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Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the effects of soman and to evaluate possible curative interventions, a series of behavioural, electrophysiological and neuropathological experiments were carried out in the guinea pig using the NMDA antagonist N-[1-(2-thienyl)cyclohexyl] piperidine (TCP) in conjunction with atropine and pyridostigmine. The NMDA antagonist TCP appeared to be very effective in the treatment of casualties who suffered from soman-induced seizures for 30 min: (i)Seizures were arrested within minutes after the TCP injection, confirmed by quantitative electroencephalogram (EEG), after fast Fourier analysis. Three hours after TCP the quantitative EEGs were completely normal in all frequency bands and remained normal during the entire 3-week intoxication period. The power shift to the lower (delta) frequency bands, indicative for neuropathology and found in control animals intoxicated only by soman, was not observed in the soman-TCP group. (ii)The gross neuropathology found in soman control animals within 48 h after soman was prevented in soman-TCP animals and was still absent in 3-week survivors. Instead, ultrastructural changes were observed, indicative of defense mechanisms of the cell against toxic circumstances. (iii)Twenty-four hours after soman, soman-TCP animals were able to perform in the shuttle box and Morris water maze. The beneficial effects of TCP on the performance in these tests during the 3-week intoxication period were very impressive, notwithstanding (minor) deficits in memory and learning. (iv)The increase in excitability after TCP was confirmed by an increase in the acoustic startle response. Taken together, these results confirmed the involvement of NMDA receptors in the maintenance of soman-induced seizures and the development of brain damage. They underline the current hypothesis that cholinergic mechanisms are responsible for eliciting seizure activity after soman and that, most likely, the subsequent recruitment of other excitatory neurotransmitters and loss of inhibitory control are responsible for the maintenance of seizures and the development of subsequent brain damage.

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Background: Assessment of exposure assessment to metal working fluids (MWF) has almost exclusively focused on inhalation exposure. Aims: To assess levels of, and factors affecting, dermal and inhalation exposure to semi-synthetic MWF, and to identify suitable dermal exposure grouping schemes among metal workers for an epidemiological survey on dermatitis of hands, forearms, and head. Methods: A cross-sectional survey was conducted in four metal working machining departments of a truck manufacturing plant, estimating dermal and inhalation exposure levels to semi-synthetic metal working fluids (SMWF) in machine operators. Dermal exposure levels to SMWF were estimated by three different methods for dermal exposure assessment (VITAE, surrogate skin pad method, and a semi-quantitative dermal exposure assessment method (DREAM)). Results: The identified factors affecting dermal exposure were similar for the three methods, although differences were found for estimated variability in dermal exposure levels between groups, within groups (among workers), and from day to day. With the VITAE method differences in exposure levels were detected between workers that were not detected with the surrogate skin pad method, and only partly with the DREAM method. Conclusions: Considering the additional effort and costs that use of the VITAE method entailed, the observational semi-quantitative DREAM method appeared to be more efficient for grouping of dermal exposure levels for the epidemiological study on dermatitis.

SUMMARY Failure to appreciate the consequences for stereological work of the simultaneous presence of complex‐shaped perforated and disc‐like non‐perforated synapses in brain tissue results in underestimation of synaptic profile length and overestimation of synaptic density when measured in randomly selected ultrathin E‐PTA slices. This problem can be solved by using serial slices and a calculation method which makes no assumptions about synaptic size and shape. A three‐dimensional reconstruction is unnecessary.