Download or read book Development of a Guinea Pig Model for Low Dose Chronic Exposure to Organophosphorus Nerve Agents written by and published by . This book was released on 2003 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: An animal dosing model and related maximum tolerated dose (MTD) were developed for repeated exposures in guinea pigs to three organophosphorus chemical warfare nerve agents (CWNA). Male animals were injected subcutaneously with sarin (GB), soman (GD) or VX once a day (Monday through Friday) for 2-, 4-, or 13-weeks. An initial 13-week study for each CWNA employed doses of vehicle (normal saline), 0.2, 0.4, 0.6, and 0.8 x the previously established acute LD50. A 2-week and 4-week exposure were also performed for each agent at doses less than the 13-week MTD to verify lack of toxicity. Animals dosed daily for 13 weeks with 0.4 x LD50 of GB or GD or with 0.2 x LD50 of VX did not display signs of acute cholinergic toxicity. In animals dosed daily for either 2- or 4-weeks, the MTDs were 0.4 x the acute LD50 for all 3 CWNA. There were no differences among these groups and their respective vehicle controls for weight gains, body temperature, complete blood cell counts, blood chemistries, nor by histopathology. At the MTD in all groups, red blood cell cholinesterase activity one hour alter the last exposure was inhibited up to 90% compared with controls.
Download or read book The Guinea Pig Model for Organophosohate Toxicology and Therapeutic Development written by Christopher Daniel Ruark and published by . This book was released on 2015 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Organophosphates (OPs) are highly toxic insecticides and nerve agents that have been designed to inhibit the hydrolysis of acetylcholine by binding to the serine active site of acetylcholinesterase (AChE). They are one of the most common causes of human poisoning worldwide and are frequently intentionally used in suicides in agricultural areas. For this reason, there is a need for therapeutics to rescue those from intoxication. Obvious ethical concerns prevent humans from being subjected to OP exposure for therapeutic efficacy and safety testing. Therefore, animal surrogates for humans must be appropriately selected. A new paradigm, described herein, incorporating both in silico and in vitro techniques may be able to reduce the use of animals in biomedical research. Historically, the guinea pig (Cavia porcellus) has been believed to be the best non-primate model for OP toxicology and therapeutic development because, similarly to humans, guinea pigs have low amounts of OP metabolizing carboxylesterase (CaE) in blood and tissues. To explore the hypothesis that guinea pigs are the most appropriate human substitute for studying OP toxicology and therapeutic development, I cloned, purified and enzymatically compared a recombinant guinea pig acetylcholinesterase (gpAChE) with the human and mouse enzyme variants. The guinea pig, mouse and human apparent inhibition constants for diisopropyl fluorophosphate were found to be 8.4+/-0.6 uM, 4.9+/-0.6 uM and 0.42+/-0.01 uM, respectively, indicating that species differences exist for OP inhibition. Furthermore, I developed a mechanistic quantitative structure-property relationship (QSPR) to predict OP and therapeutic tissue: plasma partition coefficient (Kt:pl) parameters for each species. Differences in tissue lipid, water and protein content contributed to species specific Kt:pl. For example, guinea pig and human lung Kt:pl predictions for paraoxon were found to be 0.3 and 0.17, respectively. Biological and chemical specific parameters were then incorporated into a SimBiology guinea pig and human physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) OP-therapeutic interaction model. A 7 regional compartment model was needed to adequately simulate the pharmacodynamics of VX in the brain. The OP PBPK/PD model was validated against the small amount of available data published in the literature and was used to predict and compare guinea pig and human species differences in response to exposure and therapeutic efficacy. It was found that the human is 3.45 times more sensitive than guinea pigs to VX as shown by the area under the curve in the brain, 1.14 times more sensitive than guinea pigs as shown by the area under the curve in the diaphragm and 1.11 times more sensitive as shown by the time to minimum concentration in the diaphragm. The OP PBPK/PD model structure, along with chemical parameters, can be altered to make predictions for other OP chemicals of concern. It was also shown that a constant intravenous infusion of a novel allosteric modulator that increases AChE's velocity may be an effective means of treating dermal exposure in both guinea pigs and humans. In conclusion, this dissertation carefully evaluated physiological and enzymatic differences between these two species and greatly assisted in evaluating the suitability of the guinea pig as a model for human OP toxicity testing and therapeutic development. It is recommended that the guinea pig continue to be used as an animal model for OP toxicity testing and therapeutic development as long as the in silico and in vitro techniques, developed herein, are properly utilized to extrapolate to human populations.
Download or read book The Potential Neurotoxic Effects of Low Dose Sarin Exposure in a Guinea Pig Model written by and published by . This book was released on 2002 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve agent sarin. Preliminary results suggest no effects of either repeated 0.2 or 0.4 X LD50 sarin exposure (compared with saline) on body weight or temperature, general physical signs, flinch threshold or activity level, or on EEG activity. In contrast, RBC cholinesterase levels dropped to 20% of baseline following the tenth exposure in the 0.4 group. Since this study is ongoing, data from receptor binding and brain cholinesterase assays and histopathology are still being collected and analyzed, and may be influenced by the dramatic changes in cholinesterase activity.
Download or read book Chemical Warfare Agents written by Brian J. Lukey and published by CRC Press. This book was released on 2007-12-17 with total page 752 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first edition of this book, Chemical Warfare Agents: Toxicity at Low Levels, was published just prior to the terrorist attacks of September 11th, 2001. Reflecting a greater sense of urgency within the field of chemical defense since this event, research related to chemical warfare agents (CWAs) continues to expand at a remarkable pace.
Download or read book Acute Exposure Guideline Levels for Selected Airborne Chemicals written by National Research Council and published by National Academies Press. This book was released on 2003-05-15 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report reviews documents on acute exposure guideline levels (AEGLs) for nerve agents GA (tabun), GB (sarin), GD (soman), GD, and VX, sulfur mustard, diborane, and methyl isocyanate. The documents were developed by the National Advisory Committee on Acute Exposure Guideline Levels for Hazardous Chemicals (NAC). The subcommittee concludes that the AEGLs developed in those documents are scientifically valid conclusions based on data reviewed by NAC and are consistent with the NRC reports on developing acute exposure guideline levels.
Download or read book Handbook of Toxicology of Chemical Warfare Agents written by Ramesh C Gupta and published by Academic Press. This book was released on 2015-01-21 with total page 1199 pages. Available in PDF, EPUB and Kindle. Book excerpt: Handbook of Toxicology of Chemical Warfare Agents, Second Edition covers every aspect of deadly toxic chemicals used in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this essential reference offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors and biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, and countermeasures. Expanding on the ground-breaking first edition, Handbook of Toxicology of Chemical Warfare Agents has been completely updated, presenting the most recent advances in field. Brand new chapters include a case study of the Iran-Iraq war, an overview of chemical weapons of mass destruction, explosives, Ricin, the human respiratory system, alternative testing methods, brain injuries, and more. - Unites world-leading experts to bring you cutting-edge, agent-specific information on Chemical Warfare Agents (CWA) and their adverse effects on human and animal health, and the environment - Provides you with all the information you need on CWA modes of action, detection, prevention, therapeutic treatment and countermeasures - New to this edition: a full update to reflect the most recent advances in the field and new chapters on emergency preparedness, the chemical warfare agents used in Syria, and the use of the Novichok agent in the UK
Download or read book Sourcebook of Models for Biomedical Research written by P. Michael Conn and published by Springer Science & Business Media. This book was released on 2008 with total page 756 pages. Available in PDF, EPUB and Kindle. Book excerpt: The collection of systems represented in Sourcebook of genomic programs, although this work is certainly well Models for Biomedical Research is an effort to re?ect the represented and indexed. diversity and utility of models that are used in biomedicine. Some models have been omitted due to page limitations That utility is based on the consideration that observations and we have encouraged the authors to use tables and made in particular organisms will provide insight into the ? gures to make comparisons of models so that observations workings of other, more complex, systems. Even the cell not available in primary publications can become useful to cycle in the simple yeast cell has similarities to that in the reader. humans and regulation with similar proteins occurs. We thank Richard Lansing and the staff at Humana for Some models have the advantage that the reproductive, guidance through the publication process. mitotic, development or aging cycles are rapid compared As this book was entering production, we learned of the with those in humans; others are utilized because individual loss of Tom Lanigan, Sr. Tom was a leader and innovator proteins may be studied in an advantageous way and that in scienti?c publishing and a good friend and colleague to have human homologs. Other organisms are facile to grow all in the exploratory enterprise. We dedicate this book to in laboratory settings or lend themselves to convenient analy- his memory. We will miss him greatly.
Download or read book Chemical Warfare Agents written by M. Somani Satu and published by CRC Press. This book was released on 2000-12-07 with total page 456 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many books cover the emergency response to chemical terrorism. But what happens after the initial crisis? Chlorine, phosgene, and mustard were used in World War I. Only years after the war were the long-term effects of these gases realized. In the 60s, 70s, and 80s, these and other agents were used in localized wars. Chemical Warfare Agents: Tox
Download or read book Chemical Warfare Toxicology written by Franz Worek and published by Royal Society of Chemistry. This book was released on 2016-05-06 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite ongoing efforts to prohibit the production, storage and use of chemical warfare agents recent world events highlight the enduring threat to the population from these agents. Research efforts in various countries have resulted in novel insights into chemical warfare toxicology that has enabled the development of new approaches for the diagnosis and treatment of chemical warfare poisoning. This book provides an up-to-date treatise on the diagnosis and verification of exposure, and the pre- and post-exposure treatment of poisoning. Focussing on the most important representative nerve and blistering agents, whilst also covering other potential chemical warfare agents, this book will give the reader a comprehensive overview of the many different aspects of chemical warfare agent toxicology. The text will appeal to toxicologists, biochemists and weapons specialists working in industry and academia, and anyone with an interest in chemical warfare toxicology or exposure.
Download or read book Drug Safety Evaluation written by Shayne Cox Gad and published by John Wiley & Sons. This book was released on 2016-11-18 with total page 918 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical guide presents a road map for safety assessment as an integral part of the development of new drugs and therapeutics. Helps readers solve scientific, technical, and regulatory issues in preclinical safety assessment and early clinical drug development Explains scientific and philosophical bases for evaluation of specific concerns – including local tissue tolerance, target organ toxicity and carcinogenicity, developmental toxicity, immunogenicity, and immunotoxicity Covers the development of new small and large molecules, generics, 505(b)(2) route NDAs, and biosimilars Revises material to reflect new drug products (small synthetic, large proteins and cells, and tissues), harmonized global and national regulations, and new technologies for safety evaluation Adds almost 20% new and thoroughly updates existing content from the last edition
Download or read book Toxicological Profile for RDX written by and published by . This book was released on 1995 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Handbook of Toxicology of Chemical Warfare Agents written by Ramesh C Gupta and published by Academic Press. This book was released on 2009-04-02 with total page 1182 pages. Available in PDF, EPUB and Kindle. Book excerpt: This groundbreaking book covers every aspect of deadly toxic chemicals used as weapons of mass destruction and employed in conflicts, warfare and terrorism. Including findings from experimental as well as clinical studies, this one-of-a-kind handbook is prepared in a very user- friendly format that can easily be followed by students, teachers and researchers, as well as lay people. Stand-alone chapters on individual chemicals and major topics allow the reader to easily access required information without searching through the entire book.This is the first book that offers in-depth coverage of individual toxicants, target organ toxicity, major incidents, toxic effects in humans, animals and wildlife, biosensors, biomarkers, on-site and laboratory analytical methods, decontamination and detoxification procedures, prophylactic, therapeutic and countermeasures, and the role of homeland security. - Presents a comprehensive look at all aspects of chemical warfare toxicology in one reference work. This saves researchers time in quickly accessing the very latest definitive details on toxicity of specific agents used in chemical warfare as opposed to searching through thousands of journal articles. Will include the most agent-specific information on the market - Includes detailed coverage of the most exhaustive list of agents possibly used as chemical warfare agents in one source. Section 4: Agents That Can Be Used as Weapons of Mass Destruction ? 25 chapters long. Other books on the market only include a sample selection of specific agents. Offering all possible agents detailed under one cover makes this appealing to a wider audience and saves researchers time - The Forward will be written by Dr. Tetsuo Satoh, Chiba University, Japan. He is one of the most respected, recognizable authorities on chemical warfare agents which will set the authoritative tone for the book - Covers risk to humans, animals and the environment equally. Researchers involved in assessing the risks involved with a possible chemical warfare attack and those who are developing response plans to such attacks must look at not only the risks to human health but to our wildlife and environment as well. The holistic approach taken in this book ensures that the researchers have ready access to the details no matter which aspect of the effects of CWA's they might be concerned with
Download or read book Health Aspects of Chemical and Biological Weapons written by World Health Organization and published by . This book was released on 1970 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Toxicological Profile for Pyrethrins and Pyrethroids written by and published by . This book was released on 2003 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Pharmacy Law and Practice written by Jon Merrills and published by Academic Press. This book was released on 2013-04-19 with total page 570 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pharmacy Law and Practice, Fifth Edition provides a straightforward and useable guide for students, practitioners, academics and others interested in pharmacy law and practice in the United Kingdom. This multi-dimensional book includes discussions of socio-political influences on legal developments to provide greater insight to the reader. It clearly sets out the background to regulatory issues together with simple and practical statements of what a pharmacist has to do to obey the law. As in previous editions, this book discusses topics thematically rather than by statute. It is a unique and reader-friendly guide that boils down the complex or difficult language of the law, describes the reasons behind it, and illustrates the application to pharmacy practice. - Thoroughly updated to reflect regulatory and legal developments in areas including employment law, online transactions and internet pharmacies, non-medical prescribing and more - Takes an intuitive, problem-solving approach and discusses topics thematically rather than by statute to show how all of the larger pieces fit together - The electronic version of this book contains valuable links to provide readers with the most current information in a rapidly changing subject area
Download or read book Gulf War and Health written by Committee on Health Effects Associated with Exposures During the Gulf War and published by National Academies Press. This book was released on 2000-12-12 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: The men and women who served in the Gulf War theater were potentially exposed to a wide range of biological and chemical agents. Gulf War and Health: Volume 1 assesses the scientific literature concerning the association between these agents and the adverse health effects currently experienced by a large number of veterans.
Download or read book Cyanide in Biology written by European Molecular Biology Organization and published by . This book was released on 1981 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt:
