Effective drugs are not available to protect against ß-amyloid peptide (Aß)-induced neurotoxicity. Cortical neurons from rat embryos were treated with the toxic fragment Aß25-35 at 1 p~Min the presence or absence of flupirtine, a triaminopyridine, successfully applied clinically as a nonopiate analgesic drug. Five days later 1 ‚uM Aß25-35 caused reduction of cell viability to 31.1%. Preincubation of cells with flupirtine (1 or 5~ig/ ml) resulted in a significant increase of the percentage of viable cells (74.6 and 65.4%, respectively). During incubation with Aß25-35 the neurons undergo apoptosis as determined by appearance of the characteristic stepladder-like DNA fragmentation pattern and by the TUNEL technique. Aß25-35-induced DNA fragmentation could be abolished by preincubation ofthe cells with 1 1ig/ml flupirtine. Incubation with Aß25-~35reduces the intraneuronal level of GSH from 21.4 to 7.4 nmol/10 6 cells. This depletion could be partially prevented by preincubation of the cells with flupirtine. Thus, flupirtine may be adequate for the treatment of the neuronal loss in Alzheimer's disease (where Aß accumulates in senile plaques) and probably other neurological diseases such as amyotrophic lateral sclerosis.

The biological effectiveness of monoenergetic protons was investigated with the track-segment method. Protons were accelerated by a Tandem Van de Graaff accelerator and their final energies were 3.0 and 7.4 MeV. The biological system used was Chinese hamster V-79 cells and their survival ability following proton irradiation was investigated. Cobalt-60 gamma-rays were used as reference radiation to assess proton relative biological effectiveness (RBE). Survival curves were obtained for the gamma-ray and proton irradiations, and the relation S = exp (-alpha D-beta D2) was fitted to the data and the parameters alpha and beta were determined. The RBE values, calculated on the basis of the mean inactivation dose D and other pertinent parameters, were found to be 1.7 +/- 0.1 and 2.8 +/- 0.2 for 7.4 and 3.0 MeV protons, respectively. Comparisons were made with the results published by other investigators and it was concluded that in this low energy range the biological effectiveness increases substantially with decreasing proton energy.

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Chinese hamster V-79 cells are widely used in short term screening for potential physical or chemical mutagens of the environment. A simplified version of the standard Giemsa protocol of Moorhead and the Feulgen plus Giemsa protocol of Wolff and Perry is given which permits the observations in situ of chromosome aberrations or sister chromatid exchanges and the estimation of the mitotic index in the Petri dishes for the culture of the V-79 cells.