Pharmacology Commons^™

Heat Shock Factor 1 Signaling: A Novel Pathway Implicated In Rett Syndrome Pathophysiology, Sonia Gonzalez

Dissertations

Rett syndrome (RTT) is a severe neurodevelopmental disorder that is associated with loss-of-function mutations in the methyl-CPG binding protein 2 (MECP2) gene. There are limited therapeutic options to address the wide range of social, cognitive, motor, and respiratory symptoms that patients experience throughout their lifetime. To identify novel therapeutic targets, we leveraged a rare form of RTT known as MeCP2-mutation-negative or atypical RTT. Traditionally, RTT is first diagnosed clinically and then confirmed through the identification of mutations in the MECP2 gene. However, ~5% of RTT patients are found to be MeCP2-mutation-negative (atypical), despite sharing overlapping symptomology with typical RTT. We …

Muscarinic Acetylcholine Receptor 1: Implications For Precision Medicine And Rett Syndrome Therapeutics, Mackenzie Smith

Dissertations

Rett syndrome (RTT) is a rare neurodevelopmental disorder caused by mutations in the gene coding for methyl-CpG binding protein 2 (MeCP2). Currently, there is no cure for RTT and few effective treatment options to address the social, cognitive, motor, and respiratory symptoms that patients face. With the goal of identifying novel targets, our lab performed RNA-sequencing experiments in human autopsy samples and found decreased levels of the M1 muscarinic acetylcholine receptor. We have established that potentiation of this receptor in a Mecp2+/- mouse model of RTT rescues social, cognitive, and respiratory phenotypes, providing support for using drugs that act on …

Investigating Whether Txnrd2 Is A Therapeutic Target Against Triple Negative Breast Cancer Using African American-Derived Models, Keacha Chang

Dissertations

Despite similar breast cancer incidence rates, African American (AA) women experience a 40% higher mortality rate compared to Caucasian American (CA) women. This disparity is multifactorial and particularly pronounced in the Chicago area. AA women are twice as likely to be diagnosed with triple-negative breast cancer (TNBC), often at a younger age and with more aggressive disease. TNBC is a heterogeneous subtype lacking targeted therapies and is associated with the poorest prognosis among breast cancer types. Therefore, there is an urgent need for novel therapeutic strategies for TNBC, especially those tailored to AA patients. The thioredoxin pathway is essential for …

Bridging The Gap: Psychopharmacologic Education And Side Effect Screening For Non-Prescribing Mental Health Professionals, Elaine Fitzgerald

Dissertations

Abstract

Problem: The United States is experiencing a growing demand for pediatric mental health support. Surges in mental health diagnoses and psychotropic medication prescriptions have occurred, compounded by a shortage of psychiatric providers. Non-prescribing mental health professionals are well-positioned to recognize psychotropic medication side effects. However, psychologists and counselors lack formal pharmacology education.

Methods: The quality improvement (QI) initiative was guided by the Plan-Do-Study-Act (PDSA) model. The evidence-based psychopharmacologic education for non-prescribers utilized a quasi-experimental pre- and post- test design. Data collected from clinicians included knowledge, confidence, and skill concerning psychotropic medications. The Psychotropic Medication Monitoring Checklist (PMMC) screen clients …

The Role Of Extracellular Vesicles And Their Cargo In Intercellular Communication, Chongyu Zhang

Dissertations

Extracellular vesicles (EVs) are membranous vesicles secreted by most cells. They contain lipids, proteins, and nucleic acids, including microRNAs (miRNA), and function in intercellular communication by endocytosis into other cells. EVs in diseased states carry miRNAs and proteins reflective of the changed state of cells and can be endocytosed into other cells to exert regulatory effects. Thus, EVs represent a form of paracrine genetic regulation in health and disease. Myocardial infarction (MI) and pulmonary embolism (PE) are leading causes of cardiovascular deaths worldwide. It is important to develop new diagnostic and therapeutic approaches that could lead to medical advances. Circulating …

Exploring Fused Deposition Modeling (Fdm) Three-Dimensional Printing Tablet Design Options For Pharmaceutical Dosage Forms, Guluzar Gorkem Buyukgoz

Dissertations

This dissertation examines the use of Fused Deposition Modeling (FDM) based three-dimensional (3D) printing approach for developing patient-specific dosage forms and addressing related technical challenges in such drug delivery systems. The first main objective is to explore pharmaceutical tablet design options using novel FDM 3D printing technology as the drug delivery platform such that drug form and tablet properties are tailored by considering patient age-specific formulations and dissolution control. Of the five different design options, two proposed options meet the main objective of providing similar drug release, whereas the popular option of fixed drug concentration but differing tablet size could …

Comparative Studies On Biochemical And Pharmacological Profiles Of Unfractionated Heparins & Their Depolymerized Derivatives From Bovine, Ovine And Porcine Origins, Ahmed Kouta

Dissertations

Heparin and heparin related drugs have remained the anticoagulant of choice for medical and surgical indications. These drugs are comprised of poly-component sulfated chains of varying length and biophysical structure with direct and indirect pharmacological effects. Heparins produce their therapeutic effects by multiple mechanisms involving both the cellular and humoral targets. These drugs represent natural products which are isolated from mammalian tissue rich in mast cells. Currently used heparin and LMWHs are obtained from porcine mucosal tissue. Other animal sources including bovine and ovine tissues also provide additional sources for the manufacturing of heparins. While there may be microchemical and …

Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler

Dissertations

Cardiovascular disease is the leading cause of death worldwide. A myocardial infarction (MI), commonly known as a heart attack, is a major event in cardiovascular disease characterized by reduced blood flow to the heart. The ischemia and reperfusion (I/R) injury associated with an MI results in a region of dead tissue in the heart called an infarct, the size of which influences patient prognosis. In the 1980s, it was discovered that short, non-lethal episodes of I/R, termed ischemic preconditioning (IPC), can protect the heart against a subsequent MI. Ischemic preconditioning demonstrated the phenomenon of endogenous cardioprotection. Cardioprotection has great potential …

Functionalized Carbon Nanotubes In Hydrophobic Drug Delivery, Kun Chen

Dissertations

The direct incorporation of carboxylated carbon nanotubes (f-CNTs) into hydrophobic drug particles during their formation via anti-solvent precipitation is presented. The approach is tested using two drugs namely antifungal agent Griseofulvin (GF) and antibiotic Sulfamethoxazole (SMZ) that have very different aqueous solubility. It is observed that the f-CNTs dispersed in the water serve as nucleating sites for crystallization and are readily incorporated into the drug particles without altering crystal structure or other properties. The results show that the hydrophilic f-CNTs dramatically enhance dissolution rate for both drugs. The increased degree of functionalization leads to higher hydrophilicity and therefore faster dissolution …

Examining The Regulation Of Kv7 K+ Channels In Airway Smooth Muscle Cells And Their Potential As Novel Therapeutic Targets For The Treatment Of Asthma, Jennifer Haick

Dissertations

Asthma is a disease characterized by nonspecific and exaggerated airway narrowing, termed airway hyperresponsiveness (AHR), which involves the excessive contraction of airway smooth muscle. Despite the fact that airway smooth muscle is widely studied and understood to play a role in AHR, little is known about the specifics of that role. Our laboratory recently found that Kv7 potassium (K+) channels are expressed in airway smooth muscle cells (ASMCs). Kv7 channels are voltage sensitive K+ channels whose outward flux of K+ ions promotes a negative resting membrane voltage in excitable cells, thereby opposing electrical excitability. Inhibition of K+ channels is known …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

Gabab Regulation Of Methamphetamine-Induced Associative Learning, Robin Michelle Voigt

Dissertations

Addiction is a chronic, relapsing disorder for which strikingly few effective therapies exist, and there are no FDA-approved pharmacotherapies for methamphetamine (Meth) addition. There is an immense need to identify the neurobiological underpinnings of psychostimulant addiction and develop efficacious drug therapies to compliment the current mainstay treatment of behavioral/cognitive therapy.

Re-exposure to cues associated with psychostimulants (e.g., drug paraphernalia) increase neuronal activity and can elicit drug-craving and -seeking; an effect which is profound and long-lasting. A mechanism to disrupt those brain processes which are necessary to maintain the association may reduce the incidence of cue-elicited relapse.

Conditioned place preference (CPP) …

Amyloid-β Deposition In Rat Brain: Histopathological And Functional Sequelae, Einar M. Sigurdsson

Dissertations

No abstract provided.

Characterization Of Adaptive Changes In 5-Htia Receptor Systems Induced By Repeated Injections Of 5-Ht Uptake Inhibitors, Qian Li

Dissertations

No abstract provided.

Corticosteroid Modulation Of Hippocampal Neural Activity, Dayne Y. Okuhara

Dissertations

No abstract provided.

Effect Of Af64a On Rat Brain Septo-Hippocampal And Striatal Cholinergic Systems: A Neurochemical And Molecular Analysis, Qing Ivy Fan

Dissertations

No abstract provided.

Androgen Receptors In The Hippocampus: Localization, Autoregulation, And Modulation Of Gene Expression In The Adult Male Rat, Janice E. Kerr

Dissertations

No abstract provided.

Characterization Of Central Serotonergic Alterations In Male Rats Following Prenatal Exposure To Fluoxetine, Theresa M. Cabrera

Dissertations

No abstract provided.

Comparative Pharmacologic Studies On Synthetic And Recombinant Inhibitors Of Thrombin, Demetra D. Callas

Dissertations

No abstract provided.

Pharmacologic Studies On Synthetic Analogues Of Heparin With Selective Affinity To Endogenous Serine Protease Inhibitors, Walter P. Jeske

Dissertations

No abstract provided.

Relationships Between The Expression Of Genes Involved In The Regulation Of Apoptosis And Cell Death Induced By Nitrogen Mustard In Human Colon Carcinoma Cell Lines, Greggory Bernard Herbert

Dissertations

No abstract provided.

Central Serotonergic Stimulation Of Renin Secretion, Peter Andrew Rittenhouse

Dissertations

No abstract provided.

Synaptic Transmission In The Inferior Mesenteric Ganglion Of The Rabbit: An Electrophysiological And Immunohistochemical Study, Mark Alan Simmons

Dissertations

No abstract provided.

Stress, Neurotransmitters And Avoidance Acquisition, Daniel Leo Richardson

Dissertations

No abstract provided.

Isolated Frog Brainstem Technique: Analysis Of Neural Correlates Of Mating Calling And Possible Use In Drug Studies, David Douglas Schaffer

Dissertations

No abstract provided.

The Short And Long Term Effects Of Opiates On Myenteric Neurons, Peter J. Karras

Dissertations

No abstract provided.

Peptide Systems In The Myenteric Plexus: Extracellular Recording, John T. Williams

Dissertations

No abstract provided.

Studies On The Activation And Inhibition Of Erythrocytic Delta-Aminolevulinic Acid Dehydratase (Alad), Michael James Avram

Dissertations

No abstract provided.

Actions Of L-Methyl-3-Isobutyl Xanthine On The Cat Neuromuscular Junction, Alan C. Roman

Dissertations

No abstract provided.

A Neuropharmacological Analysis Of Retinal Function In The Isolated Perfused Frog Eye, Anthony Louis Marchese

Dissertations

No abstract provided.