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Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology–assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.

Aims:  Venoms of snakes, scorpions, bees and purified venom phospholipase A2 (PLA2) enzymes were examined to evaluate the antibacterial activity of purified venom enzymes as compared with that of the crude venoms. Methods and Results:  Thirty‐four crude venoms, nine purified PLA2s and two l‐amino acid oxidases (LAAO) were studied for antibacterial activity by disc‐diffusion assay (100 μg ml−1). Several snake venoms (Daboia russelli russelli, Crotalus adamanteus, Naja sumatrana, Pseudechis guttata, Agkistrodon halys, Acanthophis praelongus and Daboia russelli siamensis) showed activity against two to four different pathogenic bacteria. Daboia russelli russelli and Pseudechis australis venoms exhibited the most potent activity against Staphylococcus aureus, while the rest showed only a moderate activity against one or more bacteria. The order of susceptibility of the bacteria against viperidae venoms was –S. aureus > Proteus mirabilis > Proteus vulgaris > Enterobacter aerogenes > Pseudomonas aeruginosa and Escherichia coli. The minimum inhibitory concentrations (MIC) against S. aureus was studied by dilution method (160–1·25 μg ml−1). A stronger effect was noted with the viperidae venoms (20 μg ml−11) as compared with elapidae venoms (40 μg ml−1). The MIC were comparable with those of the standard drugs (chloramphenicol, streptomycin and penicillin). Conclusion:  The present findings indicate that viperidae (D. russelli russelli) and elapidae (P. australis) venoms have significant antibacterial effects against gram (+) and gram (−) bacteria, which may be the result of the primary antibacterial components of laao, and in particular, the PLA2 enzymes. The results would be useful for further purification and characterization of antibacterial agents from snake venoms. Significance and Impact of the Study:  The activity of LAAO and PLA2 enzymes may be associated with the antibacterial activity of snake venoms.

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