Red cells acetylcholinesterase

Decreased. red-cell acetylcholinesterase and increased osmotic fragility (no effect at 0.25 ppm)... 

Pipecuronium bromide is a bisquaternary steroid analogue of pancuronium. In vitro pipecuronium reversibly inhibits both human red cell acetylcholinesterase and human plasma cholinesterase to an extent that might have clinical implications (1). Its potency is similar to that of pancuronium and its onset and duration are also approximately the same. Accumulation can occur (2), and maintenance doses should be one-quarter to one-sixth of the initial dose to achieve a similar effect, depending on the anesthetic technique used. 

A statement by the UN Secretary General Ban Ki-moon on 16 September, after an investigation of the attack sites and survivors by a UN inspection team said that there was clear and convincing evidence that sarin was used during the attack and that many hundreds of people were killed . The inspection team said they had found samples of sarin on the remains of rockets found on the area and that 85 % of blood samples tested from 50 survivors interviewed showed positive for sarin. Details of what tests were carried out were not provided, but red-cell acetylcholinesterase levels, the best indicator of whether exposure to an anticholinesterase has taken place, have not been published at the time of writing. 

Consistent decreases in plasma cholinesterase may not have been observed in rats and dogs because they were treated with lower doses of diisopropyl methylphosphonate. In general, depression of plasma cholinesterase, also known as pseudocholinesterase or butyrylcholinesterase, is considered a marker of exposure rather than an adverse effect. Depression of cholinesterase activity in red blood cells (acetylcholinesterase) is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity. It is considered an adverse effect. Acetylcholinesterase is found mainly in nervous tissue and erythrocytes. Diisopropyl methylphosphonate was not found to inhibit RBC... 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

More recently, B. Goldstein and McDonagh demonstrated that the native protein fluorescence (280-nm excitation, 330-nm emission) of red-cell membranes exposed in vitro to ozone at 1 ppm was a somewhat more sensitive indicator of ozone effect than other characteristics measured in the same em, including oxidation of cell-membrane sulfhydiyl groups, loss of acetylcholinesterase activity, and formation of lipid peroxide breakdown products. 

Among the specific enzymes whose activity has been reported to be decreased after in vitro ozone exposure are papain, glyceraldehyde-3-phosphate dehydrogenase, lysozyme, ribonuclease, and acetylcholinesterase. The latter enzyme appears to be particulady susceptible to free-radical and oxidative states. A loss in acetylcholinesterase activity has been reported in the red cells of humans and mice that inhaled ozone. However, there are only minimal amounts of this enzyme in lupg tissue, and, although it has been suggested that acetylcholinesterase is important in bronchial tract ciliary activity, there is no direct evidence to support this conjecture. 

In dogs poisoned with soman (Intravenously at 30 pg/kg) and treated with I at 104 mg/kg (Intravenously 31/2 min after soman), the large dose of I stopped aging of Inhibited cholinesterase and reactivated 24.0% and 35.6% of the red-cell and diaphragm cholinesterase activities, respectively. It failed to reactivate brain cholinesterase. Indeed, the brain acetylcholinesterase activity after the treatment with 1 was lower than that just before the injection of I. The last finding indicates the inability of I to cross the blood-brain barrier in significant quantities. 

Storm JE, Rozman KK, Doull J Occupational exposure limits for 30 organophosphate pesticides based on inhibition of red blood cell acetylcholinesterase. Toxicology 2000 150 1. [PMID 10996660]... 

In the clinic, esmolol s distribution half-life is 2 min and its elimination half-life is 9 min. Esmolol hydrochloride is rapidly metabolized by hydrolysis of the ester linkage, chiefly by esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase [22]. Its volume of distribution is 3.4 L kg-1, and its total clearance is 285 mL kg-1 min-1, "... which is greater than cardiac output thus the metabolism ofesmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flout [22]. As expected from such a "... high rate of blood-based metabolism, less than 2% of the drug is excreted unchanged in the wind [22]. Within 24 h after infusion, approximately... 

FIGURE 51.3. Plot of red blood cell acetylcholinesterase activity as a function of regenerated RBC sarin. 

Lorke, D.E., Hasan, M.Y., Arafat, K., Kuca, K., Musilek, K., Schmitt, A., Petroianu, G.A. (2008a). In vitro oxime reactivation of red blood cell acetylcholinesterase inhibitied by diisopropyl-fluorophosphate (DFP). J. Appl. Toxicol. 28 422-9. 

Zifrosilone (18) is a novel tight-binding inhibitor of acetylcholinesterase, which is in development as a potential therapeutic compound in the symptomatic treatment of Alzheimer s disease [72]. Pharmacokinetics and pharmacodynamics of the compound were studied in the dogs and rats after single intravenous and subcutaneous administrations. When evaluated in human healthy volunteers, the orally administered drug was well tolerated but displayed a strong dose-related inhibition of red blood cell acetylcholinesterase [73] and its development was consequently halted. 

Tahti H, Korpela M. 1985. In-vitro experiments on the effects of organic solvents on red cell membrane acetylcholinesterase. Food Chem Toxicol 24 805-806. 

Many individuals have genetic susceptibility to certain chemicals (Calabrese 1978). The influence of these genetic differences likely produces sub- and supersensitivity to OP insecticides and warfare agents (Russell and Overstreet 1987). Several enzymes with variations or polymorphisms control sensitivity to OPs red blood cell acetylcholinesterase, serum cholinesterase or pseudocholinesterase, lymphocyte neuropathy target esterase or platelet neuropathy target esterase (NTE), serum paroxonase, butyrylcholinesterase, and serum arylesterase (Costa et al. 1999 LaDu 1988 Li et al. 1993 Mutch et al. 1992). Inhibition of red blood cell acetylcholinesterase, in both the central and the peripheral nervous systems, produces acute symptoms (Mutch et al. 1992). Paroxonase and arylesterase further modify the response (LaDu 1988 Li et al. 1993). Variant, inactive butyrylcho-linesterases increase sensitivity to OPs (Lockridge and Masson 2000 Schwarz et al. 1995). OP-induced delayed polyneuropathy results... 

Organophosphorus compounds. Laboratory evidence of poisoning may be obtained by measuring decreases in the plasma pseudocholinesterase (PChE) and red blood cell acetylcholinesterase (AChE) activities. However, because of wide interindividual variability, significant depression of enzyme activity may occur but still fall within the normal range. It is most... 

Korpela M, Tahti H. 1986. The effect of selected organic solvents on intact human red cell membrane acetylcholinesterase in vitro. Toxicol Appl Pharmacol 85 257-262. 

Applicators and residents of dichlorvos (DDVP) treated structures were monitored for evidence of insecticide exposure using exposure pads, air samplers, serum and red blood cell acetylcholinesterase (AChE) tests, and urine analysis. There was no evidence of DDVP or dichloroacetic acid (DCAA) in the urine of applicators or cooperators. There were slight but significant differences (Pi0.05) in serum AChE activity of residents of treated units, but erythrocyte AChE was unchanged. Applicator AChE test results were inconclusive. It was concluded that there was not a significant risk. In terms of acute toxicity, to either the pesticide applicators or the residents of treated structures. 

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