Chemicals and Drugs Commons^™

Imaging The Tumor Microenvironment Using 1,2-Dioxetane Chemiluminescence Agents, Lucas Ryan

Chemistry Theses and Dissertations

As complex organisms, animals and humans rely on a delicate interplay between many connected systems to maintain proper cellular and whole-body function. Oxygen regulation and homeostasis are vital for proper function in healthy cells, as are core components of aerobic metabolism and efficient ATP generation to supply our energy needs. Maintaining pH homeostasis is also of primary importance; cells maintain pH homeostasis through a host of active and passive transporters to maintain pH balance both inside and outside of the cell.

Events of uncontrolled cellular proliferation, also known as cancer, survive and thrive under conditions that perturb the delicate balance …

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

University of New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff

DNP Qualifying Manuscripts

Background: According to the National Institute for Occupational Safety and Health (2016), oral anticancer agents (OAC) are hazardous drugs (HD) and require the same safe handling interventions in the home setting as in controlled health care environments. The use of a safe handling checklist for OAC administration is a way nurses can provide safe handling education to patients and caregivers and assess for understanding and competency for critical tasks. Effective home management strategies outlining caregiver protections, proper storage, administration of OACs, spill clean-up, and waste disposal could reduce exposure risks to toxic agents.

Objective: To present a safe-handling checklist …

Illicit Substance Use In Acute Care Hospitals: Creating A Safe Environment, Christina Sanford

Doctor of Nursing Practice (DNP) Projects

Problem: In January 2019, a medium-sized acute care hospital in Northern California reported new safety concerns related to patients using illicit substances in the hospital.

Context: Leaving the hospital AMA is an increasing problem in acute care hospitals among patients who use illicit substances, with a rate of 25% to 30% (Ti & Ti, 2015). Grewal et al. (2015) conducted a study of over 1,000 illicit substance users who had experienced a hospitalization, where 43.9% reported use of illicit substances while in the hospital.

Intervention: The project was the creation, implementation, testing, and evaluation of multiple interventions to improve …

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Pence-Boyce STEM Student Scholarship

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus …

The Role Of The Recently Deorphanized G-Protein Coupled Receptor, Gpr171, In Morphine Tolerance And Withdrawal, Leela Afrose

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Opioid analgesics, such as morphine, represent the gold standard pain killer and the most frequently used drugs for the treatment of moderate to severe pain. Despite being a potent analgesic, morphine has unwanted and dangerous side effects with repeated use, such as tolerance and withdrawal. Tolerance is a state when a person no longer responds to a drug and a higher dose is required to achieve the same initial pain relief. Withdrawal is a set of undesirable psychological and physiological symptoms that occur after someone stops taking a drug or reduces the dose. Morphine tolerance and withdrawal play a vital …

Design And Synthesis Of Novel No-Drug Hybrid Compound And Green Catalytic Activity Evaluation Of Synthesized Silver Nanoparticles-Halloysite Nanocomposite, Majed Abdullah Bajaber

University of New Orleans Theses and Dissertations

Acetaminophen is a well-known analgesic that can manage pain and reduce fever. SCP-1 is a derivative of acetaminophen that showed significantly reduced hepatotoxicity and nephrotoxicity comparative to acetaminophen. Nitric oxides have been well known to play a key role in a wide variety of physiological and pathophysiological important processes. It was therefore of interest to synthesize a nitric oxide donor linked to SCP-1 that could have enhanced analgesic and antipyretic activity. A furoxan CAS 1609 as NO-donor was synthesized and linked to SCP-1 successfully. The furoxan CAS 1609 was initially synthesized from tetronic acid to give 1,2- dioxime in 86 …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations & Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Great Expectations: Phosph(On)Ate Prodrugs In Drug Design—Opportunities And Limitations, Victoria Yan

Dissertations & Theses (Open Access)

Phosphate and phosphonates are chemical moieties with historical precedence in anticancer and antiviral nucleotide analogues. Synchronous to modern efforts identifying novel therapeutic targets in cancer, such chemical moieties are being investigated in the design of novel inhibitors with antineoplastic potential. A central challenge to the delivery of phosph(on)ate-containing drugs is their anionic character at physiological pH, which portends poor membrane permeability. This limitation has been successfully overcome through the use of prodrugs. When attached to the phosph(on)ate moiety, prodrugs mask the negative charge and easily enable cell permeability. Upon cellular entry, the promoieties are enzymatically or environmentally cleaved to unveil …

Assessment Of The Use Of Low Molecular Weight Diblock Copolymers For The Formation Of Stable, Tunable Droplet Interface Bilayers, Joseph Tawfik

Masters Theses

This thesis presents the use of diblock copolymers, poly(butadiene)-b-poly(ethylene oxide) (PB_m PEO_n) and poly(isoprene)-b-poly(ethylene oxide) (PI_mPEO_n), as amphiphilic molecular building blocks for the formation of synthetic polymer bilayer membranes using the droplet interface bilayer (DIB) technique. The DIB technique makes use of the self-assembly of amphiphilic macromolecules along oil-water droplet interfaces that can then be physically connected for the construction of liquid supported macromolecular bilayers at the droplet interface. These bilayer membranes are capable of hosting both naturally occurring and synthetic protein channels. This technique has been used to form synthetic bilayer membranes …

Association Study: Apoe Alleles Association With Neurodegenerative Disorders In The Hispanic Population, Kimberly Moreno

Theses and Dissertations

The purpose of this study was to assess the impact of phenotypic variables and Apolipoprotein E (APOE) alleles and its effect on cognitive statues. APOE is a gene found vastly in the Hispanic community, speculated to be linked to neurodegenerative disorders such as Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Compared demographic, clinical, and genetic features among Hispanics who were diagnosed with Alzheimer's Disease, Mild Cognitive Impairment, and psychiatric disorders (e.g., anxiety and depression) in the efforts to assess the role of APOE. In past research, APOE has been considered a pathological hallmark for neurological diseases.

Past research has …

The Life-Saving Drug That No One Knows About: Naloxone Education And The Health Belief Model, Sarah Tilford

Undergraduate Honors Theses

Naloxone hydrochloride, popularly known by the brand name Narcan, is an emergency treatment used to reverse an overdose on opioid drugs. The CDC reports upwards of 26,000 individuals saved by naloxone between 1996 and 2014 (Centers for Disease Control and Prevention, 2015). Despite this success rate, those outside of the medical field largely remain unaware of what naloxone is or how they can use it in an emergency, leading to needless loss of life. Many studies focusing on naloxone access and education have been unable to offer findings meant to increase the use and ownership of the drug by lay …

The Treatment And Management Of Chronic Pain Using Cbd, Emily Davis

Honors College Theses

Chronic pain is a common debilitating condition in the United States. The treatment of chronic pain is complex and can sometimes lead to addiction of opioid medications. However, there is another, more natural option in the treatment of chronic pain—the use of CBD, cannabidiol which is a phytocannabinoid from hemp and marijuana, for the treatment and management of chronic pain. While CBD is labeled a schedule I drug by the Food and Drug Administration in the United States, there is evidence that CBD can make an impact on the severity of pain, the amount of opioids in use, and the …

Deciphering The Ck2-Dependent Phosphoproteome And Its Integration With Regulatory Ptm Networks, Teresa Nunez De Villavicencio Diaz

Electronic Thesis and Dissertation Repository

Protein functions are regulated by the post-translational addition of covalent modifications on certain amino acids. Depending on their distance within the 3-dimensional structure, addition/removal of individual post translational modifications (PTMs) can be impacted by others. This PTM interplay constitutes an essential regulatory mechanism that interconnects the molecular networks in the cell. Protein CK2, a clinically relevant acidophilic Ser/Thr kinase, may be responsible for 10-20% of the human phosphoproteome. Such estimates agree with the number of known substrates, which continues to expand. Furthermore, the demonstration that CK2 participates in hierarchical phosphorylation and has similar sequence determinants to caspases suggest extensive PTM …

Development Of Water-Soluble Polyesters For Tissue Engineering Applications, Trent Gordon

Electronic Thesis and Dissertation Repository

The development of tunable polymers has become increasingly important for both tissue engineering and drug delivery. This thesis investigates the development of water-soluble polyesters that contain both natural and synthetic components. These polymers offer tunable chemical structures, as well as functional groups for the conjugation of crosslinking moieties or cell signaling molecules. The first series of polymers was synthesized from poly(ethylene glycol) (PEG) and aspartic acid (Asp) via a titanium catalyzed transesterification method to provide polymers with molar masses of 12 kg/mol. After deprotection, the pendent functional groups of Asp were reacted with methacrylic, maleic, and itaconic anhydride to introduce …

Genetic Variation And Sex Mediate Differential Responses To ∆-9-Tetrahydrocannabinol Among Inbred Mice, Cory Parks

Theses and Dissertations (ETD)

The plant Cannabis sativa has been used by people for both recreational and medicinal use for thousands of years, but scientific investigation of the plant and its components didn’t begin until the early nineteen hundreds when Cannabis components known as phytocannabinoids were characterized and later isolated. In the 1970’s, ∆9-tetrahydrocannabinol (THC) was isolated and recognized as the major constituent responsible for the psychoactive and intoxicating effects associated with consumption of cannabis. This opened the door for intensive research in the field that lead to the discovery of the endogenous cannabinoid system and its associated receptors, effectors of signaling, and biosynthetic …

Validation And Application Of A Novel Target-Based Whole-Cell Screen To Identify Antifungal Compounds, Christian Alexander Dejarnette

Theses and Dissertations (ETD)

Traditional approaches to drug discovery are inefficient and have several key limitations that constrain our capacity to rapidly identify and develop novel experimental therapeutics. To address this, we have devised a second-generation target-based whole-cell screening assay based on the principles of competitive fitness, which can rapidly identify target-specific and physiologically-active compounds. Briefly, strains expressing high, intermediate, and low levels of a preselected target protein were constructed, tagged with spectrally distinct fluorescent proteins (FPs), and mixed together. The pooled strains were then grown in the presence of various small molecules, and the relative growth of each strain within the mixed culture …

Analysis Of Newspaper Coverage Of Psilocybin From January 1, 1989 To December 31, 2019, Dax Oliver

Dissertations, Theses, and Capstone Projects

Psilocybin is a chemical compound that has received a lot of attention from medical researchers in recent years. However, this research is not merely a medical issue but a social and political one as well. In the 1960s, psilocybin and other psychedelic compounds were widely ingested outside of clinical settings. This alarmed some of the American public, resulting in severe legal restrictions on psilocybin use and research.

Today, many psilocybin advocates hope that it will avoid the negative public sentiment of the 1960s. To help gauge public sentiment about other psychoactive compounds, some studies have examined newspaper coverage, but there …

Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores

Psychology and Counseling Theses

Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature …

Cancer-Targeting Immunostimulatory Peptides As An Immunotherapeutic Approach To Cancer, Rachel Montel

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the synthesis and biological applications of bifunctional trimeric peptides with B7H6-derived NKp30 binding motifs that serve to activate an immunocytotoxic response in natural killer cells and a GRP78-binding motif that can target tumors that express surface GRP78. In this manner the cancer-targeting immunostimulatory peptides are anticipated to directly bind and activate effector NK92-MI cells while also recognizing and binding to target A549 tumor cells to facilitate NK cell-dependent immunocytotoxicity of the targeted tumors. The NKp30 binding peptide motifs are derived from the tumor associated B7H6 antigen that is often downregulated or shed from the surface of tumors …

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations & Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …

Identification And Structural Characterization Functional Motifs In The Porphyromonas Gingivalis Mfa1 Short Fimbria., Mohammad K. Roky

Electronic Theses and Dissertations

Porphyromonas gingivalis is a causative agent of periodontal disease, initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of the minor fimbrial protein (Mfa1) of P. gingivalis with streptococcal antigen I/II (Ag I/II). A peptide derived from Ag I/II peptide has been well characterized and shown to significantly reduce P. gingivalis colonization and bone loss in vivo, suggesting that this interaction represents a potential target for therapeutic intervention. However, the functional motifs of Mfa1 involved in the interaction with Ag I/II remain uncharacterized. A series of N- and C-terminal peptide fragments of Mfa1 were …

Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati

Doctoral Dissertations

Using mass spectrometry (MS) to obtain information about a higher order structure of protein requires that a protein’s structural properties are encoded into the mass of that protein. Covalent labeling (CL) with reagents that can irreversibly modify solvent accessible amino acid side chains is an effective way to encode structural information into the mass of a protein, as this information can be read-out in a straightforward manner using standard MS-based proteomics techniques. The differential reactivity of proteins under two or more conditions can be used to distinguish protein topologies, conformations, and/or binding sites. CL-MS methods have been effectively used for …

Gama-Lactams And The Reformatsky Reaction: New Tricks For Old Chemistry, Dylan Dupont

Honors Theses

DUPONT, DYLAN. An Alternative Synthetic Pathway to γ-Lactam Compounds

Through the Application of Novel Reformatsky-Type Chemistry. Department

of Chemistry, June 2020

ADVISOR: James C. Adrian Jr. Ph.D.

It is the intent of the present report to relate the results of our attempt to elucidate and optimize a novel preparation of γ-lactam compounds. To achieve this end, it is proposed that the use of novel Reformatsky-type chemistry may provide a viable means. Generally, it has herein been validated that employment of α-amino ketones in traditional Reformatsky chemistry will form the traditional Reformatsky ester-adduct, and that this adduct is capable of spontaneously …

Nature-Inspired Electrode Materials For Next Generation Sustainable Energy Storage, Mikhail Miroshnikov

Dissertations, Theses, and Capstone Projects

Despite revolutionizing the world of portable electronics, the contemporary lithium-ion battery (LIB) suffers from challenges associated with the cost, safety, and environmental impact of transition metal oxide-based intercalation cathodes. To alleviate these issues, naturally occurring organic molecules may serve as sustainable alternatives to traditional inorganic cathode materials. The electrochemical properties of organic compounds are derived from redox-active functional groups containing oxygen, nitrogen and sulfur. Additionally, these functional groups are capable of coordinating metal ions beyond lithium, allowing for compatibility with sodium-ion batteries (SIBs) and other earth abundant metal-based energy storage systems. However, despite competitive performance against commercialized cathode materials, much …

Designing Peptides To Bind Kappa B Dna And Mimic Nf-Kappa B Protein Complexes, Nicholas A. Markowich

Honors College Theses

Transcription factors are important proteins that regulate gene expression and protein synthesis. Transcription factors can either boost the gene’s transcription rate by helping RNA polymerase activate transcription or restrict it by interfering with RNA polymerase, thereby repressing transcription. Nuclear factor-kappa-B (NF-κB) transcription factors are a family of proteins that control the synthesis of proteins involved in many cellular processes such as inflammatory and immune responses, cell growth, and apoptosis. However, the overexpression and activation of these transcription factors is linked to deadly conditions such as cancer and neurodegenerative diseases which currently have few safe cures. The goal of this research …

I. Non-Degradable Polysiloxane Networks For Controlled Release Applications, And Ii. Additive Free, Degradable Silyl-Ether Furyl-Maleimide Networks, Caleb M. Bunton

Chemistry Theses and Dissertations

I. Two different series of non–degradable polysiloxane networks were prepared for the encapsulation and controlled release of a small molecule agent. For the first series, hydrosilylation was utilized to prepare networks of varying crosslink densities, as determined from swelling studies, from vinyl terminated and silylhydride functional poly(dimethyl)siloxanes. For the second series, the thiol-ene reaction was utilized to prepare networks of varying crosslink densities, as determined from swelling studies, from vinyl terminated and mercaptopropyl functional poly(dimethyl)siloxanes. Nile red dye was used as an encapsulated agent and dye release from each series of networks was measured using UV–vis spectroscopy to determine controllability …

Determining The Link Between Advanced Glycation Endproducts (Ages), Feeding, And Metabolism, Lauren Wimer

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Reactive a-dicarbonyls (a-DC’s), such as methylglyoxal (MGO), are unavoidable metabolites generated during glycolysis that accumulate with age and have been linked with chronic age-related metabolic diseases such as Diabetes Mellitus. Diabetes Mellitus is generally characterized by peripheral neuropathy and sustained hyperglycemia. Chronic hyperglycemia leads to an increase in glycolysis and a downstream increase in reactive a-DC’s. The human body has a natural method of detoxifying these a-DC’s. Glycolytic cells have enzymes which can detoxify a-DC’s, but if overwhelmed, a-DC’s can accumulate and react non-enzymatically with proteins, lipids and DNA to yield a group of molecules called advanced glycation end-products (AGEs). …