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Objective: To examine whether a history of nocturnal enuresis affects nighttime urinary frequency and to evaluate nocturia etiologies in adults.Materials and Methods: A total of 143 participants with at least one episode of nocturia per night were included in this study. The self-reported questionnaire collected data on demographic characteristics, medical history, history of nocturnal enuresis in elementary school, lower urinary tract symptoms, and frequency-volume charts.Results: A history of nocturnal enuresis was observed in 52.4% of participants. However, night-time urinary frequency was significantly lower in participants with a history of nocturnal enuresis in elementary school than in those without such history. On multivariate analysis, a history of nocturnal enuresis was also negatively associated with nighttime urinary frequency (P <.01). There was a collinearity effect between age and nighttime urinary frequency. A history of nocturnal enuresis did not affect the presence of nocturnal polyuria or overactive bladder in participants. However, sleep disturbances were fewer in participants with a history of nocturnal enuresis (odds ratio 0.404).Conclusion: A history of nocturnal enuresis might be negatively associated with nighttime urinary frequency due to fewer sleep disturbances. Further, progression of nocturia may depend on conditions, such as age and acquired diseases. [ABSTRACT FROM AUTHOR]

Aims To confirm the mechanisms of age-associated detrusor underactivity (DU), we examined the differences in bladder activity and connexin-43 (Cx43)-derived gap junctions in the bladders of young and old rats. Main methods Female Sprague–Dawley rats aged 3 months (young) and 12 months (old) were used. Continuous cystometry was performed under urethane anesthesia in both ages of rats. In addition, isovolumetric cystometry was performed in young rats during the intravesical application of carbenoxolone, a gap junction blocker, to confirm the role of gap junction proteins in the bladder. Western blotting analyses were performed to assess Cx43 protein expression in the bladders of both groups of rats. Bladders were also analyzed using Masson's trichrome staining and immunostaining for Cx43. Key findings Cystometric evaluations revealed that compared with young rats, bladder contractility was reduced by 27% and residual urine volume was significantly increased in old rats. However, the intercontraction intervals did not differ between the two groups. Under isovolumetric conditions, bladder contraction was suppressed after the intravesical application of carbenoxolone. In the bladders of old rats, increase of smooth muscle cell hypertrophy and fibrous tissue was observed compared with young rats. In association with these findings, immunostaining for smooth muscle Cx43 and its protein level were decreased by 28% compared with young rats. Significance These results suggest that age-related DU might be caused by the downregulation of gap junctional intercellular communication in the bladder. Consequently, the normal signals that contribute to voiding function might not be transported between detrusor muscles. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To confirm the role of alpha1-adrenoceptor (α1-AR) in the spinal cord, we investigated the effect of intrathecal application of terazosin, a non-selective α1-AR blocker, on the micturition reflex, as well as the change of α1-AR subtypes mRNA in the lumbosacral spinal cord using spinal cord injury (SCI) rats. Main methods: Adult female Sprague–Dawley rats were used 4weeks after Th9–10 spinal cord transection. 1) Continuous cystometry was performed under an awake condition to examine the effect of intrathecal terazosin, a non-selective α1-AR blocker, at the level of L6-S1 spinal cord. 2) We also investigated the effect of intravenous phenylephrine, an α1-AR agonist, with or without intrathecal terazosin. 3) Quantification of α1-AR subtype mRNA in the L6-S1 lumbosacral spinal cord was performed in normal and SCI rats. Key findings: 1) Terazosin (0.01–10μg) inhibited the number of non-voiding bladder contractions, and increased bladder capacity by 73%. 2) Phenylephrine (0.1mg/kg) reduced bladder capacity by 17%, and voiding efficiency by 20%. Intrathecal terazosin blocked the effect of intravenous phenylephrine. 3) α1-AR subtype mRNA levels was all increased after SCI. Significance: These results suggest that α1-AR facilitates the micturition reflex in the spinal cord, and α1-AR blockers applied in the lumbosacral spinal inhibits this effect. Upregulation of α1-AR in the lumbosacral spinal cord could be involved in the genesis of detrusor overactivity after SCI. Therefore, if α1-AR blockers pass the blood–brain barrier, they could act in the spinal cord to improve storage function in patients with detrusor overactivity (DO). [Copyright &y& Elsevier]

Objectives: To investigate the effects of various muscarinic acetylcholine receptor (mAChR) antagonists, including selective M2 and M3 mAChR antagonists, on bladder overactivity. It has been proposed that the urothelium modulates the activity of bladder afferent pathways. However, the differential roles of mAChR subtypes in local bladder afferent activation remain unclear. Methods: Cystometry was performed in urethane-anesthetized female rats. We examined the effects of intravesical administration of antimuscarinic agents (nonselective mAChR antagonists: atropine sulfate, tolterodine tartrate, and propiverine hydrochloride; M2-selective antagonists: dimethindene maleate and methoctramine hemihydrate; M3-selective antagonists: darifenacin hydrobromide and 4-DAMP) on bladder overactivity induced by oxotremorine-M (oxo-M; nonselective mAChR agonist). Results: Intravesical administration of oxo-M (200 μM) elicited bladder overactivity as evidenced by decreased intercontraction interval, bladder capacity, and pressure threshold. These effects were blocked by intravesical administration of nonselective or M2-selective antagonists (30-60 μM), whereas M3-selective antagonists (150 μM) did not suppress the overactivity. When instilled intravesically by itself, none of the antimuscarinic agents (nonselective, M2-selective or M3-selective antagonists) affected any cystometric parameters. Conclusions: The M2 mAChR subtype plays an important role in the local cholinergic modulation of bladder afferent activity that contributes to bladder overactivity in normal rats. Therefore, it is expected that antimuscarinic agents that have antagonistic activity against M2 mAChR can be more beneficial for the treatment of patients with overactive bladder if enhanced acetylcholine mechanisms are involved in pathogenesis of overactive bladder. [Copyright &y& Elsevier]

We examined age-associated changes in bladder and urethral coordination involving the nitric oxide (NO)/soluble guanylyl cyclase (sGC) system, which induces urethral smooth muscle relaxation, and urethral ischemic/oxidative stress changes in rats. Sixteen female Sprague-Dawley rats were divided into young (3 months old) and middle-aged (12–15 months old) groups. Urethral activity was evaluated by simultaneously recording intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) under urethane anesthesia. Sodium nitroprusside (SNP, 0.1 mg/kg), an NO donor, and BAY 41-2272, a novel NO-independent stimulator of sGC (0.1 mg/kg), were administered intravenously to both groups. N-nitro- l -arginine methyl ester hydrochloride (l -NAME, 100 mg/kg) was also injected intravenously, to inhibit NO synthase activity in both groups. Staining for the ischemic marker, hypoxia-inducible factor-1α (HIF-1α), and the oxidative stress markers, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), was performed on tissue sections of the urethra, in both groups. Baseline UPP and UPP changes were significantly lower in middle-aged rats than in young rats. After administration of SNP and BAY 41-2272, baseline UPP and UPP nadir were significantly decreased in both groups. After administration of l -NAME, UPP change/bladder contraction amplitude in young rats was still lower than at baseline but was completely restored to control levels in middle-aged rats. Immunoreactivity of HIF-1α, 8-OHdG, and MDA was higher in middle-aged rats than in young rats. Age-associated ischemic and oxidative stress in the urethra might be correlated with impairment of the NO/sGC system and with coordination of the bladder and urethra. [ABSTRACT FROM AUTHOR]

A male newborn was referred to our institute for postrenal acute renal failure with bilateral hydroureteronephrosis, electrolyte imbalance, and anuria. Voiding cystourethrography revealed no vesicoureteral reflux or posterior urethral valves. We performed bilateral percutaneous nephrostomy on the 9th post-natal day. The serum creatinine level improved to the normal range. Antegrade pyelography revealed bilateral uretero-vesical junction stenosis. Subsequently, we inserted bilateral double J urethral stents at 1 month. Bilateral ureteroneocystostomy without ureteral folding was performed at 6 months. The postoperative course was uneventful. This is the second case of postrenal acute renal failure with bilateral primary obstructive megaureters in a neonate. [ABSTRACT FROM AUTHOR]

To investigate the postoperative long-term prognosis and the factors predicting the renal function of patients with reflux nephropathy. As the serum creatinine (s-Cr) level tends to increase during infancy, the degree of reflux and renal parenchymal damage are thought to be more important factors in pediatric patients than in older patients. This study examined s-Cr, urinary protein, and blood pressure of patients who underwent anti-reflux surgery 10 years before. It also calculated the postoperative estimated glomerular filtration rate (eGFR) and examined the correlation between the eGFR and preoperative factors (age, gender, number of urinary tract infections [UTIs], primary diagnosis, reflux grade, percentage of dimercaptosuccinic acid uptake, degree of renal parenchymal damage, s-Cr abnormality, proteinuria, and hypertension), and analyzed the factors associated with the long-term prognosis. The study population was 51 infants (37 boys and 14 girls). The mean age of the patients before surgery and at the follow-up examination was 3.41 ± 3.61 and 14.63 ± 3.74 years, respectively. After surgery, the s-Cr, urinary protein, and blood pressure values showed (44.7%, 26.7%, and 18.2%, respectively) were abnormal. The postoperative eGFR was a mean 90.27 ± 20.42 ml/min/1.73 m2 and primary correlated with an older age (P = 0.0361), no UTI at the primary diagnosis (P = 0.0044), reflux grade ≥8 (P = 0.0180), degree of renal parenchymal damage (group ≥2b, P < 0.0001), s-Cr abnormality (P < 0.0001), and proteinuria (P = 0.0001) at baseline. A total of 20 patients had chronic kidney disease (CKD; Fig. 1). The multiple regression analysis of these factors revealed that an older age (P = 0.0021), reflux grade ≥8 (P = 0.0134), and degree of renal parenchymal damage (group ≥2b, P < 0.0001) were significantly associated with the long-term postoperative prognosis of reflux nephropathy. Using these three factors, this study derived a multiple regression equation estimating eGFR in the 10th year after surgery (Fig. 1). In this study, severe vesico-ureteral reflux (reflux grade ≥8) and severe renal parenchymal damage (group ≥2b) were associated with a long-term decrease in the eGFR. In particular, renal parenchymal damage was closely correlated with the postoperative eGFR; thus, this was clearly a critical factor. The age at surgery showed a better correlation with the postoperative eGFR in the multiple regression analysis; thus, age was regarded as an independent prognostic factor. The age, reflux grade, and degree of renal parenchymal damage at baseline were factors that affected the long-term postoperative prognosis of reflux nephropathy. Patients with high-grade reflux and severe renal parenchymal damage were more likely to show a reduced CKD level at 10 years after anti-reflux surgery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI). Methods: Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction. Results: At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats. Conclusion: Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI. [Copyright &y& Elsevier]

Abstract: We report a 12-year-old girl with renal cell carcinoma originating in a cyst of the left kidney. Ultrasonography revealed 2 small hyperechoic masses in the luminal side of a cyst. Although hypervascularity was not detected in the cyst by computed tomography, the possibility of malignancy could not be ruled out because of the presence of 2 solid masses. Therefore, partial left nephrectomy was performed. On histopathologic examination, the 2 solid masses within the cyst were found to be renal cell carcinoma. This patient remains disease-free at 4 years after partial nephrectomy. [Copyright &y& Elsevier]

Objectives: We investigated the effects of an arginase inhibitor on bladder overactivity and measured bladder arginase I and II mRNA levels in rats with chronic spinal cord injury (SCI). Methods: We performed awake cystometrograms 3 to 4 weeks after spinal cord transection in female rats. Cystometric parameters such as mean amplitudes and number of non-voiding contractions (NVCs), voided volume, voiding efficiency, and micturition pressure were evaluated before and after intravenous (IV) injection of an arginase inhibitor (nor-NOHA: N ω-hydroxy-nor-L-arginine) in SCI rats. We also examined the effects of an NOS inhibitor (L-NAME: N ω-nitro-L-arginine methyl ester hydrochloride) to determine whether suppression of bladder overactivity by arginase inhibition is mediated by increased production of NO. In addition, we measured mRNA levels of arginase I and II in SCI bladders using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We found that nor-NOHA (10 mg/kg, IV) significantly decreased the amplitude and number of NVCs. There were no significant changes in other parameters before and after administration of vehicle or nor-NOHA at any dose. When we administered L-NAME (20 mg/kg, IV) before nor-NOHA injection (10 mg/kg, IV), nor-NOHA–induced inhibition of NVCs was prevented. The relative levels of both arginase I and II mRNA in the bladder were significantly higher in SCI rats compared with spinal cord–intact rats. Conclusions: These results suggest that arginase inhibition can suppress SCI-induced bladder overactivity as indicated by a reduction in NVCs. Thus, arginase inhibition could be an effective treatment for neurogenic bladder overactivity in pathological conditions such as SCI. [Copyright &y& Elsevier]

The effects of intrathecal injection of tamsulosin (an alpha-1A adrenergic receptor antagonist) and naftopidil (an alpha-1D adrenergic receptor antagonist) on isovolumetric bladder contraction were investigated in rats under urethane anesthesia. Intrathecal injection of tamsulosin (10–30 μg) or naftopidil (0.1–30 μg) transiently abolished isovolumetric rhythmic bladder contraction. Following the recovery of bladder contraction, the interval between contractions was the same as the control value before the injection. The amplitude of bladder contraction was decreased by intrathecal injection of naftopidil (3–30 μg), but not by tamsulosin. Therefore, in addition to the antagonistic action of these agents on the alpha-1 adrenergic receptors of prostatic smooth muscle, both agents (especially naftopidil) may also act on the lumbosacral cord, and thus may improve collecting disorders in patients with benign prostatic hyperplasia. [Copyright &y& Elsevier]

Abstract: Aims: Alpha1D-adrenoceptors (α1D-ARs) located in the spinal cord are involved in the control of lower urinary tract function. In order to clarify the effect of α1D-ARs on storage function in the spinal cord, we examined the effect of oral administration and intrathecal injection of the α1D/A-AR antagonist, naftopidil, on bladder activity, as well as the effect of naftopidil on bladder wall histology, in female rats with spinal cord injury (SCI). Main methods: Adult female Sprague–Dawley rats with Th9–10 spinal cord transection were used. In SCI rats with or without 5mg/day of naftopidil for 4weeks, bladder activity was examined via continuous cystometry. In other SCI rats, bladder activity was examined before and after intrathecal injection of naftopidil. In addition, bladder wall histology was compared between SCI rats with or without oral administration of naftopidil for 4weeks. Key findings: Oral administration of naftopidil decreased the number of non-voiding contractions (NVCs). Intrathecal injection of naftopidil prolonged the interval between voiding contractions, decreased the maximum voiding contraction pressure and the number of NVCs, and increased bladder capacity without affecting the residual urine volume. Oral administration of naftopidil also decreased bladder wall fibrosis. Significance: The α1D/A-AR antagonist naftopidil might act on the bladder and spinal cord to improve detrusor hyperreflexia in the storage state in SCI female rats. Naftopidil also suppressed bladder wall fibrosis, suggesting that it may be effective for the treatment of neurogenic lower urinary tract dysfunction after SCI. [Copyright &y& Elsevier]

Objectives: To evaluate the changes in split renal function after retroperitoneal laparoscopic partial nephrectomy with renal hypothermia using ice-cold saline. Methods: From June 2002 to October 2009, 32 patients (median age 56 years) underwent retroperitoneal laparoscopic partial nephrectomy with hypothermia using ice-cold saline for the treatment of small renal tumors. The total renal function was monitored using the estimated glomerular filtration rate. Split renal function was evaluated using technetium-99m dimercaptosuccinic acid renal scintigraphy preoperatively and 3 months postoperatively. Results: The median renal ischemic time, including the initial 10 minutes for cooling, was 52 minutes (range 28-101). Of the patients whose renal temperature was monitored, the lowest renal temperature during cooling was 15-25°C. The median decrease in the estimated glomerular filtration rate was 7.2 mL/min/1.73 m2 (range −16.3 to 33.7). The median decrease in the contribution of the affected kidney to global renal function was 5.3% (range 0.4%-21.1%). On multivariate analysis, a shorter ischemia duration was an independent predictor of a lesser decrease in the contribution of the affected kidney (P = .0032). Conclusions: The methods we have described are simple and effective to facilitate suboptimal hypothermia. The decrease in the renal contribution of the affected kidney appeared to be minimal, although the ischemic time was relatively longer in our series. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Serotonergic neurons and amino acid neurons are involved in the central nervous control of lower urinary tract function. We investigated the role of the serotonergic system in the central regulation of micturition, as well as the relationship between serotonergic neurons and amino acid neurons in the lumbosacral cord of rats. Main methods: Under urethane anesthesia, bladder and urethral activity were recorded before and after intrathecal injection of serotonin (5-hydroxytryptamine: 5-HT), a 5-HT2A receptor antagonist (ketanserin: KET), or KET+5-HT by isovolumetric cystometry and measurement of the urethral pressure in intact rats and rats with hypogastric nerve transection (HGNT). Amino acid levels in the lumbosacral cord were also measured after intrathecal injection of 5-HT in intact rats. Key findings: In intact rats, intrathecal injection of 5-HT transiently abolished rhythmic bladder contractions, decreased the maximal bladder contraction pressure, and increased the intravesical baseline pressure and the urethral baseline pressure. Intrathecal injection of KET+5-HT also transiently abolished rhythmic bladder contractions. In HGNT rats, intrathecal injection of 5-HT transiently abolished rhythmic bladder contractions and increased the urethral baseline pressure. Intrathecal injection of 5-HT decreased the level of glycine in the lumbosacral cord. Significance: The serotonergic system may be involved in blocking the afferent pathway of the micturition reflex, increasing sympathetic activity, and secondary promotion of urethral contraction through inhibition of glycinergic neurons in the lumbosacral cord. 5-HT2A receptors may be involved in these effects on the bladder and urethra. Therefore, the serotonergic system may play a role of the maintenance of urine storage. [Copyright &y& Elsevier]

Abstract: We examined the effects of propiverine hydrochloride and naftopidil on the urinary ATP level and bladder activity after bladder stimulation in rats. Thirty-nine female rats were divided into a control group, a propiverine group, and a naftopidil group. Rats in the propiverine and naftopidil groups were administered 1ml/day of propiverine or naftopidil dissolved in water at 5mg/ml, while animals in the control group were administered 1ml of water only. After 2 weeks, 18 rats (6 per group) underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and their bladder activity was recorded. In the remaining 21 rats (7 per group), 0.1% acetic acid solution was infused into the bladder and the urinary ATP level was measured before and after stimulation (days 0–7). During cystometry with acetic acid in the control group, the interval between bladder contractions was shorter and the maximum bladder contraction pressure was higher than the results for cystometry with physiological saline. The maximum bladder contraction pressure was also increased in the naftopidil group, but such a change was not seen in the propiverine group. The urinary ATP level increased significantly in all three groups after the infusion of acetic acid, but the increase of ATP was smaller in the propiverine group (45% of control) and the naftopidil group (62% of control) than in the control group on day 0. Therefore, the inhibitory effect of propiverine and naftopidil on bladder activity may be partly due to blocking ATP release from the bladder epithelium. [Copyright &y& Elsevier]

Objectives: Frequent recurrence of superficial bladder cancer is a major problem that impairs patients’ quality of life. We studied the current treatment of superficial bladder cancer, including the economic aspects of intravesical instillation. Methods: A total of 138 superficial bladder cancers were assessed. The tumor characteristics and treatments were investigated during a mean observation period of 86 months by univariate and multivariate analyses. The costs associated with intravesical instillation of bacille Calmette-Guérin (BCG) and its side effects were subjected to cost-effectiveness analysis. Results: Tumor histologic examination revealed grade 1 in 21 lesions, grade 2 in 60 lesions, grade 3 in 40 lesions, and unclassified in 17 lesions. The pathologic stage was Stage Ta in 85 lesions, T1 in 47 lesions, and Tis in 6 lesions. Univariate and multivariate analyses showed that intravesical instillation of BCG was the most significant factor preventing recurrence, and intravesical chemotherapy had no impact on recurrence. The 5-year recurrence-free survival rate was 78% and 28% for tumors with and without BCG instillation, respectively. The cost-effectiveness ratio of BCG instillation was approximately $3900/5-yr recurrence-free period. Conclusions: Our results have indicated that BCG is an effective adjuvant therapy after transurethral resection of superficial bladder cancer in the current medical environment. [Copyright &y& Elsevier]