Chemicals and Drugs Commons^™

Self-Reported Exercise And Risk Of Osteoporosis In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Lori J. Mennen-Winchell

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer is stimulated to grow in response to testosterone. Androgen deprivation therapy (ADT) leads to chemical castration and suppression of prostate cancer cell production. Testosterone levels less then 300ng/ml decreases bone mineral density and could result in osteoporosis. Studies have shown that during the first year of ADT, fracture risk, mainly in hips and spine increases about 50%. In men, 40% of hip fractures result in death. Exercise may reduce the risk of osteoporosis and thus contribute to the prevention of hip and other fractures. There is limited data regarding whether exercise is associated with a reduced risk of …

The Design And Synthesis Of Autotaxin Inhibitors And Analogs Of Lysophosphatidic Acid, Renuka Niranjan Gupte

Theses and Dissertations (ETD)

Lysophosphatidic acid (LPA) is a naturally occurring bioactive phospholipid. It has a wide array of biological effects like cell proliferation, survival, migration, apoptosis invasion, wound healing and angiogenesis. Autotaxin (ATX) was identified as an autocrine tumor cell motility factor from A2058 melanoma conditioned medium. ATX has lysophospholipase D enzyme activity and is responsible for the cleavage of lysophophatidylcholine (LPC) leading to the generation of LPA. Antagonists of Autotaxin would have a potential therapeutic application in cancer research. Chapter 1 is an introduction of LPA and autotaxin. It provides the background and significance of the research. Chapter 2 explores the synthesis …

Novel Insights Into Ubiquitin-Like Protein E1-E2 Interactions, Asad Taherbhoy

Theses and Dissertations (ETD)

Posttranslational modification of macromolecules by ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo and NEDD8 regulate a vast array of processes in the cell. Transfer of UBLs to their target generally occurs by a series of molecular handoffs down an E1‑E2‑E3 cascade. We are interested in understanding how E1‑E2 pairs interact and mediate UBL transfer. To this effect, we studied two E1‑E2 pairs: the Sumo pathway (Sumo utilizes a canonical E1 and E2) and the Atg8 pathway (Atg8 is a UBL involved in autophagy that utilizes a non-canonical E1‑E2 pair).

Sumo conjugation is initiated by the heterodimeric Aos1‑Uba2 E1 enzyme (in …

Inflammatory Proteins, Genetic Variation, And Environmental Influences On Health Care Associated Infection Development In Sepsis, Reba Antoinette Umberger

Theses and Dissertations (ETD)

The purpose of this study was to determine the impact of baseline systemic inflammation (pro‑inflammatory cytokine, anti‑inflammatory cytokine, and their ratio), genetic variability, and environment on the development of health care associated infections (HAI) among sepsis patients during their ICU stay (up to 28 days).

Methods: A prospective observation study was conducted at the Veterans Affairs Medical Center in the Medical Intensive Care Unit over an 18 month period. A total of 78 patients were enrolled within 72 hours of presenting to the ICU with sepsis. Patient were excluded if they were receiving immunosuppressants (chemotherapy or greater than one mg/kg …

Quantification Of Lansoprazole In Oral Suspension By Ultra-High-Performance Liquid Chromatography Hybrid Ion-Trap Time-Of-Flight Mass Spectrometry, Stacy D. Brown, Justin D. Connor, Nicholas C. Smallwood, Ralph A. Lugo

ETSU Faculty Works

An LC-MS/MS method was developed and validated to be used as a stability indicating assay for the study of a 3 mg/mL lansoprazole oral suspension. The method utilizes a UPLC (ultra-performance liquid chromatography) column and unique mass spectrometric detection (ion-trap time-of-flight (IT-TOF)) to achieve a sensitive (LOD 2 ng/mL), accurate, and reproducible quantification of lansoprazole. This method reports an intraday and interday coefficient of variation of 2.98 ± 2.17% ( for each concentration for each day) and 3.07 ± 0.89% ( for each concentration), respectively. Calibration curves (5–25 μg/mL) were found to be linear with an value ranging from …

Characterization Of Amino Acid Residues Integral To Neuronal Binding Of Amyloid Beta Protein In Alzheimer’S Disease, Nicole C. Olson

Chemistry and Biochemistry

Purpose:  Alzheimer’s Disease is a neurodegenerative disease resulting from over-production and neuronal accumulation of amyloid-beta proteins (Aβ40/Aβ42). The glycine residue at position 33 and histidine residues at positions 13 and 14 are involved with binding and internalization of these proteins, actions potentially inhibited by substituting or sterically hindering these residues with an antibody specific to positions 2-11 (IgG-4.1). Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were used as a neuronal model to determine whether substitution and/or antibody block amyloid-beta’s neuronal interactions.

Methods:  PC12 cells were incubated with fluorescein-labeled-amyloid-beta-40 (F-Aβ40) or substituted F-Aβ40 derivatives (F-Aβ40-H13,14G, F-Aβ40-H13,14G;G33A), with or without …

Determination Of Protein Using Microdrop Assay, Hardik Khared

All Capstone Projects

After purification of protein, it is important to know the concentration of protein in our samples. Concentration or amount of protein in the sample is determined by different assay as BCA (bicinchoninic acid) Assay, Bradford Assay, and Lowery Assay. There are different methods available to perform these assays, which have some limitations, restrictions, advantages and disadvantages. These methods require large amounts of costly reagents, proteins and most importantly, valuable time. To overcome these problems a new method is developed called Microdrop Protein Analysis. This new method required a very small amount of reagents and protein mixtures (2-5 µʅ volume) and …

Detection Of Protein By Microdrop Analysis, Yogeshkumar Radadiya

All Capstone Projects

Analysis of protein depends particularly on protein concentration. Protein concentration measurement is the most important part in the research work to conduct protein-related studies. Although there are many methods available for this purpose, each method has certain limitations. The aim of the experiment is to develop either new or modified analytical method for the analysis and detection of protein using newly introduced micro-plate reader equipped with Take-3 microplate with the help of Gen-5 software. An ideal assay should be simple and easy to carry out. Another aspect to be taken into consideration are low inference, stability of measured components and …

Second-Hand Smoke In A University Campus: Attitudes And Perceptions Of Faculty, Staff And Students, Cecilia M. Watkins, Sandeep Mishra, Herpreet Kaur Thind, Srinivasa B. Gokarakonda, Grace Lartey, Monia Chahal

Public Health Faculty Publications

Purpose: To examine the attitudes and perceptions of faculty, staff and students concerning tobacco policies at a university campus in a tobacco producing state. Methods: A questionnaire was administered to faculty, staff and students to assess knowledge, attitudes and beliefs related to smoking and exposure to second-hand smoke on campus. A 3-wave e-mailing was used to send the questionnaire. Results: A total of 2,914 individuals responded to the questionnaire. Majority (60%) of the participants believed a smoke free policy would be a positive move and could possibly improve the quality of life for the campus community, while not negatively affecting …

The Use Of Non-Steroidal Anti-Inflammatory Drugs (Nsaids) In Treating Delayed Onset Muscle Soreness (Doms), Tiffany Windju

Kinesiology and Public Health

No abstract provided.

A Survey Of Oxidative Paracatalytic Reactions Catalyzed By Enzymes That Generate Carbanionic Intermediates: Implications For Ros Production, Cancer Etiology, And Neurodegenerative Diseases, Victoria Bunik, John Schloss, John T. Pinto, Natalia Dudareva, Arthur J L Cooper

NYMC Faculty Publications

Enzymes that generate carbanionic intermediates often catalyze paracatalytic reactions with O2 and other electrophiles not considered “normal” reactants. For example, pyridoxal 5′-phosphate (PLP)—containing pig kidney dopa decarboxylase oxidizes dopamine with molecular O2 to 3,4-dihydroxyphenylacetaldehyde at about 1% of the rate at which it catalyzes nonoxidative dopa decarboxylation. The mutant Y332F enzyme, however, catalyzes stoichiometric conversion of dopa to 3,4-dihydroxyphenylacetaldehyde, suggesting that even minor structural changes may alter or initiate paracatalytic reactions catalyzed by certain enzymes. Carbanions generated by several thiamine diphosphate (ThDP)—dependent enzymes react with different electrophiles, transforming some xenobiotics and endogenous compounds into potentially biologically hazardous products. The detrimental …

Serum 25-Hydroxyvitamin D Level And Acute-Phase Reaction Following Initial Intravenous Bisphosphonate., Tarak Srivastava, Hongying Dai, Connie J. Haney, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Follicle-Stimulating Hormone Promotes Rank Expression On Human Monocytes, Joseph G. Cannon, Barbara Kraj, Gloria Sloan

School of Medical Diagnostics & Translational Sciences Publications

Elevated serum concentrations of follicle-stimulating hormone (FSH) are associated with diminished bone density in women, beginning years before menopause and the decline in estradiol. We hypothesized that FSH promotes development of myeloid cells toward the bone-resorbing osteoclast phenotype. This was tested by isolating peripheral blood mononuclear cells from nine healthy adults, incubating them in the presence of FSH at three different concentrations spanning the physiological range, and then measuring the expression of receptor activator for NF-κB (RANK, a surface marker for osteoclasts) on CD14+ cells by flow cytometry. In the absence of FSH, 3.3±0.5% of the cells expressed high levels …

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

Chemical Composition And Product Quality Control Of Turmeric (Curcuma Longa L.), Shiyou Li, Wei Yuan, Guangrui Deng, Ping Wang, Peiying Yang, Bharat Aggarwal

Faculty Publications

Chemical constituents of various tissues of turmeric (Curcuma longa L.) have been extensively investigated. To date, at least 235 compounds, primarily phenolic compounds and terpenoids have been identified from the species, including 22 diarylheptanoids and diarylpentanoids, eight phenylpropene and other phenolic compounds, 68 monoterpenes, 109 sesquiterpenes, five diterpenes, three triterpenoids, four sterols, two alkaloids, and 14 other compounds. Curcuminoids (diarylheptanoids) and essential oils are major bioactive ingredients showing various bioactivities in in vitro and in vivo bioassays. Curcuminoids in turmeric are primarily accumulated in rhizomes. The essential oils from leaves and flowers are usually dominated by monoterpenes while those from …

Efficacy And Safety Of Dabigatran: A Comparison Of Food And Drug Administration Approved Dosing Regimens, Kenneth Lupi Pharmd, Joseph Ottinger Rph, Ms, Mba, Bcps

Department of Pharmacy

No abstract provided.

Antispasmodic And Ca++ Antagonist Potential Of Marrubiin, A Labdane Type Diterpene From Phlomis Bracteosa, Javid Hussain, Riaz Ullah, Arif-Ullah Khan, Fazal Mabood, Mohammad Raza Shah, Ahmed Al-Harrasi, Anwar Gilani

Department of Biological & Biomedical Sciences

A tricyclic labdane type diterpene was isolated for the first time from ethyl acetate soluble part of Phlomis bracteosa. Its structure was confirmed by x-ray which was found to be marrubiin. When studied in isolated rabbit jejunum, marrubiin caused concentration-dependent relaxation of spontaneous and high K+ (80 mM)-induced contractions, like that caused by verapamil, indicating that marrubiin exhibits spasmolytic activity, possibly mediated through Ca++ channel blocking action.

Click Chemistry Inspired One-Pot Synthesis Of 1, 4-Disubstituted 1, 2, 3-Triazoles And Their Src Kinase Inhibitory Activity, Dalip Kumar, V. Buchi Reddy, Anil Kumar, Deendayal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq. PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure-activity relationship analysis demonstrated that insertion of C6H5- and 4-CH3C6H4- at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32-43 µM) of 1,4-disubstituted 1,2,3-triazoles.

Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory And Anticancer Activities, Asal Fallah-Tafti, Alireza Foroumadi, Rakesh Tiwari, Amir Nasrolahi Shirazi, David G. Hangauer, Yahao Bu, Tahmineh Akbarzadeh, Keykavous Parang, Abbas Shafiee

Pharmacy Faculty Articles and Research

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. …

The Release Of Calcium In Bacillus Anthracis Pathogenicity, Natiera Magnuson, Manomita Patra, Maria Elena Reynaga, Ernesto Abel-Santos

McNair Poster Presentations

Bacillus anthracis spores form in response to starvation and can withstand extremes of heat, radiation, and chemical toxins, making B. anthracis spores ideal vehicles for infections.1 The resistance and dormancy of bacterial spores are dependent on a largely dehydrated core.2 The spore core is not only devoid of water, but contains between 0.8 to 1M calcium complexed with 2,6-pyridinedicarboxylic acid (dipicolinic acid, DPA). The DPA-calcium complex (CaDPA) helps protect DNA, RNA, and the metabolic enzymes needed for the establishment of a vegetative cell cytoplasm.3 An anthrax infection starts with the germination of B. anthracis spores in a macrophage.4 The germinated …