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  • 1
    ISSN: 1432-2307
    Keywords: Nucleolar segregation ; 4-Hydroxyaminoquinoline 1-oxide ; Rat ; DNA adducts ; Apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male 6-week-old Sprague Dawley rats were given a single intravenous injection of 4-hydroxyamino-quinoline 1-oxide (4HAQO) at a dose of 20 mg/kg in order to produce ultrastructural changes as possible morphological biomarkers for toxicity. Immunohistochemically demonstrated formation of 4HAQO-DNA adduct was correlated with the changes found. Nucleolar alteration, demonstrable by electron microscopy as segregation of nucleolar components into granular and fibrillar compartments, was evident in cells of the target organs, exocrine pancreas and adrenocortex, but not of the non-target liver parenchyma. Sequential observation clarified that such alteration was highest in frequency 6 h and 4 h after 4HAQO administration in pancreatic acinar cells and adrenocortical cells respectively. Electron microscopically, apoptotic changes of acinar cells were evident 2 h after injection of 4HAQO. DNA adduct formation was consistently demonstrated in the same target organs showing nucleolar segregation, the highest frequency being noted 4 h after 4HAQO treatment in both pancreatic acinar cells and adrenocortical cells. Our results thus indicate an identity of the target cells for nucleolar segregation and 4HAQO-DNA adduct formation which correlates with 4HAQO-toxicity. We suggest that nucleolar segregation occurs subsequent to the generation of DNA damage.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-2981
    Keywords: Control survey ; Haematology ; Inter laboratory variation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A survey was conducted to determine the accuracy and quality control of automated haematology analysers used in non-clinical toxicity studies. Pooled blood samples from male Sprague-Dawley rats were distributed to 98 laboratory facilities throughout Japan, the samples being delivered under refrigeration to each facility within 18 h of sample preparation. At each facility, the samples were analysed within 4 h of receipt. Commercially available normal human blood samples from a single lot were also analysed at the same time. Most haematological results were within the mean ±3SD (standard deviation), but some facilities gave either high or low values consistently for both human and rat samples. No facility gave high or low values to certain parameters sporadically, which suggests no problem with the accuracy of the equipment. However, it was suspected that there would be some problem in comparing analytical values determined in a unique way by specific equipment design. The use of certain equipment resulted, in rat haematocrit values in particular, being either too high or too low. In these cases, it was deemed necessary to make some adjustments or calibration changes. There were also platelet values with a ‘plus drift’ which was apparently due to contamination with, or failure to identify small red blood cells (RBC). There was no deviation in values which could be attributed solely to the mechanical operation of any of the analytical equipment. Non-standard, initial setting up of the equipment (originally intended for human use, but now used for a variety of animal species) has been recognised as the main cause for a wider range of the analytical values seen. The results of this survey suggest that it may be necessary to review equipment calibration at each facility, and to re-establish the historical background data.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-2981
    Keywords: Cold storage ; Cold transport ; Dog ; Haematology ; Parameters ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A sample surveillance programme is scheduled to be conducted on measurement methods of haematology parameters which will include the participation of over 70 facilities. In preparation for that programme, a preliminary study was conducted, at five of the facilities, on the effects of cold storage and transport on rat and dog blood samples. The blood samples used in this study were taken from healthy, untreated rats and dogs from stocks held at each facility, and were anticoagulated with EDTA-2K. The blood samples were stored undisturbed at 4–10°C. The effects of transporting samples were also investigated by placing aliquots of the same samples in a cooler (4–13°C) containing a cold insulator. Red blood cell counts (RBC), total white blood cell counts (WBC), haematocrit (HCT), haemoglobin (HGB) and platelets (PLT) were measured twice for each sample, i. e., fresh and 24 hours later, and these results were compared. Although blood sampling conditions were similar for all facilities, each facility employed its own method with respect to the analysis. Automated haematology analysers used included the Toa Sysmex E4000/CS, Toa Sysmex E5000, Coulter S-Plus STRK, Technicon H*1 and Nihon Kohden MEK-4500. In the case of rat blood samples, measured values after undisturbed cold storage, fluctuating by −2 to +1% in comparison with values before storage. Measured values after cold transport fluctuated by −2 to +7% in comparison with those before transport. It was concluded, for rat blood samples, that neither storage condition had a significant effect on the results. In the case of dog blood samples, RBC, HCT and HGB values fluctuated by +1 to +2% and 0 to +2% in comparison with prestorage and pretransport values, respectively. They were not, therefore, significantly affected by undisturbed cold storage or cold transport. However, WBC values increased by +18% after undisturbed cold storage and by +18% after cold transport. Conversely, PLT values decreased by −20% both after undisturbed cold storage and cold transport. It is known that dog blood samples are affected by cold storage, and a similar trend was observed in this study. On the basis of these results, it was concluded that the distribution of rat blood samples for the conduct of a sample survey of analytical methods under cold storage is suitable, and that it will be necessary to have the samples prepared at a single facility.
    Type of Medium: Electronic Resource
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