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Design, Synthesis, And Evaluation Of Novel Positron Emission Tomography Radiotracers, Christopher Philip Surdock 2017 University of Tennessee Health Science Center

Design, Synthesis, And Evaluation Of Novel Positron Emission Tomography Radiotracers, Christopher Philip Surdock

Theses and Dissertations (ETD)

Neuroblastoma (NB) is the most common extracranial tumor in patients under 1 year of age and it constitutes about 8-10% of all childhood cancer. It originates from neural crest cells that normally differentiate to form the sympathetic ganglia, adrenal medulla and other paraspinal sites where sympathetic nervous system tissue is present. Even with an extensive treatment regimen that typically includes surgery, chemotherapy, total body irradiation and autologous stem cell transplantation, the 5-year event-free survival is <50% for high risk patients, and there are numerous long-term side effects associated with treatment. This body of work investigated two projects for improving patient outcomes through the development of positron emission tomography (PET) radiotracers that could be used for therapy planning. The goal of the first project was to design, synthesize, and evaluate PET radiotracers that could measure the enzymatic activation of Irinotecan (CPT-11), a potent chemotherapeutic used in the treatment of colon cancer and several pediatric solid tumors. CPT-11 itself is a prodrug which is converted in vivo to SN-38, via metabolism by carboxylesterase (CE) enzymes. St. Jude Children’s Research Hospital researchers have designed a two-pronged protocol of tumor-targeted CPT-11 chemotherapy combining the complementary approaches of a) specific modulation of human CE in normal tissues to improve drug delivery, and b) tumor-targeted activation of prodrug using neural progenitor cells (NPC) transfected with a mutant human CE cDNA. The tumor-selective trafficking of NPC allows over-expression of CE within the tumor. This prodrug/activating enzyme therapeutic approach has shown extremely encouraging preclinical results in the treatment of NB (90% 1-year survival in mice). However, successful translation of this novel therapeutic approach into general clinical practice requires a better understanding of progenitor cell trafficking, duration and intensity of enzymatic activity and the ultimate biological fate of the therapeutic construct. Toward this end, PET radiotracers were developed based on extensive structure-activity relationship (SAR) studies of CE binding. The goal of the second project was to design, synthesize, and evaluate PET radiotracers that could identify the presence of the tropomyosin receptor kinase B (TrkB). TrkB is not normally found in sympathetic nervous tissue, which is the tissue NB develops from, and thus is a potential target for imaging and therapy. The presence of TrkB and its neurotrophin, brain derived neurotrophic factor (BDNF), have been reported to protect neuroblastoma tumor cells from chemotherapy-induced apoptosis via a phosphatidylinositol 3’-kinase pathway. Radiotracers were synthesized and evaluated for their ability to identify TrkB both in vitro and in vivo. PET radiosynthetic procedures were optimized to synthesize novel radiotracers for imaging targets that could help clinicians monitor therapy or identify markers that would aid in therapy planning for NB patients. The method development could be applied to future compounds that show improved chemical characteristics for synthesis and selectivity.


Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo 2016 University of Southern Mississippi

Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo

Doctoral Nursing Capstone Projects

Laparoscopic capability provides numerous benefits to patients requiring abdominal surgical procedures. However, the use of these techniques has presented the anesthesia provider with a unique set of challenges in terms of perioperative management and postoperative pain reduction. No standardized method has existed to reduce postoperative pain and improve recovery following these procedures. There were three primary goals of this project. The first goal was to conduct a meta-analysis of randomized controlled trials to determine the benefit of the use of intravenous lidocaine infusions to reduce postoperative pain in laparoscopic abdominal surgery. Twelve articles were included in the meta-analysis that pertained ...


The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary 2016 University of Louisville

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current ...


Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro MD 2016 Marshall University

Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro Md

Yanling Yan

The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in ...


Patient Portals In Pharmacist-Run Ambulatory Care Clinics: Is There “Meaningful Use”?, H. Paige Erdeljac, Melissa J. Snider, Kelly Bartsch, Raul Weiss 2016 The Arthur G. James Comprehensive Cancer Center

Patient Portals In Pharmacist-Run Ambulatory Care Clinics: Is There “Meaningful Use”?, H. Paige Erdeljac, Melissa J. Snider, Kelly Bartsch, Raul Weiss

Excerpts in Pharmacy Research Journal

Objective

The purpose of this study is to describe patient portal utilization within pharmacist-managed clinics at an academic medical center from the perspectives of the institution, healthcare team, and patient. This study measures the progress toward meeting requirements for meaningful use per the Centers for Medicare and Medicaid Services (CMS).

Methods

The study included patients in pharmacist-managed clinics and consisted of a retrospective chart review and patient survey. Primary endpoints consisted of: 1) report progress toward meeting CMS criteria for meaningful use in subset of patients seen in the pharmacy-managed clinics, 2) describe utilization of patient portal across the healthcare ...


Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch 2016 Albany College of Pharmacy and Health Sciences

Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch

Excerpts in Pharmacy Research Journal

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and gain-of-function mutations were first described in 2003. The gain-of-function mutations observed were associated with low-density lipoprotein-cholesterol (LDL-C) levels in the 400’s, in addition to premature cardiovascular disease. Subsequent loss-of-function experiments conducted in mice demonstrated marked reductions in plasma cholesterol levels in the absence of PCSK9. Physiologically, PCSK9 serves as a chaperone protein and functions to reduce low-density lipoprotein (LDL) receptor recycling; consequently, less LDL-C is removed from circulation and serum lipid concentrations become elevated. Inhibition of PCSK9 prevents LDL receptor degradation and preserves receptor recycling to the hepatocyte surface ...


Modeling With Medicinal Chemistry: Practical Innovative Technology-Based Activity To Enhance Student’S Learning Through Inter-Departmental Collaboration: Part I, Miriam Ansong, Denise Simpson, Nicole K. Stute 2016 Cedarville University

Modeling With Medicinal Chemistry: Practical Innovative Technology-Based Activity To Enhance Student’S Learning Through Inter-Departmental Collaboration: Part I, Miriam Ansong, Denise Simpson, Nicole K. Stute

Excerpts in Pharmacy Research Journal

Background: Concepts of formulary management and its applications in clinical practice is a challenge faced by many first professional year pharmacy students. This challenge may be attributed to a lack of foundational knowledge and practical skills at this level. Preparing students for lifelong learning mandates early exposure to practical application of concepts. This warrants the need for students to integrate knowledge, skills, abilities, and attitudes in clinical practice. As a result, a state-of-the-art one stop shopping structure of the day (SOD) activity was created for P1 pharmacy students to enable the authors to assess their skill sets.

Objective: The objective ...


Research And Publication Highlights, Miriam Ansong 2016 Cedarville University

Research And Publication Highlights, Miriam Ansong

Excerpts in Pharmacy Research Journal

Bibliography of completed research and book chapters


Rnai Nanotechnology: A Platform For Sirna Screening And Cancer Gene Therapy, Mayurbhai Ravikant Patel 2016 Seton Hall University

Rnai Nanotechnology: A Platform For Sirna Screening And Cancer Gene Therapy, Mayurbhai Ravikant Patel

Seton Hall University Dissertations and Theses (ETDs)

Over the past two decades, advances in RNA structural biology have improved our understanding of the structures and folding properties of naturally occurring RNAs. RNA sequences and structures participate in many specific biological functions, such as those performed by messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), micro RNA (miRNA), short-interfering RNA (siRNA), small nuclear RNA (snRNA) and many others. The noncoding RNAs, such as siRNA, do not express proteins but have been utilized in a wide range of applications, including RNA interference (RNAi) and the regulation of mRNA expression. These important biological functions have been implemented in gene ...


Repeated Zolpidem Treatment Effects On Sedative Tolerance, Withdrawal, Mrna Levels, And Protein Expression, Brittany T. Wright 2016 University of Tennessee Health Science Center

Repeated Zolpidem Treatment Effects On Sedative Tolerance, Withdrawal, Mrna Levels, And Protein Expression, Brittany T. Wright

Theses and Dissertations (ETD)

Zolpidem and benzodiazepines (BZs) potentiate the inhibitory action of gamma-Aminobutyric acid (GABA) by allosterically binding to GABAA receptors (GABAAR). Prolonged use of GABAAR positive allosteric modulators (PAM) can lead to behavioral tolerance, the diminished response to the same drug dose with repeated use, and withdrawal, a group of symptoms that occur due to abrupt end of drug treatment. Zolpidem is a short-acting, non-BZ GABAAR PAM whose potential for tolerance and withdrawal is unclear. Zolpidem demonstrates sedative efficacy similar to BZs and has become a main treatment of insomnia in lieu of BZs. Zolpidem replaced BZs due to lower incidences of ...


Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland 2016 University of Tennessee Health Science Center

Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland

Theses and Dissertations (ETD)

As a species, humans have become ever reliant on the use of antibiotics to facilitate our everyday lives. The widespread emergence of resistance to currently used antibiotics is commonly attributed to an over use in our society. Such resistance, coupled with a lack of innovation and production of novel antibiotic drugs, threatens to return humanity to an era similar to one before the discovery of the first antibiotics. The need to find new agents to be used in this fight is paramount, as well as learning from our recent failures to produce such compounds. This document will highlight my efforts ...


Incidence Of Hypomagnesemia On Proton Pump Inhibitors At The Huntington Veterans Affairs Medical Center – Ihop, Ebrahim Sabbagh, DO, Chelsey R. Houchins, James Allman, II, PharmD, Samson Teka, MD 2016 Marshall University

Incidence Of Hypomagnesemia On Proton Pump Inhibitors At The Huntington Veterans Affairs Medical Center – Ihop, Ebrahim Sabbagh, Do, Chelsey R. Houchins, James Allman, Ii, Pharmd, Samson Teka, Md

Marshall Journal of Medicine

Abstract

Title: Incidence of hypomagnesemia on proton pump inhibitors at the Huntington Veterans Affairs Medical Center – IHOP

Purpose:

Proton pump inhibitors (PPIs), both prescription and over-the-counter, are widely used for the treatment of acid-related disease states such as dyspepsia, gastroesophageal reflex disease, esophagitis, and peptic ulcers. These medications are generally considered safe in most patient populations; however, there are several adverse effects that may occur with long-term use. Hypomagnesemia is a newer complication arising in the literature following multiple case reports over the past several years, although the true incidence of hypomagnesemia associated with PPI use remains unclear at this ...


Determination Of Isotopic Abundance Of 13c/12c Or 2h/1h And 18o/16o In Biofield Energy Treated 1-Chloro-3-Nitrobenzene (3-Cnb) Using Gas Chromatography-Mass Spectrometry, Mahendra Kumar Trivedi 2016 Selected Works

Determination Of Isotopic Abundance Of 13c/12c Or 2h/1h And 18o/16o In Biofield Energy Treated 1-Chloro-3-Nitrobenzene (3-Cnb) Using Gas Chromatography-Mass Spectrometry, Mahendra Kumar Trivedi

Mahendra Kumar Trivedi

1-Chloro-3-nitrobenzene (3-CNB) is an aromatic halo-amine compound used as chemical intermediate for the production of several fine chemicals like pharmaceuticals, dyes, agricultural chemicals, etc. The stable isotope ratio analysis has drawn attention in numerous fields such as agricultural, food authenticity, biochemistry, etc. The objective of the current research was to investigate the impact of the biofield energy treatment on the isotopic abundance ratios of PM+1/PM, PM+2/PM and PM+3/PM in 3-CNB using gas chromatography - mass spectrometry (GC-MS). The sample, 3-CNB was divided into two parts - one part was denoted as control and another part was ...


Theoretical And Experimental Analysis Of The Antioxidant And Anti-Amyloid Features Of Synthetic Resveratrol Mimics, William Horton, Anne Kokel, Fanni Török, Chris Tran, Marianna Török, Bela Török 2016 University of Massachusetts Boston

Theoretical And Experimental Analysis Of The Antioxidant And Anti-Amyloid Features Of Synthetic Resveratrol Mimics, William Horton, Anne Kokel, Fanni Török, Chris Tran, Marianna Török, Bela Török

UMass Center for Clinical and Translational Science Research Retreat

Diaryl hydrazones, possessing similar structure to the popular red wine antioxidant resveratrol, have been previously identified as multitarget compounds interfering with several processes associated with the pathogenesis of Alzheimer’s disease (AD). These compounds exhibited particularly strong inhibition of the amyloid beta (A) peptide self-assembly, including blocking the formation of fibrils and oligomers, species that are widely accepted to be neurotoxic. The molecules were also powerful free radical scavengers and thus have a potential to defend against oxidative stress.

In order to learn more about the mode of action of the compounds, theoretical and experimental studies have been carried out ...


Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian 2016 University of Massachusetts Medical School

Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-Thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian

UMass Center for Clinical and Translational Science Research Retreat

Soil-transmitted helminths (STHs), most notably, hookworms, whipworms, and Ascaris, are nematodes that infect more than 1.5 billion of the poorest people and are amongst the leading causes of morbidity worldwide. Only two classes of de-worming drugs (anthelmintics) are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed to overcome emerging resistance and to produce higher cure rates. Crystal (Cry) proteins, in particular Cry5B, made by Bacillus thuringiensis (Bt) are promising new candidates. Cry5B has excellent anthelmintic properties against many free-living and parasitic nematodes, including in vivo efficacy against multiple STH ...


Invitrometrix Qcm-Based Cell Biosensor: Research Tool To Accelerate Pharmaceutical Drug Discovery Success, Abiche H. Dewilde 2016 University of Massachusetts Lowell

Invitrometrix Qcm-Based Cell Biosensor: Research Tool To Accelerate Pharmaceutical Drug Discovery Success, Abiche H. Dewilde

UMass Center for Clinical and Translational Science Research Retreat

As part of the mini-symposium entitled "Shark Tank-UMass Spin-out Life Sciences Start-ups," Dr. Dewilde discusses an example of UMass life sciences technology that has been spun out into a start-up company -- Cell QCM from UMass Lowell.


Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu 2016 University of Tennessee Health Science Center

Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu

Theses and Dissertations (ETD)

Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure ...


Upregulation Of Antibiotic Activity Of A Streptomyces Sp. Via Co-Cultures With Challenge Pathogens, Anne A. Sung 2016 University of Connecticut - Storrs

Upregulation Of Antibiotic Activity Of A Streptomyces Sp. Via Co-Cultures With Challenge Pathogens, Anne A. Sung

Honors Scholar Theses

Marine natural product drug discovery has begun to play an important role in the treatment of diseases. Early drug discovery from natural products came primarily from plants, but after the discovery and development of penicillin, scientists started looking at natural products from microorganisms. Numerous natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity in the production of biologically active secondary metabolites. Ascidians, also known as tunicates, are marine invertebrates that contain many host-associated microbes. Adult tunicates are sessile, which makes them vulnerable to predators, and thus, they are ...


Urinary Alkalisation For Symptomatic Uncomplicated Urinary Tract Infection In Women (Review), Dermot B. O'Kane, Sameer Dave, Neel Gore, Farhaan Patel, Tammy Hoffmann, Jeanne L. Trill, Chris del Mar 2016 Bond University

Urinary Alkalisation For Symptomatic Uncomplicated Urinary Tract Infection In Women (Review), Dermot B. O'Kane, Sameer Dave, Neel Gore, Farhaan Patel, Tammy Hoffmann, Jeanne L. Trill, Chris Del Mar

Christopher Del Mar

Background

Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women, characterised by dysuria and urinary frequency. Urinary alkalisers are widely used in some countries for the symptomatic treatment of uncomplicated UTI, and they are recommended in some national formularies. However, there is a lack of empirical evidence to support their use for UTI and some healthcare guidelines advise against their use.

Objectives

We aimed to look at the benefits and harms of the use of urinary alkalisers for the treatment of uncomplicated UTIs in adult women.

Search methods

We searched the Cochrane Kidney and Transplant Specialised ...


Rapid Effects Of Aldosterone And Spironolactone In The Isolated Working Rat Heart, John C. Barbato, Patrick J. Mulrow, Joseph I. Shapiro MD, Roberto Franco-Saenz 2016 Marshall University

Rapid Effects Of Aldosterone And Spironolactone In The Isolated Working Rat Heart, John C. Barbato, Patrick J. Mulrow, Joseph I. Shapiro Md, Roberto Franco-Saenz

Joseph I Shapiro MD

Chronic administration of aldosterone promotes myocardial fibrosis in rats. The Randomized Aldactone Evaluation Study reported that the aldosterone antagonist spironolactone improved outcome in patients with congestive heart failure, suggesting a deleterious effect of aldosterone in the heart. Aldosterone has been shown to have rapid nongenomic effects in different tissues including the heart. However, the hemodynamic actions of aldosterone and spironolactone are not well characterized. In this study, we examined the hemodynamic effects of aldosterone and its receptor antagonist, spironolactone, in the isolated rat heart by use of the Langendorff-Neely technique. Perfusion with 10 nmol/L aldosterone increased contractility by 45 ...


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