3-((4-(6-methylpyridin-2-yl)-5-(quinolin-6-yl)-1h-imidazol-2-yl)methyl)benzamide and Hyperplasia

To investigate the efficacy of an IN-1233-eluting covered stent in preventing tissue hyperplasia in a rabbit esophageal model.. The local animal research committee approved all experiments. Esophageal stents were placed in 40 male New Zealand rabbits (weight range, 2.8-3.2 kg). The drug group (D) received IN-1233-eluting covered stents (n = 20); the control group (C) received polyurethane-covered stents (n = 20). Drug loading of IN-1233-eluting covered stent was 10%. Four study groups were formed: C and D animals sacrificed at 4 (D4, C4) and 8 (D8, C8) weeks after stent placement (n = 10). Esophagography was used to assess the percentage of diameter stenosis. Histologic findings of the drug and control stents were compared. The Mann-Whitney U test was used to evaluate differences.. The mean percentage ± standard deviation of diameter stenosis was significantly lower in D groups than in C groups at both 4 (C4 = 36.15% ± 12.63, D4 = 7.83% ± 8.12 [P < .001]) and 8 (C8 = 50.21% ± 20.43, D8 = 27.78% ± 14.40 [P = .019]) weeks. Percentage of granulation tissue area (C4 = 33.07% ± 19.11, D4 = 21.59% ± 18.22 [P = .028]; C8 = 44.70% ± 21.71, D8 = 31.97% ± 22.54 [P = .131]), number of epithelial layers (C4 = 4.77 ± 1.55, D4 = 3.37 ± 1.73 [P = .002]; C8 = 5.50 ± 1.38, D8 = 4.50 ± 1.63 [P = .057]), and thickness of submucosal fibrosis (C4 = 2.42 mm ± 1.08, D4 = 1.62 mm ± 0.77 [P = .006]; C8 = 2.89 mm ± 1.00, D8 = 2.07 mm ± 0.71 [P = .007]) were lower in D than in C groups. Inflammatory cell infiltration was significantly higher in D than in C groups (C4 = 2.63 ± 0.81, D4 = 3.33 ± 1.09 [P = .032]; C8 = 2.20 ± 0.81, D8 = 3.00 ± 0.95 [P = .012]).. The use of an IN-1233-eluting covered stents decreased tissue hyperplasia secondary to stent placement in a rabbit esophageal model.

Topics: Animals; Benzamides; Drug-Eluting Stents; Esophagus; Hyperplasia; Male; Metals; Polyurethanes; Quinolines; Rabbits; Radiography; Statistics, Nonparametric

To evaluate the efficacy of an activin receptor-like kinase (ALK) 5 inhibitor, IN-1233, for the prevention of neointimal hyperplasia after bare stent placement in a rat common iliac artery (CIA) model.. All experiments were approved by the committee of animal research. A self-expanding metallic bare stent (2 mm × 6 mm) was inserted into the left CIA of 26 Sprague-Dawley male rats (300-360 g) under fluoroscopic guidance. IN-1233 was injected via the intraperitoneal route daily in 13 rats for 8 weeks after stent placement (group A); the other 13 rats underwent stent placement only (group B). Angiography was performed immediately and 4 weeks and 8 weeks after stent placement. Rats were sacrificed at 8 weeks after stent placement, and histologic findings were obtained. The neointimal area (NA), percentage of neointimal hyperplasia (%NH), and neointimal-to-medial area ratio (N/M) were assessed and compared between the two groups.. Stent placement was technically successful. In 25 rats, arteries with stent placement were angiographically patent, whereas 1 rat in group B had an occlusion. The NA (0.31 mm(2) ± 0.09 vs 0.56 mm(2) ± 0.17; P < .001), the %NH (26.16% ± 8.75 vs 44.71% ± 17.75; P < .001) and the N/M (1.93 ± 0.77 vs 4.77 ± 2.26; P < .001) were significantly decreased in group A compared with group B.. IN-1233 was shown in this study to be effective for the prevention of neointimal hyperplasia after bare metallic stent placement in a rat CIA model.

Topics: Animals; Benzamides; Endovascular Procedures; Hyperplasia; Iliac Artery; Injections, Intraperitoneal; Male; Metals; Prosthesis Design; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Quinolines; Radiography; Rats; Rats, Sprague-Dawley; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Stents; Time Factors; Tunica Intima

To evaluate the efficacy of an activin receptor-like kinase-5 inhibitor, IN-1233, for the prevention of tissue hyperplasia after bare stent placement in a rat urethral model.. Procedures were performed in accordance with the National Institutes of Health guidelines for humane handling of animals; approval of the committee of animal research was obtained. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra by using fluoroscopic guidance. One group of 10 rats (group A) was treated with IN-1233, the other group of 10 rats (group B) received no treatment. Retrograde urethrography was performed 4 and 8 weeks after stent placement. All rats were sacrificed at 8 weeks for histologic analysis.. Stent placement was technically successful in all rats. The average stent diameter was significantly larger in group A compared with group B at follow-up retrograde urethrography performed 4 (P = .006) and 8 (P < .001) weeks after stent placement. At histologic analysis, the percentage of granulation tissue area (P < .001), thickness of submucosal fibrosis (P < .001), and number of epithelial layers (P < .001) were significantly decreased in group A compared with group B. Inflammatory cell infiltration (P < .001) was significantly increased in group A compared with group B.. IN-1233 is effective for the prevention of granulation tissue formation after bare metallic stent placement in a rat urethral model.

Topics: Animals; Benzamides; Granulation Tissue; Hyperplasia; Male; Metals; Quinolines; Radiography; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Stents; Urethra