Front Cover -- Handbook of Toxicology of Chemical Warfare Agents -- Copyright Page -- Dedication -- Contents -- List of contributors -- Introduction -- I. Historical perspective and epidemiology -- 1 History of toxicology: from killers to healers -- 1.1 Introduction -- 1.2 Ancient times -- 1.3 The Middle Ages -- 1.4 The modern era -- 1.5 Concluding remarks and future directions -- Acknowledgment -- References -- 2 Historical perspective of chemical warfare agents -- 2.1 Introduction -- 2.2 The first sustained use of chemicals as agents of war -- 2.3 Initial countermeasures -- 2.4 Events after World War I -- 2.5 World War II -- 2.6 Post-World War II -- 2.7 Incapacitants and toxins -- 2.8 Recent experience -- 2.9 Terrorist use -- 2.10 Concluding remarks and future directions -- References -- 3 Global impact of chemical warfare agents used before and after 1945 -- 3.1 Introduction -- 3.2 Background -- 3.3 Military use of chemical weapons -- 3.4 The period between World War I and World War II -- 3.5 World War II -- 3.6 The period after World War II, and the Cold War -- 3.7 Iraq-Iran War and the Afghanistan War -- 3.8 Vietnam War -- 3.9 Development of VX agent -- 3.10 Persian Gulf War -- 3.11 Syria -- 3.12 Unintentional use of toxic chemicals -- 3.13 Terrorist use of chemical weapons -- 3.14 Negotiations -- 3.15 Concluding remarks and future directions -- Acknowledgment -- References -- 4 Sarin attacks in Japan: acute and delayed health effects in survivors -- 4.1 Part 1 Sarin attacks in Japan: acute and delayed health effects in survivors of the Matsumoto incident -- 4.1.1 Introduction -- 4.1.2 Matsumoto sarin incident -- 4.1.3 Acute impacts -- 4.1.4 Long-lasting complaints -- 4.1.5 Psychological impacts -- 4.1.6 Ten years after the sarin incident -- 4.1.7 Conclusion -- References -- Chapter 4.2 Part 2 Tokyo sarin attack: acute health effects.
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This book offers an important reference source about the most common classes of pesticides for researchers engaged in the area of neurotoxicology, metabolism, and epidemiology. The book presents details about thorough characterization of target and non-target enzymes and proteins involved in toxicity and metabolism; and epidemiology of poisonings and fatalities in people from short- and long- term exposures to these pesticides in different occupational settings on an individual country basis as well as on a global basis. The early portion of the book deals with metabolism, mechanisms and biomonitoring of anticholinesterase pesticides, while the later part deals with epidemiological studies, regulatory issues, and therapeutic intervention.
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L'articolo è disponibile sul sito dell'editore: http://www.pubs.acs.org ; Ochratoxin A (OTA) is a potent nephrotoxin and renal carcinogen in rats, but the mechanism of OTA tumorigenicity is unknown. Ochratoxin A has been shown to be negative in many genetic toxicology test in vitro. However, the potential of OTA to induce genotoxic effects has not been investigated in male rats, the most sensitive species for OTA-induced tumor formation. In this study, male F344 rats were repeatedly administered OTA (0, 250, 500, 1000, and 2000 íg/kg of body wt) or the non-chlorinated analogue ochratoxin B (OTB; 2000 íg/kg of body wt) for 2 weeks (5 days/week), and DNA breakage was analyzed in target and nontarget tissues using the comet assay both in the absence and presence of formamidopyrimidine-DNA (Fpg) glycosylase. Potential DNA-adduct formation was also analyzed in the target organ kidney by 32P-postlabeling using two different solvent systems. DNA-strand breaks were evident in liver, kidney, and spleen of animals treated with OTA, and a similar degree of DNA damage was observed in rats treated with OTB, despite the lower toxicity of OTB. Moreover, the presence of DNA damage did not correlate with histopathological alterations, which were evident in the kidney but not in the liver. In liver and kidney, the extent of DNA damage was further enhanced in the presence of Fpg glycosylase, which is known to convert oxidative DNA damage into strand breaks, suggesting the presence of oxidative DNA damage. Oxidative DNA damage as a mechanism of OTA-dependent DNA damage is consistent with the absence of lipophilic DNA adducts as assessed by 32P-postlabeling analysis. No spots indicative of OTA-related DNA adducts were observed in kidney DNA extracted from OTA-treated animals by 32P-postlabeling analysis, despite the use of synthetic standard for postulated adducts. A small, but not significant, increase in the incidence of chromosomal aberrations (essentially chromatid and chromosome-type deletions) was observed in splenocytes from rats treated with OTA in vivo and subsequently cultured in vitro to express chromosomal damage. These aberrations are also compatible with oxidative DNA lesions since they are not typically caused by chemical carcinogens which form covalent DNA adducts. Together, with the lack of evidence for formation of lipophilic DNA adducts as assessed by postlabeling, these data suggest that OTA may cause genetic damage in both target and nontarget tissues independent of direct covalent binding to DNA. ; Parts of this work were supported by the Fifth RTD Framework Program of the European Union, Project No. QLK1-2001-01614 and by USPHS Grant CA77114.
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
In: Lener , T , Gimona , M , Aigner , L , Boerger , V , Buzas , E , Camussi , G , Chaput , N , Chatterjee , D , Court , F A , del Portillo , H A , O'Driscoll , L , Fais , S , Falcon-Perez , J M , Felderhoff-Mueser , U , Fraile , L , Gho , Y S , Goergens , A , Gupta , R C , Hendrix , A , Hermann , D M , Hill , A F , Hochberg , F , Horn , P A , de Kleijn , D , Kordelas , L , Kramer , B W , Kraemer-Albers , E-M , Laner-Plamberger , S , Laitinen , S , Leonardi , T , Lorenowicz , M J , Lim , S K , Lotvall , J , Maguire , C A , Marcilla , A , Nazarenko , I , Ochiya , T , Patel , T , Pedersen , S , Pocsfalvi , G , Pluchino , S , Quesenberry , P , Reischl , I G , Rivera , F J , Sanzenbacher , R , Schallmoser , K , Slaper-Cortenbach , I , Strunk , D , Tonn , T , Vader , P , van Balkom , B W M , Wauben , M , El Andaloussi , S , Thery , C , Rohde , E & Giebel , B 2015 , ' Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper ' , Journal of Extracellular Vesicles , vol. 4 , 30087 . https://doi.org/10.3402/jev.v4.30087
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
xtracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed. ; The authors have not received any funding or benefits from industry to conduct this study. The authors acknowledge the european COST action for supporting the European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD, BM1202, www.cost.eu/COST_Actions/BMBS/ Actions/BM1202) who funded publication of this work.
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.