Shigeo Kachi

Effects of PF1022A on adult Angiostrongylus cantonensis in the pulmonary arteries and larvae migrating into the central nervous system of rats

We examined the effects of PF1022A, newly developing in Japan, on adultAngiostrongylus cantonensis in the pulmonary arteries of rats. Following five and ten successive oral doses at 10 mg/kg per day, the firststage larvae in rat faeces disappeared completely at 2 weeks after treatment. The treatment completely killed the female worms, but not the male worms. However, numbers of male worms were also decreased after the administration of either five successive oral doses at 10 mg/kg per day for four courses or five successive intraperitoneal doses at 0.5 mg/kg per day. Next, we examined the effects of PF1022A on larvalA. cantonensis migrating into the central nervous system (CNS) of rats. Following five successive oral doses at 5 or 10 mg/kg per day and five successive intraperitoneal doses at 0.5 mg/kg per day, lesser killing effects were observed on male as well as female worms. On the basis of these results it is apparent that PF1022A will become a promising anthelmintic available as treatment for tissuedwelling as well as intestinal nematodes.

Influence of PF1022A on the motility of Angiostrongylus cantonensis in vitro

Abstract Our previous in vivo studies on angiostrongyliasis showed that PF1022A had stronger killing effects against female adults than against males. No killing effects were observed against young adult worms in the central nervous system. To characterize the former in vivo action of PF1022A, in vitro effects of PF1022A on the motility of Angiostrongylus cantonensis were studied directly. Few differences in the efficacy were observed between male and female worms, but dose- and time-dependent inhibition was observed in adults treated with PF1022A at 10−7–10−11 g/ml. PF1022A was slightly less effective against young-adult worms than against adult worms. Minor effects of PF1022A were observed on the third-stage larvae. These results suggest that selectivity against adult females in vivo could be attributable to non-neuropharmacological mechanisms and that PF1022A does not pass through the blood-brain barrier in host animals.

High rate of awarding compensation for claims of injuries related to clinical trials by pharmaceutical companies in Japan: a questionnaire survey.

Introduction International norms and ethical standards have suggested that compensation for research-related injury should be provided to injured research volunteers. However, statistical data of incidence of compensation claims and the rate of awarding them have been rarely reported. Method Questionnaire surveys were sent to pharmaceutical companies and medical institutions, focusing on industry-initiated clinical trials aiming at new drug applications (NDAs) on patient volunteers in Japan. Results With the answers from pharmaceutical companies, the incidence of compensation was 0.8%, including 0.06% of monetary compensation. Of the cases of compensation claims, 99% were awarded. In turn, with the answers from medical institutions, the incidence of compensation was 0.6%, including 0.4% of serious but not death cases, and 0.04% of death cases. Furthermore, most claims for compensation were initiated by medical institutions, rather than by the patients. On the other hand, with the answers from clinical trial volunteers, 3% of respondents received compensations. These compensated cases were 25% of the injuries which cannot be ruled out from the scope of compensation. Conclusion Our study results demonstrated that Japanese pharmaceutical companies have provided a high rate of compensation for clinical trial-related injuries despite the possibility of overestimation. In the era of global clinical development, our study indicates the importance of further surveys to find each countrys compensation policy by determining how it is being implemented based on a survey of the actual status of compensation coming from statistical data.

Effects of gabergic anthelmintics at higher concentrations on the guanidine-induced twitch responses in isolated frog recturs preparations

Effects of various gabergic anthelmintics on the guanidine-induced twitch responses in isolated frog rectus preparations were examined. All gabergic anthelmintics such as milbemycin oxime, milbemycin D, avermectin B1a, invermectin, and diethylcarbamazine (DEC) showed stimulatory effects on the guanidine-induced twitch responses at their higher concentrations. Only piperazine caused inhibitory effects on the twitch responses, even at higher concentrations. The stimulation of the twitch responses by the gabergic anthelmintics was antagonized with tetrodotoxin, hemicholinium-3, dtubocurarine, and strychnine. These results suggest that all gabergic anthelmintics except piperazine stimulate the release of acetylcholine from the nerve endings and that all of them, including piperazine, have different effects on the gabergic mechanism at lower concentrations and on the cholinergic mechanism at higher concentrations.

Compatibility of Bricef Dry Syrup with Mixed Solutions

Compatibilty of Bricef Dry Syrup (cefatrizine oral suspension) with mixed solutions which were often pre scribed in our hospital was investigated in terms of changes in external appearance pH and residual potency of cefatrizine (CFT). These changes were checked immediately after and 1, 3, 5, 7 and 14 days after mixing. The results showed lowering, to some extent, of CFT potency in relatively high pH region. Especially, when dry syrup was mxed with an alkaline solution, CFT potency reduced significantly within 24 hours at room temperature. These results suggest that careful attention should be paid to the above combination since a risk of incompatibility may be involved.Color of suspensions of a few preparations changed during the storage. The change in color should be avoided to prevent anxiety in patients, though its correlation with stability of CFT is not clear. In combiantions with other solutions, the change in appearance, pH and potency of CFT was small, suggesting that such combinations be clinically recommendable.