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New Synthetic Methodologies For The Construction And Optimization Of Natural Products, Amir E. Wahba 2011 University of Mississippi

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 ...


Biopharmaceutic And Pharmacokinetic Evaluation Of Hesperidin And Hesperetin For Ocular Delivery, Ramesh Srirangam 2011 University of Mississippi

Biopharmaceutic And Pharmacokinetic Evaluation Of Hesperidin And Hesperetin For Ocular Delivery, Ramesh Srirangam

Electronic Theses and Dissertations

The bioflavonoid hesperidin and its aglycone hesperetin are promising candidates for the treatment of diabetic retinopathy and diabetic macular edema because of their pharmacological properties. The objective of this project was to characterize the biopharmaceutic and pharmacokinetic characteristics of hesperidin and hesperetin for ocular delivery, especially with respect to the distribution of these compounds to the posterior segment of the eye. Hesperidin and hesperetin were found to be water insoluble compounds. Although they demonstrated good permeability across the ocular tissues, hesperetin's permeability was found to be higher than that of hesperidin. Hesperidin demonstrated symmetrical transcorneal and transretinal permeation whereas ...


Pharmacy-Level Quality Measures And The Consumer: Preferences And Attitudes, Zainab S. Shahpurwala 2011 University of Mississippi

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 ...


Design, Synthesis, Biological Evaluation And Metabolic Stability Studies Of Sigma Receptor Ligands, Rohit Bhat 2011 University of Mississippi

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- ...


The Strategic Value Driver Model: A Methodology For Examining Value Drivers For A New Pharmaceutical Product In Diabetes, Sumit Verma 2011 University of Mississippi

The Strategic Value Driver Model: A Methodology For Examining Value Drivers For A New Pharmaceutical Product In Diabetes, Sumit Verma

Electronic Theses and Dissertations

Objective. Objective The primary objective of this study was to explore a new methodological framework—Strategic Value Driver Model (SVDM), for examining value drivers for new pharmaceutical inhaled insulin in diabetes. Methods. A cross-sectional, internet-based survey was used to collect a sample of 483 Type 2 diabetic patients via national panel of diabetic patients. The sample had two subgroups—insulin-naïve (52.9%, n=255) and insulin-user (47.1%, n=227) patients. The comparative performance of insulin syringes/vials, insulin pen and inhaled insulin was captured on four product attributes (i.e., safety, convenience, clinical efficacy and cost) after asking the ...


Nose To Brain Delivery Of Therapeutic Agents, Siva Ram Kiran Vaka 2011 University of Mississippi

Nose To Brain Delivery Of Therapeutic Agents, Siva Ram Kiran Vaka

Electronic Theses and Dissertations

The potential treatment approaches for various disorders associated with central nervous system are invasive and do not allow frequent administration. Brain targeting of drugs by intranasal route is a safe and noninvasive method of drug delivery which allows frequent administration and is certainly more patient compliant than the currently followed invasive methods. In this study, the plausibility of delivering neurotrophins [nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)], neurotrophinogenic agents (ex: carnosic acid) and antibiotics (ex: cefotaxime) to brain via nose-brain pathway using chitosan as barrier modulating agent was investigated. In vitro permeation studies of fluorescein isothiocyanate dextran ...


Factors Affecting Community Pharmacy Owners' Attitudes Toward And Likelihood To Adopt Rxsync Service(Sm), Namita Joshi 2011 University of Mississippi

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 ...


Do Statins Improve Outcomes In Patients With Asthma On Inhaled Corticosteroid Therapy? A Retrospective Analysis Of The Mississippi Medicaid Database 2002-2004., Tasneem Taher Lokhandwala 2011 University of Mississippi

Do Statins Improve Outcomes In Patients With Asthma On Inhaled Corticosteroid Therapy? A Retrospective Analysis Of The Mississippi Medicaid Database 2002-2004., Tasneem Taher Lokhandwala

Electronic Theses and Dissertations

Animal model studies and clinical trials have looked at the potential benefits of the anti-inflammatory properties of statins in asthma management with contradictory results. Therefore, the objective of this study is to determine if asthma patients on concurrent statin therapy are less likely to have asthma-related hospitalizations and emergency room (ER) visits. We conducted a retrospective cohort study using Medicaid data for 2002–2004. Asthma patients ?18 years old were identified using the ICD9 code 493.xx, from Jul 1, 2002 through Dec 31, 2003. The index date for an exposed subject was any date within the identification period, 180 ...


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 2011 University of Mississippi

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 ...


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 2011 University of Mississippi

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 ...


The Relationship Between Psychological Contract Breach, Professional Identity, And Organizational Citizenship Behaviors: An Equity Sensitivity Perspective, Leigh Ann Bynum 2011 University of Mississippi

The Relationship Between Psychological Contract Breach, Professional Identity, And Organizational Citizenship Behaviors: An Equity Sensitivity Perspective, Leigh Ann Bynum

Electronic Theses and Dissertations

Objectives: The purpose of this research was twofold. First, it tested the effects of the type of perceived psychological contract breach, equity sensitivity, and identity salience on an important employee outcome, namely organizational citizenship behaviors. Second, the research explored the effects that discipline and pharmacist status have on organizational citizenship behaviors. More precisely, the effect of equity sensitivity on the relationships between identity salience (discipline or school), type of perceived contract breach (administrative or professional) and the performance of organizational citizenship behaviors toward the School of Pharmacy by pharmacy school faculty was examined. Methods: Existing organizational citizenship, identity salience and ...


Biophysical Techniques Of Transcutaneous Drug Sampling And Drug Delivery, Srinivasa Murthy Sammeta 2011 University of Mississippi

Biophysical Techniques Of Transcutaneous Drug Sampling And Drug Delivery, Srinivasa Murthy Sammeta

Electronic Theses and Dissertations

Monitoring the time course of drug in the skin is critical for determining the frequency and dose of drug administration from safety and efficacy perspectives. Intermittent blood sampling is used as a surrogate for approximating concentration of drugs in the tissues, which leads to blood loss and discomfort to patients. A novel noninvasive technique called “Electroporation and transcutaneous sampling” (ETS) was developed for estimating the drug concentration in the skin extracellular fluid. The application of ETS technique in studying dermatokinetics of cephalexin, ciprofloxacin, and 8-methoxypsoralen was investigated. The results demonstrated the ability of ETS technique in dermatokinetic studies of drugs ...


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 2011 University of Mississippi

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 identified ...


Morinda Citrifolia L. (Noni) Improves The Quality Of Life In Adults With Osteoarthritis, Mian-Ying Wang, M. Nawal Lutfiyya, Vicki Weidenbacher-Hoper, Lin Peng, Martin S. Lipsky, Gary Anderson 2011 University of Illinois College of Medicine at Rockford

Morinda Citrifolia L. (Noni) Improves The Quality Of Life In Adults With Osteoarthritis, Mian-Ying Wang, M. Nawal Lutfiyya, Vicki Weidenbacher-Hoper, Lin Peng, Martin S. Lipsky, Gary Anderson

Community Health Faculty Publications and Presentations

Background: Morinda citrifolia Linn (noni), as a “pain killer”, has been used as a traditional medicine by Polynesians for over 2000 years. It was reported to have a broad range of therapeutic effects including analgesic and anti-inflammation. The in-vitro and in vivoanti-inflammatory and analgesic properties of noni juice (NJ) suggest that NJ may be a useful adjunctive treatment for osteoarthritis (OA). In this pilot study we explored whether NJ improves the symptoms and Quality of Life (QoL) for adults with OA. We also sought to evaluate the tolerability and safety of NJ for patients with OA in a primary ...


Biopharmaceutical Approaches For Improved Drug Delivery Across Ocular Barriers, Ketan Hippalgaonkar 2011 University of Mississippi

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 ...


Natural Products Chemistry Of Leads Acting On Mrsa, Hcv, Malaria, And Depression Disorders, Mohamed Ali Mohamed Ali Ibrahim 2011 University of Mississippi

Natural Products Chemistry Of Leads Acting On Mrsa, Hcv, Malaria, And Depression Disorders, Mohamed Ali Mohamed Ali Ibrahim

Electronic Theses and Dissertations

Nature has proven to be an endless source of abundant diversity of chemical entities with varying biological activities. The World Health Organization (WHO) estimates that 80% of the world's population depends on traditional medicine for treating their everyday health problems. According to Gordon Cragg, former director of the natural products branch of the NCI, ″Nature has produced wonderfully complex molecules that no synthetic chemist could ever dream up.″ Moreover, he emphasized that over 60% of cancer therapeutics have been derived from nature whether directly through isolation or indirectly through semi-synthesis. Various examples have been reported such as extracts from ...


Novel Approaches To The Control Of Infectious Diseases, Damaris Agathe Meujo Foping 2011 University of Mississippi

Novel Approaches To The Control Of Infectious Diseases, Damaris Agathe Meujo Foping

Electronic Theses and Dissertations

As part of our ongoing efforts to find new drug leads against infectious diseases, several terrestrial and marine macro- and microorganisms were investigated. Several bioactive molecules, presented below, were isolated from these natural products. The mass-screening of dozens of marine Actinomycetes was completed and several Streptomyces with interesting biological activity profiles identified. A few examples are the Streptomyces code H747 and the Streptomyces code H668, a bacterium from which a new (5) and two known polyethers, the antimalarial agent K41-A (6) and its C-29 analog (7) were isolated. Five new six-membered ring cyclic peroxides: plakinastreloic acid A (8), methyl plakinastreloate ...


Influence Of Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodiafiltration On The Disposition Of Doripenem, Iolanda Cirillo, Nicole Vaccaro, Dainius Balis, Rebecca Redman, Gary R. Matzke 2011 Johnson & Johnson Pharmaceutical Research & Development

Influence Of Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodiafiltration On The Disposition Of Doripenem, Iolanda Cirillo, Nicole Vaccaro, Dainius Balis, Rebecca Redman, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg intravenous infusion of doripenem were assessed in dialysis-dependent subjects with stage 5 chronic kidney disease undergoing continuous renal replacement therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were also assessed (n = 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysis-dependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater, respectively, than those in healthy ...


Target Validation Of Uk-101 And Functional Studies Of Β1i, Marie V. Wehenkel 2011 University of Kentucky

Target Validation Of Uk-101 And Functional Studies Of Β1i, Marie V. Wehenkel

Theses and Dissertations--Pharmacy

β1i is a major catalytic subunit of the immunoproteasome, an alternative form of the constitutive proteasome, and its upregulation has been demonstrated in a variety of disease states including cancer. Our lab has developed a small molecule inhibitor of β1i, dubbed UK-101. While UK-101 causes apoptosis in cancer cell lines, it was not clear whether this apoptotic effect was directly mediated by its irreversible inhibition of β1i. Since off-target effects are major roadblocks for the development of new and effective pharmaceuticals, target validation studies in this system would assist in the further progression of β1i inhibitors towards preclinical trials. Our ...


Preclinical Evaluation Of Lobeline For The Treatment Of Adhd: Comparison With Psychostimulant Therapies, Yolanda D. Williams 2011 University of Kentucky

Preclinical Evaluation Of Lobeline For The Treatment Of Adhd: Comparison With Psychostimulant Therapies, Yolanda D. Williams

Theses and Dissertations--Pharmacy

This dissertation work investigated the effect of acute and repeated in vivo administration of lobeline on dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) function. The effects of lobeline were then compared to the effects of acute and repeated in vivo administration of methylphenidate and amphetamine to determine if lobeline produced similar effects compared to these Attention Deficit Hyperactivity Disorder (ADHD) medications. These medications are considered the first line of pharmacotherapy for ADHD, although there is a growing concern associated with their potential for abuse and other side effects. This merits the need for novel ADHD treatments that have a ...


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