Pharmacology Commons^™

Development Of Targeted, Statin Loaded Nanoparticle Delivery Systems, Stephanie Judkins

Master's Theses

Statins lower endogenous production of cholesterol through their inhibition of the mevalonate pathway. Lipophilic statins in particular exhibit anti-inflammatory effects at supraphysiological doses by preventing downstream signaling through small molecule GTPases. Interest lies in development of statins as anti-inflammatory therapeutics, however, achieving effective doses locally incurs serious off-target effects. Our goal was to develop and optimize a targeted delivery system to traffic these drugs to inflamed sites and unload the drug at effective concentrations while avoiding systemic exposure. Lipophilic statins (lovastatin, simvastatin, and atorvastatin) were incorporated into polymeric nanoparticles (NPs) due to their hydrophobicity. We have shown that statins released …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz

Master's Theses

The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional …

Phosphodiesterase Inhibition As A Mechanism Of Ion Channel Modulation By Celecoxib, Christina Jean Robakowski

Master's Theses

The overall objective of this thesis work is to determine the mechanism by which celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells. The central hypothesis of the project is that celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells through inhibition of phosphodiesterase 4 (PDE4, which catalyzes the breakdown of cyclic adenosine monophosphate (cAMP)), thereby activating a cAMP/protein kinase A (PKA) signaling pathway. The aims of this thesis targeted different points in the cAMP/PKA pathway with pharmacological interventions using whole cell perforated patch clamp electrophysiology and biochemical methods.

The data suggest multiple mechanisms by which celecoxib could …

Modulation Of Synaptic Transmission By Adenosine In Layer 2/3 Of The Rat Visual Cortex In Vitro, Nicholas M. Bannon

Master's Theses

No abstract provided.

Tremulous Jaw Movements Induced By The Vmat2 Inhibitor Tetrabenazine, Samantha J. Podurgiel

Master's Theses

Parkinsonism is a movement disorder characterized by several cardinal motor symptoms: resting tremor, akinesia, bradykinesia, rigidity, and postural instability. Parkinsonian resting tremor can be modeled in rodents using the tremulous jaw movement model. Tremulous jaw movements (TJMs) are defined as “rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus.” TJMs occur in a frequency range of 3-7 Hz and are induced by a number of pharmacological manipulations that parallel those seen in human Parkinsonism including dopamine (DA) depleting agents, DA antagonists, and cholinomimetic administration. Additionally, TJMs can be attenuated using antiparkinsonian …

Kv7 K+ Channels In Airway Smooth Muscle Cells As Target For Asthma Therapy, Priyanka Prakash Kakad

Master's Theses

Airway hyperresponsiveness (AHR) is an important etiological feature of asthma, the molecular mechanisms of which are poorly understood, thus preventing development of specific and effective therapies. We investigate the role played by Kv7 voltage-activated potassium channels in the pathophysiology of AHR and evaluate the significance of their regulation in treatment of asthma. Our studies provide the first evidence for expression of multiple Kv7 channels in guinea pig and human airways and demonstrate that the expression of Kv7 channels is reduced in allergen-sensitized guinea pig airways. Our ex vivo functional studies reveal that clinically available Kv7 channel activators attenuate the bronchoconstrictor …

The Interaction Of O6-Benzylguanine And Streptozotocin In The Inactivation Of O6-Methylguanine Dna Methyltransferase And The Reversal Of 1,3 Bis (2-Chloroethyl)-1-Nitrosourea Resistance, Upendra Kumar Marathi

Master's Theses

No abstract provided.

Dopaminergic Modulation Of Basal Forebrain Cholinergic Neurons, Mary Elizabeth Muench

Master's Theses

No abstract provided.

The Spinal Origin Of Fibres Causing Vasodilation In The Cat's Submaxillary Gland, Herbert M. Stanton

Master's Theses

No abstract provided.

The Effect Of Insulin, Dextrose, And Cyanide On The Circular And The Longitudinal Muscles Of The Rabbit's Intestine, Gustav A. Hemwall

Master's Theses

No abstract provided.

The Effect Of Drugs On The Longitudinal And Circular Muscle Of The Rabbit's Intestine: A New Method Of Study, Howard Vincent Valentine

Master's Theses

No abstract provided.