Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

Effects of Terazosin and Tolterodine on Ureteral Stent Related Symptoms: A Double-Blind Placebo-Controlled Randomized Clinical Trial

Objective To evaluate the effects of terazosin and tolterodine on ureteral stent discomfort. Materials and Methods Of 163 patients assessed for eligibility, 104 patients were randomly assigned to receive placebo, 2 mg of terazosin twice daily, 2 mg of tolterodine daily, or both terazosin plus tolterodine during the stenting period. Prior to stenting and at stent removal, the International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) subscore and the Visual Analog Scale for Pain were determined. The patients also reported their analgesic use during the stenting period. Results Ninety-four patients completed the study. We noted significant decreases in the total IPSS scores (p = 0.002), irritative subscore (p = 0.039), QoL (p = 0.001), flank pain (p = 0.013), voiding pain (p = 0.01) and amount of analgesics used (p = 0.02) in the groups. However, neither the obstructive subscore nor the suprapubic pain improved significantly (p = 0.251 and p = 0.522, respectively). The patients receiving terazosin plus tolterodine experienced significant reductions in the total IPSS, irritative symptoms, QoL, flank pain, voiding pain and decreased analgesics use compared with those patients receiving placebo. However, compared with placebo, terazosin monotherapy did not affect pain levels, and tolterodine monotherapy did not improve QoL, flank pain or analgesics use. Conclusions Terazosin plus tolterodine improves ureteral stent-related complications, including irritative symptoms, the amount of analgesics used, QoL, flank pain and voiding pain but does not decrease obstructive symptoms or suprapubic pain. This trial was registered at www.clinicaltrials.gov as NCT01530243. .

Comparison between pain relief achieved by Diclofenac alone and the combination of Diclofenac and Hyoscine in the short-term treatment of ureteric colic

This study aims to determine whether the combination of diclofenac and hyoscine gives superior pain relief than diclofenac sodium alone. A prospective, non-randomized comparative study. The study was conducted in the Emergency Department of Surgical Unit III at Combined Military Hospital, Rawalpindi from October 31, 2004 to May 01, 2005. A total of 100 patients were included in the study and distributed between two equal groups. Assessment of pain relief was done at 30 and 60 minutes after the administration of drugs. The diagnosis of ureteric colic was confirmed using urine analysis, plain radiography and ultrasonography. It was a prospective non-randomized comparative trial without blinding. A quasi-experimental study. A significantly [p < 0.05] greater number of patients treated with a combination of diclofenac and hyoscine achieved pain relief after 30 minutes as compared to those treated with diclofenac alone. No significant difference was found between the treatment groups after 60 minutes of drug administration. The combination of diclofenac and hyoscine gave a faster pain relief as compared to diclofenac alone in patients of ureteric colic

Histamine H2 receptor mediated relaxation of buffalo (Bubalus bubalus) ureter.

On the buffalo ureter, histamine did not elicit any direct effect. However, it caused concentration-dependent relaxation of the tissues precontracted by carbachol, phenylephrine, norepinephrine, KCI or BaCl2 and also inhibited the contractile effect of carbachol. Metiamide selectively antagonised the relaxation and inhibition of contractile response but mepyramine did not show this effect. Isoprenaline, dobutamine, salbutamol, verapamil and papaverine neither produced any direct effect nor relaxed the carbachol-contracted tissues; norepinephrine and epinephrine had contractile effects. Hence, the histamine-induced relaxation was mediated through the activation of H2 receptors and not through adrenergic mechanisms or blockade of Ca(2+)-channels or inhibition of cyclic nucleotide phosphodiesterase.