Hiroyuki Mibu

16β-methyl-17α,21-diesterified glucocorticoids as partial agonists of glucocorticoid in rat endotoxin-induced inflammation

Objective and Design: We investigated the anti-inflammatory effects of 16β-methyl-17α,21-diesterified glucocorticoids which are well known as potent topical glucocorticoids in man on endotoxin-induced uveitis (EIU) in rats.¶Material: Female Lewis rats were used.¶Treatment: Glucocorticoids were instilled (0.01% - 1.0%) or subcutaneously injected (0.1 - 10 mg/kg) to rats.¶Methods: To elicit EIU, LPS (500 μg/kg) was injected into the footpad of rats. Twelve hours after LPS injection, cell number in aqueous humor was counted by flow cytometry. Endotoxin-induced in vivo tumor necrosis factor-α (TNF-α) production was also examined.¶Results: 16β-methyl-17α,21-diesterified glucocorticoids showed no effects or some enhancement of cell infiltration into the aqueous humor in EIU by topical instillation. Systemic injection of these glucocorticoids showed only weak inhibition of cell infiltration and TNF-α production. On the other hand, betamethasone phosphate strongly inhibited the cell infiltration and TNF-α production. Combined systemic injection of 16β-methyl-17α,21-diesterified glucocorticoids and betamethasone phosphate reduced the inhibitory effects of the latter.¶Conclusions: These results suggest that 16β-methyl-17α,21-diesterified glucocorticoids might act as partial agonists of glucocorticoid in rats.

One-Year Ocular Toxicity Study of Ofloxacin Ophthalmic Solution in Beagle Dogs

Ocular toxicity and systemic adverse effects of 0.3% ofloxacin ophthalmic solution (0.3%OFLX) which was administered 3 times daily for one year were studied in dogs.