Clinical recommendations on penile reconstructive and prosthetic surgery: a consensus statement from the Asia-Pacific Society of Sexual Medicine.

Introduction: Penile reconstructive and prosthetic surgery remains a highly specialized field where potential complications can be devastating, and unrealistic patient expectations can often be difficult to manage. Furthermore, surgical practice can vary depending on locoregional expertise and sociocultural factors. Methods: The Asia Pacific Society of Sexual Medicine (APSSM) panel of experts reviewed contemporary evidence regarding penile reconstructive and prosthetic surgery with an emphasis on key issues relevant to the Asia-Pacific (AP) region and developed a consensus statement and set of clinical practice recommendations on behalf of the APSSM. The Medline and EMBASE databases were searched using the following terms: "penile prosthesis implant," "Peyronie's disease," "penile lengthening," "penile augmentation," "penile enlargement," "buried penis," "penile disorders," "penile trauma," "transgender," and "penile reconstruction" between January 2001 and June 2022. A modified Delphi method was undertaken, and the panel evaluated, agreed, and provided consensus statements on clinically relevant penile reconstructive and prosthetic surgery, namely (1) penile prosthesis implantation, (2) Peyronie's disease, (3) penile trauma, (4) gender-affirming (phalloplasty) surgery, and (5) penile esthetic (length and/or girth enlargement) surgery. Main outcome measures: Outcomes were specific statements and clinical recommendations according to the Oxford Centre for Evidence-Based Medicine, and if clinical evidence is lacking, a consensus agreement is adopted. The panel provided statements on clinical aspects of surgical management in penile reconstructive and prosthetic surgery. Results: There is a variation in surgical algorithms in patients based on sociocultural characteristics and the availability of local resources. Performing preoperative counseling and obtaining adequate informed consent are paramount and should be conducted to discuss various treatment options, including the pros and cons of each surgical intervention. Patients should be provided with information regarding potential complications related to surgery, and strict adherence to safe surgical principles, preoperative optimization of medical comorbidities and stringent postoperative care are important to improve patient satisfaction rates. For complex patients, surgical intervention should ideally be referred and performed by expert high-volume surgeons to maximize clinical outcomes. Clinical implications: Due to the uneven distribution of surgical access and expertise across the AP region, development of relevant comprehensive surgical protocols and regular training programs is desirable. Strengths and Limitations: This consensus statement covers comprehensive penile reconstructive and prosthetic surgery topics and is endorsed by the APSSM. The variations in surgical algorithms and lack of sufficient high-level evidence in these areas could be stated as a limitation. Conclusion: This APSSM consensus statement provides clinical recommendations on the surgical management of various penile reconstructive and prosthetic surgeries. The APSSM advocates for surgeons in AP to individualize surgical options based on patient condition(s) and needs, surgeon expertise, and local resources.

The International Penile Prosthesis Implant Consensus Forum: clinical recommendations and surgical principles on the inflatable 3-piece penile prosthesis implant.

Despite significant scientific advances in the modern three-piece inflatable penile prosthesis implant surgery, it is not without surgical risks and can carry additional cosmetic and psychosocial consequences in poorly selected and consented individuals. To address this problem, an international group of key opinion leaders and high-volume prosthetic surgeons reviewed the current guidelines and clinical evidence, discussed their experiences, and formed a consensus regarding inflatable penile prosthesis surgery. The findings of this consensus panel were presented at the 17th biennial Asia Pacific Society of Sexual Medicine scientific meeting. The experts concluded that proper patient selection, informed consent and strict adherence to safe surgical principles are important to optimize clinical outcomes. Furthermore, most intraoperative complications, if recognized, can be addressed intraoperatively to enable placement of the device at the time of initial surgery. Men with significant corporal fibrosis due to Peyronie's disease, prior prosthesis explantation and priapism, and men who have undergone construction of a neophallus, as well as men who receive concurrent continence surgery, are complex cases requiring additional care and advanced techniques to obtain optimal surgical outcomes. Variability in patient care - in terms of postoperative antibiotic use, pain management, scrotal care, and cycling of the penile prosthesis implant - must be reduced to enable optimization and assessment of outcomes across patient groups.

Effect of Li-ESWT on Testicular Tissue and Function in Androgen-Deficient Rat Model.

Low-intensity extracorporeal shockwave therapy (Li-ESWT), as a microenergy therapy, has the effects of inhibiting oxidative stress, antiapoptosis, and tissue repair, which is increasingly applied to a variety of diseases. Our research aims to explore the protective effects of Li-ESWT in the aging rat model and its possible molecular mechanism through in vivo and in vitro experiments. In vitro, TM3 Leydig cells incubated with H2O2 were treated with Li-ESWT at 4 energy levels (0.01, 0.05, 0.1, and 0.2 mJ/mm2). In vivo, we employed an androgen-deficient rat model to simulate male aging and treated it with Li-ESWT at three different energy levels (0.01, 0.05, and 0.2 mJ/mm2). Li-ESWT increased the expression of vascular endothelial growth factor (VEGF) in TM3 cells, improved antioxidant capacity, and reduced apoptosis, with the effect being most significant at 0.05 mJ/mm2 energy level. In androgen-deficient rat model, LI-ESWT can improve sperm count, motility, and serum testosterone level, enhancing tissue antioxidant capacity and antiapoptotic ability, and the effect is most significant at 0.05 mJ/mm2 energy level. Therefore, Li-ESWT at an appropriate energy level can improve sperm count, motility, and serum testosterone levels in androgen-deficient rat models, reduce oxidative stress in the testis, and increase antioxidant capacity and antiapoptotic abilities. The mechanism of this condition might be related to the increased VEGF expression in Leydig cells by Li-ESWT.

A novel flavonoid derivative of icariside II improves erectile dysfunction in a rat model of cavernous nerve injury.

BACKGROUND: Icariside II (ICA II), an active flavonoid monomer, has been proven to restore post-prostatectomy erectile dysfunction in rats; however, the high cost of extraction from natural plants limits the application of ICA II. OBJECTIVE: To investigate the therapeutic effect and possible mechanism of action of YS-10, a new flavonoid compound, which was designed and synthesized based on the structure of ICA II in a rat model in of cavernous nerve injury. MATERIALS/METHODS: Eight of 32 adult male Sprague-Dawley rats were selected as the normal control (NC) group and received vehicle treatment. The remaining rats were subjected to bilateral cavernous nerve injury (BCNI) and randomized into three groups: BCNI group, BCNI + ICA II group (2.5 mg/kg/day), and BCNI + YS-10 group (2.5 mg/kg/day). The total procedure lasted for 21 days, followed by a washout period of 3 days. All animals were evaluated for erectile function, and tissues were harvested for histopathological analyses. RESULTS: It was observed that in YS-10 group, the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP) and the area under the ICP/MAP curve were effectively enhanced. The maximum ICP/MAP increased by 30% in the YS-10 group (0.86 ± 0.085) compared with the BCNI group (0.66 ± 0.058), which is close to 82% of the NC group (1.05 ± 0.033). Histopathological changes demonstrated significant reduction of smooth muscle atrophy, collagen deposition, and endothelial and neural dysfunction after YS-10 treatment, which have no statistical differences compared with ICA II group. Additionally, high-protein expression levels of ß-Catenin and cyclin D1 were observed in the treatment groups. CONCLUSION: YS-10, a novel synthesized flavonoid compound, could effectively improve erectile dysfunction in rats after BCNI by alleviating pathological impairments; this effect may associate with the upregulation of ß-Catenin and cyclin D1 in Wnt signaling pathway.

The role of tumor size, ultrasonographic findings, and serum tumor markers in predicting the likelihood of malignant testicular histology.

The clinical predictive factors for malignant testicular histology remain unclear because of the low prevalence. Therefore, the aim of this study was to investigate predictors of malignant histology for testicular masses and decide more testis-sparing surgeries before surgery. This retrospective study enrolled 325 consecutive testicular mass patients who underwent radical orchiectomy (310/325) or testicular preserving surgery (15/325) from January 2001 to June 2016. The clinicopathological factors, including tumor diameter, cryptorchidism history, ultrasound findings, serum alpha-fetoprotein, and human chorionic gonadotropin (HCG) levels, were collected retrospectively for statistical analysis. A predictive nomogram was also generated to evaluate the quantitative probability. Among all patients, 247 (76.0%) were diagnosed with a malignant testicular tumor and 78 (24.0%) with benign histology. Larger tumor diameter (per cm increased, hazard ratio [HR] = 1.284, P = 0.036), lower ultrasound echo (HR = 3.191, P = 0.001), higher ultrasound blood flow (HR = 3.320, P < 0.001), and abnormal blood HCG (HR = 10.550, P < 0.001) were significant predictive factors for malignant disease in all testicular mass patients. The nomogram generated was well calibrated for all predictions of malignant probability, and the accuracy of the model nomogram measured by Harrell's C statistic (C-index) was 0.92. According to our data, the proportion of patients who underwent radical orchiectomy for benign tumors (24.0%) was much larger than generally believed (10.0%). Our results indicated that the diameter, ultrasonic echo, ultrasonic blood flow, and serum HCG levels could predict the malignancy in testicular mass patients.

Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats.

This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg-1 ), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.

[Efficacy of microsurgical vasectomy reversal on patients after vasectomy].

OBJECTIVE: To evaluate the efficacy of microsurgical vasectomy reversal on patients after vasectomy. METHODS: In the study, 41 patients after vasectomy were admitted for microsurgical vasectomy reversal. The mean (range) age was 45 (29 to 66) years for the men. The mean duration of obstruction was 12 years. All the patients were seen by the surgeon for a complete history and physical examination. Semen analyses proved azoopermia, and their serum levels of sexual hormone were normal. They were all offered scrotal exploration. Microvasovasostomy was performed if the sperm was found in the material coming from the proximal vas lumen. The decision for microvasoepididymostomy was made during surgery, if the fluid was creamy, containing only debris or there was no fluid whatsoever when the vas was milked toward the cut end. Microvasovasostomy was performed in 40 patients, of whom 6 were with lateral microvasoepididymostomy and 1 with bilateral microvasoepididymostomy. The initial semen analysis was then done after usually 3 months postoperatively. Patency was arbitrarily defined as>10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. Postoperative patency rate and postoperative impregnation rate were followed. RESULTS: The 41 patients were followed up for 3 to 72 months, and 5 cases were lost. In the 28 patients who had obstructions for less than 15 years, 3 were lost. Sperm was found by semen analysis in 21 patients. Their sperm density was 2×10(6) to 46×10(6) sperms/mL and motility was 0% to 60%. The semen analysis revealed azoospermia in 2 patients after 12 months, who were advised to undergo intracytoplasmic sperm injection. Natural conception occurred in 6 patients followed for more than 12 months. The overall patency rate was 84% (21/25). Among the patients with a follow-up of >6 months, the natural paternity rate was 29% (6/21). In the 13 patients who had obstructions for more than 15 years, 2 were lost. The patency and pregnancy rates were 64% (7/11) and 14% (1/7) respectively. Their sperm density was 0.02×10(6) to 30× 10(6) sperms/mL and motility was 0% to 43%. CONCLUSION: Microsurgical vasectomy reversal is an effective method to treat vasal obstruction due to vasectomy. The patency and pregnancy rates are related to the time of vasectomy. The patency and pregnancy rates are higher in patients with obstruction for less than 15 years than those for more than 15 years.

[Progress of low-energy shockwave therapy in clinical application].

A shock wave is a transient pressure disturbance that propagates rapidly in three-dimensional space. It is associated with a sudden rise from ambient pressure to its maximum pressure. Shock wave therapy in urology is primarily used to disintegrate urolithiasis. Recently, low-energy shock wave therapy (LESWT), which is a novel convenient and cost-effective therapeutic modality, is extended to treat other pathological conditions including coronary heart disease, musculoskeletal disorders and erectile dysfunction. However, the exact therapeutic mechanisms and clinical safety and efficacy of LESWT remain to be investigated. Based on the results of previous studies, it is suggested that LESWT could regulate angiogenesis-related growth factors expression including endothelial nitric oxide synthase (eNOS), vessel endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA), which might induce the ingrowth of neovascularization that improves blood supply and increases cell proliferation and eventual tissue regeneration for restore pathological changes. The further studies on cellular and molecular biological changes by LESWT for clarification its mechanism and clinical safety and efficacy studies are recommended.

Penile prosthesis implantation in Chinese patients with severe erectile dysfunction: 10-year experience.

We retrospectively evaluated the clinical outcome of penile prosthesis implantation (PPI) in Chinese patients with severe erectile dysfunction (SED). From July 2000 to December 2011, 224 patients (mean age: 35.9±11.8 years, range: 20-75 years) with SED underwent PPI by experienced surgeon according to standard PPI procedure at our centre. A malleable prosthesis (AMS 650) was implanted in 45 cases (20.1%), and a three-piece inflatable prosthesis (AMS 700 CXM or AMS 700 CXR) was implanted in 179 cases (79.9%). Surgical outcomes, including postoperative complications, clinical efficacy and couple satisfaction, were evaluated over than 6 months postoperatively using medical record abstraction, IIEF-5, quality of life (QoL) scores, and the patient/partner sexual satisfaction score proposed by Bhojwani et al. Of the 224 patients eligible for the study, 201 subjects (89.7%) completed follow-up. All of patients could perform sexual intercourse post PPI with the mean postoperative IIEF-5 and QoL scores were 20.02±2.32 and 5.28±0.76, respectively, which were significantly improved compared with the preoperative scores (6.29±1.5 and 2.13±0.84, P<0.01). Of the 201 men, mechanical malfunction occurred in four cases (2.0%) and three cases were re-implanted new device, and two cases (1.0%) developed a mild curvature of the penis. Scrotal erosion with infection occurred in one case with diabetes mellitus (0.5%) and required complete removal of the implanted AMS 700 CXM. Satisfactory sexual intercourse at least twice per month was reported by 178 men (88.6%), and overall satisfaction with the PPI surgery was reported by 89.0% of men and 82.5% of partners. Patient satisfaction in the three-piece inflatable prosthesis group was higher than in the malleable prosthesis group (P<0.05). Satisfaction, however, between the types of prostheses, did not differ in the partner survey. PPI is a safe and effective treatment option for Chinese patients with SED and experienced surgeon perform PPI according to standard PPI procedure could reduce the postoperative complications of PPI and could improve patient satisfaction ratio and QoL.

Further evidence of endogenous hydrogen sulphide as a mediator of relaxation in human and rat bladder.

We investigated the expression of hydrogen sulphide (H2S) in human and rat lower urinary tract (including bladder, prostate and urethra) tissues, and we sought to determine whether H2S induces relaxation of human and Sprague-Dawley (SD) rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H2S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H2S, cystathionine ß-synthase (CBS), cystathionine γ lyase (CSE) and 3-mercaptopyruvate sulphur transferase (MPST, as known as 3-MST) by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H2S function with a transducer and recorded. All experiments were repeated six times. The endogenous H2S productivity and the H2S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine (L-Cys, a substrate of CBS, CSE and MPST) elicited relaxation in a dose-dependent manner on human bladder strips pre-contracted by acetylcholine chloride. This effect could be diminished by the ATP-sensitive potassium ion (KATP) channel blocker glibenclamide (GLB), the CSE inhibitor DL-propargylglycine (PPG) and the CBS inhibitor hydroxylamine (HA). H2S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H2S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms (LUTS) or overactive bladder (OAB).

Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats.

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

Commonly used mesenchymal stem cell markers and tracking labels: Limitations and challenges.

Early observations that cultured mesenchymal stem cells (MSCs) could be induced to exhibit certain characteristics of osteocytes and chondrocytes led to the proposal that they could be transplanted for tissue repair through cellular differentiation. Therefore, many subsequent preclinical studies with transplanted MSCs have strived to demonstrate that cellular differentiation was the underlying mechanism for the therapeutic effect. These studies generally followed the minimal criteria set by The International Society for Cellular Therapy in assuring MSC identity by using CD70, CD90, and CD105 as positive markers and CD34 as a negative marker. However, the three positive markers are co-expressed in a wide variety of cells, and therefore, even when used in combination, they are certainly incapable of identifying MSCs in vivo. Another frequently used MSC marker, Stro-1, has been shown to be an endothelial antigen and whether it can identify MSCs in vivo remains unknown. On the other hand, the proposed negative marker CD34 has increasingly been shown to be expressed in native MSCs, such as in the adipose tissue. It has also helped establish that MSCs are likely vascular stem cells (VSCs) that reside in the capillaries and in the adventitia of larger blood vessels. These cells do not express CD31, CD104b, or α-SMA, and therefore are designated as CD34+CD31-CD140b-SMA-. Many preclinical MSC transplantation studies have also attempted to demonstrate cellular differentiation by using labeled MSCs. However, all commonly used labels have shortcomings that often complicate data interpretation. The ß-gal (LacZ) gene as a label is problematic because many mammalian tissues have endogenous ß-gal activities. The GFP gene is similarly problematic because many mammalian tissues are endogenously fluorescent. The cell membrane label DiI can be adsorbed by host cells, and nuclear stains Hoechst dyes and DAPI can be transferred to host cells. Thymidine analog BrdU is associated with loss of cellular protein antigenicity due to harsh histological conditions. Newer thymidine analog EdU is easier to detect by chemical reaction to azide-conjugated Alexa fluors, but certain bone marrow cells are reactive to these fluors in the absence of EdU. These caveats need to be taken into consideration when designing or interpreting MSC transplantation experiments.

Activation of VEGF and ERK1/2 and improvement of urethral function by adipose-derived stem cells in a rat stress urinary incontinence model.

OBJECTIVE: To investigate the injected autologous adipose-derived stem cells (ADSCs) in improving stress urinary incontinence in a rodent model of parturition-related stress incontinence and the possible mechanism. METHODS: The 40 rats were developed stress urinary incontinence models by postpartum balloon dilation of the vagina for 4 hours followed by bilateral ovariectomy. ADSCs were isolated from the peri-ovarian fat and labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU). Twenty stress urinary incontinence rats received peri-urethral injection of phosphate-buffered saline as the negative controls and the other 20 stress urinary incontinence rats received peri-urethral injection of EdU-labeled ADSCc. Twenty control rats underwent sham ovariectomy without balloon dilation and served as positive controls. Four weeks later, voiding function was assessed by cystometry. Urethral histologic examination (Masson trichrome stain, picrosirius red stain, Hart elastin stain, Gordon and Sweet stain, and immunohistochemical stain) and Western blot were performed on urethral tissues. RESULTS: Both leak point pressure and bladder capacity were significantly increased in ADSC-treated rats, compared to the balloon-injured ovariectomized rats. Histologic examination revealed normalized appearance of the fibromuscular structure of the urethra as well as increased peri-urethral blood vessel density in ADSC-treated rats. On Western blot, vascular endothelial growth factor and P-extracellular signal-regulated kinases (ERKs)1/2 protein was expressed at a higher rate in tissues from ADSC-treated rats compared to phosphate-buffered saline-treated rats. CONCLUSION: Peri-urethral injection of ADSCs is associated with more normal urinary function and urethral structure in rats with parturition-related incontinence. The activation of vascular endothelial growth factor and ERK1/2 may be responsible for the paracrine effects from ADSCs.

Effects of icariside II on improving erectile function in rats with streptozotocin-induced diabetes.

Icariin and icariside II (ICA II), 2 active components isolated from herba epimedii, have a closely structural relationship. There is evidence that icariin may be useful in the treatment of erectile dysfunction (ED); however, the study on the therapeutic efficacy of ICA II on ED is currently scant. We investigated the effects of ICA II on improving erectile function of rats with streptozocin-induced diabetes. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into normal control and diabetic groups. Diabetes was induced by a one-time intraperitoneal injection of streptozocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 4 groups including a saline-treated placebo arm and 3 ICA II-treated models (1, 5, and 10 mg/kg/d). After 3 months, penile hemodynamics was measured by cavernous nerve electrostimulation (CNE) with real time intracorporal pressure assessment. Penises were harvested with subsequent histological examination (picrosirius red stain, Hart elastin stain, and immunohistochemical stain) and Western blots to explore the expression of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and transforming growth factor ß1 (TGFß1)/Smad2 signaling pathways. Diabetes significantly attenuated erectile responses to CNE. Diabetic rats had decreased corpus cavernosum smooth muscle/collagen ratio and endothelial cell content relative to the control group. The ratio of collagen I to III was significantly lower in the corpora of diabetic rats; furthermore, cavernous elastic fibers were fragmented in the diabetic animals. Neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase, and vascular endothelial growth factor were expressed at lower levels in the diabetic group; ICA II-treated diabetic rats had higher expression in the penis relative to placebo-treated diabetic animals. Both the TGFß1/Smad2/connective tissue growth factor (CTGF) signaling pathway and apoptosis were down-regulated in the penis from ICA II-treated rats. ICA II treatment attenuates diabetes-related impairment of penile hemodynamics, likely by increasing smooth muscle, endothelial function, and nNOS expression. ICA II could alter corpus cavernosum fibrous-muscular pathological structure in diabetic rats, which could be regulated by the TGFß1/Smad2/CTGF and NO-cGMP signaling pathways.

Icariin ameliorates streptozotocin-induced diabetic retinopathy in vitro and in vivo.

This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two groups; one group received ICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a placebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV), vascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a expression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at various concentrations (0, 10(1), 10(2), 10(3) nmol/mL) on neurite growth were investigated also in retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous pathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as decreased Collagen IV and Müller cell content) were noted in the retinal vessels of diabetic rats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced neurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations are indicated.

Stem cell therapy for erectile dysfunction: a critical review.

Erectile dysfunction (ED) is a prevailing health problem that seriously impacts quality of life. Current treatment options are less effective for patients having cavernous nerve (CN) injury or diabetes mellitus-related ED. These 2 types of ED are thus the main focus of past and current stem cell (SC) therapy studies. In a total of 16 studies so far, rats were exclusively used as disease models and SCs were mostly derived from bone marrow, adipose tissue, or skeletal muscle. For tracking, SCs were labeled with LacZ, green fluorescent protein, 4',6-diamidino-2-phenylindole, DiI, bromodeoxyuridine, or 5-ethynyl-2-deoxyuridine, some of which might have led to data misinterpretation. SC transplantation was done exclusively by intracavernous (IC) injection, which has been recently shown to have systemic effects. Functional assessment was done exclusively by measuring increases of IC pressure during electrostimulation of CN. Histological assessment usually focused on endothelial, smooth muscle, and CN contents in the penis. In general, favorable outcomes have been obtained in all trials so far, although whether SCs had differentiated into specific cell lineages remains controversial. Recent studies have shown that intracavernously injected SCs rapidly escaped the penis and homed into bone marrow. This could perhaps explain why intracavernously injected SCs had systemic antidiabetic effects and prolonged anti-ED effects. These hypotheses and the differentiation-versus-paracrine debate require further investigation.

[Effects of icariin and icariside II on eNOS expression and NOS activity in porcine aorta endothelial cells].

OBJECTIVE: To investigate the effects of icariin and icariside II on eNOS expression and NOS activity in endothelial cells and possible mechanisms using EGFR over-expressed porcine aorta endothelial (PAE) cell line. METHODS: The EGFR gene was transfected into PAE cells and genetic stable cell line (PAE-EGFR) was selected. 12.5 µmol/L of icariin and of icariside II were used to treat the PAE and PAE-EGFR cells respectively for 48 h, the eNOS expression in each group was observed. EGF was also used to treat the cells to observe the regulatory effects of icariin and icariside II on NOS activity. The regulatory effects of icariin and icariside II on NOS activity were also observed, and sildenafil was used as a control. RESULTS: Western blot showed that the basic value of eNOS expression was higher in PAE-EGFR group compared with that in PAE group, both of icariin and icariside II increased the eNOS expression in PAE and PAE-EGFR group (P<0.01), and the value of eNOS expression was higher in PAE-EGFR group than that in PAE group. In the PAE-EGFR cell line, the NOS activity reached (15.37 ± 1.49) u/mg when the concentration of icariside II was 10(-8) mol/L, which was 4.66 u/mg more than that in the PAE cell line. When the concentration reached 10(-7), 10(-6) or 10(-5) mol/L, the change of NOS activity in PAE-EGFR group was greater than that in PAE group (P<0.01). icariin also increased the NOS activity in PAE and PAE-EGFR cells, but the activity was 20% lower compared with icariside II group, however, Sildenafil showed no influence on NOS activity. CONCLUSION: Icariin and icariside II may increase the eNOS expression through activating EGF-EGFR pathway in PAE cell, by which endothelial cells function could be regulated and the better effect was noted in icariside II compared to icariin.

[Factors affecting the results of microsurgical vasoepididymostomy].

OBJECTIVE: To evaluate the intraoperative factors affecting the patency of microsurgical vasoepididymostomy. METHODS: From January 2009 to July 2010, 73 men with obstructive azoospermia had undergone longitudinal intussusception vasoepididymostomy (LIVE). The mean age (range) was 31 years (23 to 48) for the patients and their mean infertility was 50.9 months (2 to 180). All the patients were included in three groups by the clinical variables in surgery: anastomosis number, anastomosis sites, epididymal fluid analysis. Bilateral and lateral anastomosis was in 50 and 23 cases, respectively. The anastomosis on caput, corpus and caudal was in 19, 46, and 8 cases respectively. Motile sperm in the epididymal fuild continuing flowage could be found in 55 patients. By contrast, immotile sperm could be found in 18 patients. Semen analysis was done at the end of 3 months, and patency was arbitrarily defined as >10 000 sperm/mL in ejaculate in at least one semen analysis after surgery. RESULTS: Of all the patients, 53 were followed up. Sperm was present in the ejaculate in 38 patients postoperatively. The overall patency rate was 71.7% (38/53). Patency rates of bilateral surgery and of lateral surgery achieved 80.7% and 27.6%; of caput anastomosis 38.5%, of corpus anastomosis 78.8%, of caudal anastomosis 100%, of motile sperm with epididymal fluid continuing flowage 83.7% and of immotile sperm 40%, respectively. In the study, 17 patients (33.3%, 17/53) reported spontaneous pregnancy. CONCLUSION: Except for microsurgical technology, bilateral anastomosis, corpus or caudal anastomosis, and motile sperm with epididymal fluid continuing flowage may improve patency rate postoperatively.

[Treatments of erectile dysfunction combined with lower urinary tract symptoms associated with benign prostatic hyperplasis].

Lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS) and erectile dysfunction (ED) are common conditions seen in aging males. Although the exact mechanism of ED combined BPH/LUTS is unknown, treatment with α-adrenergic receptor resistance agents (α-ARAs) contributes to some improvement in ED, and phosphodiesterase-5 inhibitors (PDE-5I) are also of benefit to BPH/LUTS. The action mechanisms of these medications support these observed benefits, which are being studied in the basic science and clinical settings. Much remains to be investigated, but it is clear that the associations between BPH/LUTS and ED lay the foundation for future therapies and possible preventative strategies. This article has mainly summarized the advancement of epidemiology, basic research and treatment of ED combined with BPH/LUTS with α-receptor blockers and phosphodiesterase-5 inhibitors.

An open, comparative, multicentre clinical study of combined oral therapy with sildenafil and doxazosin GITS for treating Chinese patients with erectile dysfunction and lower urinary tract symptoms secondary to benign prostatic hyperplasia.

This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction (ED) and lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS). The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 (IIEF-5) scores ≤21 and International Prostate Symptom Score (IPSS) ≥10 points, were enrolled and randomly divided into Group A (168 cases; doxazosin GITS 4 mg once daily plus sildenafil 25-100 mg on demand) and Group B (82 cases; sildenafil 25-100 mg on demand). Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life (QoL) questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.