Chemicals and Drugs Commons^™

Dementia: Types, What They Are And How They Differ, Jessica N. Schnetzer

Honors Thesis

Dementia: types, what they are and how they differ centers on the known and unknown complexities of dementia. Dementia is a very complex cognitive disease that consumes the brain, an organ of which we know very little about. Even so, this common disorder is actively being researched and is the topic of special interest of this thesis research. Described are Alzheimer’s disease, Creutzfeldt-Jakob disease, Frontotemporal dementia, Huntington’s disease, Korsakoff’s syndrome, Lewy body dementia, Parkinson’s dementia, and Vascular dementia, focusing on what they are, their specific risks, diagnosis, treatment, and their differing progressions. Guidance of this study provided by thesis director …

Network Approaches To Elucidate The Determinants Of Protein Topology And Stability, Zeinab Haratipour

Chemistry & Biochemistry Theses & Dissertations

Predicting three-dimensional structures of proteins from sequence information alone, remains one of the most profoundly challenging and intensely studied problems in basic science. It has uniquely garnered the interdisciplinary efforts of biologists, biochemists, computer scientists, mathematicians and physicists. The advancement of computational methods to study fundamental features of proteins also enables insights that are either difficult to explore experimentally or complimentary to further interpret experimental data. In the present research and through the combined development and application of molecular dynamics and network science approaches we aimed to elucidate the role of geographically important amino acids and evolutionarily conserved long-range interactions …

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …

Gesea Biosciences - Core Shell Pellet Manufacturing Device, Claire Edelman, Maria Medrano, Rachel Longoria

Biomedical Engineering

No abstract provided.

Analysis Of Oxidatively Damaged Proteins By Mass Spectrometry, Vincent Saullo

Electronic Thesis and Dissertation Repository

As humans age, exposure to oxidative stress may induce protein degradation or aggregation; both resulting in loss of protein function. Protein oxidative damage remains a dominant pathology in many common ailments. To combat these pathologies, scientists must understand the nature of oxidative modifications and their effects on protein structure and dynamics. This work employs a range of mass spectrometry (MS) methods to characterize and analyze the effects of oxidative damage on the model protein myoglobin (Mb). Mb was oxidized using tert-butyl hydroperoxide, and the resulting modifications were characterized by top-down and bottom-up MS workflows. Hydrogen/deuterium exchange MS indicated elevated structural …

Synthesis And Preliminary Ex Vivo Testing Of Sirna Targeting Tcrb: A Proposed Therapy For The Treatment Of Autoimmunity, Nicholas J. Magazine

LSU Doctoral Dissertations

Abstract

Background:

As of 2018, the United States National Institutes of Health estimate that over half a billion people worldwide are affected by autoimmune disorders. Though these conditions are prevalent, treatment options remain relatively poor, relying primarily on various forms of immunosuppression which carry potentially severe side effects and often lose effectiveness overtime. Given this, new forms of therapy are needed. We propose small-interfering RNA (siRNA) for hypervariable regions of the T-cell receptor β-chain gene (TCRb) as a highly targeted, novel means of therapy for the treatment of autoimmune disorders.

Objectives:

To develop methods to produce siRNA targeting …

Experimental And Computational Tools For Single Cell Analysis In Cancer Diagnostics, Manibarathi Vaithiyanathan

LSU Doctoral Dissertations

Substantial evidence shows that cellular heterogeneity commonly exists within an isogenic or clonal population. Whether in isolation or caused through a combination of the above events, cellular heterogeneity can dramatically influence cellular decision making and cell fate, however, this can be masked by the average response from a population. One approach to solve this issue is to analyze a population at the individual cell level. The goal of this work is to develop high-throughput experimental and computational platforms to screen and quantify single cancer cells for specific intracellular enzyme activities. An interdisciplinary approach was taken to 1) better understand the …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Antidepressant Effects On Rem Sleep, Mitchel Adams

Biology and Microbiology Graduate Students Plan B Research Projects

Individuals who deal with depression are typically prescribed antidepressants in order to alleviate the depressive symptoms that they may be having. Polysomnographic sleep research has revealed that depression is associated with altered sleep architecture and distorted REM sleep quality.² Specifically, increased REM sleep duration and density have proved to be markers that predict recurrence and relapse for depressed individuals. REM sleep serves to stimulate regions of the brain that are important with learning and memory consolidation. However, an increased duration of REM sleep in depressed individuals proves to be unfavorable. Antidepressants drugs aim to weaken sleep quality, which is …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Review Of Drug And Biologics Recalls: 2009 Through 2019, Vimala Devi Gollamudi

Master's Theses and Doctoral Dissertations

This study analyzed drugs and biologics recalls for the period of 2009 and 2019. The data used in the study was generated from Food and Drug Administration records. A total of 466 drugs and 84 biologics were recalled during the 11-year period. The common causes of drug product recalls included contamination, defective products, and mislabeling. Defective product, mislabeling, and defective packaging were observed to be the common causes of recall for biologics. Injectables have the highest percentage of recalls in drug products, and blood and blood products had the highest percentage of recalls in biologics. Controlling the contamination of injectable …

The Role Of Nicotine In Exacerbating The Inflammatory Response In Macrophages Infected With Mycobacterium Avium Paratuberculosis In Crohn's Disease Smokers, Dania Alqasrawi

Electronic Theses and Dissertations, 2020-

It is a fact that cigarette smoke (CS) has negative effects on patients with Crohn's disease (CD), whereas CS seems to provide protection to patients with Ulcerative Colitis (UC). The mechanism of how CS ingredients or nicotine modulate inflammatory phenotypic response in IBD subsets remained unclear. Unlike UC, CD has been associated with genetic disposition, immuno-dysregulation and infection by pathogens mainly Mycobacterium avium paratuberculosis (MAP). In this study, we investigated the cellular and molecular effects of pure nicotine and tobacco extracts from HLE-nicotine rich-plant and LAMD-nicotine less-plant in infected macrophages. Unlike LAMD extracts, Nicotine (4ug/mL) and HLE extracts (0.18%) significantly …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Identification Of Imiquimod As A Potential Combination For Anti-Cd47 Antibodies In Cancer Therapy, Nicole Brittaney Pang

Scripps Senior Theses

The avenues of targeted immunotherapy offers a promise of less toxic treatment options for those battling different forms of cancer. Specifically, the process of hijacking a patient’s own immune system to fight cancer from within versus using external treatments like chemotherapy which is extremely damaging to the patient. One such avenue includes the usage of monoclonal antibodies as an effective modality for immunotherapy. Cluster of Differentiation 47 (CD47), also known as the ‘don’t eat me signal’, aids in cell proliferation and evasion of phagocytosis and has been found to be a target for stopping tumorigenesis. Previous research has been successful …

Organic Compound Farnesol Reduces Disease Severity And Onset In Mouse Model Of Multiple Sclerosis, Lacey B. Sell

EWU Masters Thesis Collection

No abstract provided.

The Effectiveness Of Cannabidiol In Rheumatic Disease Pain: A Systematic Review, Mary C. Wiczek

All Graduate Theses, Dissertations, and Other Capstone Projects

Cannabinoids have long been a part of human culture and medicine, and more recently have been rediscovered for their potential use in the management of rheumatic disease pain. The objective of this review was to evaluate the known clinical effectiveness of cannabidiol treatment for rheumatic disease related pain. The legality and current regulation of these products was also reviewed to establish the current status of federal and state rules regarding their clinical use. Basic definitions of the terms used to differentiate cannabidiol from other cannabinoid products was also outlined. A systematic literature search was then conducted to explore the current …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Determining The Antibacterial Activity And Mode Of Action Of Tirandamycin, Hailey Bouchard

CMC Senior Theses

Tirandamycin is a small molecule natural product that has been isolated from various species of marine and terrestrial Streptomyces. The natural product has shown antibacterial activity against an array of Gram-positive and Gram-negative bacteria, showing promise as a pharmaceutical drug. Tirandamycin has 14 known derivatives, many of which have been created synthetically. Some of its derivatives are particularly potent against the high-risk bacteria vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae and Escherichia coli. However, the antibacterial potency of these derivatives has not been tested systematically leading to the possibility of discovering more potent …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Development Of A Method For The Detection And Quantification Of Various Benzodiazepines And Z-Drugs In Human Blood And Qualitative Identification In Urine Samples Using Liquid Chromatography Mass Spectrometry (Lc-Ms/Ms), Haley Michel

Williams Honors College, Honors Research Projects

This method developed in the toxicology department at the Cuyahoga County Medical Examiner’s Office (CCMEO) detects 40 benzodiazepines and metabolites along with several z-drugs in blood and urine by liquid chromatography tandem mass spectrometry. A sample amount of 0.5 mL was used to detect analytes in postmortem drug facilitated sexual assault and impaired driving cases. Twenty-nine analytes met criteria for quantification while the remaining 14 were used as qualitative indicators. Bias and precision results for quality controls met criteria, staying within ±15% except for clonazolam and etizolam which were within ±20%. Quantitative reporting criteria which included dilution integrity was met …

Analyzing The Effects Of Opioids On Cortical Pore Networks In Rabbit Tibiae And Femora, Kassidy Wilson

Williams Honors College, Honors Research Projects

The following project was approved by the Institutional Animal Care and Use Committee (IACUC) (Protocol number #18-11-12 ARC). This study was completed as a subset of Dr. Andronowski's overarching lab project. Femora and tibiae were procured from New Zealand White rabbits to study the prolonged effects of opioid use in bone remodeling. This specific project analyzed the effects of opioids on the pore networks and the pore orientation.

Non-Pharmacological Interventions For Alcohol, Marijuana, And Opioid Use During Pregnancy: A Systematic Review, Hannah Safranek, Madeline Frausto, Amy King, Stoneking Madison

Williams Honors College, Honors Research Projects

The purpose of this review is to analyze evidence on prevalence of opioid, alcohol and marijuana use during pregnancy and answer the PICOT question: In pregnant women addicted to or using marijuana, opioids, and alcohol, how do non-pharmacological interventions, compared to standard care of pharmacological interventions alone, affect health outcomes in mothers and neonates between birth to hospital discharge? Diagnosis of substance use disorder is increasing and with it comes increased risk of complications to mother and neonate including neonatal abstinence syndrome (NAS), fetal alcohol syndrome (FAS) and other negative neonatal and maternal outcomes. Evidence was identified on the online …

Metformin’S Role In The Prevention Of Type 2 Diabetes In Individuals Diagnosed With Prediabetes: A Systematic Literature Review, Jillian Williamson

All Graduate Theses, Dissertations, and Other Capstone Projects

The United States is facing a growing epidemic of unchecked and untreated individuals with prediabetes. While lifestyle interventions have remained the gold standard of treatment, has this been enough? A literature review was carried out to identify metformin’s role in treatment and management of prediabetes as well as perceived barriers to its prescribing. A total of 24 articles met inclusion criteria. Main findings include (a) metformin is effective in reducing the incidence of diabetes, though not as effective as lifestyle interventions; (b) certain populations did benefit more from metformin usage then other populations; (c) there was more treatment compliance with …

Ethanol Sustains Phosphorylated Tau Protein Immunofluorescence In The Cultured Neonatal Rat Hippocampus: Implications For Fetal Alcohol Spectrum Disorders, Caleb Seth Bailey

Theses and Dissertations--Psychology

Fetal Alcohol Spectrum Disorders (FASDs) are comprised of developmental, behavioral, and cognitive abnormalities caused by prenatal alcohol exposure, affecting an estimated 2%-5% of childrenand costing up to $4 billion annually in the United States alone. Although some behavioral therapies can help, the biochemical mechanisms that underpin FASDs need further elucidation for development of more efficacious therapeutics. The tau protein modulates cytoskeletal structure in neurons, and thereby plays an integral role in proper development and function of the central nervous system, but its function is altered by its phosphorylation state, such that increased phosphorylation reduces tau protein function. The tau protein …

Protein-Bound Uremic Toxins Lowering Effect Of Sevelamer In Pre-Dialysis Chronic Kidney Disease Patients With Hyperphosphatemia: A Randomized Controlled Trial, Kullaya Takkavatakarn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events, and all-cause mortality in chronic kidney disease (CKD). This study was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Methods: After 2 weeks of the run-in period, 40 pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either daily 2,400 mg of sevelamer or 1,500 mg of calcium carbonate for 24 weeks. Serum p-cresyl sulfate, indoxyl sulfate, fibroblast growth factor 23 (FGF23), lipid profiles, and high sensitivity C-reactive protein (hs-CRP) were evaluated. The primary …

Hear Me Roar, Abigail R. Seethoff

Graduate Student Theses, Dissertations, & Professional Papers

Hear Me Roar, a compilation of personal essays interspersed with short forms, grapples with the nuances of compliance versus autonomy in the context of the male gaze, beauty standards, and pop culture. The collection also explores what it means to treasure something—another person, an object—and how to express and deepen that affection.