Physiology Commons^™

Calponin And Cytoskeleton Dynamics In Macrophage Functions And The Pathogenesis Of Atherosclerosis, Rong Liu

Wayne State University Dissertations

Arterial atherosclerosis is an inflammatory disease. Macrophages play a major role in the pathogenesis and progression of atherosclerotic lesions. Modulation of macrophage function is a therapeutic target for the treatment of atherosclerosis. Calponin is an actin-filament-associated regulatory protein that inhibits the activity of myosin-ATPase and dynamics of the actin cytoskeleton. Encoded by the Cnn2 gene, calponin isoform 2 is expressed at significant levels in macrophages. Deletion of calponin 2 increases macrophage migration and phagocytosis. In the present study, we investigated the effect of deletion of calponin 2 in macrophages on the pathogenesis and development of atherosclerosis. The results showed that …

Muscle Metaboreflex And Arterial Baroreflex: Action, Interaction And Altered Control In Heart Failure, Jasdeep Kaur

Wayne State University Dissertations

Stimulation of skeletal muscle afferents by metabolites that accumulate in the exercising muscle elicits a large pressor response, termed the muscle metaboreflex. Muscle metaboreflex activation during submaximal exercise induces large increases in arterial pressure, cardiac output, heart rate and ventricular contractility however, the vascular responses have varied in previous studies. We addressed three specific questions: 1) what are the mechanism(s) regulating the non-ischemic vasculature during muscle metaboreflex activation in normal subjects, 2) whether muscle metaboreflex activation vasoconstricts the ischemic active muscle from which this reflex originates and if this vasoconstriction is exaggerated in heart failure and 3) how do the …

An Analysis Of Plasticity In The Rat Respiratory System Following Cervical Spinal Cord Injury And The Application Of Nanotechnology To Induce Or Enhance Recovery Of Diaphragm Function, Janelle Lorien Walker

Wayne State University Dissertations

Second cervical segment spinal cord hemisection (C2Hx) results in ipsilateral hemidiaphragm paralysis. However, the intact latent crossed phrenic pathway can restore function spontaneously over time or immediately following drug administration.

WGA bound fluorochromes were administered to identify nuclei associated with diaphragm function in both the acute and chronic C2Hx models. WGA is unique in that it undergoes receptor mediated endocytosis and is transsynaptically transported across select physiologically active synapses. Comparison of labeling in the acutely injured to the chronically injured rat provided an anatomical map of spinal and supraspinal injury induced synaptic plasticity. The plasticity occurs over time in the …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

The Impact Of Myeloperoxidase And Its Related Oxidants On Metaphase Ii Mouse Oocyte Quality, Faten Nuri Shaeib

Wayne State University Dissertations

Inflammatory reactions mediated by oxidative stress (OS) have been implicated in the deterioration of oocyte quality, which may lead to subfertility. Oxidative stress generated from enhancement of activated macrophages secondary to an inflammatory response are the major source of reactive oxygen species (ROS) such as superoxide (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and hypochlorous acid (HOCl), as well as, the pro-inflammatory enzyme myeloperoxidase (MPO). Previously, it has been shown that these ROS have deleterious effect on oocytes; however the link between inflammation through macrophage activity and oocyte quality remains unclear. In this work, we investigated: 1) the mechanism through …

The Role Of Alarmins, Invariant Nkt Cells And Senescence In The Pathophysiology Of Sterile Intra-Amniotic Inflammation, Olesya Plazyo

Wayne State University Dissertations

Preterm birth is defined as the delivery of a live baby prior to the 37th week of gestation. It is the leading cause of neonatal mortality worldwide. Preterm neonates are at a higher risk for short- and long-term complications, and prematurity places significant burden on our society. Elucidation of the mechanisms that lead to spontaneous preterm labor will enable development of therapies to prevent this syndrome. We aimed to study pathological inflammation that is implicated in the pathophysiology of spontaneous preterm labor.

Pathological inflammation can be initiated by the activation of innate immunity either by microorganisms or alarmins, which are …

Role Of Secretory Granule Heterogeneity In Calcium-Triggered Exocytosis, Tejeshwar Rao

Wayne State University Dissertations

The sympathetic nervous system is activated by a variety of threats to organismal homeostasis. The adrenomedullary chromaffin cell is the core effector of sympathetic activity in the peripheral nervous system. By design, the chromaffin cell secretory response is mutable so that release can be rapidly tuned to drive context-dependent changes in physiological function. However, the mechanisms by which this tuning is achieved with such high temporal fidelity and context specificity remain unclear. This represents a major gap in our understanding of the sympatho-adrenal system since it is known to modify the function of nearly every organ system in the body. …

Co-Ingestion Of Carbohydrate With Branched-Chain Amino Acids Or L-Leucine Does Not Preferentially Increase Serum Igf-1 And Expression Of Myogenic-Related Genes In Response To A Single Bout Of Resistance Exercise, Rui Li, Maria Pontes Ferreira, Matthew B. Cooke, Paul La Bounty, Bill Campbell, Mike Greenwood, Darren S. Willoughby, Richard B. Kreider

Nutrition and Food Science Faculty Research Publications

This study determined if the co-ingestion of carbohydrate (CHO) with branched-chain amino acids (BCAA) or L-leucine (LEU) preferentially affected serum IGF-1 and the expression of myogenic-related genes in response to resistance exercise (RE). Forty one, college-age males were randomly assigned to 1 of 4 groups: CHO, CHO-BCAA, CHO-LEU, or placebo (PLC). Resistance exercise consisted of 4 sets of leg press and leg extension at 80% 1RM. Supplements were ingested peri-exercise, and venous blood and muscle biopsies were obtained pre-exercise (PRE), and at 30, 120, and 360 min post-exercise. Serum IGF-1 was determined with ELISA, and skeletal muscle mRNA expression of …

Unstable Ventilatory Control During Sleep After High Spinal Cord Injury: The Contribution Of Chemosensitivity And Hypoventilation, Amy Therese Bascom

Wayne State University Dissertations

ABSTRACT

UNSTABLE VENTILATORY CONTROL DURING SLEEP AFTER HIGH SPINAL CORD INJURY: THE CONTRIBUTION OF CHEMOSENSITIVITY AND HYPOVENTILATION

by

Amy T. Bascom

May 2015

Advisor: Dr. Harry G. Goshgarian

Major: Anatomy and Cell Biology

Degree: Doctor of Philosophy

A high prevalence of sleep-disordered breathing (SDB) after spinal cord injury (SCI) has been reported in the literature; however, the underlying mechanisms are not well understood. My studies had 2 aims: 1) to determine the effect of the withdrawal of the wakefulness drive to breathe on the degree of hypoventilation in SCI patients and able-bodied controls and 2) to determine the response of …

Preclinical Evaluation Of Infrared Light Therapy In A Rat Model Of Neonatal Hypoxic-Ischemic Encephalopathy, Christian Andrew Reynolds

Wayne State University Dissertations

Hypoxic events encountered during the perinatal period leading to pathologic decreases in fetal cerebral oxygen availability are detrimental resulting in neonatal hypoxic-ischemic encephalopathy (HIE). This work focused on the characterization of a rat model of neonatal HIE for use in the preclinical evaluation of infrared light therapy (IRL). Consistent with results from previous IRL efficacy studies using a rat model of adult global brain ischemia, IRL treatment attenuated cerebral injury resulting from hypoxia-ischemia in the neonatal rat. Thus, and perhaps most importantly, this work contributes to the development of a potential novel therapeutic approach in the management of brain injuries …

Crebh, A Novel Liver Clock Keeper For Energy Metabolism, Ze Zheng

Wayne State University Dissertations

Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Cyclic AMP responsive element binding protein 3-like 3 (CREB3L3, also known as CREBH) is a liver-enriched, endoplasmic reticulum (ER)-tethered transcription factor known to regulate hepatic acute-phase response and energy homeostasis under stress conditions. Here, we demonstrate that CREBH is regulated by the circadian clock and functions as a diurnal regulator of hepatic lipid and glucose metabolism. CREBH is required to maintain circadian profiles of blood triglycerides, fatty acids, and glucose as well as hepatic glycogen storage. CREBH rhythmically regulates expression levels and amplitudes …

Trophoblast Retrieval And Isolation From The Cervix (Tric) For Non-Invasive Prenatal Genetic Diagnosis And Prediction Of Abnormal Pregnancy Outcome, Rani Fritz

Wayne State University Dissertations

The placenta is vital for the short- and long-term health of the fetus, and significantly impacts the health of the mother. During the first and second trimesters of pregnancy, extravillous trophoblast (EVT) cells invade the uterus and remodel the maternal spiral arteries, which, if inadequate, leads to pregnancy complications, including early pregnancy loss (EPL), preeclampsia (PE), and intra-uterine growth restriction (IUGR). EVT migration into the uterine wall is dependent on growth factors and cytokines that signal between maternal and fetal tissues. The epidermal growth factor (EGF) signaling system plays a significant role in trophoblast function. Using immunocytochemistry (ICC), we evaluated …

The Acute And Chronic Effects Of Resveratrol On Renal Function And Blood Pressure, Kevin L. Gordish

Wayne State University Dissertations

We investigated the acute and chronic effects of resveratrol on renal function and blood pressure. We hypothesized that resveratrol would act as a renal vasodilator through a nitric oxide-dependent mechanism. In our acute studies, we found an intravenous bolus of resveratrol influenced changes in renal hemodynamics by increasing renal blood flow and decreasing renal vascular resistance. The mechanism of renal vasodilation was nitric oxide dependent and through a reduction of endogenous reactive oxygen species. Resveratrol-induced renal vasodilation was not influenced by COX metabolism and vasodilatory prostanoids. We found with continuous intravenous resveratrol infusion induced significant renal vasodilation while not altering …

Investigation Of Whether Sedentary And Physically Active Conditions Lead To Altered Gabaergic Signaling In The Rvlm, Maryetta Donna Dombrowski

Wayne State University Dissertations

Investigation of whether sedentary and physically active conditions lead to altered GABAergic signaling in the RVLM

MD Dombrowski, and PJ Mueller

Department of Physiology, Wayne State University, School of Medicine, Detroit, MI

A sedentary lifestyle is a major risk for cardiovascular disease. Cardiovascular disease has been associated with elevated basal sympathetic nerve activity. The rostral ventrolateral medulla is a bilateral brainstem region that is an important for the control of resting and reflex control of sympathetic nerve activity and blood pressure. The activity of these neurons in this region is tonically inhibited by the neurotransmitter γ-butyric amino acid (GABA). Interestingly, …

Self-Construal Moderates Testosterone Reactivity To Competitive Outcomes, Keith Welker

Wayne State University Dissertations

Previous research shows that testosterone reactivity to competitive outcomes predicts aggressive behavior in men. However, some studies have failed to find these effects, and it has been suggested that individual differences moderate the relationships between competitive outcomes, testosterone fluctuations, and aggressive behavior. The current research examined whether one individual difference--self-construal--would moderate these effects. In Study 1, participants were assigned to win or lose a competitive video game and engaged in a reactive aggression task. Results indicated that increases in testosterone in response to winning and decreases in response to losing occurred in men with independent, not interdependent, self-construals. These changes …

Ribonomic Control During Global Brain Ischemia And Reperfusion, Haihui Wang

Wayne State University Dissertations

Abstract

RIBONOMIC CONTROL DURING GLOBAL BRAIN ISCHEMIA AND REPERFUSION

by HAIHUI WANG

August 2014

Advisor: Donald J. DeGracia, Ph.D.

Major: Physiology

Degree: Doctor of Philosophy

The study presented here used "omic" technology to look at the mechanism behind the selective delayed death of hippocampus CA1 neurons after transient global brain ischemia. The main findings are summarized:

1. The main form of ELAV protein family member detected in CA1/CA3 in Hu protein immunoprecipitation and polysomes was HuB (Rel-N1). HuB is present in control CA3, 8 hr reperfused CA3, and 8 hr reperfused CA1, but absent from control CA1. AUF-1, hnRNP K, …

Peri-Exercise Co-Ingestion Of Branched-Chain Amino Acids And Carbohydrate In Men Does Not Preferentially Augment Resistance Exercise-Induced Increases In Pi3k/Akt-Mtor Pathway Markers Indicative Of Muscle Protein Synthesis, Maria Pontes Ferreira, Rui Li, Matthew Cooke, Richard B. Kreider, Darryn S. Willoughby

Nutrition and Food Science Faculty Research Publications

The effects of a single bout of resistance exercise (RE) in conjunction with peri-exercise branched chain amino acid (BCAA) and carbohydrate (CHO) ingestion on skeletal muscle signaling markers indicative of muscle protein synthesis (MPS) were determined. It was hypothesized that CHO + BCAA would elicit a more profound effect on these signaling markers compared to CHO. Twenty-seven males were randomly assigned to CHO, CHO + BCAA, or placebo (PLC) groups. Four sets of leg presses and leg extensions were performed at 80% 1RM. Supplements were ingested 30 min and immediately prior to and after RE. Venous blood and muscle biopsy …

Regulation Of Nkcc2 Trafficking By Vesicle Fusion Proteins Vamp2 And Vamp3 In The Thick Ascending Limb, Paulo Sebastian Caceres Puzzella

Wayne State University Dissertations

The thick ascending limb (TAL) in the kidney regulates extracellular fluid volume and blood pressure. The Na/K/2Cl cotransporter NKCC2 plays a central role in NaCl absorption by the TAL and blood pressure. NKCC2 trafficking to the apical membrane is a major mechanism to control NKCC2 activity. However, little is known about the proteins that mediate NKCC2 trafficking. Inhibition of the vesicle fusion proteins VAMP2 and VAMP3 blunts the increase in surface NKCC2 expression and NaCl absorption in response to stimulation by cAMP. In other cells, VAMPs mediate fusion of exocytic vesicles with the plasma membrane. Whether VAMP2 and VAMP3 mediate …

Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong

Wayne State University Dissertations

Mitochondrial fusion and fission, collectively termed mitochondrial dynamics, are among the core mechanisms responsible for maintaining mitochondrial health and functional integrity. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. Recent studies suggest that i) mitochondrial dynamics, particularly, mitochondrial fission, serves as a mediator of cell fate in the setting of ischemia-reperfusion (IR) injury, and, ii) inhibition of DRP1 and mitochondrial fission provides cardioprotection against IR injury. However, the precise role of DRP1 translocation to mitochondria in the pathogenesis of myocardial ischemia-reperfusion injury has not been established.

Using an established model of hypoxia-reoxygenation (HR) in cultured HL-1 cardiomyocytes, …

Muscle Metaboreflex Control Of Cardiovascular Function In Hypertension, Marty Daniel Spranger

Wayne State University Dissertations

Skeletal muscle ischemia during or immediately following exercise leads to the accumulation of metabolites (e.g., lactate, proton and diprotonated phosphate) which activate chemoreceptive afferents within the muscle leading to a reflex increase in sympathetic outflow generating substantial increases in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) - termed the muscle metaboreflex. When the reflex is activated during submaximal dynamic exercise, the pressor response occurs via increased CO with no net peripheral vasoconstriction. When metaboreflex activation is sustained during the recovery from exercise (i.e., post-exercise muscle ischemia - (PEMI)), whereas MAP remains elevated for as long as …

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 Nh2-Hypervariable Region Modulates The Binding Affinity Of Troponin T For Tropomyosin, Chinthaka Kaushalya Amarasinghe

Wayne State University Theses

The troponin complex plays a central role in the allosteric function of sarcomeric thin filaments by enacting conformational changes during the Ca2+-regulated contraction and relaxation of striated muscle. The troponin subunit T (TnT) has two binding sites for tropomyosin (Tm) and is responsible for anchoring the troponin complex to the thin filament. Although the C-terminal and middle regions of the TnT polypeptide chain are highly conserved among the three muscle type isoforms, the hypervariable N-terminal region has evolutionarily diverged significantly among isoforms. Previous studies have shown that the N-terminal variable region fine-tunes Ca2+ regulation of muscle contractility via modulation of …

Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang

Wayne State University Dissertations

ABSTRACT

BLAST-INDUCED TINNITUS: A COMBINED BEHAVIORAL, MEMRE, AND ELECTROPHYSIOLOGY STUDY

by

JESSICA OUYANG

May 2014 Advisor: Drs. Steve Cala & Jinsheng Zhang

Major: Physiology

Degree: Doctor of Philosophy

Tinnitus and hearing loss are the frequent auditory-related co-morbidities of blast trauma. The etiology of blast-induced tinnitus is also muddled by brain mechanisms associated with emotional and cognitive problems such as anxiety, memory loss, and depression. We set out to develop a realistic and ecologically valid model to address changes of cognitive status and psychological state that are associated with blast- induced tinnitus. In this study, 19 adult rats were randomly divided …

The Effect Of Body Position On Cerebral Bllod Flow, Cognition, Cardiac Output, Map,And Motor Function In Patients Undergoing Shoulder Surgery : Lateral Versus Beach Chair Position Under General Anesthesia, Kelley Labonty

Wayne State University Dissertations

ABSTRACT

The Effect of Body Position on Changes in Cerebral Blood Flow, Cognition, and Motor Function in Patients Undergoing Shoulder Surgery: Lateral versus Beach Chair Position Under General Anesthesia

By

KELLEY LABONTY

December 2013

Advisor: Dr. Steven Cala

Major: Physiology

Degree: Doctor of Philosophy

This study aims to determine if there are alterations in cerebral perfusion in patients undergoing general anesthesia in the sitting position. With the reporting of 15 catastrophic cerebral vascular accidents recently being published during shoulder surgery in the sitting position, an increase of 90 times from previously reported data, there has become a clear need for …

Altered Morphology And Composition Of Zymogen Granules In Acute Pancreatitis, Amanda Flack

Wayne State University Dissertations

In healthy physiology, pancreatic digestive enzymes secreted following a meal are stored as inactive zymogens within membrane bound secretory vesicles called Zymogen Granules (ZG), and activated extracellularly. In acute pancreatitis however, the digestive enzymes are prematurely activated within the cell, resulting in autodigestion of the tissue. Pancreatitis is a gastrointestinal disorder in which there are over 200,000 hospitalizations per year with a 5% mortality rate. It has been demonstrated that in acute pancreatitis the digestive enzymes are blocked from being secreted and are activated within the cell leading to acinar cell and surrounding pancreatic tissue death. Little is known about …

Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman

Wayne State University Dissertations

Junctional SR is an important and unique ER subdomain in the adult myocyte that releases Ca2+ through the actions of an exclusive set of resident proteins. Cardiac calsequestrin (CSQ2) undergoes two co-translational modifications: N-linked glycosylation on 316Asn, and phosphorylation by protein kinase CK2 on a cluster of 3 serines in its tail. In the heart, CSQ2 molecules undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. To investigate CSQ2 protein processing in cardiomyopathy models, studies were performed to test whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced into …

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, …

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 …