Chemicals and Drugs Commons^™

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 …

Genotype-Phenotype Study In Patients With Valosin-Containing Protein Mutations Associated With Multisystem Proteinopathy, Ebaa Al-Obeidi, Sejad Al-Tahan, Abhilasha Surampalli, Namita Goyal, Annabel K. Wang, Andreas Hermann, Molly Omizo, Charles D. Smith, Tahseen Mozaffar, Virginia Kimonis

Neurology Faculty Publications

Mutations in valosin‐containing protein (VCP), an ATPase involved in protein degradation and autophagy, cause VCP disease, a progressive autosomal dominant adult onset multisystem proteinopathy. The goal of this study is to examine if phenotypic differences in this disorder could be explained by the specific gene mutations. We therefore studied 231 individuals (118 males and 113 females) from 36 families carrying 15 different VCP mutations. We analyzed the correlation between the different mutations and prevalence, age of onset and severity of myopathy, Paget's disease of bone (PDB), and frontotemporal dementia (FTD), and other comorbidities. Myopathy, PDB and FTD was present in …

A Purification And In Vitro Activity Assay For A (P)Ppgpp Synthetase From Clostridium Difficile, Astha Pokhrel, Asia Poudel, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

Kinase and pyrophosphokinase enzymes transfer the gamma phosphate or the beta-gamma pyrophosphate moiety from nucleotide triphosphate precursors to substrates to create phosphorylated products. The use of γ-³²-P labeled NTP precursors allows simultaneous monitoring of substrate utilization and product formation by radiography. Thin layer chromatography (TLC) on cellulose plates allows rapid separation and sensitive quantification of substrate and product. We present a method for utilizing the thin-layer chromatography to assay the pyrophosphokinase activity of a purified (p)ppGpp synthetase. This method has previously been used to characterize the activity of cyclic nucleotide and dinucleotide synthetases and is broadly suitable for …

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 …

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 …

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 …

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 …

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.

A Study Of Hormonal Effects In Cervical Smear Samples Using Raman Spectroscopy, D. Traynor, P. Kearney, I. Ramos, C. M. Martin, J. J. O'Leary, Fiona Lyng

Articles

Raman spectroscopy is a powerful tool that has the potential to be used as a screening method for cervical cancer. It is a label-free, low-cost method providing a biochemical fingerprint of a given sample. The objective of this study was to address patient-to-patient variability contributed by hormonal effects due to the menstrual cycle, the use of hormone-based contraceptives (HC) and the onset of menopause, and to determine if these changes would affect the ability to successfully identify dyskaryotic cells. Raman spectra were recorded from unstained ThinPrep cervical samples (45 cytology negative and 15 high-grade dyskaryosis (high-grade squamous intraepithelial lesion, HSIL) …

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) …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …

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, …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

The Effects Of Hormone Replacement Therapy (Hrt) On Surgically Postmenopausal Women: A Review Of The Literature, Leslie M. Hertweck

Honors Undergraduate Theses

The primary purpose of this research was to examine the effects of HRT in women with acute estrogen deficiency from surgically induced menopause. The secondary purpose was to evaluate how HRT improves symptoms of acute estrogen deficiency and quality of life (QOL) in women using hormone supplementation. Peer reviewed articles published from 2000 to 2017 that were written in the English language with a focus on the use of HRT in women with acute estrogen deficiency after surgical menopause were evaluated for relevance. Evidence suggests the primary reason for decreased use of HRT is the associated risks outweighing the benefits; …

The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter

Honors Undergraduate Theses

Background: Disruptive technology describes technology that is significantly more advanced than previous iterations, such as: 3D printing, genetic manipulation, stem cell research, innovative surgical procedures, and computer-based charting software. These technologies often require extensive overhauls to implement into older systems and must overcome many difficult financial and societal complications before they can be widely used. In a field like healthcare that makes frequent advancements, these difficulties can mean that the technology will not be utilized to its full potential or implemented at all.

Objective: To determine the inhibiting factors that prevent disruptive technology from being implemented in conventional healthcare.

Methods: …

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.