The mammalian circadian pacemaker is located in the suprachiasmatic nucleus (SCN), which is composed of dorsomedial (dm) and ventrolateral (vl) regions. The molecular clockwork responsible for the SCN rhythmicity consists of clock genes and their transcriptional‐translational feedback loops. The rat SCN rhythmicity and clockwork are affected by the photoperiod. The aim of this study was to elucidate development of the rat SCN rhythmicity, namely of the rhythmicity of the dm‐ and vl‐SCN and of expression of clock genes and to ascertain when the photoperiod starts to affect the SCN rhythmicity. Rhythmicity of the dm‐SCN, measured as the rhythm in spontaneous c‐FOS production, developed earlier than that of the vl‐SCN, which was measured as the rhythm in c‐FOS photoinduction. However, photoperiodic affection of the rhythmicity occurred earlier in the vl‐SCN than in the dm‐SCN. From the 4 clock genes (Per1, Per2, Cry1 and Bmal1) studied, the expression of Bmal1 and Per1 was rhythmic already in 1‐day‐old rats; at this age, the Per2 mRNA rhythm just started to form and no rhythm in Cry1 expression was detected. After the second postnatal day, all 4 genes were expressed in a rhythmic manner. Thereafter, the rhythms matured gradually via increasing amplitude. Per1 and Per2 mRNA rhythms started to be affected by the photoperiod at the 10th postnatal day. The data suggest that the rhythms in clock genes expression in the rat SCN develop mostly postnatally. The molecular clockwork may start to be photoperiod‐dependent around the 10th postnatal day.
The effect of pretreatment with stobadine (a novel drug with cardioprotective properties) on the activity of glutathione peroxidase was studied in the heart of mice after Co60 irradiation. Exposure to 6.5 Gy caused significant decrease in the activity of the enzyme (p < 0.01). Treatment with stobadine (70.07 mg/kg) 1 or 2 h before irradiation resulted in activity enhancement in comparison with the nonpretreated irradiated group (p < 0.01). We conclude that the radical scavenging mechanism may be involved in the protection exerted by stobadine. The results are in agreement with those obtained by the micronucleus test.
Effect of amikacin at suprainhibitory (2 or 4 x MIC) or supra-subinhibitory concentrations (2 or 4 x MIC + 0.2 x MIC) on bacterial growth, cytotoxicity and cell surface hydrophobicity of three Acinetobacter baumannii strains was studied. Amikacin at suprainhibitory concentrations induced postantibiotic effects (PAEs; suppression of bacterial growth after short time exposure of bacteria to the antibiotic) against all A. baumannii strains. PAEs ranged from 1.2 to 2.9 h (2 x MIC) and 3.5 to 6.3 h (4 x MIC). Supra-subinhibitory concentrations of amikacin (2 x MIC + 0.2 x MIC) manifested a more significant delay of bacterial regrowth (PA SMEs) for two strains (6.6 or 7.5 h) in comparison with PAEs. One strain under these conditions as well as all strains treated with amikacin at 4 x MIC + 0.2 x MIC did not show any regrowth. Amikacin at all concentrations tested significantly reduced cytotoxic activity of A. baumannii evaluated on alveolar epithelial type II cells. Survival of type II cells after application of antibiotic-treated A. baumannii was in the range of 88 to 101% of the control cells. Cell surface hydrophobicity of amikacin-treated bacteria was practically unchanged varying between 94 and 100.9% as compared to the controls.
The mechanism of toxicity of selected asbestos substitute mineral fibres was examined and compared to that of asbestos. Alveolar macrophages and type II cells were isolated from Fischer 344 rats and after 20 h cultivation various concentration of fibres alone (amosite, wollastonite, rockwool or glass fibres) or in combination with cigarette smoke were added to cells and the cultivation continued for another 24 h. After finishing the exposure the number of alkaline phosphatase positive type II cells was counted, the comet assay was used to detect DNA damage (strand breaks) in both cell types and ultrastructural changes were evaluated by transmission electron microscopy. The decrease of the number of alkaline positive type II cells was dose dependent in all cases. The number of DNA strand breaks (SBs) in both cell types was enhanced after exposure to all types of fiber, the enhancement was dose dependent, the highest level of SBs was observed after amosite exposure. The combined exposure to mineral fibres and cigarette smoke showed synergic effect on the level of SBs. Transmission electron microscopy showed that already 1 microg x cm(-2) amosite caused destruction of AM while other fibres were phagocytized.
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