RESUMO
BACKGROUND: Radiofrequency ablation (RFA) is a common method for alleviating chronic back pain by targeting and ablating of facet joint sensory nerves. High-intensity focused ultrasound (HIFU) is an emerging, non-invasive, image-guided technology capable of providing thermal tissue ablation. While HIFU shows promise as a potentially superior option for ablating sensory nerves, its efficacy needs validation and comparison with existing methods. METHODS: Nine adult pigs underwent fluoroscopy-guided HIFU ablation of eight lumbar medial branch nerves, with varying acoustic energy levels: 1000 (N=3), 1500 (N=3), or 2000 (N=3) joules (J). An additional three animals underwent standard RFA (two 90 s long lesions at 80°C) of the same eight nerves. Following 2 days of neurobehavioral observation, all 12 animals were sacrificed. The targeted tissue was excised and subjected to macropathology and micropathology, with a primary focus on the medial branch nerves. RESULTS: The percentage of ablated nerves with HIFU was 71%, 86%, and 96% for 1000 J, 1500 J, and 2000 J, respectively. In contrast, RFA achieved a 50% ablation rate. No significant adverse events occurred during the procedure or follow-up period. CONCLUSIONS: These findings suggest that HIFU may be more effective than RFA in inducing thermal necrosis of the nerve.
RESUMO
Understanding signal transduction mechanisms that drive differentiation of adult or embryonic stem cells (ESCs) is imperative if they are to be used to cure disease. While the list of signaling pathways regulating stem cell differentiation is growing, it is far from complete. Indentifying regulatory mechanisms and timecourse commitment to cell lineages is needed for generating pure populations terminally differentiated cell types, and in ESCs, suppression of teratoma formation. To this end, we investigated specific signaling mechanisms involved in cardiomyogenesis, followed by manipulation of these pathways to enhance differentiation of ESCs into cardiomyocytes. Subjecting nascent ESC-derived cardiomyocytes to a proteomics assay, we found that cardiomyogenesis is influenced by up- and down-regulation of a number of kinases, one of which, cGMP-dependent protein kinase (PKG), is markedly down-regulated during differentiation. Delving further, we found that manipulating the PKG pathway using PKG-specific inhibitors produced significantly more cardiomyocytes from ESCs when compared to ESCs left to differentiate without inhibitors. In addition, we found combinatorial effects when culturing ESCs in inhibitors to PKG and PKC isotypes. Consequently, we have generated a novel hypothesis: Down-regulation of PKG and specific PKC pathways are necessary for cardiomyogenesis, and when manipulated, these pathways produce significantly more cardiomyocytes than untreated ESCs.
