Qiyun Yang

Insulin resistance is an independent determinate of ED in young adult men.

Background Insulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease. Aim To evaluate whether IR was related to ED in young adult patients. Methods A total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD). Results IR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED. Conclusions Compared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.

Neurotrophic Effect of Adipose Tissue-Derived Stem Cells on Erectile Function Recovery by Pigment Epithelium-Derived Factor Secretion in a Rat Model of Cavernous Nerve Injury

The paracrine effect is the major mechanism of stem cell therapy. However, the details of the effects mechanism remain unknown. The aim of this study is to investigate whether adipose tissue-derived stem cells (ADSCs) can ameliorate cavernous nerve injury-induced erectile dysfunction (CNIED) rats and to determine its mechanism. Twenty-eight days after intracavernous injection of 5-ethynyl-2-deoxyuridine- (EdU-) labeled ADSCs, the erectile function of all the rats was evaluated by intracavernosal pressure (ICP). The ADSCs steadily secreted detectable pigment epithelium-derived factor (PEDF) in vitro. The expression of PEDF increased in the penis of the bilateral cavernous nerve injury (BCNI) group for 14 days and then gradually decreased. On day 28 after the intracavernous injection, the ADSCs group exhibited a significantly increased ICP compared with the phosphate buffered saline- (PBS-) treated group. Moreover, the neuronal nitric oxide synthase (nNOS) and S100 expression in penile dorsal nerves and the smooth muscle content to collagen ratio in penile tissues significantly increased. Furthermore, elevated PEDF, p-Akt, and p-eNOS were identified in the ADSCs group. This study demonstrated that intracavernous injection of ADSCs improved erectile function, repaired the nerve, and corrected penile fibrosis. One potential mechanism is the PEDF secretion of ADSCs and subsequent PI3K/Akt pathway activation.

Transplantation of human urine-derived stem cells transfected with pigment epithelium-derived factor to protect erectile function in a rat model of cavernous nerve injury.

The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs genetically modified with pigment epithelium-derived factor (PEDF) could protect the erectile function and cavernous structure in a bilateral cavernous nerve injury-induced erectile dysfunction (CNIED) rat model. USCs were cultured from the urine of six healthy male donors. Seventy-five rats were randomly divided into five groups (n = 15 per group): sham, bilateral cavernous nerve (CN) crush injury (BCNI), USC, USCGFP+, and USCGFP/PEDF+ groups. The sham group received only laparotomy without CN crush injury and intracavernous injection with phosphate-buffered saline (PBS). All of the other groups were subjected to BCNI and intracavernous injection with PBS, USCs, USCsGFP+, or USCsGFP/PEDF+, respectively. The total intracavernous pressure (ICP) and the ratio of ICP to mean arterial pressure (ICP/MAP) were recorded. The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. The USC and USCGFP/PEDF+ groups displayed more significantly enhanced ICP and ICP/MAP ratio (p < 0.05) 28 days after cell transplantation. Immunohistochemistry (IHC) and Western blot analysis demonstrated that the protection of erectile function and the cavernous structure by USCsGFP/PEDF+ was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and a smooth muscle marker (smoothelin), an enhanced smooth muscle to collagen ratio, decreased expression of transforming growth factor-β1 (TGF-β1), and decreased cell apoptosis in the cavernous tissue. The paracrine effect of USCs and USCsGFP/PEDF+ prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernous tissue.

Erectile Dysfunction in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Outcomes from a Multi-Center Study and Risk Factor Analysis in a Single Center

The aim of this study was to investigate the prevalence of erectile dysfunction (ED) in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and explore the influence of UPOINT domains, National Institutes of Health-CP symptom index (NIH-CPSI) and other factors on ED prevalence. This was a prospective study of consecutive patients with CP/CPPS seen at 11 tertiary hospitals during January–July 2014. ED was diagnosed as a score of<21 on the International Index of Erectile Function (IIEF-5). Patients from one center were evaluated by the UPOINT system and NIH-CPSI. Each patient was assessed using clinical examination, asocio-demographic questionnaire, the Patient Health Questionnaire (PHQ), the Pain Catastrophizing Scale (PCS), NIH-CPSI and IIEF-5.1406 patients from 11 centers (mean age, 32.18 years; range 18–60 years) were enrolled. ED was found in 638/1406 patients (45.4%), and was categorized as mild in 291(45.6%), moderate in 297(46.6%) and severe in50(7.7%). 192 patients from one center(mean age,31.3 years; range 18–57 years) were further studied.IIEF-5 score correlated negatively with NIH-CPSI(r = 0.251), PHQ (r = 0.355) and PCS (r = 0.322)scores (P<0.001).PHQ score correlated positively with NIH-CPSI (r = 0.586) and PCS(r = 0.662) scores (P<0.001).NIH-CPSI, PHQ, PCS and IIEF-5 scores did not differ significantly between class IIIA and IIIB CP/CPPS. Multivariate logistic regression showed that UPOINT psychological (P) domain and NIH-CPSI symptom severity were independent risk factors for ED in CP/CPPS. It is concluded that psychological factors and symptom severity are independent risk factors for ED in CP/CPPS.

MP89-12 NEUROTROPHIC EFFECT OF ADIPOSE TISSUE-DERIVED STEM CELLS ON ERECTILE FUNCTION RECOVERY BY PIGMENT EPITHELIUM-DERIVED FACTOR SECRETION IN A RAT MODEL OF CAVERNOUS NERVE INJURY

understood. We evaluated the effect of cAMP-dependent protein kinase A (PKA) agonist Colforsin treatment on the phosphorylation of nNOS, nNOS uncoupling, and an oxidative stress in the penis and major pelvic ganglia (MPG), and erectile function status in a rat model of bilateral cavernous nerve injury (BCNI), which mimics nerve injury following prostatectomy. METHODS: Adult male Sprague Dawley rats were divided into BCNI and sham group. Each group included 2 subgroups: vehicle and Colforsin (0.1 mg/kg i.p. injection). After 3 days, erectile function (intracavernosal pressure) was measured and penes and MPG were collected for molecular analyses of phospho(P)-nNOS (Ser-1412 and Ser-847), total nNOS, nNOS uncoupling (by Western blot) and oxidative stress (hydrogen peroxide [H2O2] and superoxide by microdialysis method and Western blot). RESULTS: Erectile function was decreased (p<0.05) after BCNI and normalized (p<0.05) by Colforsin treatment. nNOS uncoupling and nNOS phosphorylation on both positive (Ser-1412) and negative (Ser-847) sites were increased (p<0.05) after BCNI in both the penis and MPG and normalized (p<0.05) by Colforsin treatment. nNOS protein expression was decreased (p<0.05) after BCNI in the penis (but not in MPG) and was unaffected by Colforsin treatment. Reactive oxygen species were increased (p<0.05) in the penis and gp-91 phox (subunit of NADPH oxidase) and active caspase 3 were increased (p<0.05) in the MPG in BCNI group and normalized (p<0.05) by Colforsin treatment. VASP phosphorylation Ser-157 (PKA target) was decreased (p<0.05) after BCNI in the MPG and was normalized by Colforsin treatment. CONCLUSIONS: BCNI inhibits nNOS function in the penis and MPG by causing its uncoupling and deranging its phosphorylation, and increasing oxidative stress, resulting in erectile dysfunction. PKA agonist reverses these molecular changes and preserves penile erection in the face of BCNI. These data demonstrate the novel regulation of nNOS signaling in the penis and MPG after BCNI.

MP41-14 HUMAN URINE-DERIVED STEM CELLS GENETICALLY-MODIFIED WITH PEDF IMPROVE CAVERNOUS NERVE INJURY-INDUCED ERECTILE DYSFUNCTION IN A RAT MODEL

CONCLUSIONS: Our results are very promising and statistically significant. We found improved erections on ultrasound and by patient reporting. The majority of patients expressed satisfaction with overall results following injections. Previously, safety data from multiple institutions has been reported on ProFlo Amniotic Fluid. This is the first study to evaluate the effectiveness of ProFlo AF injections. ProFlo AF needs larger studies but may prove to be a safe, effective and noninvasive treatment in men with ED.