Effects of tadalafil to prevent injury on corpus cavernosum after vascular or nervous peri-prostatic bundle injury. Experimental model in rats

Abstract Purpose: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. Methods: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. Results: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). Conclusions: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.

Penile alterations at early stage of type 1 diabetes in rats

ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ)-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS) in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

ABSTRACT Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus reflex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

Use of nanoparticles to monitor human mesenchymal stem cells transplanted into penile cavernosum of rats with erectile dysfunction

PURPOSE: This study was performed to examine the treatment of erectile dysfunction by use of superparamagnetic iron oxide nanoparticles-labeled human mesenchymal stem cells (SPION-MSCs) transplanted into the cavernous nerve injured cavernosa of rats as monitored by molecular magnetic resonance imaging (MRI). MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into three groups of 10 rats each: group 1, sham operation; group 2, cavernous nerve injury; group 3, SPION-MSC treatment after cavernous nerve injury. Immediately after the cavernous nerve injury in group 3, SPION-MSCs were injected into the cavernous nerve injured cavernosa. Serial T2-weighted MRI was done immediately after injection and at 2 and 4 weeks. Erectile response was assessed by cavernous nerve stimulation at 2 and 4 weeks. RESULTS: Prussian blue staining of SPION-MSCs revealed abundant uptake of SPION in the cytoplasm. After injection of 1x10(6) SPION-MSCs into the cavernosa of rats, T2-weighted MRI showed a clear hypointense signal induced by the injection. The presence of SPION in the corpora cavernosa was confirmed with Prussian blue staining. At 2 and 4 weeks, rats with cavernous nerve injury had significantly lower erectile function than did rats without cavernous nerve injury (p<0.05). The group transplanted with SPION-MSCs showed higher erectile function than did the group without SPION-MSCs (p<0.05). The presence of SPION-MSCs for up to 4 weeks was confirmed by MRI imaging and Prussian blue staining in the corpus cavernosa. CONCLUSIONS: Transplanted SPION-MSCs existed for up to 4 weeks in the cavernous nerve injured cavernosa of rats. Erectile dysfunction recovered and could be monitored by MRI.

Effect of Mesenchymal Stem Cells Associated to Matrixen on the Erectile Function in the Rat Model with Bilateral Cavernous Nerve Crushing Injury

To evaluate the effect of mesenchymal stem cells (MSCs) and MSCs mixed with Matrixen as a cell carrier on the erectile dysfunction caused by bilateral cavernous nerve crushing injury.

White male Sprague-Dawley rats were divided into 4 groups: sham-operated control group (n = 5), bilateral cavernous nerve crushing group (BCNC group, n = 10), BCNC administered with MSCs group (n = 10,1×106 in 20 µL), BCNC administered with Matrixen group (n = 10.1×106 in 20 µL), BCNC administered with MSCs/Matrixen group (n = 10.1×106 in 20 µL). After functional assessment at 4 weeks, major pelvic ganglion (MPG) and penile tissue were collected. Immunofluorescent staining of MPG was performed with PKH26 and Tuj1. Western blot analysis of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) were done in corpus cavernosum.

ICP/MAP ratios of BCNC with MSCs and MSCs/Matrixen groups were significantly increased compared with BCNC and BCNC with Matrixen group. Moreover, ICP/MAP ratios of MSCs/Matrixen group were significantly increased compared with BCNC with MSCs group. In MPG, the more implantation of MSCs and increased expression of nerve cells were observed in MSCs/Matrixen group compared with BCNC with MSCs group. Significant increase expression of eNOS and nNOS was also noted in BCNC with MSCs/Matrixen group.

The erectile function was more preserved in MSCs/Matrixen group compared with the administration of MSCs alone in the rats with bilateral cavernous nerve crushing injury. Therefore, we consider that the use of transplant cell carrier such as Matrixen may help the implantation of MSCs and improve the therapeutic effect of MSCs. .

Progress in diagnosis of neurogenic erectile dysfunction / 法医学杂志

Recently, with application of evoked potentials technology in the test of somatic and autonomic nerves, quantitative sensory testing in the detection of small nerve fiber function, and functional magnetic resonance imaging in the detection of senior central function, the detection of neural function has become more accurate. This article reviews the progress and application of diagnostic methods about neurogenic erectile dysfunction in order to provide a reference for forensic diagnosis and research in the future.

Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy

OBJECTIVE: To evaluate the change in penile size r bilateral nerve sparing retropubic radical prostatectomy (BNSRRP) and possible effect of Tadalafil. MATERIALS AND METHODS: A total of 65 patients underwent BNSRRP and they were evaluated prospectively for a whole year of follow-up . The patients were randomized to control without rehabilitation (Group 1) or Tadalafil rehabilitation group (Group 2). The patients were evaluated at months 3, 6 and 12 postoperatively for erectile function, penile measurements (flaccid penile length, penile length at maximum erection, penile circumference at flaccid status, and penile circumference at maximum erection), penile abnormalities and general health status. Statistical analysis was performed by Chi-Square test and significance was defined as p value < 0.05. RESULTS: In Group 1 there was significant decrease in penile measurements at month 3 compared to preoperative measurements. There was decrease in all parameters at month 6 compared to month 3 but only the decrease in penile length at maximum erection was significant. There were no significant differences between postoperative months 6 and 12 for all measurements. In Group 2 there was a tendency to decrease in all measurements at month 3 compared to baseline. There was no significant difference for penile measurements between postoperative 3rd and 6th months and between 6th month and the first year. CONCLUSION: Although further large sampled trials are needed to describe the possible positive effect of tadalafil or other PDE5-I's on penile size after BNSRRP, tadalafil rehabilitation is effective in preserving penile size especially in the early postoperative period after BNSRRP.

Experimental model of human corpus cavernosum smooth muscle relaxation

PURPOSE: To describe a technique for en bloc harvesting of the corpus cavernosum, cavernous artery and urethra from transplant organ donors and contraction-relaxation experiments with corpus cavernosum smooth muscle. MATERIALS AND METHODS: The corpus cavernosum was dissected to the point of attachment with the crus penis. A 3 cm segment (corpus cavernosum and urethra) was isolated and placed in ice-cold sterile transportation buffer. Under magnification, the cavernous artery was dissected. Thus, 2 cm fragments of cavernous artery and corpus cavernosum were obtained. Strips measuring 3 x 3 x 8 mm3 were then mounted vertically in an isolated organ bath device. Contractions were measured isometrically with a Narco-Biosystems force displacement transducer (model F-60, Narco-Biosystems, Houston, TX, USA) and recorded on a 4-channel Narco-Biosystems desk model polygraph. RESULTS: Phenylephrine (1µM) was used to induce tonic contractions in the corpus cavernosum (3 - 5 g tension) and cavernous artery (0.5 - 1g tension) until reaching a plateau. After precontraction, smooth muscle relaxants were used to produce relaxation-response curves (10-12M to 10-4 M). Sodium nitroprusside was used as a relaxation control. CONCLUSION: The harvesting technique and the smooth muscle contraction-relaxation model described in this study were shown to be useful instruments in the search for new drugs for the treatment of human erectile dysfunction.

Techniques of nerve-sparing and potency outcomes following robot-assisted laparoscopic prostatectomy: [review]

PURPOSE: Nerve sparing radical prostatectomy is the gold standard for the treatment of prostate cancer. Over the past decade, more and more surgeons and patients are opting for a robot-assisted procedure. The purpose of this paper is to briefly review different techniques and outcomes of nerve sparing robot assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS: We performed a MEDLINE search from 2001 to 2009 using the keywords “robotic prostatectomy”, “cavernosal nerve”, “pelvic neuroanatomy”, “potency”, “outcomes” and “comparison”. Extended search was also performed using the references from these articles. RESULTS: Several techniques of nerve sparing are available in literature for RALP, which have been described in this manuscript. These include, “the veil of Aphrodite”, “athermal retrograde neurovascular release”, “clipless antegrade nerve sparing” and “clipless cautery free technique”. The comparative and the non comparative series showing outcomes of RALP have been described in the manuscript. CONCLUSIONS: The basic principles for nerve sparing revolve around minimal traction, athermal dissection, and approaching the correct planes. It has not been documented if any one technique is better than the other. Regardless of technique, patient selection, wise clinical judgment and a careful dissection are the keys to achieve optimal oncological outcomes following RALP.

Advance of neurogenic erectile dysfunction therapy by stem cells / 法医学杂志

Neurogenic erectile dysfunction (NED) commonly results from erectile nerve damage. Recent researches have focused on the preclinical study of stem cell-based therapies targeted at repairing and protecting nervi erigentes. In this paper, researches of NESCs, MDSCs, ASCs and MSCs in NED are reviewed. Early studies have demonstrated that stem cells and gene modified stem cells were effective to the therapy of ED, even likely to cure ED. Stem cells are expected to be applied in the clinical therapy of NED. Stem cells as a new therapy technique will bring up a new challenge in forensic clinical medicine.

Gating of the dorsal penile nerve inputs by norepinephrine at the medial preoptic area in rats.

The medial preoptic area neurons related to male sexual behaviour in rats were identified by their responses to dorsal penile nerve stimulation. These neurons were further tested with norepinephrine applied iontophoretically. From the 21 medial preoptic area neurons recorded in urethane anaesthetized rats, 17 neurons responded to dorsal penile nerve stimulation. Excitatory and inhibitory responses were found in almost equal number of neurons. 14 neurons responded to norepinephrine application, out of which six neurons were excited and eight were inhibited. The direction of changes produced by dorsal penile nerve stimulation and norepinephrine application were similar in 10 neurons. The results suggest that the sensory inputs from the genitalia are possibly gated by norepinephrine at the level of the medial preoptic area. Afferent information from the genitalia carried by dorsal penile nerve and the availability of norepinephrine at the level of the medial preoptic area probably help in maintaining adequate level of sexual arousal.

Tramadol along with local anaesthetics in the penile block for the children undergoing circumcision.

OBJECTIVE: This study was to find out the total duration of postoperative analgesia following circumcision in children when Tramadol was used as an adjunct to local anaesthetics in penile block. METHODS: Forty children of age 5 - 13 yrs, ASA I & II were enrolled in this study. Patients were premedicated with ketamine and atropine intramuscularly prior to separation from their parents and IV cannulation. Penile block was then performed under strict aseptic precautions with paramedian approach by 3 cm long 23 g ordinary needle where 4 ml of mixture of local anaesthetics and tramadol was given on each side of the base of penis at 11 and 2 o clock positions. Duration of analgesia was recorded from the time of completion of surgery till the patients' first complain of pain and when additional analgesic was given. Intraoperative analgesia duration achieved by the penile block was not included in this study due to unavoidable overlapping of sedation and analgesia produced by the premedicated IM Ketamine (4-5 mg/kg) ,which lasts for 25 minutes to 30 minutes. Unless complicated, this is the usual surgery time in our hospital for this procedure. Because of this reason, the sedation score was not used in this study. Moreover, paediatric sedation score remains too impractical and unreliable in our context. RESULTS: Addition of Tramadol with local anaesthetics in penile block prolonged the postoperative analgesia even up to 40 hours. CONCLUSION: Tramadol as an adjunct with Local Anaesthetics extends the duration of postoperative analgesia and can be used safely for this purpose in the children.

The central conduction time in posterior tibial and pudendal nerve somatosensory evoked potentials

The somatosensory evoked potentials (SEPs), following stimulation of both the posterior tibial nerve (PTSEP) and pudendal nerve (PNSEP), comprise of the lumbar negative, subcortical and cortical potential. These can be used to assess the long somatosensory pathway, including peripheral, intraspinal and intracranial conduction along the entire length. This study aimed to compare the central conduction time between the PTSEP and the PNSEP, and to investigate the relationship between the intraspinal and intracranial conduction time in the SEP pathway. The SEPs following stimulation of the posterior tibial nerve at the ankle and the pudendal nerve at the shaft of the penis were analyzed in 20 normal male subjects. The central conduction of the PNSEP was found to be slower than that of the PTSEP (p <0.05). This difference is due to a delay in conduction rather than that of intracranial conduction.

Reconstrucción fálica total: informe de un caso. Comunicación preliminar / Total reconstruction of the phallus: report of a case. preliminary communication

La reconstrucción total del falo es ahora técnicamente factible. Es posible la restauración de la función sexual en el paciente con el neofalo utilizando el colgajo neurosensorial radial del antebrazo. El neofalo inervado desarrolla sensasión táctil y erógena en seis a ocho meses después del procedimiento. En esta comunicación preliminar se informa la experiancia quirúrgica de los autores con una neofaloplastia con colgajo radial del antebrazo de un solo tiempo en un paciente joven de 18 años de edad, quien sufrió un traumatismo genital mecánico. Seis meses después de la intervención el congajo se encuentra bien integrado y con aspecto aceptable, y cuenta con una uretra completa funcional. Su prótesis peneana semirrígida experimentó extrusión, y se planea colocarle una prótesis insuflable

Experimental evidence for endothelium dependent relaxation and neuronal nitric oxide in corpus cavernosum

It is known that penile erection is mediated primarily through the release of a nonadrenergic noncholinergic (NANC) neurotransmitter which has been recently identified as nitric oxide (NO). To evaluate whether the endothelium is involved in neurally mediated relaxation in corpus cavernosum, we determined electrical field stimulation (EFS) induced relaxation in both the presence and absence of endothelium, and we tested the effect of an inhibitor of NO synthase, NG-nitro-L-arginine (NOARG), in the absence of endothelium to examine if de-endothelialized tissue can still generate NO. Isolated corpus cavernosal strips from New Zealand White rabbits were used for isometric tension study using organ chambers. The endothelium was removed through denuding tissue. After the tissue was contracted with norepinephrine, EFS was performed at frequencies of 5, 15 and 40 Hz in the presence of guanethidine and atropine to evaluate NANC-selective nerural relaxation. The relaxation induced by EFS was observed after preincubation with NOARG(10(-4) M) for 30 minutes. L-arginine (10(-3) M) was then added for 30 minutes in the presence of NOARG before a second set of EFS studies were performed. Following norepinephrine precontraction, EFS relaxed corporal strips in both the intact and de-endothelialized strips. However, deendothelialization significantly impaired EFS induced relaxation (p< 0.05). NOARG attenuated relaxation induced by EFS and the addition of L-arginine reversed the inhibitory effect of NOARG in the strips with endothelium. In the strips without endothelium, NOARG still inhibited EFS induced relaxation. This relaxation was reversed by the addition of L-arginine.

Pápulas perladas del pene: estudio clínico-histológico y ultraestructural / Pearly penile papules: clinical-histological and ultrastructural study

En diez pacientes con edades comprendidas entre 19 y 24 quienes presentaban pápilas perladas del pene típicas, se hizo estudio histológico y ultraestructural. Cortes coloreados con HE demostraron un eje proliferativo conjuntivo- vásculo-celular en dermis superior empujando el epitelio suprayacente. Con el microscopio electrónico se puso de manifiesto proliferación intensa de miofibroblastos, algunos macrófagos, ocasionales mastocitos y abundantes vasos sanguíneos. No se observaron partículas virales, cambios citológicos ni arquitecturales del epitelio sugestivo de infección por VPH. En este estudio se confirma que las pápilas perladas del pene son angiofibromas originados fundamentalmente por la proliferación de miofibroblastos