Effects of smoking upon reproduction.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Takenaga.
Explore the source record for details and available documents.
To show the possibility of sustained-release insulin formulation composed of PLGA, the optimum one was administered to BioBreeding rat, a model of spontaneous type I diabetes mellitus (IDDM). Every 2 weeks subcutaneous administration made their blood glucose level depend on the insulin release and food intake. However, all of them kept alive with little change or rather a little gain in body weight. Furthermore, some of pregnant rats with intermittent treatment bore fetuses, although additional insulin therapy seemed necessary. Therefore, the formulation could become a new tool as a provider of basal insulin for IDDM patients.
In order to enhance the lipophilicity and develop the efficacy of ascorbic acid (ASA), we synthesized lecithinized ascorbic acid (PC-AS), in which a lecithin was covalently bound to ASA. Its pharmacological activity was also evaluated. The IC50 value of scavenge superoxide anions generated from hypoxanthine in combination with xanthine oxidase, indicated that the antioxidative activity of PC-AS (IC50; 22.19 microM) was about 60% of that shown by ASA (IC50; 13.35 microM). Also, PC-AS suppressed in vitro cell growth of Meth A-T, a highly metastatic cell line established by us. Although its potency (IC50; 110.0 microM) was a little lower than that of ASA, dramatic suppression was observed under serum-free culture conditions (IC50; 13.0 microM). In addition, N-acetylcysteine (NAC), an antioxidant, showed an additive inhibitory effect on cell growth in combination with PC-AS and ASA. Biodistribution studies revealed that PC-AS persisted longer in the blood (AUC0-240 min; 182.8 nmole min ml-1) than ASA (AUC0-240 min; 79.35 nmole min ml-1). It should be noted that intravenous preadministration of PC-AS significantly and dose-dependently reduced the number of colony formation in an experimental murine pulmonary metastasis model. ASA had little effect. [3H]-labeled Meth A-T cells predominantly accumulated in the lung, metastatic target organ, which was reduced by PC-AS. Our in vivo study showed that PC-AS could not totally prevent pulmonary invasion of Meth A-T cells, however, PC-AS effectively inhibited the number of metastatic colony formation. PC-AS's potency was superior to that of unmodified ASA. These findings might be in part ascribed to changes to lecithinization-induced biodistribution, antioxidative activity and cytotoxicity.