Amelioration of lead toxicity on rat liver with Vitamin C and silymarin supplements.

The aim of the present study was to investigate the impact of the combined administration of Vitamin C and silymarin on lead toxicity. Male albino rats were subdivided into three groups: the first was a control group, the second received lead acetate in diet as 500 mg/kg diet daily, the third received the same lead acetate dose and supplemented with Vitamin C (1 mg/100g body weight) and silymarin (1 mg/100g body weight) by gastric tube three times per week. Blood samples were taken after 2, 4 and 6 weeks of treatment. Significant lead-induced elevations in serum ALT, AST, GGT and ALP activities were observed after different periods of treatment. However, serum LDLc was decreased. The intensities of RNA and apoptotic fragments of DNA were measured as optical density by Gel-pro program. Lead acetate decreased the intensity of DNA at 6 weeks and induced apoptotic DNA fragments reversibly with time. After 2 weeks of lead administration dilation and congestion of terminal hepatic veins and portal vein branches were observed. Lead also induced hepatocyte proliferation without any localized distribution among zones 1-3. Portal inflammatory infiltrate with disruption of the limiting plates (interface hepatitis), steatosis, apoptosis and mild fibrosis were detected especially by sixth week of lead administration. Combined treatment of lead-exposed animals with Vitamin C and silymarin showed marked improvement of the biochemical, molecular and histopathological findings. These experimental results strongly indicate the protective effect of Vitamin C and silymarin against toxic effects of lead on liver tissue.

Sacral nerve stimulation for refractory urge symptoms in elderly patients.

OBJECTIVE: The presence of an overactive detrusor (OD) is becoming more prevalent in the elderly and may severely influence the social life and activities of daily living in the senior, otherwise healthy, person. There is a marked age-dependent increase in OD above the age of 65 years, which is mainly attributed to dysfunction, with loss of voluntary control, of the micturition reflex and decreased perception of bladder fullness. MATERIAL AND METHODS: Herein, we evaluate the outcome of sacral nerve stimulation in five patients aged >65 years derived from a large, multinational, randomized, prospective study. RESULTS: The effect on symptoms was excellent in two subjects. There was a moderate improvement in another subject and a variable but eventually small effect in the remaining two patients. The results appeared to be more favourable in younger patients. CONCLUSION: Our findings suggest that the outcome of sacral nerve stimulation is more unpredictable in the elderly, a fact that should be considered when counselling the patient. However, it should be remembered that, even for the older, active person, urge incontinence may have a severe impact on quality of life and that the majority of patients treated with an implant will benefit from this treatment.

Long-term effectiveness of sacral nerve stimulation for refractory urge incontinence.

OBJECTIVES: To evaluate the long-term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. STUDY DESIGN AND METHODS: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3- to 7-day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. RESULTS: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8+/-14.8 (range 12-60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. CONCLUSION: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long-term benefit through an average of 30.8 months.

Efficacy of sacral nerve stimulation for urinary retention: results 18 months after implantation.

PURPOSE: We investigate the efficacy of sacral neurostimulation in patients with idiopathic urinary retention in a prospective, randomized multicenter trial. MATERIALS AND METHODS: A total of 177 patients with urinary retention refractory to standard therapy were enrolled in the study. Greater than 50% improvement in baseline voiding symptoms during a 3 to 7-day percutaneous test stimulation qualified a patient for surgical implantation of an InterStim parallel system. Of the patients who qualified for implantation 37 were randomly assigned to a treatment and 31 to a control group. Patients in the treatment group underwent early surgical implantation of the sacral nerve stimulation system, while implantation was delayed in the control group for 6 months. Followup evaluations, including voiding diary analysis and temporary deactivation of the stimulator at 6 months, were conducted at 1, 3, 6, 12 and 18 months after implantation in the treatment group, and after 3 and 6 months in the control group. RESULTS: Compared to the control group, patients implanted with the InterStim system had statistically and clinically significant reductions in the catheter volume per catheterization (p <0.0001). Of the patients treated with implants 69% eliminated catheterization at 6 months and an additional 14% had a 50% or greater reduction in catheter volume per catheterization. Therefore, successful results were achieved in 83% of the implant group with retention compared to 9% of the control group at 6 months. Temporary inactivation of sacral nerve stimulation therapy resulted in a significant increase in residual volumes (p <0.0001) but effectiveness of sacral nerve stimulation was sustained through 18 months after implant. CONCLUSIONS: Results of this prospective, randomized clinical study demonstrate that sacral nerve stimulation is effective for restoring voiding in patients with retention who are refractory to other forms of treatment.

Long-term results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention.

Many patients have chronic, debilitating symptoms of voiding dysfunction that are refractory to conventional medical or surgical therapies. This multicenter, prospective study evaluated the long-term effectiveness of sacral nerve stimulation using the implantable Medtronic InterStim therapy for urinary control in patients with otherwise intractable complaints of urinary urge incontinence, urgency-frequency, or retention. Each patient first underwent temporary, percutaneous sacral nerve test stimulation. If at least a 50% reduction in target symptoms was documented for at least 3 days, patients received a permanent Medtronic InterStim sacral nerve stimulation system that includes a surgically implanted lead and neurostimulator. Regular follow-up was conducted with outcome data. We report here on patients who have been observed from 1.5 to 3 years postimplantation. The results demonstrate that after 3 years, 59% of 41 urinary urge incontinent patients showed greater than 50% reduction in leaking episodes per day with 46% of patients being completely dry. After 2 years, 56% of the urgency-frequency patients showed greater than 50% reduction in voids per day. After 1. 5 years, 70% of 42 retention patients showed greater than 50% reduction in catheter volume per catheterization. We conclude that the Medtronic InterStim therapy for urinary control system is an effective therapy with sustained clinical benefit for patients with intractable symptoms of urinary urge incontinence, urgency-frequency, or retention.

Neuromodulation reduces urinary frequency in rats with hydrochloric acid-induced cystitis.

OBJECTIVE: To evaluate the effect of sacral neuromodulation on interstitial cystitis (IC) and determine the underlying mechanism of neuromodulation in the treatment of IC. Materials and methods Twenty Sprague-Dawley rats (body weight 220-250 g) were randomly divided into four equal groups; normal controls, a sham treatment (IC induced by 0.4 mol/L HCl, + saline), a second sham treatment (HCl-induced IC + acetic acid) and a stimulated group (HCl-induced IC + acetic acid, with electrical stimulation). In the last group bilateral electrodes were implanted into the S1 dorsal foramina and electrical stimulation applied for 8 h/day for 3 weeks. Acetic acid was instilled into the bladder to induce c-fos expression. After 3 weeks the rats were perfused with 4% paraformaldehyde, spinal segments dissected out and an immunocytochemical method used to stain the segments for fos protein encoded byc-fos. RESULTS: The mean (SEM) micturition frequency (voids/17 h) in the sham groups increased from 10.8 (2.7) to 23.4 (3.4) 3 weeks after the intravesical instillation of HCl. The micturition frequency in the stimulated group, at 16.2 (2.7), was significantly less than in the sham group (P = 0.04) after electrical stimulation for 3 weeks. There was no significant difference in the mean (SEM) number of fos-positive neurones in the L6 spinal cord segment between the stimulated and the sham + acetic acid group, at 43.6 (9.4) and 35.8 (7.8) cells/section, respectively (P = 0.32). CONCLUSIONS: In rats with HCl-induced cystitis, electrical stimulation reduced the micturition frequency, but not by inhibiting afferent c-fibre activity.

Poly(vinyl chloride) ion-selective electrodes for piribedil determination.

Piribedil (PD) ion-selective electrodes have been constructed from poly(vinyl chloride) matrix membrane containing piribedil-tetraphenylborate (PD-TPB) as the electroactive component with dibutylphthalate or dioctylphthalate as the plasticizing solvent mediator. The electrodes displayed a linear response over the concentration range 2.0 x 10(-5) to 10(-2) M PD. The working pH ranges of the electrodes were 3.5-6.4 and 3.0-6.0, and the isothermal coefficients of the cells were 0.00129 and 0.00096 V/degrees C respectively. The electrodes were used for the determination of the diprotonated PD species, the most successful being that based on dioctylphthalate solvent mediator. The electrodes show a linear response over the concentration range of 8.0 x 10(-6) to 10(-2) M PD, with Nernstain slope 30 mV/PD concentration decade when preconditioned by soaking in distilled water for 30 min. The electrodes exhibit good selectivity for the PD with respect to a large number of inorganic cations and organic substances of biological fluids. Piribedil is determined successfully in pure solutions and in tablets or in biological fluids using the standard additions and potentiometric titration methods. The membrane withstood soaking in distilled water for more than 5 months.

Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.

PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.

Neuromodulation reduces c-fos gene expression in spinalized rats: a double-blind randomized study.

PURPOSE: Neuromodulation of the sacral nerve roots is effective to treat various voiding dysfunctions, but the underlying mechanism of neuromodulation is not known. The objective of this study is to evaluate whether inhibition of afferent c-fiber activity is the underlying mechanism of sacral nerve root neuromodulation. MATERIALS AND METHODS: Twenty-nine female Sprague-Dawley rats weighing 220 to 250 gm. were divided into 4 groups: normal control (normal rats without any procedure; n = 5), sham with saline (spinalized rats at T9 with saline bladder instillation; n = 7), sham with acetic acid (spinalized rats at T9 with acetic acid bladder instillation; n = 8) and stimulation group (spinalized rats at T9 with acetic acid bladder instillation plus electrical stimulation; n = 9). A cystometrogram was performed 10 days after spinal cord transection to confirm the development of bladder hyperreflexia. Bilateral electrode wires were implanted into S1 dorsal foramina and electrical stimulation was performed 8 hours a day for three weeks. The rats were perfused with 4% paraformaldehyde and an immunocytochemical method was used to stain fos-protein that was encoded by c-fos gene. A double-blind method was used in counting fos-protein positive neurons. RESULTS: Bladder hyperreflexia developed in all spinalized rats 10 days after spinal cord transection. Peak bladder pressure was found significantly reduced after neuromodulation (30.4 +/- 4.2 cm. water) compared with the same rats before neuromodulation (82.4 +/- 10.2 cm. water; p = 0. 007). The number of fos-protein positive neurons in the L6 spinal cord segment in the neuromodulation group (93.2 +/- 13.3 cells/section) decreased significantly when compared with the sham with acetic acid group (160.6 +/- 25.0 cells/section; p = 0.02). There was no significant difference in c-fos expression between the sham with saline group (90.5 +/- 15.6 cells/section) and the neuromodulation group (p = 0.92). CONCLUSIONS: Sacral dorsal root neuromodulation reduces c-fos gene expression and bladder hyperreflexia in spinalized rats, through inhibition of afferent c-fiber activity.

Role of C-afferent fibres in the mechanism of action of sacral nerve root neuromodulation in chronic spinal cord injury.

OBJECTIVE: To determine whether sacral root neuro-modulation (a promising therapeutic modality in patients with refractory voiding and storage problems) has its effect through the blockade of C-afferent fibres that form the afferent limb of a pathological reflex arc responsible for the dysfunction of bladder storage. MATERIALS AND METHODS: The study comprised 39 female Sprague Dawley rats divided into three equal groups: normal controls (group 1); spinally transected at T10 (group 2); spinally transected and electrically stimulated bilaterally at S1 for 6 h daily (group 3). Three weeks after transection the rats were assessed using urodynamics; substance P, neurokinin A and calcitonin gene-related peptide (CGRP) were extracted from the dorsal root ganglia (DRG) of the L5 and L6 roots and quantified by radioimmunoassay. RESULTS: Spinally transected rats developed urinary bladder hyper-reflexia after 3 weeks. This was associated with a significant increase in the neuropeptide content of the DRG of L6. Electrostimulation of S1 significantly decreased the neuropeptide content of L6. In contrast, transection and S1 neurostimulation did not affect the neuropeptide content of the L5 DRG, except for CGRP, which increased after spinal transection and decreased with neurostimulation. CONCLUSIONS: In spinally transected rats, sacral root neurostimulation abolished bladder hyper-reflexia and attenuated the rise in neuropeptide content of the L6 DRG. These results suggest that the blockade of C-afferent fibre activity is one of the mechanisms of action of sacral root neuromodulation.

Induction of neuronal and inducible nitric oxide synthase in the motoneurons of spinal cord following transient abdominal aorta occlusion in rats.

BACKGROUND: Motoneurons in the spinal cord are especially vulnerable to ischemic injury and selectively destroyed after transient ischemia. Nitric oxide (NO) has been implicated in both neurodegneration and neuroprotection to ischemic insult. To evaluate the role of NO in pathophysiology to spinal cord ischemia, the expression of neuronal and inducible nitric oxide synthase (n-NOS and i-NOS) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the motoneurons of the lumbosacral spinal cord was examined in a rat model with transient abdominal aorta (TAA) occlusion. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into sham-operated (n = 12) and TAA occlusion (n = 24) groups. TAA occlusion was induced by placement of a microvascular clamp around the abdominal aorta for 20 min. Three sham-operated and six TAA occlusion animals were sacrificed at each time interval at 4, 24, and 48 h and 7 days after operation. Tissue sections obtained from the lumbosacral spinal cord were processed for n-NOS, i-NOS, NADPH-d, and hematoxylin-eosin (HE) staining. Histological changes of motoneurons in ventral horn were assessed by HE staining. RESULTS: In sham-operated control animals, n-NOS-, i-NOS-, and NADPH-d-positive neurons were barely detectable in the ventral horn of the spinal cord. At 4 h after TTA occlusion, n-NOS and NADPH-d expression became evident in the motoneurons and was markedly enhanced at 24 and 48 h. i-NOS expression was also induced in the ventral horn motoneurons of the lumbosacral spinal cord at the same time points. Enzymatic expression in the motoneurons was diminished 7 days after operation. Hyperchromatic neurons indicative of cell death were observed in HE-stained specimens 7 days following TAA occlusion. CONCLUSIONS: The rapid induction of n-NOS, i-NOS, and NADPH-d in the motoneurons of ventral horn suggests that NO may be involved in the selective and delayed neuronal death in the spinal cord to the ischemic insult.

Electrical stimulation has no adverse effect on pregnant rats and fetuses.

PURPOSE: Electrical stimulation has been considered a contraindication in pregnant women with various voiding dysfunctions, because of the potential to cause teratogenicity or abortion. However, it is not known whether electrical stimulation can cause fetal malformation or abortion. The purpose of this study is to evaluate whether electrical stimulation has any adverse effect on pregnant rats and fetuses. MATERIALS AND METHODS: Twenty Sprague-Dawley pregnant rats were divided into two groups: electrical stimulation group (n = 10) and sham controls (n = 10). Rats in the stimulation group were stimulated 7 hours every day from Day 4 to Day 20 of gestation. All pregnant rats were sacrificed and fetuses were examined at near term (Day 20 of gestation). The number of fetuses, resorptions, fetal liability, body weight and gross appearance were recorded. Viscera and skeleton stained with Alizarin Red S were examined under stereoscope. RESULTS: All pregnant rats were healthy during the gestation period and no abortions were noted. Fetal body weight in the stimulation group (2.27 +/- 0.51 gm.) was not significantly different from sham group (2.13 +/- 0.51 gm.; p = 0.91). No significant difference was found in the number of resorptions between both groups. All fetuses were alive at the time of cesarean section. No fetal malformation was observed in gross appearance, viscera and skeleton of all rats. CONCLUSIONS: Electrical stimulation did not have any adverse effect on pregnant rats and their fetuses. Termination of pregnancy is not advised for prospective mothers when electrical stimulation has been performed inadvertently in early pregnancy.

Sacral root neuromodulation in the treatment of various voiding and storage problems.

This paper reviews the use of sacral neuromodulation as a treatment modality for patients with bladder dysfunction. The dual functions of the urinary bladder are to act as a reservoir and to evacuate under voluntary control. Bladder dysfunction is a descriptive term describing the loss or the impairment of one or both of these functions. In the first part of the manuscript we describe the different components of sacral neuromodulation: the screening test known as percutaneous nerve evaluation (PNE), which involves screening patients who could potentially benefit from the therapy. Those who show a satisfactory response will have a permanent neuroprosthesis implanted. The technical aspects of both components of neuromodulation are described in detail, as well as the technical difficulties encountered. In the second part we present our long-term results in patients with sacral neuromodulation. Sacral neuromodulation is a safe and efficient therapeutic modality that helps patients with refractory voiding dysfunction restore their bladder function.

Sacral nerve stimulation for treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group.

PURPOSE: A prospective, randomized study was performed to evaluate sacral nerve stimulation for the treatment of refractory urinary urge incontinence. MATERIALS AND METHODS: Primary outcome variables were obtained from voiding diaries. After baseline evaluation candidates who satisfied inclusion criteria were enrolled into the study. Test stimulation results determined eligibility for randomization into a stimulation (treatment) or delay (control) group. The stimulation group included 34 patients who underwent implantation and were followed for 6 months. The delay group comprised 42 patients who received standard medical therapy for 6 months and then were offered implantation. The stimulation group completed a therapy evaluation test (on versus off) after 6 months. RESULTS: At 6 months the number of daily incontinence episodes, severity of episodes and absorbent pads or diapers replaced daily due to incontinence were significantly reduced in the stimulation compared to the delay group (all p<0.0001). Of the 34 stimulation group patients 16 (47%) were completely dry and an additional 10 (29%) demonstrated a greater than 50% reduction in incontinence episodes 6 months after implantation. Efficacy appeared to be sustained for 18 months. During the therapy evaluation test the group returned to baseline levels of incontinence when stimulation was inactivated. Urodynamic testing confirmed that sacral nerve stimulation did not adversely affect voiding function. Complications included implantable pulse generator site pain in 15.9% of the patients, implant site pain in 19.1% and lead migration in 7.0%. Surgical revision was required in 32.5% of patients with implants to resolve a complication. There were no reports of permanent injury or nerve damage. CONCLUSIONS: Sacral nerve stimulation is safe and effective in treating refractory urinary urge incontinence.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

OBJECTIVE: To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. MATERIALS AND METHODS: Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. RESULTS: Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. CONCLUSIONS: This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

Stimulator design and subsequent stimulation parameter optimization for controlling micturition and reducing urethral resistance.

An implantable computerized electrical stimulation system designed to induce bladder evacuation in animal models (dogs) after spinal cord transection has been realized and evaluated. This fully programmable system is based on a handheld device and generates a wide range of stimuli through multichannel implantable miniaturized stimulator. Using the new bladder stimulator and inducing reversible fatigue to the external sphincter via the pudendal nerve enables us to reduce the bladder outlet resistance, resulting in the proper emptying of the bladder during stimulation without the need for sacral nerve rhizotomies and the pudendal nerve neurectomies. Four chronically affected dogs were studied to determine the optimal stimulation parameters for inducing a sphincter fatigue that would reliably empty the bladder for the duration of the experiment. These parameters were: maximum amplitude of 1.5 mA +/- 0.5 SD, stimuli composed of a high frequency signal of 200 Hz +/- 50 SD modulated by a low frequency signal of 10 Hz +/- 5 SD, pulse width controlled by a duty-cycle of 20% +/- 10 SD, sacral nerve stimulation of 50 s +/- 25 SD and fatiguing duration of 20 s +/- 5 SD.

Vasoactive intestinal peptide and impotence in experimental diabetes mellitus.

OBJECTIVE: To determine whether a defect in vasoactive intestinal peptide (VIP)-mediated vasodilatation underlies diabetic impotence. MATERIALS AND METHODS: Rats treated with streptozotocin for 8 weeks developed diabetes, as shown by hyperglycaemia and glycosuria, and had significant impairment of sexual function, as determined by tests of sexual behavior. The VIP content of the penis and major pelvic ganglion, the VIP release by the penis in vitro and the responsiveness of the vasculature of the penis in vivo to intracavernous VIP injection were determined. RESULTS: In diabetic rats, the VIP content of the major pelvic ganglion and penis was markedly increased, while the acetylcholine content of the penis was normal. The amount of VIP released in vitro by high potassium concentration or veratridine was similar for penile tissue slices of normal and diabetic rats. Intracavernous injection of VIP induced erection in the control rats but not in diabetic rats, whereas intracavernous injection of the adenylate-cyclase activator forskolin produced erection in both control and diabetic rats. CONCLUSION: Because VIP induces vasodilatation by activating adenylate cyclase, and forskolin produced erection in the diabetic rats, the failure of VIP to produce erection in these rats is unlikely to be due to a defect in the second-messenger mechanism or in the properties of vascular smooth muscle. Thus, a defect at the level of the VIP receptor or of the associated G-protein possibly explains the failure of intracavernous VIP to produce erection in the diabetic rats. Hence, an abnormality in VIP is a component of sexual dysfunction in the diabetic rat and the defect is at the level of the VIP receptor or associated G-protein.

Long-term results of penile venous ligation for corporeal venous occlusive dysfunction.

OBJECTIVE: To evaluate the long-term results of penile venous ligation in patients with erectile dysfunction due to venous incompetence of the corpora cavernosa. DESIGN: A retrospective case study with follow-up longer than 22 months. SETTING: A university teaching hospital. PATIENTS: Thirty-two men with penile corporeal dysfunction, ranging in age from 33 to 77 years (mean 45 years). The duration of impotence ranged from 8 to 66 months (mean 29 months). The results were evaluated by chart review and patient questionnaire. INTERVENTION: Ligation of the penile cavernosal and crural veins. MAIN OUTCOME MEASURES: Penile-brachial index (PBI), peak flow rate in the cavernosal arteries after injection of papaverine, penile rigidity and maintenance of perfusion rate during cavernosometry, all measured preoperatively and compared postoperatively, and major venous leakage, defined as leakage into both the deep and the intermediate systems. RESULTS: Ten (31%) of the 32 patients had a good result (full rigid erection without adjuvant therapy postoperatively) and 9 (28%) showed improvement (full erection with intracorporeal injection). Of the 13 (41%) failures, 7 had temporary improvement, ranging from 6 to 20 months. Preoperative penile rigidity, PBI and peak blood-flow velocity were significantly higher in patients with good results than in those with poor results (68% versus 40%, p < 0.05). Major venous leakage occurred in 12 of 13 patients with poor results but in only 1 of the patients with good results. CONCLUSIONS: The success or failure of penile venous ligation should not be evaluated during the 1st year after the procedure. The presence of minor leakage and penile rigidity greater than 60% are good predictors of the success of the procedure.

Diabetes mellitus increases nitric oxide synthase in penises but not in major pelvic ganglia of rats.

OBJECTIVE: To determine the effect of diabetes mellitus (DM) on erectile function and evaluate the levels of nitric oxide synthetase (NOS) activity in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Rats were studied at 9 weeks and 14 weeks after the induction of DM by streptozotocin and compared with untreated control rats. Erectile potency was assessed physiologically by testing and recording mating behaviour. NOS activity was assayed in penile tissues and major pelvic ganglia (MPG) by conversion of [3H] L-arginine to [3H] citrulline. Histological, ultrastructural and immunohistochemical studies of penile tissues were performed in similar groups of rats. RESULTS: Diabetes mellitus adversely and significantly degraded all parameters of mating behaviour, thus indicating defective erectile potency. However, NOS activities in penile tissues from both groups of diabetic rats were significantly higher than those in controls (P < 0.01). In MPG, NOS activities were not significantly different between diabetic and control rats (P > 0.05). Histological, ultrastructural and immunohistochemical studies of penile tissues revealed no significant differences between control and diabetic rats, indicating an intact effector organ (smooth muscles) in rats with up to 14 weeks of DM. CONCLUSION: The impotence frequently observed in diabetic subjects would suggest that despite the increase in NOS activity in the penis, the pharmacological action of nitric oxide is impaired.