Pharmacy and Pharmaceutical Sciences Commons^™

Medication-Related Problems Experienced By Patients During Transitions To Assisted Living, Deanna Flora

Theses and Dissertations

Medication reconciliation is a systematic and comprehensive review of medication regimens during care transitions aiming to prevent adverse drug events. Poorly executed transitions negatively impact patient welfare and cause financial burden. Medication-related problems (MRPs) experienced during transitions to an assisted living facility (ALF) were evaluated. Data was collected from pharmacy records for transitions to an ALF over three months, including demographics, medications, potentially inappropriate medications, and MRPs. MRPs were categorized and summarized using descriptive statistics. Forty-five patients (71% female) experienced 59 transitions. Average age was 85.6 years. Median length of stay away from the ALF was three days. There were …

The Economic Burden Of Opioid Poisoning In The United States And Determinants Of Increased Costs In Opioid Poisoning, Timothy Inocencio

Theses and Dissertations

Introduction: Opioid poisoning has been rapidly increasing in the past decade, and has been driven in large part due to increases in opioid prescribing. This has been accompanied by intervention efforts aimed at preventing and reversing opioid poisoning through naloxone prescription programs. Current literature have not quantified the economic burden of opioid poisoning. Understanding this information can help inform these efforts and bring light to this growing problem. In addition understanding various determinants of increased costs can help to identify the types of populations more likely to have greater costs. Main Objectives: The objectives are 1) to quantify the economic …

The Role Of Megalin In The Transport Of Aminoglycosides Across Human Placenta, Amal Akour

Theses and Dissertations

Background: Intra-amniotic infections (IAIs) are common complications of labor and delivery. If inadequately treated, these infections can lead to significant morbidity and mortality in the mother and the fetus. Intrapartum aminoglycoside (AG) administration is recommended for the management of IAIs. AGs are known to cross the placenta and achieve bactericidal concentrations in fetal serum. However, the highest and most persistent fetal levels are achieved in renal tissue. So, the fetus may be vulnerable to the nephrotoxic effects of AGs. Megalin, a 600 kDaendocytic receptor, is responsible for the uptake of AGs into renal proximal tubular epithelial cells. This receptor is …

Costs And Use Of Oral Anti-Cancer Medications Among Senior Medicare Part D Beneficiaries, Nantana Kaisaeng

Theses and Dissertations

Oral cancer drugs are branded and expensive medications that generally do not have generics available. The restrictions of the Medicare Part D program, including the coverage gap and high cost-sharing, and the high cost of oral chemotherapy may lead to patients’ non-adherence to medication. Few studies have examined the cost and utilization of oral anti-cancer medications. This study will be the first to examine the costs associated with the use of oral anti-cancer medications and the impact of cost-sharing and type of prescription drug subsidy on medication discontinuation in the Medicare Part D elderly population. Objectives: To determine the usage …

A New Approach To Dried Blood Spot Analysis For Newborn Screening Using High Resolution Liquid Chromatography Tandem Mass Spectrometry, John H. Miller Iv

Theses and Dissertations

The primary purpose of newborn screening is to quickly identify children that are at risk of having a specific disorder in order to start treatment, prevent early death and reduce the chances of permanent physical or mental damage. The current and widely accepted approach used for identification of metabolism disorders involves a flow injection analysis with mass spectrometry detection of acylcarnitines and amino acids. Although this approach is widely accepted and has shown to be sufficient for identification of multiple metabolism disorders the method is not fully quantitative and results often have to be confirmed by second-tier tests. The primary …

Capture And Characterization Of Dioxygen Reactive Intermediates In Cyp51 Catalysis, Gareth Kent Jennings

Theses and Dissertations

The cytochromes P450 (CYPs) are a superfamily of biological catalysts that are ubiquitous throughout the biological domain. CYPs are heme-b containing monooxygenases which oxidize substrates with the help of accessory redox partners. CYP substrates include endogenous compounds required for many biological functions and homeostasis, such as steroids, as well as the majority of clinically used drugs and environmental xenobiotics. The majority of studies that have been performed to date are on P450cam (CYP101) from Pseudomonas putida. Of the numerous reactions catalyzed by CYPs, unactivated carbon-carbon bond cleavage, is one of particular versatility. Being unique in their catalytic mechanisms, the C-C …

Influence Of Electrostatic Charge Upon The Deposition Behavior Of Pharmaceutical Aerosols Within Cascade Impactors, Megha Mohan

Theses and Dissertations

Cascade impactors, routinely used for in vitro particle size characterization of pharmaceutical aerosols, are calibrated using dilute, charge-neutralized, monodisperse aerosols. But pharmaceutical aerosols are known to generate concentrated, inherently charged, polydisperse aerosol clouds. A computational model of the Andersen Cascade Impactor (ACI) suggested that the presence of charge on aerosol particles may influence their deposition within the ACI, but experimental validation of the model is warranted. This dissertation investigates the influence of electrostatic charge upon the deposition behavior of aerosols within cascade impactors, to address the impact of charge on particle size characterization. The influence of applied charge upon the …

Α2-Adrenoceptor And 5-Ht3 Serotonin Receptor Ligands As Potential Analgesic Adjuvants, Genevieve Alley

Theses and Dissertations

There continues to be a need for more effective analgesics. The α2-adrenoceptor (AR) agonist clonidine is an analgesic whose use is severely limited by undesirable side effects. meta-Chlorophenylguanidine (MD-354), an agent developed in our laboratory, selectively potentiates the antinociceptive effects of clonidine in a biphasic manner. Mechanistic studies suggest that both 5-HT3 receptor and α2-AR mechanisms are involved. To further evaluate mechanisms underlying the analgesia-potentiating effect of clonidine by MD-354, pharmacological studies using more established 5-HT3 receptor agonists: meta-chlorophenylbiguanide (mCPBG) and centrally-acting SR57227A, and non-selective α2-adrenoceptor ligand TDIQ, administered alone and in combination with clonidine, were conducted in mouse antinociceptive …

Discovery And Biophysical Characterization Of Allosteric Inhibitors Of Factor Xia (Fxia), Malaika Argade

Theses and Dissertations

Thrombosis is one of the leading causes of mortality and morbidity that is associated with myocardial infarction, stroke and pulmonary embolism. Anti-thrombotic agents which intend to reduce the occurrence and severity of thrombosis usually target the enzymes of the coagulation cascade. FXIa, a 160 kDa homodimer is gaining popularity of late as a potential target for anti-thrombotic agents due to its relative safety. A number of inhibitors which target the active site of FXIa have been reported but to our knowledge there have been no inhibitors which act via an allosteric mechanism. The aim of this project was to screen …

Assessment Of The Role Of Solute Carrier Drug Transporters In The Systemic Disposition Of Fluoroquinolones: An In Vitro - In Vivo Comparison, Aditi Mulgaonkar

Theses and Dissertations

Fluoroquinolones (FQ) are broad-spectrum charged antimicrobials exhibiting excellent tissue/fluid permeation. Thus, FQ disposition depends essentially on active transport and facilitative diffusion. Although most early transporter studies investigating renal elimination of FQs have focused on apical efflux of FQs from renal proximal tubule cell (RPTC) into urine, their basolateral uptake mechanism(s) from blood into RPTC (i.e., first step to tubular secretion) has not yet been explored in detail. Renally expressed SLC22 members: organic anion (OATs) and cation (OCTs) transporters are known to transport such small organic ionic substrates (molecular weight ~400 Da). Hence it is of interest to explore the role …

In Vitro In Vivo Methods And Pharmacokinetic Models For Subcutaneously Administered Peptide Drug Products, Amit Somani

Theses and Dissertations

Over the last several years, injectable drugs have been a growing area for the treatment of various therapeutic conditions and they are projected to comprise an even larger proportion among the drugs that will be available in the years to come. The injectable drugs are administered by various routes such as intramuscular (IM), intravenous (IV), subcutaneous (SC) and others, however, the majority of these drugs are administered subcutaneously. Even though subcutaneous delivery has been utilized for a number of years, very little is known about the processes governing the absorption of macromolecules from the interstitial space; and the resulting impact …

Prediction Of Human Systemic, Biologically Relevant Pharmacokinetic Properties Based On Physicochemical Properties Of Calcium Channel Blockers, Tafif Abdullah Al

Theses and Dissertations

This research explored quantitative relationships (QSPKR) between different molecular descriptors and pertinent, systemic PK properties for 14 calcium channel blockers (CCB). Physicochemical properties (PC) such as molecular weight (MW), molar volume (MV), calculated logP (clogP), pKa, calculated logD7.4 (clogD), % ionized at pH 6.3 and pH 7.4, hydrogen bond donors (HBD), hydrogen bond acceptors (HBA), and number of rotatable bonds (nRot) were chosen as possible predictor variables for systemic PK properties for CCB, obtained from pertinent literature, assessing the PK of CCB after intravenous administration to healthy humans. All PC properties and molecular descriptors were computed using ACD-solubility/DB 12.01. Total …

Towards Understanding The Mechanism Of Action Of Abused Cathinones, Rakesh Vekariya

Theses and Dissertations

The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft into the presynaptic terminus and plays a critical role in maintaining the normal function of dopaminergic neurons. DAT is the major target of widely abused psychostimulant drugs, including cocaine and amphetamine. DAT also figures into disease states, and it is a target for therapeutic drugs. It is known that cathinone and methcathinone, β-keto analogs of amphetamine and methamphetamine, respectively, produce pharmacological actions similar to amphetamine. Cathinone and methcathinone analogs are recently gaining in popularity on the clandestine market (e.g. ‘bath salts’). Cathinone and methcathinone analogs as well as …

Preparation And Evaluation Of Deconstruction Analogs Of 7-Deoxykalafungin As Akt Inhibitors, Sudha Korwar

Theses and Dissertations

Pyranonaphthoquinone lactones have been recently found to be selective inhibitors of the serine-threonine kinase AKT/PKB. AKT/PKB plays a major role in tumorigenesis, hence these compounds have a great potential to act as anti-cancer agents. They act by a novel bioreductive alkylation mechanism of inhibition of AKT/PKB. In this work, 7-deoxykalafungin, a pyranonaphthoquinone lactone and its deconstruction analogs were synthesized. The structural features of the compounds necessary to inhibit AKT1 potently and selectively were determined. It was observed that compounds with a pyran ring were more potent in inhibiting AKT1. Conversely, flexible compounds were found to be weak inhibitors of AKT1. …

Small Molecules As Negative Allosteric Modulators Of Alpha7 Nachrs, Osama Alwassil

Theses and Dissertations

Alpha7 Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in essential physiological functions and play a role in disorders such as Alzheimer’s disease. MD-354 (3-chlorophenylguanidine; 21), the first small–molecule negative allosteric modulator (NAM) at alpha7 nAChRs, served as a lead in developing structure–activity relationships for NAMs at a7 nAChRs. MD-354 (21) also binds at 5-HT3 receptors. Analogs of MD-354 with structural features detrimental to 5-HT3 receptor affinity were evaluated in patch-clamp recordings and an aniline N-methyl analog resulted in a more potent and selective NAM than MD-354. A new N-methyl series of compounds was synthesized in which the 3-position was replaced …

Development And Comparison Of Risk-Adjusted Models To Benchmark Antibiotic Use In The University Healthsystem Consortium Hospitals, Omar Moh'd Musa Ibrahim

Theses and Dissertations

Background. Infectious diseases societies recommend that hospitals risk-adjust their antimicrobial use before comparing it to their peers, a process called benchmarking. The purpose of this investigation is to apply and compare 3 risk-adjustment procedures for benchmarking hospital antibacterial consumption (AbC). Two standardization of rates procedures, direct and indirect standardization, are compared with one another as well as with regression modeling. Methods. Total aggregate adult AbC for 52 systemic antibacterial agents was measured in 70 hospitals that subscribed to the University HealthSystem Consortium Clinical Resource Manager database in 2009 and expressed as days of therapy (DOTs) per either 1000 patients days …

Synthesis And Biological Evaluation Of Second Generation Anibamine Analogues As Novel Anti-Prostate Cancer Agents, Shilpa Singh

Theses and Dissertations

Prostate cancer is the most prevalent non-cutaneous cancer among men. Since the 19th century when Virchow first introduced the concept of inflammation in cancer, chemokines and their receptors have garnered a lot of interest. Chemokine receptor CCR5 has been especially implicated in many disease states and recently found to be over expressed in prostate cancer cell lines. Anibamine, a natural CCR5 antagonist discovered in 2004, has been found to have significant anti-prostate cancer activity at micromolar level. To optimize this compound and also discover a novel pharmacophore, exploration of the original structure was carried out. Significant modifications were made to …

Therapeutic Drug Monitoring Of Factor Viii Prophylaxis Using Its Plasma Coagulant Activity And Global Hemostasis Biomarkers: A Pharmacokinetic/Pharmacodynamic Pilot Study, Hawaj Maitham Al

Theses and Dissertations

Background: The current clinical practice of factor VIII (FVIII) prophylaxis revolves around converting patients with severe hemophilia A, hereafter simply referred to as hemophilia, phenotype (defined as plasma factor VIII coagulant activity [FVIII:C] <1 IU dL-1) to moderate hemophilia phenotype (defined as plasma FVIII:C from 1–5 IU dL-1). However, a wide inter-individual variation in bleeding tendency is observed despite changes in plasma FVIII:C (pharmacokinetic [PK] changes). Therefore, monitoring FVIII prophylaxis by global hemostasis biomarkers (pharmacodynamic [PD] response) can potentially be beneficial. Objective: To conduct appropriate PK/PD modeling using plasma FVIII:C and global hemostasis (platelet function and blood viscoelastic) biomarkers in severe hemophilia. Methods: Nine non-bleeding severe hemophiliacs (plasma FVIII:C <1 IU dL-1) with variant bleeding tendency (5 frequent bleeders and 4 infrequent bleeders) were infused with a recombinant factor FVIII (rFVIII) prophylactic dose (mean = 32.1 international units per kilogram [IU kg-1]). Blood was collected at baseline and 0.5-, 1-, 2-, 4-, 8-, 12-, 24- and 48-hours (h) post-dose for plasma FVIII:C, platelet function (platelet contractile force [PCF], clot elastic modulus [CEM] and force onset time [FOT]) and blood viscoelastic (reaction-time [R], kinetics-time [K] and maximum amplitude [MA]) biomarkers and activated partial thromboplastin time (aPTT). Non-compartmental analysis (NCA) was performed using standard methods. Compartmental analysis (CA) and PK/PD modeling were performed by non-linear regression. Correlation and analysis of variance (ANOVA) were used to explore the role of clinically relevant modifiers of bleeding tendency, as appropriate. ANOVA was used to assess inter-group differences in pertinent PK and PD parameters. P value <0.05 significance level was pre-specified for all statistical tests. Results: Mean (±SD) volume of distribution at steady state (Vss), total clearance (CLtot) and terminal half-life (t1/2) from NCA were 40.5 (±11.2) milliliter per kilogram (mL kg-1), 2.9 (±1.2) milliliter per hour per kilogram (mL h-1 kg-1) and 11.6 (±6.2) h, respectively. Mean (±SD) Vss and CLtot from the one-compartment body model (CA) were 39.6 (±8.9) mL kg-1 and 3.1 (±1.3) mL h-1 kg-1, respectively. The mean (±SD) baseline effect (E0) and slope from the PK/PD linear modeling were: for aPTT, 48.9 (±4.4) seconds (sec) and -0.025 (±0.009) second deciliter per international unit (sec dL IU-1), respectively; for PCF, 0.3 (±0.3) kilodynes (kdynes) and 0.008 (±0.004) kilodynes deciliter per international unit (kdynes dL IU-1), respectively; and for CEM, 0.0 (±0.0) kilodynes per square centimeter (kdynes cm-2) and 0.032 (±0.016) kilodynes deciliter per international unit per square centimeter (kdynes dL IU-1 cm-2), respectively. The mean (±SD) maximum effect (Emax) and half the maximum effective concentration (EC50) from the PK/PD sigmoidal Emax model were: for FOT, 70.1 (±16.9) % reduction and 87.8 (±31.4) IU dL-1 for FOT, respectively; for R, 74.9 (±26.0) % reduction and 68.5 (±28.4) IU dL-1, respectively; and for K, 73.2 (±36.4) % reduction and 67.2 (±29.0) IU dL-1, respectively. MA was not PK/PD modeled due to its low sensitivity. Conclusions: Plasma FVIII:C remained ≥1 IU dL-1 over the prophylactic interval. FOT and R were the most sensitive biomarkers at lower plasma FVIII:C. PCF and CEM were more sensitive than K and aPTT at lower plasma FVIII:C. MA was the least sensitive biomarker. Correlation and inter-group differences did not reach statistical significance (small sample size). These results may be used to assess risk of bleeding and dose-optimize FVIII prophylaxis in severe hemophilia.

Quantitative Analysis Of Multiple Charged Large Molecules In Human Or Rat Plasma Using Liquid Chromatography Tandem Mass Spectrometry, Matthew Halquist

Theses and Dissertations

Immunoassays have traditionally been employed for the determination of plasma concentration-time profiles for pharmacokinetic studies of therapeutic proteins and peptides. These ligand binding assays have high sensitivity but require significant time for antibody generation (1 to 2 years) for assay development. Despite high sensitivity, these assays suffer from cross-reactivity that can lead to inaccurate results. As an alternative to immunoassays, this dissertation was focused on the development and validation of assays that can be used for quantitative analysis of peptides or proteins in plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two approaches were considered for measurement of proteins and …

In Vitro Methods To Predict Aerosol Drug Deposition In Normal Adults, Renishkumar Delvadia

Theses and Dissertations

This research was aimed at the development and validation of new in vitro methods capable of predicting in vivo drug deposition from dry powder inhalers, DPIs, in lung-normal human adults. Three physical models of the mouth, throat and upper airways, MT-TB, were designed and validated using the anatomical literature. Small, medium and large versions were constructed to cover approximately 95% of the variation seen in normal adult humans of both genders. The models were housed in an artificial thorax and used for in vitro testing of drug deposition from Budelin Novolizer DPIs using a breath simulator to mimic inhalation profiles …

A Cellular Automata Model Of Enantiomer Interactions With Beta-Cyclodextrin, Desoi Darren

Theses and Dissertations

The binding mechanisms of molecules to cyclodextrins continues to be studied to better explain the interactions occurring. The majority of published models focus on one-to-one molecular binding thermodynamics to explain experimental results. They rely on physical concepts of energies and forces to guide the actions of molecules expressed mathematically in terms of differential and non-linear equations. These models are limited in scope due to their complexity and are not easily expanded to study many diverse analytes. Conversely, cellular automata uses simple mathematical idealizations of systems governed by deterministic and probabilistic rules that are easily adaptable to many types of molecular …

Enhanced Interleukin-1 Activity Contributes To Exercise Intolerance In Patients With Systolic Heart Failure, Benjamin W. Van Tassell, Ross A. Arena, Stefano Toldo, Eleonora Mezzaroma, Tania Azam, Ignacio M. Seropian, Keyur Shah, Justin Canada, Norbert F. Voelkel, Charles A. Dinarello, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.

Methods and Results

We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P

Conclusions

These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies …

Atorvastatin With Or Without An Antibody To Pcsk9 In Primary Hypercholesterolemia, Eli M. Roth, James M. Mckenny, Corinne Hanotin, Gaelle Asset, Evan A. Stein

Pharmacotherapy and Outcomes Science Publications

Background

Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.

Methods

We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to …

A Gga Plus U Approach To Effective Electronic Correlations In Thiolate-Ligated Iron-Oxo (Iv) Porphyrin, Justin Elenewski, John C. Hackett

Medicinal Chemistry Publications

High-valent oxo-metal complexes exhibit correlated electronic behavior on dense, low-lying electronic state manifolds, presenting challenging systems for electronic structure methods. Among these species, the iron-oxo (IV) porphyrin denoted Compound I occupies a privileged position, serving a broad spectrum of catalytic roles. The most reactive members of this family bear a thiolate axial ligand, exhibiting high activity toward molecular oxygen activation and substrate oxidation. The default approach to such systems has entailed the use of hybrid density functionals or multi-configurational/multireference methods to treat electronic correlation. An alternative approach is presented based on the GGA+U approximation to density functional theory, in …

On The Specificity Of Heparin/Heparan Sulfate Binding To Proteins. Anion-Binding Sites On Antithrombin And Thrombin Are Fundamentally Different, Philip D. Mosier, Chandravel Krishnasamy, Glen E. Kellogg, Umesh R. Desai

Medicinal Chemistry Publications

Background

The antithrombin–heparin/heparan sulfate (H/HS) and thrombin–H/HS interactions are recognized as prototypic specific and non-specific glycosaminoglycan (GAG)–protein interactions, respectively. The fundamental structural basis for the origin of specificity, or lack thereof, in these interactions remains unclear. The availability of multiple co-crystal structures facilitates a structural analysis that challenges the long-held belief that the GAG binding sites in antithrombin and thrombin are essentially similar with high solvent exposure and shallow surface characteristics.

Methodology

Analyses of solvent accessibility and exposed surface areas, gyrational mobility, symmetry, cavity shape/size, conserved water molecules and crystallographic parameters were performed for 12 X-ray structures, which include 12 …

Pyridoxal 5′-Phosphate Is A Slow Tight Binding Inhibitor Of E. Coli Pyridoxal Kinase, Mohini S. Ghatge, Roberto Contestabile, Martino L. Di Salvo, Jigar V. Desai, Amit Gandhi, Christina M. Camara, Rita Florio, Isabel N. Gonzalez, Alessia Parroni, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Pyridoxal 5′-phosphate (PLP) is a cofactor for dozens of B6 requiring enzymes. PLP reacts with apo-B6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4′-aldehyde moiety forms covalent adducts with other compounds and non-B6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell …

Crystal Structures Of Human Pyridoxal Kinase In Complex With The Neurotoxins, Ginkgotoxin And Theophylline: Insights Into Pyridoxal Kinase Inhibition, Amit Gandhi, Jigar V. Desai, Mohini S. Ghatge, Martino L. Di Salvo, Stefano Di Biase, Richmond Danso-Danquah, Faik N. Musayev, Roberto Contestabile, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. …

Design, Synthesis, And In Vitro And In Vivo Biological Studies Of A 3′-Deoxythymidine Conjugate That Potentially Kills Cancer Cells Selectively, Qiong Wei, Dejun Zhang, Anna Yao, Liyi Mai, Zhiwei Zhang, Qibing Zhou

Medicinal Chemistry Publications

Thymidine kinases (TKs) have been considered one of the potential targets for anticancer therapeutic because of their elevated expressions in cancer cells. However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity in cancer cells despite effective antiviral activity. 3′-Deoxythymidine phenylquinoxaline conjugate (dT-QX) was designed as a novel nucleobase analog to target TKs in cancer cells and block cell replication via conjugated DNA intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX selectively kills a variety of cancer cells including liver carcinoma, breast adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in normal cells such as …

Predictors Of Carbapenem Resistant Gram-Negative Bacteria In A Consortium Of Academic Medical Center Hospitals, Mera Ababneh

Theses and Dissertations

Background: Gram-negative resistance is a growing problem worldwide. It is generally believed that rates of resistant bacteria within a hospital are a function of antibiotic use, resistant organisms brought into the hospital, infection control efforts, and underlying severity of patient illness. The relative contribution of each to a particular resistance phenotype is unclear. P. aeruginosa is responsible for many hospital acquired infections and it may become resistant to carbapenems. In addition, newer threats to the future utility of the carbapenems are carbapenemase-producing K. pneumoniae Purpose: To determine if there is an association between the volume and composition of antibiotic use, …

Factors Influencing Pharmacists’ Decision To Report Adverse Events Related To Dietary Supplements, Ali M. Alhammad

Theses and Dissertations

Background: The increasing consumption of dietary supplements (DS) has drawn the attention of regulatory agencies, researchers and healthcare professionals. The US Food and Drug Administration (FDA) does not require premarketing assessment of DS considering them safe unless proven otherwise. However, the reporting rate of DS adverse events (DS-AE) is low. Objective: To describe pharmacists’ attitudes and knowledge of DS and DS information resources, and to determine the importance of selected attributes in pharmacists’ decisions to report a DS-AE. Methods: A convenience sample of practicing pharmacists in Virginia was surveyed using a web-based self-administered questionnaire. A conjoint analysis exercise was developed …