Chemicals and Drugs Commons^™

Stability Of Extemporaneously Prepared Lansoprazole Suspension At Two Temperatures, Jordan T. Morrison, Ralph A. Lugo, Jim C. Thigpen, Stacy D. Brown

ETSU Faculty Works

OBJECTIVE The purpose of this study was to examine the stability of a generic lansoprazole product in a 3 mg/mL sodium bicarbonate suspension under room temperature and refrigerated conditions. METHODS Lansoprazole suspensions (3 mg/mL) were prepared in triplicate using an 8.4% sodium bicarbonate vehicle for each storage condition (room temperature and refrigerated). During 1 month, samples from each replicate were periodically removed and analyzed for lansoprazole concentration by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Each sample was spiked with 10 mg/L omeprazole to serve as the internal standard. A positive electrospray LC-MS/MS method was validated over the calibration range of 5 …

Novel Cis-Restricted Β-Lactam Combretastatin A-4 Analogues Display Anti-Vascular And Anti-Metastatic Properties In Vitro, Seema M. Nathwani, Lisa M. Greene, Linda Hughes, Miriam Carr, Niamh O'Boyle, Susan Mcdonnell, Mary J. Meegan, Daniela M. Zisterer

Articles

No abstract provided.

Cytoplasmic Actin: Structure And Function, Justin Konig

The Science Journal of the Lander College of Arts and Sciences

Cytoplasmic actin plays a crucial role in cellular structure, cell motility, intracellular transportation, and the cell cycle. Two isoforms of cytoplasmic actin have been identified, β and γ. Although their amino acid sequence is nearly identical, these two isoforms are encoded by different genes located on different chromosomes. Recent research has found that, despite their similarities, the two isoforms of cytoplasmic actin have distinct functions. This paper will review the structural and functional differences between the two isoforms, concluding with a discussion of some mutations that have been linked to disease.

Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as …

Is Reduction Of Caffeine Intake Effective In Reducing The Symptoms Of Panic Attack In Panic Disorder Patients?, Elizabeth Wasson

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective for this selective EMB review is to determine whether or not the reduction of caffeine intake is effective in reducing the symptoms of panic attack in panic disorder patients.

STUDY DESIGN: Review of three English language randomized control trials published in 2007, 2008, and 2009.

DATA SOURCES: The double-blind placebo-controlled randomized control trials were obtained via PubMed.

OUTCOMES MEASURED: The prevalence of a clinical panic attack. Pre and post caffeine/placebo administration questionnaires were given to the participants. These surveys included the Subjective Units of Disturbance Scale (SUDS) and the Diagnostic Symptom Questionnaire (DSQ). …

A Novel Selective Lipid Uptake Pathway Contributing To Ldl-Induced Macrophage Foam Cell Formation, Jason M. Meyer

Theses and Dissertations--Molecular and Cellular Biochemistry

Atherosclerosis is a disease characterized by cholesterol-rich plaques within the intima of medium and large arteries. Cholesterol deposition is thought to occur by infiltration of low-density lipoprotein (LDL) into lesions followed by uptake into macrophages, generating lipid-loaded “foam cells.” Foam cells can also be generated in vitro by treatment of macrophages with LDL or oxidized LDL (oxLDL). The purpose of the current investigation was to determine the contribution of selective cholesteryl ester (CE) uptake versus whole-particle uptake during LDL-induced foam cell formation in cultured macrophages. Murine bone marrow-derived macrophages (BMMs) exhibited significant cholesterol accumulation when treated with LDL as indicated …

The Mesocorticolimbic Dopamine Pathway Reconstituted In Vitro: Glutamate Receptors And Corticosteroid-Methamphetamine Neurotoxicity, Jennifer N. Berry

Theses and Dissertations--Psychology

Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the …

High Fat Diet Induced Obesity In A Mouse Model For Colorectal Cancer, Kennerly Clinton Patrick

Theses and Dissertations

Obesity is widely correlated with the incidence of colorectal cancer (CRC). The exact mechanisms that link obesity to CRC risk have not yet been fully established, and only a limited number of animal models are available to study pathways involved in obesity-related colon carcinogenesis. The objective of this study was to determine the influence of HFD-induced obesity on AOM/DSS-mediated colorectal tumorigenesis, tumor proliferation, and symptom severity. Male C57BL/6 mice were fed a novel high fat diet, designed to mimic the standard American diet (12 % saturated fat & 28 % unsaturated fat), at 4 weeks of age until 16 weeks …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Quantitative Measures Of Estrogen Receptor Expression In Relation To Breast Cancer-Specific Mortality Risk Among White Women And Black Women, Huiyan Ma, Yani Lu, Polly A. Marchbanks, Suzanne G. Folger, Brian L. Strom, Jill A. Mcdonald, Michael S. Simon, Linda K. Weiss, Kathleen E. Malone, Ronald T. Burkman, Jane Sullivan-Halley, Dennis M. Deapen, Michael F. Press, Leslie Bernstein

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality.

Methods

We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …

Mass Spectrometry And Tandem Mass Spectrometry Characterization Of Protein Patterns, Protein Markers And Whole Proteomes For Pathogenic Bacteria, Jennifer Intelicato-Young

Theses and Dissertations

There have been many recent reviews published on MALDI-TOF MS (matrix assisted laser desorption/ionization time-of-flight) MS (mass spectrometry) for identification of bacteria particularly with relevance to clinical microbiology. MALDI-TOF MS is now a mature technique for bacterial identification with great promise. The purpose of this review is to put into perspective MALDI-TOF MS and other widely used mass spectrometry methods for characterization of proteins. MALDI-TOF MS is used for rapid determination of a mass pattern of proteins for bacterial characterization; these proteins

are generally not identified. Alternatively, after gel separation, MALDI TOF-TOF MSMS (tandem mass spectrometry) or on-line LC-ESI MS-MS …

Role Of Microrna-155 In A Mouse Model Of Colon Cancer., Claire Mitchell Midyette

Theses and Dissertations

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that …

Development Of Proteomic Characterization And Speciation Techniques Utilizing Tryptic Peptides With Maldi-Tof Ms And Lc-Esi Ms-Ms, Jennifer Marie Kooken

Theses and Dissertations

The characterization of microbes which can be opportunists and pathogens (e.g., methicillin resistant Staphylococcus aureus (MRSA)) is important in understanding and potentially treating diseases caused by various bacterial species. Common genera found in the human skin micro-biome include Micrococcus and Staphylococcus, but there only a limited number of tests to differentiate these genera and/or species. My research reflects methods development from distinguishing one closely related genera from another and then expanded to species identification. Tryptic peptides were analyzed by MALDI TOF MS and the mass profiles compared with those of a reference strain in both genus and species identification. Aconitate …

Synthesis And Biochemical Activities Of Antiproliferative Amino Acid And Phosphate Derivatives Of Microtubule-Disrupting Beta-Lactam Combretastatins, Niamh M. O'Boyle, Lisa M. Greene, Niall O. Keely, Shu Wang, Tadhg S. Cotter, Daniela M. Zisterer, Mary J. Meegan

Articles

The synthesis and biochemical activities of novel water-soluble β-lactam analogues of combretastatin A-4 are described. The first series of compounds investigated, β-lactam phosphate esters 7a, 8a and 9a, exhibited potent antiproliferative activity and caused microtubule disruption in human breast carcinoma-derived MCF-7 cells. They did not inhibit tubulin polymerisation in vitro, indicating that biotransformation was necessary for their antiproliferative and tubulin binding effects in MCF-7 cells. The second series of compounds, β-lactam amino acid amides (including 10k and 11l) displayed potent antiproliferative activity in MCF-7 cells, disrupted microtubules in MCF-7 cells and also inhibited the polymerisation of …

Raman Micro Spectroscopy Study Of The Interaction Of Vincristine With A549 Cells Supported By Expression Analysis Of Bcl-2 Protein, Haq Nawaz, Amaya Garcia, Aidan Meade, Fiona Lyng, Hugh Byrne

Articles

Understanding the interaction of anticancer drugs with model cell lines is important to elucidate the mode of action of these drugs as well as to develop cost effective and rapid screening methods. Raman spectroscopy has been demonstrated to be a valuable technique for high throughput, noninvasive analysis. The interaction of vincristine with a human lung adenocarcinoma cell line (A549)was investigated using Raman micro spectroscopy. The results were correlated with parallel measurements from the MTT cytotoxicity assay, which yielded an IC₅₀ value of 0.10 ± 0.03 μM. The Raman spectral data acquired from vincristine treated A549 cells was analysed to …

Avoidance Disruptive Effect Of Clozapine And Olanzapine Is Potentiated By Increasing The Test Trials: Further Test Of The Motivational Salience Hypothesis, Min Feng, Nan Sui, Ming Li

Department of Psychology: Faculty Publications

Antipsychotic drugs suppress animals’ ability to avoid an aversive stimulus in the conditioned avoidance response model (CAR). This behavioral effect is thought to reflect antipsychotic activity and is suggested to be mediated by a drug’s action in attenuating the motivational salience of a conditioned stimulus (CS). In the present study, we tested whether atypical antipsychotic drugs clozapine and olanzapine act through this behavioral mechanism by manipulating the number of avoidance test trials. We reasoned that more CS trials in the present of clozapine or olanzapine would afford the drug more opportunities to decrease the motivational salience of the CS, thus …

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage

David Hage Publications

This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …

Differential Modulation Of Functional Dynamics And Allosteric Interactions In The Hsp90-Cochaperone Complexes With P23 And Aha1: A Computational Study, Kristin Blacklock, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric interactions of the molecular chaperone Hsp90 with a large cohort of cochaperones and client proteins allow for molecular communication and event coupling in signal transduction networks. The integration of cochaperones into the Hsp90 system is driven by the regulatory mechanisms that modulate the progression of the ATPase cycle and control the recruitment of the Hsp90 clientele. In this work, we report the results of computational modeling of allosteric regulation in the Hsp90 complexes with the cochaperones p23 and Aha1. By integrating protein docking, biophysical simulations, modeling of allosteric communications, protein structure network analysis and the energy landscape theory we …

Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes …