Jiuhong Yuan

COX-2-10aa-PGIS Gene Therapy Improves Erectile Function in Rats after Cavernous Nerve Injury

INTRODUCTION Erectile dysfunction (ED) is a very common complication after radical prostatectomy. COX-2-10aa-PGIS is a newly engineered protein with COX-2 and prostacyclin synthase activities that converts arachidonic acid directly to prostacyclin (prostaglandin I2 [PGI2]). PGI2 is a potent smooth muscle relaxant. AIM The purpose of this study was to explore the effect and mechanism of COX-2-10aa-PGIS gene therapy in penile rehabilitation. METHODS Bilateral cavernous nerve crush (BCNC) in adult Sprague-Dawley rats was used to mimic radical prostatectomy-induced ED. Sprague-Dawley rats were randomly assigned into four groups: 1. sham surgery; 2. BCNC; 3. BCNC + null control recombinant adenovirus intracavernous injection; and 4. BCNC + Ad-COX2-10aa-PGIS intracavernous injection. Twenty-eight days later, intracavernosal pressure (ICP) was recorded under cavernous nerve stimulation; in the meantime, the mean arterial pressure (MAP) was monitored. At the end of the measurement, the penis was harvested and processed for (i) immunohistochemistry analysis of endothelial nitric oxide synthase (eNOS), alpha-smooth muscle actin (α-SMA), and transforming growth factor beta-1 (TGF-β1); (ii) Massons trichrome stain for smooth muscle/collagen ratios; (iii) Western blot of eNOS, α-SMA, TGF-β1, and COX2-10aa-PGIS; and (iv) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis. MAIN OUTCOME MEASURES Erectile function was evaluated by ICP/MAP. Smooth muscle and endothelium functions in corpora cavernosum were assessed by Massons trichrome stain, immunohistochemistry, and Western blot. Apoptosis was identified by TUNEL assay. RESULTS The results were the following: 1. COX2-10aa-PGIS gene therapy improved erectile function (82%, compared with control) in the BCNC rat model; 2. COX2-10aa-PGIS gene therapy increased eNOS (121%) and α-SMA (118%) expression and decreased TGF-β1 (45%) expression; 3. COX2-10aa-PGIS gene therapy reduced cell apoptosis after cavernous nerve injury (64%); and 4. COX2-10aa-PGIS gene therapy improved smooth muscle/collagen ratios (81%). CONCLUSION Our data demonstrated that COX2-10aa-PGIS improved erectile function after cavernous nerve injury through antifibrotic and anti-apoptotic mechanisms.

Phosphodiesterase type 5 inhibitors for the treatment of post-nerve sparing radical prostatectomy erectile dysfunction in men

Prostate cancer (PCa) is the most common solid neoplasm diagnosed in developed countries. Nerve-sparing radical prostatectomy (NS-RP) has been widely accepted as the best choice treatment for localised PCa. However, erectile dysfunction (ED) and urinary incontinence are commonly observed after NS-RP. Using meta-analysis, we examined if phosphodiesterase type 5 inhibitors (PDE5-Is) could improve the symptoms of ED in patients undergoing NS-RP. This review contained seven randomised placebo-controlled trials with a total of 2,655 male patients. Patients in PDE5-Is group showed significant improvement in the International Index of Erectile Function-Erectile Function domain score (IIEF-EF), Global Assessment Questionnaire (GAQ), Sexual Encounter Profile question 2 (SEP-2) and SEP-3. Although the incidence of treatment-emergent adverse events (TEAEs) were high in both groups (56.44% vs. 40.63%), the safety profile were acceptable, with low incidence of discontinuation rate due to adverse events. Therefore, PDE5-Is are recommended for the treatment of post-NS-RP ED. Patients should be informed of possible adverse events.

Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored.

A meta-analysis of extracorporeal shock wave therapy for Peyronie’s disease

The efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie’s disease (PD) has been controversial for a very long time. We aimed to evaluate the efficiency of ESWT for PD and provide possible evidence on the basis of a meta-analysis of existing comparative studies. All controlled studies, including randomized controlled trials (RCTs), cohort studies and case-control studies, that focused on the efficiency of ESWT for PD, were prospectively identified through comprehensive searches of PubMed, the Cochrane Library and Embase databases. We conducted a meta-analysis of these studies. Six studies including 443 patients were selected for the meta-analysis. Pooling data of these studies showed that ESWT could significantly increase the percentage of men with lessening of penile plaques (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.11–3.85, P=0.02), relief of pain (OR 4.46, 95% CI 2.29–8.68, P<0.0001) and complete remission of pain (OR 5.86, 95% CI 2.66–12.92, P<0.0001). However, insignificant differences were found in improvement of penile curvature (OR 1.88, 95% CI 0.97–3.65, P=0.06) and sexual function (OR 2.22, 95% CI 0.69–7.11, P=0.18) between ESWT and placebo groups. Further, similar results were shown for sensitivity and publication bias analysis when only RCTs were included. However, sporadic complications caused by ESWT were reported, but no patient needed additional treatment aside from conservative observation. ESWT may be an effective and safe treatment for lessening of penile plaques and relieving pain for men with PD, but not for improving of penile curvature and sexual function.

Advantages and limitations of sleep-related erection and rigidity monitoring: a review

Over the past decades, sleep-related erection and rigidity monitoring has been used to differentiate psychogenic from organic erectile dysfunction (ED), due to the involuntary nature of erections in sleep. This study retrospectively reviewed all available literature focusing on sleep-related erection and rigidity monitoring through a systematic PubMed search. To date, there are mainly seven methods and their modifications, including: sleep laboratory testing, the mercury strain gauge, the stamp test, the erectometer, the Snap gauge, the RigiScan, and nocturnal electrobioimpedance volumetric assessment. This study analyzes and summarizes the advantages and limitations of seven monitoring methods. This study indicates that both of the above methods possess the capacity to assess erectile quality and provide guidance to the diagnosis, etiology, and differential diagnosis of ED. However, some limitations still exist for the application. New devices which can continuously monitor kinds of variables, including sleep-related erection, axial and radial rigidity, and oxygen saturation are needed.

Reduction in Peyronie's-like plaque size using a vacuum erection device in a rat model of Peyronie's disease via the TGF-β/SMAD signalling pathway

Peyronies disease (PD) is a fibrotic disorder of the tunica albuginea (TA). This study aimed to determine the therapeutic effects of a vacuum erection device (VED) in an animal model of PD and explore the possible mechanisms. Twenty‐seven male Sprague‐Dawley rats were used. The sham group (group A) (N = 9) received a 50‐μl‐saline vehicle injection into the TA, while the remaining 18 rats (groups B and C) received a TGF‐β1 injection into the TA. The treatment group (group C) underwent VED therapy for 10 days after the TGF‐β1 injection. Erectile function was then assessed at day 42. Rats injected with TGF‐β1 showed significantly lower intracavernous pressures than those in the sham group (p < 0.0001). After VED therapy, erectile function was significantly better in the treatment group than in the PD group (group B) (p < 0.0147). Massons trichrome staining confirmed Peyronies‐like plaques at the TGF‐β1 injection site in the PD group. Furthermore, the treatment group showed markedly smaller fibrotic plaque sizes than the PD group. A significant increase in TGF‐β1, SMAD2, SMAD3 and p‐SMAD2/3 protein expression was observed 6 weeks after the TGF‐β1 injection. However, the expression of the same proteins decreased after VED therapy. Protein expression trends were confirmed using immunohistochemistry analysis. The findings of this study demonstrate that VED therapy can reduce Peyronies‐like plaque size in a rat model of PD while simultaneously improving erectile function.

Isoflurane inhalation anesthesia should be a new requirement in intracavernosal pressure detection—the gold standard of erectile function assessment

Intracavernosal pressure (ICP) is gold standard for the detection of erectile function in animals, but no consensus has yet been achieved on what kind of anesthetic protocol should be applied. A total of 16 adult male Sprague-Dawley rats were randomized into two groups. In group A, chloral hydrate was injected intraperitoneally. Rats in group B were induced in 5% isoflurane for 3 min and then maintained in 1.0–1.5% isoflurane. Mean arterial pressure (MAP), respiratory rate (RR) and heart rate were monitored during all experiments. After ICP detection, tail vein and carotid artery blood were collected. The maximum ICP value, MAP and ICP/MAP ratio in group B was significantly higher than in that of group A. The RR in group A was lower than in that of group B, but the heart rate in group A was higher than in group B. There were no significant differences in both pO2 and pCO2 between groups. While the data showed that animals in group A were relatively hypoxemic. Isoflurane inhalation anesthesia in detection of erectile function could offer a relatively more stable physical state than in that under the effect of chloral hydrate intraperitoneal anesthesia. Isoflurane inhalation anesthesia is more suitable for ICP test.

Penile transplantation: A long way to routine clinical practice

Organ transplantation is an ideal treatment for certain late-stage diseases. With the report of a penile transplantation in Tygerberg Hospital, South Africa, this topic has, once again, aroused exploration in the field. At present, two penile transplantation operations have been performed and gained some positive results. Patients can gain void standing, erectile function and better cosmetic appearance. However, debates and potential risks still exist. Here, we briefly review the progress of studies in this filed and discusses the potential risks and debates in penile transplantation.

Lysyl oxidase family members in urological tumorigenesis and fibrosis

Lysyl oxidase (LOX) is an extracellular copper-dependent monoamine oxidase that catalyzes crosslinking of soluble collagen and elastin into insoluble, mature fibers. Lysyl oxidase-like proteins (LOXL), LOX isozymes with partial structural homology, exhibit similar catalytic activities. This review summarizes recent findings describing the roles of LOX family members in urological cancers and fibrosis. LOX/LOXL play key roles in extracellular matrix stability and integrity, which is essential for normal female pelvic floor function. LOX/LOXL inhibition may reverse kidney fibrosis and ischemic priapism. LOX and LOXL2 reportedly promote kidney carcinoma tumorigenesis, while LOX, LOXL1 and LOXL4 suppress bladder cancer growth. Multiple studies agree that the LOX propeptide may suppress tumor growth, but the role of LOX in prostate cancer remains controversial. Further studies are needed to clarify the exact effects and mechanism of LOX/LOXL on urological malignancies.

Effect of lysyl oxidase (LOX) on corpus cavernous fibrosis caused by ischaemic priapism

Penile fibrosis caused by ischemic priapism (IP) adversely affects patients’ erectile function. We explored the role of lysyl oxidase (LOX) in rat and human penes after ischemic priapism (IP) to verify the effects of anti‐LOX in relieving penile fibrosis and preventing erectile dysfunction caused by IP in rats. Seventy‐two rats were randomly divided into six groups: control group, control + β‐aminopropionitrile (BAPN) group, 9 hrs group, 9 hrs + BAPN group, 24 hrs group, and 24 hrs + BAPN group. β‐aminopropionitrile (BAPN), a specific inhibitor of LOX, was administered in the drinking water. At 1 week and 4 weeks, half of the rats in each group were randomly selected for the experiment. Compared to the control group, the erectile function of IP rats was significantly decreased while the expression of LOX in the corpus cavernosum was significantly up‐regulated in both 9 and 24 hrs group. Proliferated fibroblasts, decreased corpus cavernosum smooth muscle cells/collagen ratios, destroyed endothelial continuity, deposited abnormal collagen and disorganized fibers were observed in IP rats. The relative content of collage I and III was not obviously different among the groups. β‐aminopropionitrile (BAPN) could effectively improve the structure and erectile function of the penis, and enhance recovery. The data in this study suggests that LOX may play an important role in the fibrosis of corpus cavernosum after IP and anti‐LOX may be a novel target for patients suffering with IP.