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  • 1
    Digitale Medien
    Digitale Medien
    Steroids decrease uptake of carboplatin in rat gliomas – Uptake improved by intracarotid infusion of bradykinin analog, RMP-7 (1997)
    Springer
    Journal of neuro-oncology 34 (1997), S. 131-138 
    Details
    ISSN: 1573-7373
    Schlagwort(e): blood-brain barrier ; bradykinin ; brain tumor ; carboplatin ; glucocorticoid ; RG2 glioma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A blood-tumor barrier (BTB) limits delivery of antitumoragents to brain tumors. This study sought todetermine whether dexamethasone (DXN) treatment of rats withintracranial gliomas would 1) further impair delivery ofcarboplatin to brain tumors, and 2) whether intracarotidinfusion of the bradykinin analog, RMP-7, would improvedelivery during concurrent DXN treatment. Wistar rats withRG2 gliomas were utilized and a unidirectional transport,Ki, of radiolabeled [14C] carboplatin was determined usingquantitative autoradiography. In DXN pretreatment animals, 3 mg/kg/dayof DXN was administered intraperitoneally for 3 daysprior to Ki determinations. At 10 days aftertumor implantation, Ki of [14C] carboplatin into DXN-treatedtumors and brain surrounding tumor (BST) was significantlylower compared to non-DXN treated tumors and BST(3.30 ± 0.91 vs. 4.47 ± 1.80, p〈 0.05, and 0.94 ± 0.84 vs. 2.18± 0.79, p 〈 0.05, respectively). Intracarotid infusionof RMP-7 (0.1 mg/kg/min) significantly increased the Kifor carboplatin in DXN-treated tumors (6.35 ± 3.10vs. 3.30 ± 0.91, p 〈 0.01), however, RMP-7increased Ki to a greater extent in tumorsnot pretreated with DXN (12.07 ± 3.60 vs.4.47 ± 1.80, p 〈 0.0001). Our studiesshow that dexamethasone decreases transport of carboplatin intobrain tumors. Intracarotid infusion of RMP-7 selectively increasescarboplatin transport to tumors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1005706329630
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  • 2
    Digitale Medien
    Digitale Medien
    Intravenous Infusion of RMP-7 Increases Ocular Uptake of Ganciclovir (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 80-85 
    Details
    ISSN: 1573-904X
    Schlagwort(e): blood-ocular barriers ; bradykinin ; drug delivery ; retina ; guinea pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The ability of intravenous (i.v.) infusions of the bradykinin agonist, RMP-7, to permeabilize the blood-ocular barriers (BOB) to the antiviral agent ganciclovir was investigated in guinea-pigs. Methods. Different i.v. dosing regimens included pre-treatment with RMP-7 (0.2 μg/kg/min for 5 min) followed by either [3H]-ganciclovir (1 μCi/0.2 ml/min) alone, and/or co-infusion with RMP-7 and [3H]-ganciclovir. At specific times the animals were sacrificed, their eyes removed, and the retina and lens epithelium dissected and analyzed for the amount of radioactivity. Results. Using the ratio of tissue vs. integrated plasma radioactivity concentration, a two-fold increase in ganciclovir steady-state levels were observed in the retina as well as lens epithelium following RMP-7 pretreatment. Peak uptake effects were achieved with a 4.5 min ganciclovir infusion. Neither longer infusions of ganciclovir alone, nor co-infusions of RMP-7 and ganciclovir further enhanced the uptake effects. Kinetic analysis indicated that RMP-7 increased the rate of ganciclovir entry (K IN) in studied ocular tissues, while the efflux of drug (K OUT) was not affected by this treatment. Finally, ganciclovir retina:plasma ratios elevated by RMP-7 pre-treatment, remained higher than control ratios within 60 min following cessation of 4.5 min ganciclovir infusion. Conclusions. These data offer further evidence that BOB and in particular the blood-retinal barrier can be permeabilized via bradykinin receptor stimulation. As the i.v. infusions of RMP-7 enhanced the retinal uptake of ganciclovir, it is suggested that a combination of RMP-7 and ganciclovir may provide a novel approach for treating cytomegalo-virus retinis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1012011618785
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  • 3
    Digitale Medien
    Digitale Medien
    Intravenous Cereport (RMP-7) Enhances Delivery of Hydrophilic Chemotherapeutics and Increases Survival in Rats with Metastatic Tumors in the Brain (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1212-1219 
    Details
    ISSN: 1573-904X
    Schlagwort(e): blood-brain tumor barrier ; bradykinin ; brain metastases ; carboplatin ; carmustine ; paclitaxel ; vinorelbine ; gemcitabine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. The following experiments determined whether intravenous infusions of Cereport enhance delivery of chemotherapeutics and prolong survival in rats with metastatic tumors in the brain. Methods. Autoradiography and scintillation were used to examine uptake of the lipophilic (paclitaxel and carmustine) and the hydrophilic (carboplatin) chemotherapeutic agents, as well as the large hydrophilic marker, 70 kDa dextran. Cereport was also tested in combination with the chemotherapeutic drugs carboplatin, vinorelbine, gemcitabine and carmustine to determine if Cereport could enhance the survival benefit beyond that provided by chemotherapy alone. Results. Cereport enhanced the uptake of carboplatin and dextran, but not paclitaxel or carmustine. The pattern of Cereport's uptake effect with carboplatin revealed that Cereport selectively increased the proportion of highly permeable regions. Survival was significantly enhanced when Cereport was combined with either carboplatin, vinorelbine, or gemcitabine, but not carmustine, compared to each chemotherapeutic agent alone. Conclusions. These data provide the first evidence that Cereport, or any receptor-mediated approach intended to enhance the permeability of the blood-brain tumor barrier, can increase the delivery hydrophilic drugs to metastatic tumors in the brain, increasing survival in tumor-bearing rats.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1023/A:1026462629438
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