rimexolone and Otitis-Media-with-Effusion

Otitis media with effusion (OME) is a common childhood disease that is characterized by an accumulation of fluid in the middle ear. Chronic OME can also lead to sensorineural hearing loss (SNHL). Nitric oxide (NO), an inflammatory mediator (IM) of OME, is a free radical known to regulate cell proliferation, cell death, and angiogenesis. Previous studies have shown that nitric oxide may cause SNHL through outer hair cell (OHC) cytotoxicity. This experiment was designed to determine whether glucocorticoids, dexamethasone, fluticasone propionate, or rimexolone, can reduce the concentration of NO in middle ear effusion (MEE).. Fifty-three chinchillas were divided into 7 groups, vehicle vs. each glucocorticoid at 0.1% and 1.0% concentrations. Due to anesthesia complications, N ranged from 6 to 9 per group. Two hundred microlitres of each test article was injected into the bullae of each animal. Two hours later, lipopolysaccharide (LPS) (0.3mg in solution) was added. Test articles were re-administered at 24 and 48h post-LPS induction. After 96h, animals were euthanized and the MEE was collected.. All three glucocorticoids numerically reduced NO concentration in the middle ear when administered at 0.1%, but only FP showed a significant reduction. At 1.0% concentrations, all 3 steroids significantly reduced NO concentration.. This study suggests that glucocorticoid treatment reduces NO concentration in the MEE and may protect the ear from the SNHL caused by NO.

Topics: Androstadienes; Animals; Chinchilla; Dexamethasone; Fluticasone; Glucocorticoids; Lipopolysaccharides; Nitric Oxide; Otitis Media with Effusion; Pregnadienes

The lipopolysaccharide (LPS)-induced chinchilla otitis media (OM) model was proven useful in screening anti-inflammatory agents for topical use. Both 1% rimexolone and 1% dexamethasone are effective in reducing the volume of middle ear effusion and mucosal thickness compared with control groups. Topical corticosteroid therapy was efficacious in reducing middle ear mucosal inflammation.. OM is one of the most common diseases in the pediatric population. Our previous studies have shown that treatment with systemic antibiotics and corticosteroids was more efficacious than antibiotics alone. The purpose of this study was to determine the effectiveness of topically applied corticosteroids on the outcome of OM. The long-term goal of this study was to develop a better method of OM treatment by demonstrating effectiveness of topically applied anti-inflammatory agents, such as corticosteroids, avoiding systemic side effects.. Three experimental groups were studied in chinchillas. OM with effusion was induced in all groups by injecting LPS. Group 1 consisted of controls in three subgroups as follows. Control-LPS alone, vehicle of dexamethasone (control-dexa), vehicle of rimexolone (control-rimex). Group 2 was treated with dexamethasone and included subgroups of separate concentrations of dexamethasone: 0.1% and 1% suspensions. Group 3 was treated with rimexolone and included subgroups of separate concentrations of rimexolone: 0.1% and 1% suspensions. A total of 58 animals were used: 18 for controls and 40 for experimental groups. All test substances (saline, control-dexa, control-rimex, dexamethasone and rimexolone, 200 microl) were injected at -2, 48 and 60 h; LPS was injected at 0 h. Animals were monitored by daily otomicroscopy. After 4 days, samples of middle ear effusion (MEE) were collected for analysis and temporal bones were harvested for histopathological studies.. At the end of 4 days, only in five ears (3/20 with 1% dexamethasone, 1/20 with 1% rimexolone, and 1/20 with 0.1% rimexolone) had the fluid diminished to the point of being unobservable. The volume of MEE, thickness of mucoperiosteum, and the degree of inflammation of middle ear mucosa with 1% dexamethasone and 1% rimexolone was significantly less compared with other groups.

Topics: Administration, Topical; Animals; Chinchilla; Dexamethasone; Disease Models, Animal; Female; Glucocorticoids; Male; Microscopy; Mucous Membrane; Otitis Media with Effusion; Periosteum; Pregnadienes; Random Allocation; Temporal Bone