Ko Kobayashi

Ejaculatory disorder caused by alpha‐1 adrenoceptor antagonists is not retrograde ejaculation but a loss of seminal emission

Aim: The etiology of the ejaculatory disorder induced by alpha‐1 blockers is still controversial, although it has been suggested to be retrograde ejaculation. The aim of this study was to investigate the distribution of alpha‐1 adrenoceptor subtype mRNA in human seminal vesicles, and to analyze the prevalence and etiology of the disorder in healthy men.

Inhibition of Seminal Emission Is the Main Cause of Anejaculation Induced by a New Highly Selective α1A-Blocker in Normal Volunteers

INTRODUCTION Recent studies have highlighted the influence of alpha1-adrenoceptor antagonists on ejaculatory function. AIM We evaluated the effect of a new, highly selective alpha1A-blocker, silodosin, on ejaculatory function of normal volunteers. METHODS The study included 15 healthy male urologists who voluntarily participated in the study. They took 4 mg of silodosin or a placebo twice daily for 3 days in a randomized, double-blind crossover design. MAIN OUTCOME MEASURES We investigated the ejaculatory volume, sperm count in urine after ejaculation, and fructose concentration in seminal plasma before and after administration of the agents. RESULTS All volunteers on silodosin had a complete lack of ejaculation. Three days after completion of silodosin, the mean ejaculatory volume recovered to the baseline level. There was no sperm in urine after ejaculation under silodosin administration in any volunteer. CONCLUSIONS All volunteers on silodosin had anejaculation and did not show post-ejaculate sperm in their urine. The mechanism of ejaculatory dysfunction caused by silodosin is a loss of seminal emission.

Orgasm is preserved regardless of ejaculatory dysfunction with selective α1A-blocker administration

We evaluated whether ejaculatory dysfunction induced with a selective α1A-blocker influenced orgasm. Fifteen healthy male volunteers took silodosin or a placebo in a randomized, double-blind crossover design. We investigated the ejaculatory volume before and after administration of the agents. After each ejaculation, participants self-reported the answers to an original questionnaire, which was about discomfort on ejaculation, orgasm and satisfaction with the discomforting ejaculation. All participants on silodosin had a complete lack of seminal emission and expulsion. All participants felt orgasm in spite of a complete lack of seminal emission. Of the 15, 12 (80%) who had a somewhat uncomfortable feeling during orgasm were dissatisfied with this feeling, although 9 of the 12 reported that its degree was mild. Orgasm is preserved regardless of the loss of seminal emission with silodosin administration. Although most participants reported mild discomfort during orgasm, they were greatly dissatisfied with the loss of seminal emission.

Outcome analysis for conservative management of peyronie's disease

Background:  We retrospectively analysed the outcomes of conservative management of Peyronies disease and determined the factors predicting successful outcome.

Erectile dysfunction following nerve‐sparing radical retropubic prostatectomy and its treatment with sildenafil

Abstract  Background:  We retrospectively evaluated the erectile function after nerve‐sparing radical retropubic prostatectomy (RRP) and the efficacy of sildenafil for erectile dysfunction (ED) following RRP according to the preoperative erectile function.

Acute Normovolemic Hemodilution for Radical Retropubic Prostatectomy and Radical Cystectomy

OBJECTIVES Radical retropubic prostatectomy (RRP) and radical cystectomy (RCx) are well tolerated and widely performed. Because intraoperative blood loss is one of the most common problems, we performed acute normovolemic hemodilution (ANH) to prevent allogenic blood transfusion (ABT). In this study we tried to clarify the safety, effectiveness and problems of ANH at urologic operations. METHODS The study included 169 patients who underwent RRP and 97 patients underwent RCx from April 2003 to March 2006. The eligible patients for ANH were required to have preoperative hemoglobin of 12 g/dL or more without history of myocardial ischemia. The amount of blood collected was 800 mL in RRP and 800 mL or 1200 mL in RCx. Neoadjuvant chemotherapy was performed in 11 (11.3%) of 97 patients with RCx. RESULTS ANH was available in 164 (97.0%) of 169 patients in RRP and 41 (42.3%) of 97 patients in RCx. All 11 (11.3%) patients who received neoadjuvant chemotherapy before RCx revealed anemia and all were excluded from ANH. No patients had an hypovolemic event develop during the autologous blood being stored. The median volume of intraoperative blood loss was 1400 mL in 164 RRP and 19 patients (11.6%) required ABT. In 41 patients undergoing RCx, the median volume of blood loss was 1720 mL and 13 patients (32.5%) required ABT. In the postoperative period, no patients had cardiovascular or pulmonary complications develop originated from ANH. CONCLUSIONS ANH is a safe and useful method of transfusion during RRP and RCx. ANH can be recommended for patients who need these operations.

Inhibition of Interleukin‐6 Attenuates Erectile Dysfunction in a Rat Model of Nerve-Sparing Radical Prostatectomy

INTRODUCTION The precise mechanisms underlying erectile dysfunction (ED) occurring after cavernous nerve (CN)-sparing surgery remain to be determined. Aim.  To evaluate the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) after CN injury, and the effect of inhibiting IL-6 bioactivity on nerve injury-related ED. METHODS Male Sprague-Dawley rats were divided into three groups: sham operation; bilateral CN dissection without crushing or cutting; and bilateral CN resection. In the interventional experiment, male rats underwent bilateral CN dissection, and anti-rat IL-6 antibody in phosphate-buffered saline (PBS) or vehicle alone was injected intraperitoneally immediately and 24 hours after CN dissection. MAIN OUTCOME MEASURES One, 3, 7, 28, and 56 days after surgery, the expression of IL-6 and IL-6R in the major pelvic ganglion (MPG) was examined by real-time polymerase chain reaction. In the interventional experiment, erectile function was assessed by determining intracavernous pressure divided by arterial pressure (ICP/AP) during electrical pelvic nerve stimulation at 4 weeks after surgery in the anti-IL-6-injected rats and PBS-injected rats. The degree of nerve injury was also evaluated by retrograde dye tracing with Fluorogold. RESULTS The expression levels of IL-6 and IL-6R were increased in the early period of CN injury, as compared with the sham group. IL-6 expression on day 1 was particularly enhanced. Four weeks after CN dissection, the anti-IL-6 group had greater ICP/AP and more FG-positive cells than the PBS group. CONCLUSIONS Expression levels of IL-6 in the MPG were increased in the acute phase following CN injury. Inhibition of IL-6 bioactivity attenuated ED following CN dissection. Thus, the suppression of excess inflammatory responses in the acute phase may lead to improvements in ED occurring after nerve-sparing radical prostatectomy.

Nerve injury‐related erectile dysfunction following nerve‐sparing radical prostatectomy: A novel experimental dissection model

Objectives:  To establish a new experimental rat model in order to define the mechanisms of erectile dysfunction (ED) and to evaluate the changes of neuronal nitric oxide synthase (nNOS) in the pelvic ganglia following nerve‐sparing radical prostatectomy.

Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury

INTRODUCTION We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model. METHODS Male Sprague-Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 10(6) cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbeccos modified Eagles medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium). MAIN OUTCOME MEASURES To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction. RESULTS The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05). CONCLUSION Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

Age-related alteration of neurturin receptor GFRa2 and nNOS in pelvic ganglia.

Neurturin is a neurotrophic factor that is widely expressed in cavernous tissue and retrogradely transported to penis-projecting neurons via its receptor, glial cell line derived neurotrophic factor family receptor alpha-2 (GFRa2). To investigate the influence of aging on neural function on the penis, we examined the expression of GFRa2 mRNA in the major pelvic ganglion and its relationship to neuronal nitric oxide synthase (nNOS)- and tyrosine hydroxylase (TH)-positive neurons. GFRa2 and nNOS mRNA expression levels in RT-PCR showed age-related decreases in 1-, 3-, 6-, 12-, 18- and 24-month-old rats. In situ hybridization also revealed that the number of GFRa2-positive neurons in pelvic ganglia decreased with aging. A double-labeling study revealed the co-expression of GFRa2 and nNOS, which simultaneously decreased in old adult (24 months) and young castrated rats compared with young adult rats (3 months). These results suggest that aging and castration influence the numbers of nNOS- and GFRa2-positive neurons. Higher age might affect not only cavernous tissue but also the neural plasticity of the cavernous nerve related to erectile function.