Organophosphorus-induced delayed neuropathy: a simple and efficient therapeutic strategy.

Organophosphorus (OP) used as pesticides and hydraulic fluids can produce acute poisoning known as OP-induced delayed neuropathy (OPIDN), whose effects take long time to recover. Thus a secure therapeutic strategy to prevent the most serious effects of this poisoning would be welcome. In this study, tri-o-cresyl phosphate (TOCP, 500 mg/kg p.o.) was given to hens, followed or not by nimodipine (1mg/kg i.m.) and calcium gluconate (Ca-glu 5mg/kg i.v.). Six hours after TOCP intoxication, neuropathy target esterase (NTE) activity inhibition was observed, peaking after 24h exceeding 80% inhibition. A fall in the plasmatic calcium levels was noted 12h after TOCP was given and, in the sciatic nerve, Ca(2+) fell 56.4% 24h later; at the same time calcium activated neutral protease (CANP) activity increased 308.7%, an effect that lasted 14 days. Any bird that received therapeutic treatment after TOCP intoxication presented significant signs of OPIDN. These results suggest that NTE may be implicated in the regulation of calcium entrance into cells being responsible for the maintenance of normal function of calcium channels, and that increasing CANP activity is responsible to triggering OPIDN. Thus, with one suitably adjusted dose of nimodipine as well as Ca-glu, we believe that this treatment strategy may be used in humans with acute poisoning by neuropathic OP.

The effect of pH on horseradish peroxidase-catalyzed oxidation of melatonin: production of N1-acetyl-N2-5-methoxykynuramine versus radical-mediated degradation.

There is a growing body of evidence that melatonin and its oxidation product, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), have anti-inflammatory properties. From a nutritional point of view, the discovery of melatonin in plant tissues emphasizes the importance of its relationship with plant peroxidases. Here we found that the pH of the reaction mixture has a profound influence in the reaction rate and products distribution when melatonin is oxidized by the plant enzyme horseradish peroxidase. At pH 5.5, 1 mm of melatonin was almost completely oxidized within 2 min, whereas only about 3% was consumed at pH 7.4. However, the relative yield of AFMK was higher in physiological pH. Radical-mediated oxidation products, including 2-hydroxymelatonin, a dimer of 2-hydroxymelatonin and O-demethylated dimer of melatonin account for the fast consumption of melatonin at pH 5.5. The higher production of AFMK at pH 7.4 was explained by the involvement of compound III of peroxidases as evidenced by spectral studies. On the other hand, the fast oxidative degradation at pH 5.5 was explained by the classic peroxidase cycle.

Importância da linha de base pré-exposição das colinesterases (ChES) no controle ocupacional a praguicidas organofosforados e carbamatos / Importance of red cell and plasma cholinesterase pre-exposure baseline into monitoring organophosphate and carbamate pesticides occupational exposed workers

Os efeitos tóxicos mais imediatos de uma intoxicação por organofosforados ou carbamatos devem-se à inibição das colinesterases (ChES). Contudo, as faixas de variação de atividade tanto interindividual como intraindividual das ChEs são muito largas o que dificulta a interpretação dos resultados da atividade das ChEs de trabalhadores expostos a organofosforados e carbamatos. Utilizando-se o método de Nabb & Whitfield (1967) para analisar sangue de 48 trabalhadores, os resultados mostraram que a colinesterase eritrocitária (ChE-Er) variou de 10,1 a 19,7 μmol/min/mL e a colinesterase plasmática (ChE-PI) de 2,2 a 6,9 μmol/min/ML. Apesar de grande variação interindividual, com a linha de base pré-exposição que utiliza a variação intraindividual foi possível correlacionar sintomas de intoxicação leve a exposição ocupacional ao carbamato, com queda na atividade da ChE-Er menor que 30% da atividade da linha de base pré-exposição...

Cholinesterase measurements with an automated kit.

BACKGROUND: The Test-mate kit determines acetylcholinesterase (AChE, EC 3.1.1.7) and hemoglobin content of a drop of blood, displaying enzyme activities normalized to 25 degrees C. Previous models produced inconsistent results at different temperatures. This report focuses on the current model, ChE 400, and two instruments of a previous OP model. METHODS: AChE activities were determined by the Ellman assay, using the three kits and a 96-well microplate reader. Temperatures ranged from 10 to 37 degrees C. Fetal bovine serum was the source of AChE. RESULTS: Normalized activities decreased below 20 degrees C in the ChE model and below 25 degrees C in the OP models. Activities of the same serum sample differed between the three Test-mate kits, ranging from 1.03 to 1.49 micromoles/min/ml. Percent errors were greater than with the microplate reader at all temperatures. CONCLUSIONS: Neither we nor the manufacturer recommend the current Test-mate model for fieldwork. Nevertheless, there have been field measurements with Test-Mate kits, and we recommend that an enzyme activity standard be run in parallel with their use.