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  • 1
    Electronic Resource
    Electronic Resource
    Disposition of125I-labeled recombinant human tumor necrosis factor in the tumor-bearing mouse (1989)
    Springer
    Biotherapy 1 (1989), S. 7-18 
    Details
    ISSN: 1573-8280
    Keywords: disposition ; distribution ; excretion ; Meth A sarcoma ; pharmacokinetics ; tumornecrosis factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Disposition of [125I]rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation. Afteri.v. administration, [125I]rHu-TNF measured by radioactivity and immunoreactivity biphasically decreased in plasma. Tumor level of [125I]rHu-TNF was the maximum at 1 h, then decreased and finally remained essentially constant. After i.t. administration, plasma level reached the maximum at 1 h. Tumor level decreased quickly and then became essentially constant. [125I]rHu-TNF was suggested to be degraded to small fragments in the tumor. Significant distribution of [125I]rHu-TNF was found in the kidney, lung, liver and tumor. Most tissue levels decreased with time in parallel with plasma levels. [125I]rHu-TNF radioactivity was found in proximal convoluted tubules of kidney and in those areas of tumor consisting of degenerating cells with pyknotic nuclei. Urine contained most of administered radioactivity, which being neither immunoreactive nor protein-bound.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02170131
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  • 2
    Electronic Resource
    Electronic Resource
    Mode of antitumor action of recombinant human tumor necrosis factor on the sarcoma Meth A transplanted in the mouse (1989)
    Springer
    Biotherapy 1 (1989), S. 47-57 
    Details
    ISSN: 1573-8280
    Keywords: cytotoxicity ; Meth A sarcoma ; mode of action ; tumor necrosis factor ; vasculan collapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mode of antitumor action of rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation with respect to time course, dose-response relationships and selectivity of the effects. The maximal cytotoxic effect on tumor cells revealed by inhibition of DNA synthesis and maximal lesional effect on tumor vasculature revealed by change in blood pool-size in the tissue were detected at 30 min and I h after administration of rHu-TNF, respectively. The dose-response relationship between cytotoxic and tumoricidal effects of rHu-TNF was irrespective of administration route. ED50s of these antitumor effects afteri.v. administration of rHu-TNF were about 50 times as high as ED50s afteri.t. administration. ED50 ofi.t. given rHu-TNF for vascular effect was about 20 times as high as that for cytotoxicity while ED50 ofi.v. rHu-TNF for vascular effect was only 2–3 times as high as that for cytotoxicity. The whole body autoradiographies with [125I] HSA giveni.v. to see the blood influx into tumor tissue and [14C]thymidine given i.v. to see DNA synthesis in the whole body after administration of rHu-TNF revealed that the distribution of radioactivity was markedly changed in the tumor alone without any detectable change in other whole body tissues. In conclusion, thein vivo antitumor effect of rHu-TNF giveni.t. ori.v., appears to be exerted through the direct action on Meth A sarcoma rather than indirectly on tumor vasculature. Under present conditions, the effect of rHu-TNF in the whole body tissues seems rather selective on cells and vasculature of the tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02170135
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  • 3
    Electronic Resource
    Electronic Resource
    Metabolites of loperamide in rats (1979)
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 6 (1979), S. 253-259 
    Details
    ISSN: 0306-042X
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Following intraperitoneal administratin to rats of [14C]loperamide, [carbonyl-14C] 4-(p-chlorophenyl)-4-hydroxyl-N,N-dimethyl-α,α-diphenyl-1-piperidinebutyramide, metabolites in feces and urine were separated, and identified by means of mass spectrometry. In feces, six metabolites were identified in addition to the unchanged drug. The main metabolic pathways involved are dealkylation in the dimethyl amide moiety to give desmethyl- and didesmethylloperamide, both of which were in turn monohydroxylated either in the α-phenyl ring or possibly in the α-carbon in the piperidine ring. It is noteworthy that metabolites hydroxylated in the piperidine ring were isolated as pyridinium derivatives, possibly due to spontaneous aromatization of its 2,4-dihydroxy-4-(p-chlorophenyl)piperidine ring. In urine, only two metabolites were found and identified to be desmethyl- and didesmethylloperamide, since [14C]loperamide was excreted into urine only in a small amount.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bms.1200060606
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    Paper (German National Licenses)
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