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  • 1
    Electronic Resource
    Electronic Resource
    Comparison of the adrenalytic activity of mitotane and a methylated homolog on normal adrenal cortex and adrenal cortical carcinoma (1993)
    Springer
    Cancer chemotherapy and pharmacology 31 (1993), S. 459-466 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mitotane is an important adrenalytic drug for the treatment of adrenal cancer whose use is limited by toxicity. Reports from another laboratory indicated that a methylated homolog of Mitotane (Mitometh) tested in guinea pigs possessed comparable adrenalytic activity but was less toxic than Mitotane. This observation prompted us to undertake a comparative study of these two drugs on the basis that Mitometh may be a superior agent for the treatment of adrenal cancer. Preliminary studies in guinea pigs failed to show a significant adrenalytic effect for either Mitotane or Mitometh. Thus, we extended the study to 13 mongrel dogs weighing 12–15 kg that were treated daily with Mitometh or Mitotane (50–100 mg/kg) for 6 or 12 days. Cortisol decreased to undetectable levels and adrenocorticotropic hormone (ACTH) rose to 10 times the baseline levels within 72 h in Mitotane-treated animals. Despite the achievement of similar drug levels, Mitometh treatment in dogs failed to suppress cortisol or increase ACTH. To determine whether these differences were due to differences in bioavailability, we measured the relative concentration of Mitotane and Mitometh in homogenates of adrenal cortex obtained from Mitotane- and Mitometh-treated dogs. The adrenal concentration of Mitometh determined in Mitometh-treated dogs was 5 times higher than the concentration of Mitotane measured in Mitotane-treated animals. Whereas the adrenal glands of Mitotane-treated dogs showed hemorrhage and necrosis, the Mitometh-treated animals showed no adrenal damage. Despite the lack of adrenalytic activity, Mitometh maintained its toxicity as demonstrated by microscopic evidence of hepatic necrosis and an increase in hepatic enzymes. The adrenalytic effects of both agents was also studied in vitro using a human functioning adrenal cortical carcinoma cell line. NCI-H295. Whereas Mitotane strongly suppressed cell growth, Mitometh had a weaker effect. We conclude that Mitometh is not likely to be effective in the therapy of adrenal cancer. Moreover, the results of this study are supportive of the view that metabolic transformation of Mitotane is in some way linked to its adrenalytic action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685036
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Normal Flora and Acute Inflammation (1966)
    [s.l.] : Nature Publishing Group
    Nature 210 (1966), S. 1072-1073 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Because of the importance, in terms of host resistance, of events occurring during the early hours of acute inflammation, the effect of the normal flora on the mobilization of leucocytes and on the increase in vascular permeability to protein was assessed. This was accomplished by comparing the ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/2101072a0
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  • 3
    Electronic Resource
    Electronic Resource
    High doses of neomycin sulfate and the absorption of glucose and xylose from the rat small intestine (1966)
    Springer
    Digestive diseases and sciences 11 (1966), S. 923-929 
    Details
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neomycin sulfate, at doses of 250 mg./kg. or 2 gm./kg., was instilled intragastrically, in male Fisher-strain rats daily for 21 days. Pair-fed controls received an equal amount of saline intragastrically for an equal period. After 3 weeks of treatment animals were tested by our modification of the Cori method to assess the absorption of xylose, glucose, and a mixture of xylose and glucose. Rats receiving neomycin at both doses demonstrated an enhanced absorption of glucose. A significant reduction in the absorption of xylose was noted in animals treated with 2 gm./kg. of neomycin. When glucose and xylose were administered together to rats receiving 2 gm./kg. of neomycin, a significant reduction in the absorption of xylose and an enhancement in the absorption of glucose was observed. Histologic examination revealed no constant alterations in the appearance of the small intestinal mucosa of the neomycin-treated rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02233080
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