Electrochemical features of the interaction between (R)-/(S)-methyl-2- (5-fluorouracil-1-acetamide)-3-phenylpropionate and DNAs

Cyclic voltammetry was exploited to understand the interaction between chiral methyl-2-(5- fluorouracil-1-acetamide)-3-phenylpropionate molecules (denoted as (R)- or (S)-5FUPPM) and double-stranded (ds) or G-quadruplex (G4) DNAs. Using Fe(CN)63- as the redox mark, experiments illustrate that the anodic peak of Fe(CN)63- oxidation decreases as the concentration of 5FUPPM in the solution is increased. Calculation with the Langmuir equation yields the binding equilibrium constant of 9.1 × 103 for the dsDNA and (S)-5FUPPM and of 3.3 × 103 for dsDNA and (R)-5FUPPM, suggesting that (S)-5FUPPM has more favorable interaction with dsDNA. On the other hand, the calculated binding constant between G4-DNA and (S)-5FUPPM is 1.6 × 104, as opposed to 3.2 × 104 between G4-DNA and (R)-5FUPPM. The results suggest that the binding selectivity of (R)-5FUPPM with DNAs, defined with (KG4-DNA/KdsDNA), is about 5 times larger than that of (S)-5FUPPM and DNAs, which is consistent with their inhibition rate on tumor cell. The information achieved here suggests that electrochemical characterization can provide useful information for the screening of new drug candidates.

The serum matrix metalloproteinase-9 level is an independent predictor of recurrence after ablation of persistent atrial fibrillation

OBJECTIVES: This study investigated whether the serum matrix metalloproteinase-9 level is an independent predictor of recurrence after catheter ablation for persistent atrial fibrillation. METHODS: Fifty-eight consecutive patients with persistent atrial fibrillation were enrolled and underwent catheter ablation. The serum matrix metalloproteinase-9 level was detected before ablation and its relationship with recurrent arrhythmia was analyzed at the end of the follow-up. RESULTS: After a mean follow-up of 12.1±7.2 months, 21 (36.2%) patients had a recurrence of their arrhythmia after catheter ablation. At baseline, the matrix metalloproteinase-9 level was higher in the patients with recurrence than in the non-recurrent group (305.77±88.90 vs 234.41±93.36 ng/ml, respectively, p=0.006). A multivariate analysis showed that the matrix metalloproteinase-9 level was an independent predictor of arrhythmia recurrence, as was a history of atrial fibrillation and the diameter of the left atrium. CONCLUSION: The serum matrix metalloproteinase-9 level is an independent predictor of recurrent arrhythmia after catheter ablation in patients with persistent atrial fibrillation.