Conceptual DFT As a Novel Chemoinformatics Tool for Studying

Total Page:16

File Type:pdf, Size:1020Kb

Conceptual DFT As a Novel Chemoinformatics Tool for Studying Open Chem. 2019; 17:1133–1139 Research Article Norma Flores-Holguín, Juan Frau, and Daniel Glossman-Mitnik* Conceptual DFT as a Novel Chemoinformatics Tool for Studying the Chemical Reactivity Properties of the Amatoxin Family of Fungal Peptides https://doi.org/10.1515/chem-2019-0129 Received Sep 12, 2019; accepted Oct 24, 2019 1 Introduction Abstract: The chemical structures and molecular reac- Amatoxins are a group of deadly toxins found in Amanita tivities of the Amatoxin group of fungi-derived peptides fungi consisting of nine octapeptides with a bicycle struc- have been determined by means of the consideration of ture which are named as α-amanitin, β-amanitin, 훾- a model chemistry that has been previously validated as amanitin, ϵ-amanitin, amanullinic acid, amanin, amani- well-behaved for our purposes. The reactivity descriptors namide, amanullin and proamanullin. These toxins are of- were calculated on the basis of a methodological frame- ten associated with another group of bicyclic peptides, the work built around the concepts that are the outcome of the phallotoxins, which only contain seven amino acids in the so called Conceptual Density Functional Theory (CDFT). ring [1]. This procedure in connection with the different Fukui func- Amatoxins are found in mushrooms of the genera tions allowed to identify the chemically active regions Amanita, Galerina, Lepiota, and Conocybe from the fungal within the molecules. By considering a simple protocol phylum Basidiomycetes. α-amanitin poisoning causes irre- designed by our research group for the estimation of the versible liver damage and is responsible for 90% of fatal pKa of peptides through the information coming from the incidents with mushrooms. Amatoxins are synthesized as chemical hardness, these property has been established a 35 amino acid precursor, which is then cleaved, macrocy- for the different molecular systems explored in this re- clized and further modified including the introduction of search. The information reported through this work could the covalent tryptathionine bond between a cysteine and be of interest for medicinal chemistry researchers in using a tryptophan, the defining feature of amatoxins. The iden- this knowledge for the design of new medicines based on tity of the enzymes and the order in which these reactions the studied peptides or as a help for the understanding of take place remain experimentally undetermined. Precur- the toxicity mechanisms exerted by them. sor peptides containing the N-terminal signature sequence MSDIN have been identified, as well as the protease that Keywords: Amatoxins; Computational Chemistry; CDFT catalyzes the cleavage of the leader sequence (POPA) and Descriptors; Chemoinformatics; pKa the macrocyclase enzyme (POPB). These are the only en- zymes involved in amanitin biosynthesis characterized to date, and both belong to the prolyl oligopeptidase super- family. An extensive kinetic characterization of the macro- cyclase from Galerina marginata revealed similarities with other prolyl oligopeptidases, as well as pronounced prod- uct inhibition caused by the long recognition sequence *Corresponding Author: Daniel Glossman-Mitnik: Laborato- [2, 3]. rio Virtual NANOCOSMOS, Departamento de Medio Ambiente y Chemoinformatics is an important field of research Energía, Centro de Investigación en Materiales Avanzados, Chi- which involves several procedures for the management of huahua, Chih 31136, Mexico; Departament de Química, Univer- chemical information and can be considered a wonderful sitat de les Illes Balears, Palma de Mallorca 07122, Spain; Email: [email protected] instrument for the design of new medicines in the pharma- Norma Flores-Holguín: Laboratorio Virtual NANOCOSMOS, Depar- ceutical industry. The majority of the applications depen- tamento de Medio Ambiente y Energía, Centro de Investigación en dent on Chemoinformatics look to make forecasts about Materiales Avanzados, Chihuahua, Chih 31136, Mexico the natural properties of molecular systems starting from Juan Frau: Departament de Química, Universitat de les Illes Balears, a background built over their associated chemical struc- Palma de Mallorca 07122, Spain Open Access. © 2019 N. Flores-Holguín et al., published by De Gruyter. This work is licensed under the Creative Commons Attri- bution 4.0 License 1134 Ë N. Flores-Holguín et al. tures, and the computational displaying of them by consid- sidered for the final optimization of the resulting molec- ering a tight coupling of biological and organic data. For ular structures because it has been shown that it allows this reason, the connections among biology and chemistry the verification of the ’Koopmans in DFT’ (KID) procedure portrayed by the techniques assoaciated to Computational [11, 23–30]. In the same way, the process for the calcu- Chemistry are very important. For a given molecular sys- lation of the electronic properties and the chemical reac- tem, the structure and its assoaciated chemical properties tivity descriptors of the fungal peptides involved the use may be estimated and visualized on the basis of its related of MN12SX/Def2TZVP/H2O model chemistry through the electron density, and it is in this way that molecular de- consideration of the previously optimized molecular struc- scriptors will without a doubt be identified with molecu- tures. lar properties; nonetheless, the degree of this link will rely upon the particular descriptors, properties and group of molecules considered in the analysis [4]. 3 Results and Discussion This research seeks to obtain the chemical reactivity information of the fungal peptides under study by means As mentioned in the Computational Methodology sec- of the consideration of the Density Functional Theory tion, the MN12SX/DefTZVP/H2O model chemistry com- (DFT) derived concepts. There is a lot of research where bined with the SMD (Solvent Model Based on the Density) the Conceptual DFT is used to relate the reactivity of sev- solvent model [31] was used for the calculation of the elec- eral compounds with biological activity [5–11]. The under- tronic properties of each peptide after using calculation standing of the chemical reactivity properties of the Ama- analysis procedures to determine whether all the struc- toxin molecules will be crucially achieved by means of the tures agree with the minimum energy requirements. All consideration of the Fukui functions to extract the infor- the calculations were performed in the presence of water mation about the reactivity of the peptides which can be as the solvent because the potential bioactivity and toxic- of potential utility in the process of designin new pharma- ity of this fungal peptides is intimately related with the ab- ceutical drugs [12–16]. The information reported through sorption, distribution, metabolism and excretion that take this work could be of interest for medicinal chemistry re- place within the organisms. The graphical sketches of the searchers in using this knowledge for the developing of molecular structures of the Amatoxins are shown in Fig- new medicines based on the studied peptides or as a help ure 1 below. for the understanding of the toxicity mechanisms exerted Following Becke’s ideas [32] and the studies by by them. Baerends et al concluding that the HOMO-LUMO gap of the Kohn-Sham (KS) system can be used as an effective mea- sure of the molecular optical gap [33, 34], ground state cal- 2 Computational Methodology culations were used for the determination of the maximum absorption wavelength that belongs to the fungal peptides The determination of the conformers of the nine fun- of the Amatoxin family to find the respective λmax values gal molecules belonging to the Amatoxin group was per- through the application of chosen model chemistry to de- formed by using the ChemAxon Calculator plugins in- termine the HOMO-LUMO gaps. As we have shown in our cluded in MarvinView 17.15 available from ChemAxon (Bu- previous research [23–29], the KID procedure is also valid dapest, Hungary), a graphical display software considered in the presence of water as the solvent and represents an of utility for the study of chemical structures and reac- advantage over the use of the vertical I and A for the calcu- tions. The procedure stated by choosing the most stable lation of the global descriptors because it avoids the sep- conformer for each peptide by doing Molecular Mechanics arate calculation of the radical cation and anion which calculations through the overall MMFF94 force field [17– could be difficult for molecules of the size considered here. 21]. The resulting lowest energy conformers for each pep- Therefore, the results for the calculation of the electronic tide obtained during this process were then reoptimized properties of the Amatoxins fungal peptides are displayed through the Density Functional Tight Binding (DFTBA) Table 1. functionality accesible within the Gaussian 09 software [22]. By considering the experience acquired in the previ- ous research of our group [11, 23–30], the model chemistry based on the association of the MN12SX functional with the Def2TZVP basis set using water as the solvent was con- Conceptual DFT as a Novel Chemoinformatics Tool for Studying the Amatoxin Family of Fungal Peptides Ë 1135 (a) α-amanitin (b) β-amanitin (c) 훾-amanitin (d) ϵ-amanitin (e) amanullinic acid (f) amanin (g) amaninamide (h) amanullin (i) proamanullin Figure 1: Graphical sketches of the molecular structures of a) α-amanitin; b) β-amanitin; c) 훾-amanitin; d) ϵ-amanitin; e) amanin,
Recommended publications
  • Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins
    Send Orders for Reprints to [email protected] Recent Patents on Anti-Cancer Drug Discovery, 2014, 9, 35-65 35 Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins Franco Dosio1,*, Barbara Stella1, Sofia Cerioni1, Daniela Gastaldi2 and Silvia Arpicco1 1Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, I-10125, Italy; 2Dipartimento di Bio- tecnologie Molecolari e Scienze per la Salute, University of Torino, Torino, I-10125, Italy Received: December 13, 2012; Accepted: February 21, 2013; Revised: March 7, 2013 Abstract: Antibody-delivered drugs and toxins are poised to become important classes of cancer therapeutics. These bio- pharmaceuticals have potential in this field, as they can selectively direct highly potent cytotoxic agents to cancer cells that present tumor-associated surface markers, thereby minimizing systemic toxicity. The activity of some conjugates is of particular interest receiving increasing attention, thanks to very promising clinical trial results in hematologic cancers. Over twenty antibody-drug conjugates and eight immunotoxins in clinical trials as well as some recently approved drugs, support the maturity of this approach. This review focuses on recent advances in the development of these two classes of biopharmaceuticals: conventional toxins and anticancer drugs, together with their mechanisms of action. The processes of conjugation and purification, as reported in the literature and in several patents, are discussed and the most relevant results in clinical trials are listed. Innovative technologies and preliminary results on novel drugs and toxins, as reported in the literature and in recently-published patents (up to February 2013) are lastly examined. Keywords: Antibody drug conjugate, anticancer agents, auristatins immunotoxin, calicheamicins, cross-linkers, duocarmycins, maytansinoids.
    [Show full text]
  • AMATOXIN MUSHROOM POISONING in NORTH AMERICA 2015-2016 by Michael W
    VOLUME 57: 4 JULY-AUGUST 2017 www.namyco.org AMATOXIN MUSHROOM POISONING IN NORTH AMERICA 2015-2016 By Michael W. Beug: Chair, NAMA Toxicology Committee Assessing the degree of amatoxin mushroom poisoning in North America is very challenging. Understanding the potential for various treatment practices is even more daunting. Although I have been studying mushroom poisoning for 45 years now, my own views on potential best treatment practices are still evolving. While my training in enzyme kinetics helps me understand the literature about amatoxin poisoning treatments, my lack of medical training limits me. Fortunately, critical comments from six different medical doctors have been incorporated in this article. All six, each concerned about different aspects in early drafts, returned me to the peer reviewed scientific literature for additional reading. There remains no known specific antidote for amatoxin poisoning. There have not been any gold standard double-blind placebo controlled studies. There never can be. When dealing with a potentially deadly poisoning (where in many non-western countries the amatoxin fatality rate exceeds 50%) treating of half of all poisoning patients with a placebo would be unethical. Using amatoxins on large animals to test new treatments (theoretically a great alternative) has ethical constraints on the experimental design that would most likely obscure the answers researchers sought. We must thus make our best judgement based on analysis of past cases. Although that number is now large enough that we can make some good assumptions, differences of interpretation will continue. Nonetheless, we may be on the cusp of reaching some agreement. Towards that end, I have contacted several Poison Centers and NAMA will be working with the Centers for Disease Control (CDC).
    [Show full text]
  • Meeting Key Synthetic Challenges in Amanitin Synthesis with a New Cytotoxic Analog: 50-Hydroxy- Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 50-hydroxy- Cite this: Chem. Sci., 2020, 11, 11927 0 † All publication charges for this article 6 -deoxy-amanitin have been paid for by the Royal Society of Chemistry Alla Pryyma, Kaveh Matinkhoo, Antonio A. W. L. Wong and David M. Perrin * Appreciating the need to access synthetic analogs of amanitin, here we report the synthesis of 50-hydroxy- Received 29th July 2020 60-deoxy-amanitin, a novel, rationally-designed bioactive analog and constitutional isomer of a-amanitin, Accepted 2nd October 2020 that is anticipated to be used as a payload for antibody drug conjugates. In completing this synthesis, we DOI: 10.1039/d0sc04150e meet the challenge of diastereoselective sulfoxidation by presenting two high-yielding and rsc.li/chemical-science diastereoselective sulfoxidation approaches to afford the more toxic (R)-sulfoxide. drug-tolerant cell subpopulations.7 Examples include ADCs for Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Introduction targeting human epidermal growth factor receptor 2 and pros- 8 9 a-Amanitin, the deadliest of the amatoxins produced by the tate specic membrane antigen. With but a few exceptions, death-cap mushroom Amanita phalloides, is a potent, orally nearly all bioconjugates to a cytotoxic amanitin have emerged 1 a available inhibitor of RNA polymerase II (pol II) (Ki 10 nM), from naturally-sourced -amanitin. To date, conjugation that has been validated as a payload for targeted cancer handles used for a-amanitin-based bioconjugates include the d- 2a therapy.2 First described in 1907 3 and isolated in 1941,4 a- hydroxyl of (2S,3R,4R)-4,5-dihydroxyisoleucine (DHIle), the 10 0 amanitin is a compact bicyclic octapeptide that has been asparagine side chain, and the 6 -hydroxyl of the tryptathio- 11 indispensable for probing RNA pol II-catalysed transcription in nine staple.
    [Show full text]
  • 615.9Barref.Pdf
    INDEX Abortifacient, abortifacients bees, wasps, and ants ginkgo, 492 aconite, 737 epinephrine, 963 ginseng, 500 barbados nut, 829 blister beetles goldenseal blister beetles, 972 cantharidin, 974 berberine, 506 blue cohosh, 395 buckeye hawthorn, 512 camphor, 407, 408 ~-escin, 884 hypericum extract, 602-603 cantharides, 974 calamus inky cap and coprine toxicity cantharidin, 974 ~-asarone, 405 coprine, 295 colocynth, 443 camphor, 409-411 ethanol, 296 common oleander, 847, 850 cascara, 416-417 isoxazole-containing mushrooms dogbane, 849-850 catechols, 682 and pantherina syndrome, mistletoe, 794 castor bean 298-302 nutmeg, 67 ricin, 719, 721 jequirity bean and abrin, oduvan, 755 colchicine, 694-896, 698 730-731 pennyroyal, 563-565 clostridium perfringens, 115 jellyfish, 1088 pine thistle, 515 comfrey and other pyrrolizidine­ Jimsonweed and other belladonna rue, 579 containing plants alkaloids, 779, 781 slangkop, Burke's, red, Transvaal, pyrrolizidine alkaloids, 453 jin bu huan and 857 cyanogenic foods tetrahydropalmatine, 519 tansy, 614 amygdalin, 48 kaffir lily turpentine, 667 cyanogenic glycosides, 45 lycorine,711 yarrow, 624-625 prunasin, 48 kava, 528 yellow bird-of-paradise, 749 daffodils and other emetic bulbs Laetrile", 763 yellow oleander, 854 galanthamine, 704 lavender, 534 yew, 899 dogbane family and cardenolides licorice Abrin,729-731 common oleander, 849 glycyrrhetinic acid, 540 camphor yellow oleander, 855-856 limonene, 639 cinnamomin, 409 domoic acid, 214 rna huang ricin, 409, 723, 730 ephedra alkaloids, 547 ephedra alkaloids, 548 Absorption, xvii erythrosine, 29 ephedrine, 547, 549 aloe vera, 380 garlic mayapple amatoxin-containing mushrooms S-allyl cysteine, 473 podophyllotoxin, 789 amatoxin poisoning, 273-275, gastrointestinal viruses milk thistle 279 viral gastroenteritis, 205 silibinin, 555 aspartame, 24 ginger, 485 mistletoe, 793 Medical Toxicology ofNatural Substances, by Donald G.
    [Show full text]
  • WSC 2000-01 Conference 1
    The Armed Forces Institute of Pathology Department of Veterinary Pathology WEDNESDAY SLIDE CONFERENCE 2002-2003 CONFERENCE 17 12 February 2003 Conference Moderator: LTC Gary Zaucha, DVM Diplomate, ACVP, ABT, and ACVPM Chief, Department of Comparative Pathology Walter Reed Army Institute of Research Silver Spring, MD 20910 CASE I – 1614-1 (AFIP 2850109) Signalment: 5-month-old outbred female Swiss-Webster mouse History: Sentinel mouse in a laboratory colony housed on dirty bedding from other mouse cages, part of an infectious disease surveillance program. Euthanized due to lethargy and unthriftiness. Gross Pathology: Stomach distended approximately three times by gas, fluid, and partially digested food. Kidneys shrunken, pale, and pitted. Multifocal hemorrhagic necrosis and thrombosis of the ovaries bilaterally. Laboratory Results: Negative for all murine infectious pathogens tested in the colony surveillance program by serology, respiratory and intestinal cultures, fecal examination, anal tape, and skin scrapings. Contributor’s Morphologic Diagnosis: Kidney: Chronic nephropathy characterized by membranous glomerulopathy, lymphoplasmacytic adventitial vasculitis and perivasculitis, tubular degeneration, ectasia, and regeneration with protein, hemoglobin, cellular, waxy, and granular casts, and lymphoplasmacytic and histiocytic interstitial nephritis, severe. Contributor’s Comment: This case is consistent with the previously reported syndrome of gastric dilatation and chronic nephropathy in mice exposed to dirty bedding [1]. Although the mean age of affected mice in the published report was 10 months, similar lesions are sometimes found in animals as young as 3 or 4 months of age. The kidney disease appears immune-mediated and is presumably the result of chronic high antigen exposure, although there may be more than one inciting process.
    [Show full text]
  • Toxic Fungi of Western North America
    Toxic Fungi of Western North America by Thomas J. Duffy, MD Published by MykoWeb (www.mykoweb.com) March, 2008 (Web) August, 2008 (PDF) 2 Toxic Fungi of Western North America Copyright © 2008 by Thomas J. Duffy & Michael G. Wood Toxic Fungi of Western North America 3 Contents Introductory Material ........................................................................................... 7 Dedication ............................................................................................................... 7 Preface .................................................................................................................... 7 Acknowledgements ................................................................................................. 7 An Introduction to Mushrooms & Mushroom Poisoning .............................. 9 Introduction and collection of specimens .............................................................. 9 General overview of mushroom poisonings ......................................................... 10 Ecology and general anatomy of fungi ................................................................ 11 Description and habitat of Amanita phalloides and Amanita ocreata .............. 14 History of Amanita ocreata and Amanita phalloides in the West ..................... 18 The classical history of Amanita phalloides and related species ....................... 20 Mushroom poisoning case registry ...................................................................... 21 “Look-Alike” mushrooms .....................................................................................
    [Show full text]
  • New Developments in Amatoxin Poisoning
    New Developments in Amatoxin Poisoning ACMT Annual Scientific Meeting San Juan, PR March 15, 2013 Disclosure S Todd Mitchell MD,MPH Principal Investigator: Prevention and Treatment of Amatoxin Induced Hepatic Failure With Intravenous Silibinin ( Legalon® SIL): An Open Multicenter Clinical Trial Consultant: Madaus-Rottapharm Amatoxin Poisoning: Overview • 95%+ of all fatal mushroom poisonings worldwide are due to amatoxin containing species. • 50-100 Deaths per year in Europe is typical. • Growing Problem in North America, especially Northern Califoriia USA 1976-2005: 126 Reported Cases 2006: 48 Reported Cases, 4 Deaths Summer 2008: 2 Deaths on East Coast September/October 2012: 2 deaths, 1 transplant among 15 total cases on the East Coast. Mexico 2005 & 2006: 19 Reported Deaths. Countless more in SE Asia, Indian Sub-Continent, South Africa Assam, India March 2008: 20 Deaths Swat, Pakistan 2006: Watsonville September 2006 • 57 yo former ER nurse, electrical contractor ingests 8 mushrooms from his property at 1800 on September 8. • Onset of sx ~0200. • Mushrooms identified as Amanita Phalloides by local expert amateur mycologist ~1500. • Presented to ER 24 hours post ingestion: BUN 37, Creat 2.0, Hgb 20.2, Hct 60.5, ALT 96. • Transfer to UCSF 9/10. INR 2.2, ALT 869 after Rx with hydration, antiemetics, repeated doses of charcoal, IV NAC, and IV PEN G. • 72 Hours: INR 4.5, ALT 2274, Bil 4.0. • Liver Transplant 9/14. 2007 Santa Cruz Cohort • EM age 82. ALT 12224, INR 5.4, Factor V 9% @ 72 hours. ALT 3570, INR 1.7, Factor V 49% @ 144 hours. Died from anuric renal failure 1/11.
    [Show full text]
  • Determination of Mushroom Toxin Alpha-Amanitin in Serum by Liquid Chromatography-Mass Spectrometry After Solid-Phase Extraction
    Original article UDC: 615.918:582.28 doi:10.5633/amm.2015.0102 DETERMINATION OF MUSHROOM TOXIN ALPHA-AMANITIN IN SERUM BY LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY AFTER SOLID-PHASE EXTRACTION Maja Vujović1,2, Ivana Ilić3, Vesna Kilibarda4 University of Niš, Faculty of Medicine, Department of Pharmacy, Serbia1 Institute of Forensic Medicine, Niš, Serbia2 University of Niš, Faculty of Medicine, Serbia3 Military Medical Academy Belgrade, National Poison Control Centre, Serbia4 Alpha-amanitin is a cyclic peptide which belongs to a large group of mushroom toxins known as amatoxins. Being responsible for the majority of fatal mushroom poisonings, they require rapid detection and excretion from the body fluids. In accordance with these requirements, a simple and an accurate method was developed for successful identification and quantification of alpha-amanitin in serum with electrospray liquid chromatography–mass spectrometry (LC-ESI-MS) after collision-induced dissociation. The method conforms to the established International Conference on Harmonization Q2A/Q2B 1996 guidelines on the validation of analytical methods. Linearity, precision, extraction recovery and stability test on blank serum spiked with alpha-amanitin and stored in different conditions met the acceptance criteria. The obtained calibration curve was linear over the concentration range 5-100 ng/mL with a lower limit of quantification (LOQ) of 5 ng/mL and limit of detection (LOD) of 2.5 ng/mL. The mean intra- and inter-day precision and accuracy were 6.05% and less than ±15% of nominal values, respectively. The neutral solid phase extraction with copolymer hydrophilic–lipophilic balance cartridges was found optimal for sample preparation with the mean recovery of 91.94%.
    [Show full text]
  • A Report on Mushrooms Poisonings in 2018 at the Apulian Regional Poison Center
    Scientific Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Sep 03; 8(E):616-622. https://doi.org/10.3889/oamjms.2020.4208 eISSN: 1857-9655 Category: E - Public Health Section: Public Health Disease Control A Report on Mushrooms Poisonings in 2018 at the Apulian Regional Poison Center Leonardo Pennisi1, Anna Lepore1, Roberto Gagliano-Candela2*, Luigi Santacroce3, Ioannis Alexandros Charitos1 1Department of Emergency/Urgent, National Poison Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, Foggia, Italy; 2Department of Interdisciplinary Medicine, Forensic Medicine, University of Bari, Bari, Italy; 3Ionian Department, Microbiology and Virology Lab, University of Bari, Bari, Italy Abstract Edited by: Sasho Stoleski BACKGROUND: The “Ospedali Riuniti’s Poison Center” (Foggia, Italy) provides a 24 h telephone consultation in Citation: Pennisi L, Lepore A, Gagliano-Candela R, Santacroce L, Charitos IA. A Report on Mushrooms clinical toxicology to the general public and health-care professionals, including drug information and assessment of Poisonings in 2018 at the Apulian Regional Poison Center. the effects of commercial and industrial chemical substances, toxins but also plants and mushrooms. It participates Open Access Maced J Med Sci. 2020 Sep 03; 8(E):616-622. in diagnosis and treatment of the exposure to toxins and toxicants, also throughout its ambulatory activity. https://doi.org/10.3889/oamjms.2020.4208 Keywords: Poisoning; Intoxication; Epidemiology; Poison center; Mushroom poisoning METHODS: To report data on the epidemiology of mushroom poisoning in people contacting our Poison Center we *Correspondence: Roberto Gagliano-Candela, made computerized queries and descriptive analyses of the medical records database of the mushroom poisoning Department of Interdisciplinary Medicine, Forensic in the poison center of Foggia from January 2018 to December 2018.
    [Show full text]
  • Conference 1 C O N F E R E N C E 16 29 January 2020 18 August, 2021 Dr
    Joint Pathology CeJointnter Pathology Center Veterinary PatholVeterinaryogy Service Pathologys Services WEDNESDAY SLIDE CONFERENCE 2021-2022 WEDNESDAY SLIDE CONFER ENCE 2019-2020 Conference 1 C o n f e r e n c e 16 29 January 2020 18 August, 2021 Dr. Ingeborg Langohr, DVM, PhD, DACVP Professor Department of Pathobiological Sciences Louisiana S tate University School of Veterinary Medicine Baton RouJointge, L APathology Center Silver Spring, Maryland CASE I: CASE S1809996 1: 1 ((4152313JPC 4135077-00) ). Microscoptan/purple.ic Descr ipThetio n:medullary The inte rstitparenchymaium was within thedisrupted section isby diff dozensusel yof infilt brightra tedred btoy dull purple SignalmeSignalment:nt: A 3-mont h-old, male, mixed- moderate linesto lar thatge radiatednumbers from of pre thedomi levelna ofntl they renal crest breed pig 6(-Susmonth scrofa-old )male (intact) mastiff (Canis mononuclethroughar cell thes a lonmedulla.g with edema. There familiaris). is abunda nt type II pneumocyte hyperplasia History: This pig had no previous signs of lining alveolar septae and many of the illness, andHistory: was found dead. The patient was referred to a veterinary medicalalveola r spaces have central areas of Gross Patholteachingogy : hospitalApprox imfollowingately 70% an o facute, 1-dayne- crotic macrophages admixed with other the lungs,history primar ofily lethargy in the c andrani ainappetencel regions o fthat quicklymononucle ar cells and fewer neutrophils. the lobes, progressedwere patch toy obtundation. dark red, and Bloodwork firm performedOc casionally there is free nuclear basophilic comparedat to thethe rDVMmore norevealedrmal ar etooas ofhigh lun tog. read ALT, elevated ALP (805 U/L), hypoalbuminemia (2.7 Laboratorg/dL)y re suandlts: hypoglycemia Porcine reprodu (23 cmg/dL).tive PT and and respiraaPTTtory weresyndrome both prolonged (PRRS) PCat >100R wa secs and >300 positive frsec,om sprespectively.lenic tissue, Protein and P RandRS IHCbilirubin were was strongdetectedly immunore on a urineactive dipstick.
    [Show full text]
  • Poisonous Mushrooms; a Review of the Most Common Intoxications A
    Nutr Hosp. 2012;27(2):402-408 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Revisión Poisonous mushrooms; a review of the most common intoxications A. D. L. Lima1, R. Costa Fortes2, M. R.C. Garbi Novaes3 and S. Percário4 1Laboratory of Experimental Surgery. University of Brasilia-DF. Brazil/Paulista University-DF. Brazil. 2Science and Education School Sena Aires-GO/University of Brasilia-DF/Paulista University-DF. Brazil. 3School of Medicine. Institute of Health Science (ESCS/FEPECS/SESDF)/University of Brasilia-DF. Brazil. 4Institute of Biological Sciences. Federal University of Pará. Brazil. Abstract HONGOS VENENOSOS; UNA REVISIÓN DE LAS INTOXICACIONES MÁS COMUNES Mushrooms have been used as components of human diet and many ancient documents written in oriental coun- Resumen tries have already described the medicinal properties of fungal species. Some mushrooms are known because of Las setas se han utilizado como componentes de la their nutritional and therapeutical properties and all over dieta humana y muchos documentos antiguos escritos en the world some species are known because of their toxicity los países orientales se han descrito ya las propiedades that causes fatal accidents every year mainly due to medicinales de las especies de hongos. Algunos hongos misidentification. Many different substances belonging to son conocidos por sus propiedades nutricionales y tera- poisonous mushrooms were already identified and are péuticas y de todo el mundo, algunas especies son conoci- related with different symptoms and signs. Carcino- das debido a su toxicidad que causa accidentes mortales genicity, alterations in respiratory and cardiac rates, cada año, principalmente debido a errores de identifica- renal failure, rhabidomyolisis and other effects were ción.
    [Show full text]
  • AMATOXINS in EDIBLE MUSHROOMS H. FAULSTICH* And
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Volume 64, number I FEBS LETTERS April 1976 AMATOXINS IN EDIBLE MUSHROOMS H. FAULSTICH* and M. COCHET-MEILHAC** Max-Planck-Institut fiir medizinische Forschungp Abteilung Naturstoff-Chemie, Jahnstr. 29, D-69 Heidelberg, F. R. G., and **Institut de Chimie Biologique, Unit& de Recherche sur le Cancer de I’INSERM et Centre de Neurochimie du C.N.R.S., FacultP de Midecine, F-67085 Strasbourg, France Received 9 February 1976 1. Introduction 2. Materials and methods The toxic cyclopeptides in Amanita phalloides All mushrooms of the Amanita species, except mushrooms weigh about 0.05% of the fresh tissue. A. rubescens and A. pantherina, were harvested near Two-thirds of this weight are phallotoxins, mostly the Trento (Italy) in 1974. The others were collected acidic compounds phallacidin and phallisacin [ 1,2] , near Heidelberg in 1975. The tissues (20-80 g) were the rest being amatoxins, predominantly cr-amanitin. homogenized in a Star mixer together with a two-fold A combination of chromatographic procedures [3] volume of methanol and then kept under stirring at permits the spectrophotometric determination of up 70°C for 1 h. After centrifugation the supernatant to 11 toxic compounds [4] in single mushrooms. The was evaporated in vacua. The residues were thoroughly sensitivity of this analysis is limited to 0.1 pg of each dried, washed with dry ether and dissolved in 2 ml of toxin, this being sufficient, however, to determine 5 water. The amatoxins were extracted from these different amatoxins in A.
    [Show full text]