Example of How Amehsi Specification Indicators Can Be Mapped to Health
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Meat Curing and Sodium Nitrite
MEDIA MYTHCRUSHER Meat Curing and Sodium Nitrite The use of nitrite to produce cured meats like salami, ham, bacon and hot dogs, is a safe, regulated practice that has distinct public health benefits. However, much confusion and even mythology surrounds nitrite. Being mindful of key words and statistics and providing appropriate context can help reporters improve the accuracy of their coverage and the information that is passed on to readers and viewers. We’ve compiled ten tips to improve accuracy when writing about the use of sodium nitrite in cured meats. #1: Nitrite is not ‘unnatural’. Before the terms nitrate and nitrite are often used refrigeration was available, humans salted and interchangeably, meat companies mainly use dried meat to preserve it. It was discovered sodium nitrite to cure meat, not sodium nitrate. that the nitrate in saltpeter was extremely At the turn of the 20th century, German effective in causing a chemical reaction known scientists discovered nitrite (and not nitrate) as “curing.” Not only did this give meat a was the active form of these curing salts. When distinct taste and flavor, it also preserved it and added directly, rather than as nitrate, meat prevented the growth of Clostridium botulinum, processors can have better control of this which causes botulism. important curing ingredient and more closely manage how much they are adding. Later on, scientists came to understand that nitrate naturally found in the environment #3: Cured meats are a miniscule source of converts to nitrite when in the presence of total human nitrite intake. Scientists say that certain bacteria. -
Inhibition of Grb2‑Mediated Activation of MAPK Signal Transduction
566 ONCOLOGY LETTERS 4: 566-570, 2012 Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line RONG GUI1, DENGQING LI1, GUANNAN QI1,2, ALI SUHAD2 and XINMIN NIE1 1Clinical Laboratory Centre of the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China; 2Hormones and Cancer Research Unit, Royal Victoria Hospital, McGill University, Quebec H3A 1A1, Canada Received March 12, 2012; Accepted June 22, 2012 DOI: 10.3892/ol.2012.774 Abstract. The nitroreductase oxidored-nitro domain Introduction containing protein 1 (NOR1) gene may be involved in the chemical carcinogenesis of hepatic cancer and nasopharyn- The oxidored-nitro domain containing protein 1 (NOR1) gene geal carcinoma (NPC). We have previously demonstrated that was previously cloned in our laboratory at the Third Xiangya NOR1 overexpression is capable of converting the monofunc- Hospital (Hunan, China) using suppression subtractive hybrid- tional alkylating agent 5-(aziridin-1-yl)-2,4-dinitrobenzamide ization and cDNA microarrays (1,2). By examining the human (CB1954) into a toxic form by reducing the 4-nitro group of genome working sequence, it has been identified that that the CB1954. Toxic CB1954 is able to enhance cell killing in the NOR1 gene is located on 1p34.3 and contains 10 exons and NPC cell line CNE1; however, the underlying mechanisms 9 introns. Additionally, the PROSITE database identified remain unknown. Using cDNA microarrays and quantitative two possible cAMP and cGMP-dependent protein kinase real-time PCR, we previously discovered that NOR1 increases phosphorylation sites, two tyrosine phosphorylation sites the expression of growth factor receptor-bound protein 2 and four N-myristoylation sites in NOR1. -
Role of Sodium/Calcium Exchangers in Tumors
biomolecules Review Role of Sodium/Calcium Exchangers in Tumors Barbora Chovancova 1, Veronika Liskova 1, Petr Babula 2 and Olga Krizanova 1,2,* 1 Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 45 Bratislava, Slovakia; [email protected] (B.C.); [email protected] (V.L.) 2 Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic; [email protected] * Correspondence: [email protected]; Tel.: +4212-3229-5312 Received: 6 August 2020; Accepted: 29 August 2020; Published: 31 August 2020 Abstract: The sodium/calcium exchanger (NCX) is a unique calcium transport system, generally transporting calcium ions out of the cell in exchange for sodium ions. Nevertheless, under special conditions this transporter can also work in a reverse mode, in which direction of the ion transport is inverted—calcium ions are transported inside the cell and sodium ions are transported out of the cell. To date, three isoforms of the NCX have been identified and characterized in humans. Majority of information about the NCX function comes from isoform 1 (NCX1). Although knowledge about NCX function has evolved rapidly in recent years, little is known about these transport systems in cancer cells. This review aims to summarize current knowledge about NCX functions in individual types of cancer cells. Keywords: sodium-calcium exchanger; cancer cells; calcium; apoptosis 1. Background Intracellular calcium ions are considered the most abundant secondary messengers in human cells, since they have a substantial diversity of roles in fundamental cellular physiology. Accumulating evidence has demonstrated that intracellular calcium homeostasis is altered in cancer cells and that this alteration is involved in tumor initiation, angiogenesis, progression and metastasis. -
Reduced Renal Methylarginine Metabolism Protects Against Progressive Kidney Damage
BASIC RESEARCH www.jasn.org Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage † James A.P. Tomlinson,* Ben Caplin, Olga Boruc,* Claire Bruce-Cobbold,* Pedro Cutillas,* † ‡ Dirk Dormann,* Peter Faull,* Rebecca C. Grossman, Sanjay Khadayate,* Valeria R. Mas, † | Dorothea D. Nitsch,§ Zhen Wang,* Jill T. Norman, Christopher S. Wilcox, † David C. Wheeler, and James Leiper* *Medical Research Council Clinical Sciences Centre, Imperial College, London, United Kingdom; †Centre for Nephrology, UCL Medical School Royal Free, London, United Kingdom; ‡Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia; §Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom; and |Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC ABSTRACT Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine- metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific -
(12) United States Patent (10) Patent No.: US 7.803,838 B2 Davis Et Al
USOO7803838B2 (12) United States Patent (10) Patent No.: US 7.803,838 B2 Davis et al. (45) Date of Patent: Sep. 28, 2010 (54) COMPOSITIONS COMPRISING NEBIVOLOL 2002fO169134 A1 11/2002 Davis 2002/0177586 A1 11/2002 Egan et al. (75) Inventors: Eric Davis, Morgantown, WV (US); 2002/0183305 A1 12/2002 Davis et al. John O'Donnell, Morgantown, WV 2002/0183317 A1 12/2002 Wagle et al. (US); Peter Bottini, Morgantown, WV 2002/0183365 A1 12/2002 Wagle et al. (US) 2002/0192203 A1 12, 2002 Cho 2003, OOO4194 A1 1, 2003 Gall (73) Assignee: Forest Laboratories Holdings Limited 2003, OO13699 A1 1/2003 Davis et al. (BM) 2003/0027820 A1 2, 2003 Gall (*) Notice: Subject to any disclaimer, the term of this 2003.0053981 A1 3/2003 Davis et al. patent is extended or adjusted under 35 2003, OO60489 A1 3/2003 Buckingham U.S.C. 154(b) by 455 days. 2003, OO69221 A1 4/2003 Kosoglou et al. 2003/0078190 A1* 4/2003 Weinberg ...................... 514f1 (21) Appl. No.: 11/141,235 2003/0078517 A1 4/2003 Kensey 2003/01 19428 A1 6/2003 Davis et al. (22) Filed: May 31, 2005 2003/01 19757 A1 6/2003 Davis 2003/01 19796 A1 6/2003 Strony (65) Prior Publication Data 2003.01.19808 A1 6/2003 LeBeaut et al. US 2005/027281.0 A1 Dec. 8, 2005 2003.01.19809 A1 6/2003 Davis 2003,0162824 A1 8, 2003 Krul Related U.S. Application Data 2003/0175344 A1 9, 2003 Waldet al. (60) Provisional application No. 60/577,423, filed on Jun. -
By Norepinephrine and Inactivated by NO and Cgmp (Medial Basal Hypothalami/Luteinizing Hormone-Releasing Hormone/Camp/Arginine/Nitroarginine Methyl Ester) G
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 4246-4250, April 1996 Physiology Nitric oxide synthase content of hypothalamic explants: Increased by norepinephrine and inactivated by NO and cGMP (medial basal hypothalami/luteinizing hormone-releasing hormone/cAMP/arginine/nitroarginine methyl ester) G. CANTEROS*, V. RErroRI*, A. GENARO*, A. SUBURO*, M. GIMENO*, AND S. M. MCCANNtt *Centro de Estudios Farmacologicos y Botanicos, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Serrano 665, 1414 Buenos Aires, Argentina; and tPennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808-4124 Contributed by S. M. McCann, December 26, 1995 ABSTRACT Release of luteinizing hormone (LH)- pituitary gland. There it releases LH, which induces ovulation releasing hormone (LHRH), the hypothalamic peptide that and ovarian steroid secretion in females and testosterone controls release of LH from the adenohypophysis, is con- secretion in males (3). Since NO controls LHRH release in the trolled by NO. There is a rich plexus of nitric oxide synthase arcuate nucleus-median eminence region, where axons of (NOS)-containing neurons and fibers in the lateral median LHRH neurons terminate on the portal capillaries (2), we eminence, intermingled with terminals of the LHRH neurons. expected to find NOergic neurons in this region. Indeed, in the To study relations between NOS and LHRH in this brain present study we found a large number of NOergic cell bodies region, we measured NOS activity in incubated medial basal and fibers in the arcuate-median eminence region. hypothalamus (MBH). NOS converts [l4C]arginine to equimo- This study was initiated to determine if we could measure lar quantities of [14C]citrulline plus NO, which rapidly decom- NOS activity in incubated medial basal hypothalami (MBHs) poses. -
Tetrahydrobiopterin Loading Test in Hyperphenylalaninemia
003 1-399819113005-0435$03.00/0 PEDIATRIC RESEARCH Vol. 30, No. 5, 1991 Copyright 0 199 1 International Pediatric Research Foundation, Inc. Pr~ntc.d in U.S. A Tetrahydrobiopterin Loading Test in Hyperphenylalaninemia ALBERT0 PONZONE, ORNELLA GUARDAMAGNA, SILVIO FERRARIS, GIOVANNI B. FERRERO, IRMA DIANZANI, AND RICHARD G. H. COTTON InstiflifeofPediatric Clinic(A.P., O.G., S.F., G.B.F., I.D.], University of Torino, 10126 Torino, Italy and Olive Miller Laboratory [R.G.H.C.],Murdoch Institute, Royal Children's Hospital, Vicroria,Australia 3052 ABSTRACT. Some cases of primary hyperphenylalanine- PKU to describe some cases clinically unresponsive to a Phe- mia are not caused by the lack of phenylalanine hydroxyl- restricted diet and later shown to be due to BH4 deficiency ase, but by the lack of its cofactor tetrahydrobiopterin. ( 1-4). These patients are not clinically responsive to a phenylal- By analyzing all the essential components of the complex anine-restricted diet, but need specific substitution therapy. hydroxylation system of aromatic amino acids, it became appar- Thus, it became necessary to examine all newborns ent that a defect in the BH4 recycling enzyme DHPR (EC screened as positive with the Guthrie test for tetrahydro- 1.66.99.7) and two defects in BH4 synthetic pathway enzymes, biopterin deficiency. Methods based on urinary pterin or guanosine triphosphate cyclohydrolase I (EC 3.5.4.16) and 6- on specific enzyme activity measurements are limited in PPH4S, may lead to cofactor deficiency resulting in HPA and in their availability, and the simplest method, based on the impaired production of dopamine and serotonin (5-7). -
Exisulind, a Novel Proapoptotic Drug, Inhibits Rat Urinary Bladder Tumorigenesis1
[CANCER RESEARCH 61, 3961–3968, May 15, 2001] Exisulind, a Novel Proapoptotic Drug, Inhibits Rat Urinary Bladder Tumorigenesis1 Gary A. Piazza, W. Joseph Thompson,2 Rifat Pamukcu, Hector W. Alila, Clark M. Whitehead, Li Liu, John R. Fetter, William E. Gresh, Jr., Andres J. Klein-Szanto, Daniel R. Farnell, Isao Eto, and Clinton J. Grubbs Cell Pathways, Inc., Horsham, Pennsylvania 19044 [G. A. P., W. J. T., R. P., H. W. A., C. M. W., L. L., J. R. F., W. E. G.]; Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [A. J. K.]; Southern Research Institute, Birmingham, Alabama 35205 [D. R. F.]; and The University of Alabama at Birmingham, Birmingham, Alabama 35205-7340 [I. E., C. J. G.] ABSTRACT systemic or intravesical delivery of chemotherapeutic drugs, which produce relatively modest efficacy and are associated with serious Exisulind (Aptosyn) is a novel antineoplastic drug being developed for side effects and/or delivery complications. The high rate of mortality the prevention and treatment of precancerous and malignant diseases. In from urinary bladder cancer and the high incidence of disease recur- colon tumor cells, the drug induces apoptosis by a mechanism involving cyclic GMP (cGMP) phosphodiesterase inhibition, sustained elevation of rence emphasize the need for new therapeutic agents alone or in cGMP, and protein kinase G activation. We studied the effect of exisulind combination with existing therapies. Research to identify the specific on bladder tumorigenesis induced in rats by the carcinogen, N-butyl-N- molecular defects involved in bladder tumorigenesis has identified (4-hydroxybutyl) nitrosamine. Exisulind at doses of 800, 1000, and 1200 mutations in a number of genes (i.e., ras and p53) or altered expres- mg/kg (diet) inhibited tumor multiplicity by 36, 47, and 64% and tumor sion of proteins (cyclin D and p21 WAF1/CIP1), which are known to incidence by 31, 38, and 61%, respectively. -
Nitrosamines EMEA-H-A5(3)-1490
25 June 2020 EMA/369136/2020 Committee for Medicinal Products for Human Use (CHMP) Assessment report Procedure under Article 5(3) of Regulation EC (No) 726/2004 Nitrosamine impurities in human medicinal products Procedure number: EMEA/H/A-5(3)/1490 Note: Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Table of contents Table of contents ...................................................................................... 2 1. Information on the procedure ............................................................... 7 2. Scientific discussion .............................................................................. 7 2.1. Introduction......................................................................................................... 7 2.2. Quality and safety aspects ..................................................................................... 7 2.2.1. Root causes for presence of N-nitrosamines in medicinal products and measures to mitigate them............................................................................................................. 8 2.2.2. Presence and formation of N-nitrosamines -
S-Nitrosylation Drives Cell Senescence and Aging in Mammals By
S-nitrosylation drives cell senescence and aging in PNAS PLUS mammals by controlling mitochondrial dynamics and mitophagy Salvatore Rizzaa,1, Simone Cardacib,1, Costanza Montagnaa,c,1, Giuseppina Di Giacomod,2, Daniela De Zioa, Matteo Bordid, Emiliano Maiania, Silvia Campellod,e, Antonella Borrecaf, Annibale A. Pucag,h, Jonathan S. Stamleri,j, Francesco Cecconia,d,k, and Giuseppe Filomenia,d,3 aDanish Cancer Society Research Center, Center for Autophagy, Recycling and Disease, 2100 Copenhagen, Denmark; bDivision of Genetics and Cell Biology, Institute for Research and Health Care San Raffaele (IRCCS) Scientific Institute, 20132 Milan, Italy; cInstitute of Sports Medicine Copenhagen, Bispebjerg Hospital, 2400 Copenhagen, Denmark; dDepartment of Biology, Tor Vergata University, 00133 Rome, Italy; eIRCCS Fondazione Santa Lucia, 00146 Rome, Italy; fInstitute of Cellular Biology and Neuroscience, National Research Council, 00143 Rome, Italy; gCardiovascular Research Unit, IRCCS Multimedica, 20138 Milan, Italy; hDipartimento di Medicina e Chirurgia, University of Salerno, 84084 Fisciano Salerno, Italy; iInstitute for Transformative Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106; jHarrington Discovery Institute, University Hospitals Case Medical Center, Cleveland, OH 44106; and kDepartment of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital, 00146 Rome, Italy Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 1, 2018 (received for review January 9, 2018) S-nitrosylation, a prototypic redox-based posttranslational modifi- found in experimental models of aging, supporting the idea that cation, is frequently dysregulated in disease. S-nitrosoglutathione GSNOR preserves cellular function. reductase (GSNOR) regulates protein S-nitrosylation by function- The free radical theory of aging postulates that oxidative ing as a protein denitrosylase. -
Proceeding of the Symposium NITRIC OXIDE Basic Regulations And
Proceeding of the Symposium NITRIC OXIDE Basic Regulations and Pharmacological Interventions September 21-24, 2005, Tucepi, Croatia Abstracts are presented in the alphabetical order of the first author names and are printed without editing in the submitted form. The Editorial Office of Physiological Research disclaims any responsibility for errors that may have been made in abstracts submitted by the authors. Vol. 55 Physiol. Res. 2006 1P VASODILATORY RESPONS ES UNDER HYPOXIC responses of myocardium to NOD and in adaptive responses of these CONDITION: ROLE OF PGI2 AND NO hearts to ischemic stress. The results point also to the possible I. Juránek, V. Bauer, J. Donnerer1, F. Lembeck1, B.A. Peskar1 relationship between ERK pathway and activation of eNOS and/or Institute of Experimental Pharmacology, Slovak Academy of Sciences, tissue MMP-2. Bratislava, Slovakia; 1Institute of Experimental and Clinical 1. Strohm et. al., J. Cardiovasc. Pharmacol. 2000, 36:218-229 Pharmacology, Medical University, Graz, Austria. Supported by VEGA SR No 2/3123/25, 2/5110/25, APVT 51-013802, SP51/0280900/ 0280901, SP51/028000/0280802. Aim of the present study was to test hypothesis that low availability of oxygen in hypoxic tissue should inhibit oxygenation of arachidonic acid and thereby result in inhibition of eicosanoid synthesis in vivo. Perfusion of the isolated rabbit ear with normoxic or hypoxic medium DUAL ROLE OF NO IN SUSCEPTIBILITY TO ISCHEMIA/ was applied. Eicosanoid biosynthesis and functional responses of the REPERFUSION INJURY IN THE RAT HEART vascular bed were followed. Simultaneous recording of prostaglandin I2 E. Andelová, M. Pintérová, P. Šimoncíková, M. Barancík, M. release and peripheral resistance of t he preparation revealed that lack of Ondrejcáková, *O. -
Coronary Microvascular Dysfunction in CAD: Consequences and Potential Therapeutic Applications
4 Coronary Microvascular Dysfunction in CAD: Consequences and Potential Therapeutic Applications Alan N. Beneze1, Jeffrey M. Gold4 and Betsy B. Dokken1,2,3 1University of Arizona College of Medicine 2University of Arizona Department of Medicine, Section of Endocrinology 3University of Arizona Sarver Heart Center 4Inpatient Physicians Consultants, Tucson, Arizona USA 1. Introduction Substantial research and clinical effort has been directed toward the understanding, identification and management of coronary artery disease (CAD). As a result, the processes of cholesterol accumulation and inflammation that lead to large vessel occlusions have been fully elucidated. In contrast to those with CAD, many patients have symptoms of angina and reductions in coronary flow reserve despite normal coronary angiography of the large epicardial arteries. In this situation the vessels that limit flow to myocardium are the more distal epicardial prearterioles and intramyocardial arterioles – vessels typically too small to be directly visualized by conventional coronary angiography. These vessels comprise the coronary microcirculation. Coronary microvascular dysfunction (CMVD), in contrast to CAD, continues to be poorly understood and difficult to manage. In addition, the presence of CMVD can be a confounding factor in the management of patients with CAD. 2. Anatomy and physiology of the coronary microcirculation The coronary arterial network is generally divided into three sequential morphological zones. The large epicardial coronary arteries decrease in diameter from 2-5 to 500 microns as they branch off of the aorta and travel distally along the epicardium. Distal to the large coronary arteries are epicardial pre-arterioles that decrease in diameter from 500 to 100 microns. Finally, the pre-arterioles give rise to intramyocardial arterioles that measure 100 microns or less in diameter.