departmental bulletin paper

Background: Angiotensin II (AngII) increases reactive oxygen species (ROS) and induces glomerular sclerosis. Toll-like receptor 4 (TLR4)-mediated inflammation enhances the renal impairment in renal inflammatory diseases. The relationship between TLR4 and AngII-induced glomerular sclerosis is unknown.Methods: Mice lacking TLR4 function (Tlr4^{lps-d}) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a sub-depressor dose of the AngII receptor blocker irbesartan along with AngII for 2 weeks. We then assessed the expressions of NADPH oxidase and monocyte chemoattractant protein-1 (MCP-1) and the inflammatory cell recruitment in the glomeruli. We also evaluated the mesangial matrix proliferation and ROS.Results: AngII and NE equally increased the systolic blood pressure compared to the control mice (p<0.05). In the WT mice treated with AngII, we observed glomerular sclerosis, an increase in NADPH oxidase, MCP-1 and the infiltration of macrophages as well as ROS content in the glomeruli compared to the control mice (p<0.05), whereas the Tlr4^{lps-d} mice showed little effects of AngII on these indices. In addition, the sub-depressor-dose irbesartan treatment reversed these changes. NE had little effects on these indices. Conclusions: TLR4 plays an important role in AngII-induced oxidative stress, inflammation and glomerular sclerosis through the AT1 receptor.

Aims: To clarify the usefulness of preservative-free ophthalmic preparations equipped with a filter. Methods: A total of 1,615 samples of in-use ophthalmic preparations were examined for microbial contamination. Results: Of 1,094 samples of preservative-containing ophthalmic preparations, 31 (2.8%) showed microbial contamination. Of 289 samples of preservative-free ophthalmic preparations without a filter, 6 (2.1%) were contaminated, consisting of 4 (13.8%) of 29 samples of hospital preparations and 2 (0.8%) of 260 samples of commercially available new quinolone antimicrobial agents. On the other hand, the microbial contamination rate in preservative-free ophthalmic preparations equipped with a filter was 0% (0 of 232 samples).The major contaminants detected in these preservative-containing ophthalmic preparations and preservative-free ophthalmic preparations without a filter were glucose-nonfermentative Gram-negative bacilli such as Pseudomonas fluorescens, Acinetobacter spp., and P. aeruginosa, coagulase (-) staphylococci, and Candida spp. The contaminant level was 10-99 colony forming units (CFU)/mL in 37.8% (14 of 37 samples), and 10^2 - 10^6 CFU/mL in 62.2% (23 of 37 samples). Conclusions: Preservative-free ophthalmic preparations equipped with a filter not only have zero risk of the oculotoxic effects of preservatives, but are also safe in terms of their lack of microbial contamination.