Physiology Commons^™

Adenosine A2b Receptor Effects On Post-Mi Remodeling And Cardiac Fibroblast Function, Enbo Zhan

Wayne State University Dissertations

Adenosine A_2B receptor (A_2BR) appear to contribute to chronic inflammation. This receptor is highly expressed in macrophages and cardiac fibroblasts, cells which play key roles in inflammation and healing following myocardial infarction (MI). A_2BR have been shown to induce collagen production and promote organ fibrosis, although the reports of A_2BR role on MI are limited and conflicting. The results of cardiac fibroblast (CF) studies however suggest that non-selective A_2BR stimulation inhibits collagen expression. The hypothesis of the present study was that deletion of A_2BR reduces adverse remodeling in post-MI, …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

The -9/+9 Polymorphism Of The Bradykinin Receptor Beta 2 Gene And Athlete Status: A Study Involving Two European Cohorts., Marek Sawczuk, Yevgeniya I. Timshina, Irina V. Astratenkova, Agnieszka Maciejewska-Karłowska, Agata Leońska-Duniec, Krzysztof Ficek, Leysan J. Mustafina, Paweł Cięszczyk, Tomasz Klocek, Ildus I. Ahmetov

Human Biology Open Access Pre-Prints

Background: Previous studies concerning the relevance of the BDKRB2 gene polymorphisms revealed that the absence (–9 allele) of a 9 base pair sequence in exon 1 of the BDKRB2 gene is correlated with higher skeletal muscle metabolic efficiency, glucose uptake during exercise, as well as endurance athletic performance. Aim: The aim of the study was to investigate the association between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of east-European athletes. Therefore, we examined the genotype distribution of the BDKRB2 9/+9 polymorphic site in a group of Polish athletes and confirmed the results obtained in a replication …

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 …

Cardiovascular Fitness Associated With Cognitive Performance In Heart Failure Patients Enrolled In Cardiac Rehabilitation, Sarah Garcia, Michael L. Alosco, Mary Beth Spitznagel, Ronald Cohen, Naftali Raz, Lawrence Sweet, Richard Josephson, Joel Hughes, Jim Rosneck, Morgan L. Oberle, John Gunstad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Reduced cognitive function is common in persons with heart failure (HF). Cardiovascular fitness is a known contributor to cognitive function in many patient populations, but has only been linked to cognition based on estimates of fitness in HF. The current study examined the relationship between fitness as measured by metabolic equivalents (METs) from a standardized stress test and cognition in persons with HF, as well as the validity of office-based predictors of fitness in this population.

Methods

Forty-one HF patients enrolled in cardiac rehabilitation completed a standardized exercise stress test protocol, a brief neuropsychological battery, the 2-minute step …

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. …

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 …

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 …

Mrna Granules And Ischemic Preconditioning, Michelle Rei Smith

Wayne State University Theses

Brain ischemia and reperfusion that occurs after stroke and cardiac arrest, causes translation arrest (TA) in neurons which is irreversible in neurons that will undergo delayed neuronal death. TA is linked to mRNA granules, which are involved in ischemia-induced stress genes translation. Ischemic preconditioning (IPC) is the most protective response known that protects neurons from a lethal ischemic insult. In this thesis I studied the effects of (1) sublethal durations of ischemia, (2) IPC and (3) cycloheximide (CHX) on the formation of mRNA granules at 1 hour of reperfusion and the colocalization of HuR in the mRNA granules. All durations …

Sex Differences In The Cardiac Beta-Adrenergic Receptor Contractile Response, Victoria Mcintosh

Wayne State University Dissertations

Premenopausal females are at a reduced risk for developing cardiovascular disease as compared to males; this sex difference is not present following menopause. &beta-adrenergic receptors are pharmaceutical targets in the treatment of cardiovascular disease, and sex differences in &beta-adrenergic responsiveness have been demonstrated. However, limited studies have addressed the mechanism(s) underlying these differences. To investigate these sex differences, studies were performed using isolated perfused hearts from male, intact female and ovariectomized female mice, as well as male and female ventricular myocytes. Female hearts exhibited blunted contractile responses to the &beta-adrenergic receptor agonist isoproterenol (ISO) compared to males but not ovariectomized …

Investigation Of Posttranscriptional Regulation After Global Brain Ischemia And Reperfusion Injury, Jeffrey J. Szymanski

Wayne State University Dissertations

The final cause of death in most patients revived after cardiac arrest is ischemia and reperfusion (I/R) injury in the brain. Survival after brain I/R injury depends on the expression of new stress response proteins such as heat shock protein 70 (HSP70). Little is known about why recovering neurons are able to express new stress response proteins while neurons that will die can transcribe RNA but do not translated protein in early reperfusion. Previous studies suggested that the mRNA-binding protein HuR may regulate hsp70 mRNA in reperfused neurons through a novel cytoplasmic structure, the mRNA granule. To determine the roles …

Effects Of Diet Type And Supplementation Of Glucosamine, Chondroitin, And Msm On Body Composition, Functional Status, And Markers Of Health In Women With Knee Osteoarthritis Initiating A Resistance-Based Exercise And Weight Loss Program, Teresa Magrans-Courtney, Colin Wilborn, Christopher Rasmussen, Maria Pontes Ferreira, Lori Greenwood, Bill Campbell, Chad M. Kerksick, Erica Nassar, Rui Li, Mike Iosia, Matt Cooke, Kristin Dugan, Darryn Willoughby, Luann Soliah, Richard B. Kreider

Nutrition and Food Science Faculty Research Publications

Background: The purpose of this study was to determine whether sedentary obese women with knee OA initiating an exercise and weight loss program may experience more beneficial changes in body composition, functional capacity, and/or markers of health following a higher protein diet compared to a higher carbohydrate diet with or without GCM supplementation.

Methods: Thirty sedentary women (54 ± 9 yrs, 163 ± 6 cm, 88.6 ± 13 kg, 46.1 ± 3% fat, 33.3 ± 5 kg/m²) with clinically diagnosed knee OA participated in a 14-week exercise and weight loss program. Participants followed an isoenergenic low fat higher …

Effect Of Dimethylarginine Dimethylaminohydrolase In The Development Of Salt Sensitivity, Samar Abdulla Nasser

Wayne State University Dissertations

Salt sensitivity is associated with a rise in blood pressure (BP) occurring during sodium loading and/or a fall in BP during sodium restriction that exceeds random fluctuations in BP. Salt sensitivity is more common in African American than Caucasian hypertensives and is also present, in normotensive African Americans. The mechanism or mechanisms resulting in salt-sensitive hypertension are multiple and include both activation of the renin angiotensin system via increases in angiotensin II and reductions in the endogenous vasodilator, nitric oxide (NO). An important means of NO downregulation is through asymmetric dimethylarginine (ADMA), an endogenous NO inhibitor, which is largely metabolized …

Muscle Metaboreflex Control Of Coronary Blood Flow And Ventricular Contractility During Dynamic Exercise In Normal And Heart Failure Conditions, Matthew Coutsos

Wayne State University Dissertations

Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. In heart failure, cardiac output does not increase with MMA presumably due to impaired left ventricular contractility, and large decreases in coronary vascular conductance are observed. The purpose of this dissertation is to determine whether the muscle metaboreflex-induced restraint of coronary vasodilation functionally limits coronary blood flow and …

Molecular Mechanisms Of Snare Assembly And Expulsion Of Intravesicular Contents In Cell Secretion, Leah Jiyoung Zhang

Wayne State University Dissertations

For nearly half a century, it was believed that during cell secretion, membrane-bound secretory vesicles completely merge at the cell plasma membrane resulting in the diffusion of intra-vesicular contents to the cell exterior and the compensatory retrieval of the excess membrane by endocytosis. This explanation made no sense or logic, since following cell secretion partially empty vesicles accumulate as demonstrated in electron micrographs. Furthermore, with the `all or none' mechanism of cell secretion by complete merger of secretory vesicle membrane at the cell plasma membrane, the cell is left with little regulation and control of the amount of content release. …

Mechanisms Of Translation Arrest Following Focal Brain Ischemia, Monique K. Lewis

Wayne State University Dissertations

MECHANISMS OF TRANSLATION ARREST FOLLOWING FOCAL BRAIN

ISCHEMIA

by

MONIQUE K. LEWIS

August 2011

Advisor: Dr. Donald DeGracia

Major: Physiology

Degree: Doctor of Philosophy

The loss of blood flow to the brain is termed ischemia and the subsequent resumption of blood flow is termed reperfusion. Brain ischemia and reperfusion (I/R) occurs primarily following resuscitation from cardiac arrest and stroke and presents one of the most significant clinical challenges. At present, there are no clinically effective pharmacologic interventions to halt brain damage following I/R. The major Aim of this dissertation will be to investigate possible mechanisms involved in neuron death following …

Destruction Of Biological Tetrapyrrole Macrocycles By Hypochlorous Acid And Its Scavenging By Lycopene, Dhiman Maitra

Wayne State University Dissertations

Hypochlorous acid (HOCl) is a potent oxidant generated by the hemoprotein myeloperoxidase. Although HOCl plays an important role in the innate immune response,sustained high levels of HOCl has been implicated to play a harmful role. In several pathological conditions such as atherosclerosis, endometriosis and sickle cell disease where HOCl is elevated there are reports of significant free iron accumulation. Free iron is toxic since it can lead to the generation of other secondary free radicals such as hydroxyl radical by Fenton reaction. The exact source and mechanism by which the free iron is generated is not clearly understood. This work …

Cell Lineage Choice During Differentiation Of Trophoblast Stem Cells (Tsc) Is Dependent On Oxygen Levels, And Mediated By Stress Enzyme Pathways And Mitochondrial Function, Sichang Zhou

Wayne State University Dissertations

In general, stress is defined as a noxious factor in a broad spectrum (chemical, biological or physical). Stress response of human body can be divided into three levels----integrate, organ/tissue or cellular response. Trophoblast tem cell (TSC) is one of the earliest differentiated stem cell within blastocyst, which is the stage of preimplantation embryo developed from fertilized egg. Different from another pluripotent embryonic stem cell, which is derived from inner cell mass in blastocyst and develop into fetus, multipotent TSC will specifically differentiate into all kinds of cell subtypes consisting of placenta by which nutrient and oxygen from mom as well …

Mechanisms Of Persistent Translation Arrest Following Global Brain Ischemia And Reperfusion, Jill Theresa Jamison

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF PERSISTENT TRANSLATION ARREST FOLLOWING GLOBAL BRAIN ISCHEMIA and REPERFUSION

by

JILL T. JAMISON

December 2011

Advisor: Donald J. DeGracia, Ph.D.

Major: Physiology

Degree: Doctor of Philosophy

The information presented here studies the mechanisms that underlie persistent translation arrest (TA) following global brain ischemia and reperfusion (I/R). To summarize the main findings I have discovered a new mechanism for prolonged post-ischemic TA that correlated exactly with in vivo translation rates and correlated precisely with cell outcome. Through the extensive colocalization studies, my results indicate that the mRNA granules are ribonomic structures involved with mRNA regulation. This finding is …

The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White

Wayne State University Dissertations

Post-operative adhesion development occurs in the vast majority of patients following abdominal surgery and is a natural occurrence of peritoneal-wound healing. These fibrous bands may form within the first 5-7 days post-surgery and have the ability to cause a distortion in the normal anatomical positioning of abdominal organs. Consequently, adhesions are major contributors to small bowel obstruction, infertility, and severe pelvic and abdominal pain. Physiological processes responsible for adhesion formation remain obscure though it is believed to involve cell migration, proliferation, and differentiation of several cell types including mesothelial cells, fibroblasts, and inflammatory and immune cells. Substances released from these …

Effect Of Exogenous Leptin On Thrombotic And Metabolic Profiles Of Fvb/B6 Lipodystrophic Mice, Hoda Chaouki Kadouh

Wayne State University Theses

Lipodystrophy caused by fat deficiency contributes to metabolic disease for which several treatment modalities have been implemented, with leptin therapy being the most effective to date. In addition to playing a role in energy homeostasis and metabolism, leptin was also shown to play a pro-thrombotic role in mice. This role was not examined in fatless mice, neither was thrombosis measured. The AZIP/F-1 (FVB) lipodystrophic mouse appeared to have a prolonged arterial occlusion time (p〈0.05) in a trial done in our lab, with clotting factors being normal. The present study was designed to observe the thrombotic and metabolic characteristics of fatless …

Neural And Humoral Control Of Regional Vascular Beds Via A1 Adenosine Receptors Located In The Nucleus Of The Solitary Tract, Joseph Martin Mcclure

Wayne State University Dissertations

Previous studies from our laboratory showed that activation of NTS A₁ adenosine

receptors yields variable hemodynamic responses with prevailing pressor and iliac

vasoconstrictor responses. These responses are accompanied with differential

activation of regional sympathetic activity (adrenal>>renal≥lumbar) and inhibition of

baroreflex mechanisms at the level of the NTS. The variability of the hemodynamic

responses was a result of simultaneous Β-adrenergic vasodilation counteracted with

sympathetic and unknown humoral vasoconstriction. Among many potential

vasoconstrictors vasopressin, angiotensin II and circulating norepinephrine were

considered. Therefore, blood pressure and iliac vascular responses evoked by

selective stimulation of NTS A₁ adenosine receptors (CPA 330 …

The Impact Of Mitochondria On Preimplantation Development In The Rhesus Macaque, Tiffini Charieace Gibson

Wayne State University Dissertations

Assisted Reproduction Technologies (ART) have been used to treat infertility since 1790. In the centuries following, dramatic advances have been made in the field of infertility research through the employment of a variety of species. Despite these advances, determination of oocyte and embryo quality remains largely subjective. Ascertainment of methods to measure oocyte and embryo quality to improve selection in ART clinics and increase pregnancy success rates is imperative. These methods are only possible with a more comprehensive understanding of the cellular and molecular properties of oocytes and preimplantation embryos. A key component of all cells, including oocytes and embryos, …

Motivational Profiles And Their Associations With Achievement Outcomes, Bo Shen, Nate Mccaughtry, Jeffrey J. Martin, Mariane Fahlman

Kinesiology, Health and Sport Studies

With the belief that theoretical integration in motivation may help us better understand motivational behavior, we designed this study to explore adolescents’ motivational profiles and their associations with knowledge acquisition, leisure-time exercise behaviors, and cardiorespiratory fitness. Middle school students from a large urban inner-city school district (N = 603, ages 12–14) completed questionnaires assessing motivational constructs and leisure-time exercise behavior. Knowledge and cardiorespiratory fitness were also assessed with a knowledge test and the Progressive Aerobic Cardiovascular Endurance Run (PACER) test, respectively. Using hierarchical cluster analysis, we found that students’ motivation in physical education could be explained from a multi-theoretical …

Student Physical Activity Patterns: Grade, Gender, And Activity Influences, Pamela Hodges Kulinna, Jeffrey J. Martin, Qin Lai, Amy Kliber, Brett Reed

Kinesiology, Health and Sport Studies

The purpose of this study was to determine how physical education students' cardiovascular responses as determined by mean heart rate, standard deviation of heart rate, and percentage of time in target heart rate zone varied according to student characteristics. Participants were 505 students in Grades 3 through 12. The Polar Accurex Plus heart rate telemetry system was used to measure the physiological load on the cardiovascular system. Three-way ANOVA results suggested that heart rate patterns in physical education varied according to gender, grade, and activity. For example, secondary school girls were more active in individual activities while secondary school boys …