Medicine and Health Sciences Commons^™

Survey Of Congenital Heart Surgeons’ Preferences For Antimicrobial Prophylaxis For Pediatric Cardiac Surgery Patients, Chad A. Knoderer, Emily M. Anderson, Elaine G. Cox

Scholarship and Professional Work – COPHS

Patients with congenital heart defects are a unique population with generally immature immune systems. Fragility in the postoperative period may contribute to surgical site infections (SSIs), a life threatening complication for this population. The need for postoperative antimicrobial prophylaxis for these patients is a standard of care that is indisputable. When choosing an antimicrobial regimen for surgical prophylaxis, consideration should be given to balancing the prevention of nosocomial infections, avoiding emergence of bacterial resistance, and minimizing drug toxicities and cost.

Racial And Ethnic Disparities In Treatment Of Dementia Among Medicare Beneficiaries, Ilene H. Zuckerman, Priscilla T. Ryder, Linda Simoni-Wastila, Thomas Shaffer, Masayo Sato, Lirong Zhao, Bruce Stuart

Scholarship and Professional Work – COPHS

Objectives—Numerous studies have documented disparities in health care utilization between non-Hispanic White and minority elders. We investigated differences in anti-dementia medication use between non-Hispanic White and minority community-dwelling Medicare beneficiaries with dementia.

Methods—Using multivariate analysis with generalized estimating equations, we estimated prevalence ratios (PRs) for anti-dementia medication use by race/ethnicity for 1,120 beneficiaries with dementia from years 2001 through 2003 of the Medicare Current Beneficiary Survey.

Results—After adjusting for demographics, socioeconomics, health care access and utilization, comorbidities, and service year, we found that anti-dementia medication use was approximately 30% higher among non-Hispanic Whites compared to other racial/ethnic groups (PR = …

Different Requirements Of The Swi/Snf Complex For Robust Nucleosome Displacement At Promoters Of Heat Shock Factor And Msn2- And Msn4-Regulated Heat Shock Genes, Tamara Y. Erkina, P. A. Tschetter, Alexander M. Erkine

Scholarship and Professional Work – COPHS

The stress response in yeast cells is regulated by at least two classes of transcription activators—HSF and Msn2/4, which differentially affect promoter chromatin remodeling. We demonstrate that the deletion of SNF2, an ATPase activity-containing subunit of the chromatin remodeling SWI/SNF complex, eliminates histone displacement, RNA polymerase II recruitment, and heat shock factor (HSF) binding at the HSP12 promoter while delaying these processes at the HSP82 and SSA4 promoters. Out of the three promoters, the double deletion of MSN2 and MSN4 eliminates both chromatin remodeling and HSF binding only at the HSP12 promoter, suggesting that Msn2/4 activators are primary determinants of …

Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester

Natural Sciences and Mathematics | Faculty Scholarship

Domoic acid (DA) is a potent toxin produced by bloom-forming phytoplankton in the genus Pseudo-nitzschia, which is responsible for causing amnesic shellfish poisoning (ASP) in humans. ASP symptoms include vomiting, diarrhea, and in more severe cases confusion, loss of memory, disorientation, and even coma or death. This paper describes the development and validation of a rapid, sensitive, enzyme linked immunosorbent assay test kit for detecting DA using a monoclonal antibody. The assay gives equivalent results to those obtained using standard high performance liquid chromatography, fluorenylmethoxycarbonyl high performance liquid chromatography, or liquid chromatography—mass spectrometry methods. It has a linear range …

Pdgf-Driven Proliferation, Migration, And Il8 Chemokine Secretion In Human Corneal Fibroblasts Involve Jak2-Stat3 Signaling Pathway, Neeraj Vij, Ajay Sharma, Mahesh Thakkar, Sunilima Sinha, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: Platelet-derived growth factor (PDGF) is associated with corneal fibroblast migration and proliferation and plays an important role in corneal wound healing. However, the intracellular mechanisms of PDGF-mediated functions in corneal fibroblasts are poorly understood. We tested the hypothesis that PDGF functional activities in the cornea involve the Janus kinase-2/signal transducers and activators of transcription-3 (JAK2-STAT3) signaling pathway and whether PDGF induces the expression of suppressors of cytokine signaling 3 (SOCS3), belonging to the novel family of feedback regulators of cytokine and growth factor activities.

Methods: Human corneal fibroblast (HSF) cultures were used as an in vitro model for functional …

Adenylyl Cyclase Type 6 Overexpression Selectively Enhances Ss-Adrenergic And Prostacyclin Receptor Mediated Inhibition Of Rat Cardiac Fibroblast Function Due To Co-Localization In Lipid Rafts, Xiaoqiu Liu, Muthusamy Thangavel, Shu Qiang Sun, Joseph Kaminsky, Penden Mahautmr, Jeremiah Stitham, John Hwa, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor β and inhibited by agents that elevate 3′,5′-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this …

N-Hexanoyl Chitosan Stabilized Magnetic Nanoparticles: Implication For Cellular Labeling And Magnetic Resonance Imaging, Shanta R. Bhattarai, Remant B. Kc, Sun Y. Kim, Manju Sharma, Myung S. Khil, Pyoung H. Hwang, Gyung H. Chung, Hak Y. Kim

Wayne State University Associated BioMed Central Scholarship

Abstract

This project involved the synthesis of N-hexanoyl chitosan or simply modified chitosan (MC) stabilized iron oxide nanoparticles (MC-IOPs) and the biological evaluation of MC-IOPs. IOPs containing MC were prepared using conventional methods, and the extent of cell uptake was evaluated using mouse macrophages cell line (RAW cells). MC-IOPs were found to rapidly associate with the RAW cells, and saturation was typically reached within the 24 h of incubation at 37°C. Nearly 8.53 ± 0.31 pg iron/cell were bound or internalized at saturation. From these results, we conclude that MC-IOPs effectively deliver into RAW cells in vitro and we also …

Analysis Of Residual Solvents In Pharmaceuticals By Comprehensive Two-Dimensional Gas Chromatography, Cristina Marie Crimi

Seton Hall University Dissertations and Theses (ETDs)

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Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for conjugation. We further …

Drug Selection And Adverse Drug Reactions: Balancing Outcomes And Costs, Enrique Seoane-Vazquez

Pharmacy Faculty Articles and Research

"Regulatory agencies approve drugs for marketing when the ratio of risk to benefit of the drugs is positive, i.e. the potential benefit of using the drug justifies the risk of drug related adverse reactions (ADR). At the point of approval of a drug there is not adequate information about all possible negative outcomes arising from its use in clinical practice. The information is even more limited for patient subgroups, diseases and treatment combinations that were not evaluated in the clinical trials required for approval. Therefore, performing post-marketing pharmacoepidemiological studies is necessary for a better understanding of drug use in usual …

The Mechanism Of Silver Dissolution For Biomedical Devices And Hygienic Coating Applications., Yanmei Ma

Doctoral

This work focuses on the mechanism of silver dissolution for biomedical and hygienic coating applications. The research work began from the investigation of silver dissolution behaviour from pure silver and silver-platinum alloys in solutions with or without chloride using the technique of cyclic volammetry (CV). A zero resistance amperometry (ZRA) measurement was carried out to study the effect of platinum on the silver dissolution behaviour in 0.89%wt. NaCI solution. The mechanism of silver dissolution from pure silver and silver-platinum alloys in 0.89%wt. NaCI solution was proposed by an equivalent circuit model under the investigation of electrochemical impedance spectroscopy (EIS). It …

Effects Of Smoking And Gender On Tetrahydroisoquinolines And Beta-Carbolines In A Healthy Population And During Alcohol Detoxification, Satjit Singh Brar

Theses and Dissertations

The purpose of this investigation was to evaluate the effects of smoking and gender on 1) tetrahydroisoquinolines (TIQs) and beta-carbolines (BCs) in a population of healthy subjects and 2) TIQs in an alcohol-dependent population undergoing in-patient detoxification. Comparison in plasma TIQs between the populations was additionally conducted. To support the clinical investigations, a HPLC-FD method was developed and validated to assess plasma concentrations of BCs, harman and norharman, while a HPLC-ESI-MS/MS method was validated to quantify the TIQs, R/S-salsolinol along with dopamine. Forty-one young volunteers were recruited including 19 nonsmokers (NS), 11 light smokers (LS) and 11 heavy smokers (HS), …

Tumor Epithelial Cell Matrix Metalloproteinase 9 (Mmp-9) Is A Prognostic Marker In Colorectal Cancer, Ds Zuzga, Av Gibbons, P Li, Wj Lubbe, I Chervoneva, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Presented at American Association Cancer Research in 2008

Zuzga D.S., Gibbons A.V., Li P., Lubbe W.J., Chervoneva I., Pitari G.M. “Tumor epithelial cell MMP-9 is a prognostic marker in colorectal cancer”. In: American Association for Cancer Research Special Conference, Molecular Diagnostics in Cancer Therapeutic Development: Proceedings; 2008 Sept 22-25; Philadelphia, PA. Abstract A40.

Colorectal cancer is the second leading cause of cancer-related mortality indeveloped nations. Mortality from colon cancer largely reflects metastasis, thespread of the disease to distant sites. Early diagnosis of pre-metastatic diseaseand accurate stratification of patients with metastasis is pivotal to decreasemortality rates from colon cancer by effectively …

Selective Regulation Of Cardiomyocyte Signaling By Rgl2, Leah M. Allen

University of Kentucky Doctoral Dissertations

A key cardiovascular signaling molecule involved in both physiologic and pathologic regulation of cardiomyocytes is the small molecular weight G-protein, Ras. Differential effects of Ras are mediated by multiple effector molecules, including the RalGEFs which activate Ral. Studies performed in cardiomyocytes have indicated a role for Ral in cardiac hypertrophic signaling and the RalGEF family member, Rgl2, was shown to specifically interact with Ras in the heart. Therefore, I hypothesized that Rgl2 was an important Ras effector that would regulate cardiomyocyte signaling.

To elucidate the potential importance of Rgl2 in regulating cardiomyocyte signaling, a gain-of-function approach was utilized in which …

Treatment Of Industrial Wastewater Containing Active Pharmaceutical Ingredients With A Membrane Bioreactor, With The Aim Of Reducing Resource Consumption, Pádraig Colm Ó'Maolcatha

Theses

The biodegradation of a selected active pharmaceutical ingredient (API) during wastewater treatment in a membrane bioreactor (MBR) was examined experimentally. A comparison study was conducted by operating a conventional activated sludge (CAS) pilot plant in parallel to the MBR. The MBR was operated under varying conditions of pH (pH6 and pH8), MLSS (6g/L and l0g/L) and SRT (20 days and 30 days) according to a full factorial design of experiments. In the CAS, pH and SRT were altered as above but MLSS was maintained at 3-4g/L. Comparable average API removal results of 95.5% and 95.7% were obtained for the MBR …

Investigation Of Inosine And Hypoxanthine As Biomarkers Of Cardiac Ischemia In Plasma Of Non-Traumatic Chest Pain Patients And A Rapid Analytical System For Assessment, Don E. Farthing

Theses and Dissertations

Each year in the U.S., approximately 7-8 million patients with non-traumatic chest pain visit hospital emergency departments (ED) for medical evaluation. It is estimated that approximately 2-5% of these patients are experiencing acute cardiac ischemia, but due to the shortcomings of current test methods, they are incorrectly diagnosed and discharged without appropriate treatment provided, thus leading to poor patient outcome and potential medical malpractice litigation.The goals of this research were to evaluate plasma samples for potential biomarker(s) of acute cardiac ischemia prior to heart tissue necrosis, and to ultimately develop a rapid method for detection of the potential biomarker(s) in …

Design, Synthesis, And Pharmacological Evaluation Of A Series Of Novel, Guanidine And Amidine-Containing Neonicotinoid-Like Analogs Of Nicotine: Subtype-Selective Interactions At Neuronal Nicotinic-Acetylcholine Receptor., Aaron Joseph Haubner

University of Kentucky Doctoral Dissertations

The current project examined the ability of a novel series of guandine and amidine-containing nicotine analogs to interact with several native and recombinantlyexpressed mammalian neuronal nicotinic-acetylcholine receptor (nAChR) subtypes. Rational drug design methods and parallel organic synthesis was used to generate a library of guanidine-containing nicotine (NIC) analogs (AH compounds). A smaller series of amidine-containing nicotine analogs (JC compounds) were also synthesized. In total, >150 compounds were examined. Compounds were first assayed for affinity in a high-throughput [³H]epibatidine radioligand-binding screen. Lead compounds were evaluated in subtype-selective binding experiments to probe for affinity at the α₄β_{2 …}

A Novel Class Of Immunoproteasome Catalytic Subunit Lmp2 Inhibitor And Its Therapeutic Potentials In Cancer, Yik Khuan (Abby) Ho

University of Kentucky Doctoral Dissertations

The immunoproteasome, known to play an important role in MHC class I antigen processing and presentation, have been linked to neurodegenerative diseases and hematological cancers. However, the pathophysiological functions of the immunoproteasome in these diseases are still not very well established. This can be attributed mainly to the lack of appropriate molecular probes that selectively target the immunoproteasome catalytic subunits. Herein, we report the development of a small molecular inhibitor (AM) that selectively targets the major catalytic subunit, LMP2, of the immunoproteasome. We show that the compound covalently modifies the LMP2 subunit with high specificity in human prostate …

Physical And Computational Models Of Human Lung For Optimizing Respiratory Drug Delivery, Mohammed Ali

Theses and Dissertations

Respiratory drug particles aerosolized from the commercially available drug delivery devices may charge electrostatically. Investigations of the relevance of this charge on deposition in the human lung are just quite a few and they started early eighties though the aerosol science study is a decade old discipline. Additionally, the localized deposition of drug particles at desired sites such as inflamed tissue and appropriate receptors has been recognized by clinical investigators as being critical factors for the effective administration of respiratory drugs. To accomplish these tasks, it is imperative to undertake in vitro and in silico studies of medicinal drug aerosol …

Bringing In The Green: Pharma Stands To Win Hearts, Minds, And Tax Credits By Launching An Eco Bandwagon, Porcher L. Taylor Iii, David E. Kitchen

School of Professional and Continuing Studies Faculty Publications

A green mind-set can lead to a black bottom line. Becoming nvironmentally friendly can help boost brand image and ROi -- and pharma can get there with a few easy steps.

First, with about 90,000 sales representatives on the road, the industry could lead a revolution in transportation if it bought hybrid cars. By replacing the current fleet, the benefits would be substantial. Each hybrid is cheaper to maintain, more fuel-efficient, and leaves a far smaller greenhouse-gas footprint on the environment. Imagine extrapolating these benefits to thousands of ca rs: That's an environmentally friendly signature that shows leadership in the …

Application Of Linear Free Energy Relationships In The Prediction Of Triglyceride/Water Partition Coefficients And Lipid Bilayer Permeability Coefficients Of Small Organic Molecules And Peptides, Yichen Cao

University of Kentucky Doctoral Dissertations

Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the …

A Capillary-Based Microfluidic System For Immunoaffinity Separations In Biological Matrices, Michael Peoples

Theses and Dissertations

The analysis of biological samples in clinical or research settings often requires measurement of analytes from complex and limited matrices. Immunoaffinity separations in miniaturized formats offer selective isolation of target analytes with minimal reagent consumption and reduced analysis times. A prototype capillary-based microfluidic system has been developed for immunoaffinity separations in biological matrices with laser-induced fluorescence detection of labeled antigens or antibodies. The laboratory-constructed device was assembled from two micro syringe pumps, a microchip mixer, a micro-injector, a diode laser with fused-silica capillary flow cell, and a separation capillary column. The columns were prepared from polymer tubing and packed under …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

Compounds of the formula having anti-tumor activity, wherein R₁ and R₂ are as described herein

Implementing Pharmacy Informatics In College Curricula: The Aacp Technology In Pharmacy Education And Learning Special Interest Group, Ross E. Vanderbush, H. Glenn Anderson Jr., William K. Fant, Brad S. Fujisaki, Patrick M. Malone, Paul L. Price, Maria C. Pruchnicki, Teresa L. Sterling, Kara D. Weatherman, Karl G. Williams

Pharmacy Practice & Administration

Many professional organizations have initiatives to increase the awareness and use of informatics in the practice of pharmacy. Within education we must respond to these initiatives and make technology integral to all aspects of the curriculum, inculcating in students the importance of technology in practice. This document proposes 5 central domains for organizing planning related to informatics and technology within pharmacy education. The document is intended to encourage discussion of informatics within pharmacy education and the implications of informatics in future pharmacy practice, and to guide colleges of pharmacy in identifying and analyzing informatics topics to be taught and methods …

Honaker, Marion Earl, 1914-2006 (Sc 1510), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid only for Manuscripts Small Collection 1510. Letters, 1985-1997 (19); military papers, 1942-1990 (14); photos (21); newspapers clippings, 1942, 1992-2006 (5); of Marion Earl Honaker, Bowling Green, Kentucky, a Navy pharmacist mate stationed in the Pacific Area during World War II.

A Quantitative Synthesis Of The Medicinal Ethnobotany Of The Malinké Of Mali And The Asháninka Of Peru, With A New Theoretical Framework, Nathaniel Bletter

Publications and Research

Background: Although ethnomedically and taxonomically guided searches for new medicinal plants can improve the percentage of plants found containing active compounds when compared to random sampling, ethnobotany has fulfilled little of its promise in the last few decades to deliver a bounty of new, laboratory-proven medicinal plants and compounds. It is quite difficult to test, isolate, and elucidate the structure and mechanism of compounds from the plethora of new medicinal plant uses described each year with limited laboratory time and resources and the high cost of clinical trials of new drug candidates.

Methods: A new quantitative theoretical framework of mathematical …

Tigecycline In The Treatment Of Complicated Intra-Abdominal And Complicated Skin And Skin Structure Infections, M. L. Townsend, M. W. Pound, R. H. Drew

Pharmacy Practice

Tigecycline, a glycylcycline related to the tetracycline class of antibiotics, represents a new option for the treatment of complicated intra-abdominal and complicated skin and skin structure infections. It displays favorable activity in vitro against the most common causative Gram-positive, Gram-negative and anaerobic pathogens. In addition, tigecycline demonstrates activity against drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and organisms (such as Escherichia coli and Klebsiella pneumoniae) producing extended-spectrum beta-lactamases. Tigecycline lacks activity in vitro against Pseudomonas and Proteus spp. In randomized clinical trials, tigecycline administered intravenously twice daily has demonstrated efficacy similar to comparators for a variety …

Efficacy Of Cognitive Therapy And Pharmacotherapy In Depression: A Meta-Analysis, Daniel B. Michel

Loma Linda University Electronic Theses, Dissertations & Projects

A meta-analysis comparing the long-term effectiveness of cognitive behavioral therapy (CBT) and pharmacotherapy in preventing relapse following treatment discontinuation was performed using published studies of depressed participants. Twenty-three articles met inclusionary criteria and were included in the analyses. Weighted effect sizes and moderators, treatment type, were calculated using statistical analysis software. Initially, fixed effects models were applied to the data, but due to significant between-group heterogeneity that could not be fully explained by treatment type, mixed effect models were used to account for the residual heterogeneity. Results indicated that overall, depressed individuals treated to remission with CBT evidence decreased relapse …

Development And Evaluation Of Brain Tumor Targeted Liposome Delivery System For Paclitaxel, Murali Krishna Divi

Theses and Dissertations (ETD)

Primary brain tumors are a relatively common cause of cancer-related deaths. High-grade gliomas are the most common type of primary brain cancer, and the affected patients have a median survival of less than 1 year. Almost all malignant gliomas are incurable with the present standards of healthcare. Currently accepted therapeutic adjuvants to surgery, such as radiotherapy and chemotherapy, provide only a minor improvement in the disease course and life expectancy for patients diagnosed with malignant gliomas. Often, chemotherapy has failed to make any significant impact on the prognosis of disease because of significant local and systemic toxicity, problems with transport …

Age-Associated Hepatic Drug Transporter Expression And Its Implications For Pediatric Pharmacotherapyflexibility Affect Dna Topoisomerase I Function, Lisa Tang

Theses and Dissertations (ETD)

Members of the ATP-binding cassette (ABC) family of drug transporter proteins translocate various endogenous and exogenous substrates across intra- and extracellular membranes. Two specific ABC transporters, the multidrug resistance 1/P-glycoprotein (MDR1/P-gp) and the multidrug resistance protein 2 (MRP2), serve as major hepatic transporters that mediate the biliary excretion of various organic anions and cations along with glutathione-, glucuronate-, or sulfate-conjugates of several drug substrates. However, very little is known about the expression of these transporters in the early infant and childhood ages of human development. We, therefore, characterized the ontogeny of these transporters by measuring their gene and protein expression. …