Oxime-induced reactivation of acetylcholinesterase inhibited by organophosphinates.

The comparative potency of oximes for reactivation of inhibited eel acetylcholinesterase (AChE) in vitro is dependent on the organophosphinate inhibitor. Some of the data, dealing with a reference organophosphonate, support the conclusion of other investigators that the oxime potency order is also dependent on the inhibiting phosphonate. This work was done to identify more clearly the nature of phosphinylated AChE with regard to oxime reactivation potency and the potential of phosphinates as pretreatment drugs to protect AChE against organophosphonate poisoning. We have determined the reactivation potency of four oximes--2-PAM, HI-6, TMB-4 and toxogonin--against four phosphinates--4-nitrophenyl methyl(phenyl)phosphinate (PMP), 4-nitrophenyl chloromethyl(phenyl)phosphinate (CPMP), 4-nitrophenyl trifluoromethyl(phenyl)phosphinate and 4-nitrophenyl bis(2-thienyl)phosphinate. For comparison, the phosphonate sarin (GB, isopropyl methylphosphonofluoridate) was included. Incubation of the inhibited enzyme (I-AChE) at 25 degrees C was with 0.30 microM oxime for PMP, 3.0 microM oxime for sarin and CPMP and 100 microM oxime for the two remaining phosphinates. AChE activity was assayed spectrophotometrically for 3.0 min at 272.5 nm at 25 degrees C in 0.10 M MOPS buffer (pH 7.60) using phenyl acetate as substrate. When sarin was the inhibitor (0% spontaneous recovery after a 2-h incubation), the order of oxime reactivation was 2-PAM (46%) greater than or equal to toxogonin (33%) = TMB-4 (31%) greater than HI-6 (9%) after 2-h incubations. For PMP (12% spontaneous recovery after a 2-h incubation) the oxime order was toxogonin (67%) greater than TMB-4 (53%) greater than 2-PAM (40%) after 2-h incubations.(ABSTRACT TRUNCATED AT 250 WORDS)

Temporary threshold shifts produced by exposure to low-frequency noises.

Groups of human subjects were exposed for 8 or 24 h to an octave-band noise centered at 63, 125, or 250 Hz. For a 24-h exposure at 84 dBA, temporary threshold shifts (TTS) increased for 8-12 h and then either decreased or remained constant. Although TTS was less than 20 dB, complete recovery for many of the subjects required as long as 48 h. Accordingly, the higher level exposure which was planned at 94 dBA for 24 h was reduced to 90 dBA for 8 h. For this condition TTS increased throughout the 8-h exposure. TTS from the 90-dBA noise for 8 h exceeded the TTS produced by the 84 dBA; however, recovery from the 24-h exposure required as long as 48 h, whereas recovery from the 8-h exposure required only 12-24 h. Thus the time required for recovery is determined in part by the duration of exposure. TTS was not always maximal 1/2-1 oct above the band of noise, but was maximal in the frequency regions of better auditory sensitivity (350 to 750 Hz). For the 250-Hz condition, TTS increased about 1.5 dB per dB increase in noise level, whereas for the 63- and 125-Hz conditions TTS increased less than 1 dB per dB increase in noise level. More data are needed to specify the relation between TTS and the level of low-frequency noises.

Threshold shifts in chinchillas exposed to octave bands of noise centered at 63 and 1000 Hz for three days(a).

Audiograms were obtained on eight binaural chinchillas trained on a shuttlebox avoidance procedure. Four of the animals were exposed to three successive levels of an octave band of noise centered at 63 Hz: 100 dB SPL (74 dBA), 110 dB SPL (84 dBA), and 120 dB SPL (94 dBA). The other four animals were also exposed to three successive levels of an octave band of noise centered at 1000 Hz: 75 dB SPL (75 dBA), 85 dB SPL (85 dBA), and 95 dB SPL (95 dBA). All exposure durations were 75 h. Little threshold shift (TS) resulted from the lower two exposure levels of the 63-Hz noise band. At the 120-dB exposure level, maximum TS of 43 dB occurred at 2000 Hz. Permanent threshold shifts (PTSs) of 16 dB at 2000 Hz and 11 dB at 1400 Hz were found. Exposure to the three levels of the 1000-Hz noise band produced TSs of 20, 45, and 61 dB at 1400 Hz. The 95-dB exposure level resulted in PTSs of 6 dB at 1400 Hz and 9 dB AT 2000 Hz. The major results were (1) high-frequency hearing loss to a low-frequency noise and (2) that noise bands matched within 1 dBA were not equally hazardous as dictated by damage-risk criteria. The 63-Hz noise band produced nearly twice as much PTS as the 1000-Hz noise band.