DOCSLIB.ORG

Download Product Insert (PDF)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Download Product Insert (PDF) PRODUCT INFORMATION Dihydroartemisinin Item No. 19846 CAS Registry No.: 71939-50-9 Formal Name: (3R,5aS,6R,8aS,9R,10S,12R,12aR)-decahydro- 3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]- 1,2-benzodioxepin-10-ol O O Synonyms: DHQHS 2, Dihydroqinghaosu O MF: C H O 15 24 5 O FW: 284.4 H H Purity: ≥98% HO Supplied as: A crystalline solid H Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Dihydroartemisinin is supplied as a crystalline solid. A stock solution may be made by dissolving the dihydroartemisinin in the solvent of choice, which should be purged with an inert gas. Dihydroartemisinin is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF). The solubility of dihydroartemisinin in these solvents is approximately 16, 10, and 20 mg/ml, respectively. Dihydroartemisinin is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, dihydroartemisinin should first be dissolved in DMF and then diluted with the aqueous buffer of choice. Dihydroartemisinin has a solubility of approximately 0.5 mg/ml in a 1:1 solution of DMF:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day. Description Dihydroartemisinin is an active metabolite of the antimalarial drugs artemether (Item No. 11815) and artesunate (Item No. 11817).1 It is often used as part of an artemisinin combination therapy with piperaquine.2-4 References 1. Wang, Z., Liu, M., Liang, X., et al. A flow cytometry-based quantitative drug sensitivity assay for all Plasmodium falciparum gametocyte stages. PLoS One 9(4), 1-9 (2014). 2. Askling, H.H., Bruneel, F., Burchard, G., et al. Management of imported malaria in Europe. Malar. J. 11, 1-15 (2012). 3. Henrich, P.P., O’Brien, C., Sįenz, F.E., et al. Evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model. Antimicrob. Agents Chemother. 58(1), 183-195 (2014). 4. Pascual, A., Parola, P., Benoit-Vical, F., et al. Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum. Malar. J. 11, 1-9 (2012). WARNING CAYMAN CHEMICAL THIS PRODUCT IS FOR RESEARCH ONLY - NOT FOR HUMAN OR VETERINARY DIAGNOSTIC OR THERAPEUTIC USE. 1180 EAST ELLSWORTH RD SAFETY DATA ANN ARBOR, MI 48108 · USA This material should be considered hazardous until further information becomes available. Do not ingest, inhale, get in eyes, on skin, or on clothing. Wash thoroughly after handling. Before use, the user must review the complete Safety Data Sheet, which has been sent via email to your institution. PHONE: [800] 364-9897 WARRANTY AND LIMITATION OF REMEDY [734] 971-3335 Buyer agrees to purchase the material subject to Cayman’s Terms and Conditions. Complete Terms and Conditions including Warranty and Limitation of Liability information can be found on our website. FAX: [734] 971-3640 [email protected] Copyright Cayman Chemical Company, 06/17/2020 WWW.CAYMANCHEM.COM.
Load more

Recommended publications
  • A Screening-Based Approach to Circumvent Tumor Microenvironment
    JBXXXX10.1177/1087057113501081Journal of Biomolecular ScreeningSingh et al. 501081research-article2013 Original Research Journal of Biomolecular Screening 2014, Vol 19(1) 158 –167 A Screening-Based Approach to © 2013 Society for Laboratory Automation and Screening DOI: 10.1177/1087057113501081 Circumvent Tumor Microenvironment- jbx.sagepub.com Driven Intrinsic Resistance to BCR-ABL+ Inhibitors in Ph+ Acute Lymphoblastic Leukemia Harpreet Singh1,2, Anang A. Shelat3, Amandeep Singh4, Nidal Boulos1, Richard T. Williams1,2*, and R. Kiplin Guy2,3 Abstract Signaling by the BCR-ABL fusion kinase drives Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Despite their clinical activity in many patients with CML, the BCR-ABL kinase inhibitors (BCR-ABL-KIs) imatinib, dasatinib, and nilotinib provide only transient leukemia reduction in patients with Ph+ ALL. While host-derived growth factors in the leukemia microenvironment have been invoked to explain this drug resistance, their relative contribution remains uncertain. Using genetically defined murine Ph+ ALL cells, we identified interleukin 7 (IL-7) as the dominant host factor that attenuates response to BCR-ABL-KIs. To identify potential combination drugs that could overcome this IL-7–dependent BCR-ABL-KI–resistant phenotype, we screened a small-molecule library including Food and Drug Administration–approved drugs. Among the validated hits, the well-tolerated antimalarial drug dihydroartemisinin (DHA) displayed potent activity in vitro and modest in vivo monotherapy activity against engineered murine BCR-ABL-KI–resistant Ph+ ALL. Strikingly, cotreatment with DHA and dasatinib in vivo strongly reduced primary leukemia burden and improved long-term survival in a murine model that faithfully captures the BCR-ABL-KI–resistant phenotype of human Ph+ ALL.
    [Show full text]
  • Treatment Failure Due to the Potential Under-Dosing of Dihydroartemisinin-Piperaquine in a Patient with Plasmodium Falciparum Uncomplicated Malaria
    INFECT DIS TROP MED 2019; 5: E525 Treatment failure due to the potential under-dosing of dihydroartemisinin-piperaquine in a patient with Plasmodium falciparum uncomplicated malaria I. De Benedetto1, F. Gobbi2, S. Audagnotto1, C. Piubelli2, E. Razzaboni3, R. Bertucci1, G. Di Perri1, A. Calcagno1 1Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Torino, Italy 2Department of Infectious–Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Italy 3Unit of Infectious Diseases, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy ABSTRACT: — Background: Dihydroartemisinin/piperaquine (DHA-PPQ) 40/320 mg is approved for the treatment of Plasmodium falciparum uncomplicated malaria. Different recommendations are provided by WHO guidelines and drug data sheet about dosing in overweight patients. We report here a treatment failure likely caused by sub-optimal dosing of dihydroartemisinin-piperaquine in a case of uncomplicated P. fal- ciparum malaria in a returning traveler from Burkina Faso. INTRODUCTION kg). They, therefore, provided an updated dosing body weight dosing schedule in their 2015 guidelines for Dihydroartemisinin/piperaquine (DHA-PPQ) 40/320 malaria treatment that provides for a dose of 200/1600 mg tablet formulation is approved for the treatment mg (5 tablets) in individuals > 80 kg1. of Plasmodium falciparum uncomplicated malaria in adults and children > 6 months and > 5 kg of body weight. Following WHO guidelines, the daily
    [Show full text]
  • Eurartesim (Piperaquine Tetraphosphate
    ® Eurartesim (piperaquine tetraphosphate/ dihydroartemisinin ) Guide for Healthcare Professionals (Physician Leaflet) REVISED EDITION 2016 This guide is intended to provide you with information regarding the safe use of Eurartesim and to support you in providing information and counseling to your patients. Guide for Healthcare Professionals – Final English version, dated 05 August 2016 Pag.2 About Eurartesim Eurartesim tablets contain two active antimalarial ingredients: dihydroartemisinin (DHA) and piperaquine tetraphosphate (PQP). The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. Eurartesim is effective against Plasmodium falciparum malaria in adults and children. Data are available from large clinical trials that involved over 2600 patients in Africa and Asia, of whom over 1000 were children under 5 years of age. The studies were designed to compare the safety and efficacy of Eurartesim with the established artemisinin combination therapies artemether/lumefantrine (in Africa) and artesunate/mefloquine (in Asia). Eurartesim was shown to be at least as effective as the comparator agents and well tolerated, overall. The DHA component of Eurartesim reaches high concentrations within the parasitised erythrocytes and shows rapid schizontocidal activity by means of free-radical damage to parasite membrane systems. The exact mechanism of action of the PQP component is unknown, but is thought to mirror that of chloroquine, a close structural analogue. PQP has shown good activity against chloroquine- resistant Plasmodium strains in vitro and has a long half-life (20–22 days) resulting in a sustained antimalarial effect. This medicinal product is subject to additional monitoring.
    [Show full text]
  • Current Antimalarial Therapies and Advances in the Development of Semi-Synthetic Artemisinin Derivatives
    Anais da Academia Brasileira de Ciências (2018) 90(1 Suppl. 2): 1251-1271 (Annals of the Brazilian Academy of Sciences) Printed version ISSN 0001-3765 / Online version ISSN 1678-2690 http://dx.doi.org/10.1590/0001-3765201820170830 www.scielo.br/aabc | www.fb.com/aabcjournal Current Antimalarial Therapies and Advances in the Development of Semi-Synthetic Artemisinin Derivatives LUIZ C.S. PINHEIRO1, LÍVIA M. FEITOSA1,2, FLÁVIA F. DA SILVEIRA1,2 and NUBIA BOECHAT1 1Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos Farmanguinhos, Fiocruz, Departamento de Síntese de Fármacos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil 2Universidade Federal do Rio de Janeiro, Programa de Pós-Graduação em Química, Avenida Athos da Silveira Ramos, 149, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil Manuscript received on October 17, 2017; accepted for publication on December 18, 2017 ABSTRACT According to the World Health Organization, malaria remains one of the biggest public health problems in the world. The development of resistance is a current concern, mainly because the number of safe drugs for this disease is limited. Artemisinin-based combination therapy is recommended by the World Health Organization to prevent or delay the onset of resistance. Thus, the need to obtain new drugs makes artemisinin the most widely used scaffold to obtain synthetic compounds. This review describes the drugs based on artemisinin and its derivatives, including hybrid derivatives and dimers, trimers and tetramers that contain an endoperoxide bridge. This class of compounds is of extreme importance for the discovery of new drugs to treat malaria. Key words: malaria, Plasmodium falciparum, artemisinin, hybrid.
    [Show full text]
  • Front-Line Glioblastoma Chemotherapeutic Temozolomide Is Toxic
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of East Anglia digital repository 1 Front-line glioblastoma chemotherapeutic temozolomide is toxic 2 to Trypanosoma brucei and potently enhances melarsoprol and 3 eflornithine 4 5 Dietmar Steverding *, Stuart A. Rushworth 6 7 Bob Champion Research & Education Building, Norwich Medical School, University of East 8 Anglia, Norwich, NR4 7UQ, UK 9 10 11 12 __________ 13 * Tel: +44-1603-591291; fax: +44-1603-591750. 14 E-mail address: [email protected] 15 1 16 A B S T R A C T 17 18 Sleeping sickness is an infectious disease that is caused by the protozoan parasite 19 Trypanosoma brucei. The second stage of the disease is characterised by the parasites 20 entering the brain. It is therefore important that sleeping sickness therapies are able to cross 21 the blood-brain barrier. At present, only three medications for chemotherapy of the second 22 stage of the disease are available. As these trypanocides have serious side effects and are 23 difficult to administer, new and safe anti-trypanosomal brain-penetrating drugs are needed. 24 For these reasons, the anti-glioblastoma drug temozolomide was tested in vitro for activity 25 against bloodstream forms of T. brucei. The concentration of the drug required to reduce the 26 growth rate of the parasites by 50% was 29.1 μM and to kill all trypanosomes was 125 μM. 27 Importantly, temozolomide did not affect the growth of human HL-60 cells up to a 28 concentration of 300 μM.
    [Show full text]
  • Malaria Chemoprevention with Monthly Dihydroartemisinin
    Kwambai et al. Trials (2018) 19:610 https://doi.org/10.1186/s13063-018-2972-1 STUDY PROTOCOL Open Access Malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: study protocol for a multi-centre, two-arm, randomised, placebo-controlled, superiority trial Titus K. Kwambai1,2,3* , Aggrey Dhabangi4, Richard Idro4, Robert Opoka4, Simon Kariuki1, Aaron M. Samuels5, Meghna Desai5, Michael Boele van Hensbroek6, Chandy C. John7, Bjarne Robberstad8, Duolao Wang3, Kamija Phiri9 and Feiko O. ter Kuile1,3 Abstract Background: Children hospitalised with severe anaemia in malaria endemic areas in Africa are at high risk of readmission or death within 6 months post-discharge. Currently, no strategy specifically addresses this period. In Malawi, 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment courses of artemether- lumefantrine given at discharge and at 1 and 2 months prevented 30% of all-cause readmissions by 6 months post- discharge. Another efficacy trial is needed before a policy of malaria chemoprevention can be considered for the post- discharge management of severe anaemia in children under 5 years of age living in malaria endemic areas. Objective: We aim to determine if 3 months of PMC with monthly 3-day treatment courses of dihydroartemisinin- piperaquine is safe and superior to a single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths (composite primary endpoint) by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia of any or undetermined cause.
    [Show full text]
  • Surveillance for Falsified and Substandard Medicines in Africa and Asia by Local Organizations Using the Low-Cost GPHF Minilab
    RESEARCH ARTICLE Surveillance for falsified and substandard medicines in Africa and Asia by local organizations using the low-cost GPHF Minilab Albert Petersen1*, Nadja Held2, Lutz Heide2*, on behalf of the DifaÈm-EPN Minilab Survey Group¶ a1111111111 1 DifaÈm - German Institute for Medical Mission, TuÈbingen, Germany, 2 Pharmaceutical Institute, Eberhard Karls-University TuÈbingen, TuÈbingen, Germany a1111111111 a1111111111 ¶ Membership of the DifaÈm-EPN Minilab Survey Group is provided in the Acknowledgments a1111111111 * [email protected] (AP); [email protected] (LH) a1111111111 Abstract OPEN ACCESS Background Citation: Petersen A, Held N, Heide L, on behalf of Substandard and falsified medical products present a serious threat to public health, espe- the DifaÈm-EPN Minilab Survey Group (2017) cially in low- and middle-income countries. Their identification using pharmacopeial analysis Surveillance for falsified and substandard is expensive and requires sophisticated equipment and highly trained personnel. Simple, medicines in Africa and Asia by local organizations using the low-cost GPHF Minilab. PLoS ONE 12(9): low-cost technologies are required in addition to full pharmacopeial analysis in order to e0184165. https://doi.org/10.1371/journal. accomplish widespread routine surveillance for poor-quality medicines in low- and middle- pone.0184165 income countries. Editor: Yoel Lubell, Mahidol-Oxford Tropical Medicine Research Unit, THAILAND Methods Received: May 30, 2017 Ten faith-based drug supply organizations in seven countries of Africa and Asia were each Accepted: August 19, 2017 equipped with a Minilab of the Global Pharma Health Fund (GPHF, Frankfurt, Germany), suitable for the analysis of about 85 different essential medicines by thin-layer chromatogra- Published: September 6, 2017 phy.
    [Show full text]
  • Has Doxycycline, in Combination with Anti-Malarial Drugs, a Role to Play In
    Gaillard et al. Malar J (2018) 17:469 https://doi.org/10.1186/s12936-018-2621-x Malaria Journal OPINION Open Access Has doxycycline, in combination with anti‑malarial drugs, a role to play in intermittent preventive treatment of Plasmodium falciparum malaria infection in pregnant women in Africa? Tiphaine Gaillard1, Manon Boxberger2,3, Marylin Madamet2,3,4 and Bruno Pradines2,3,4* Abstract According to the World Health Organization (WHO), Plasmodium falciparum malaria during pregnancy is responsible for deleterious consequences for the mother and her child. The administration of intermittent preventive treatment (IPTp) with sulfadoxine–pyrimethamine (SP) at each antenatal care visit as early as 13 weeks of gestation until the time of delivery is a strategy that is currently recommended by WHO for the prevention of malaria in pregnancy. However, the emergence and the spread of the resistance to SP in Africa raise the question of the short-term efectiveness of the strategy. Dihydroartemisinin–piperaquine 120 mg/960 mg once a day for 3 consecutive days administered at least three times during the pregnancy might be an option for IPTp. The combination of 200 mg of doxycycline once a day for 3 consecutive days seems to be a good option to retard the emergence and the spread of resistance to artemisinin-based combination therapy (ACT) in Africa and improve the efectiveness of ACT in term of preterm births, neonatal morbidity and mortality. Contrary to preconceived ideas, scientifc and medical data suggest that the risk of congenital malformations in the fetus or of tooth staining in infants whose mothers take doxycycline and hepatotoxicity during pregnancy is very low or non-existent.
    [Show full text]
  • Piperaquine for the Post-Discharge Management of Severe
    Post-discharge Malaria Chemoprevention (PMC) study PMC Protocol v4.0 (Amendment) 06Feb18 Malaria Chemoprevention with monthly treatment with dihydroartemisinin- piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: A 3-year, multi-centre, parallel-group, two-arm randomised placebo controlled superiority trial Short Title: Post-discharge Malaria Chemoprevention (PMC) study Study Identifiers: KEMRI: LSTM REC: Norway REC: Uganda REC: Primary Registry #2965 #14.034 #2014/1911 #2015-125 Clinicaltrials.gov NCT02671175 Chief Investigator: • Prof Feiko ter Kuile, KEMRI/CDC and LSTM, Pembroke Place, L3 5QA Liverpool, United Kingdom: +44 151 705 3287; and P.O. Box 1578, Kisumu 40100, Mobile: +254 708 739 228; E- mail: [email protected] Country Co-Principal Investigators: Uganda • Dr Richard Idro, Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, P.O Box 7072, Kampala Uganda; Mobile +256 774274173, E-mail: [email protected] • Dr Robert Opoka, College of Health Sciences, Makerere University, P.O Box 7072, Kampala Uganda, Mobile + 256 772996164, Email: [email protected] Kenya • Dr Simon Kariuki, KEMRI Centre for Global Health Research (CGHR) and CDC Collaboration, P.O. Box 1578, Kisumu 40100. Mobile: + 254 725 389 246; E-mail: [email protected] • Dr Titus Kwambai, Kenya Ministry of Health, POBox 486 KISUMU 40100, and KEMRI Centre for Global Health Research (CGHR), P.O. Box 1578, Kisumu 40100. Mobile: +254 723354238; E- mail: [email protected]
    [Show full text]
  • Rapid and Quantitative Antimalarial Drug Efficacy Testing Via the Magneto-Optical Detection of Hemozoin
    www.nature.com/scientificreports OPEN Rapid and quantitative antimalarial drug efcacy testing via the magneto‑optical detection of hemozoin Petra Molnár1,2,4*, Ágnes Orbán1,2, Richard Izrael1,3,4, Réka Babai1,4, Lívia Marton1, Ádám Butykai2, Stephan Karl5,6, Beáta G. Vértessy1,4* & István Kézsmárki1,2,7* Emergence of resistant Plasmodium species makes drug efcacy testing a crucial part of malaria control. Here we describe a novel assay for sensitive, fast and simple drug screening via the magneto‑ optical detection of hemozoin, a natural biomarker formed during the hemoglobin metabolism of Plasmodium species. By quantifying hemozoin production over the intraerythrocytic cycle, we reveal that hemozoin formation is already initiated by ~ 6–12 h old ring‑stage parasites. We demonstrate that the new assay is capable of drug efcacy testing with incubation times as short as 6–10 h, using synchronized P. falciparum 3D7 cultures incubated with chloroquine, piperaquine and dihydroartemisinin. The determined 50% inhibitory concentrations agree well with values established by standard assays requiring signifcantly longer testing time. Accordingly, we conclude that magneto‑optical hemozoin detection provides a practical approach for the quick assessment of drug efect with short incubation times, which may also facilitate stage‑specifc assessment of drug inhibitory efects. Drug resistance constitutes a long-standing major issue in the fght against malaria. Adaptation of Plasmodium parasites to antimalarial drugs poses a serious threat to both existing drugs and new drug candidates. As a recent example, the development of artemisinin-based drugs was honored by the Nobel Prize in Medicine 2015, yet, resistance of Plasmodium against artemisinins and artemisinin combination therapies may soon become a global issue, as documented by annual reports of WHO 1.
    [Show full text]
  • WHO Technical Document of the Use of Non-Pharmaceutical Forms of Artemisia
    Malaria Policy Advisory Committee Meeting 2–4 October 2019, Geneva, Switzerland Background document for Session 3 WHO technical document of the use of non-pharmaceutical forms of Artemisia October 2019 Introduction Research on the herbal remedies used in the past has led to the discovery of malaria treatments that have saved millions of lives. The powdered bark of the cinchona tree was used to treat malaria, initially in South America and later across the globe. Quinine was first isolated from cinchona tree bark in 1820, and the pure compound quickly demonstrated greater potency than the hot infusions of the bark. With the availability of the pure compound, appropriate dosage could be established and the first modern chemotherapeutic agent against malaria was born (1,2). Today, the most widely used antimalarial treatments, artemisinin-based combination therapies (ACTs), are produced using the pure artemisinin compound extracted from plant Artemisia annua. A full malaria treatment course with an ACT costs less than US$ 2 to procure. There are still ACTs available, capable of treating all malaria strains globally, despite artemisinin partial resistance in South East Asia and resistance to some of the partner drugs used in ACTs. However, for those in need in malaria-endemic countries, ACTs are not always available, are only available at high prices, or are of substandard quality. These difficulties are used as part of the argument in promoting Artemisia plant materials as affordable and self-reliant medicines against malaria. Traditional herbal remedies have several limitations, especially when they are utilized for treating potentially fatal diseases such as malaria.
    [Show full text]
  • The WHO Guidelines for the Treatment of Malaria (MTG)
    AMAZON MALARIA INITIATIVE (AMI)/ RAVREDA IX Annual Evaluation Meeting Santa Cruz, Bolivia 25 March 2010 Dr Peter OLUMESE Global Malaria Programme WHO, Geneva TheThe WHOWHO GuidelinesGuidelines forfor thethe treatmenttreatment ofof malariamalaria (MTG)(MTG)...... ...provide comprehensible, global and evidence-based guidelines for the formulation of policies and protocols for the treatment of malaria z provide a framework for development of specific diagnosis and treatment protocols in countries – Taking in account national and local malaria drug resistance pattern and health services capacity z It is not a clinical management manual for the treatment of malaria z 2nd Edition (2010) – (release date 9 March 2010) www.who.int/malaria/docs/TreatmentGuidelines2010.pdf 2 | Guidelines for the Treatment of Malaria ContentsContents andand scopescope ofof thethe MTGMTG z Malaria diagnosis and treatment – policies and strategies from a clinical and a public health perspective – What to use – in diagnosis, curative/palliative treatment – How and where to use • Indications, contraindications and precautions • Best practices in clinical management • Strategies for the use of medicines 3 | Guidelines for the Treatment of Malaria TheThe WHOWHO GuidelinesGuidelines forfor thethe TreatmentTreatment ofof Malaria...Malaria... ...provides evidence based recommendations for the treatment of: z uncomplicated malaria z severe malaria 9 in special groups (young children, pregnant women, HIV /AIDS) 9 in travellers (from non-malaria endemic regions) 9 in epidemics
    [Show full text]