Medizin - Open Access LMU - Teil 07/22 Archiv

A generalised formulation of microdosimetry clarifies the linkages between the spatial distribution of energy deposits, their proximity function, and the specific energy. The role of the proximity function suggest that it may replace, for various purposes, the inchoate distribution. The Fourier transform of the proximity function is the product of the Fourier transform of the inchoate distribution with its conjugate. This operation causes the loss of phase information, and the reconstruction problem - the reconstruction of the inchoate distribution from its proximity function - can, therefore, not be resolved by a mere deconvolution. For any finite point pattern one can, however, show that its proximity function permits, in principle, the reconstruction. Numerical examples with 2-dimensional patterns of up to 30 points have consistently led to unique solutions, apart from reflections. While there is a finite algorithm, it is readily seen that the number of steps becomes excessive when the number of points in the pattern increases. The reconstruction problem can, thus, be solved in principle but not necessarily in practice. A more general approach must thus be based on numerical optimisation. The algorithm starts with an assumed initial point pattern and utilises a suitable measure for the difference between its proximity function and that of the original pattern. Minimising this difference can lead to the original or to a similar pattern. With simple algorithms one obtains convergence only for patterns of few points; but improved optimisation methods are likely to provide more general solutions.

Linear energy transfer, L, is currently used as reference parameter for the quality factor in radiation protection, and this practice is likely to be continued in an impending revision of the quality factor. But the numerical convention is not, at present, actually applied to photon or electron fields; their quality factor is, instead, summarily equated to unity. The current trend of tightened dose limits in radiation protection may create the need for precise computations of quality factors even for photon and electron radiations. Such computations can, however, not be performed in terms of unrestricted linear energy transfer. The reasons for this difficulty are explained, and the formulae for the quality factor as an integral over electron fluence and restricted linear energy transfer are given. A correct energy balance in this and in a variety of linked dosimetric relations requires a modification of the definition of restricted linear energy transfer. For large energy cut-off values the correction is of minor importance, but for small cut-off values - such as those invoked in biophysical considerations - the modification is essential.

Applications of the variance-covariance technique are presented that illustrate the potential of the method. The dose mean lineal energy, yD, can be determined in time-varying radiation fields where the fluctuations of the dose rate are substantially in excess of the stochastic fluctuations of the energy imparted. An added advantage is, that yD is little influenced by noise that affects both detectors simultaneously. The variance-covariance method is thus stable with respect to dose rate fluctuations and other temporal variations of a radiation field, and to various influences of noise and electronic artefacts. The dose mean lineal energy obtained at different simulated diameters agrees well with experimental data by other authors and can be determined for small simulated diameters (below 100 nm).

The microdosimetric quantities energy imparted, lineal energy, and specific energy are defined with reference to certain volumes but are quantified in terms of frequency distributions of possible values without regard to spatial interrelations. Computer simulations of the patterns of energy deposits seem, therefore, only loosely related to the microdosimetric distributions. In a more general formulation one treats the specific energy and the related microdosimetric quantities as point functions; one deals then with the spatial distribution of their random values and not merely with the frequency of different values. A further extension of the formalism admits reference regions of vanishing size; the inchoate distribution of energy deposits is then the limit case of specific energy. The definitions are related to Matheron's concept of the regularisation of a spatial variable; this is a convolution process that permits a flexible mathematical treatment. One resulting possibility is the definition of specific energy with reference not to the conventional geometry of a sphere or a cylinder but to a disperse region of support. This extension provides distributions of specific energy that are relevant to diffusion or transport processes and it can help to free biophysical models from a one-sided fixation on the concept of geometric targets. The formalism is applied also to the definition of the proximity functions and the related spatial autocorrelation functions.

The current definitions of microdosimetric and dosimetric quantities use the notion of 'ionizing radiation'. However, this notion is not rigorously defined, and its definition would require the somewhat arbitrary choice of specified energy cut-off values for different types of particles. Instead of choosing fixed cut-off values one can extend the system of definitions by admitting the free selection of a category of types and energies of particles that are taken to be part of the field. In this way one extends the system of dosimetric quantities. Kerma and absorbed dose appear then as special cases of a more general dosimetric quantity, and an analogue to kerma can be obtained for charged particle fields; it is termed cema. A modification that is suitable for electron fields is termed reduced cema.

Die neue Bewertung der Krebsmortalität der Überlebenden von Hiroshima und Nagasaki führt zu einer erhöhten Risikoschätzung für Strahlen-Kanzerogenese.

The actions of the reductant ascorbic acid on rat neocortical neurons in vitro was investigated by means of intracellular recordings. At a concentration (500 μM), which reduced the magnitude of dopamine degradation in oxygen-saturated saline solutions by about 50%, ascorbic acid reversibly depressed synaptic potentials and enhanced direct excitability of cortical neurons. The latter effect was not reversible within the observation period. Ascorbic acid did not alter membrane potential and input resistance of the neurons. On the basis of our results we conclude that ascorbic acid is not a useful reductant to avoid oxidation of catecholamines in oxygen-saturated solutions used in electrophysiological experiments in vitro.

The actions of the phosphodiesterase inhibitor denbufylline on the excitability of hippocampal neurons were investigated by means of extracellular and intracellular recordings. Denbufylline, which has been shown to selectively inhibit a low KM, Ca2+/calmodulin-independent phosphodiesterase isozyme, concentration-dependently increased the amplitude of the extracellularly recorded CAI population spike evoked by electrical stimulation of the Schaffer collateral/commissural pathway. Concentration-response-curves yielded an EC50 for denbufylline of 0.76 M. In comparison, the nonselective phosphodiesterase inhibitor 3-isobutyl-lmethylxanthine (IBMX) also produced an increase in the amplitude of the population spike. From the concentration-response-curve, which was steeper than that of denbufylline, an EC50 for IBMX of 1.04 M was obtained. However, despite their similar EC50 values, denbufylline was found to be significantly more potent at lower concentrations (

1. Intracellular microelectrodes were used to obtain recordings from neurons in layer II/III of rat frontal cortex. A bipolar electrode positioned in layer IV of the neocortex was used to evoke postsynaptic potentials. Graded series of stimulation were employed to selectively activate different classes of postsynaptic responses. The sensitivity of postsynaptic potentials and iontophoretically applied neurotransmitters to the non-N-methyl-D-asparate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As reported previously, low-intensity electrical stimulation of cortical layer IV evoked short-latency early excitatory postsynaptic potentials (eEPSPs) in layer II/III neurons. CNQX reversibly antagonized eEPSPs in a dose-dependent manner. Stimulation at intensities just subthreshold for activation of inhibitory postsynaptic potentials (IPSPs) produced long-latency (10 to 40-ms) EPSPs (late EPSPs or 1EPSPs). CNQX was effective in blocking 1EPSPs. 3. With the use of stimulus intensities at or just below threshold for evoking an action potential, complex synaptic potentials consisting of EPSP-IPSP sequences were observed. Both early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced by CNQX. This effect was reversible on washing. This disinhibition could lead to enhanced excitability in the presence of CNQX. 4. Iontophoretic application of quisqualate produced a membrane depolarization with superimposed action potentials, whereas NMDA depolarized the membrane potential and evoked bursts of action potentials. At concentrations up to 5 microM, CNQX selectively antagonized quisqualate responses. NMDA responses were reduced by 10 microM CNQX. D-Serine (0.5-2 mM), an agonist at the glycine regulatory site on the NMDA receptor, reversed the CNQX depression of NMDA responses.

The effects of the cholinoceptor agonist, carbachol (CCh), were examined in the rat hippocampal slice preparation. Intracellular recordings from CA1 pyramidal neurones revealed that CCh (1–3 μM) inhibited excitatory postsynaptic responses evoked by stimulation of the Schaffer collateral/commissural pathway while, at the same time, direct excitability was enhanced. Extracellularly, CCh produced a concentration-dependent reduction of the amplitude of the field excitatory postsynaptic potential (field EPSP) recorded in the CA1 apical dendritic region. The muscarinic receptor antagonist, pirenzepine, competitively antagonized the effects of CCh on the field EPSP with a pA2 of 7.4. These results confirm earlier reports of a presynaptic inhibitory action of CCh in the hippocampal CA1 region and provide strong evidence that this effect is mediated by muscarinic receptors of the M1 subtype.