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  • 1
    ISSN: 1573-6903
    Keywords: Serotonin synthesis ; tracers ; amino acids ; brain uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The uptake and trapping constants for labeled tryptophan (Trp) via the serotonin (5-hydroxytryptamine; 5-HT) metabolic pathway and for the incorporation of Trp into proteins, and α-[14C]methyl-L-tryptophan (α-MTrp) were measured. Measurements were done in rats treated with either saline or probenecid (200 mg/kg). In addition, the blood-brain barrier (BBB) permeability surface area products for Trp (PST) and α-MTrp (PSα) were measured in normal rats. The results suggest that, in both groups of rats, there is a highly significant correlation (p 〈 0.05; Pearson Product Moment Correlation (PPMC) between the brain uptake and trapping constants for α-MTrp and those of Trp via the 5-HT metabolic pathway, but there is no significant correlation (p 〉 0.05; PPMC) between either of these constants and the PS products of either compound. There is also no significant correlation (p 〉 0.05; PPMC) between the constant for the Trp incorporation into proteins with any of the other parameters. For all parameters, except Trp incorporation into proteins (α-MTrp is not incorporated into proteins), there was a highly significant correlation (p 〈 0.001) between the quantities measured for Trp and α-MTrp. The data presented here strongly suggests that the brain uptake and trapping of α-MTrp relates to brain 5-HT synthesis, and does not relate to the BBB transport or protein incorporation of Trp. On the basis of these results, as well as those previously reported, we concluded that trapping (unidirectional uptake) of α-MTrp can be converted to the 5-HT synthesis rates in the brain. From this also follows that labeled α-MTrp is a good tracer for in vivo evaluation of the brain 5-HT synthesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7373
    Keywords: cisplatin ; intracarotid chemotherapy ; multi-tracer autoradiography ; blood brain barrier ; cerebral blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was designed to find the reliable parameter(s) for the detection of early neurotoxicity following intracarotid (IC) administration of cisplatin. IC administration was performed for 60 minutes in female Wistar rats derived into four groups according to the dose given (1 mg, 1.2 mg, and 1.5 mg of cisplatin, and normal saline in control rats). Blood-brain barrier (BBB) permeability and local cerebral blood flow (LCBF) were measured by a double-tracer autoradiography technique using 1-[14 C]-α-aminoisobutyric acid (14 C-AIB) and 4-[18 F] fluoroantipyrine (18 F-FAP), respectively. Blood chemistry and neuropathology were also examined. BBB permeability was incereased only on the ipsilateral side. This increase was dose-dependent, preceded the brain necrosis, and was statistically significant in the hypothalamus [1.2 mg group), auditory cortex and caudoputamen (1.5 mg group). Renal dysfunction was often observed. The changes in the LCBF did not occur until brain necrosis was noticeable. These findings demonstrate that the increase in the BBB permeability provides a sensitive and reliable indication of an early toxicity to brain tissue following IC administration of cisplatin.
    Type of Medium: Electronic Resource
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