Physiology Commons^™

The Role Of Oxidative Stress In The Pathogenesis Of Epithelial Ovarian Cancer, Nicole Marie King

Wayne State University Dissertations

Ovarian cancer is the leading cause of death from gynecologic malignancies yet the underlying pathophysiology is not clearly established. The disease is usually diagnosed in the advanced stage and carries a poor prognosis. The 5-year survival rate is greater than 75% if diagnosis of the cancer occurs at an early stage; however, this rate drops to 20% when the tumor has spread beyond its origin. Thus, a method for early detection is critically needed, which can help prolong, or even save lives. Currently, an effective screening test for ovarian cancer is lacking. Many tests have been evaluated but have been …

Characterization Of High-Voltage-Activated Calcium Channels In Retinal Bipolar Cells, Qi Lu

Wayne State University Dissertations

Retinal bipolar cells, conveying visual information from photoreceptors to ganglion cells, segregate visual information into multiple parallel pathways through their diversified cell types and physiological properties. Voltage-gated Ca²⁺ channels could be particularly important underlying the diversified physiological properties of different BCs. In this dissertation, I investigated the high-voltage-activated (HVA) calcium current in retinal bipolar cells in mice. In the first part of my dissertation, I characterized multiple bipolar cell-expressing GFP and/or Cre transgenic mouse lines. In the second part of my dissertation, by performing whole-cell patch-clamp recordings, I examined the electrophysiological properties of HVA calcium currents among CBCs and …

Thick Ascending Limb Nitric Oxide Production And Inhibition Of Nkcc2 Activity Are Impaired In Angiotensin Ii-Induced Hypertension, Vanesa Daniela Ramseyer

Wayne State University Dissertations

Cardiovascular disease is the leading cause of death in the US. Hypertension, which affects about 30 % of the US population, is an important risk factor in the development of this disease. Inappropriately elevated sodium reabsorption by the kidney contributes to hypertension; therefore, studying the mechanisms that lead to enhanced sodium transport is important in understanding this pathology. The thick ascending limb (THAL) reabsorbs 30% of the filtered sodium chloride load. Nitric oxide (NO) produced by NO synthase type 3 (NOS3) increases cyclic GMP (cGMP) and inhibits THAL transport by reducing Na/K/2Cl cotransporter type 2 (NKCC2) activity. Interestingly, in angiotensin …

Mechanisms Mediating Modulation Of The Cardiopulmonary Chemoreflex Control Of Regional Sympathetic Outputs By Adenosine A1 And A2a Receptors In The Nts, Zeljka Minic

Wayne State University Dissertations

ABSTRACT

by

ZELJKA MINIC

August 2013

Advisor: Dr. Tadeusz J. Scislo

Major: Physiology

Degree: Doctor of Philosophy

Adenosine is an important neuromodulator of cardiovascular control at the level of the nucleus of the solitary tract (NTS) where cardiovascular and other autonomic reflexes are primarily integrated. Levels of adenosine increase in the NTS during life threatening hypotension, ischemia and hypoxia. Adenosine may modulate cardiovascular reflexes to correct hemodynamic imbalance, acting via A₁ and A_2a receptors which inhibit and facilitate neurotransmitter release, respectively. Previous studies from our laboratory showed that NTS A₁ adenosine receptors inhibit the arterial baroreflex whereas …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

Modulation Of Renin Secretion By Renal Cortical Interstitial Calcium, Douglas K. Atchison

Wayne State University Dissertations

Renin is secreted from the juxtaglomerular (JG) cells of the afferent arteriole of the kidney, and is the rate-limiting enzyme of the renin-angiotensin system. Renin is quantified in vivo as plasma renin activity (PRA). Acutely elevating plasma calcium decreases PRA, but the mechanisms by which this occurs is unknown. The overall goal of our study was to determine how elevated plasma calcium decreases PRA. The calcium-sensing receptor (CaSR) is a ubiquitously expressed receptor that translates changes in plasma calcium into changes in intracellular signaling. JG cells are basolaterally bordered by the renal cortical interstitium, and parathyroid hormone (PTH) positively regulates …

Fatty Acid Fate In Determining Oxidation And Inflammation In Adipose Tissue, Emilio Patrick Mottillo

Wayne State University Dissertations

Adipose tissue (AT) is a critical regulator of energy balance through its ability to store or oxidize free fatty acids (FFAs). White adipose tissue (WAT) functions as an anabolic organ to sequester and release FAs, in contrast brown adipose tissue (BAT) is a catabolic organ that oxidizes FAs. However, a comprehensive understanding of the role that FFAs play in the function of WAT and BAT is needed. Here we demonstrate that intracellular FAs enhance the expression of inflammatory cytokines by β3-AR activation in adipocytes, in which the expression of PAI-1 is partly mediated by the de novo synthesis of ceramides/sphingolipids. …