Activation of peroxisome proliferator-activated receptor (PPAR) delta by GW501516, a specific PPARdelta ligand, significantly inhibited interleukin (IL)-1beta-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-beta, and was mediated through the up-regulation of IL-1 receptor antagonist. The inhibitory effect of GW501516 on VSMC proliferation was associated with cell cycle arrest at the G1 to S phase transition, which was accompanied by the induction of p21 and p53 along with decreased cyclin-dependent kinase 4 expression. Inhibition of cell migration by GW501516 was associated with the down-regulation of matrix metalloproteinase (MMP)-2 and MMP-9 in IL-1beta-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1beta-stimulated VSMC proliferation. These results suggest that PPARdelta plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs.
SUMMARY
BackgroundAlthough the aetiology of globus (the sensation of a lump in the throat) remains unclear, gastro-oesophageal reflux disease is associated with globus. A short-term trial with a high-dose proton pump inhibitor has been shown to be a sensitive tool for diagnosing gastro-oesophageal reflux disease.
New imaging technologies have been applied in endoscopy to improve the detection and differentiation of subtle mucosal changes using a digital contrast method. Among them, i-SCAN technology is the most recently developed image-enhancing technology. We investigated whether i-SCAN could improve the detection rate of reflux esophagitis. Interobserver agreement between endoscopists was compared with conventional white light (WL) endoscopic examination. We performed a prospective randomized controlled trial. A consecutive series of 514 subjects that underwent an esophagogastroduodenoscopy for health inspection were enrolled and randomized into the i-SCAN group (n = 246) and WL group (n = 268). An esophagogastroduodenoscopy with video recording was used for detecting reflux esophagitis, and reflux esophagitis were categorized by the modified Los Angeles (LA) classification. The total number of reflux esophagitis identified by WL and i-SCAN was 58 (21.7%) and 74 (30.1%), respectively. The diagnostic yield of reflux esophagitis was significantly higher (P = 0.034) in the i-SCAN group (30.1%) as compared to the WL group (21.6%). Using the modified LA classification, the detection rate of minimal changes was significantly higher (P = 0.017) in the i-SCAN group (11.8%) as compared to the WL group (5.6%), but the detection rates of LA-A and LA-B were not significantly different between the two groups (P = 0.897 and P = 0.311, respectively). After comparison of the interobserver agreement using randomly selected video clips, the i-SCAN group showed better agreement than the WL group (Kappa value, 0.793 vs. 0.473). Compared to WL endoscopy, applying i-SCAN in daily practice can improve the diagnostic yield of reflux esophagitis by detecting more minimal changes in the squamo-columnar junction of the esophagus and can improve the interobserver agreement of the modified Los Angeles classification.
A seven-month-old, entire, male miniature schnauzer dog was referred with acute vomiting, inappetence and depression primarily as a result of a gastric foreign body (pine cones). During investigations, thoracic radiographs revealed increased volume of the right lung lobes, deviated cardiomediastinal structures and elevation of the heart from the sternum. Thoracic computed tomography revealed left cranial lung lobe hypoplasia and extension of the right cranial lung parenchyma across the midline to the left hemithorax. Branches of the right pulmonary vessels and bronchi also crossed the midline and extended to the left caudal lung lobe. These findings suggested that the right and left lungs were fused. In humans this finding is consistent with horseshoe lung, which is an uncommon congenital malformation. To the authors' knowledge, this case represents the first report of such a pulmonary anomaly in a dog.
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