In cholinesterase

Diagnosis of organophosphate poisoning (including methyl parathion) can be confirmed by evaluation of serum (plasma) cholinesterase and erythrocyte cholinesterase. However, cholinesterase inhibition is not specific for organophosphates. For example, carbamate insecticides also result in cholinesterase inhibition, which is usually transitory. Erythrocyte cholinesterase measurement is a specific test for... 

Procedure Allelochemical and a compound belonging to natural artificial pesticides and medicinal drugs is preliminary added into the reaction media (see section Add). The difference in cholinesterase activity (measured as shown in sections 15.3) between a control (without the substance added) and the experimental variant is estimated. The results are compared with the effects of the cholinesterase inhibitors neostigmine and physostigmine. 

Reduction in cholinesterase activity levels of various tissues (blood, brain) is one of the earliest signs of chlorpyrifos intoxication. Cholinesterase reductions have been demonstrated in turkeys fed diets containing 50 mg chlorpyrifos/kg (estimated daily dose of 0.7 mg/kg BW) for 20 days (Schlinke et al. 1969) in chickens fed diets of 25 mg/kg (estimated daily dose of 0.94 mg/kg BW) for 20 days (Schlinke 1970) in quail (Coturnix coturnix) given a single (sublethal) esophageal... 

It may be noted that many of the anticholinesterases of the competitive type are equally potent as inhibitors of a- and / -cholinesterases. We should add, however, that the existence of an anionic site in / -cholinesterases has been questioned.1... 

Nervous system effects may occur in humans after occupational exposure to disulfoton (Wolfe et al. 1978). In this study, mean disulfoton concentrations of 0.460.633 mg/m caused a 22.8% depression in erythrocyte cholinesterase activity in workers at a pesticide-fertilizer mixing operation. The workers were exposed to disulfoton for 9 weeks, and there were no reports of adverse clinical signs due to disulfoton exposure. The study was limited in that baseline blood cholinesterase activities were obtained 2 weeks after the initial exposure and were compared with cholinesterase activities at 9 weeks. Therefore, the actual depression in cholinesterase activity over a 9-week period was probably >22.8%. In addition, these workers were also dermally exposed to disulfoton (see Section 2.2.3.4) therefore, the 22.8% depression in cholinesterase activity was probably due to both inhalation and dermal exposure. Despite these limitations, the study concluded that because this depression in cholinesterase activity was only associated with dry mixing operations, the wet mixing operations are less hazardous to workers. 

Although some steroids have been reported to reduce the toxic effects of some insecticides, the steroid ethylestrenol decreased the rate of recovery of depressed cholinesterase activity in disulfoton- pretreated rats (Robinson et al. 1978). The exact mechanism of this interaction was not determined. Ethylestrenol alone caused a small decrease in cholinesterase activity, and, therefore, resulted in an additive effect. Rats excreted less adrenaline and more noradrenaline when given simultaneous treatments of atropine and disulfoton compared with rats given disulfoton alone (Brzezinski 1973). The mechanism of action of disulfoton on catecholamine levels may depend on acetylcholine accumulation. In the presence of atropine, the acetylcholine effect on these receptors increases the ability of atropine to liberate catecholamines. 

Fig. 27 RBC (tme) as well as pseudocholinesterase inhibition was measured several times in this study. A surprisingly large reduction in cholinesterase levels can be well tolerated when EA 3443 is present. Small doses (unspecified) of VX were used here, producing shorter periods of antidotal effect, lasting only a few hours following each treatment.

Chlorpyrifos does not have enough vapor pressure to present a vapor hazard however, if it is dispersed as a mist, particulate inhalation is possible. Five of seven spray workers exposed to 0.5% chlorpyrifos emulsion showed more than 50% reduction in cholinesterase within 2 weeks. Symptoms were not reported. 

Because atropine has never been found to have reactivating activity in vitro, the reactivation that occurred in the rats treated with atropine sulfate is assumed to be spontaneous. It is apparent from Table 3 that addition of 2-PAM I to atropine increased cholinesterase reactivation by 40.5% in the parotid gland, by 127.8% in the gastrocnemius muscle, and by 8.2% in the brain. The especially large change in cholinesterase activity in skeletal muscle suggests that this may be the principal site at which 2-PAM I antagonizes inhibition of cholinesterase. 

The decrease in cholinesterase activity was accompanied by increases in the total acetylcholine concentration in the pontomedullary region of 52% in the rats given armin alone and of 25% in those given both armin and IV. 

These patients may also exhibit symptoms of excessive stimulation of muscarinic receptors (abdominal cramps, diarrhea, increased salivation, excessive bronchial secretions, miosis, bradycardia). Small doses of edrophonium (1-2 mg intravenously) will produce no relief or even worsen weakness if the patient is receiving excessive cholinesterase inhibitor therapy. On the other hand, if the patient improves with edrophonium, an increase in cholinesterase inhibitor dosage may be indicated. Clinical situations in which severe myasthenia (myasthenic crisis) must be distinguished from excessive drug therapy (cholinergic crisis) usually occur in very ill myasthenic patients and must be managed in hospital with adequate emergency support systems (eg, mechanical ventilators) available. 

Interionic Distances and Number of Anionic Sites in Cholinesterases... 

S. Andreescu and J.-L. Marty, Twenty years research in cholinesterase biosensors From basic research to practical applications, Biomol. Eng., 23 (2006) 1-15. 

Holmstedt B. Cholinesterase inhibitors an introduction. In Cholinesterase and cholinesterase inhibitors. Giacobini E (Ed.). Martin Dunitz, London, 2000,... 

The results of this investigation indicate no detectable inhibition of the cholinesterase activity of either plasma or erythrocytes as a result of handling Vapona Resin Vaporizers under the conditions of this experiment or of maintaining Vaporizers in direct contact with the skin for 30 minutes per day on 5 successive days. The fluctuations in cholinesterase activity were well within the normal range of day-to-day variation. The second determination of the cholinesterase activity of the plasma of subject 6 was unusually high. No explanation can be offered for this unusually high value, except to note that the specimen was Very milky (the probable result of lipemia) and that it was taken on the day following the death of the subjects mother. 

Handling the Vaporizers does not appear to cause any significant decrease in cholinesterase activity among those doing the handling, nor is the cholinesterase activity affected by the prolonged contact of the Vaporizers with the skin of the forearm. In the ordinary days work, the householder or the pest control operator would not be expected to handle the Vaporizer as much as 30 minutes each day even under the most unusual conditions. Under ordinary circumstances, the contact of the resin vaporizer with the skin would not persist for 30 minutes in any one day and would not be continued day after day. 

A method to set REIs would account for the rate of dermal absorption, the rate of foliar contact and the rate of change in cholinesterase. These factors were used in the Popendorf and Leffingwell (1982) Unified Field Model for determining REIs. This model also accounts for the relative rate of DFR dissipation, and differences in potency based on the dermal LD50 of the pesticide. The Unified Field Model is an elegant technique that takes into account many variables affecting exposure and cholinesterase inhibition as a response. Ultimately, the rate of cholinesterase inhibition, and not a fixed level of inhibition, is the primary... 

Model Parent Compound Series. Experimental partition coefficient data for a variety of substituted benzenes and seven other related parent compound series (phenoxyacetic acid, phenylacetic acid, benzoic acid, benzyl alcohol, phenol, aniline, nitrobenzene) were reported in 1964 by Fujita et al. (II). The ir values (see Equation 3) derived for individual substituents in each of the above-mentioned parent compound series have since been frequently used (with varying degrees of success) by many investigators to approximate tt values for the corresponding substituents in other related parent compounds for which no experimental partitioning data are available. For example, Hansch and Deutsch (26), in a correlation study of structure—activity relationships in cholinesterase inhibitors, used tr values derived for aromatic ring substituents (X) in the phenoxyacetic acid series... 

Dacre, J.C. 1984. Toxicology of some anticholinesterases used as chemical warfare agents - a review. In Cholinesterases Fundamental and Applied Aspects, M. Brzin, E.A. Barnard and D. Sket, eds., Walter de Gruyter, New York. pp. 415-426. 

Bajgar, J., Bartosova, L., Kuca, K., Jim, D., Fusek, J. (2007). Changes in cholinesterase activities in the rat blood and brain after sarin intoxication preheated with butyrylcholinesterase. Drug Chem. Toxicol. 30 351-9. 

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