In the therapy of ocular diseases, different active pharmaceutical ingredients are often instilled concomitantly as different ophthalmic solutions at an appropriate interval (unfixed-combination therapy) or simultaneously as one formulation (fixed-combination therapy). In this study, we aimed to compare the in vitro cytotoxicity of fixed- and unfixed-combination ophthalmic solutions using the glaucoma therapeutic agents, timolol and brimonidine. Cultured human corneal epithelial cell line was used as a test system. Exposure period was set at 5 min. Compared with the fixed-combination treatment, the unfixed-combination treatment (timolol followed by brimonidine, and vice versa) led to a significant reduction in the percentage of cell viability. In conclusion, it was suggested that a fixed-combination ophthalmic solution was expected to cause less cellular damage to the ocular surface, compared to an unfixed-combination ophthalmic solution.
S-(1, 2-Dichlorovinyl)-L-cysteine (DCVC) is derived from trichloroethylene (TCE) and known to cause renal cell injury after metabolic activation by cysteine conjugate β-lyase. We examined the in vivo disposition of [35S] DCVC in mice after intraperitoneal administration at a dose of 30 mg/kg (2.42 MBq/6 mg/mL). DCVC and its related-substances were absorbed rapidly and distributed highly in the kidneys. Whole-body autoradiography analyses revealed high accumulation of DCVC and its related-substances in hyaline cartilage of growth plates of the femoral epiphysis, vertebral endplates of the spinal column, costal cartilage, and tracheal cartilage, in addition to the kidneys. These findings suggest that TCE and DCVC are likely to be a cause of damaged cartilage.
Ovariectomized rats were used as an animal model of osteoporosis in this study. They were given ad libitum access to a diet with high or low calcium to phosphorus ratio, or a normal diet, for a period of 10 weeks and effects on osteoporosis were assessed. Our results showed that the experimental diets affect urine levels of calcium and phosphorus, but do not affect the levels of biochemical, histopathological, or bone-related biomarkers. These results indicate that the administration of feed with different ratios of calcium to phosphorus (the phosphorus content was kept constant and the calcium content varied from 0.2× to 5× relative to the phosphorus content) over a period of 10 weeks does not accelerate the development of osteoporosis in ovariectomized rats with normal renal function to maintain homeostasis.