A mechanism for ion selectivity in potassium channels: computational studies of cation-pi interactions.

A combination of computational methods has been used to evaluate the interaction between the pi face of a benzene molecule and the monovalent cations of lithium, sodium, potassium, and rubidium. In the gas phase, the ions are strongly bound, and the affinity for benzene follows the expected electrostatic trend (lithium, largest; rubidium, smallest). However, in an aqueous environment, a reordering occurs such that the potassium ion is preferred over all the other ions for 2:1 benzene:ion complexes. The selectivity sequence parallels that seen in voltage-gated potassium channels. Given that several conserved aromatic residues are present in the pore region of such channels, these results suggest that the cation-pi interaction may be responsible for the ion selectivity in potassium channels.

Fractionation effect on radiation-induced growth retardation of tibia in rabbits and rats.

A study of the sensitivity to fractionation of the growing tibia of rabbits and rats was conducted by comparing the growth of the treated right bone to that of the untreated left side in each individual animal using radiographic measurements. The experimental endpoint was the percentage of normal growth 24 weeks after irradiation in rabbits and 14 weeks after treatment in rats. The results show clear dose-response relationships in all experimental arms. A clear-cut fractionation effect was demonstrated in both species. The alpha/beta-ratios determined by maximum likelihood analysis according to the LQ-model with graded responses were 3.2 Gy (95% C.I. 1.1; 5.6) in rabbits and 6.9 Gy (5.3; 8.7) in rats, when all data were included in the calculations. When single-dose data were excluded the alpha/beta-values were -0.6 Gy (-3.1; 2.3) in rabbits and 5.0 Gy (3.5; 7.0) in rats. Our data provide further evidence that low doses per fraction should be used when irradiation of the epiphysis cannot be avoided in pediatric patients.

Acute response of pig skin to irradiation with 12C-ions or 200 kV X-rays.

The acute response of pig skin to treatment with high energy carbon ions (plateau region) at the Gesellschaft für Schwerionenforschung (GSI, Darmstadt, Germany) was compared with changes after 200 kV x-irradiation. Carbon doses isoeffective to the x-ray doses were computed with a recently established model for calculation of the biological effect of heavy ions. Clinical changes and physiological symptoms (blood flow, erythema, trans-epidermal water loss, skin hydration) were scored. The parameters analyzed were maximum and mean values of each symptom during days 24 to 70 after irradiation, and the quantal endpoints for the establishment of dose effect curves were the median values of these. With exception of the maximum change in the red blood cell concentration (p < 0.02) no significant differences could be found in the response to x-rays and RBE-corrected heavy ions. These results indicate that the model is valid for the calculation of biological effects of 12C-ions (plateau region) and may at least for epidermis be applied to treatment planning.

Response of pig lung to irradiation with accelerated 12C-ions.

The response of pig lungs to irradiation with 12C-ions was assessed in two experiments to validate the procedures for heavy ion therapy planning at the Gesellschaft für Schwerionenforschung (GSI) and to explore their range of applicability. In both experiments, the target volume (spread-out Bragg peak, SOBP) was planned to be a 4 cm long cylinder with a diameter of 4 cm. Doses in the SOBP were prescribed to be equivalent to 5x4 Gy, 5x5.5 Gy and 5x7 Gy of x-rays in the first experiment, and to 5 fractions of 7 Gy and 9 Gy in the second experiment. The lung response in the first experiment was less than expected on the basis of earlier experiments with photons. Pneumonitis reaction and chronic fibrotic changes were observed outside the prescribed high-dose region. In the second experiment, the effects were more pronounced than had been expected on the basis of the first experiment. Changes were most intense in the high-dose region, but were also seen throughout the lung along the beam channel. Moreover, significant skin reactions were observed at the beam entrance site in all animals and - less pronounced - at the beam exit site in 3 of the 6 animals. In conclusion, the complex irradiation geometry of the pig lung, the changes of body weight between the two experiments, and insufficient accounting for a change in the relative biological effectiveness (RBE) computation led to substantial deviations of the observed reactions from expectations, the reasons for which could be identified in a subsequent analysis. The less pronounced lung reaction in the first experiment was due to an overestimation of RBE in a preliminary version of the algorithm for its determination. The extension of the fibrotic reaction resulted from the smear-out of the high-dose region due to density variations in tissue structures, respiratory movement, and limited positioning accuracy. The skin reactions at the entrance port reflect the different treatment geometry in the two experiments. The one unexplained observation is the mild skin reaction that was observed in the second experiment at the beam exit site.