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  • 1
    ISSN: 1432-0738
    Keywords: Nephrotoxicity ; Cytostatic drug ; Celiptium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Celiptium (N2-methyl-9-hydroxy-ellipticinium) is an antitumoral agent used to treat bone metastases from breast carcinomas. This new drug appeared to be of great interest because of the absence of hepato-or myelotoxicity. Three different investigators recently mentioned cases of celiptium-induced renal failure. We therefore undertook a study of renal function and morphology in female Wistar rats. Two single i.v. doses (10 or 20 mg/kg) were administered and animals were sacrificed 4, 8, 15, 28 and 60 days after injection. One group of rats received multiple doses, 5 mg/kg/week for 8 weeks. No mortality was observed. With the 10 mg/kg single dose creatinine clearance (Ccr) and urinary enzymes did not change, and tubular lesions were rare. With the 20 mg/kg single dose CCr decreased on day 4 and returned to normal on day 28. Urinary enzyme excretion (AAP, NAG, γGT) increased. Renal lesions were diffuse with tubular necrosis, luminal dilation and later (day 28) interstitial cellular infiltration. These lesions persisted on day 60 and appeared to be irreversible. Ultrastructural studies showed numerous large fat droplets in proximal tubular cells. Glycerol concentrations in renal cortex homogenates were increased while phospholipids are slightly decreased. With 5 mg/kg every week (multiple doses) Ccr decreased and tubular lesions similar to the observed with the 20 mg/kg single dose were seen. Thus celiptium induced dose-dependent nephrotoxicity in rats with prolonged tubular alterations. Since it has been shown that renal tubular cells metabolized celiptium in vitro into electrophilic intermediates, we suggest that free radicals and quinone derivatives may contribute to peroxidation of unsaturated fatty acids and play a role in the nephrotoxicity of the drug.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 61 (1988), S. 506-508 
    ISSN: 1432-0738
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-601X
    Keywords: PACS. 24.10.-i Nuclear-reaction models and methods – 25.70.Lm Strongly damped collisions – 25.70.Pq Multifragment emission and correlations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The prompt component at intermediate velocity of light charged particles is investigated. An improved coalescence model coupled to the intra-nuclear cascade code ISABEL is used to obtain light complex particle energy spectra and multiplicities as a function of impact parameter. The results are compared with experimental data from the 36Ar + 58Ni experiment at 95 MeV/nucleon, performed with the INDRA 4π detection system. The calculated prompt component is found to rather well reproduce proton spectra. For complex light charged particles the calculated components well populate the high energy part of spectra. Prompt emission can therefore explain the large transverse energies experimentally observed at mid-rapidity.
    Type of Medium: Electronic Resource
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