Hajime Terao

Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice

BACKGROUND: Low-dose and long-term administration of macrolide antibiotics into patients with chronic airway inflammatory diseases could favorably modify their clinical conditions. However, the therapeutic mode of action of macrolides is not well understood. Free oxygen radicals, including nitric oxide (NO), are well recognized as the important final effector molecules in the development and the maintenance of inflammatory diseases. PURPOSE: The influence of macrolide antibiotics on NO generation was examined in vivo. METHODS: Male ICR mice, 5 weeks of age, were orally administered with either roxithromycin, clarithromycin, azithromycin or josamycin once a day for 2-4 weeks. The mice were then injected intraperitoneally with 5.0 mg/kg lipopolysaccharide (LPS) and the plasma NO level was examined 6 h later. RESULTS: Although pre-treatment of mice with macrolide antibiotics for 2 weeks scarcely affected NO generation by LPS injection, the administration of macrolide antibiotics, except for josamycin, for 4 weeks significantly inhibited LPS-induced NO generation. The data in the present study also showed that pre-treatment of mice with macrolide antibiotics for 4 weeks significantly suppresses not only production of pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, but also inducible nitric oxide synthase mRNA expressions, which are enhanced by LPS injection. CONCLUSION: These results strongly suggest that suppressive activity of macrolide antibiotics on NO generation in response to LPS stimulation in vivo may, in part, account for the clinical efficacy of macrolides on chronic inflammatory diseases.

Palatoplasty and Growth of the Temporal Bone Mastoid Air Cells

Objectives The present study was undertaken to analyze the relationship between the method used for manipulation of the levator veli palatini muscle and the area of the mastoid air cells in patients with cleft palate. Design Retrospective study. Patients The subjects were 50 patients seen for surgical treatment of cleft palate. Interventions Palatoplasty was carried out using the mucosal flap method in 25 patients and the mucoperiosteal flap method in 25 patients. In the mucosal flap method, the levator veli palatini muscle was overlapped and sutured, followed by posterior movement of the muscle bundle (the posterior relocation group). In the mucoperiosteal flap method (the control group), the mucoperiosteal flap was pushed back, followed by end-to-end suturing of the muscle. The area of the mastoid air cells was measured on X-rays when patients were 5 years old. Results The mastoid air cell area did not differ significantly between the posterior relocation group (mean, 5.00 cm2; range, 1.66 to 19.7 cm2) and the control group (mean, 5.3 cm2; range, 2.29 to 15.9 cm2). Conclusion No significant growth of mastoid air cells was noted following posterior relocation of the levator veli palatini muscle. Thus, in cases of cleft palate in which significant growth of mastoid air cells is not expected following reconstruction of the levator veli palatini muscle, the results confirm the view that tympanic ventilation tube insertion is the most suitable method for the treatment of otitis media.