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  • brain cell cultures  (1)
  • sarcomas  (1)
  • teratogenesis  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Use of aggregating cell cultures for toxicological studies (1988)
    Springer
    Cellular and molecular life sciences 44 (1988), S. 817-823 
    Details
    ISSN: 1420-9071
    Keywords: Aggregating cell cultures ; brain cell cultures ; liver cell cultures ; teratogenesis ; toxicology ; antimitotic drugs ; cholera toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Relatively simple techniques are now available which allow the preparation of large quantities of highly reproducible aggregate cultures from fetal rat brain or liver cells, and to grow them in a chemically defined medium. Since these cultures exhibit extensive histotypic cellular reorganization and maturation, they offer unique possibilities for developmental studies. Therefore, the purpose of the present study was to investigate the usefulness of these cultures in developmental toxicology. Aggregating brain cell cultures were exposed at different developmental stages to model drugs (i.e., antimitotic, neurotoxic, and teratogenic agents) and assayed for their responsiveness by measuring a set of biochemical parameters (i.e., total protein and DNA content, cell type-specific enzyme activities) which permit a monitoring of cellular growth and maturation. It was found that each test compound elicited a distinct, dose-dependent response pattern, which may ultimately serve to screen and classify toxic drugs by using mechanistic criteria. In addition, it could be shown that aggregating liver cell cultures are capable of toxic drug activation, and that they can be used in co-culture with brain cell aggregates, providing a potential model for complementary toxicological and metabolic studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01941177
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Saturable metabolism of continuous high-dose ifosfamide with Mesna and GM-CSF: A pharmacokinetic study in advanced sarcoma patients (1999)
    Springer
    Annals of oncology 10 (1999), S. 1087-1094 
    Details
    ISSN: 1569-8041
    Keywords: high-dose ifosfamide ; metabolism ; pharmacology ; sarcomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The aim of this study was to assess the pharmacology, toxicity and activity of high-dose ifosfamide/mesna ± GM-CSF administered by a five-day continuous infusion at a total ifosfamide dose of 12–18 g/m2 in adult patients with advanced sarcomas. Patients and methods: Between January 1991 and October 1992 32 patients with advanced or metastatic sarcoma were entered the study. Twenty-seven patients were pretreated including twenty-three with prior ifosfamide at less than 8 g/m2 total dose/cycle. In 25 patients (27 cycles) extensive pharmacokinetic analyses were performed. Results: The area under the plasma concentration-time curve (AUC) for ifosfamide increased linearly with dose while the AUC's of the metabolites measured in plasma by thin-layer chromatography did not increase with dose, particularly that of the active metabolite isophosphoramide mustard. Furthermore the AUC of the inactive carboxymetabolite did not increase with dose. Interpatient variability of pharmacokinetic parameters was high. Dose-limiting toxicity was myelosuppression at 18 g/m2 total dose with grade 4 neutropenia in five of six patients and grade 4 thrombocytopenia in four of six patients. Therefore the maximum tolerated dose was considered to be 18 g/m2 total dose. There was one CR and eleven PR in twenty-nine evaluable patients (overall response rate 41%). Conclusion: Both the activation and inactivation pathways of ifosfamide are non-linear and saturable at high-doses although the pharmacokinetics of the parent drug itself are dose linear. Ifosfamide doses greater than 14–16 g/m2 per cycle appear to result in a relative decrease of the active metabolite isophosphoramide mustard. These data suggest a dose-dependent saturation or even inhibition of ifosfamide metabolism by increasing high dose ifosfamide and suggest the need for further metabolic studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008386000547
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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