Morphokinetic features in human embryos: Analysis by our original high-resolution time-lapse cinematography-Summary of the past two decades.

Background: The pioneering work by Dr. Payne et al. in time-lapse cinematography for observation of the morphokinetic features of human embryos inspired us to develop a new in vitro culture system with high-resolution time-lapse cinematography (hR-TLC) back in 2001. Methods: This in vitro culture system was capable of maintaining stable culture and was constructed on an inverted microscope stage. Embryos were observed and photographed noninvasively for an extended period, up to 7 days. The obtained images were displayed at a speed of 30 frames per second and individually analyzed. Results: Using hR-TLC, human fertilization and subsequent embryonic development were visualized, revealing the time course of phenomena and many unusual dynamics. Conclusion: In this review, we summarize the results of our hR-TLC analysis of early human embryonic development over the past 20 years. In the near future, it is expected that the vast amount of information obtained by hR-TLC will be integrated into the AI system for further analysis and to provide feedback that will have the potential to improve clinical practice. In the era of SDGs and environmental awareness, we should be cautious about the direction in which AI can be utilized to avoid any further harm to the planet.

Extent of pelvic lymph node dissection improves early oncological outcomes for patients with high-risk prostate cancer without lymph node involvement after robot-assisted radical prostatectomy.

BACKGROUND: We investigated the effect of the extent of pelvic lymph node dissection (LND) on biochemical recurrence (BCR) in patients with prostate cancer (PCa) without lymph node involvement (LNI) treated with robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed data from 378 patients who underwent RARP with LND at our hospital between October 2010 and June 2019. The BCR-free survival rate was determined using Kaplan-Meier analysis, and Cox regression analysis was used to investigate BCR prognostic factors. The total score calculated from the D'Amico risk classification and the percentage of positive biopsy cores were used for analysis. Patients were classified into 3 BCR risk groups (low risk: 0-3 points, intermediate risk: 4-5 points, and high risk: 6-8 points). RESULTS: Limited LND was performed in 161 patients (42.6%), extended LND in 217 patients (57.4%), and BCR was confirmed in 66 patients (17.5%) after RARP. Both univariate and multivariate analyses showed no significant difference in the association between the extent of LND and BCR. The Kaplan-Meier curve for BCR generated using our risk classification for patients with PCa without LNI showed no significant association between the extent of LND and BCR in the low-risk group (p = 0.790). A significantly improved BCR-free survival was observed in the extended LND group among patients with PCa at intermediate risk or higher (p < 0.05). CONCLUSION: According to our risk classification, BCR may be less likely to occur when extended LND is performed during RARP for patients with localized PCa at intermediate risk or higher.

PDE5 inhibitors and male reproduction: Is there a place for PDE5 inhibitors in infertility clinics or andrology laboratories?

The objective of this review study is to evaluate the therapeutic role of PDE5 inhibitors (PDE5is) in the amelioration of oligoasthenospermia in infertile males. PDE5is have a beneficial influence on the secretory function of the Leydig and Sertoli cells, the biochemical environment within the seminiferous tubule, the contractility of the testicular tunica albuginea, and the prostatic secretory function. In several studies, the overall effect of sildenafil and vardenafil increased quantitative and qualitative sperm motility. Furthermore, some studies indicate that PDE5is influence positively the sperm capacity to undergo capacitation under biochemical conditions that are known to induce the sperm capacitation process. Additional research efforts are necessary in order to recommend unequivocally the usage of sildenafil, vardenafil, or avanafil for the alleviation of male infertility.

Impact of positive surgical margin status in predicting early biochemical recurrence after robot-assisted radical prostatectomy.

BACKGROUND: We investigated the association between positive surgical margin (PSM) status and biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) to develop a prognostic factor-based risk stratification model for BCR. METHODS: We analyzed the data of 483 patients who underwent RARP at our hospital between October 2010 and April 2019; 435 patients without neoadjuvant therapy were finally included. The BCR-free survival rate was determined using Kaplan-Meier analysis. Effects of the PSM status, including the number of PSMs, Gleason score (GS) at a PSM, and the maximum PSM length for BCR, were investigated using Cox regression analysis. RESULTS: BCR was confirmed after RARP in 61 patients (14.0%), and PSM was confirmed in 74 patients (17.0%); PSM was a significant predictor of BCR (p < 0.001). The median number of PSMs was 2 (1-6), and the median maximum length of PSM was 6.0 (2.0-17.0) mm. Multivariable analysis showed lymph node invasion (p < 0.001), GS of ≥ 7 at a PSM (p = 0.022) and a maximum PSM length of > 6.0 mm (p = 0.003) were significant predictors of BCR. We classified the patients without lymph node invasion into good-, intermediate-, and poor-risk groups according to the other two risk factors (presence of 0, 1, and 2 factors, respectively) and rates of 1-year BCR-free survival (100.0, 72.7, and 48.1%, respectively). CONCLUSION: Higher GS at PSM and greater length of PSM were significant predictors of BCR after RARP, and console surgeons should be careful to prevent PSM during RARP.

Intravesical prostatic protrusion may affect early postoperative continence undergoing robot-assisted radical prostatectomy.

BACKGROUND: In this study, we investigated the effect of preoperative prostate morphology, especially intravesical prostatic protrusion (IPP), on continence after robot-assisted radical prostatectomy (RARP). METHODS: Retrospective analysis was applied to patients who underwent RARP between October 2010 and July 2014. The following parameters were assessed in all patients: age, body mass index (BMI), prostate-specific antigen, magnetic resonance imaging and pressure-flow studies findings. The impact of preoperative and intraoperative factors on postoperative urinary incontinence (UI) was assessed using multivariate logistic regression analysis. To evaluate the effects of IPP, the patients were divided into groups according to the IPP length: Group 1, < 5 mm and Group 2, ≥ 5 mm. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, Quality of Life index and the number of pads used were assessed. RESULTS: A total of 119 patients were eligible for this study. Multivariate analyses showed that IPP (odds ratio (OR) 1.14, 95% confidence interval (CI) 1.02-1.28, p < 0.05) and nerve-sparing (NS) (OR 0.23, 95% CI 0.18-0.61, p < 0.01) were significant factors related to UI in the first month after RARP. Twelve months after RARP, multivariate analyses revealed that only NS is a factor related to postoperative UI (OR 0.23, 95% CI 0.18-0.61, p < 0.01). The comparison of Groups 1 and 2 indicated significant differences in age (p < 0.01), prostate volume (p < 0.01), total IPSS and voiding symptom score (p < 0.05), compliance (p < 0.01), and detrusor pressure at maximum flow (p < 0.01). Group 1 had a higher continence rate (38.0%) than Group 2 (20.8%) in the first month after RARP (p < 0.05), but the difference was no longer significant from the third month after RARP. The total IPSS and voiding symptom scores were significantly different between the two groups before RARP, however, the significant difference disappeared from the first month after RARP. CONCLUSIONS: The data suggest that IPP affects early postoperative UI. Although NS was strongly involved in UI in the early and later stages after RARP, IPP had no effect on UI in the later stages.

Small-volume lymph node involvement and biochemical recurrence after robot-assisted radical prostatectomy with extended lymph node dissection in prostate cancer.

BACKGROUND: We investigated prognostic factors for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node (LN) dissection. METHODS: We included 173 patients who underwent RARP with extended pelvic LN dissection without neoadjuvant therapy at our hospital between October 2010 and April 2018. BCR was defined as prostate serum antigen (PSA) levels ≥ 0.2 ng/mL; BCR-free survival rates were determined using Kaplan-Meier analysis. We used Cox regression analysis to evaluate effects of PSA and pathologic variables on BCR. RESULTS: Median follow-up was 27.9 (range 6.1-86.9) months. Five-year BCR-free survival was 89.5%. In multivariate analysis, positive LNs (HR 7.117; 95% CI 2.826-17.925; P < 0.001) and Gleason score (GS) ≥ 8 (HR 2.612; 95% CI 1.051-6.489; P = 0.039) were significant predictors of BCR. Patients with 1 or 2 positive LNs (n = 10) had significantly higher BCR-free survival rates than patients with ≥ 3 positive LNs (n = 5). We, therefore, stratified the patients as low-risk (GS < 8 and no positive LNs), intermediate-risk: (either GS ≥ 8 or positive LNs) and high-risk (both GS ≥ 8 and positive LNs). Their 1-year BCR-free survival rates were low-risk: 94.6%, intermediate-risk: 88.5%, and high-risk: 33.3% (P < 0.05). CONCLUSIONS: Patients with 1-2 positive LNs and GS < 8 have low risk for BCR; close observation without immediate adjuvant hormonal therapy can be considered for these patients.

Effects of a micronutrient supplementation combined with a phosphodiesterase type 5 inhibitor on sperm quantitative and qualitative parameters, percentage of mature spermatozoa and sperm capacity to undergo hyperactivation: A randomised controlled trial.

The main objective of this study was to evaluate the effects of a micronutrient supplementation (MS) combined with avanafil on sperm function. Oligoasthenospermic men (n = 217) were treated daily for 90 days with either an MS (45 men, Group A), l-carnitine (44 men, Group B), MS plus avanafil (43 men, Group C) or avanafil (43 men, Group D); another group of 42 men with oligoasthenospermia (Group E) received no treatment. Sperm parameters were evaluated before and after the end of treatment in each Group A, B, C and D respectively. The same sperm parameters were measured in each participant of Group E before and at the 90-day experimental period. Within Groups A, C or D, the total percentage of motile spermatozoa, the hypoosmotic swelling test (HOST) result and the percentage of hyperactivated spermatozoa after incubation under conditions known to induce sperm capacitation were significantly greater after MS or MS plus avanafil treatment, or avanafil treatment than before the respective treatment. We suggest that MS or MS plus avanafil combined administration or avanafil alone improves sperm membrane permeability with an overall result improvement in sperm motility, outcome of HOST and increase in the percentage of hyperactivated spermatozoa.

Effective treatment of neurogenic detrusor overactivity in multiple sclerosis patients using desmopressin and mirabegron.

INTRODUCTION: Multiple sclerosis (MS) is the commonest progressive neurological disease affecting young people. With advancing disease, management of neurogenic detrusor overactivity (NDO) based on antimuscarinics may prove inadequate and if based on botulinum toxin, may necessitate clean intermittent self-catheterization. The aim of the study was to evaluate the effectiveness of combined mirabegron and desmopressin administration in the treatment of NDO in patients with MS. MATERIALS AND METHODS: Sixty patients diagnosed with MS and NDO were evaluated. All had received treatment with solifenacin 10 mg/daily for 3 months and were displeased with the results. Patients were divided in four groups. In Group A (n = 15) patients continued receiving solifenacin 10 mg/daily; in Group B (n = 15) patients received mirabegron 50 mg/daily; in Group C (n = 15) patients received desmopressin 120 mcg/daily and in Group D (n = 15) patients received mirabegron 50 mg/daily and desmopressin 120 mcg/daily. All patients were assessed with a 3 day bladder diary at the beginning and at the end of the treatment. RESULTS: All patients in Groups A, B and C did not demonstrate statistically significant changes at the end of the treatment period in their 3 day bladder diary and in the presence of urinary infections. In Group D, a statistically significant improvement was noted in the mean change from baseline to end of treatment in micturition episodes (3.5 +/- 0.4 micturition/24h), in urgency episodes (2.3 +/- 0.2) and mean number of urinary incontinence (1.0 +/- 0.2 episodes/24h). CONCLUSIONS: Treatment with mirabegron and desmopressin revealed both effectiveness and safety in patients with NDO and MS.

Testicular torsion-detorsion and potential therapeutic treatments: A possible role for ischemic postconditioning.

Testicular torsion is a common urological emergency among adolescent boys and young men. Rotation of the testis and twisting of the spermatic cord rapidly leads to ischemia, resulting in a loss of germ cells. Thus, prompt diagnosis and urgent surgical intervention are required, but the subsequent release of the torsion induces reperfusion injury, which causes further damage to the ischemic testis. Testicular torsion-detorsion (ischemia-reperfusion) injury triggers the generation of reactive oxygen species, pro-inflammatory cytokines, neutrophil recruitment, lipid peroxidation, anoxia and apoptosis, which carry a significant risk of subsequent infertility. Previously, the effects of numerous pharmacological agents and treatments have been evaluated to prevent testicular ischemia-reperfusion injury in animal models. We propose a new treatment, especially postconditioning, to prevent adverse effects of ischemia-reperfusion injury after testicular torsion-detorsion.

Olmesartan ameliorates urinary dysfunction in the spontaneously hypertensive rat via recovering bladder blood flow and decreasing oxidative stress.

PURPOSE: As hypertension (HT) is one of the risk factors for lower urinary tract symptoms, we investigated the effect of an angiotensin II type I receptor blocker, olmesartan, on bladder dysfunction in the spontaneously hypertensive rat (SHR). MATERIALS AND METHODS: Twelve-week-old male SHRs were administered perorally with olmesartan (0, 1, or 3 mg/kg/day) or nifedipine (30 mg/kg/day) for 6 weeks. Wistar rats were used as normotensive controls. The effects of olmesartan or nifedipine on blood pressure (BP), bladder blood flow (BBF), urodynamic parameters, tissue levels of malondialdehyde (MDA), nuclear factor erythroid 2-related factor 2 (Nrf2), and nerve growth factor (NGF) were measured in the bladder. Localization of 4-hydroxy-2-nonenal (4-HNE), Nrf2, and NGF in the bladder was shown by immunohistochemistry. RESULTS: The SHRs showed significant increase in BP, micturition frequency, and expression of MDA, 4-HNE, Nrf2, and NGF when compared to the control Wistar rats. Conversely, there was a decrease in BBF and single voided volume in SHRs when compared to Wistar rats. Treatment with olmesartan and nifedipine significantly improved BP. However, only olmesartan significantly ameliorated urodynamic parameters and oxidative damage compared to the non-treated SHR. The immunoreactivities of 4-HNE, Nrf2, and NGF in SHR urothelium and blood vessels were increased compared to the control. Treatment with a high dose of olmesartan decreased the expressions of 4-HNE, Nrf2, and NGF in the bladder. CONCLUSION: Our data suggest that BP, BBF, and oxidative stress may be responsible for the functional changes in HT-related bladder dysfunction. Olmesartan significantly ameliorated this bladder dysfunction.

Lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction: are these conditions related to vascular dysfunction?

Although the pathogenesis of lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction is poorly understood and thought to be multifactorial, it has been traditionally recognized that these conditions increase with age. There is increasing evidence that there is an association between cardiovascular disease and lower urinary tract symptoms as well as benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction in elderly patients. Age might activate systemic vascular risk factors, resulting in disturbed blood flow. Hypertension, diabetes, hyperlipidemia and atherosclerosis are also linked to the etiology of lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction. In the present review, we discuss the relationship between decreased pelvic blood flow and lower urinary tract symptoms, benign prostatic hyperplasia/benign prostatic enlargement and erectile dysfunction. Furthermore, we suggest possible common mechanisms underlining these urological conditions.

Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat.

PURPOSE: As increasing evidence suggest that α(1)-blockers prevent benign prostatic hyperplasia related overactive bladder and nocturia in the human, we investigated the effects of silodosin and naftopidil on hypertension-related bladder dysfunction in the spontaneously hypertensive rat (SHR) model. MATERIALS AND METHODS: Twelve-week-old male SHRs received no treatment or treatment with silodosin (100 µg/kg, p.o.) or naftopidil (10 or 30 mg/kg, p.o.) once daily for 6 weeks. Wistar rats were used as normotensive controls. After 6-week treatment, voiding functions were estimated by metabolic cages (dark- and light-cycle separately) and cystometric studies. Furthermore, the bladder blood flow (BBF) was measured employing the hydrogen clearance method. RESULTS: SHRs showed significant increases in micturition frequency, and decreases in BBF and single voided volume in both metabolic cages and cystometrograms compared to the Wistar group. Treatment with silodosin normalized the decreased BBF, and treatment with naftopidil increased the BBF in a dose-dependent manner in the SHR group. Although treatment with silodosin and the high dose of naftopidil significantly inhibited micturition frequency in one day, only treatment with the high dose of naftopidil significantly inhibited micturition frequency and urine production in the light-cycle compared to the non-treated SHRs. Although treatment with silodosin and the high dose of naftopidil significantly increased single voided volume, only treatment with silodosin significantly inhibited non-voiding contractions in the cystometrgrams. CONCLUSION: Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production.

Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring.

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father's age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father's age contributes to his offspring's higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father's advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father's advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring's diseases is crucial, so that they can be effectively guided through their reproductive years.

Antioxidant treatment with edaravone or taurine ameliorates diabetes-induced testicular dysfunction in the rat.

Diabetes mellitus with the subsequent generation of reactive oxygen species represents a major risk factor for testicular dysfunction (TD). We investigate whether administration of antioxidants edaravone and taurine could prevent type 1 diabetes-induced TD in the rat. Six-week-old male Wistar rats were divided into four groups. Group A was treated with citrate-phosphate buffer plus normal saline, whereas in the other three groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally). Subsequently, the diabetic rats were treated for 4 weeks either with normal saline (group B), edaravone (10 mg/Kg/day, intraperitoneally; group C), or taurine (500 mg/Kg/day, intraperitoneally; group D). Body, testicular, and epididymal weight, serum glucose, malondialdehyde levels, 8-Hydroxy-2'-deoxyguanosine(8-OH-dG) levels, testicular catalase activity, and serum testosterone levels were determined. Histological examination and the Johnsen score were used to observe and evaluate, respectively, the morphological changes in the testes. TUNEL assay was used to examine DNA fragmentation. Mating studies were performed in order to evaluate the fertility potential of male rats in each group. Edaravone or taurine treatment prevented significantly the decreased body, testicular, and epididymal weight induced by diabetes. Moreover, edaravone or taurine significantly decreased the diabetes-induced malondialdehyde levels, 8-OHdG levels, the morphological damage, and the number of apoptotic cells. Taurine, but not edaravone, increased significantly the testicular catalase activity. The antioxidant treatment had no effect on the fertility potential of the diabetic rats. The morphological damage, increased lipid peroxidation, and apoptosis in testicular tissue can be significantly relieved by edaravone or taurine treatment through suppressing the increased oxidative stress in the rat testis.

Effect of silodosin on detrusor overactivity in the male spontaneously hypertensive rat.

UNLABELLED: Recently, several studies have suggested that detrusor overactivity (DO) is the result of bladder ischaemia. Hypertension could affect pelvic arterial blood flow, resulting in loss of smooth muscle in the bladder with resultant loss of bladder compliance. Spontaneously hypertensive rats are considered a valuable tool for exploring the pathogenesis of DO. Some reports indicate that α(1) adrenoceptor antagonists improve chronic ischaemia of the lower urinary tract in patients with LUTS, with concomitant improvement of their symptoms as well as improvement of DO through an increased bladder blood flow (BBF) in the rat with bladder outlet obstruction. However, the mechanism of improvement of silodosin on storage or irritative symptoms is not well investigated and is still unclear. Silodosin prevents hypertension-related DO in the SHR via several possible mechanisms. One possible mechanism of the efficacy of silodosin to the DO includes the improvement of the BBF. OBJECTIVE: To investigate the effect of the α(1A) selective adrenoceptor antagonist, silodosin, on hypertension-related detrusor overactivity (DO) and its possible mechanism in spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: Twelve-week-old male SHRs received treatment with silodosin (100 µg/kg perorally) once daily for 6 weeks; vehicle-treated Wistar rats and vehicle-treated SHRs were used for our study. Six weeks after silodosin treatment, voiding functions were estimated by voiding behaviour and cystometric studies in all groups. The bladder blood flow was measured by the hydrogen clearance method, and tissue levels of nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the expressions of α1 adrenoceptor subtype mRNAs in the bladder were investigated by real-time PCR method. RESULTS: The SHRs showed significant increases in blood pressure, micturition frequency and tissue levels of NGF and CGRP in the bladder. Moreover, the SHRs showed significant decreases in bladder blood flow and single voided volume estimated by both voiding behaviour and cystometric studies compared with those in the Wistar rats. Six weeks of treatment with silodosin significantly ameliorated hypertension-related alterations of these variables with concomitant small changes of blood pressure. The expression levels of α1 adrenoceptor subtype mRNAs in the bladder were similar in all the groups and the rank order was α1A = α1D > α1B in all groups. However, there were no significant differences in the expressions of α(1A) adrenoceptor mRNAs between any groups. CONCLUSION: The data in the present study suggest that silodosin normalizes hypertension-related DO in SHRs, which could be related to its effect on the increased blood flow in the bladder.

Pharmacological preconditioning of ATP-sensitive potassium channel openers on acute urinary retention-induced bladder dysfunction in the rat.

UNLABELLED: What's known on the subject? and What does the study add? Acute urinary retention (AUR) and catheterization for AUR (AURC) or drainage of the urine is a well established cause of bladder dysfunction. Previously, we reported that the induction of AURC significantly reduced contractile responses to both carbachol and KCl compared with a control group, and that this reduction was prevented by nicorandil and cromakalim in a dose-dependent manner; however, although we reported a possible beneficial effect of nicorandil and cromakalim on bladder dysfunction caused by AURC, its molecular mechanism is still unknown. Our study establishes that nicorandil and cromakalim, but not glibenclamide, prevent AURC-induced bladder dysfunction via up-regulation of both K(IR)6.1 and K(IR)6.2 with a subsequent decrease in oxidative stress and decreased induction of apoptosis in the bladder. OBJECTIVE: To investigate whether ATP-sensitive potassium (K(ATP)) channel openers prevent bladder injury after acute urinary retention (AUR) and subsequent catheterization for AUR (AURC) in the rat. MATERIALS AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into five groups: a sham-operated control group, an AUR group, and three AUR groups treated with: nicorandil (10 mg/kg); cromakalim (300 µg/kg); or glibenclamide (5 mg/kg). AUR was induced by intravesical infusion of 3.0 mL of saline via cystostomy with simultaneous clamping of the penile urethra and, after 30 min of AUR, the bladder was allowed to drain for 60 min. After the experimental period, bladder function was assessed using organ bath techniques (carbachol and KCl), and by measuring tissue levels of 8-isoprostane, a marker of oxidative stress. The participation levels of K(ATP) channel pores were investigated using ELISA and real-time PCR methods, respectively. The degree of apoptosis was estimated using the TUNEL method in the bladder smooth muscle and epithelium. RESULTS: The AURC group showed significantly decreased contractile responses to carbachol and KCl, and significant increases in tissue 8-isoprostane levels and apoptosis index in the epithelium compared with the control group. Nicorandil and cromakalim, but not glibenclamide, significantly prevented these AURC-induced alterations. The expressions of K(IR)6.1 and K(IR)6.2 mRNAs were significantly up-regulated by the induction of AURC. Nicorandil and cromakalim, but not glibenclamide, significantly up-regulated expressions of K(IR)6.1 and K(IR)6.2 mRNAs in the bladder compared with the AUR group. CONCLUSION: Our data indicate that nicorandil and cromakalim, but not glibenclamide, prevent AURC-induced bladder dysfunction via activation of K(ATP) channels, with a subsequent decrease in oxidative stress and decreased induction of apoptosis.

Hydroxyfasudil ameliorates penile dysfunction in the male spontaneously hypertensive rat.

Hypertension represents a major risk factor for erectile dysfunction. Although the etiology of hypertension-induced erectile dysfunction is multifactorial and still unknown, Rho-Rho kinase pathway is one of the key factors. To investigate whether administration of hydroxyfasudil, a Rho kinase inhibitor could prevent dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the SHR (spontaneously hypertensive rat), twelve-week-old male SHRs were treated with hydroxyfasudil (3 or 10 mg/kg, i.p.) once a day for 6 weeks. Wistar rats and SHRs treatment with vehicle were used as age-matched controls. Penile cGMP concentrations and Rho kinase activities were determined, and penile function was estimated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The participation mRNA levels of eNOS and participation protein levels of eNOS and phosphorylated eNOS were investigated by quantitative real-time PCR methods and immunoblot analysis, respectively. The SHR showed significantly decreased cGMP concentrations, increased Rho kinase activities, norepinephrine-induced hyper-contractions, and acetylcholine-induced hypo-relaxations in the penile tissue. Treatment with hydroxyfasudil significantly improved the decreased penile cGMP concentrations, the increased Rho kinase activities, the increased norepinephrine-induced contractions, and the decreased acetylcholine-induced relaxation in a dose-dependent manner. Although there were no significant differences in expression protein levels of eNOS among any of the groups, down-regulation of eNOS mRNAs as well as phosphorylated eNOS were significantly ameliorated after treatment with hydroxyfasudil. Our data suggest that hydroxyfasudil ameliorates hypertension-associated dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle possibly via inhibition of the Rho-Rho kinase pathway and activation of NO-eNOS pathway in the SHR.

Nicorandil ameliorates hypertension-related bladder dysfunction in the rat.

AIMS: There is increasing evidence that ischemia is one of the main etiology in overactive bladder (OAB), and that nicorandil prevents OAB. We investigated the effect of nicorandil on hypertension-related bladder dysfunction in spontaneously hypertensive rats (SHRs). METHODS: Twelve-week-old SHRs received six-weeks treatment with nicorandil (0, 3, or 10 mg/kg, i.p. every day). Wistar rats were used for normotensive controls. Six weeks after nicorandil treatment, the bladder blood flow was estimated by hydrogen clearance method, and the bladder functions were estimated by voiding behavior studies and functional studies. Tissue levels of nerve growth factor (NGF) were measured by ELISA method. Furthermore, the participation levels of K(ATP) channel pores were investigated by real-time PCR. RESULTS: SHRs showed significant increases in blood pressure, micturition frequency, tissue levels of NGF and expressions of both K(IR) 6.1 and K(IR) 6.2 mRNAs, and a significant decrease in the bladder blood flow. The carbachol-induced contractile responses were similar in all groups. Although both doses of nicorandil failed to decrease the blood pressure, nicorandil significantly decreased the micturition frequency, tissue levels of NGF and increased the bladder blood flow in a dose dependent manner. The expressions of K(IR) 6.1 and K(IR) 6.2 mRNAs were slightly up-regulated by the low dose of nicorandil, whereas the high dose of nicorandil significantly up-regulated those expressions compared to non-treated SHRs. CONCLUSIONS: These data indicate that nicorandil prevents hypertension-related bladder dysfunction in the SHR, which may be related to its effect on the increased blood flow in the bladder.

Evaluation of Overactive Bladder Symptoms in Patients Recovering from Post-Acute COVID-19 Syndrome.

Purpose: Coronavirus disease (COVID-19) is a multi-organ viral infection with many manifestations. However, its impact on the genitourinary system is nowadays under investigation. This study aimed to evaluate the consequences on bladder function in patients suffering from post-acute COVID-19 syndrome (PACS) transferred to inpatient rehabilitation for long-term care after initial treatment for COVID-19 pathophysiology. Materials and Methods: All the patients were initially asked the question (after having recovered from the acute stage of COVID-19 disease): "Have you noticed a sudden, uncontrolled need to urinate and sometimes a urine leakage accompanying the voiding desire?" Sixty-six out of 147 patients responded positively to this question and were assessed with the AUA Urology Care Foundation Overactive Bladder Assessment Tool (AUA-OAB-tool). All included men were evaluated with the IPSS score. Results: The median age of patients was 59.5 (range 44-72). We identified 44 patients with newly diagnosed OAB (Group A; post-COVID assessment) and 22 with worsening OAB symptoms (Group B). The mean symptom score ± standard deviation in Group A patients was 18.25 ± 2.11 (using the above AUA OAB tool). In the patients of Group B, there was an increase in the above score from 10.43 ± 1.52 (pre-COVID condition) to 17.87 ± 1.89 (post-COVID assessment). In patients of Group A, the total quality of life (QOL) score was 17.74 ± 2.34. Patients in Group B presented an escalation in total QOL score from 9.04 ± 1.41 (pre-COVID) to 18.84 ± 1.96 (post-COVID condition). There was no statistically significant difference in symptoms and QOL scores between men and women in groups A and B. There were 11 men in Group A and 5 in Group B with an IPSS score >20. Conclusion: OAB symptoms may be essential to PACS syndrome and influence quality of life, delaying full recovery.

Varicoceles in Men With Non-obstructive Azoospermia: The Dilemma to Operate or Not.

The knowledge on male reproduction is constantly expanding, especially in treating infertility due to non-obstructive azoospermia (NOA). Varicocele is occasionally diagnosed in a subpopulation of males with NOA. Varicocele repair in NOA-men may contribute to the reappearance of spermatozoa in semen. However, spontaneous pregnancies are observed in only a small percentage of NOA-men post-varicocelectomy. Additionally, it has been reported that the repair of varicocele in NOA-men (before the performance of sperm retrieval techniques) may increase the testicular sperm recovery rate. In addition, it increases the pregnancy rate in intracytoplasmic sperm injection (ICSI) programs in NOA-men without spermatozoa in the semen post-varicocelectomy. In addition, to the improvement in Sertoli cellular secretory function, varicocelectomy may increase the secretory function of Leydig cells, which subsequently results in improved androgen production, raising the probability to negate the need for testosterone replacement therapy in cases of late-onset hypogonadism. On the other hand, the benefit of varicocelectomy in patients with NOA is still debatable. The current review study aims to provide a critical and extensive review of varicocele repair in males with NOA. This study additionally focuses on the impact of varicocele repair on sperm retrieval rates and its influence on the ICSI outcomes for those couples who remain negative for spermatozoa in their semen samples post-varicocelectomy.