ABSTRACT
The increasing prevalence of antibiotic resistance causes an urgent need for alternative agents to combat drug-resistant bacterial pathogens. Plant-derived compounds are promising candidates for the treatment of infections caused by antibiotic-resistant bacteria. Hinokitiol (ß-thujaplicin), a natural tropolone derivative found in the heartwood of cupressaceous plants, has been widely used in oral and skin care products as an antimicrobial agent. The aim of this work was to study the synergy potential of hinokitiol with antibiotics against Staphylococcus aureus, which is an extremely successful opportunistic pathogen capable of causing nosocomial and community-acquired infections worldwide. The MIC was determined by the broth microdilution method, and the effect of combinations was evaluated through fractional inhibitory concentration indices (FICI). The mechanism behind this synergy was also investigated by using fluorescence spectroscopy and high-performance liquid chromatography (HPLC). The MICs of hinokitiol alone against most S. aureus strains were 32 µg/mL. Selectively synergistic activities (FICIs of ≤0.5) were observed for combinations of this phytochemical with tetracyclines against all tested strains of S. aureus. Importantly, hinokitiol at 1 µg/mL completely or partially reversed tetracycline resistance in staphylococcal isolates. The increased accumulation of tetracycline inside S. aureus in the presence of hinokitiol was observed. In addition, hinokitiol promoted the uptake of ethidium bromide (EB) in bacterial cells without membrane depolarization, suggesting that it may be an efflux pump inhibitor. IMPORTANCE The disease caused by S. aureus is a public health issue due to the continuing emergence of drug-resistant strains, particularly methicillin-resistant S. aureus (MRSA). Tetracyclines, one of the old classes of antimicrobials, have been used for the treatment of infections caused by S. aureus. However, the increased resistance to tetracyclines together with their toxicity have limited their use in the clinic. Here, we demonstrated that the combination of hinokitiol and tetracyclines displayed synergistic antibacterial activity against S. aureus, including tetracycline-resistant strains and MRSA, offering a potential alternative approach for the treatment of infections caused by this bacterium.
ABSTRACT
Success of the modified maze procedure after valvular operation with giant atria and permanent atrial fibrillation (AF) remains suboptimal. We report an aggressive approach for these patients utilizing biatrial reduction plasty with a reef imbricate suture technique concomitantly with valvular and maze procedure for AF. From January 1999 to December 2006, 122 consecutive Chinese patients with permanent AF and biatrial enlargement who required mitral valve+/-tricuspid valve (TV) surgery underwent aggressive left atrial reduction combined with radiofrequency bipolar full maze procedure. Left atrial dimensions were measured by TTE or TEE. There were 71 women (58.1%) and 51 men (41.9%) and their mean age was 45+/-9.5 years. Mean duration of AF was 48.4+/-21.4 months. All patients underwent left atrial reduction plasty with reef imbricate suture technique and full maze procedure. Their preoperative left atria measured 64+/-12 mm in the enlarged left atria (ELA) group and 86+/-17 mm in the giant left atria (GLA). Mitral valve replacement (MVR) combined with TV repair was performed in 102 patients (83%) while 21 patients underwent MVRs combined with aortic valve replacements (17%). Sixty-six (54%) patients required additional procedures and 61 (50%) of the patients also underwent left atrial appendage clot evacuation. Postoperative left atrial size was reduced to 49+/-8 mm (ELA) and 51+/-11 mm (GLA), respectively (P<0.05). Ninety-three of 122 (76%) patients were restored in normal sinus rhythm after one year clinical follow-up. Aggressive biatrial reduction plasty combined with full maze procedure is an effective treatment for patients with permanent AF undergoing concomitant valvular surgery. Further studies utilizing the reef imbricate suture technique for atrial reduction need to subsequently be evaluated.
