Anti-Helicobacter pylori activity of ethoxzolamide

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 × 10-9, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action

Reanalysis and Limited Repair Parsing: Leaping off the Garden Path

This chapter develops a theory of reanalysis called limited repair parsing. Repair parsers deal with the problem of local ambiguity in part by modifying previously built structure when the chosen structure later proves to be inconsistent. This modification of existing structure distinguishes repair parsing from parallel or multi-path parsing, least-commitment parsing, backtracking, or reparsing strategies. Parsers with a limited capability for repair are psycholinguistically important because they can potentially explain the contrasts between difficult garden path structures (when repair fails) and unproblematic local ambiguities (when repair is successful or easy). Although the idea of repair has been implicit in some psycholinguistic work (and emerged explicitly in the diagnosis model of Fodor & Inoue, 1994, and the NL-Soar model of Lewis, 1993), there has been no clear formulation of the general class of repair parsers. This chapter makes a first step toward such a formulation, show..