Antifungal and immunomodulatory activity of a novel cochleate for amphotericin B delivery against Sporothrix schenckii.

INTRODUCTION: Sporotrichosis is an emergent subcutaneous mycoses caused by species of the Sporothrix schenckii complex. Amphotericin B (AmB) remains the main antifungal drug for the treatment of systemic infections, but its use is limited by toxicity reasons. AFCo3 is a novel cochleate containing detoxified LPS, which exhibits drug delivery and immunomodulating properties. Here, AFCo3 was used as the vehicle for AmB to evaluate the immunomodulatory and antifungal efficacy against S. schenckii in vitro and in vivo. METHODS AND RESULTS: The minimum inhibitory concentrations of AFCo3-AmB and AmB were 0.25 and 1µg/mL respectively. The minimum fungicidal concentration was 0.5µg/mL for AFCo3-AmB and 2µg/mL for AmB. AFCo3-AmB was less cytotoxic than AmB for peritoneal macrophages, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and reduced the AmB-induced hemolysis in murine erythrocytes. AFCo3-AmB improved the intracellular killing of phagocytized yeast and it enhanced the in vitro production of IL-1ß, TNF-α and NO in peritoneal macrophages. Moreover, AFCo3-AmB was more effective than AmB in reducing spleen and liver fungal burden after repeated (five days) intraperitoneal administration of 5mg/kg of AmB, in a Balb/c model of systemic infection, associated to a significant induction of Th1/Th17 response. Finally, blood chemistry revealed that AFCo3-AmB did not cause changes suggestive of nephrotoxicity, such as increases in total proteins, albumin, creatinine and blood urea nitrogen that were caused by free AmB. CONCLUSIONS: AFCo3-AmB exhibited a significant immunomodulator action, reduced toxicity and improved antifungal action against S. schenckii, suggesting a potential use as AmB delivery for systemic sporotrichosis treatment.

Titanium surface topography after brushing with fluoride and fluoride-free toothpaste simulating 10 years of use.

OBJECTIVES: To conduct a controlled study contrasting titanium surface topography after procedures that simulated 10 years of brushing using toothpastes with or without fluoride. METHODS: Commercially pure titanium (cp Ti) and Ti-6Al-4V disks (6 mm Ø×4 mm) were mirror-polished and treated according to 6 groups (n=6) as a function of immersion (I) or brushing (B) using deionised water (W), fluoride-free toothpaste (T) and fluoride toothpaste (FT). Surface topography was evaluated at baseline (pretreatment) and post-treatment, using atomic force microscope in order to obtain three-dimensional images and mean roughness. Specimens submitted to immersion were submerged in the vehicles without brushing. For brushed specimens, procedures were conducted using a linear brushing machine with a soft-bristled toothbrush. Immersion and brushing were performed for 244 h. IFT and BFT samples were analysed under scanning electron microscope with Energy-Dispersive X-ray Spectroscopy (EDS). Pre and post-treatment values were compared using the paired Student T-test (α=.05). Intergroup comparisons were conducted using one-way ANOVA with Tukey post-test (α=.05). RESULTS: cp Ti mean roughness (in nanometers) comparing pre and post-treatment were: IW, 2.29±0.55/2.33±0.17; IT, 2.24±0.46/2.02±0.38; IFT, 2.22±0.53/1.95±0.36; BW, 2.22±0.42/3.76±0.45; BT, 2.27±0.55/16.05±3.25; BFT, 2.27±0.51/22.39±5.07. Mean roughness (in nanometers) measured in Ti-6Al-4V disks (pre/post-treatment) were: IW, 1.79±0.25/2.01±0.25; IT, 1.61±0.13/1.74±0.19; IFT, 1.92±0.39/2.29±0.51; BW, 2.00±0.71/2.05±0.43; BT, 2.37±0.86/11.17±2.29; BFT, 1.83±0.50/15.73±1.78. No significant differences were seen after immersions (p>.05). Brushing increased the roughness of cp Ti and of Ti-6Al-4V (p<.01); cp Ti had topographic changes after BW, BT and BFT treatments whilst Ti-6Al-4V was significantly different only after BT and BTF. EDS has not detected fluoride or sodium ions on metal surfaces. CONCLUSIONS: Exposure to toothpastes (immersion) does not affect titanium per se; their use during brushing affects titanium topography and roughness. The associated effects of toothpaste abrasives and fluorides seem to increase roughness on titanium brushed surfaces.

Plástica periodontal em reabilitações implanto-suportadas: estética, função e / Periodontal plastic surgery around implant supported prosthesis: esthetic, function and marginal homeostasis

Com a sedimentação dos conhecimentos sobre a superfície osso-implante, passou-se a pesquisar e valorizar a interface tecido mole-implante, uma vez que a mesma serve como selado biológico, protegendo o tecido ósseo contra a ação de agressores externos. Desta forma se torna um item importante para a longevidade da osseointegração. O favorecimento da estética local deve ser levado em conta, já que em áreas sem mucosa ceratinizada há uma maior ocorrência de recessões gengivais. Este artigo tem o objetivo de demonstrar, por meio de aumento e/ou criação de mucosa ceratinizada, o manuseio de tecido mole via cirurgia plástica periodontal na Implantodontia tanto para otimização da estética quanto para manutenção da homeostasia marginal.