Recent advances in telomerase-based medicine for targeting cancers

[Curriculum Vitae & Summary] International Symposium on Tumor Biology in Kanazawa 2004 / Kanazawa, Japan February 12 and 13, 200

Isoflurane induces c-Fos expression in the area postrema of the rat

IntroductionVolatile anesthetics are speculated to cause postoperative nausea and vomiting via stimulation of the chemoreceptor trigger zone (CTZ). However, the precise mechanism underlying the emetic action of these drugs is not well understood. In this study, we assessed whether isoflurane induced the expression of c-Fos, a neuronal activation marker, in the area postrema (AP), the locus of the CTZ, in rats, which do not have vomiting action.Materials and methodsMale rats were exposed to 1.3% isoflurane for 0-240min, or to various concentrations of isoflurane (0, 1.3%, or 2.6%) for 120min. Finally, the rats were exposed to 1.3% isoflurane for 120min after ondansetron administration. After the treatments, immunohistochemistry of the rat AP was performed using c-Fos antibody staining.ResultsOne-way analysis of variance showed that isoflurane exposure significantly increased c-Fos expression in the AP; however, the rats pretreated with 4mg/kg ondansetron showed significantly decreased c-Fos expression. Moreover, we evaluated the effect of the anesthetic on inducing pica in the rats, and found that kaolin intake was not influenced by isoflurane exposure.ConclusionOverall, these results suggest that isoflurane activates AP neurons and may be involved in the emetic mechanism of isoflurane. This study further suggests the feasibility of using rats as a model for studying emetic mechanisms of drugs, despite their lack of vomit action

Influence of nitrous oxide on granule cell migration in the dentate gyrus of the neonatal rat

For several decades, the neurotoxicities of anesthetics to the developing brain have been reported by many researchers focusing on various phenomena such as apoptosis, neurodegeneration, electrophysiological aberrations, and behavioral abnormalities. According to these reports, signals via N-methyl-D-aspartate receptors (NMDA-r) and/or γ-aminobutyric acid type A receptors (GABA(A)-r) are implicated in the anesthetic neurotoxicity. On the other hand, during brain development, NMDA-r and GABA(A)-r are also recognized to play primary roles in neural cell migration. Therefore, anesthetics exposed in this period may influence the neural cell migration of neonates, and increase the number of hilar ectopic granule cells, which are reported to be a cause of continuous neurological deficits. To examine this hypothesis, we investigated immunohistochemically granule cell distribution in the hippocampal dentate gyrus of Wistar/ST rats after nitrous oxide (N2O) exposure. At postnatal day (P) 6, 5-bromo-2'-deoxyuridine (BrdU) was administered to label newly generated cells. Then, rats were divided into groups (n = 6 each group), exposed to 50% N2O at P7, and evaluated at P21. As a result, we found that ectopic ratios (ratio of hilar/total granule cells generated at P6) were decreased in rats at P21 compared with those at P7, and increased in N2O exposed rats for over 120 min compared with the other groups. These results suggest that 50% N2O exposure for over 120 min increases the ratios of ectopic granule cells in the rat dentate gyrus