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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Relationship of neuropathy target esterase inhibition to neuropathology and ataxia in hens given organophosphorus esters.

Adult White Leghorn hens were acutely exposed to 3 dosages of the following organophosphorus compounds: mipafox, tri-ortho-tolyl phosphate (TOTP), phenyl saligenin phosphate, and diisopropylphosphorofluoridate (DFP). Neuropathy target esterase ( NTE) activity was measured in brain and spinal cord 4 or 48 h after exposure. Ataxia was assessed using an 8-point rating scale on days 9 through 21 after administration, and neuropathological examination was conducted on samples collected from perfusion-fixed animals on day 21. Morphological alterations were indicated by lesion scores between 0 (no lesions) and 4 (diffuse involvement of spinal cord tracts and > 25% degeneration of peripheral nerve fibers). Dosages of mipafox (30 mg/kg i.p.), TOTP (500 mg/kg p.o.), phenyl saligenin phosphate (2.5 mg/kg i.m.) and DFP (1 mg/kg s.c.) that were capable of inhibiting NTE > 80% in both brain and spinal cord preceded ataxia which reached maximal levels (scores of 7-8), and development of lesions scored as 4. Hens were notably impaired (ataxia scores of 3-4) 21 days after administration of dosages of mipafox (3 and 6 mg/kg), TOTP (90 mg/kg), phenyl saligenin phosphate (0.1 and 0.2 mg/kg), and DFP (0.4 mg/kg) when spinal cord NTE was inhibited 40-75%. Lesions were, however, only noted in spinal cord and peripheral nerves of hens given TOTP or DFP (scores 1-3). These data indicate that inhibition of spinal cord NTE > 80% was predictive of severe ataxia and extensive pathology in the hen and that less NTE inhibition was indicative of less severe ataxia and a lower score for neuropathological damage.[1]


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