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Articles 1 - 12 of 12
Full-Text Articles in Chemicals and Drugs
Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko
Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko
Theses and Dissertations
Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …
Examining The Behavioral And Phyisiolgical Effects Of D-Methamphetamine Administered Via E-Cigarette Aerosolization, Srikethan Mahavadi
Examining The Behavioral And Phyisiolgical Effects Of D-Methamphetamine Administered Via E-Cigarette Aerosolization, Srikethan Mahavadi
Theses and Dissertations
Abstract
EXAMINING THE BEHAVIORAL AND PHYISIOLGICAL EFFECTS OF D-METHAMPHETAMINE ADMINISTERED VIA E-CIGARETTE AEROSOLIZATION
By Srikethan Mahavadi, B.S.
A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University
Virginia Commonwealth University, 2021
Principal Investigator: Dr. Keith Shelton, PhD., Department of Pharmacology & Toxicology
E-cigarettes have become increasing popular worldwide. They are primarily used as a means to deliver nicotine to users, but these devices may also be used to administer a wide range of other substances including psychomotor stimulants such as d-methamphetamine. Methamphetamine has been widely abused throughout the United States …
Behavioral Screening And Chiral Bioanalysis Of Emerging Stimulant-Type Drugs In Rats, Tyson R. Baird
Behavioral Screening And Chiral Bioanalysis Of Emerging Stimulant-Type Drugs In Rats, Tyson R. Baird
Theses and Dissertations
The epidemic of drug use in the United States and elsewhere in the world has resulted in tragic loss of life and substantial economic costs. Novel psychoactive substances (NPS) are one of the contributors to this problem, and the lack of information about many of these drugs compounds their risk. This dissertation proposes a strategy to use intracranial self-stimulation (ICSS) as a behavioral screening tool to assess emerging drugs of abuse for their abuse potential in order to generate a proactive threat assessment. A series of stimulant-type drugs including methcathinone, α-pyrrolidinohexanophenone (α-PHP), cocaine, and the phenyltropane analogs of cocaine WIN35428 …
Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook
Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook
Theses and Dissertations
Non-small Cell Lung Cancer (NSCLC) originates from numerous different cell types in the lungs and is among the deadliest of cancers. Head and Neck Squamous Cell Carcinomas (HNSCC) are derived from the mucosal membranes of the oral cavity, pharynx, and larynx. Both NSCLC and HNSCC are predominately caused by tobacco smoke inhalation and as such mutations in the tumor suppressor gene TP53 are common. Since similarities exist in the root cause of NSCLC and HNSCC, they may also share similarities in treatment methods. Cisplatin is a platinum-based DNA damaging agent that has been used as a cancer chemotherapy for decades. …
Reward-Related Effects Of Amphetamines Administered By Electronic Cigarette, Lucas Wohler
Reward-Related Effects Of Amphetamines Administered By Electronic Cigarette, Lucas Wohler
Theses and Dissertations
While e-cigarette vaporizers are primarily used for the delivery of nicotine, they can also be used to administer a wide range of other substances of abuse including stimulants such as d-amphetamine and methamphetamine. Methamphetamine and prescription amphetamines are widely abused throughout the United States and across the world leading us to believe there may be abuse potential with vaping methamphetamine as vaping becomes increasingly popular. In the present study, methamphetamine and amphetamine vapor were assessed using vapor capture methods. The vapor samples were then analyzed using liquid chromatography mass spectroscopy (LC-MS). Three experiments were carried out to examine the abuse …
Pharmacodynamics Of Monoamine Transporter Releasing Agents And Reuptake Inhibitors, Alexa Holloway
Pharmacodynamics Of Monoamine Transporter Releasing Agents And Reuptake Inhibitors, Alexa Holloway
Theses and Dissertations
Ligands of the human monoamine transporters encompass a wide range of both illicit and therapeutic drugs that act upon neural circuitry related to reward, motivation, and the processing of salient stimuli. The present study utilizes two methods for analyzing transporter substrates and inhibitors in order to characterize activity and assess potency. The first measures transient changes in intracellular calcium as a surrogate for transporter activity by harnessing the electrical coupling of monoamine transporters and L-type calcium channels. This is used to analyze novel chimera of the strong hDAT inhibitors methylphenidate and ��-PPP in order to assess the contribution of specific …
Glycosaminoglycan Mimetics For The Treatment Of Cancer And Lung Inflammation, Shravan Morla
Glycosaminoglycan Mimetics For The Treatment Of Cancer And Lung Inflammation, Shravan Morla
Theses and Dissertations
Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar and either uronic acid or galactose. They are expressed on virtually all mammalian cells, usually covalently attached to proteins, forming proteoglycans. GAGs are highly negatively charged due to an abundance of sulfate and carboxylic acid groups, and are structurally very diverse, with differences arising from chain length, the type of monomeric units, the linkages between each monomeric unit, the position of sulfate groups, and the degree of sulfation. GAGs are known to interact with a multitude of proteins, impacting diverse physiological and pathological processes. In addition, …
Pharmacologic Profiling Of Novel Compounds Via Fluorometric Analyses Of Monoamine Transporter Responses, Ashkhan Hojati
Pharmacologic Profiling Of Novel Compounds Via Fluorometric Analyses Of Monoamine Transporter Responses, Ashkhan Hojati
Theses and Dissertations
In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is …
5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala
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 …
Bromodomain And Extraterminal Domain (Bet) Inhibitor Rvx-208 Ameliorates Periodontal Bone Loss, Nicholas J. Clayton
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 …
Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant
Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant
Theses and Dissertations
Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …
Chronic Behavioral And Cognitive Deficits In A Rat Survival Model Of Organophosphate Toxicity, Beverly Huang
Chronic Behavioral And Cognitive Deficits In A Rat Survival Model Of Organophosphate Toxicity, Beverly Huang
Theses and Dissertations
Organophosphates (OPs) are a major class of pesticides and nerve agents that elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for the degradation of the neurotransmitter acetylcholine in the central and peripheral nervous systems. Acetylcholine accumulation following extensive AChE inhibition leads to an acute cholinergic syndrome characterized by autonomic dysfunction, involuntary movements, muscle fasciculations, respiratory distress, and seizures. Despite their classification as moderate to highly toxic, OP pesticides are the most widely used class of insecticides in the U.S., and are even more commonly used worldwide. Additionally, there is a growing concern that OP nerve agents could be …