DOCSLIB.ORG

Proceedings of the XXXVI International Congress of Physiological Sciences (IUPS2009) Function of Life: Elements and Integration

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Volume 59 · Supplement 1 · 2009 Volume 59 · Supplement 1 · 2009 The XXXVI International Congress of Volume 59 · Supplement 59 Volume 1 · 2009 · pp 1–XX Physiological Sciences (IUPS2009) International Scientific Program Committees (ISPC) ISPC Chair Yoshihisa Kurachi Vice Chair Ole Petersen ISPC from IUPS Council Akimichi Kaneko (IUPS President) Irene Schulz (IUPS Vice President) Pierre Magistretti (IUPS Vice President) Malcolm Gordon (IUPS Treasurer) ISPC IUPS2009 Members and Associated Members Proceedings of the XXXVI International Congress of Physiological Sciences (IUPS2009) Commission I Locomotion Commission VII Comparative Physiology: Hans Hoppeler, Masato Konishi, Hiroshi Nose Evolution, Adaptation & Environment Function of Life: Elements and Integration Commission II Circulation/Respiration Malcolm Gordon, Ken-ichi Honma, July 27–August 1, 2009, Kyoto, Japan Yung Earm, Makoto Suematsu, Itsuo Kodama Kazuyuki Kanosue Commission III Endocrine, Reproduction & Commission VIII Genomics & Biodiversity Development David Cook, Hideyuki Okano, Gozoh Tsujimoto Caroline McMillen, Yasuo Sakuma, Toshihiko Yada Commission IX Others Commission IV Neurobiology Ann Sefton, Peter Hunter, Osamu Matsuo, Quentin Pittman, Harunori Ohmori, Fumihiko Kajiya, Tadashi Isa, Tadaharu Tsumoto, Megumu Yoshimura Jun Tanji Commission V Secretion & Absorption Local Executives Irene Schulz, Miyako Takaki, Yoshikatsu Kanai Yasuo Mori, Ryuji Inoue Commission VI Molecular & Cellular Biology Cecilia Hidalgo, Yoshihiro Kubo, Katsuhiko Mikoshiba, Masahiro Sokabe, Yukiko Gotoh Proceedings of the XXXVI International Congress of Physiological Sciences (IUPS2009) Function of Life: Elements and Integration July 27–August 1, 2009, Kyoto, Japan Hosted by the Physiological Society of Japan (PSJ) and the Science Council of Japan Organizing Committee Honorary Presidents: The Late Setsuro Ebashi Masao Ito Members: Toshinori Hongo Advisory Board: Ken-ichi Honma Akimichi Kaneko Katsumasa Kawahara President: Yoshio Maruyama Yasushi Miyashita Osamu Matsuo Katsuhiko Mikoshiba Vice Presidents: Harunori Ohmori Yoshihisa Kurachi (ISPC Chair) Hideyuki Okano Satoshi Kurihara (Treasurer) Taketoshi Ono Yasunobu Okada (Secretary) Tadaharu Tsumoto Proceedings of the 86th Annual Meeting of the Physiological Society of Japan President: Yoshinori Marunaka IUPS2009 Pledged support for IUPS2009: In addition to The Physiological Society of Japan, the following sources provide support for IUPS2009. Assembly for Myocardial Physiology Biophysical Society of Japan The Center for Advanced Medical Engineering and Infomatics, Osaka University Genomic Drug Discovery Forum Global COE Program "An in silico medicine-oriented worldwide open platform, Osaka University" Global COE Program "Education and Research Center for Stem Cell Medicine, Keio University" Global COE Program "Formation of a strategic base for biodiversity and evolutionary research: from genome to ecosystem, Kyoto University" Grant-in-Aid for Creative Scientific Research, "Function and regulatory system of water transporting aquaporin channels" Grant-in-Aid for Scientific Research on Priority Area, "Cell signaling" Grant-in-Aid for Scientific Research on Priority Area, "Cellular sensor" Grant-in-Aid for Scientific Research on Priority Area, "G-protein signal" Grant-in-Aid for Scientific Research on Priority Area, "Mechanisms of sex differentiation" Grant-in-Aid for Scientific Research on Priority Area, "Transportsome on biomembrane systems: its molecular assembly and physiological function" ICORP/SORST Cell Mechanosensing Project International Academy of Cardiovascular Sciences, Japan Section International Cardiothoracic & Vascular Anesthesia Academy International Conference on Control and Disease of Sodium Dependent Transportation Proteins and Ion Channels (ICSDT) Japan Neuroendocrine Society The Japan Neuroscience Society Japan Society for Adaptation Medicine Japan Society for Cell Biology Japan Society of Pain Clinicians Japan Society of Smooth Muscle Research The Japanese Association of Anatomists Japanese Association for Study of Pain The Japanese Circulation Society Japanese College of Angiology The Japanese Pharmacological Society Japanese Society for Chronobiology Japanese Society for Behavioral Neuroendocrinology Japanese Society for Microcirculation Japanese Society of Aerospace and Environmental Medicine Japanese Society of Biometeorology Japanese Society of Clinical Neurophysiology Japanese Society of Clinical Physiology The Japanese Society of Electrocardiology The Japanese Society of Lymphology Japanese Society of Nephrology Japanese Society of Pathophysiology Japanese Society of Physical Fitness & Sports Medicine The Japanese Society of Sleep Research The Journal of Physiology The Pharmaceutical Society of Japan Credits The societies listed below will provide medical credentials to their members upon their participation in IUPS2009. Japan Society of Obstetrics and Gynecology Japan Society of Pain Clinicians Japan Society of Ryodoraku Medicine The Japanese Circulation Society Japanese Society of Anesthesiologists The Japanese Society of Child Neurology Japanese Society of Clinical Neurophysiology Japanese Society of Nephrology Japanese Society of Neurology IUPS2009 2 Wallace Fenn Lecture BIOPHYSICAL DISSECTION OF NEUROTRANSMITTER RELEASE Erwin Neher Named Lectures Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Germany The ‘Calyx of Held', a glutamatergic presynaptic terminal in the auditory pathway is large enough that quantitative biophysical techniques, such as voltage clamp, Ca++ fluorimetry and Ca++ uncaging can be applied. Using these experimental tools, we have studied the role of Ca++ and other second messengers in neurotransmitter release and short-term synaptic plasticity (see E. Neher and T. Sakaba, 2008, Neuron 59, 861 for review). We found that the ++ concentration of free calcium ([Ca ]i) has at least three roles i) it triggers neurotransmitter release in a highly cooperative fashion ii) it accelerates linearly the recruitment of new releasable synaptic vesicles during ongoing stimulation and iii) it mediates short-term facilitation. Recruitment of vesicles is rate-limiting for neurotransmitter release during sustained high-frequency activity. Therefore, the acceleration of this process by Ca++ has a very important modulatory role. Surprisingly we found that this process is not limited by the availability of vesicles or the assembly of a molecular release machinery. Rather, new vesicles rapidly enter a state in which they can be released by caged Ca++. Another slower step is required to bring them near Ca++ channels, such that they may also be released by short action potentials. IUPS President's Lecture PROTON-MEDIATED FEEDBACK FROM HORIZONTAL CELLS TO CONES IN THE RETINA: A MECHANISM OF RECEPTIVE FIELD SURROUND FORMATION Akimichi Kaneko School of Health Science, Kio University, Japan Feedback from horizontal cells (HCs) to cone photoreceptors plays a key role in the center-surround receptive field organization of retinal cells. In cone photoreceptors of the newt retinal slices the voltage-dependent calcium current (ICa) was enhanced by surround illumination. Enrichment of the pH buffering capacity of the extracellular solution increased cone ICa, and blocked any additional increase by surround illumination. Hyperpolarization of HCs by CNQX augmented cone ICa, whereas depolarization of HCs by kainate suppressed cone ICa. From these results, we propose that pH changes in the synaptic clefts, caused by the membrane voltage change of HCs, mediate the feedback from HCs to cone photoreceptors. When HCs, isolated from the goldfish retina, were depolarized by kainate or high-K+ medium, the pH of the immediate external surface (pHs) of HCs was lowered. The pH change was suppressed by 400 nM bafilomycin A1, an inhibitor of vacuolar type +H pump (V-ATPase). The V-ATPase was immunocytochemically identified on the plasma membrane of dissociated HCs. These results confirm that protons are released from HCs and caused the pH change around the cone terminals. [Supported by JSPS Grants.] IUPS 2009 July 27 - August 1, 2009 in Kyoto Named Lectures T. P. Feng Lecture THE COMPUTATIONAL LOGIC OF NETWORKS IN MOTION, FROM ION CHANNELS TO BEHAVIOUR Sten E Grillner Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden In all vertebrates from primates including man to fish and lamprey, the basic neuronal organization controlling patterns of motor behaviour such as locomotion, breathing, and posture are organized in a similar or identical way. These networks form a motor infrastructure used to initiate all the movements that each species can perform. These networks in turn can be selected through subpopulations of cells in the basal ganglia, which play an important role for the selection of motor programs. The networks generating the locomotor movements are located in the spinal cord. They are responsible for the sequential activation of the different limb muscle in each locomotor cycle. The activity level is controlled by locomotor command centres in the brainstem, conserved throughout the vertebrate phylum. To elucidate the intrinsic function of these pattern generating networks and command systems we have developed the lamprey nervous system as an experimental model. We now understand the cellular bases of the brainstem spinal cord networks generating goal-directed locomotion and control of body orientation. The detailed synaptic interaction has been identified, as well as
Recommended publications
  • Valorisation of Codfish (Gadus Morhua L.) Salting Processing Wastewater Through the Extraction of High Added Value Compounds

    Valorisation of Codfish (Gadus Morhua L.) Salting Processing Wastewater Through the Extraction of High Added Value Compounds

    Valorisation of codfish (Gadus morhua L.) salting processing wastewater through the extraction of high added value compounds Thesis submitted to the Universidade Católica Portuguesa to attain the degree of PhD in Biotechnology – with specialisation in Environmental Engineering By VINCENZA FERRARO September 2011 Valorisation of codfish (Gadus morhua L.) salting processing wastewater through the extraction of high added value compounds Thesis submitted to the Universidade Católica Portuguesa to attain the degree of PhD in Biotechnology – with specialisation in Environmental Engineering By VINCENZA FERRARO Under the academic supervision of Prof. Paula Maria Lima Castro Under the co-supervision of Prof. Maria Manuela Estevez Pintado September 2011 To my Family and Faustino Without whose encouragement, understanding and support, I could not have finished my PhD course. Thank you so much Preface Preface The research work published in this PhD dissertation has been developed at WeDoTech -Companhia de Ideias e Tecnologias, Lda., spin-off enterprise of the College of Biotechnology of Catholic University of Portugal, in Porto, through an Early Stage Research grant inside the InSolEx-RTN Programme (Innovative Solution for Extracting high value natural compounds-Research and Training Network) of Marie Curie Actions, under the 6th Frame Programme of the European Research Area. VI Acknowledgements Acknowledgements I would like to express my gratitude to my academic supervisors Prof. Maria Paula Lima Castro and Prof. Maria Manuela Estevez Pintado, whose expertise, understanding and patience added considerably to my graduate and professional experience. I really appreciate not only their vast knowledge and skills in many areas but also the human relationship they guided me with through the very intense PhD research period at the College of Biotechnology of the Catholic University of Portugal.
  • Service History July 2012 AGM - September 2018 AGM

    Service History July 2012 AGM - September 2018 AGM

    Service History July 2012 AGM - September 2018 AGM The information in this Service History is true and complete to the best of The Society’s knowledge. If you are aware of any errors please let the Governance and Risk Manager know by email: [email protected] Service History Index DATES PAGE # 5 July 2012 – 24 July 2013 Page 1 24 July 2013 – 1 July 2014 Page 14 1 July 2014 – 7 July 2015 Page 28 7 July 2015 – 31 July 2016 Page 42 31 July 2016 – 12 July 2017 Page 60 12 July 2017 – 16 September 2018 Page 82 Service History: July 2012 AGM – Sept 2018 AGM Introduction Up until 2006 the service history of The Society’s members was captured in Grey Books. It was also documented between 1990-2013 in The Society’s old database iMIS, which will be migrated to the CRM member directory adopted in 2016. This document collates missing service history data from July 2012 to September 2018. Grey Books were relaunched as ‘Grey Records’ in 2019 beginning with the period from the September AGM 2018 up until July AGM 2019. There will now be a Grey Record published every year reflecting the previous year’s service history. The Grey Record will now showcase service history from Member Forum to Member Forum (typically held in the Winter). 5 July 2012 – 24 July 2013 Honorary Officers (and Trustees) POSITION NAME President Jonathan Ashmore Deputy President Richard Vaughan-Jones Honorary Treasurer Rod Dimaline Education & Outreach Committee Chair Blair Grubb Meetings Committee Chair David Wyllie Policy Committee Chair Mary Morrell Membership & Grants Committee
  • After Simulated Gastrointestinal Digestion: in Vitro Intestinal Protection, Bioavailability, and Anti-Haemolytic Capacity

    After Simulated Gastrointestinal Digestion: in Vitro Intestinal Protection, Bioavailability, and Anti-Haemolytic Capacity

    Journal of Functional Foods 15 (2015) 365–375 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.elsevier.com/locate/jff Antioxidant peptides from “Mozzarella di Bufala Campana DOP” after simulated gastrointestinal digestion: In vitro intestinal protection, bioavailability, and anti-haemolytic capacity Gian Carlo Tenore a,*, Alberto Ritieni a, Pietro Campiglia b, Paola Stiuso c, Salvatore Di Maro a, Eduardo Sommella b, Giacomo Pepe b, Emanuela D’Urso a, Ettore Novellino a a Department of Pharmacy, Università di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy b Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Via Ponte Don Melillo, 1, Salerno 84084, Italy c Department of Biochemistry and Biophysics, Second University of Naples, Italy ARTICLE INFO ABSTRACT Article history: The bioactive properties of milk and milk-products are largely attributed to the peptides Received 19 January 2015 released during gastrointestinal digestion. Nevertheless, no similar studies on “Mozzarella Received in revised form 24 March di Bufala Campana DOP” (MBC), the European name given to a unique protected origin des- 2015 ignation buffalo milk product, are available so far. A novel antioxidant peptide (MBCP) after Accepted 26 March 2015 MBC gastrointestinal digestion was identified and its in vitro intestinal protection, bioavailability, Available online 14 April 2015 and anti-haemolytic capacity were assayed. A 0.2 mg/mL MBCP incubation dose made H2O2- stressed CaCo2 cell line proliferation increase by about 100%. Less than 10% hydrolysis in Keywords: the apical solution and about 10% concentration in the basolateral solution indicated for Mozzarella di Bufala Campana DOP MBCP good stability and bioavailability, respectively.
  • New Approaches to Studies of Paracellular Drug Transport in Intestinal Epithelial Cell Monolayers

    New Approaches to Studies of Paracellular Drug Transport in Intestinal Epithelial Cell Monolayers

    &RPSUHKHQVLYH6XPPDULHVRI8SSVDOD'LVVHUWDWLRQV IURPWKH)DFXOW\RI3KDUPDF\ 1HZ$SSURDFKHVWR6WXGLHVRI 3DUDFHOOXODU'UXJ7UDQVSRUWLQ,QWHVWLQDO (SLWKHOLDO&HOO0RQROD\HUV %< 67$))$17$9(/,1 $&7$81,9(56,7$7,6836$/,(16,6 8336$/$ Dissertation for the Degree of Doctor of Philosophy (Faculty of Pharmacy) in Pharmaceutics presented at Uppsala University in 2003 ABSTRACT Tavelin, S., 2003. New Approaches to Studies of Paracellular Drug Transport in Intestinal Epithelial Cell Monolayers. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 285. 66 pp. Uppsala. ISBN 91-554-5582-4. Studies of intestinal drug permeability have traditionally been performed in the colon-derived Caco-2 cell model. However, the paracellular permeability of these cell monolayers resembles that of the colon rather than that of the small intestine, which is the major site of drug absorption following oral administration. One aim of this thesis was therefore to develop a new cell culture model that mimics the permeability of the small intestine. 2/4/A1 cells are conditionally immortalized with a temperature sensitive mutant of SV40T. These cells proliferate and form multilayers at 33°C. At cultivation temperatures of 37–39°C, they stop proliferating and form monolayers. 2/4/A1 cells cultivated on permeable supports expressed functional tight junctions. The barrier properties of the tight junctions such as transepithelial electrical resistance and permeability to hydrophilic paracellular markers resembled those of the human small intestine in vivo. These cells lacked functional expression of drug transport proteins and can therefore be used as a model to study passive drug permeability unbiased by active transport. The permeability to diverse sets of drugs in 2/4/A1 was comparable to that of the human jejunum for both incompletely and completely absorbed drugs, and the prediction of human intestinal permeability was better in 2/4/A1 than in Caco-2 for incompletely absorbed drugs.
  • Tight Junction Claudins and the Kidney in Sickness and in Health

    Tight Junction Claudins and the Kidney in Sickness and in Health

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1788 (2009) 858–863 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Review Tight junction claudins and the kidney in sickness and in health Daniel F. Balkovetz ⁎ Veterans Administration Medical Center, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA article info abstract Article history: The epithelial cell tight junction has several functions including the control of paracellular transport between Received 24 March 2008 epithelial cells. Renal paracellular transport has been long recognized to exhibit unique characteristics within Received in revised form 24 June 2008 different segments of the nephron, functions as an important component of normal renal physiology and has Accepted 8 July 2008 been speculated to contribute to renal related pathology if functioning abnormally. The discovery of a large Available online 16 July 2008 family of tight junction associated 4-transmembrane spanning domain proteins named claudins has advanced our understanding on how the paracellular permeability properties of tight junctions are Keywords: fi Metabolic acidosis determined. In the kidney, claudins are expressed in a nephron-speci c pattern and are major determinants Acute kidney injury of the paracellular permeability of tight junctions in different nephron segments.
  • Women Physiologists

    Women Physiologists

    Women physiologists: Centenary celebrations and beyond physiologists: celebrations Centenary Women Hodgkin Huxley House 30 Farringdon Lane London EC1R 3AW T +44 (0)20 7269 5718 www.physoc.org • journals.physoc.org Women physiologists: Centenary celebrations and beyond Edited by Susan Wray and Tilli Tansey Forewords by Dame Julia Higgins DBE FRS FREng and Baroness Susan Greenfield CBE HonFRCP Published in 2015 by The Physiological Society At Hodgkin Huxley House, 30 Farringdon Lane, London EC1R 3AW Copyright © 2015 The Physiological Society Foreword copyright © 2015 by Dame Julia Higgins Foreword copyright © 2015 by Baroness Susan Greenfield All rights reserved ISBN 978-0-9933410-0-7 Contents Foreword 6 Centenary celebrations Women in physiology: Centenary celebrations and beyond 8 The landscape for women 25 years on 12 "To dine with ladies smelling of dog"? A brief history of women and The Physiological Society 16 Obituaries Alison Brading (1939-2011) 34 Gertrude Falk (1925-2008) 37 Marianne Fillenz (1924-2012) 39 Olga Hudlická (1926-2014) 42 Shelagh Morrissey (1916-1990) 46 Anne Warner (1940–2012) 48 Maureen Young (1915-2013) 51 Women physiologists Frances Mary Ashcroft 56 Heidi de Wet 58 Susan D Brain 60 Aisah A Aubdool 62 Andrea H. Brand 64 Irene Miguel-Aliaga 66 Barbara Casadei 68 Svetlana Reilly 70 Shamshad Cockcroft 72 Kathryn Garner 74 Dame Kay Davies 76 Lisa Heather 78 Annette Dolphin 80 Claudia Bauer 82 Kim Dora 84 Pooneh Bagher 86 Maria Fitzgerald 88 Stephanie Koch 90 Abigail L. Fowden 92 Amanda Sferruzzi-Perri 94 Christine Holt 96 Paloma T. Gonzalez-Bellido 98 Anne King 100 Ilona Obara 102 Bridget Lumb 104 Emma C Hart 106 Margaret (Mandy) R MacLean 108 Kirsty Mair 110 Eleanor A.
  • The Era of International Space Station Utilization Table of Contents

    The Era of International Space Station Utilization Table of Contents

    Perspectives on Strategy From International Research Leaders The Era of International Space Station Utilization Table of Contents Executive Summary 3 Scientifi c Disciplines and Potential 7 Gravity-dependent Processes in the Physical Sciences 7 Fundamental Physics 9 Gravity-dependent Processes in the Life Sciences 10 Human Health Research 12 Psychology and Space Exploration 14 Earth and Space Observations 15 Exploration and Technology Development 16 Commercial Development 17 Education 18 Space Agency Perspectives 21 Biographical Sketches 35 Notes and References 40 Editorial Board Canadian Space Agency: Nicole Buckley, Perry Johnson-Green European Space Agency: Martin Zell Japan Aerospace Exploration Agency: Tai Nakamura Roscosmos: George Karabadzhak, Igor Sorokin National Aeronautics and Space Administration: Tara Ruttley, Ken Stroud Italian Space Agency: Jean Sabbagh Managing Editor Tracy L. Thumm, NASA Executive Editor Julie A. Robinson, NASA Astronaut Peggy Whitson looks at the plants grown in the Advanced AstrocultureTM (ADVASC) green house. Image: NASA ISS005E08001 The Era of International Space Station Utilization Manfred Dietel Charité Berlin, Germany Berndt Feuerbacher International Astronautical Federation, France Vladimir Fortov Joint Institute for High Temperature Russian Academy of Sciences, Russia David Hart University of Calgary, Canada Life Sciences Advisory Committee, Canadian Space Agency Charles Kennel Scripps Institution of Oceanography, USA Space Studies Board, National Academy of Sciences, USA Oleg Korablev Space Research
  • THE GRAND HARMONIOUS SYMMETRY of JAPAN: an Investigation in Uncanny Flag Similarities Christopher J. Maddish

    THE GRAND HARMONIOUS SYMMETRY of JAPAN: an Investigation in Uncanny Flag Similarities Christopher J. Maddish

    THE GRAND HARMONIOUS SYMMETRY OF JAPAN: An Investigation in Uncanny Flag Similarities Christopher J. Maddish The 47 prefectures of Japan have unique flags, whose designs came from various sources. Many flags employ a stylized version of Japanese alphabet in either Hiragana or Katakana on a solid field. Like most sub‐national flags, they are strongly influenced by the national colors and design. Conventional wisdom assumes this process of sub‐national flag selection is a fairly random, yet attenuated to the cultural tastes the particular nation. The thesis of this paper is that a pattern can be found among the prefectural flags of Japan. The revolutionary and rather uncanny pattern is that each prefecture’s flag has a kind of “harmonious twin”. This paper will first describe the methodology of how flags are paired, followed by several illustrative examples. This is a new system of classification of flags based on groups limited to two. This paper’s title, the Grand Harmonious Symmetry of Japan, hints that the flags of Japan exhibit a certain degree of harmony and the title itself exhibits a subtle relationship to Japan. By way of uncanny historical, geographical, and cultural events a pattern of harmonious symmetry will be presented. On the left is the name of Japan written in Japanese as Nihon, literally translated as Sun‐ Source. The upper kaniji that looks like a digital eight means sun, the lower kanji means source, book, and root. To the right is the classical name of Japan, Yamato. The upper kanji means grand or big. The kanji on the lower right means harmony.
  • Role of Cation- Selective Apical Transporters in Paracellular Absorption

    Role of Cation- Selective Apical Transporters in Paracellular Absorption

    A NOVEL MECHANISM FOR INTESTINAL ABSORPTION OF THE TYPE II DIABETES DRUG METFORMIN: ROLE OF CATION- SELECTIVE APICAL TRANSPORTERS IN PARACELLULAR ABSORPTION William Ross Proctor III A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Pharmacy. Chapel Hill 2010 Approved by Advisor: Dhiren R. Thakker, Ph.D. Chairperson: Moo J. Cho, Ph.D. Reader: James M. Anderson, M.D., Ph.D. Reader: Kim L.R. Brouwer, Pharm.D., Ph.D. Reader: Joseph W. Polli, Ph.D. Reader: Zhiyang Zhao, Ph.D. © 2010 William Ross Proctor III ALL RIGHTS RESERVED ii ABSTRACT William Ross Proctor III: A Novel Mechanism for Intestinal Absorption of the Type II Diabetes Drug Metformin: Role of Cation-selective Apical Transporters in Paracellular Absorption (Under the direction of Dhiren R. Thakker, Ph.D.) Metformin, a widely prescribed anti-hyperglycemic agent, is very hydrophilic with net positive charge at physiological pH, and thus should be poorly absorbed. Instead, the drug is well absorbed (oral bioavailability of 40-60%), although the absorption is dose- dependent and variable; the drug accumulates in enterocytes during oral absorption. To date, the transport processes associated with the intestinal absorption of metformin are poorly understood. This dissertation work describes an unusual and novel intestinal absorption mechanism for metformin. The absorption mechanism involves two-way transport of metformin across the apical membrane of enterocytes that is mediated by cation-selective transporters, and facilitated diffusion across the paracellular route, working in concert to yield high and sustained absorption Metformin absorption was evaluated in the well established model for intestinal epithelium, Caco-2 cell monolayers.
  • Effect of Metformin on Maternal and Fetal Outcomes in Obese

    Effect of Metformin on Maternal and Fetal Outcomes in Obese

    Articles Eff ect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial Carolyn Chiswick, Rebecca M Reynolds, Fiona Denison, Amanda J Drake, Shareen Forbes, David E Newby, Brian R Walker, Siobhan Quenby, Susan Wray, Andrew Weeks, Hany Lashen, Aryelly Rodriguez, Gordon Murray, Sonia Whyte, Jane E Norman Summary Background Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult Lancet Diabetes Endocrinol 2015 off spring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal Published Online hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising July 10, 2015 drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. http://dx.doi.org/10.1016/ S2213-8587(15)00219-3 See Online/Comment Methods We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health http://dx.doi.org/10.1016/ Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks’ gestation who had a BMI of S2213-8587(15)00234-X 30 kg/m² or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated Tommy’s Centre for Maternal block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum and Fetal Health, Medical of 2500 mg) or matched placebo daily from between 12 and 16 weeks’ gestation until delivery of the baby. Randomisation Research Council (MRC) Centre for Reproductive Health was stratifi ed by study site and BMI band (30–39 vs ≥40 kg/m²).
  • Remarks at the Lyndon B. Johnson Space Center in Houston April 14, 1998

    Remarks at the Lyndon B. Johnson Space Center in Houston April 14, 1998

    Apr. 14 / Administration of William J. Clinton, 1998 Remarks at the Lyndon B. Johnson Space Center in Houston April 14, 1998 Thank you very much. Once again, I'm de- your Land Commissioner, Garry Mauro, and lighted to be back here. I have to beg your your State Senator, Rodney Ellis, for being here, pardon for starting this program a little late, and the other city officials who are here, Don but when I get here, I get involved in what Boney, Sylvia Garcia. Judge Eckels, thank you I'm doing. And besides that, John Glenn wanted for coming. I'd like to thank Colonel Curt to make sure I saw every single square inchÐ Brown, who is the commander for the mission [laughter]Ðof space he would be living and ma- Senator Glenn is going to. And you see his neuvering inÐwhich didn't take all that long whole team back here, including a member from to see, actually. [Laughter] But we've had a Japan and a member from Europe, who is a wonderful day. native from Madrid, Spain. And we're glad to I want to thank Dan Goldin for doing a mar- have all of them here. velous job. One thing he did not mention was I'd like to thank David Wolfe and all the the fact that he made the decision, which I other astronauts that showed me around, and strongly supported, to continue our involvement also the folks on the Neurolab team that talked with the Mir, to participate with our partners to me by long distance.
  • Permeability and Modulation of the Intestinal Epithelial Barrier

    Permeability and Modulation of the Intestinal Epithelial Barrier

    Permeability andmodulatio n ofth e intestinal epithelial barrier invitr o ErwinDuize r Promotores Dr.J.H .Koema n Hoogleraar in de Toxicologic Landbouwuniversiteit Wageningen Dr.P.J . van Bladeren Bijzonder hoogleraar ind eToxicokinetie k en Biotransformatie Landbouwuniversiteit Wageningen enTN OVoeding ,Zeis t Co-promotor Dr.ir .J.P .Grote n Hoofd Afdeling Verklarende Toxicologic TNOVoeding ,Zeis t ^6SS pMo^1 \ Permeability andmodulatio n ofth e intestinal epithelial barrier invitr o Erwin Duizer Proefschrift ter verkrijging van de graad van doctor op gezag van derecto r magnificus, van de Landbouwuniversiteit Wageningen, dr. C. M. Karssen in het openbaar te verdedigen opwoensdag 16juni 1999 desnammidag s te vier uur in de Aula. Permeability and modulation of the intestinal epithelial barrier in vitro Erwin Duizer ThesisWageninge n Agricultural University, The Netherlands - Withreferences , -Wit h summary in Dutch ISBN 90-5808-067-6 Subject headings: intestinal epithelium / Caco-2/ IEC-18/ paracellular Cover: Confocal laser scanning microscopy image of filter-grown IEC-18 cells labeled witha polyclonal anti-ZO-1antibod y and visualized with aTRITC-conjugate d streptavidin- biotin system. Print: ADDIX,Wij k bij Duurstede The investigations described in this thesis were carried out at theToxicolog y Division of the TNONutritio n and Food Research Institute (Zeist, Netherlands). Financial support for the publication of this thesis waskindl y provided by TNONutritio n and Food Research Institute andth e Dutch Alternatives to Animal Experiments Platform. ^MO^'i^55 STELLINGEN behorende bij het proefschrift "Permeability and modulation of the intestinal epithelial barrier invitro " vanErwi n Duizer, te verdedigen op woensdag 16jun i 1999,o m 16.00uu r teWageningen .