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Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.
Investigation of the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin to provide a kinetic basis for the proper assessment of in vivo data. Expand
Improvement of the cold storage of blood vessels with a vascular preservation solution. Study in porcine aortic segments.
Iron chelators, but also optimized base solutions, are options to improve the storage of vascular endothelium and both endothelial cell survival and mitochondrial membrane potential were significantly better preserved than in the clinically used solutions HTK, University of Wisconsin and Perfadex, or in physiological saline. Expand
Detoxification of G- and V-series nerve agents by the phosphotriesterase OpdA
Abstract Intoxication by organophosphorous (OP) insecticides and nerve agents is often lethal and currently available therapeutics are often ineffective. A range of catalytic and stoichiometric OPExpand
Structural requirements for effective oximes--evaluation of kinetic in vitro data with phosphylated human AChE and structurally different oximes.
The determination of reactivation rate constants with bispyridinium oximes revealed that no single oxime had an adequate reactivating potency with AChE inhibited by structurally different OP, underline the necessity to investigate in detail the kinetic properties of novel oximes. Expand
Oximes in organophosphate poisoning: 60 years of hope and despair.
Multiple aspects, including intrinsic toxicity, in vitro reactivation potency, efficacy and pharmacokinetics, as well as the impact of the causative OP have to be considered. Expand
Reactivation kinetics of a series of related bispyridinium oximes with organophosphate-inhibited human acetylcholinesterase--Structure-activity relationships.
The reactivation kinetics of a series of bispyridinium oximes bearing one or two oxime groups at different positions and having an oxybismethylene or a trimethylene linker under identical conditions with human AChE inhibited by structurally different OP indicate that the position of the oxime group(s) is decisive for the reactivating potency. Expand
Efficacy of the rePON1 mutant IIG1 to prevent cyclosarin toxicity in vivo and to detoxify structurally different nerve agents in vitro
In vitro and in vivo results indicate that IIG1 may be considered as a promising candidate bioscavenger to protect against the toxic effects of a range of highly toxic nerve agents. Expand
Catalytic bioscavengers in nerve agent poisoning: A promising approach?
This work states that further research is necessary to improve the catalytic activity, substrate spectrum and in vivo biological stability of enzyme mutants, and the use of catalytic bioscavengers for detoxification of nerve agents in the systemic circulation prior to distribution into target tissues. Expand
Effectiveness of a substituted β-cyclodextrin to prevent cyclosarin toxicity in vivo.
Results of this proof of concept study indicate that 6-OxP-CD may be considered as a potential small molecule scavenger to protect against the toxic effects of a range of highly toxic OP nerve agents. Expand
Effect of MB327 and oximes on rat intestinal smooth muscle function.
The antimuscarinic effect of MB327 was compared to that of established oximes and atropine in a rat jejunum smooth muscle model and showed a fully reversible smooth muscle relaxing effect at lower concentrations than all tested oximes. Expand