Medical Physiology Commons^™

The Minimum M3-M4 Loop Length Of Neurotransmitter-Activated Pentameric Receptors Is Critical For The Structural Integrity Of Cytoplasmic Portals, Daniel T. Baptista-Hon, Tarek Z. Deeb, Jeremy J. Lambert, John A. Peters, Tim G. Hales

Pharmacology and Physiology Faculty Publications

The 5-HT₃A receptor homology model, based on the partial structure of the nicotinic acetylcholine receptor from Torpedo marmorata, reveals an asymmetric ion channel with five portals framed by adjacent helical amphipathic (HA) stretches within the 114-residue loop between the M3 and M4 membrane-spanning domains. The positive charge of Arg-436, located within the HA stretch, is a rate-limiting determinant of single channel conductance (γ). Further analysis reveals that positive charge and volume of residue 436 are determinants of 5-HT₃A receptor inward rectification, exposing an additional role for portals. A structurally unresolved stretch of 85 residues constitutes …

Vegf And Sympathetic Perivascular Nerves Contribute To Hypoxic Remodeling Of Ovine Cranial Arteries, Olayemi Olufikayo Adeoye

Loma Linda University Electronic Theses, Dissertations & Projects

Chronic hypoxia complicates many pregnancies and can result in postnatal pathologies that include compromised fetal cardiovascular structure and function. Mechanisms involved remain unclear. Because hypoxia increases production of VEGF, known to modulate smooth muscle (SM) phenotype, this thesis explored the hypothesis that VEGF contributes to hypoxic fetal vascular remodeling through direct effects on SM cells and indirectly through perivascular nerves. Using a chronic hypoxia sheep model, this work demonstrated that: 1) hypoxia potently upregulates VEGF receptor expression but not endogenous VEGF level in fetal ovine carotid arteries; 2) both chronic hypoxia and VEGF exert similar effects on smooth muscle contractile …

Vbp15, A Glucocorticoid Analogue, Is Effective At Reducing Allergic Lung Inflammation In Mice, Jesse M. Damsker, Blythe C. Dillingham, Mary C. Rose, Molly A. Balsley, Christopher R. Heier, Alan M. Watson, Erik J. Stemmy, Rosalyn A. Jurjus, Tony Huynh, Kathleen Tatem, Kitipong Uaesoontrachoon, Dana M. Berry, Angela S. Benton, Robert J. Freishtat, Eric P. Hoffman, John M. Mccall, Heather Gordish-Dressman, Stephanie L. Constant, Erica K.M. Reeves, Kanneboyina Nagaraju

Pharmacology and Physiology Faculty Publications

Asthma is a chronic inflammatory condition of the lower respiratory tract associated with airway hyperreactivity and mucus obstruction in which a majority of cases are due to an allergic response to environmental allergens. Glucocorticoids such as prednisone have been standard treatment for many inflammatory diseases for the past 60 years. However, despite their effectiveness, long-term treatment is often limited by adverse side effects believed to be caused by glucocorticoid receptor-mediated gene transcription. This has led to the pursuit of compounds that retain the anti-inflammatory properties yet lack the adverse side effects associated with traditional glucocorticoids. We have developed a novel …

Oxidation Of Thrombomodulin Methionine 388 In Cigarette Smokers, Samrat B. Thapa

Graduate Theses and Dissertations

This work tested the hypothesis that oxidation of methionine 388 in thrombomodulin is higher in cigarette smokers, and thus a likely contributor towards the hypercoagulable state in smokers. Thrombomodulin, a protein cofactor found on endothelial cell surfaces, regulates the activity of thrombin. Thrombin bound to thrombomodulin no longer converts fibrinogen to fibrin, but instead activates Protein C which, in turn, stops the coagulation cascade by inactivation of clotting factors. The oxidation of methionine 388 of thrombomodulin has been shown in vitro to dramatically decrease the anticoagulant cofactor activity of thrombomodulin. The blood of cigarette smokers is more prone to clot …

Effect Of Racing Flats On Running Economy In Male Adolescent Runners, Paul Hafen

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to investigate whether running economy differs in racing flats versus standard running shoes in high school cross-country runners. In order to measure running economy the oxygen cost of running (mL O₂∙kg^-1∙min^-1) was measured in 20 male adolescent runners (mean age = 16.25 ± 0.97 years, 5 km best time = 17.52 ± 0.78 min) when running two separate trials at a controlled speed. The speed was determined by estimating treadmill running speed at 85% of each runner's VO_2max. Each trial required the participants to run while …

Oxidative Stress For An Acute Bout Of Bikram Yoga In Healthy, Trained Adults, Kimberly Anne Trocio

UNLV Theses, Dissertations, Professional Papers, and Capstones

BACKGROUND:Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original "hot" yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate …

Maintenance Of Mitochondrial Genomic Integrity In The Absence Of Manganese Superoxide Dismutase In Mouse Liver Hepatocytes., Anthony R. Cyr, Kyle E. Brown, Michael L. Mccormick, Mitchell C. Coleman, Adam J. Case, George S. Watts, Bernard W. Futscher, Douglas R. Spitz, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously expressed mitochondrial antioxidant enzyme that is essential for mammalian life. Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal stage, which renders the longitudinal study of the biochemical and metabolic effects of Sod2 loss difficult. However, multiple studies have demonstrated that tissue-specific knockout of Sod2 in murine liver yields no observable gross pathology or injury to the mouse. We hypothesized that Sod2 loss may have sub-pathologic effects on liver biology, including the acquisition of reactive oxygen species-mediated mitochondrial DNA mutations. To evaluate this, we established …

Association Between The Luteinizing Hormone/Chorionic Gonadotropin Receptor (Lhcgr) Rs4073366 Polymorphism And Ovarian Hyperstimulation Syndrome During Controlled Ovarian Hyperstimulation, Travis J. O'Brien, Mariah M. Kalmin, Arthur F. Harralson, Adam M. Clark, Ian Gindoff, Samuel J. Simmens, David Frankfurter, Paul Gindoff

Pharmacology and Physiology Faculty Publications

Background

The aim of this study was to determine the relationship between a purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation (COH).

Methods

This was a prospective study of 172 patients undergoing COH at the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a region encompassing the insLQ polymorphism was sequenced. We also investigated a polymorphism (rs4073366 G > C) that was 142 bp frominsLQ. The association of the insLQ and rs4073366 alleles and outcome to COH (number of mature follicles, …

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …

Periodic Arrays Of Gold Nano-Disks Coupled With Evanescent Spectroscopy, Hao Jiang, Touraj Manifar, Aref Bakhtazad, Hossein Hojjati, Jayshr Sabarinathan, Silvia Mittler

Physiology and Pharmacology Publications

We study and analyze various spectral features of gold nano-disk arrays coupled with the evanescent field of an optical waveguide using finite difference time domain simulations for comparison to our previous work on this topic (Jiang et al, Journal of Lightwave Technology 27, no.13, (2009): 2264-2270). We find that the quadrupolar and dipolar peaks are both heavily dependent on the coherent interactions of the periodic array and show comparable performance for refractive index sensing applications. We also find sharp extinction peaks and dips in the simulated spectra, but they are not sensitive to the index change of the surface-bound layer. …

Acute Vibration Induces Transient Expression Of Anabolic Genes In The Murine Intervertebral Disc, Matthew R. Mccann, Priya Patel, Kim L. Beaucage, Yizhi Xiao, Corey Bacher, Walter L. Siqueira, David W. Holdsworth, S. Jeffrey Dixon, Cheryle A. Séguin

Physiology and Pharmacology Publications

No abstract provided.

Orientation Distribution Of Highly Oriented Type I Collagen Deposited On Flat Samples With Different Geometries, Qamrun Nahar, David Minh Luan Quach, Behafarid Darvish, Harvey A. Goldberg, Bernd Grohe, Silvia Mittler

Physiology and Pharmacology Publications

The structural arrangement of type I collagen in vivo is critical for the normal functioning of tissues, such as bone, cornea, tendons and blood vessels. At present, there are no established low-cost techniques for fabricating aligned collagen structures for applications in regenerative medicine. Here, we report on a straightforward approach to fabricate collagen films, with defined orientation distributions of collagen fibrillar aggregates within a matrix of oriented collagen molecules on flat sample surfaces. Langmuir Blodgett (LB) technology was used to deposit thin films of oriented type I collagen onto flat substrates exhibiting various shapes. By varying the shapes of the …

Surface Immobilized Gold Nanoparticles By Organometallic Chemical Vapor Deposition On Amine Terminated Glass Surfaces, Erden Ertorer, Jessica C. Avery, Laura C. Pavelka, Silvia Mittler

Physiology and Pharmacology Publications

We describe the growth of surface immobilized gold nanoparticles with organometallic chemical vapour deposition (OMCVD) on amine terminated surfaces, utilizing (trimethylphospine)methylgold ((CH3)3PAuCH3) precursor. Samples fabricated using different deposition times were characterized by UV-Vis spectroscopy and scanning electron microscopy. Particle stability on the samples was tested by washing and rinsing treatments with various organic solvents. A biotin-streptavidin scheme was applied to demonstrate the biosensing capabilities of the samples. The size, interparticle distance, and shape of the gold nanoparticles demonstrated that OMCVD is a simple, economic, and fast way to fabricate surface bonded and stable gold nanoparticles. The plasmonic properties, the stability …

Influence Of Electrostatic Forces On The Particle Propulsion In The Evanescent Field Of Silver Ion-Exchanged Waveguides, Dmytro Gebenniko, Silvia Mittler

Physiology and Pharmacology Publications

The effect of electrostatic interaction between carboxylate- and amino-functionalized polystyrene particles and a charged waveguide surface on the propulsion speed in an optical tweezers is considered as a function of pH and ionic strength. It was shown that with the variation of the pH of the aqueous solution, the particles were immersed in, a systematic change of propulsion speed with a maximum speed could be achieved. The appearance of a maximum speed was ascribed to changes in the particle-waveguide separation as a result of the combination of two forces: Coulomb repulsion/attraction and induced dipole forces. The highest maximum speed at …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

Defining The Role Of Reactive Oxygen Species, Nitric Oxide, And Sphingolipid Signaling In Tumor Necrosis Factor - Induced Skeletal Muscle Weakness, Shawn Stasko

Theses and Dissertations--Physiology

In many chronic inflammatory diseases, patients suffer from skeletal muscle weakness, exacerbating their symptoms. Serum levels of tumor necrosis factor-alpha (TNF) and sphingomyelinase are increased, suggesting their possible role in the progression of this weakness. This dissertation focuses on the role that reactive oxygen species (ROS) and nitric oxide (NO) play in mediating TNF-induced skeletal muscle weakness and to what extent sphingolipid signaling mediates cellular response to TNF.

The first aim of this work was to identify which endogenous oxidant species stimulated by TNF contributes to skeletal muscle weakness. In C57BL/6 mice (n=38), intraperitoneal injection of TNF elicited a 25% …

Molecular Mechanisms Related To Endotoxemia In Primary Human Cardiomyocytes In Culture, Atijah J. Collins

PCOM Biomedical Studies Student Scholarship

Cardiovascular disease (CVD) is the leading cause of death in the United States and has been for the past 80 years. Development of novel therapeutic agents to address the large number of CVD deaths requires an in depth understanding of the structural and functional properties of human cardiomyocytes. Over the last few years we have been developing an in vitro paradigm to assess molecular cardiodynamics in Primary Human Cardiomyocyte in culture (PHCC). We tested the hypothesis whether endotoxemia would exhibit a marked decrease in contractile proteins and cause apoptosis in PHCC. In the current series of experiments, we induced endotoxemia …

Lipid Targets In Clinical Practice: Successes, Failures And Lessons To Be Learned, M Dunne, Oscar Mac Ananey, V Maher

Articles

Abstract

INTRODUCTION:

Optimal risk factor control is integral to managing patients with proven coronary heart disease (CHD+) and for those at risk of coronary heart disease (CHD-). The primary aim of the study was to assess the success rate of reaching lipid risk factor targets in a multiple risk factor clinic.

METHODS:

A retrospective audit was conducted in 488 patients (CHD+, n = 112; CHD-, n = 376) who attended the Cardiovascular Risk Factor Clinic at Tallaght Hospital, Dublin in 2009 and 2010.

RESULTS:

Risk factor targets achieved in CHD+ and CHD- patients were LDLc (54/62 %), HDLc (67/67 %), …

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

Neurophysiological Impact And Modeling-Independent Elucidation Of Inactivation Pathways In A-Type K+ Channels, J.D. Fineberg, David Ritter, Manuel Covarrubias

Department of Molecular Physiology and Biophysics Faculty Papers

Poster presented at Society for Neuroscience

Abstract:

A-type voltage-gated K⁺ channels auto-regulate their function by undergoing fast inactivation. Independent of molecular mechanisms, this inactivation can proceed after channel opening (open-state inactivation, OSI) or from a closed state prior to opening (closed-state inactivation, CSI). We hypothesize that the specific neurophysiological roles of A-type Kv channels depend on whether they undergo OSI, CSI or both (CSI+OSI). To explore these possibilities, we introduced Markov kinetic schemes of the A-type Kv4 conductance into a computational model of the hippocamcal CA1 neuron assuming either CSI or CSI+OSI and compared the properties of the somatic …