The chondroprotective agent ITZ-1 inhibits interleukin-1beta-induced matrix metalloproteinase-13 production and suppresses nitric oxide-induced chondrocyte death.
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In a screening program aimed at discovering anti-osteoarthritis (OA) drugs, we identified an imidazo[5,1-c][1,4]thiazine derivative, ITZ-1, that suppressed both interleukin-1beta (IL-1beta)-induced proteoglycan and collagen release from bovine nasal cartilage in vitro and suppressed intra-articular infusion of IL-1beta-induced cartilage proteoglycan degradation in rat knee joints. ITZ-1 did not inhibit enzyme activities of various matrix metalloproteinases (MMPs), which have pivotal roles in cartilage degradation, while it selectively inhibited IL-1beta-induced production of MMP-13 in human articular chondrocytes (HAC). IL-1beta-induced MMP production has been shown to be mediated by extracellular signal-regulated protein kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) family signal transduction molecules. An ERK-MAPK pathway inhibitor (U0126), but not a p38 kinase inhibitor (SB203580) or a JNK inhibitor (SP600125), also selectively inhibited IL-1beta-induced MMP-13 production in HAC. Furthermore, ITZ-1 selectively inhibited IL-1beta-induced ERK activation without affecting p38 kinase and JNK activation, which may account for its selective inhibition of MMP-13 production. Inhibition of nitric oxide (NO)-induced chondrocyte apoptosis has been another area of interest as a therapeutic strategy for OA, and ITZ-1 also suppressed NO-induced death in HAC. These results suggest that ITZ-1 is a promising lead compound for a disease modifying anti-OA drug program. (+info)
Titanium mini-plate for securing septal cartilage--a case of high-impact nasal trauma.
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Effects of proteoglycan extracted from nasal cartilage of salmon heads on maturation of dendritic cells derived from human peripheral blood monocytes.
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Dendritic cells (DCs) play an essential role in the immune system. The transition from immature DC (iDCs) to mature DCs (mDCs) requires appropriate stimuli such as pro-inflammatory cytokines. Proteoglycans (PGs) are one of the main components of extracellular matrix, and some types of PGs are known to induce maturation of murine DCs. Recent studies have investigated the potential benefits of PG from nasal cartilage of salmon head (S-PG). This study investigated the effects of S-PG on maturation of human monocyte-derived DCs. iDCs were prepared from human monocytes using the appropriate cytokines and then stimulated by S-PG alone. In another experiment, iDCs were stimulated by a combination of pro-inflammatory cytokines (MIX) plus S-PG. Although the stimulation of S-PG alone did not induce phenotypic maturation from iDCs, CD40 expression on DCs stimulated by S-PG alone was lower than that of iDCs. In contrast, the phenotypic and functional characteristics of DCs stimulated by MIX+S-PG were similar to those of DCs stimulated by MIX alone. As a result, S-PG did not demonstrate a significant effect with regard to maturation of human monocyte-derived DCs. (+info)
Type II and VI collagen in nasal and articular cartilage and the effect of IL-1alpha on the distribution of these collagens.
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Good results after endonasal cartilage closure of nasal septal perforations.
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INTRODUCTION: Surgical closure of nasal septal perforations is a challenging procedure. Several approaches and techniques have been described with different levels of success. We report our experience in nasal septal perforation surgery. MATERIAL AND METHODS: We reviewed a sample of 19 patients who underwent surgical closure of nasal septal perforations. The perforations varied in size from 3 mm to 25 mm (mean 13 mm). Outcome was assessed on the basis of a comparison of the preoperative and final follow-up assessment of perforation size and symptoms. The surgical technique is based on an endonasal approach with dissection of bilateral bipedicled mucoperichondrial/-periosteal advancement flaps and interposition of a septal or conchal cartilage graft. RESULTS: Symptomatic resolution was documented for 18 of the 19 patients (95%). Complete closure was accomplished in 16 patients (84%) without major complications. We observed no graft donor site morbidity. CONCLUSION: The technique described uses recognized surgical principles to reconstruct the original nasal architecture and physiology. The results achieved sustain that the method offers both durability and strength. The endonasal approach leaves no scars, reduces risk of tip-rotation and offers sufficient view and space for instrumentation. We conclude that this method is suitable for treatment of perforations up to a vertical height of at least 25 mm. (+info)