Artigo Revisado por pares

A neural tube defect specific form of acetylcholinesterase in amniotic fluid

1983; Elsevier BV; Volume: 135; Issue: 2 Linguagem: Inglês

10.1016/0009-8981(83)90140-7

ISSN

1873-3492

Autores

James R. Bonham, John Atack,

Tópico(s)

Environmental Toxicology and Ecotoxicology

Resumo

Organophosphate nerve agents (OPNAs) are highly toxic organophosphorus compounds (OPs) characterized according to their mechanism of action as substances influencing cholinergic nerve transmission via inhibition of acetylcholinesterase (AChE; EC 3.1.1.7). The manifestation of intoxication comprises nicotinic, muscarinic, and central symptoms. Some OPs are capable of causing a delayed neurotoxicity. Cholinesterases (AChE and butyrylcholinesterase, EC 3.1.1.8., BChE) could be characterized as the main enzymes involved in the toxic effect of these compounds including their different molecular forms. The activity of both AChE and BChE (in different molecular forms) is influenced mainly by inhibitors and other factors such as physiological and pathological states. Nevertheless, the determination of cholinesterase activity is a key diagnostic tool for diagnosis of poisoning with cholinesterase inhibitors (OPs and carbamates). There are different approaches for the determination of cholinesterase activity. The most frequently used method is based on the hydrolysis of thiocholine esters and subsequent colorimetric detection of the free thiol (-SH; sulfhydryl) group of the released thiocholine. The diagnosis of OP/NA poisoning is based on anamnesis, the clinical status of the intoxicated person/organism, and on cholinesterase activity determination in the blood. In the case of intoxication with NAs, red blood cell AChE is more diagnostically relevant than BChE activity in the plasma. This enzyme is a good diagnostic marker for intoxication with OP pesticides. Some other biochemical examinations are recommended, especially arterial blood gas, blood pH, minerals, and some other specialized parameters usually not always available in all clinical laboratories. For example: (1) determination of free OPNA or its metabolites (either in the blood or urine), (2) fluoride reactivation test, or (3) reactivation/adducts analysis after enzymatic digestion. These specialized analyses are important for prognosis of the intoxication, selection of effective treatment, and for retrospective analysis of the toxic agent of exposure.Systematic monitoring of blood cholinesterases of workers exposed to nerve agents began at this department in 1963. Hestrin’s method was used initially, but results obtained were not very reproducible or valid. Moreover, practical use of this method for routine determination was relatively complicated. Therefore, a method developed by Winter in 1964 began to be used. This employed an automatic colorimeter Auto Analyzer for the activity of AChE in erythrocytes (red blood cells). In 1971, a new method was introduced (Ellman’s method modified for Auto Analyzer). Good correlation between these two methods was obtained and, beginning in 1972, it was used for routine screening. The instrumentation was changed in 1976 (Auto Analyzer–Vitatron spectrophotometer) and a slight modification was made to the method. During the last 10 years, a new spectrophotometer (Uvicon and later Helios α) has been used. A good number of workers were examined, however, only selected persons were chosen for monitoring and their data were analyzed in more detail. Currently, cholinesterase activity is measured using an automated biochemical analyzer.

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