RESUMO
OBJECTIVES: To assess contact lens preservative uptake and release from multipurpose solutions (MPS) and subsequent acquisition of lens antibacterial activity. METHODS: Kinetics of uptake and release of poly (hexamethylene biguanide hydrochloride) (PHMB) or polyquaternium-1 (PQ-1) from various contact lenses were studied initially with the pure compounds and then after soaking in MPS containing these compounds. Lenses soaked in MPS were tested for antibacterial activity. RESULTS: Only lenses with a negatively charged component absorbed these preservatives. For lenses containing methacrylic acid (MA), uptake of PHMB from preservative-only solution was fast, yet little was released, in contrast to its rapid release from lenses containing other anionic groups. This trend persisted with PHMB-containing MPS. PQ-1 from preservative-only solution was only absorbed by lenses containing MA and was released from MA-containing hydrogels, but not significantly from an MA-containing silicone hydrogel. Lens uptake of PQ-1 was much lower from MPS and release was essentially undetectable from all lenses evaluated. Antibacterial lens activity was acquired by lenses containing MA after an overnight soak in MPS containing PQ-1, and for balafilcon A and omafilcon A after 5 exchanges in PHMB-containing MPS. Acquired activity was maintained during cycling between artificial tear protein solution and MPS. CONCLUSIONS: Lens preservative uptake and its subsequent release are dependent on lens chemistry, preservative nature, and other MPS components. A few lens/solution combinations acquired antibacterial activity after one or more overnight soaks in MPS, depending on the nature of the anionic lens component and the preservative. Uncharged lenses did not acquire antibacterial activity.
Assuntos
Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Soluções para Lentes de Contato/química , Lentes de Contato Hidrofílicas , Conservantes Farmacêuticos/química , Anti-Infecciosos/farmacologia , Biguanidas/química , Biguanidas/farmacologia , Soluções para Lentes de Contato/farmacologia , Humanos , Conservantes Farmacêuticos/farmacologiaRESUMO
Invasion of epithelial cells represents a potential pathogenic mechanism for Pseudomonas aeruginosa. We explored the role of mitogen-activated protein kinase kinases (MEK 1/2) and the extracellular signal-regulated kinases (ERK 1/2) in P. aeruginosa invasion. Treatment of corneal epithelial cells with MEK inhibitors, PD98059 (20 microM) or UO126 (100 microM), reduced P. aeruginosa invasion by approximately 60% without affecting bacterial association with the cells (P=0.0001). UO124, a negative control for UO126, had no effect on bacterial internalization. Infection of cells with an internalization-defective flhA mutant of P. aeruginosa was associated with less ERK 1/2 tyrosine phosphorylation than infection with wild-type invasive P. aeruginosa. An ERK-2 inhibitor, 5-iodotubercidin (20 microM), reduced P. aeruginosa invasion by approximately 40% (P=0.035). Together, these data suggest that P. aeruginosa internalization by epithelial cells involves a pathway(s) that includes MEK and ERK signaling proteins.