sildenafil-citrate and Inflammatory-Bowel-Diseases

Controlled trials have demonstrated the efficacy of sildenafil for "mixed etiology" erectile dysfunction, but this may not be the case if there is underlying pelvic parasympathetic nerve damage. We aimed to determine the efficacy of sildenafil after rectal excision for rectal cancer and inflammatory bowel disease.. Patients with erectile dysfunction after rectal excision were randomly assigned in a double-blind manner to sildenafil or placebo groups. After unblinding, placebo patients crossed over to open sildenafil. Primary end points were improvement in erectile function on a global efficacy question and erectile function questionnaire scores. Secondary end points were frequency and severity of side effects.. Thirty-two patients were randomly assigned, and two dropped out before randomization. Fourteen received sildenafil, and 18 received placebo. Eleven (79 percent) of 14 responded to sildenafil, on global efficacy assessment, compared with 3 (17 percent) of 18 taking placebo (mean difference, 61.9 percent; 95 percent confidence interval, 34.4 to 89.4 percent; P = 0.0009). Sildenafil improved both erectile function domain scores (mean difference, 13.3; 95 percent confidence interval, 7.9 to 18.7; P = 0.0001) and total International Index of Erectile Function scores (mean difference, 30.6; 95 percent confidence interval, 18.7 to 42.6; P < 0.0001) from pretreatment baseline scores. Placebo did not produce improvement in either erectile function (mean difference, 1.7; 95 percent confidence interval, -0.8 to 4.2; P = 0.16) or total International Index of Erectile Function scores (mean difference, 5; 95 percent confidence interval, -1.1 to 11.1; P = 0.1). Ten (100 percent) of 10 crossover patients not responding to placebo did respond to sildenafil (difference, 100 percent; P < 0.0001). Sildenafil improved both erectile function domain scores (mean difference, 16.8; 95 percent confidence interval, 9.7 to 24; P = 0.002) and total International Index of Erectile Function scores (mean difference, 29.5; 95 percent confidence interval, 15.8 to 43.2; P = 0.003) from precrossover baseline scores. Seven (50 percent) of 14 patients on sildenafil compared with 4 (22 percent) of 18 on placebo experienced side effects (difference, 28 percent; 95 percent confidence interval, -4.4 to 60.4 percent; P = 0.14), 91 percent of which were mild and well tolerated.. Sildenafil completely reverses or satisfactorily improves postproctectomy erectile dysfunction in 79 percent of patients. Side effects are usually mild and well tolerated. The damage incurred by the pelvic nerves after proctectomy, less profound than after prostatectomy, is likely to result in a partial parasympathetic nerve lesion.

Topics: Adult; Aged; Aged, 80 and over; Cross-Over Studies; Double-Blind Method; Erectile Dysfunction; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Parasympathetic Nervous System; Patient Satisfaction; Pelvis; Piperazines; Placebos; Postoperative Complications; Purines; Rectal Neoplasms; Rectum; Sildenafil Citrate; Sulfones; Vasodilator Agents

To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant-antioxidant status and apoptosis in rats with colitis.. Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30 mg/ml; 0.8 ml) given intrarectally to Sprague-Dawley rats. Sildenafil (25 mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7 days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25 mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25 mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-10 assays.. The macroscopic lesion score of the colitis group was reduced by SIL (p < 0.01) and this effect was abolished by l-NAME (p < 0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p < 0.01 and p < 0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p < 0.001). Sildenafil also reduced the elevated MPO of the colitis group (p < 0.001) and this effect was reversed by L-NAME (p < 0.01). Increase in lucigenin CL and serum TNF-α levels in the colitis group were also prevented by SIL (p < 0.001 and p < 0.01, respectively).. Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant-antioxidant status, prevention of apoptosis, superoxide production and cytokine release.

Topics: Animals; Apoptosis; Colitis; Female; Glutathione; Inflammatory Bowel Diseases; Interleukin-10; Male; Malondialdehyde; NG-Nitroarginine Methyl Ester; Peroxidase; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sildenafil Citrate; Sulfones; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha

We aimed to assess objectively the integrity of the parasympathetic neural pathway that controls the inflow choke vessels to the corpora cavernosa in a group of male patients with postproctectomy erectile dysfunction.. The study group was male patients with erectile dysfunction after proctectomy for rectal cancer and inflammatory bowel disease identified by sexual function questionnaire. The group underwent two consecutive nights of home nocturnal penile tumescence monitoring with the Nocturnal Electrobioimpedance Volumetric Assessment device. The control group was also monitored. It comprised preoperative potent patients with rectal cancer and inflammatory bowel disease who had not yet undergone a variety of surgical procedures. Demographics and nocturnal penile tumescence parameters were recorded, including number, duration, and percentage increase in penile volume of tumescent events.. Thirty-four impotent study group and 28 potent control group patients underwent nocturnal penile tumescence monitoring. The groups were well matched for mean age (difference, 1.4 years; 95 percent confidence interval, -5.8 to 8.6 years) and proportion with rectal cancer (difference, 6 percent; 95 percent confidence interval, -1 to 13 percent). The number of nocturnal penile tumescent events was greater for the potent group than for the control group (mean rank, 40.4 vs. 24.2; P = 0.0004). There was no significant difference between the mean duration (difference, 2.6 minutes; mean rank, 27.9 vs. 34.4; P = 0.16) or the mean penile volume increase (difference, 5.4 percent increase; mean rank, 30.6 vs. 32.6; P = 0.66) for tumescent events between the study and control groups. Mean age was significantly higher in complete than in partial impotence (60.9 vs. 53.1 years; difference, 7.8 years; 95 percent confidence interval, 0.1 to 15.5 years). There was a nonsignificant trend to a lower mean number of tumescence events among sildenafil responders than among nonresponders (3.5 vs. 4.8 events; mean rank, 11.2 vs. 17.3; P = 0.14).. Nocturnal penile tumescence activity is diminished but not ablated by the trauma of surgical dissection. This suggests that some of the cavernous nerves that govern inflow to the corpora cavernosa are intact after surgery and that the nerve lesion responsible for erectile dysfunction is partial, and it explains why the response to sildenafil in such patients is surprisingly high.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Electric Impedance; Erectile Dysfunction; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Monitoring, Physiologic; Penis; Piperazines; Purines; Rectal Neoplasms; Retrospective Studies; Severity of Illness Index; Sildenafil Citrate; Statistics, Nonparametric; Sulfones; Surveys and Questionnaires; Vasodilator Agents