Molecular and cell models of biological effects of heavy ion radiation

The nitric oxide (NO) production by porcine aortic valve endothelial cells was estimated in cusps incubated at 37 degrees C by measuring their cyclic GMP content and the nitrite levels of the incubation medium. After a stabilization period, incubation for 5 min with acetylcholine, bradykinin, ADP and bovine thrombin resulted in a receptor-mediated increase in cyclic GMP which could be blocked by EGTA, N-omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA). Incubation with lipopolysaccharide (endotoxin) from E. coli O111:B4 or bovine for 5 h, dose-dependently increased nitrite production as well as cyclic GMP content. The elevated nitrite production was completely abolished in the presence of the protein synthesis inhibitor cycloheximide, was reduced by more than 50% by dexamethasone but was not affected by EGTA. L-NMMA dose-dependently reduced the increased nitrite production and cyclic GMP content. These results suggest that besides the presence of a constitutive NO synthase in porcine aortic valve endothelial cells thrombin, like lipopolysaccharide, triggers the de novo expression of an inducible Ca(2+)-independent NO synthase.     

Panel discussion: Do non-targeted effects impact the relation between microdosimetry and risk?

An invited panel discussed with the participants of the Symposium their views on the impact of non-targeted effects on the relationship between microdosimetry and risk. The discussion was wide ranging and lively, with divergences of opinion. At one end was the view that understanding microscopic features and distributions of radiation was an essential component to understanding risk, especially at low doses, and additionally that substantial questions and uncertainties arose from lack of information on the mechanisms and consequences of non-targeted effects. At the other end, it was held that microdosimetry and non-targeted effects are irrelevant to practical radiation protection because protection practice is already securely founded on macroscopic organ doses and direct epidemiological observations of risk. A summary of the discussion is provided in the sequence in which it took place. The session illustrated the underlying mixture of fundamental and practical issues and the need for increased scientific knowledge.     

Uveitis in dogs and cats: guidelines for the practitioner

Uveitis is a commonly misdiagnosed ophthalmic condition with a wide aetiological base and often the cause cannot be established. Uveitis can be associated with systemic diseases like feline infectious peritonitis, feline immunodeficiency virus, feline leukaemia virus, lymphoma, toxoplasmosis and canine ehrlichiosis. The classification and general clinical signs of uveitis are discussed. Applicable clinical cases, manifestations and diagnostic methods of the selected diseases are mentioned, and a general approach to the treatment of uveitis is given.     

Occurrence of volatile nitrosamines in spice premixes

Nitrosamines have been found in spice-curing salt premixes which were used in meat products. A number of premixes were analysed using gas chromatography and high resolution mass spectrometry and the presence of N-nitrosopiperidine was confirmed in the majority of the premixes. After storage for 6 months levels of N-nitrosopiperidine had increased in most instances, and N-nitrosopyrrolidine was detected in several samples.     

A universal threshold concept for hydrophobic mycolata in activated sludge foaming

Recent studies using quantitative fluorescence in situ hybridization (FISH) have supported the principle that there are mycolata concentration thresholds, above which foaming is likely to occur. In this study, we surveyed 14 wastewater treatment plants (WWTPs) in the UK, using quantitative FISH, to establish that the principle of a mycolata threshold (2 x 10(6) mycolata cells ml(-1) mixed liquor suspended solids) is an empirical though widely held value. In addition, we designed, optimized and applied probes for members of the less hydrophobic mycolata genera Corynebacterium and Dietzia, to show that these organisms dominated the mycolata populations in two non-foaming WWTPs where the mycolata concentrations were above the threshold value. We propose that the mycolata threshold value is only applicable to hydrophobic members of the mycolata.     

Stage specificity, dose response, and doubling dose for mouse minisatellite germ-line mutation induced by acute radiation

Germ-line mutation induction at mouse minisatellite loci by acute irradiation with x-rays was studied at premeiotic and postmeiotic stages of spermatogenesis. An elevated paternal mutation rate was found after irradiation of premeiotic spermatogonia and stem cells, whereas the frequency of minisatellite mutation after postmeiotic irradiation of spermatids was similar to that in control litters. In contrast, paternal irradiation did not affect the maternal mutation rate. A linear dose-response curve for paternal mutation induced at premeiotic stages was found, with a doubling dose of 0.33 Gy, a value close to those obtained in mice after acute spermatogonia irradiation using other systems for mutation detection. High frequencies of spontaneous and induced mutations at minisatellite loci allow mutation induction to be evaluated at low doses of exposure in very small population samples, which currently makes minisatellite DNA the most powerful tool for monitoring radiation-induced germ-line mutation.     

Production and dosimetry of copper L ultrasoft x-rays for biological and biochemical investigations

Ultrasoft x-rays provide a unique tool for investigating the intracellular mechanisms of radiation action. Secondary electrons are produced with a well defined energy and a range comparable with that of critical structures in the cell. Copper L characteristic x-rays of weighted average energy of 956 eV interact within the cell, mainly with the oxygen atom, typically producing a photoelectron with energy 424 eV (95%) followed by an Auger electron with an average energy of 505 eV, with a combined continuous slowing down approximation (csda) range of approximately 40 nm. The attenuation through the cell is similar to that of carbon K x-rays (277 eV, single electron), therefore a useful comparison can be made due to similar dose-averaging factors but different electron configurations (total range, and pairs versus singlets). The production, absorption, dosimetry and biological implications of Cu L x-rays using the Medical Research Council cold cathode source is described extending the number of energies available for study in the ultrasoft region. Design parameters were optimized to overcome the inherently low L-characteristic-to-bremsstrahlung yield ratio. Surface absorbed dose rates of 1 Gy min-1 have been obtained with a bremsstrahlung contamination of less than 0.5%. A confocal microscope was used to make thickness measurements on live cells to allow careful determination of the mean absorbed dose. Survival curves for V79-4 Chinese hamster cells were obtained, showing that Cu L x-rays are substantially more lethal per unit dose than are hard x-rays or gamma-rays, with a relative biological effectiveness (RBE) of 1.8. The data are consistent with the hypothesis that clustered damage at the DNA/chromatin level produced by low-energy electrons is biologically more effective.