ATSDR Case Studies in Environmental Medicine Nitrate/Nitrite Toxicity
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Non-Commercial Use Only
only use Non-commercial 14th International Conference on Thalassaemia and Other Haemoglobinopathies 16th TIF Conference for Patients and Parents 17-19 November 2017 • Grand Hotel Palace, Thessaloniki, Greece only use For thalassemia patients with chronic transfusional iron overload... Make a lasting impression with EXJADENon-commercial film-coated tablets The efficacy of deferasirox in a convenient once-daily film-coated tablet Please see your local Novartis representative for Full Product Information Reference: EXJADE® film-coated tablets [EU Summary of Product Characteristics]. Novartis; August 2017. Important note: Before prescribing, consult full prescribing information. iron after having achieved a satisfactory body iron level and therefore retreatment cannot be recommended. ♦ Maximum daily dose is 14 mg/kg body weight. ♦ In pediatric patients the Presentation: Dispersible tablets containing 125 mg, 250 mg or 500 mg of deferasirox. dosing should not exceed 7 mg/kg; closer monitoring of LIC and serum ferritin is essential Film-coated tablets containing 90 mg, 180 mg or 360 mg of deferasirox. to avoid overchelation; in addition to monthly serum ferritin assessments, LIC should be Indications: For the treatment of chronic iron overload due to frequent blood transfusions monitored every 3 months when serum ferritin is ≤800 micrograms/l. (≥7 ml/kg/month of packed red blood cells) in patients with beta-thalassemia major aged Dosage: Special population ♦ In moderate hepatic impairment (Child-Pugh B) dose should 6 years and older. ♦ Also indicated for the treatment of chronic iron overload due to blood not exceed 50% of the normal dose. Should not be used in severe hepatic impairment transfusions when deferoxamine therapy is contraindicated or inadequate in the following (Child-Pugh C). -
Nitroso and Nitro Compounds 11/22/2014 Part 1
Hai Dao Baran Group Meeting Nitroso and Nitro Compounds 11/22/2014 Part 1. Introduction Nitro Compounds O D(Kcal/mol) d (Å) NO NO+ Ph NO Ph N cellular signaling 2 N O N O OH CH3−NO 40 1.48 molecule in mammals a nitro compound a nitronic acid nitric oxide b.p = 100 oC (8 mm) o CH3−NO2 57 1.47 nitrosonium m.p = 84 C ion (pKa = 2−6) CH3−NH2 79 1.47 IR: υ(N=O): 1621-1539 cm-1 CH3−I 56 Nitro group is an EWG (both −I and −M) Reaction Modes Nitro group is a "sink" of electron Nitroso vs. olefin: e Diels-Alder reaction: as dienophiles Nu O NO − NO Ene reaction 3 2 2 NO + N R h 2 O e Cope rearrangement υ O O Nu R2 N N N R1 N Nitroso vs. carbonyl R1 O O O O O N O O hυ Nucleophilic addition [O] N R2 R O O R3 Other reaction modes nitrite Radical addition high temp low temp nitrolium EWG [H] ion brown color less ion Redox reaction Photochemical reaction Nitroso Compounds (C-Nitroso Compounds) R2 R1 O R3 R1 Synthesis of C-Nitroso Compounds 2 O R1 R 2 N R3 3 R 3 N R N R N 3 + R2 2 R N O With NO sources: NaNO2/HCl, NOBF4, NOCl, NOSbF6, RONO... 1 R O R R1 O Substitution trans-dimer monomer: blue color cis-dimer colorless colorless R R NOBF OH 4 - R = OH, OMe, Me, NR2, NHR N R2 R3 = H or NaNO /HCl - para-selectivity ΔG = 10 Kcal mol-1 Me 2 Me R1 NO oxime R rate determining step Blue color: n π∗ absorption band 630-790 nm IR: υ(N=O): 1621-1539 cm-1, dimer υ(N−O): 1300 (cis), 1200 (trans) cm-1 + 1 Me H NMR (α-C-H) δ = 4 ppm: nitroso is an EWG ON H 3 Kochi et al. -
Pneumocystis Pneumonia and Disseminated
1614 BRITISH MEDICAL JOURNAL VOLUmE 286 21 MAY 1983 Br Med J (Clin Res Ed): first published as 10.1136/bmj.286.6378.1614-a on 21 May 1983. Downloaded from Pneumocystis pneumonia and discussions, and Dr B Jameson and Dr D G Fleck for their valuable assistance disseminated toxoplasmosis in a with the pneumocystis and toxoplasma serology. Ammann A, Cowan M, Wara D, et al. Possible transfusion-associated male homosexual acquired immune deficiency syndrome (AIDS)-California. Morbidity and Mortality Weekly Report 1982;31 :652-4. 2 Du Bois RM, Branthwaite MA, Mikhail JR, et al. Primary pneumocystis Within the past two years 788 cases of the apparently new and carinii and cytomegalovirus infections. Lancet 1981 ;ii: 1339. potentially lethal syndrome of acquired immune deficiency have been Oswald GA, Theodossi A, Gazzard BG, et al. Attempted immune stimula- reported in the United States.' Only three cases have been reported in tion in the "gay compromise syndrome." Br MedJ' 1982;285:1082. the United Kingdom.2-4 We report a case in a previously healthy 37 4 Maurice PDL, Smith NP, Pinching AJ. Kaposi's sarcoma with benign course in a homosexual. Lancet 1982;i:571. year old male homosexual who was initially diagnosed and treated for Task force on acquired immune deficiency syndrome, Centers for Disease pneumocystis pneumonia and subsequently died of widespread Control. Update on acquired immune deficiency syndrome (AIDS)- toxoplasmosis. United States. Morbidity and Mortality Weekly Report 1982;31:507-14. (Accepted 4 March 1983) Case report The patient presented with an eight week history of malaise, non-produc- Departments of Microbiology and Medicine, St Thomas's Hospital, tive cough, night sweats, diarrhoea, anorexia, and weight loss. -
Nitrocompounds, Aliphatic: Physical & Chemical Properties
Nitrocompounds, Aliphatic: Physical & Chemical Properties, Encyclopaedia of Occupational Health and Safety, Jeanne Mager Stellman, Editor-in-Chief. International Labor Organization, Geneva. 2011 Chemical Name Colour/Form Boiling Point Melting Molecular Solubility in Relative Density Relative Vapour Inflam. Flash Auto CAS-Number (°C) Point (°C) Weight Water (water=1) Vapour Pressure/ Limits Point (ºC) Ignition Density (Kpa) Point (º C) (air=1) AMYL NITRITE yellowish, transparent 99 117.1 sl sol 0.8828 4.0 110-46-3 liquid 1-CHLORO-1-NITRO- 124.5 109.51 insol 1.2837 ETHANE 598-92-5 2-CHLORO-2-NITRO- liquid 133.6 123.55 0.5 ml sol in 1.197 4.3 8.5 mm Hg 57 ° C oc PROPANE 100 ml @ 20 ° C/20 ° @ 25 ° C 594-71-8 @ 20 ° C C 1-CHLORO-1-NITRO- liquid 143 123.54 0.5ml/100 ml 1.209 0.3 5.8 mm Hg 62 oc PROPANE @ 25 ºC 600-25-9 CHLOROPICRIN slightly oily liquid; 112 -69.2 164.4 sol 1.6558 5.7 5.7 mm Hg 76-06-2 colourless; faint yellow @ 0 º C liquid. 1,1-DICHLORO-1-NI- colourless liquid 124 143.9 0.25 ml/100 m 1.4271 5.0 16.0 mm Hg 76 oc TROETHANE l @ 25 ºC 594-72-9 DIETHYLENE GLYCOL liquid 161 -11.6 sl sol 1.377 DINITRATE @ 25 ºC 693-21-0 ETHYLENE GLYCOL yellowish, oily liquid; 197-200 -22.3 152.06 insol 1.4918 5.24 7 Pa 215 cc 114 DINITRATE colourless 628-96-6 ETHYLENE GLYCOL pale yellow, viscous liquid 197-200 -22.3 152.06 sl sol 1.4978 218 DINITRATE mixed with NITROGLYCERIN (1:1) 53569-64-5 ETHYL NITRATE colourless liquid 87.2 ° C at 762 94.6 ° C 91.07 1.3 g in 100 1.1084 at 20 ° 3.1 lower, 4.0% 10 625-58-1 mm Hg ml C/4 ° C by vol @ 55 ° C ETHYL -
Systems Biology Reveals Reprogramming of the S-Nitroso
www.nature.com/scientificreports OPEN Systems biology reveals reprogramming of the S‑nitroso‑proteome in the cortical and striatal regions of mice during aging process Maryam Kartawy, Igor Khaliulin & Haitham Amal* Cell aging depends on the rate of cumulative oxidative and nitrosative damage to DNA and proteins. Accumulated data indicate the involvement of protein S‑nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modifcation (PTM) of cysteine thiols, in diferent brain disorders. However, the changes and involvement of SNO in aging including the development of the organism from juvenile to adult state is still unknown. In this study, using the state‑of‑the‑ art mass spectrometry technology to identify S‑nitrosylated proteins combined with large‑scale computational biology, we tested the S‑nitroso‑proteome in juvenile and adult mice in both cortical and striatal regions. We found reprogramming of the S‑nitroso‑proteome in adult mice of both cortex and striatum regions. Signifcant biological processes and protein–protein clusters associated with synaptic and neuronal terms were enriched in adult mice. Extensive quantitative analysis revealed a large set of potentially pathological proteins that were signifcantly upregulated in adult mice. Our approach, combined with large scale computational biology allowed us to perform a system‑level characterization and identifcation of the key proteins and biological processes that can serve as drug targets for aging and brain disorders in future studies. Nitric oxide (NO) is produced in diferent organs and tissues, including the central and peripheral nervous sys- tem, and is one of the most important signaling molecules in the body1,2. At low concentrations, it participates in cell signaling and may have therapeutic value for brain injury 3. -
The History of Glyceryl Trinitrate As a Prescription Drug
patches for transdermal delivery and in tablet form. It ARTICLE may also be injected. Th e history of glyceryl trinitrate as a prescription drug Anthony Butler Abstract A number of prescribed drugs possessing a nitro group (-NO2) are vasodilators and are used to relieve the symptoms of angina pectoris. Th e most widely pre- scribed drug in this group is glyceryl trinitrate (GTN). It was fi rst synthesized by an Italian chemist, Ascanio Sobrero, in 1847. Its clinical use was pioneered by phy- sicians including William Murrell and Sir Th omas Lauder Brunton, and it is now an established remedy for the condition. Its mode of action in vivo was a com- plete mystery until the discovery in the 1980s of nitric oxide (NO) as the naturally occurring messenger mol- ecule that triggers the process of vasodilation. However, exactly how the nitro group in GTN is converted into NO is still uncertain, although the general belief is that an enzyme is responsible. Introduction Th e nineteenth and twentieth centuries witnessed a Figure 1. Ascanio Sobrero. (Source: University of Torino surge in the number of new compounds made in the Archive) laboratory that were available for testing as possible drugs. Not only were the physical properties (colour, GTN was fi rst synthesised by an Italian, Ascanio So- crystal form, melting point and so on) of new com- brero (1812-1888) around 1847. (Figure 1). He was born pounds recorded, but the discoverer might do a few in the small town of Casale Monferrato in the Pied- simple tests to see whether the compound had any in- mont region of Italy and studied medicine at the near- teresting biological properties. -
NITROGYLCERIN and ETHYLENE GLYCOL DINITRATE Criteria for a Recommended Standard OCCUPATIONAL EXPOSURE to NITROGLYCERIN and ETHYLENE GLYCOL DINITRATE
CRITERIA FOR A RECOMMENDED STANDARD OCCUPATIONAL EXPOSURE TO NITROGYLCERIN and ETHYLENE GLYCOL DINITRATE criteria for a recommended standard OCCUPATIONAL EXPOSURE TO NITROGLYCERIN and ETHYLENE GLYCOL DINITRATE U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Public Health Service Center for Disease Control National Institute for Occupational Safety and Health June 1978 For »ale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 DISCLAIMER Mention of company name or products does not constitute endorsement by the National Institute for Occupational Safety and Health. DHEW (NIOSH) Publication No. 78-167 PREFACE The Occupational Safety and Health Act of 1970 emphasizes the need for standards to protect the health and provide for the safety of workers occupationally exposed to an ever-increasing number of potential hazards. The National Institute for Occupational Safety and Health (NIOSH) evaluates all available research data and criteria and recommends standards for occupational exposure. The Secretary of Labor will weigh these recommendations along with other considerations, such as feasibility and means of implementation, in promulgating regulatory standards. NIOSH will periodically review the recommended standards to ensure continuing protection of workers and will make successive reports as new research and epidemiologic studies are completed and as sampling and analytical methods are developed. The contributions to this document on nitroglycerin (NG) and ethylene glycol dinitrate (EGDN) by NIOSH staff, other Federal agencies or departments, the review consultants, the reviewers selected by the American Industrial Hygiene Association, and by Robert B. O ’Connor, M.D., NIOSH consultant in occupational medicine, are gratefully acknowledged. The views and conclusions expressed in this document, together with the recommendations for a standard, are those of NIOSH. -
C-Nitroso-Substituted Ligands of Poly(ADP-Ribose) Polymerase (Zinc Rmger/Drug-Induced Cell Death) WILLIAM G
Proc. Nati. Acad. Sci. USA Vol. 89, pp. 7703-7707, August 1992 Pharmacology Induction of endonuclease-mediated apoptosis in tumor cells by C-nitroso-substituted ligands of poly(ADP-ribose) polymerase (zinc rmger/drug-induced cell death) WILLIAM G. RICE*t, CHRISTOPHER D. HILLYERt, BRAD HARTEN*, CATHERINE A. SCHAEFFER*, MARK DORMINY*, DIXON A. LACKEY III*, EVA KIRSTEN§, JEROME MENDELEYEV§, KALMAN G. BUKI§, ALAEDDIN HAKAM§, AND ERNEST KUNt§ *Division of Hematology and Oncology, Department of Pediatrics, and tDepartment of Pathology and Laboratory of Medicine and the Winship Cancer Center, Emory University School of Medicine, Atlanta, GA 30322; and §Laboratory for Environmental Toxicology and Chemistry, The Romberg Tiburon Center, San Francisco State University, P.O. Box 855, Tiburon, CA 94920 Communicated by John Baldeschwieler, May 19, 1992 ABSTRACT 6-Nitroso-1,2-benzopyrone and 3-ni- Assays. For cell proliferation tests, cells were cultured in trosobenzamide, two C-nitroso compounds that inactivate the 96-well tissue culture plates at 3 x 103 cells per well (250-gl eukaryotic nuclear protein poly(ADP-ribose) polymerase total volume per well) for 2 hr (or the indicated length oftime) [NAD+:poly(adenosine diphosphate D-ribose) ADP-D-ribosyl- in the absence or presence of various concentrations of transferase, ADPRT, EC 2.4.2.30] at one zinc-ringer site, NOBA or NOBP; thereafter 0.5 ,uCi of [methyl-3H]thymidine completely suppressed the proliferation of leukemic and other (85 Ci/mmol; 1 Ci = 37 GBq) was added per well and its malignant human cells and subsequently produced cell death. incorporation into DNA following an 18-hr incubation was Tumoricidal concentrations of the drugs were relatively harm- determined radiochemically (6). -
US5489610.Pdf
|||||||| US00548961OA United States Patent 19 11 Patent Number: 5,489,610 Fung et al. 45) Date of Patent: 8 Feb. 6, 1996 54 SUSTAINED RELEASE ORGANIC NITRITE 58 Field of Search .................................... 514/506, 509, THERAPY 514/645, 740 75 Inventors: Ho-Leung Fung, Getzville; John A. 56) References Cited Bauer, Williamsville, both of N.Y. U.S. PATENT DOCUMENTS 73 Assignee: Research Foundation of the State 5,278,192 l/1994 Fung et al. .............................. 514f645 University of New York, Albany, N.Y. OTHER PUBLICATIONS * Notice: The portion of the term of this patent Derwent Abstracts 78–35053A, "Medicaments for Treating disclaimed.subsequent to Jan. 11, 2011, has been Cardiardiogenic Shock”, Fribolinis is et al. (1978). Patent Abstracts of Japan, vol. 12, No. 467, Dec. 7, 1988, 21 Appl. No.: 199,280 "Tape Preparation'. 22, PCT Filed: Jun. 30, 1993 Primary Examiner-Frederick Krass Attorney, Agent, or Firm-Kirschstein et al. 86 PCT No.: PCT/US93/06235 (57) ABSTRACT S371 Date: Mar. 1, 1994 A method of treating a patient suffering from a condition S 102(e) Date: Mar. 1, 1994 requiring vasodilator therapy, comprising long term, con 87 PCT Pub. No.: WO94/01103 tinuous adminstration of an organic nitrite to the patient in a dosage form capable of delivering a sufficient therapeutic PCT Pub. Date:Jan. 20, 1994 amount of nitrite to the bloodstream of the patient thereby providing effective vasodilator therapy for at least 24 hours Related U.S. Application Data without the development of tolerance in the patient. The a method of the invention is useful in treating conditions such 63 Continuation-in-part of Ser. -
The Formation of Methemoglobin and Sulfhemoglobin During Sulfanilamide Therapy
THE FORMATION OF METHEMOGLOBIN AND SULFHEMOGLOBIN DURING SULFANILAMIDE THERAPY J. S. Harris, H. O. Michel J Clin Invest. 1939;18(5):507-519. https://doi.org/10.1172/JCI101064. Research Article Find the latest version: https://jci.me/101064/pdf THE FORMATION OF METHEMOGLOBIN AND SULFHEMOGLOBIN DURING SULFANILAMIDE THERAPY By J. S. HARRIS AND H. 0. MICHEL (From the Departments of Pediatrics and Biochemistry, Duke University School of Medicine, Durham) (Received for publication April 8, 1939) Cyanosis almost invariably follows the admin- during the administration of sulfanilamide. Wen- istration of therapeutic amounts of sulfanilamide del (10) found spectroscopic evidence of met- (1). This cyanosis is associated with and is due hemoglobin in every blood sample containing over to a change in the color of the blood. The dark- 4 mgm. per cent sulfanilamide. Evelyn and Mal- ening of the blood is present only in the red cells loy (11) have found that all patients receiving and therefore must be ascribed to one of two sulfanilamide show methemoglobinemia, although causes, a change in the hemoglobin itself or a the intensity is usually very slight. Finally Hart- staining of the red cells with some product formed mann, Perley, and Barnett (12) found cyanosis during the metabolism of sulfanilamide. It is the associated with methemoglobinemia in almost ev- purpose of this paper to assay quantitatively the ery patient receiving over 0.1 gram sulfanilamide effect of sulfanilamide upon the first of these fac- per kilogram of body weight per day. They be- tors-that is, upon the formation of abnormal lieved that the intensity of the methemoglobinemia heme pigments. -
The Role of Nonhemoglobin Proteins and Reduced Glutathione in the Protection of Hemoglobin from Oxidation in Vitro
The Role of Nonhemoglobin Proteins and Reduced Glutathione in the Protection of Hemoglobin from Oxidation In Vitro A. S. Hill Jr., … , G. E. Cartwright, M. M. Wintrobe J Clin Invest. 1964;43(1):17-26. https://doi.org/10.1172/JCI104889. Research Article Find the latest version: https://jci.me/104889/pdf Journal of Clinical Investigatiox Vol. 43, No. 1, 1964 The Role of Nonhemoglobin Proteins and Reduced Glutathione in the Protection of Hemoglobin from Oxidation In Vitro * A. S. HILL, JR., A. HAUT, G. E. CARTWRIGHT, AND M. M. WINTROBE (From the Department of Medicine, University of Utah College of Medicine, Salt Lake City, Utah) A deficiency of reduced glutathione in erythro- human erythrocytes by Allen and Jandl (10) led cytes of freshly shed blood (1-4) or in erythro- these authors to conclude that GSH per se pro- cytes exposed to certain chemical compounds (5) tects hemoglobin from oxidation and that no ad- has been associated with shorter red cell survival ditional factors are required; conversely, Szein- and, in most cases, with the accumulation of oxi- berg and Marks (11) found that GSH affords no dation products of hemoglobin, including methe- protection to human hemoglobin against oxidative moglobin, sulfhemoglobin, and Heinz bodies. changes. The earlier report of Foulkes and Studies of "primaquine-sensitive" hemolytic dis- Lemberg (12) that GSH might oxidize hemo- ease have emphasized as a characteristic feature globin, along with the studies by Szeinberg and an "unstable" reduced glutathione (GSH) in the Marks (11) and Allen and Jandl (10), casts red cells, attributed to limited availability of re- doubt on the applicability to humans of the con- duced TPN (TPNH), the result, in turn, of a cept (13, 14), based on studies of rat blood (7, deficiency of the enzyme, glucose-6-phosphate 8), that an adequate amount of reduced glutathi- dehydrogenase - (G6PD). -
Cocaine/Heroin Induced Rhabdomyolysis and Ventricular Fibrillation B Mccann, R Hunter, J Mccann
264 CASE REPORTS Emerg Med J: first published as 10.1136/emj.19.3.270 on 1 May 2002. Downloaded from Cocaine/heroin induced rhabdomyolysis and ventricular fibrillation B McCann, R Hunter, J McCann ............................................................................................................................. Emerg Med J 2002;19:264–265 PaO2: 24.3 kPa; base deficit: 18.0 mmol/l; lactate: 8.4 mmol/l. A case of cardiorespiratory arrest in a 28 year old Creatine phosphokinase: 90 500 IU/l (normal range 33–194). man after cocaine and heroin ingestion is described. The Urine: myoglobin: positive; cocaine metabolites: positive; arrest is attributed primarily to hyperkalaemia/ opioids: positive. rhabdomyolysis—a recognised consequence of each of Consequent upon his rhabdomyolysis he developed acute these drugs. The administration of naloxone may have renal failure requiring haemodialysis, disseminated intravas- been contributory. He developed acute renal failure, cular coagulopathy and right lower limb compartment disseminated intravascular coagulopathy with consequent syndrome requiring fasciotomy. Echocardiogram showed a lower limb compartment syndrome requiring fasciotomy. left ventricular ejection fraction of 53%. Respiratory function Ventricular fibrillation was identified at thoracotomy. remained stable. At day 10 (after tracheostomy) he had spon- taneous eye opening, flexed to pain and had no response to verbal commands. Brain stem reflexes were intact. Computed tomographic scan of his brain was normal. 28 year old man was brought to the emergency depart- The patient died two months later. Cause of death was ment after intravenous ingestion of cocaine and heroin. bronchopneumonia complicating multiorgan failure. AHe was noted to be pale, cyanosed, bradypnoeic (6/min), and hypotensive (70/40). DISCUSSION Initial treatment consisted of oxygen via a facemask, and 800 Rhabdomyolysis is a well documented complication of cocaine µg of naloxone intravenously.