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  • 1
    UID:
    b3kat_BV047327782
    Umfang: Illustrationen, Diagramme
    ISBN: 978-3-428-14077-0
    In: pages:687-697
    In: Krisenmanagement - Notfallplanung - Bevölkerungsschutz / hrsg. von Christoph Unger ..., Berlin, 2013, Seite 687-697, 978-3-428-14077-0
    Sprache: Deutsch
    Mehr zum Autor: Steinritz, Dirk 1978-
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  • 2
    UID:
    edochu_18452_27238
    Umfang: 1 Online-Ressource (15 Seiten)
    ISSN: 1618-2642 , 1618-2642
    Inhalt: Apart from the well-known sulfur mustard (SM), additional sulfur-containing blistering chemical warfare agents exist. Sesquimustard (Q) is one of them and five times more blistering than SM. It is a common impurity in mustard mixtures and regularly found in old munitions but can also be used in pure form. Compared to the extensive literature on SM, very little experimental data is available on Q and no protein biomarkers of exposure have been reported. We herein report for the first time the adduct of Q with the nucleophilic Cys34 residue of human serum albumin (HSA) formed in vitro and introduce two novel bioanalytical procedures for detection. After proteolysis of this HSA adduct catalyzed either by pronase or by proteinase K, two biomarkers were identified by high-resolution tandem mass spectrometry (MS/HR MS), namely a dipeptide and a tripeptide, both alkylated at their Cys residue, which we refer to as HETETE-CP and HETETE-CPF. HETETE represents the Q-derived thio-alkyl moiety bearing a terminal hydroxyl group: “hydroxyethylthioethylthioethyl.” Targeting both peptide markers from plasma, a micro liquid chromatography–electrospray ionization tandem mass spectrometry method working in the selected reaction monitoring mode (μLC-ESI MS/MS SRM) was developed and validated as well suited for the verification of exposure to Q. Fulfilling the quality criteria defined by the Organisation for the Prohibition of Chemical Weapons, the novel methods enable the detection of exposure to Q alone or in mixtures with SM. We further report on the relative reactivity of Q compared to SM. Based on experiments making use of partially deuterated Q as the alkylating agent, we rule out a major role for six-membered ring sulfonium ions as relevant reactive species in the alkylation of Cys34. Furthermore, the results of molecular dynamics simulations are indicative that the protein environment around Cys34 allows adduct formation with elongated but not bulky molecules such as Q, and identify important hydrogen bonding interactions and hydrophobic contacts. Graphical abstract
    Inhalt: Peer Reviewed
    In: Heidelberg : Springer, 412,28, Seiten 7723-7737, 1618-2642
    Sprache: Englisch
    URL: Volltext  (kostenfrei)
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  • 3
    UID:
    edochu_18452_27246
    Umfang: 1 Online-Ressource (10 Seiten)
    ISSN: 1618-2642 , 1618-2642
    Inhalt: Sulfur mustard (SM) is a banned chemical warfare agent recently used in the Syrian Arab Republic conflict causing erythema and blisters characterized by complicated and delayed wound healing. For medical and legal reasons, the proof of exposure to SM is of high toxicological and forensic relevance. SM reacts with endogenous human serum albumin (HSA adducts) alkylating the thiol group of the cysteine residue C34, thus causing the addition of the hydroxyethylthioethyl (HETE) moiety. Following proteolysis with pronase, the biomarker dipeptide C(-HETE)P is produced. To expand the possibilities for verification of exposure, we herein introduce a novel biomarker produced from that alkylated dipeptide by derivatization with propionic anhydride inducing the selective propionylation of the N-terminus yielding PA-C(-HETE)P. Quantitative derivatization is carried out at room temperature in aqueous buffer within 10 s. The biomarker was found to be stable in the autosampler at 15 °C for at least 24 h, thus documenting its suitability even for larger sets of samples. Selective and sensitive detection is done by micro liquid chromatography-electrospray ionization tandem-mass spectrometry (μLC-ESI MS/MS) operating in the selected reaction monitoring (SRM) mode detecting product ions of the single protonated PA-C(-HETE)P (m/z 379.1) at m/z 116.1, m/z 137.0, and m/z 105.0. The lower limit of detection corresponds to 32 nM SM in plasma in vitro and the limit of identification to 160 nM. The applicability to real exposure scenarios was proven by analyzing samples from the Middle East confirming poisoning with SM. Graphical abstract
    Inhalt: Peer Reviewed
    In: Heidelberg : Springer, 413,19, Seiten 4907-4916, 1618-2642
    Sprache: Englisch
    URL: Volltext  (kostenfrei)
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  • 4
    UID:
    almafu_BV001780800
    Umfang: VIII, 80 S. : graph. Darst.
    Anmerkung: München, TU., Diss., 1988
    Schlagwort(e): Hochschulschrift
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  • 5
    UID:
    almahu_BV024934954
    Umfang: 80 S. : , graph. Darst.
    Anmerkung: München, Techn. Univ., Diss., 1988
    Sprache: Deutsch
    Schlagwort(e): Hochschulschrift
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  • 6
    UID:
    almafu_9961259729802883
    Umfang: 1 online resource (360 pages)
    Ausgabe: 3. Auflage.
    ISBN: 3-13-192913-8
    Weitere Ausg.: ISBN 3-13-108973-3
    Sprache: Deutsch
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  • 7
    UID:
    almahu_9949737678002882
    Umfang: 1 online resource (333 p.)
    ISBN: 1-5231-0476-7 , 1-78262-241-1
    Serie: Issues in toxicology ; 26
    Inhalt: This book provides an up-to-date treatise on the on-going research into the toxicology of chemical warfare agents, the diagnosis and verification of exposure, and the pre- and post-exposure treatment of poisoning.
    Anmerkung: Description based upon print version of record. , Cover; Chemical Warfare Toxicology Volume 1: Fundamental Aspects; Preface; References to Material in the National Archives; Contents; Chapter 1 - Development, Historical Use and Properties of Chemical Warfare Agents; 1.1 Introduction; 1.2 Brief History of CW; 1.2.1 Prior to 1914; 1.2.2 The 1914-18 War (WWI); 1.2.2.1 Overview; 1.2.2.2 Irritants; 1.2.2.3 Chlorine; 1.2.2.4 Phosgene; 1.2.2.5 Sulfur Mustard; 1.2.2.6 Other Agents; 1.2.3 The Inter-War Years; 1.2.4 The 1939-1945 War (WWII); 1.2.5 Post WWII and the Cold War Years; 1.2.6 The Middle East; 1.2.7 Terrorism , 1.2.8 Chemical Weapons Convention1.3 Classification, Properties and Modes of Use of CW Agents; 1.3.1 Classification; 1.3.2 Physicochemical Properties; 1.3.2.1 Gaseous and Liquid Agents; 1.3.2.2 Solid Agents; 1.3.3 Ease of Production; 1.4 Main Classes of Chemical Agents; 1.4.1 Lung Injurants (Choking Agents); 1.4.1.1 Chlorine; 1.4.1.2 Phosgene and Diphosgene; 1.4.1.3 Perfluoroisobutene; 1.4.2 Blood Agents; 1.4.2.1 Hydrogen Cyanide; 1.4.2.2 Cyanogen Chloride; 1.4.3 Vesicants (Blister Agents); 1.4.3.1 Sulfur Mustard; 1.4.3.2 Nitrogen Mustards; 1.4.3.3 Lewisite; 1.4.4 Nerve Agents , 1.4.4.1 Tabun and DFP1.4.4.2 Sarin, Soman, Cyclosarin and 2-Methyl GF; 1.4.4.3 V Agents; 1.4.4.4 Other Nerve Agents; 1.4.5 Riot Control Agents; 1.4.6 Incapacitants; 1.4.7 Future Developments; References; Chapter 2 - Toxicology of Vesicants; 2.1 Introduction; 2.2 Sulfur Mustard; 2.2.1 Mechanism of Action; 2.2.1.1 Chemical Reactivity; 2.2.1.2 Alterations to DNA; 2.2.1.3 Alterations to Other Cellular Components and Processes; 2.2.2 Toxicokinetics, Metabolism and Distribution; 2.2.2.1 Studies in Animals , 2.2.2.2.2 Other Routes of Exposure.No systematic studies describe the kinetics of SM following other routes of exposure in humans. In part...2.2.2.3 In vitro Studies; 2.2.3 Acute Toxicity; 2.2.3.1 Studies in Animals; 2.2.3.1.1 Oral Exposure.There are few reports on the oral toxicity of SM. In one study, the oral lethal dose, 50% (LD50) of SM [administer...; 2.2.3.1.2 Dermal Exposure.Since the first research efforts in 1917-1918, a large range of animal species have been exposed to SM liquid an...
    Weitere Ausg.: ISBN 1-84973-969-2
    Sprache: Englisch
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  • 8
    UID:
    almahu_9949737676902882
    Umfang: 1 online resource (346 p.)
    ISBN: 1-5231-0477-5 , 1-78262-807-X
    Serie: Issues in toxicology ; 27
    Inhalt: This book provides an up-to-date treatise on the on-going research into the toxicology of chemical warfare agents, the diagnosis and verification of exposure, and the pre- and post-exposure treatment of poisoning.
    Anmerkung: Description based upon print version of record. , Cover; Chemical Warfare Toxicology Volume 2: Management of Poisoning; Preface; References to Material in The National Archives; Contents; Chapter 1 - Treatment of Nerve Agent Poisoning; 1.1 Introduction; 1.2 OP Compounds; 1.2.1 General Remarks That Are Relevant for Therapy; 1.2.2 Toxicology of OP Compounds; 1.2.2.1 Toxicokinetic Aspects Relevant for Therapy; 1.2.2.2 Toxicodynamics of Nerve Agents; 1.2.2.2.1 Reactions of Nerve Agents with AChE.OP compounds, i.e. nerve agents and pesticides, inhibit serine esterases such as AChE (E.C. ... , 1.2.2.2.2 Binding of Nerve Agents to Other Targets.As highly reactive compounds, nerve agents are able to interact with a variety of prote...1.3 Protective Measures and Decontamination; 1.4 Clinical Picture of Nerve Agent Poisoning; 1.4.1 Acute Nerve Agent Poisoning; 1.4.1.1 Central Nervous System; 1.4.1.2 Autonomic Nervous System; 1.4.1.2.1 Sympathetic Nervous System.Nicotinic ACh receptors are located at paravertebral sympathetic ganglions. In response to the pregan... , 1.4.1.2.2 Parasympathetic Nervous System.ACh is the primary neurotransmitter of the parasympathetic nervous system and neurotransmission o...1.4.1.3 Somatic Nervous System; 1.4.1.4 Conclusion; 1.4.2 Intermediate Syndrome; 1.4.3 Organophosphate Induced Delayed Neuropathy; 1.5 Pretreatment; 1.6 Differences Between Nerve Agent and OP Compound Pesticide Poisoning; 1.7 Therapeutic Regimen of Nerve Agent Poisoning; 1.7.1 General Considerations; 1.7.2 Atropine; 1.7.2.1 Self and Buddy Aid; 1.7.2.2 Treatment by Medical Specialists; 1.7.3 Oximes; 1.7.3.1 General Background , 1.7.3.2 Effectiveness of Oximes in Nerve Agent Poisoning1.7.3.3 Interaction with Persisting Poison Load; 1.7.3.4 Oxime Dosing Strategies; 1.7.3.5 Monitoring of Oxime Therapy; 1.7.3.6 Obidoxime; 1.7.3.7 Pralidoxime; 1.7.3.8 HI-6; 1.7.3.9 Benzodiazepines; 1.7.3.10 Magnesium; 1.7.3.11 Alkalinization by Sodium Bicarbonate; 1.7.3.12 Supportive Treatment; 1.8 Summary and Outlook; References; Chapter 2 - Nerve Agents: Catalytic Scavengers as an Alternative Approach for Medical Countermeasures; 2.1 Introduction; 2.2 The Scavenger Concept; 2.3 Endogenous Bioscavengers; 2.4 Stoichiometric Scavengers , 2.5 Pseudo-Catalytic Scavengers2.6 Catalytic Scavengers; 2.7 Requirements for Operational Catalytic Scavengers; 2.8 Potential Enzymes; 2.8.1 Phosphotriesterases; 2.8.1.1 Bacterial PTEs; 2.8.1.2 Human Paraoxonase; 2.8.1.3 Other Mammalian PTEs; 2.8.2 Engineered ChEs and CaEs; 2.8.3 Oxidases; 2.8.3.1 Glutathione S-Transferases; 2.8.3.2 Laccases; 2.9 Catalytic Antibodies; 2.10 Artificial Enzymes; 2.11 Future Directions; References; Chapter 3 - Nicotinic Receptors as Targets for Nerve Agent Therapy; 3.1 Introduction; 3.2 Current Therapy for Nerve Agent Poisoning , 3.3 Potential Benefits of Nicotinic Antagonists in Nerve Agent Poisoning
    Weitere Ausg.: ISBN 1-78262-803-7
    Sprache: Englisch
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