Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of chronic suppurative otitis media caused by Pseudomonas aeruginosa remains a challenging problem. The virulence of Pseudomonas is related to its secretion of two matrix metalloproteinases, alkaline protease and elastase. This experiment examines the effects of a synthetic inhibitor of matrix metalloproteinases GM 6001, or N-(2(R)-2(hydroxyamido carbonylmethyl)-4-methylpentanoyl)-L-tryptophane methylamide), in a chinchilla Pseudomonas otitis media model. Thirty chinchillas underwent bilateral subtotal tympanic membrane perforations. Twenty-four chinchillas underwent bilateral middle ear inoculation with P. aeruginosa. Chinchillas were divided into four groups of six animals after the establishment of otitis media. Animals in one group were controls; the other three groups received either gentamicin, GM 6001, or gentamicin plus GM 6001 into the external auditory canal three times daily for 4 weeks. Clearance of Pseudomonas infection occurred in three ears of three animals, all in gentamicin groups, with or without GM 6001. Otorrhea (p = 0.0014) and external canal erythema (p = 0.025) were mild in the two gentamicin groups and moderate in the GM 6001 group when compared with bacterial controls. Animals in the GM 6001 group had the highest survival rate, less severe facial paralysis, and less vestibular toxicity than the gentamicin, gentamicin plus GM 6001, or control groups, although these differences were not statistically significant. This pilot study showed encouraging results for a role of ototopical protease inhibitors in the treatment of Pseudomonas otitis media.
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PMID:Inhibition of proteases in Pseudomonas otitis media in chinchillas. 886 89

The aetiopathogenesis of chronic otitis media with effusion (OME) in children is not yet fully understood. OME is characterized by metaplasia of the epithelium and accumulation of sticky, glue-like effusion in the middle ear containing different mediators of inflammation, including activation fragments of the complement system. Here we examined whether the fluid phase complement activation is reflected in the middle ear mucosa and how the mucosa is protected against the cytolytic activity of complement. Mucosal biopsies from 18 middle ears of children with a history of chronic OME were taken. The biopsies were analysed by immunofluorescence microscopy after staining for complement fragments iC3b/C3c, C3d and C9, and regulators membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and protectin (CD59). There was a strong staining for iC3b/C3c, and a weaker one for C3d and C9 on the surface of the middle ear epithelial cells of OME patients but not in controls without OME. MCP was expressed on the hyperplastic three to four outer cell layers of the epithelium, while CD59 was expressed throughout the middle ear mucosa. The results suggest a strong ongoing complement activation and consequent inflammation in the middle ear cavity. Unrestricted complement damage of the epithelial lining is prevented by the strong expression of MCP and CD59.
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PMID:Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion. 1036 Dec 26