ABSTRACT
@#Introduction: Disease-modifying anti rheumatic drugs (DMARDs) provide the mainstay for the treatment of rheumatoid arthritis (RA). Adverse effects (AEs) in DMARDs among RA patients are usually related with methotrexate (MTX) use, the common conventional DMARDs. Genetic variant such as single nucleotide polymorphism (SNP) in gene transcribing dihydrofolate reductase (DHFR) (i.e, 829C>T, rs12517451) has been correlated with drug AEs in MTX-treated RA. The prevalence of the DHFR rs12517451 SNP has been reported in other populations, but not in Malaysian. The aim of this study was to determine the prevalence of the DHFR rs12517451 SNP and its association with drug AEs among MTX-treated RA patients from Kelantan, Malaysia. Methods: A total of 78 RA patients receiving MTX (alone or in combination) were included in this study. Based on evidence of clinically perceived drug AEs in MTX-treated RA patients, 33 and 45 samples were assigned as cases and controls, respectively. The genotype of the patients was determined using the polymerase chain reaction-restriction fragment length polymorphism method and validated by sequencing analysis. Results: Minor allele frequency (MAF) for DHFR rs12517451 in cases and controls were 28.8% and 32.2% but there was no significant difference (p=0.727) for the possession of the minor allele T between the two groups. The most reported AEs among cases were haematological effects, gastrointestinal toxicity, and skin problems resulting in 21% withdrawal of MTX. Conclusion: We did not find significant association of the DHFR rs12517451 with drug AEs in MTX-treated RA patients. Our findings warrant replication in a larger patient cohort.
ABSTRACT
This study evaluated in vitro activity of 9 flavonoids in combination with vancomycin or oxacillin against vancomycin-intermediate Staphylococcus aureus [VISA] ATCC 700699 by employing the checkerboard method to obtain Minimal inhibitory concentration [MIC] and fractional inhibitory concentration [FIC] index. Six flavonoids namely hesperitin, rutin, naringenin, flavones, naringin and 3, 7-dihyroxyflavone which exhibited notable inhibitory activity [MIC values 4] were observed. In time kill studies, oxacillin-flavone combination at synergistic concentration demonstrated bactericidal effect at 24 h period with concentration-dependent manner on the VISA strain. Following 1 h exposure, the combination also produced persistent effect on the bacteria growth for 2.9 hrs at 1x sub-MIC and more than 24 h at 5x of sub-MIC and there was a significant difference between both concentrations [p<0.05]. Vancomycin-flavone combination, however, showed no concentration-dependant effect and lower PAE values [1.159 h and 2.322 h at 1x and 5x sub-MIC, respectively] on the VISA strain. In conclusion, flavone markedly intensifies the susceptibility of oxacillin against VISA and the combination can be implicated for further interaction studies at molecular level