Corticosteroid-Antibiotic Interactions in Bacteria that Cause Corneal Infection.

Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted. Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells. Results: The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations. Conclusions: Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration. Translational Relevance: When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.

10-Phenyltriazoyl Artemisinin is a Novel P-glycoprotein Inhibitor that Suppresses the Overexpression and Function of P-glycoprotein.

BACKGROUND: The effect of drugs on ATP-binding cassette transporters, especially permeabilityglycoprotein (P-gp), is an important consideration during new anti-cancer drug development. OBJECTIVE: In this context, the effects of a newly synthesized artemisinin derivative, 10-(4-phenyl-1H-1,2,3- triazol)-artemisinin (5a), were evaluated on P-gp expression and function. METHODS: Reverse transcript polymerase chain reaction and immunoblotting techniques were used to determine the effect of 5a on P-gp expression in LS174T cells. In addition, the ability of 5a to work as either a substrate or an inhibitor of P-gp was investigated through different methods. RESULTS: The results revealed that 5a acts as a novel P-gp inhibitor that dually suppresses the overexpression and function of P-glycoprotein. Co-treatment of LS174T cell line, human colon adenocarcinoma cell line, with 5a and paclitaxel recovered the anticancer effect of paclitaxel by controlling the acquired drug resistance pathway. The overexpression of P-gp induced by rifampin and paclitaxel in a colorectal cell line was suppressed by 5a which could be a novel inhibitory substrate inhibiting the transport of paclitaxel by P-gp. CONCLUSION: The results revealed that 5a can be classified as a type B P-gp inhibitor (with both substrate and inhibitor activities) with an additional function of suppressing P-gp overexpression. The results might be clinically useful in the development of anticancer drugs against cancers with multidrug resistance.

A new wide-angle arthroscopic system: a comparative study with a conventional 30° arthroscopic system.

PURPOSE: To compare users' hand movements in performing validated shoulder arthroscopic tasks between a 30° and a wide-angle arthroscopic system, using phantom models with an optical motion analysis system. METHODS: Twelve orthopaedic residents were enrolled and randomly allocated into two groups. In order to compensate for any learning effect, a Latin square counterbalancing technique was used. An optical motion analysis system was used with markers affixed to pre-designed sites; each participant conducted four validated shoulder arthroscopic tasks using both arthroscopic systems. Each participant was instructed to perform the experiment three times with each arthroscope. The time taken, total path length, number of movements, and average acceleration were analysed. RESULTS: Significant differences were observed for the time taken, number of movements, and average acceleration between the two arthroscopic systems (P < 0.05 for all). However, the time taken was not significant. The mean total path length measured 53 ± 38 cm with the 30° arthroscope, while the mean with the wide-angle arthroscope was significantly shorter, at 36 ± 22 cm. The mean number of movements with the 30° and wide-angle arthroscopes were 1974 ± 1305 and 1233 ± 990, respectively, while the average accelerations were 2.6 ± 1.3 and 1.2 ± 0.6 cm/s(2), respectively. The mean time taken was 13 % faster when using the wide-angle arthroscopic system, although this was not statistically significant. CONCLUSION: The wide-angle arthroscopic system improved the arthroscope manoeuvre in terms of the total path length, number of movements, and average acceleration required for experimental arthroscopy. This system may help surgeons triangulate the arthroscope and surgical instruments during surgery by expanding the field of view.