicians Find Encouraging And Discouraging About Electronic Prescribing: A Quantitative Study, Krutika Satish Jariwala

Electronic Theses and Dissertations

Research objective. While the adoption of e-prescribing is growing, the Institute of Medicine's recommendations that all prescriptions be routed electronically by 2010 certainly has not been met. Therefore, the objective of this study is to compare the factors that physicians find encouraging and discouraging about e-prescribing based on their e-prescribing adoption status. Study design. Cross-sectional, descriptive design. An Internet-based survey was sent to national convenience sample of physicians. Using e-prescribing literature, 44 items were developed concerning various factors related to the adoption of e-prescribing. Physicians rated how much the factors encouraged them or discouraged them about e-prescribing. Analysis procedures included …

Part A: Studies Towards Total Synthesis Of An Anticancer And Antifungal Natural Product, Pseudolaric Acid B; Part B: Synthesis And Biological Evaluation Of Berkeleyamide A And Its Derivatives, Swapnil Jayant Kulkarni

Electronic Theses and Dissertations

Part A: Studies towards total synthesis of an antifungal and anticancer agent, Pseudolaric acid B. Marked by the uncontrolled cell proliferation, cancer is one of the deadliest diseases, accounting for about 7.0 million deaths in 2007. Cancer is second leading cause of death worldwide, according to the American Cancer Society. Cancer chemotherapy has evolved through many years of painstaking research, and as a result, today we are able to cure at least some of cancers. One of the major impediments in the development of new drugs for treating cancer is that most of the approved drugs are themselves toxic and …

Market Response To Food And Drug Administration's Safety Warnings: A Case Study Using An Interrupted Time Series Analysis Of The Medicare Database For 2006-2008, Hafiz Oko-Osi

Electronic Theses and Dissertations

Objectives: To evaluate the impact of a safety warning on the utilization rates of thiazolidinedione oral anti-diabetes medication using an interrupted time series analysis. Methods: We extracted data from a five percent national sample of Medicare Part D beneficiaries for the periods between January 2006 and December 2008. Beneficiaries with Part D claims for thiazolidinediones were classified into appropriate-use, at risk, and contraindicated groups based on certain comorbid conditions. We assessed the effects of the May 2007 FDA safety warning about an ongoing safety review of rosiglitazone's potential to increase cardiovascular risks on thiazolidinedione utilization rates using an interrupted time …

Use Of Structure-And Ligand-Based Drug Design Tools For The Discovery Of Small Molecule Inhibitors Of Cysteine Proteases For The Treatment Of Malaria And Sars Infection, Falgun Shah

Electronic Theses and Dissertations

A wide array of molecular modeling tools were utilized to design and develop inhibitors against cysteine protease of P. Falciparum Malaria and Severe Acute Respiratory Syndrome (SARS). A number of potent inhibitors were developed against cysteine protease and hemoglobinase of P. falciparum , referred as Falcipains (FPs), by the structure-based virtual screening of the focused libraries enriched in soft-electrophiles containing compounds. Twenty one diverse, non-peptidic, low micromolar hits were identified. A combined data mining and combinatorial library synthesis approach was performed to discover analogs of virtual screening hits and establish the structure-activity relationships (SAR). However, the resulting SAR of the …

Biopharmaceutical Approaches For Improved Drug Delivery Across Ocular Barriers, Ketan Hippalgaonkar

Electronic Theses and Dissertations

The eye is protected from the external environment by various physiological and anatomical barriers. These barriers through there protective actions drastically diminish the ocular bioavailability of drugs. The corneal epithelium acts as a major barrier towards the permeation of hydrophilic agents, whereas poor aqueous solubility presents a formulation challenge for lipophilic compounds. Additionally, P-glycoprotein (P-gp) expressed on the retinal pigmented epithelium (RPE P-gp) limits the penetration of substrates, in therapeutically relevant concentrations, into the back-of-the-eye.

In the present research, use of penetration enhancers (chitosan, benzalkonium chloride (BAK) and ethylenediaminetetraacetic acid (EDTA)) and formulation approaches (cyclodextrins and solid lipid nanoparticles (SLNs)) …

Synthesis Of A Water Soluble Resveratrol Derivative As A Potential Anti-Cancer Drug., Augustine Essel

Electronic Theses and Dissertations

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized …

Trends In International Compulsory Licensing Of Pharmaceuticals Since The Institution Of The Trade-Related Aspects Of Intellectual Property Protection (Trips) Agreement, Reed F. Beall

Electronic Theses and Dissertations

The Trade-related Aspects of Intellectual Property Rights (TRIPS) Agreement went into effect for World Trade Organization (WTO) members in 1995. The agreement defines minimum standards of patent protection that must eventually be observed by all signatories. TRIPS includes "compulsory licensing", a policy that allows for states under certain conditions to permit the use of a patented innovation without the consent of the patent holder. This paper considers instances of compulsory licenses (CLs) aimed to increase access to pharmaceuticals during urgent public health scenarios. The WTO maintains no registry of CLs; therefore, this research is an effort to catalog as many …

Fungi-Derived Natural Products With Binding Affinities For Human Opioid Or Cannabinoid Receptors, Jiangtao Gao

Electronic Theses and Dissertations

Both opioid and cannabinoid receptors belong to the large superfamily of GPCRs and play an important role in a variety of processes including pain, craving, neurodegeneration, metabolic regulation, anxiety and immune function. Therefore, recent advances and discoveries in opioid and cannabinoid receptors have paved the way for a very exciting future for opioid and cannabinoid receptors-based therapies to potentially treat a variety of conditions. However, the growing realizations of the complexity of these two receptors regulation in physiological and pathological conditions have discouraged the development of new therapeutics. So, it is important for us to identify new chemical scaffolds which …

Preparation And Characterization Of Lyophilized Cyclodextrin Complexes Of A Hemisuccinate Ester Of Delta-9-Tetrahydrocannabinol For Transmucosal Delivery, Sampada Bhaskar Upadhye

Electronic Theses and Dissertations

Delta-9- Tetrahydrocannabinol (THC) is the primary active ingredient of the plant Cannabis sativa (marijuana), responsible for the majority of the pharmacological effects. The most promising clinical applications of THC approved by the Food and Drug Administration (FDA) are for the control of nausea and vomiting associated with chemotherapy and for appetite stimulation of AIDS patients suffering from anorexia and wasting syndrome. The only dosage form currently approved by FDA is an oral, soft gelatin capsule (e.g. Marinol®). In addition, orally administered THC from Marinol® has shown slow and variable absorption due to low oral solubility and first pass metabolism. Our …

Pharmacists' Rating Of Relevance Of Available Information In Deciding The Validity Of Opioid Medication Prescriptions, Leonardo Roberto Torres

Electronic Theses and Dissertations

Pharmacists are tasked with making decisions regarding the validity of prescriptions. Some have proposed factors that should be considered when evaluating a prescription's validity. Yet, there is little known about the decision process that pharmacists employ at the time of dispensing and what information pharmacists deem relevant in that decision-making process. Using an online survey instrument, a sample of community pharmacists were divided into three groups and presented with a prescription scenario. They were asked to rate the relevance of information, which is proposed to be appropriate and inappropriate, available at the time of dispensing. They were asked to consider …

Willingness To Influence Indication-Based Off-Label Prescribing: An Investigation Of Hospital Pharmacists, Ram Sankar Basak

Electronic Theses and Dissertations

Off-label prescribing is a comand legal practice in the United States. However, off-label prescribing occurs oftentimes with inadequate evidence of effectiveness. Such practice, especially when prescribing for disease conditions different from approved clinical indications (indication-based off-label prescribing), brings about controversy and raises different issues with various stakeholders. Although indication-based off-label prescribing offers advantages in terms of providing innovative therapy, it raises concerns because the safety and efficacy of such use may not be evaluated adequately. Thus, the objective of the study was to examine whether pharmacists are willing to influence physicians while evaluating an indication-based off-label medication order. Based on …

Type 2 Diabetes In Children: Estimates Of Epidemiology, Quality Of Care, Costs And Resource Utilization In A Medicaid Population, Vennela Thumula

Electronic Theses and Dissertations

Objective: the primary goal of this study was to assess the current state of diabetes, specifically type 2 diabetes in Mississippi Medicaid enrolled pediatric population. Background: Diabetes is the most prevalent pediatric chronic condition. Recent trends indicate that type 2 diabetes in children is increasing. Epidemiology estimates of type 2 diabetes in children and adolescents are limited. Quality of care and their health care utilization estimates are not available. Methods: 2002 - 2004 Mississippi Medicaid claims data were used for this study. A combination of ICD-9 codes (250.0x - 250.9x, where x=0 or 2) and/or oral hypoglycemic (OHG) drug use …

Synthesis Of Marine Chemicals And Derivatives As Potential Anti-Cancer Drugs., Laude Bannerman-Akwei

Electronic Theses and Dissertations

Two natural marine compounds, 3-bromo-4,5-dihydroxybenzaldehyde 2 and 2,3-dibromo-4,5-dihydroxybenzaldehyde 5 together with two novel derivatives, 3-bromo-5-(tert-butyl-dimethyl-silanyloxy)-4-hydroxybenzaldehyde 3 and 1-bromo-2,3-dimethoxy-5-nitrooxy-methylbenzene 9, were synthesized. Compounds 2, 3, and 5 were evaluated for their biological activity towards the inhibition of prostate cancer cell growth using staurosporine a a positive control. All three compounds have shown significant inhibition of prostate cancer cell growth. Compound 9 is yet to be evaluated.

Cytotoxic Effects Of Ruthenium Compounds On Human Cancer Cell Lines., Katie Beth Brown

Electronic Theses and Dissertations

Chemotherapy is the most common cancer treatment. Traditionally, platinum-based drugs are used in chemotherapy. More recently, researchers have focused on ruthenium based compounds as a substitute for the platinum compounds. Ruthenium-based compounds appear to be less toxic to healthy cells than traditional platinum-based compounds. In this study, 7 ruthenium-based compounds were tested on HT-29 (colon) and MCF-7 (breast) human cancer cell lines with the specific aim of determining whether or not any of the ruthenium-based compounds exhibited cytotoxic properties. In addition, levels of vascular endothelial growth factor (VEGF) production were tested in supernate from the cancer cells treated with various …