Medicine and Health Sciences Commons^™

The Evaluation Of The Prokinetic Action Of A Luminally Restricted 5-Ht4 Receptor Agonist In Mice, Emma Schoeling

Graduate College Dissertations and Theses

Serotonin (5-HT) is a neurotransmitter mainly produced in the enteric nervous system (ENS) of the gastrointestinal (GI) system. Serotonin has widespread function throughout the body including regulating mood, cognition, sleep, sex, and appetite. In the context of the gut, the monoamine modulates vasodilation, mucus secretion, pain, and peristaltic reflexes for motility. The 5-HT4 receptor is expressed on enteric epithelial cells and nerve terminals in the intestinal mucosa. The agonists available to act on these receptors are a favorable target to promote epithelial healing, recovery from colitis or constipation, and epithelial cell proliferation. The non-absorbable, luminally restricted, 5-HT4R agonist (5HT4-LA1; Takeda …

Designer Biologics Composed Of Hepatocyte Growth Factor, Fibroblast Growth Factor 2 And Immunoglobulin G For Treatment Of Acute Myocardial Infarction, Benjamin Liebman

Graduate College Dissertations and Theses

ABSTRACT Coronary artery disease leading to myocardial infarction (a.k.a. MI, heart attack) is one of the leading causes of death globally. Each year an estimated 605,000 Americans suffer a heart attack, which equates to one MI every 40 seconds. As such, MI represents one of the largest health burdens to society. The current standard of care is revascularization therapy achieved by fibrinolytics and Percutaneous Coronary Intervention (PCI); both of which re-open occluded proximal arteries to restore blood flow to the affected areas. Despite revascularization therapy, 30-50% of patients exhibit a form of reperfusion injury termed “no/low-reflow” in which the blood …

Transdermal Testosterone For Menopause-Related Hyposexual Desire Disorder: Current Guidelines And Provider Perceptions, Knowledge, And Practice, Kelly Christine White

Graduate College Dissertations and Theses

Hypoactive sexual desire or low libido in women are collectively referred to as hypoactive sexual desire disorder (HSDD). HSDD is estimated to occur in 10% to 15% of adult women. HSDD is likely the most common female sexual dysfunction (FSD) in menopausal women. The hallmark of the diagnosis is personal distress and interpersonal difficulties resulting from low sex drive. Most women will not seek help for this problem. Studies have suggested that primary care providers and gynecologic healthcare providers report not feeling qualified to treat patients with sexual dysfunction, especially HSDD. Testosterone, specifically transdermal testosterone, has been suggested to play …

Regulation Of Middle Meningeal Artery Diameter By Pacap And Atp-Sensitive Potassium Channels, Arsalan Urrab Syed

Graduate College Dissertations and Theses

Migraine is one of the most prevalent contributors to the global burden of mental and neurological disorders. It is a complex episodic condition that presents as intense recurrent unilateral headaches lasting hours to days that can be accompanied by nausea, photophobia, phonophobia and other neurological symptoms. The causes of migraine appear multifactorial and are not fully understood. However, activation of the trigeminovascular system and sphenopalatine parasympathetic neurons and the resulting vasodilation of meningeal arteries have been associated with the development of migraine pain. Recently, the neurotransmitter and neurotrophic peptide pituitary adenylate cyclase activating polypeptide (PACAP) has been implicated in this …

Ubiquitin Ligase Trim32 And Chloride-Sensitive Wnk1 As Regulators Of Potassium Channels In The Brain, Eugene Miler Cilento

Graduate College Dissertations and Theses

The voltage-gated potassium channel Kv1.2 impacts membrane potential and therefore excitability of neurons. Expression of Kv1.2 at the plasma membrane (PM) is critical for channel function, and altering Kv1.2 at the PM is one way to affect membrane excitability. Such is the case in the cerebellum, a portion of the brain with dense Kv1.2 expression, where modulation of Kv1.2 at the PM can impact electrical activity of neurons and ultimately cerebellum-dependent learning. Modulation of Kv1.2 at the PM can occur through endocytic trafficking of the channel; however mechanisms behind this process in the brain remain to be defined.

The goal …

Traumatic Brain Injury Causes Endothelial Dysfunction In Mesenteric Arteries 24 Hrs After Injury, Ivette Ariela Nunez

Graduate College Dissertations and Theses

Traumatic brain injury (TBI) is the most frequent cause of death in children and young adults in the United States. Besides emergency neurosurgical procedures, there are few medical treatment options to improve recovery in people who have experienced a TBI. Management of patients who survive TBI is complicated by both central nervous system and peripheral systemic effects. The pathophysiology of systemic inflammation and coagulopathy following TBI has been attributed to trauma-induced endothelial cell dysfunction; however, there is little knowledge of the mechanisms by which trauma might impact the functions of the vascular endothelium at sites remote from the injury. The …

Mechanoregulation Of Leading Edge Pka Activity During Ovarian Cancer Cell Migration, Andrew J. Mckenzie

Graduate College Dissertations and Theses

Ovarian cancer is the deadliest of all the gynecologic cancers and is known for its clinically occult and asymptomatic dissemination. Most ovarian malignancies are diagnosed in the late stages of the disease and the high rate of morbidity is thought to be due, in part, to the highly metastatic nature of ovarian carcinomas. Cancer metastasis relies on the ability of cells to migrate away from primary tumors and invade into target tissues. Though the processes are distinct, cancer cell invasion relies on the underlying migration machinery to invade target tissues.

Cell migration requires the coordinated effort of numerous spatially-regulated signaling …