Chronic rhinosinusitis osteoblasts differ in cellular properties from normal bone.

BACKGROUND: Osteitis, characterized by bony thickening and remodeling, is often considered a hallmark of recalcitrant rhinosinusitis. However, there is limited literature examining the bone in chronic rhinosinusitis (CRS) pathology. In this study we cultured osteoblasts from bone harvested during sinus surgery as well as from nondiseased controls to compare their cellular properties. METHODS: Sinus bone was collected during sinus and skull-base surgery and placed in proliferation media. Outgrowth of cells occurred at 2 weeks and the cells were confirmed to be osteoblasts by alkaline phosphatase staining. Cellular adhesion was determined by replating and counting adhered cells at 4 hours. Proliferation of cells plated for 24 hours was assayed by measuring [(3) H]-thymidine incorporation. Calcium content was measured by changing cells to differentiation media and measuring the calcium content on days 7, 14, and 21. RESULTS: Alkaline phosphatase assay showed more than 90% of osteoblasts staining in all samples. Osteoblasts from patients with CRS had significant decreases in adhesion (p < 0.01) compared to osteoblasts from skull-base patients. There was a significant (p < 0.05) increase in calcium content in rhinosinusitis samples compared with the nondiseased sinus bone samples. CONCLUSION: To date, this is the first known study that shows a direct comparison of osteoblast properties between patients with and without CRS. Our results indicate that there are fundamental phenotypic differences in adhesion and mineralization between osteoblasts in patients with CRS compared to controls.

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury.

HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat(1-72)-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND.