Abstract. Potential utility of halothane-anesthetized guinea pigs for detecting drug-induced repolarization delay was analyzed in comparison with urethane-anesthesia (n = 4 for both groups). Basal QT interval was significantly greater under halothane-anesthesia than urethaneanesthesia (192 ± 7 vs 132 ± 5 ms, respectively), whereas the reverse was true for the heart rate (190 ± 7 vs 248 ± 11 beats / min, respectively). The typical I Kr -blocker dl-sotalol (0.1 to 3 mg/ kg, i.v.) induced dose-related bradycardia and QT interval prolongation under each anesthesia. The extent of maximum prolongation in the QT interval was greater under halothaneanesthesia than urethane-anesthesia (+101 ± 15 vs +49 ± 3 ms, respectively), whereas that of peak change in the heart rate was smaller under the former than the latter (−49 ± 8 vs −63 ± 5 beats / min, respectively). Pretreatment of the animals under urethane-anesthesia with the selective I Ks blocker chromanol 293B (n = 6) increased the extent of the dl-sotalol-induced QT interval prolongation to +57 ± 8 ms, which was only 0.56 times of that under the halothaneanesthesia, whereas the pretreatment increased the peak change in the heart rate to −76 ± 12 ms. These results indicate that the halothane-anesthesia may effectively sensitize the guinea-pig heart to pharmacological I Kr blockade.
The effect of simultaneous administration of vitamin C (ascorbic acid), L-cystein (Cys) and vitamin E (tocopherol) on the melanogenesis in vivo and in vitro was studied. Forty-eight brownish guinea pigs were divided into 4 groups as follows: VC group, VC+Cys group, VC+Cys+VE group and control group. They were given these vitamins by oral administration every day. UV-B exposure (0.384 J/cm2) on their depleted back skin was done at the day 8, 10, 12, 15 17 and 19. After UV-B irradiation, vitamins were administrated further 3 weeks. The luminosity score was measured using a Color Reader CR-11 (Minolta, Co) and the numbers of DOPA-positive melanocytes of their back skin were counted. B16 melanoma cells were incubated with VC, N-acetyl cystein (NAC) and VE. After 4 days of incubation, cells were harvested. The melanin contents and the tyrosinase activities in cells were measured. The luminosity score in the VC+VE+Cys group was higher than those in the other groups. The numbers of DOPA-positive melanocytes of guinea pigs treated with VC, VE and Cys were significantly decreased compared with those in VC group. In B16 melanoma cells, simultaneous treatment of VC, VE and NAC was the most effective to decrease the melanin contents and to inhibit tyrosinase activity.
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