Pharmacy and Pharmaceutical Sciences Commons^™

Molecular Staging Estimates Occult Tumor Burden In Colorectal Cancer, Alex Mejia, Stephanie Schulz, Terry Hyslop, David S. Weinberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor cells in regional lymph nodes are a key prognostic marker of survival and predictive marker of response to adjuvant chemotherapy in colorectal cancer. However, clinicopathologic techniques to detect lymph node metastases remain imperfect, and ~30% of patients with lymph nodes negative by histology (pN0) develop recurrent disease, reflecting occult metastases that escape detection. These observations underscore an unmet clinical need for accurate approaches to identify occult nodal metastases in colorectal cancer patients. GUCY2C is a receptor whose expression normally is restricted to intestinal epithelial cells, but is universally over-expressed by colorectal cancer cells. A prospective, multicenter, blinded clinical trial …

Expression Of The Intestinal Biomarkers Guanylyl Cyclase C And Cdx2 In Poorly Differentiated Colorectal Carcinomas., Brody Winn, Rosemarie Tavares, Andres Matoso, Lelia Noble, Jacqueline Fanion, Scott A Waldman, Murray B Resnick

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylyl cyclase C, a receptor for bacterial diarrheagenic enterotoxins, is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by reverse transcriptase-polymerase chain reaction is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well-differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A …

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 …

In-Vitro Metabolism And Protein Binding Of 5-Hmf, A Potential Antisickling Agent, Taghrid Obied

Theses and Dissertations

Purpose. 5-HMF is a potential antisickling agent forming a Schiff-adduct with hemoglobin (Hb). In-vitro studies were designed to identify the metabolic pathways of 5-HMF in human hepatic cytosol, to assess inter-species differences in its hepatic metabolism, and to predict in-vivo PK properties. Moreover, metabolism of 5-HMF in human RBCs was investigated. Finally, in-vitro studies were done to characterize 5-HMF binding kinetics with human Hb and albumin (HSA). Methods. NAD+ reduction was monitored at 340 nm in human hepatic cytosol for 5-HMF (26 mM) and prototypical ADH and ALDH substrates in the presence or absence of their inhibitors. Furthermore, concentration-dependency studies …

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 …

Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights, Sinead Ryan, Jesus Maria Frias, David H. Haddleton, David J. Brayden

Articles

Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel combed-shaped end-functionalised poly(PEG) methyl ether methacrylate) (sCT-P) comb-shaped polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40 kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E …

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 …

Computational Prediction And Analysis Of The Napp – Dr6 Interaction: Implications For Alzheimer's Research, Joseph Audie, Sergei Y. Ponomarev

Chemistry & Physics Faculty Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that involves a devastating clinical course and lacks an effective treatment. A biochemical model for neuronal development, recently proposed by Nikolaev and co-workers, hinges on a novel protein-protein interaction between the death cell receptor six (DR6) ectodomain and an N-terminal fragment of amyloid precursor protein (NAPP). The model provides a coherent and satisfying framework for better understanding AD pathophysiology. Moreover, the DR6-NAPP interaction offers a tempting target for novel pharmacological intervention. Given all of this, we constructed a structural model of the DR6-NAPP interaction using the neurotrophin p75 receptor as a template. …

Evaluation Of Concurrent Medications Pre- And Post Initiation Of Long-Acting Injectable Antipsychotic Therapy, Lindsay Pokallus Pharmd, Laurence Karper Md, Jessica Price Pharmd, Bcps

Department of Pharmacy

No abstract provided.

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 …

Lamin B Receptor, Ada L. Olins, Gale Rhodes, David B. Mark Welch, Monika Zwerger, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

Lamin B Receptor (LBR) is an integral membrane protein of the interphase nuclear envelope (NE). The N-terminal end resides in the nucleoplasm, binding to lamin B and heterochromatin, with the interactions disrupted during mitosis. The C-terminal end resides within the inner nuclear membrane, retreating with the ER away from condensing chromosomes during mitotic NE breakdown. Some of these properties are interpretable in terms of our current structural knowledge of LBR, but many of the structural features remain unknown. LBR apparently has an evolutionary history which brought together at least two ancient conserved structural domains (i.e. Tudor and sterol reductase). This …

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 …

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic (Pk) Properties Based On Quantitative Structure Pharmacokinetic Relationships (Qspkr) And Interspecies Pharmacokinetic Allometric Scaling (Pk-As), Prajakta Badri

Theses and Dissertations

This research developed validated QSPKR and PK-AS models for predicting human systemic PK properties of three, preselected, pharmacological classes of drugs, namely opioids, β-adrenergic receptor ligands (β-ARL) and β-lactam antibiotics (β-LAs) using pertinent human and animal systemic PK properties (fu,, CLtot, Vdss, fe) and their biologically relevant unbound counterparts from the published literature, followed by an assessment of the effect of different molecular descriptors on these PK properties and on the PK-AS slopes for CLtot and Vdss from two species (rat and dog). Lipophilicity (log (D)7.4) and molecular weight (MW) were found to be the most statistically significant and biologically …

Resolution Of Clinical Signs In Trauma Intensive Care Unit Patients Following Diagnosis Of Ventilator-Associated Pneumonia, Kathryn A. Connor, Joseph M. Swanson, G. Christopher Wood, Bradley A. Boucher, Louis J. Magnotti

Pharmacy Faculty/Staff Publications

PURPOSE: The ATS/IDSA Ventilator-Associated Pneumonia (VAP) guidelines suggest that clinical improvement of VAP should be apparent within 3-6 days. Anecdotally, such improvement has not been noted in trauma patients at our institution. The current study was conducted to evaluate resolution of clinical signs of VAP following diagnosis.

METHODS: Critically injured adults admitted to the trauma intensive care unit (TICU) from 6/1/06-12/31/07 and subsequently diagnosed with VAP were retrospectively reviewed. Clinical signs, including derangements of maximum temperature (Tmax), white blood cell (WBC) count and Pa02/FiO2, were evaluated on days 1-16 following VAP diagnosis. Data are presented as mean ± SD unless …

A Potent And Selective Inhibitor Of Cdc42 Gtpase, Zurab Surviladze, Anna Waller, J. Jacob Strouse, Cristian G. Bologa, Oleg Ursu, Virginia M. Salas, Genevieve K. Phillips, John F. Parkinson, Elsa Romero, Angela Wandinger-Ness, Larry A. Sklar, Chad E. Schroeder, Denise S. Simpson, Julica Nöth, Jenna Wang, Jennifer E. Golden, Jeffrey Aubé

Pharmacy Faculty Publications

Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and …

Impact Of Levalbuterol Versus Albuterol In Kentucky Medicaid Patients, Velma Henry

MPA/MPP/MPFM Capstone Projects

Problem:

Asthma is a chronic pulmonary disease that occurs in approximately 10 percent of the population worldwide and is associated with a significant increase in direct medical expenditures. Levalbuterol and racemic albuterol are two short-acting β2-agonists (SABA) prescribed for the treatment of asthma. Racemic albuterol has been used for more than 40 years but is associated with several side effects including tremor. When levalbuterol was approved in 2005 its manufacturer and several studies suggested that using levalbuterol results in better respiratory parameters, fewer hospitalizations, less adverse effects and therefore, lower overall treatment costs and hence less need for β-adrenergic agonist …

Investigation Of A Metal Complexing Route To Arene Trans-Dihydrodiols, Crystal O'Connor

Masters

In this work, a route for the conversion of arene cis-dihydrodiols to their trans isomers was examined. Arene trans-dihydrodiols are potentially important chiral building blocks in synthetic chemistry and are more stable than their cis analogues. While the cis-arene dihydrodiols can be produced on a relatively large scale by fermentation, their trans isomers cannot. The principal aim of this work was to carry out studies in tandem to inform the development of the synthetic pathway to convert arene cis-dihydrodiols to their trans isomers by (a) the synthesis of organometallic intermediates and (b) investigation of their reactivity by means of kinetic …

Gene Delivery In The Equine Cornea: A Novel Therapeutic Strategy, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To determine if hybrid adeno-associated virus serotype 2/5 (AAV5) vector can effectively deliver foreign genes into the equine cornea without causing adverse side effects. The aims of this study were to: (i) evaluate efficacy of AAV5 to deliver therapeutic genes into equine corneal fibroblasts (ECFs) using enhanced green fluorescent protein (EGFP) marker gene and (ii) establish the safety of AAV5 vector for equine corneal gene therapy.

Animal Material—Primary ECF cultures were harvested from healthy donor equine corneas. Cultures were maintained at 370C in humidified atmosphere with 5% CO2.

Procedure—AAV5 vector expressing EGFP under control of hybrid cytomegalovirus (CMV) + chicken …

Vector Delivery Technique Affects Gene Transfer In The Cornea In Vivo, Rajiv R. Mohan, Ajay Sharma, Tyler C. Cebulko, Ashish Tandon

Pharmacy Faculty Articles and Research

Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.

Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for …