Chemicals and Drugs Commons^™

An Extensible Mathematical Model Of Glucose Metabolism. Part I: The Basic Glucose-Insulin-Glucagon Model, Basal Conditions And Basic Dynamics, Caleb L. Adams, D. Glenn Lasseigne

Mathematics & Statistics Faculty Publications

A basic model highlighting the counter-regulatory roles of insulin and glucagon is proposed to start a series of models designed to explore continuous rein control and major aspects of glucose metabolism. The three-by-three dynamical system uses black boxes to model unit processes such as the dependencies of insulin secretion rate and the glucagon secretion rate on blood glucose concentration. The dependency of basal conditions on insulin resistance and any defects in insulin or glucagon secretion are shown. Since over-production of hepatic glucose exists early in the history of diabetes, it is important that mathematical models should account for this effect …

Better Living Through Chemistry: Addressing Emerging Antibiotic Resistance, Nathan P. Coussens, Ashley L. Molinaro, Kayla J. Culbertson, Tyler Peryea, Gergely Zahoránszky-Köhalmi, Matthew D. Hall, Dayle A. Daines

Biological Sciences Faculty Publications

The increasing emergence of multidrug-resistant bacteria is recognized as a major threat to human health worldwide. While the use of small molecule antibiotics has enabled many modern medical advances, it has also facilitated the development of resistant organisms. This minireview provides an overview of current small molecule drugs approved by the US Food and Drug Administration (FDA) for use in humans, the unintended consequences of antibiotic use, and the mechanisms that underlie the development of drug resistance. Promising new approaches and strategies to counter antibiotic-resistant bacteria with small molecules are highlighted. However, continued public investment in this area is critical …

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic …

Gene Regulation In The Hypothalamic-Pituitary-Gonadal Axis Of The Green Anole Lizard (Anolis Carolinensis)., Joshua N. Peters

All Graduate Theses, Dissertations, and Other Capstone Projects

Studies examining the hypothalamic-pituitary-gonad axis (HPG) in Anolis carolinensis provide insight into the regulation of this axis under extremely different reproductive conditions. Molecular studies indicate that kisspeptin proteins, transcribed from kiss1 and kiss2 genes, are produced in the hypothalamus where they bind G protein-coupled receptor 54 (GPR54), activating the HPG axis. Gonadotropin inhibitory hormone (GnIH) and its receptors, G protein-coupled receptor 147 and 74 (GPR147 and GPR74), down regulate HPG axis function. In this experiment we examined HPG axis gene expression in the green anole lizard (Anolis carolinensis), a seasonally breeding species with higher steroid hormone levels in the breeding …

On The Efficacy Of High-Dose Ascorbic Acid As Anticancer Treatment: A Literature Survey, Florentin Smarandache, Victor Christianto

Branch Mathematics and Statistics Faculty and Staff Publications

Vitamin C (ascorbic acid, ascorbate) has a controversial history in cancer treatment. Emerging evidence indicates that ascorbate in cancer treatment deserves re-examination. As research results concerning ascorbate pharmacokinetics and its mechanisms of action against tumor cells have been published, and as evidence from case studies has continued to mount that ascorbate therapy could be effective if the right protocols were used, interest among physicians and scientists has increased.

Medication Education In The Pediatric Rheumatology Clinic, Ashley M. Cooper, Julia G. Harris

Posters

No abstract provided.

Naturally Occurring 3rs, 7r, 11r-Phytanic Acid Suppresses In Vitro T-Cell Production Of Interferon-Gamma, Tomonori Nakanishi, Ibuki Motoba, Mayuko Anraku, Ryoji Suzuki, Yuto Yamaguchi, Laurie Erickson, Satoshi Kawahara

Hebrew Theological College Publications and Research

Background: Among the eight stereoisomers of phytanic acid (PA), the 3RS, 7R, 11R-isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3RS, 7R, 11R-PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3RS, 7R, 11R-PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study …

Population Pharmacokinetic/Pharmacodynamic Modeling Of Depot Testosterone Cypionate In Healthy Male Subjects, Youwei Bi, Paul J. Perry, Michael Ellerby, Daryl J. Murry

Faculty Publications & Research of the TUC College of Pharmacy

A randomized, double-blind clinical trial was conducted to investigate long-term abuse effects of testosterone cypionate (TC). Thirty-one healthy men were randomized into a dose group of 100, 250, or 500 mg/wk and received 14 weekly injections of TC. A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize testosterone concentrations and link exposure to change in luteinizing hormone and spermatogenesis following long-term TC administration. A linear one-compartment model best described the concentration-time profile of total testosterone. The population mean estimates for testosterone were 2.6 kL/day for clearance and 14.4 kL for volume of distribution. Weight, albumin, and their changes from baseline were …

Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration, Jessica Behnke

Dissertations, Master's Theses and Master's Reports

Within the past few decades, lactate research has expanded from initial findings deeming lactate as a dead-end metabolic product to recognition of lactate’s role as a potential energy substrate in the CNS. Due to the tight relationship between lactate and energy metabolism, interest in the scientific community has been mounting around associations among metabolic dysregulation, elevated lactate and neurodegenerative states such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, ischemia/reperfusion (AD, PD, ALS, I/R injuries), and physiological aging, however underlying cellular mechanisms and/or facilitators for neuronal degeneration pathologies still remain unknown. Here, we tested several hypotheses that implicate L-lactate to various neurodegenerative …

Chronic Lymphocytic Leukemia: A Review Of Front-Line Treatment Options, With A Focus On Elderly Cll Patients, Alma O'Reilly, James Murphy, Sarah Rawe, Mary Garvey

Articles

Chronic lymphocytic leukemia (CLL) remains the most prevalent form of leukemia in the Western world, with no cure to date. Ongoing and essential research into this heterogeneous disease has led to a number of new treatment options becoming available to CLL patients in the past decade. The present review presents the recent developments in the field of CLL treatment, with the main focus on elderly patients and CLL patients with coexisting comorbidities. The review discusses the current treatment regimens that provide the most promising outcomes for patients in this subgroup, with a number of important clinical trials summarized. These clinical …

Functionalizing Titanium Implants With Bioactive Peptides To Increase Osseointegration, Neil Bernard

Williams Honors College, Honors Research Projects

Orthopedic surgeries have continued to increase, but the material of choice remains constant: titanium. Titanium has become the benchmark implant material due to its durability and non-immunogenic properties. However, while high rates of success are correlated with joint replacement surgery, certain patients with predisposed diseases such as diabetes or arthritis may have increased complications.¹ This can be due to lack of osseointegration due to decreased bone formation and mineralization,² which will lead to increased rates of infection or aseptic loosening of the implant from the bone. ³ Current methods to alleviate these complications include invasive revisional surgeries, which …

Calling Attention To The Growing Heroin Epidemic And How To Fight It, Kendal Rozaieski

Williams Honors College, Honors Research Projects

The purpose of this study was to explore the experience of creating a grassroots heroin awareness organization on a university campus through qualitative research. Various meeting types were attended as the grassroots efforts began: a student organization dedicated to the cause, the campus Alcohol and Other Drug Board, a local community treatment center agency, multiple University of Akron faculty members, and other heroin awareness groups in the community. Through observation and journaling of these meetings, I am sharing my experience based off analyzed field notes. After analyzation of these notes, common themes related to the formation of this kind of …

Heparan Sulfate, A New Target For Platinum In Metastatic Tnbc, Samantha J. Katner

Theses and Dissertations

Abstract

Heparan Sulfate, A New Target for Platinum in Metastatic TNBC

Author: Samantha J. Katner, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Virginia Commonwealth University, 2018

Advisor: Dr. Nicholas Farrell, Professor, Chemistry Department

Heparan sulfate proteoglycans (HSPGs), composed of the linear polysaccharide heparan sulfate (HS) conjugated to a protein core, are located on the cell surface and extracellular matrix. The HS chains display varying degrees of sulfation, which constitutes the molecular recognition motif for many HS-protein interactions. HSPGs, associated growth factors, and heparanase promote tumor progression by facilitating invasion, angiogenesis, …

Regulation Of Prostaglandin D2 And Angiogenesis-Related Factors From Human Skin Mast Cells By Interleukin-6 And Resveratrol, Cody Cody Mchale

Theses and Dissertations

Mast cells are classically recognized as the effector cells of Immunoglobulin E (IgE)-mediated hypersensitivity reactions (i.e. allergic reactions). Mast cells also play an important role in the innate immune response to parasitic helminth infection. Allergic disease including allergic rhinitis, asthma, atopic dermatitis, and anaphylaxis, is a major health concern in the United States with greater than 60 million Americans suffering from allergy and asthma. In addition, mast cells have more recently been implicated in non-allergic disease including various human cancers, which will affect approximately 39.6% of U.S. men and women. Therefore, understanding the immunological and molecular mechanisms that regulate mast …

Pharmacy Driven Best Possible Admission Medication History At A Pediatric Institution, Damon Pabst, Charity Thompson, Brandon French, Brian O'Neal, Garret Matthews, Zeb Benner, Joshua Meade

Posters

No abstract provided.

Medication Timeliness In Emergency Department In Pediatric Sickle Cell Disease Population Presenting With Vaso-Occlusive Episode, Derrick Goubeaux, Kaitlyn Hoch, Gerald Woods, Julie Routhieaux, Maureen Guignon, Valerie Mcdougall Kestner

Posters

No abstract provided.

Modulation Of Electron Transport By Metformin In Cardiac Protection: Role Of Complex I, Ahmed Abdul Hussein Mohsin

Theses and Dissertations

Modulation of mitochondrial complex I during reperfusion reduces cardiac injury. Complex I exists in two structural states: active (A) and deactive (D) with transition from A→D during ischemia. Reperfusion reactivates D→A with an increase in ROS production. Metformin preserves the D-Form. Our aim was to study the contribution of maintenance of deactivation of complex I during early reperfusion by metformin to protect against ischemia reperfusion injury. Our results showed that metformin decreased H9c2 cardiomyoblast apoptosis and total cell death following simulated ischemia for six hours followed by reoxygenation for twenty four hours compared to untreated cells. Reactive oxygen species (ROS) …

Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer

Biological Sciences Faculty Publications

Viral gain-of-function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …

The Good, The Bad, And The Ugly Of Calcium Supplementation: A Review Of Calcium Intake On Human Health., Kelvin Li, Xia-Fang Wang, Ding-You Li, Yuan-Cheng Chen, Lan-Juan Zhao, Xiao-Gang Liu, Yan-Fang Guo, Jie Shen, Xu Lin, Jeffrey Deng, Rou Zhou, Hong-Wen Deng

Manuscripts, Articles, Book Chapters and Other Papers

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, …

Characterization Of Tetraethyl Orthosilicate-Based Dynamic Hydrogels For Use As Reversible 3-D Cell Culture Matrices, Krisitan Stipe

Graduate Student Theses, Dissertations, & Professional Papers

No abstract provided.

Design, Synthesis And Biological Evaluation Of Inhibitors Against Both Human And Mouse Microsomal Prostaglandin E2 Synthase-1 Enzymes, Kai Ding

Theses and Dissertations--Chemistry

As the principal pro-inflammatory prostanoid, prostaglandin E₂ (PGE₂) serves as mediator of pain and fever in inflammatory reactions. The biosynthesis of PGE₂ starts from arachidonic acid (AA). Cyclooxygenase (COX)-1 and/or COX-2 converts AA to prostaglandin H₂ (PGH₂), and PGE₂ synthases transform PGH₂ to PGE₂. Current mainstream approach for treating inflammation-related symptoms remains the application of traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs). As both categories shut down the biosynthesis of all downstream prostanoids, their application renders several deleterious effects including gastrointestinalulceration and cardiovascular risk. Microsomal prostaglandin …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

Effect Of Energy Metabolism On Nf-Kb Activity In Ovarian Cancer, Simren K. Bagri

UROP Posters

NF-kB is a transcription factor involved in cancer cell growth and survival. The activation of NF-kB can be assessed by monitoring phosphorylation of RelA p65 at Ser-536, which is a surrogate of the NF-kB transcription factor activation. The objective of this study was to determine if the loss of ATP leads to NF-kB deficiency and thus, apoptotic cell death of “bad” cells in ovarian cancer cells. The independent variables were metformin (Met), an anti-diabetic medicine, another compound MinB functionally similar to Met and a glucose transporter inhibitor BAY-876. The dependent variables were the resulting effect of Met and MinB on …

The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey

UROP Posters

The aim of this study is to observe cell proliferation, cell viability, apoptosis, and autophagy on acute myeloid leukemia (AML) cell lines, NB4 and U937, with the drug repurposing of mefloquine (MQ). Methods such as the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and trypan blue staining have shown a decrease in live cells with high concentrations of mefloquine. Using their average perspective IC50 values of MQ concentration, Western blotting was applied by means of apoptosis and autophagy markers to determine if the induction of apoptosis and inhibition of autophagy was present in MQ-treated AML cells. The experiment will be continued with more …

The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace

UROP Posters

There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and …

Ph-Dependent Silica Nanoparticle Dissolution And 1 Cargo Release, Giorgia Giovaninni, Colin J. Moore, Andrew John Hall, Hugh Byrne, Vladimir Gubala

Articles

The dissolution of microporous silica nanoparticles (NP) in aqueous environments of different biologically relevant pH was studied in order to assess their potential as drug delivery vehicles. Silica NPs, loaded with fluorescein, were prepared using different organosilane precursors (tetraethoxysilane, ethyl triethoxysilane or a 1:1 molar ratio of both) and NP dissolution was evaluated in aqueous conditions at pH 4, pH 6 and pH 7.4. These conditions correspond to the acidity of the intracellular environment (late endosome, early endosome, cytosol respectively) and gastrointestinal tract (‘fed’ stomach, duodenum and jejunum respectively). All NPs degraded at pH 6 and pH 7.4, while no …

Exploring Alternative Therapeutic Interventions For The Treatment Of Leigh Syndrome, Stephanie Martin

Theses and Dissertations

Leigh syndrome is the most common mitochondrial disease, affecting 1:40,000 live births. It manifests with symptoms including ataxia, cognitive impairment, motor difficulties, and stroke. Leigh syndrome is a genetic condition caused by mutations in either the nuclear DNA or mitochondrial DNA that affects the assembly of the electron transport chains. Death typically occurs around 2-3 years of age, due to respiratory failure, as the body cannot produce sufficient ATP for survival. The genetic basis of Leigh syndrome means that there is no cure, and current treatments of the symptoms have proven ineffective. This thesis proposes two different therapeutic approaches for …

In Vitro Genetic Code Expansion And Selected Applications, Emil S. Iqbal

Theses and Dissertations

The ability of incorporation non-canonical amino acids (ncAAs) using translation offers researchers the ability of extend the functionality of proteins and peptides for many applications including synthetic biology, biophysical and structural studies, and discovery of novel ligands. Here we describe the three projects where the addition of ncAAs to in vitro translation systems creates useful chemical biology techniques. In the first, a fluorinated histidine derivative is used to create a novel affinity tag that allows for the selective purification of peptides from a complex mixture of proteins. In the second, the high promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P) …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …