Medical Physiology Commons^™

Osteoarthritis, Cerebrovascular Dysfunction And The Common Denominator Of Inflammation: A Narrative Review, B. K. Al-Khazraji, C. T. Appleton, F. Beier, T. B. Birmingham, J. K. Shoemaker

Physiology and Pharmacology Publications

© 2018 The Author(s) Objective: Population-based cohort studies suggest an association between osteoarthritis (OA) and cerebrovascular disease, yet the mechanisms underlying vascular comorbidities in OA remain unclear. The purpose of this narrative review is to discuss the literature examining inflammation in OA with a focus on physiological mechanisms, and whether overlapping mechanisms exist in cerebrovascular dysfunction. Method: A literature search was conducted in PubMed using combinations of search terms: osteoarthritis, cerebrovascular (disease/dysfunction/risk), cardiovascular (disease/dysfunction/risk), aging/ageing, inflammation, inflammatory mediators, cytokine, c-reactive protein, interleukin, advanced glycation end-products, metabolic syndrome, reactive oxidative species, cognitive impairment, (vascular-related) dementia, small cerebral vessel disease, endothelial function, …

Maternal Nicotine Exposure Leads To Augmented Expression Of The Antioxidant Adipose Tissue Triglyceride Lipase Long-Term In The White Adipose Of Female Rat Offspring., Nicole Barra, Taylor Vanduzer, Alison C. Holloway, Daniel B. Hardy

Physiology and Pharmacology Publications

Globally, approximately 10-25% of women smoke during pregnancy. Since nicotine is highly addictive, women may use nicotine containing products like nicotine replacement therapies for smoking cessation, but the long-term consequences of early life exposure to nicotine remain poorly defined. Our laboratory has previously demonstrated that maternal nicotine exposed (MNE) rat offspring exhibit hypertriglyceridemia due to increased hepatic de novo lipogenesis. Hypertriglyceridemia may also be attributed to impaired white adipose tissue (WAT) lipid storage; however, the effects of MNE on WAT are not completely understood. We hypothesize that nicotine-induced alterations in adipose function (e.g. lipid storage) underlie dyslipidemia in MNE adults. …

Multi-Scale Fluid Flow Analysis Of The Cardiovascular System, Zaid Mahmood

Doctoral Dissertations and Master's Theses

The hypoplastic left heart syndrome (HLHS) is one of the rarest congenital heart diseases affecting infants. Out of 150 babies born, one baby suffers from congenital heart disease. Furthermore, nine percent out of those suffering from congenital heart disease specifically suffer from hypoplastic left heart syndrome (HLHS). To this end, the Fontan operation which is a procedure to generate a harmonic blood flow in single functioning ventricle patients has been executed to palliate HLHS patients. In this operation, the inferior vena cava (IVC) and the superior vena cava (SVC), carrying the low-oxygenated blood returning from the lower and upper body …

Melatonin Attenuates Oxidative Stress And Modulates Inflammatory Response After Experimental Burn Trauma, Minka Hristova, Ganka Bekyarova, Milena Atanasova, Maria Tzaneva

Journal of Mind and Medical Sciences

Introduction. Thermal injury activates an inflammatory response. Melatonin possesses anti-oxidant and anti-inflammatory properties. The objective of the present work was to study melatonin effects on the inflammatory response under conditions of oxidative stress during the early stage of thermal injury.

Materials and methods. We used 24 white male rats of Wistar breed, randomly divided into three experimental groups. Group one was the control, group two was inflicted with burn trauma, and group three was inflicted with burn trauma, with melatonin application following the thermal injury. Melatonin was applied twice in doses of 10 g/kg b.m. immediately after the burn trauma …

The Mind-Body Problem; Three Equations And One Solution Represented By Immaterial-Material Data, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

Human life occurs within a complex bio-psycho-social milieu, a heterogeneous system that is integrated by multiple bidirectional interrelations existing between the abstract-intangible ideas and physical-chemical support of environment. The mind is thus placed between the abstract ideas/ concepts and neurobiological brain that is further connected to environment. In other words, the mind acts as an interface between the immaterial (abstract/ intangible) data and material (biological) support. The science is unable to conceives and explains an interaction between the immaterial and material domains (to understand nature of the mind), this question generating in literature the mind-body problem. We have published in …

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships In Healthy Humans, Matthew Sherwood, Richard A. Mckinley, Danielle Boeke, Jason G. Parrker, Lindsey K. Mcintire, Justin M. Nelson, Catherine Fletchall, Natasha Alexander, Amanda Mcconnell, Chuck Goodyear, Jeremy T. Nelson, Nathaniel R. Bridges

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling At The Mouse Neuromuscular Junction, Xueyong Wang, J. Michael Mcintosh, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion …

Trpm7 Current Inactivation: Evidence For Inside-Out Signaling, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 channels conduct metal cations such as Na+, K+, Ca2+ and Mg2+. In the presence of external Ca2+/Mg2+ TRPM7 has a steeply outwardly rectifying current-voltage (I-V) relation. In the absence of Ca2+/Mg2+ the IV becomes semi-linear. This has been explained by the removal of pore blockade by divalent cations (e.g. Ca2+o/Mg2+o). TRPM7 channels are inhibited by cytoplasmic Mg2+ in a voltage-independent manner, primarily by a reversible reduction in the overall number of conducting channels. Here, we have examined the consequences of external Ca2+ removal and reintroduction on TRPM7 current kinetics. In whole-cell patch clamp with low internal Mg2+, we rapidly …

Inactivation Of Trpm7 Kinase In Mice Results In Enlarged Spleens, Reduced T-Cell Proliferation And Diminished Store-Operated Calcium Entry, Pavani Beesetty, Krystyna Blanka Wieczerzak, Jennifer Gibson, Taku Kaitsuka, Charles Tuan Luu, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca2+ in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates. TRPM7 current magnitudes in WT and KD mouse T cells were, however, similar. We tested the dependence of T-cell …

Physiological And Cognitive Factors Related To Human Performance During The Grand Canyon Rim-To-Rim Hike, Kristin Divis, Clifford Anderson-Bergman, Robert Abbott, Victoria Newton, Glory Emmanuel-Aviña

Journal of Human Performance in Extreme Environments

Exposure to extreme environments is both mentally and physically taxing, leading to suboptimal performance and even life-threatening emergencies. Physiological and cognitive monitoring could provide the earliest indicator of performance decline and inform appropriate therapeutic intervention, yet little research has explored the relationship between these markers in strenuous settings. The Rim-to-Rim Wearables at the Canyon for Health (R2RWATCH) study is a research project at Sandia National Laboratories funded by the Defense Threat Reduction Agency to identify which physiological and cognitive phenomena collected by non-invasive wearable devices are the most related to performance in extreme environments. In a pilot study, data were …

Loss Of The Intellectual Disability And Autism Gene Cc2d1a And Its Homolog Cc2d1b Differentially Affect Spatial Memory, Anxiety, And Hyperactivity, Marta Zamarbide, Adam Oaks, Heather Pond, Julia Adelman, M. Chiara Manzini

Pharmacology and Physiology Faculty Publications

Hundreds of genes are mutated in non-syndromic intellectual disability (ID) and autism spectrum disorder (ASD), with each gene often involved in only a handful of cases. Such heterogeneity can be daunting, but rare recessive loss of function (LOF) mutations can be a good starting point to provide insight into the mechanisms of neurodevelopmental disease. Biallelic LOF mutations in the signaling scaffold CC2D1Acause a rare form of autosomal recessive ID, sometimes associated with ASD and seizures. In parallel, we recently reported that Cc2d1a-deficient mice present with cognitive and social deficits, hyperactivity and anxiety. In Drosophila, loss of the only …

Optimization Of Wavelength Selection For Multispectral Image Acquisition: A Case Study Of Atrial Ablation Lesions, Huda Asfour, S. Guan, Narine Muselimyan, Luther M. Swift, Murray Loew, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

In vivo autofluorescence hyperspectral imaging of moving objects can be challenging due to motion artifacts and to the limited amount of acquired photons. To address both limitations, we selectively reduced the number of spectral bands while maintaining accurate target identification. Several downsampling approaches were applied to data obtained from the atrial tissue of adult pigs with sites of radiofrequency ablation lesions. Standard image qualifiers such as the mean square error, the peak signal-to-noise ratio, the structural similarity index map, and an accuracy index of lesion component images were used to quantify the effects of spectral binning, an increased spectral distance …

Group Ii Innate Lymphoid Cells And Microvascular Dysfunction From Pulmonary Titanium Dioxide Nanoparticle Exposure, Alaeddin Bashir Abukabda, Carroll Rolland Mcbride, Thomas Paul Batchelor, William Travis Goldsmith, Elizabeth Compton Bowdridge, Krista Lee Garner, Sherri Friend, Timothy Robert Nurkiewicz

Faculty & Staff Scholarship

Background: The cardiovascular effects of pulmonary exposure to engineered nanomaterials (ENM) are poorly understood, and the reproductive consequences are even less understood. Inflammation remains the most frequently explored mechanism of ENM toxicity. However, the key mediators and steps between lung exposure and uterine health remain to be fully defined. The purpose of this study was to determine the uterine inflammatory and vascular effects of pulmonary exposure to titanium dioxide nanoparticles (nano-TiO2). We hypothesized that pulmonary nano-TiO2 exposure initiates a Th2 inflammatory response mediated by Group II innate lymphoid cells (ILC2), which may be associated with an impairment in uterine microvascular …

Experimental Intravascular Hemolysis Induces Hemodynamic And Pathological Pulmonary Hypertension: Association With Accelerated Purine Metabolism, Victor P. Bilan, Frank Schneider, Enrico M. Novelli, Eric E. Kelley, Sruti Shiva, Mark T. Gladwin, Edwin K. Jackson, Stevan P. Tofovic

Faculty & Staff Scholarship

Pulmonary hypertension (PH) is emerging as a serious complication associated with hemolytic disorders, and plexiform lesions (PXL) have been reported in patients with sickle cell disease (SCD). We hypothesized that repetitive hemolysis per se induces PH and angioproliferative vasculopathy and evaluated a new mechanism for hemolysis-associated PH (HA-PH) that involves the release of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) from erythrocytes. In healthy rats, repetitive admin- istration of hemolyzed autologous blood (HAB) for 10 days produced reversible pulmonary parenchymal injury and vascular remodeling and PH. Moreover, the combination of a single dose of Sugen-5416 (SU, 200mg/kg) and 10-day …

Hcn2 Channels In The Ventral Tegmental Area Regulate Behavioral Responses To Chronic Stress, Peng Zhong, Casey R. Vickstrom, Xiaojie Liu, Ying Hu, Laikang Yu, Han-Gang Yu, Qing-Song Liu

Faculty & Staff Scholarship

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization- activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was …

Sympatho-Excitatory Response To Pulmonary Chemosensitive Spinal Afferent Activation In Anesthetized, Vagotomized Rats, Julia A. Shanks, Zhiqiu Xia, Steven J. Lisco, George J. Rozanski, Harold D. Schultz, Irving H. Zucker, Han-Jun Wang

Journal Articles: Cellular & Integrative Physiology

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application …

Rhythm: An Open Source Imaging Toolkit For Cardiac Panoramic Optical Mapping, Christopher Gloschat, Kedar Aras, Shubnam Gupta, N. Rokhana Faye, Hanyu Zhang, Matthew W. Kay, Igor R Efimov, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Fluorescence optical imaging techniques have revolutionized the field of cardiac electrophysiology and advanced our understanding of complex electrical activities such as arrhythmias. However, traditional monocular optical mapping systems, despite having high spatial resolution, are restricted to a two-dimensional (2D) field of view. Consequently, tracking complex three-dimensional (3D) electrical waves such as during ventricular fibrillation is challenging as the waves rapidly move in and out of the field of view. This problem has been solved by panoramic imaging which uses multiple cameras to measure the electrical activity from the entire epicardial surface. However, the diverse engineering skill set and substantial resource …

Novel Antioxidant Properties Of Doxycycline, Dahn L. Clemens, Michael J. Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob D. Mcgowan, Carlos D. Hunter, Sarah L. Schlichte, Jun Tian, Lynell W. Klassen, James R. O'Dell, Geoffrey M. Thiele, Ted R. Mikuls, Matthew C. Zimmerman, Daniel R. Anderson

Journal Articles: Cellular & Integrative Physiology

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen …

Influence Of Resistance Training On Vascular Function, Hemodynamic, And Perceived Exertion Responses To Fixed Submaximal Workloads In Patients With Coronary Disease, Kerstin Grafe

Master's Theses and Doctoral Dissertations

PURPOSE: To determine the impact of superimposed resistance training (RT) in aerobically trained coronary patients on systolic blood pressure (SBP), heart rate (HR), rating of perceived exertion (RPE; 6–20 scale), and rate pressure product (RPP) at fixed submaximal workloads following a 12-week RT intervention. Additionally, pre-and post-RT measures of brachial artery reactivity, an index of endothelial function, were obtained. METHODS: Fifteen low risk coronary patients (13 men, 2 women; mean ± SD age = 66.1 ± 5.1 yrs) completed a progressive 12-week RT program that complemented their regular aerobic training regimen. Prior to training, SBP, HR, RPP, and RPE were …