Excessive methaemoglobinaemia and multi-organ failure following 4-DMAP antidote therapy

Kerger, Heinz; Dodidou, Petroula; Passani-Kruppa, Daniela; Grüttner, J.; Birmelin, M.; Volz, Alexander; Waschke, Klaus F.

doi:10.1016/j.resuscitation.2005.02.008

Cited by 15 publications

(9 citation statements)

References 24 publications

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“…Importantly, the final effective concentration in the fish is likely considerably lower than that in the surrounding aqueous media as a result of penetration and the potential conversion to HCN and loss as a gas 30 . These phenotypes closely parallel the observed effects with lethal and sublethal doses of cyanide in a wide range of animals ranging from trout to humans 3, 31–34 . The definition of such stereotypic effects of cyanide on cardiac or neuronal physiology and on survival formed the basis for subsequent automation and screening in the zebrafish model to identify novel countermeasures for cyanide exposure.…”

Section: In Vivo Screens For Chemical Warfare Countermeasuressupporting

confidence: 72%

Changing the scale and efficiency of chemical warfare countermeasure discovery using the zebrafish

Peterson

MacRae

2013

Drug Discovery Today: Disease Models

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As the scope of potential chemical warfare agents grows rapidly and as the diversity of potential threat scenarios expands with non-state actors, so a need for innovative approaches to countermeasure development has emerged. In the last few years, the utility of the zebrafish as a model organism that is amenable to high-throughput screening has become apparent and this system has been applied to the unbiased discovery of chemical warfare countermeasures. This review summarizes the in vivo screening approach that has been pioneered in the countermeasure discovery arena, and highlights the successes to date as well as the potential challenges in moving the field forward. Importantly, the establishment of a zebrafish platform for countermeasure discovery would offer a rapid response system for the development of antidotes to the continuous stream of new potential chemical warfare agents.

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Section: In Vivo Screens For Chemical Warfare Countermeasuressupporting

confidence: 72%

Changing the scale and efficiency of chemical warfare countermeasure discovery using the zebrafish

Peterson

MacRae

2013

Drug Discovery Today: Disease Models

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“…In such an event, ready access to cyanide antidotes could transform a potentially devastating situation into a manageable one. Existing cyanide antidotes require administration by qualified personnel and have several associated toxicities that limit their utility . More importantly, they are limited in their mode of action.…”

Section: Rationalementioning

confidence: 99%

“…The education core focuses on the educational component of the U54 mission, executing it through the interdisciplinary training of a new generation of countermeasure scientists focusing on fostering interactions between countermeasure scientists and a range of emerging biologic disciplines. The metabolomics core offers scientific integration across the other disciplines within the program …”

Section: Specific Components and Their Interactionsmentioning

confidence: 99%

A countermeasure development pipeline

MacRae

Boss

Brenner

et al. 2016

Annals of the New York Academy of Sciences

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We have developed an integrated pipeline for countermeasure discovery that, under the auspices of the National Institutes of Health Countermeasures Against Chemical Threats network, is one of the few efforts within academia that by design spans the spectrum from discovery to phase I. The successful implementation of this approach for cyanide would enable efficient proof-of-concept studies that would lay the foundation for a generalizable strategy for parallel mechanistic studies and accelerated countermeasure development in the face of new and emerging chemical threats.

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“…This is especially true when industrial chemical substances have been swallowed, as a huge variety of toxic substances must be taken into account (1). In cases for which there is no specific antidote, treatment is very difficult (2). MOT is the failure of different organs that have been damaged by known or unknown compounds.…”

Section: Introductionmentioning

confidence: 99%

Successful Treatment of Multiorgan Toxicity Induced by Explosive Agent With Repeated Hemodialysis: A Case Report

Arefi¹,

Mohammadi²

2016

Jundishapur J Nat Pharm Prod

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Introduction: Acute poisoning by oral ingestion of mixed hazardous materials can lead to multiorgan toxicity and may represent a special challenge in clinical management, in particular if little is known about the effects of the involved agents. This is especially true when industrial chemical substances have been swallowed, as a huge variety of toxic substances must be taken into account. Case Presentation: This case report describes the management of this potentially life-threatening situation in a 21-year-old man with multiorgan system failure, who developed gastrointestinal bleeding, anemia, renal dysfunction, altered visual acuity, seizure, jaundice, and ascites due to multiorgan toxicity. This patient was successfully treated with repeated hemodialysis, and survived. He was discharged from the hospital with an acceptable level of morbidity. Conclusions:In cases of oral-based multiple hazardous substance toxicity without a specific antidote, hemodialysis seems to be the best treatment. The problems created by multiorgan toxicity and the issues involved in the decision-making process are discussed in the management of this extraordinarily overwhelming complication.

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Excessive methaemoglobinaemia and multi-organ failure following 4-DMAP antidote therapy

Cited by 15 publications

References 24 publications

Changing the scale and efficiency of chemical warfare countermeasure discovery using the zebrafish

Changing the scale and efficiency of chemical warfare countermeasure discovery using the zebrafish

A countermeasure development pipeline

Successful Treatment of Multiorgan Toxicity Induced by Explosive Agent With Repeated Hemodialysis: A Case Report

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