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Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo.

ABSTRACT: BACKGROUND AND PURPOSE: Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney. EXPERIMENTAL APPROACH: Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry. KEY RESULTS: Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 x 10(-11) M) than in distal specimens (EC50=7.4 x 10(-10) M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney. CONCLUSIONS AND IMPLICATIONS: Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.

SUBMITTER: Chaignat V

PROVIDER: S-EPMC2483393 | biostudies-other | 2008 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundWhether selective non-steroidal anti-inflammatory drugs (NSAIDs) has equally efficacy with non-selective NSAIDs in preventing heterotopic ossification (HO) after total hip arthroplasty (THA) was controversial. The purpose of this meta-analysis was to assess the efficacy and safety of selective NSAID versus non-selective NSAIDs for the prevention of HO after THA.MethodsPubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Google Search Engine, and China National Knowledge Infrastructure databases was searched for randomized controlled trials (RCTs) were comparing selective NSAID versus non-selective NSAIDs for preventing HO after THA. The primary outcomes were overall HO incidence, Brooker classification HO incidence, gastrointestinal side effects, the occurrence of excessive bleeding and discontinuation caused by gastrointestinal side effects (DGSE). Data were analyzed using Stata 12.0.ResultsA total of 8 RCTs involving 1636 patients were included in the meta-analysis. There was no significant difference between the nonselective NSAIDs group and the selective NSAIDs group in the overall incidence of HO (relative risk, RR = 0.91, 95% confidence intervals, CI 0.78-1.06, P = .203), Brooker I HO (RR = 1.02, 95% CI 0.85-1.23, P = .794), Brooker II HO (RR = 1.00, 95% CI 0.66-1.52, P = .996). Brooker III HO (RR = 0.98, 95% CI 0.37-2.62, P = .971). And the occurrence of excessive bleeding (RR = 0.67, 95% CI 0.24-1.92, P = .458). The selective NSAIDs group was associated with a significant decrease in gastrointestinal side effects (RR = 0.35, 95% CI 0.18-0.71, P = .004) and discontinuation caused by gastrointestinal side effects compared with the nonselective NSAIDs group (RR = 0.28, 95% CI 0.11-0.66, P = .004).ConclusionThe available evidence indicates selective NSAIDs were as effective as non-selective NSAIDs in preventing HO after THA. And selective NSAIDs were associated with less gastrointestinal side effects than non-selective NSAIDs. Considering the limitation of current meta-analysis, more RCTs need to identify the optimal NSAIDs drug for HO after THA.

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Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo.

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