In patients with SES restenosis, PEB provided much better clinical, angiographic outcomes than conventional BA.

Background: Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. Aims:To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/ V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers.Methods: This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs])in 24 hours were evaluated as primary pharmacodynamic endpoints.Results: Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related.Conclusions: Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm). | 535TAKEUCHI ET Al.

Celecoxib exerts protective effects on mandibular condylar chondrocytes under CTS stimulation by diminishing degradation and restoring synthesis of ECM.

Background Excessive mechanical stress causes inflammation and destruction of cartilage and is considered one of the cause of osteoarthritis (OA). Expression of semaphorin 3A (Sema3A), which is an axon guidance molecule, has been confirmed in chondrocytes. However, there are few reports about Sema3A in chondrocytes, and the effects of Sema3A on inflammation in the cartilage are poorly understood. The aim of this study was to examine the role of Sema3A in inflammation caused by high magnitude cyclic tensile strain (CTS). Methods Expression of Sema3A and its receptors neuropilin-1 (NRP-1) and plexin-A1 (PLXA1) in ATDC5 cells was examined by Western blot analysis. ATDC5 cells were subjected to CTS of 0.5 Hz, 10% elongation with added Sema3A for 3 h. Gene expression of IL-1β, TNF-ɑ, COX-2, MMP-3, and MMP-13 was examined by qPCR analysis. Furthermore, the phosphorylation of AKT, ERK, and NF-κB was detected by Western blot analysis. Results Added Sema3A inhibited the gene expression of inflammatory cytokines upregulated by CTS in a dose-dependent manner. Addition of Sema3A suppressed the activation of AKT, ERK, and NF-κB in a dose-dependent manner. Conclusions Sema3A reduces the gene expression of inflammatory cytokines by downregulating the activation of AKT, ERK, and NF-κB pathways in ATDC5 cells under CTS.

Synovial fluid of the joint decreases friction between the cartilage surfaces and reduces cartilage wear during articulation. Characteristic changes of synovial fluid have been shown in patients with osteoarthritis (OA) in the temporomandibular joint (TMJ). OA is generally considered to be induced by excessive mechanical stress. However, whether the changes in synovial fluid precede the mechanical overloading or vice versa remains unclear. In the present study, our purpose was to examine if the breakdown of joint lubrication affects the frictional properties of mandibular condylar cartilage and leads to subsequent degenerative changes in TMJ. We measured the frictional coefficient in porcine TMJ by a pendulum device after digestion with hyaluronidase (HAase) or trypsin. Gene expressions of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), type II collagen, and histology were examined after prolonged cyclic loading by an active pendulum system. The results showed that the frictional coefficient increased significantly after HAase (35%) or trypsin (74%) treatment. Gene expression of IL-1β, COX-2, and MMPs-1, -3, and -9 increased significantly in enzyme-treated TMJs after cyclic loading. The increase in the trypsin-treated group was greater than that in the HAase-treated group. Type II collagen expression was reduced in both enzyme-treated groups. Histology revealed surface fibrillation and increased MMP-1 in the trypsin-treated group, as well as increased IL-1β in both enzyme-treated groups after cyclic loading. The findings demonstrated that the compromised lubrication in TMJ is associated with altered frictional properties and surface wear of condylar cartilage, accompanied by release of pro-inflammatory and matrix degradation mediators under mechanical loading.