piperidines and Urethral-Stricture

Strictures of the urethra are the most common cause of obstructed micturition in younger men and there is frequent recurrence after initial treatment. This review was performed to determine the best strategy for stricture recurrence prevention following urethral endoscopic management.. We reviewed the published literature in PubMed, the Cochrane Library, and Google Scholar focusing on this intractable problem regardless of language restrictions. Outcomes of interest included the study methods and the applied strategy's efficacy. The level of evidence and grade of recommendations of included studies were appraised with an Oxford Centre for Evidence-Based Medicine Scale.. Currently, numerous techniques, including catheterization, repeated dilation, brachytherapy, and intraurethral use of various antifibrosis agents, have been employed to oppose the process of wound contraction or regulate the extracellular matrix. But unfortunately, none of these techniques or agents have demonstrated efficacy with enough evidence.. Although lots of strategies are available, still, we do not have a suitable, single optimum solution for all the conditions. The clinical decision of stricture-recurrence-prevention techniques should be carefully tailored to every individual patient. As the studies are not sufficient, more efforts are warranted to address this interesting but challenging issue.

Topics: Animals; Anti-Bacterial Agents; Brachytherapy; Catheterization; Dilatation; Endoscopy; Fibrosis; Humans; Piperidines; Quinazolinones; Rats; Secondary Prevention; Steroids; Urethra; Urethral Stricture; Urinary Catheterization

We developed a reproducible animal model for the induction of urethral stricture in the rabbit and evaluated the role of halofuginone in limiting stricture formation.. A total of 20 New Zealand male rabbits were used in the first phase of the experiment. Bulbar urethral stricture was induced by electrocoagulation. The animals were then randomly assigned to 2 groups of 10 each, which received a diet containing halofuginone or a normal diet. In the second phase electrocoagulation induced stricture was treated with visual internal urethrotomy in 45 rabbits. These rabbits were randomly assigned to 2 groups, namely a halofuginone and a control group.. In the first phase stricture developed in 2 study rabbits (20%) vs 10 controls (100%). In the second phase 37 rabbits were evaluable (8 died). Recurrent stricture was observed in 5 of the 18 study rabbits (27%) vs 14 of the 19 controls (73%).. Halofuginone is effective in limiting the occurrence of de novo urethral stricture and recurrent stricture after visual internal urethrotomy. This antifibrotic molecule may become an important therapy to treat urethral stricture and/or recurrence following endoscopic manipulation of stricture in humans.

Topics: Administration, Oral; Animals; Electrocoagulation; Fibrosis; Male; Piperidines; Protein Synthesis Inhibitors; Quinazolines; Quinazolinones; Rabbits; Secondary Prevention; Urethra; Urethral Stricture

Urethral strictures are narrowing of the urethra caused by fibrosis due to excessive collagen production in response to an insult. We evaluated the effects of halofuginone, a potent inhibitor of collagen alpha1(I) gene expression, on experimentally induced urethral strictures in vivo and on rat urethral fibroblasts in vitro.. Applying coagulation current to the male rat urethra produced urethral strictures. Halofuginone was given to the animals for 7 days, starting on the day of stricture formation, either orally at 1 and 5 ppm in the diet or by injection of 0.03% halofuginone solution into the urethra. All rats were sacrificed on day 21. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, collagen content by sirius red staining and urethral morphology by urethrogram.. Coagulation current produced reproducible strictures with a typical urethrogram appearance, which were associated with increases in collagen alpha1(I) gene expression and collagen content at the stricture site. Halofuginone injected into the urethra or orally at 5 ppm normalized the urethrogram and prevented increases in collagen alpha1(I) gene expression and collagen content. Halofuginone at a concentration of 10-8 M. inhibited the collagen secreted by fibroblasts derived from the rat male urethra, which was due to inhibition of the collagen alpha1(I) gene expression.. Halofuginone prevented stricture formation and may become an important mode of therapy in the prevention of restenosis during urethral stricture formation.

Topics: Animals; Collagen; Disease Models, Animal; Immunohistochemistry; In Situ Hybridization; Male; Piperidines; Protein Synthesis Inhibitors; Quinazolines; Quinazolinones; Rats; Rats, Sprague-Dawley; Urethral Stricture