sildenafil-citrate and Peripheral-Nerve-Injuries

The sciatic nerve is a peripheral nerve and is more vulnerable to compression with subsequent short- or long-term neuronal dysfunction. The current study was designed to elucidate the possible ameliorative effect of L-carnitine and sildenafil (SIL) on sciatic nerve crush injury. We sought to determine the effects of L-carnitine, a neuroprotective and a neuro-modulatory agent, and SIL citrate, a selective peripheral phosphodiesterases inhibitor, on modulating neuro-degenerative changes due to sciatic nerve compression.. The comparative effect of L-carnitine (at an oral dose of 20 mg/kg/day) or SIL citrate (20 mg/kg/day orally) administration for 21 days was studied in a rat model of sciatic nerve compression. Sciatic nerve sections were subjected to biochemical, histological, ultrastructure, and immunohistochemical studies to observe the effects of these treatments on neurofilament protein.. The sciatic nerve crush injury group (group II) showed a significant decrease in tissue catalase (CAT), superoxide dismutase (SOD) and increase in malondialdehyde (MDA) as compared to control group (p < 0.01). Histological changes in the form of degenerated and vacuolated axoplasm with areas of nerve fibre loss and pyknotic nuclei were reported. The blood vessels were dilated, congested with areas of haemorrhage and mononuclear cell infiltration. Histo-morphometrically, a statistically significant reduction in the nerve fibres' number, mean axon cross-sectional area, myelin sheath thickness and a significant increase in collagen fibres' percentage (p < 0.05) as compared to control group. Immunohistochemically, neurofilament protein was significantly downregulated as proved by a significant reduction in mean area per cent of neurofilament expression. L-carnitine ameliorated the studied parameters through its neuroprotective effect while SIL, a selective peripheral phosphodiesterases (PDE-5) inhibitor, improved crush injury parameters but with less extent than L-carnitine.. These findings indicate the valuable effects of L-carnitine administration compared to that of SIL citrate in alleviating the serious debilitating effects of sciatic nerve crush injury. Our results provide a new insight into the scope of neuroprotective and neuro-regenerative effects of L-carnitine in a sciatic nerve compression model.

Topics: Animals; Carnitine; Citrates; Crush Injuries; Female; Nerve Regeneration; Neurofilament Proteins; Peripheral Nerve Injuries; Phosphoric Diester Hydrolases; Rats; Sciatic Nerve; Sciatic Neuropathy; Sildenafil Citrate

In this study, we investigated whether sildenafil, a cyclic guanosine monophosphate-dependent phospodiesterase-5 inhibitor, could promote functional nerve regeneration after surgical section and repair of the sciatic nerve in rats. Nerve regeneration was studied in a rat sciatic nerve transected and repair model. The animals were randomly assigned to one of the following 3 treatment groups (n = 20/group): sildenafil-treated group 1 (5 mg/kg/d subcutaneously, for 7 days), sildenafil-treated group 2 (5 mg/kg/d subcutaneously, for 42 days), and control group given saline solution (once per day subcutaneously). Walking track analysis, electromyography, and histological evaluation were performed on day 90 after repair operation. The results showed that the sciatic functional index of sildenafil-treated group 1 (data) was slightly better than that of sildenafil-treated group 2 (data) and control group (data) on postoperative day 90. However, the difference was not statistically significant (P = 0.073). No significant differences of the motor nerve conduction velocity were found between experimental groups [18 (2.4) and 20 (4.1 m/s)] and saline control group [19.5 (3.0) m/s] (P = 0.68). Comparison of myelinated axon count of regenerated nerve of the rat between the sildenafil-treated group 1, sildenafil-treated group 2, and saline group was also not significantly different (P = 0.56). In conclusion, administration of sildenafil after nerve repair surgery was found to have positive but insignificant effects on several parameters of nerve regeneration. Further studies could clarify this trend suggesting enhanced nerve regeneration mediated by sildenafil.

Topics: Animals; Axons; Combined Modality Therapy; Drug Administration Schedule; Electromyography; Injections, Subcutaneous; Male; Nerve Regeneration; Neural Conduction; Peripheral Nerve Injuries; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Sciatic Nerve; Sildenafil Citrate; Sulfones; Treatment Outcome

To assess sexual dysfunction in sexually active men after radical cystectomy (RC) and to determine whether sildenafil citrate can improve erectile dysfunction after surgery.. The baseline and follow-up data from 49 sexually active male patients (mean age 57.8 +/- 9.1 years) undergoing RC (1995 to 2002) were obtained. Of the 49 patients, 16 (33%) had undergone nerve-sparing RC; 38 (78%) had undergone orthotopic diversion; 8 (16%) had undergone ileal conduit diversion; and 3 (6%) had undergone cutaneous continent diversion. The data were assessed using the abridged 5-item International Index of Erectile Function questionnaire, referred to as the Sexual Health Inventory for Men (SHIM).. At a mean follow-up of 47.6 +/- 22.7 months, the total mean SHIM score decreased from 22.08 +/- 3.96 to 4.33 +/- 5.72 after RC (P <0.05). Of the 49 patients, 42 (86%) did not have erections sufficient for vaginal penetration. Of these 42 patients, 22 (52%) tried sildenafil citrate. Of these 22 patients, only 2 (9%) responded positively, with a total mean SHIM score of 23.50 +/- 2.12. Although the mean SHIM score after orthotopic substitution (5.24 +/- 6.21) was statistically significant compared with that after ileal conduit (1.13 +/- 0.33) and cutaneous continent (1.33 +/- 0.58) diversions, this was not clinically significant.. Male erectile dysfunction after RC is a prevalent problem. In our series, only 9 (14%) of 49 sexually active men were potent after surgery. Of these 9 potent patients, 8 (89%) had undergone nerve-sparing RC. Of concern, only 52% of the patients with erectile dysfunction sought treatment after RC.

Topics: Aged; Carcinoma; Comorbidity; Coronary Disease; Cystectomy; Diabetes Mellitus; Drug Evaluation; Drug Resistance; Erectile Dysfunction; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Patient Acceptance of Health Care; Patient Satisfaction; Peripheral Nerve Injuries; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Spouses; Sulfones; Surveys and Questionnaires; Urinary Bladder Neoplasms; Urinary Diversion