Pharmacy and Pharmaceutical Sciences Commons^™

Treatment Of Vaso-Occlusive Pain Related To Sickle Cell Disease In Pediatric Patients: A Systematic Review, Rebecca L. Tourtellotte

Senior Honors Projects

Sickle cell disease is a rare inherited disorder that affects the shape of red blood cells. Symptoms generally begin by three years of age. Complications of sickle cell disease include vaso-occlusive crises, acute chest syndrome, infections, pulmonary hypertension, priapism, stroke, as well as problems with various organ systems. Vaso-occlusive crises are the most common reason for hospitalization in patients with sickle cell disease. A vaso-occlusive crisis is an episode of pain, described as sharp, intense, and throbbing, most commonly occurring in the lower back, leg, hip, abdomen, or chest. It typically begins at night and lasts 3-14 days. No cure …

Simplified Reversed Chloroquines To Overcome Malaria Resistance To Quinoline-Based Drugs, Bornface Gunsaru, Steven J. Burgess, Westin Morrill, Jane X. Kelly, Shawheen Shomloo, Martin J. Smilkstein, Katherine May Liebman, David H. Peyton

Chemistry Faculty Publications and Presentations

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from in vitro heme binding and beta-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against Plasmodium falciparum similar to those of CQ, although other mechanisms of action may be relevant to their activities.

Withaferin A Synergistically Enhances The Effects Of Paclitaxel Against Lung Cancer., Al Hassan Kyakulaga

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer-related deaths among both men and women in the U.S and worldwide. Today, paclitaxel (PAC) or taxol alongside platinum-based drugs is the most widely used agent as the first-line regimen for advanced NSCLC. However, due to toxicity, drug resistance, solubility and efficacy issues, efficacy has plateaued. In the present study, the potential of a novel plant-derived steroidal-lactone, withaferin A (WFA), for clinical use alongside PAC to improve efficacy against NSCLC was explored. The anticancer effects of PAC and WFA alone, and in combination against the in vitro cell proliferation, cell adhesion, migration and …

Mannitol Prescribing Practices With Cisplatin Before And After An Educational Newsletter Intervention, Morgan Corbin, John B. Bossaer

ETSU Faculty Works

Background: Mannitol has been used in the past for the prevention of cisplatin-induced nephrotoxicity. Studies on its efficacy have conflicting results. An educational newsletter was designed for local oncologists on the conflicting data of mannitol use in preventing cisplatin-induced nephrotoxicity. Purpose: The purpose of this study was to determine whether a pharmacist-created newsletter intervention led to changes in the mannitol prescribing practices of local oncologists. Methods: A newsletter describing the paucity of evidence to support mannitol use to prevent cisplatin-induced nephrotoxicity was distributed via e-mail to local oncologists in October 2010. Mannitol prescribing rates were retrospectively evaluated before and after …

Characterization Of Novel Cannabinoid Receptor 2-Selective Agonists At The Biochemical And Cellular Levels: Leads For Therapeutic Agents, Ashley M. Hine

Honors Scholar Theses

Putative cannabinoid receptor 2 (CB₂)-selective agonists were identified from a library of commercially available compounds via inhibition of cAMP accumulation in high throughput screening. Binding affinity and receptor subtype selectivity were assessed using heterologous competition binding assays against the known cannabinoid orthosteric ligand CP55940. Test compounds ASX0152383 and CSC003141 preferentially bound to CB₂, with no detection of binding to CB₁ up to 1 mM. CMB038865 exhibited nearly 100-fold selectivity for CB₁ over CB₂, while CZ000026 bound non-preferentially to both receptors in the low micromolar range. To determine the extent of G protein …

An Exploratory Study Of The Utilization Of Evidence-Based Pharmacological Treatment On Heart Failure Patients In Mississippi And Its Impact On Readmission, Keri A. Barron

Dissertations

The purpose of this study was to explore the relationship of adherence to evidence-based guidelines for pharmacologic management by select Mississippi hospitals and their hospital readmission rates. This was an exploratory study with a retrospective design. This design offered insight into the relationship between readmissions of heart failure patients and adherence to the national guidelines for the pharmacologic treatment of heart failure. The study took place in a hospital in the southeastern section of the United States. Data were collected from a database of patients with heart failure seen between January 2011 and June 2014.

The unit of analysis for …

Translational Pharmacokinetic-Pharmacodynamic Modeling And Simulation In The Development Of Spectinamides, A Novel Class Of Anti-Tuberculosis Agents, Chetan Rathi

Theses and Dissertations (ETD)

New chemotherapeutic agents are urgently needed to control the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of tuberculosis, which still remains an important public health challenge globally. Recently, spectinamides have emerged as a novel class of anti-tuberculosis agents that overcomethe native drug efflux. Spectinamides bind to the 30S bacterial ribosomal subunit which interferes with ribosomal translocation, and ultimately results in inhibition of protein synthesis. They have potent in vitro activity against drug resistant Mycobacterium tuberculosis (Mtb), and also demonstrated sustained efficacy in (Mtb)-infected mouse models. Pharmacokinetic (PK)/ pharmacodynamic (PD) analyses play a critical role in identifying …

Biodegradable Polymeric Biomaterials In Different Forms For Long-Acting Contraception And Drug Delivery To The Eye And Brain, Dileep Reddy Janagam

Theses and Dissertations (ETD)

Efficacy of many of the new and existing therapeutics is often hampered by the lack of an effective and compliant method of delivery. Typically, drugs have poor water solubility, short half-lives, and low permeability across the biological membranes. The result is low bioavailability of the drugs at the target site and can cause toxicity and side effects at high doses. Often the conventional dosage forms fail to overcome these limitations. In the recent decades, biodegradable polymeric drug delivery systems have emerged as promising candidates to solve the challenges of poor solubility, low permeability and sustained release owing to the advantages …

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.

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Age-Associated Expression Patterns Of Oatp 1b1 And Oatp 1b3 And Their Effect On The Disposition Of Fexofenadine, Margaret Mary Thomson

Theses and Dissertations (ETD)

As part of the drug disposition process (absorption, distribution, metabolism, excretion), an often overlooked aspect is transport. In order for drugs to be metabolized and excreted from the body they go through the liver or other drug removal organs. For drugs that are polar or are large they must rely upon transport mechanisms to transport them across the biomembranes of the drug removal organs. OATP1B1 and OATP1B3 are transporters on the sinusoidal membrane of the liver which work in concert with the drug metabolizing enzymes as part of the drug removal process. It is known that the development of each …

Discovery Of Natural Product-Based Antimycobacterial Agents Effective Against Non-Replicating Bacilli, Shajila Siricilla

Theses and Dissertations (ETD)

New antimycobacterial molecules that kill non-replicating Mycobacterium tuberculosis (Mtb) were identified by screening libraries of synthetic natural products. De novo screening of a 400-membered library of aurachin RE analogs resulted in discovery of UT-317 ((R)-20). UT-317 is a selective vitamin K2 biosynthesis (MenA) inhibitor that killed replicating and non-replicating Mtb at 2.31 μg/mL (MIC) and 0.85 μg/mL, respectively. A 50-membered library of capuramycin analogs was evaluated in their enzymatic inhibitory activities against translocase I (MraY/MurX) and prenyl-phosphate-GlcNAc-1-phosphate transferase (WecA). UT-01320 (45) is identified as a selective WecA inhibitor that kills both replicating and non-replicating Mtb at 1.50 μg/mL (MIC) and …

Synthesis Of 20s-Hydroxyvitamin D3 Analogs And Their 1Α-Hydroxyl Derivatives As Potent Anti-Inflammatory Agents, Zongtao Lin

Theses and Dissertations (ETD)

Rheumatoid arthritis (RA) is one of the autoimmune diseases, and is affecting 2.5 million Americans in total. Among the treatment options of RA, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the only steroidal drug used clinically for anti-inflammatory and immune diseases. However, long-term use of 1,25(OH)2D3 (625 µg/day) in human would result in hypercalcemia (toxicity), and 1,25(OH)2D3 has substantial hypercalcemic effects (toxicity) in mice at a dose as low as only 2 µg/kg. Fortunately, during the investigation of novel metabolic pathway of vitamin D3 by cytochrome P450 enzymes, we found 20S-hydroxyvitamin D3 [20S(OH)D3] as a good lead compound. 20S(OH)D3 suppressed disease symptoms at …

Biophysical And Biochemical Screening Approaches For Antimicrobial Drug Discovery Targeting S. Aureus Clpp, Aman Preet Singh

Theses and Dissertations (ETD)

The discovery of antibacterial drugs has been among most significant achievements of mankind in saving millions of lives across the planet from infectious diseases. With rise in resistance to almost all existing chemotypes, the design of next generation novel antibiotics has become much more challenging and difficult. The early 21st century witnessed the advancement of multiple novel chemotypes during golden age of antibiotics however the pace of antibiotic drug discovery has slowed down tremendously, contributing to life threatening antimicrobial discovery void since 1980’s. Therefore the need to develop novel antibiotics with unique mechanism of action to leverage against multi drug …

The Development Of Methods To Account For Physiologic Dynamic Changes And Their Effects On The Pharmacokinetics Of Therapeutic Monoclonal Antibodies And Other Therapeutics, Josiah Thomas Ryman

Theses and Dissertations (ETD)

Physiologic changes in the body can drastically affect the clearance of a medication, and therefore increase the variability in exposure to the medication. Physiologic changes that can have a profound effect on the exposure of a medication can stem from changes CYP enzymes, transport proteins, binding protein expression, organ function, immune reactivity, and health status to name a few; with the focus of this dissertation on the dynamic changes in the ontogeny of MRP2 (an apical liver transport protein) and the dynamic changes caused by an immune response to a therapeutic monoclonal antibody (mAb). Several approaches can be used to …

The Pharmacognosy And Therapeutic Efficacy Of Turmeric (Curcuma Longa): A Systematic Review, Maghan Ballantyne

Senior Honors Projects

Turmeric is a well-known natural product, native to Southeast Asia, commonly

used for a variety of cultural traditions and health benefits. Generally referred

to as curcumin, it is a member of the Zingiberaceae, or ginger family, utilized

for its roots and known for its vibrant yellow hue. Culturally, it is primarily

incorporated into cooking and as an integral part of religious rituals and

ceremonies. Chemically, turmeric is classified as a phenolic compound, made

up of many curcuminoids, each with varying levels of activity. Therapeutically,

its health benefits include anti-inflammatory, anti-hyperlipidemia, anti-oxidant

and anti-pruritic properties. The pharmacognosy of curcumin modulates

inflammatory …

April 2017, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Skrining Dan Evaluasi Aktivitas Kitinase Dari Sembilan Isolat Bakteri Lokal, Baitha Palanggatan Maggadani, Siswa Setyahadi S, Harmita Harmita

Pharmaceutical Sciences and Research

Chitinase is an enzyme that degrades chitin on β-1,4-acetamido-2-deoxy-D-glycoside bound to produce Chitin oligosaccharide or its soluble monomer, N-acetylglucosamine (NAG). Chitinase are usually produced naturally by chitinolytic microorganism that are found in soil or water environment. Chitinase have been widely used for biocontrol agents of plant pests. The product from chitinase hydrolysis can be used as antiinflammatory agent and anti hyperpigmentation. This research was aimed to screen and evaluate the chitinolytic ability of 9 isolate. The best isolate was the one which produced high chitinolytic activity and hydrolyzed chitin into NAG. 9 isolate were examined and BPPTCC-2 was the best …

Parameter Fisikokimia Dan Analisis Kadar Allyl Disulfidedalam Ekstrak Etanol 70% Bawang Putih (Allium Sativum L.)Dengan Perbandingan Daerah Tempat Tumbuh Parameter, Rini Prastiwi, Siska Siska, Nila Marlita

Pharmaceutical Sciences and Research

Garlic (Allium sativum L.) is one of the medicinal plants that has a potential to be developed to become a traditional medicine. Traditional medicinal products and medicinal plants which have good quality are determined by the quality and safety of the extract. One of many factors that can affect the quality is the growing area. This research aimed to compare the value of physicochemical parameters as well as the levels of compounds responsible for pharmacological activity in ethanol 70% extract of garlic obtained from two growing areas, Bogor and Wonosobo. The test results obtained from garlic extract of Bogor were: …

Perbandingan Efektifitas Antara Minyak Atsiri Kulit Batang Kayu Manis (Cinnamomum Burmannii) Dengan Temephos Sebagai Larvasida Aedes Aegypti, Muhamad Rizki Al Kamal, Neneng Syarifah Syafei, Gita Tiara Dewi Nasution

Pharmaceutical Sciences and Research

Dengue fever is a major health issue in the world. Preventive measure with temephos/abate has long been used to combat this problem. Istiana et al reported that there were cases of resistance of Aedes aegypti larvae to temephos in various parts of the world, including Indonesia. Indonesian Cinnamon (Cinnamomum burmannii) has been proven to possess larvacide effect and can be used as an alternative insecticide. This research was meant to compare the larvacide effect of Indonesian cinnamon (Cinnamomum burmannii) essential oil to the larvacide effect of temephos against Aedes aegypti larvae. This research used laboratory experimental design analysis. The total …