Elevated L-Lactate Drives Major Cellular Pathologies Associated With Neurodegeneration,
2018
Michigan Technological University
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,
2018
Institute of Technology Sligo
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 …
Calling Attention To The Growing Heroin Epidemic And How To Fight It,
2018
The University of Akron
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 …
Pharmacy Driven Best Possible Admission Medication History At A Pediatric Institution,
2018
Children's Mercy Hospital
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,
2018
Children's Mercy Hospital
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,
2018
Virginia Commonwealth University
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,
2018
Old Dominion University
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 …
Exploring Alternative Therapeutic Interventions For The Treatment Of Leigh Syndrome,
2018
University of South Carolina
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 …
Operation Of The Leica Sp8 Multiphoton Confocal System Using Single Or Multiple Fluorochromes,
2018
University of South Carolina
Operation Of The Leica Sp8 Multiphoton Confocal System Using Single Or Multiple Fluorochromes, Amy E. Rowley
Theses and Dissertations
The goal of this thesis is to systematically examine each decision made in obtaining images on the Leica SP8 Multiphoton Confocal Microscope and discuss the basic operating parameters in order to generate publication quality images. The capabilities of the LAS X software are discussed along with an in depth discussion of each icon in order, beginning with the Configuration icon, moving then to Acquire, and a brief overview of the possible imaging processing functions within the Process icon. At the conclusion of this thesis, the reader should feel comfortable with the operation of a confocal system and understand the tradeoffs …
Regulation Of Prostaglandin D2 And Angiogenesis-Related Factors From Human Skin Mast Cells By Interleukin-6 And Resveratrol,
2018
University of South Carolina
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 …
Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore,
2018
Virginia Commonwealth University
Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade
Theses and Dissertations
Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …
5-Ht2b Receptor-Mediated Cardiac Valvulopathy,
2018
VCU School of Pharmacy, Dept. of Medicinal Chemistry
5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala
Theses and Dissertations
5-HT2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …
Drug Delivery With Light,
2018
Virginia Commonwealth University
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 …
Bromodomain And Extraterminal Domain (Bet) Inhibitor Rvx-208 Ameliorates Periodontal Bone Loss,
2018
Virginia Commonwealth University
Bromodomain And Extraterminal Domain (Bet) Inhibitor Rvx-208 Ameliorates Periodontal Bone Loss, Nicholas J. Clayton
Theses and Dissertations
Periodontal disease affects 47% of Americans over 30 and is a growing global concern. Current treatments for periodontal disease focus on the mechanical elimination of periodontal biofilms. Very few treatments are available that target the rampant, unregulated host immune response that is ultimately responsible for tissue degradation. BET proteins have been shown to play critical roles in inflammatory gene regulation and are therefore potentially ideal therapeutic targets for treating periodontal disease. RVX-208 is a selective BET-inhibitor with a high affinity for Bromodomain 2 (BD2) as compared to BD1 in BET proteins. Our previous studies have shown that RVX-208 inhibits inflammatory …
Design, Synthesis And Biological Evaluation Of Inhibitors Against Both Human And Mouse Microsomal Prostaglandin E2 Synthase-1 Enzymes,
2018
University of Kentucky
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,
2018
University of Kentucky
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,
2018
Virginia Commonwealth University
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,
2018
Virginia Commonwealth University
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,
2018
Virginia Commonwealth University
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 …
Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy,
2018
Technological University Dublin
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 …
