Cholinesterase definition

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

A comprehensive approach to a states response to a chemical terrorism includes having a plan not only for the crisis and consequence management phases of the incident, but also for all elements required for complete resolution of the event. This may include the necessity to definitively establish whether chemical agents were used, to provide supporting evidence to confirm other analyses, or to provide the forensic proof required to support a criminal prosecution. The collection and analysis of biomedical samples - blood, urine or other tissue from affected humans or animals - is one of the means for providing such information. Although current capabilities such as urinary thiodyglycol excretion or plasma cholinesterase activity can be performed, there is scope for far more sensitive and specific assessments that overcome the limitations of these approaches. 

Journal reports by Bell and Gershon indicated that tetrahydroaminoacridine (THA), a cholinesterase inhibitor, was effective in reversing delirium induced by Ditran (JB-329) as a form of psychiatric treatment It is interesting that their use of Ditran for this purpose was similar to the atropine coma treatment method reported more than a decade earlier by Forrer, Miller et al. In our study, five subjects were given 5.0 mcg/kg of oral BZ on two occasions, 8-14 days apart 60 mcg/kg of THA was administered iv four hours after the time of the second BZ dose. We observed definite partial reversal of impairment soon after injection, but it was brief. An unexpected observation was the general tendency by the subjects to become impaired more rapidly and intensely by BZ on the second occasion - a finding that was later confirmed in a more careful study. 

Pseudo-ChE (also known as butyryl-, plasma, and nonspecific cholinesterase) has a widespread distribution, with enzyme especially abundant in the liver, where it is synthesized, and in the plasma. In spite of the abundance of pseudo-ChE, its physiological function has not been definitively identified. It does, however, play an important role in the metabolism of such clinically important compounds as succinylcholine, procaine, and numerous other esters. 

Appendix B reviews some important animal studies of cholinesterase reactivator chemicals. The extensive literature reviewed offers little definitive information with which to project possible long-term effects or delayed sequelae in human subjects tested at Edgewood. These compounds have a short biologic half-life of 1 to 3 h. However, no chronic studies were found. Consequently, the carcinogenic potential of cholinesterase reactivators remains... 

The optimal duration of treatment with cholinesterase inhibitors has not been definitively established. Most randomized controlled trials in patients with mild to moderate Alzheimer s disease have been 26 weeks in duration or less. However, some data (mostly open-label continuation data of placebo-controlled trials) suggest continued benefits with treatment for 1 year or longer (Bullock and Dengiz 2005 Doody et al. 2001a Farlow et al. 2000 Grossberg et al. 2004 Lyketsos et al. 2004 Mohs et al. 2001 Pirttila et al. 2004 Raskind et al. 2000, 2004 Rogers et al. 2000 Small et al. 2005 Wilcock et al. 2003 Winblad et al. 2001). 

FIGURE 12—34. Palliative responders to cholinesterase inhibitor therapy in Alzheimer s disease. Yet another response to cholinesterase inhibition can be no immediate improvement but a definite slowing in the expected rate of decline. 

The drug is a quaternary ammonium salt which is observed to be a reversible inhibitor of cholinesterase activity having activities very much akin to those of neostigmine, but is definitely much slower in onset and of longer duration. 

Agent GB (Sarin). RfDe = 2 x 10 mg kg d". A LOAEL was identified in a 90-d oral study in rats. A total uncertainty factor of 3000 was applied to account for protection of sensitive subpopulations (10), animal-to-human extrapolation (10), LOAEL-to-NOAEL extrapolation (3), extrapolation from a subchronic to chronic exposure (3), and incomplete data base (3). An uncertainty factor of 3 rather than 10 was used to extrapolate from a subchronic to chronic exposure because of the unlikelihood that the LOAEL would have been substantially lower if the exposure had continued for a longer period of time. The LOAEL-to-NOAEL uncertainty factor of 3 was used because the endpoint, cholinesterase inhibition, was not associated with any physical signs of clinical toxicity. A pilot multigeneration reproductive toxicity study on GB was inconclusive however, because the available evidence indicates that organophosphate cholinesterase inhibitors such as GB are not likely to be reproductive toxins, the lack of definitive results was not considered critical. Therefore, a UFd of 3, not the default value of 10, was applied. 

The existence of the two distinct cholinesterases and their fxmctional definition as specific cholinesterase and pseudocholinesterase was first introduced by Mendel and Rudney in the early 1950s. By the early 1990s, these definitions were well complemented by theoretical... 

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