Intravesical nerve growth factor antisense therapy for bladder hypersensitivity induced by psychological stress.

This study assessed the relationship between NGF expression in the bladder and bladder hypersensitivity caused by psychological stress using water avoidance stress (WAS) in rats by modulating the NGF expression using intravesical liposome-complexed NGF antisense oligonucleotide (OND) therapy on WAS-induced bladder dysfunction. Female Wistar rats were divided into control and WAS groups, the latter of which received WAS sessions for 10 days with or without the OND pretreatment. Rats underwent cystometry with or without intravesical application of low-dose protamine sulfate (LD-PS), or pain behavior measurements after LD-PS application. After functional evaluations, the bladder was harvested for histology and molecular studies. WAS rats with or without LD-PS showed shortened intercontraction intervals and increased pain behaviors compared to control rats, which was improved by OND-treatment. Histological studies revealed that LD-PS provoked urothelial exfoliation in WAS rats. Compared to controls, protein assay showed increased NGF levels, and RT-PCR showed increases of TRPV1 and TRPA1 and a decrease in Cx43 in WAS rat bladders, which were improved by OND-treatment. WAS caused bladder hypersensitivity, which was improved by NGF antisense OND treatment. NGF upregulation in the bladder may be a therapeutic target for the treatment of psychological stress-induced bladder dysfunction.

Transient receptor potential ankyrin 1 channels in the bladder mediate low temperature elicited bladder overactivity in rats.

AIMS: This study aimed to investigate whether pathways involving transient receptor potential ankyrin 1 (TRPA1) channels in the urinary bladder mediate the bladder overactivity elicited by exposure to a low temperature in rats. METHODS: At postnatal week 10, female Sprague-Dawley (SD) rats were intraperitoneally injected with the TRPA1 channel antagonist, HC030031, at room temperature (RT) and subsequently exposed to low temperature (LT). Bladder specimens treated with HC030031 were evaluated for contractions through cumulative addition of the TRPA1 channel agonist trans-cinnamaldehyde. Two days before cystometric investigation, small interfering RNA (siRNA) targeting TRPA1 was transfected into urinary bladders. Then, cystometric investigations were performed on rats subjected to TRPA1 siRNA transfection at both RT and LT. Expression of TRPA1 channels in the urinary bladder was assessed through immunohistochemistry and real-time reverse transcription-polymerase chain reaction. RESULTS: At RT, micturition patterns were unaffected by HC030031 treatment. However, upon exposure to LT, rats treated with HC030031 exhibited a reduction of LT-elicited bladder overactivity, as evidenced by inhibited decreases in voiding interval, micturition volume, and bladder capacity. Additionally, HC030031 inhibited trans-cinnamaldehyde-induced contractions. Immunohistochemical analysis showed the presence of TRPA1 channels in the urinary bladder. Notably, rats with TRPA1 siRNA-transfected bladders could partially inhibit bladder overactivity during LT exposure. CONCLUSIONS: These findings indicate that pathways involving TRPA1 channels expressed in the urinary bladder could mediate the LT-elicited bladder overactivity.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model.

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity and the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4, and 6 wk post-SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, nonvoiding contractions were confirmed at 2 wk post-SCI and did not increase over time to 6 wk. In 2-wk SCI mice, EUS-EMG measurements revealed detrusor sphincter dyssynergia, but periodic EMG reductions during bladder contraction were hardly observed. At 4 wk, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency. At 6 wk, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of transient receptor potential vanilloid 1 and acid-sensing ion channels (ASIC1-ASIC3) in SCI mice with a decrease of ASIC2 and ASIC3 at 6 wk compared with 4 wk, whereas Piezo2 showed a slow increase at 6 wk. Protein assay showed SCI-induced overexpression of bladder brain-derived neurotrophic factor with a time-dependent decrease post-SCI. These results indicate that detrusor overactivity is established in the early phase, whereas detrusor sphincter dyssynergia is completed later at 4 wk with an improvement at 6 wk post-SCI, and that mechanosensitive channels may be involved in the time-dependent changes.NEW & NOTEWORTHY This is the first paper to evaluate the time-course changes of bladder dysfunction associated with mechanosensitive channels in a mouse model.

Effect of oxybutynin patch versus mirabegron on nocturia-related quality of life in female overactive bladder patients: A multicenter randomized trial.

OBJECTIVES: To investigate the effect of oxybutynin patch versus ß3-adrenoceptor agonist mirabegron on nocturia-related quality of life in female overactive bladder patients. METHODS: In the present study, female overactive bladder patients were enrolled. The patients were randomly allocated into two groups: the oxybutynin patch group and the mirabegron group. Each of the drugs was given for 8 weeks. The changes in the total Nocturia Quality of Life Questionnaire score were evaluated. Parameters on a frequency volume chart were also evaluated. RESULTS: In total, 100 patients (51 oxybutynin patch, 49 mirabegron) were treated with oxybutynin patch or mirabegron. The changes in the Nocturia Quality of Life Questionnaire score 4 weeks after administration were 3.8 ± 18.6 and 8.7 ± 13.1 with the oxybutynin patch group and the mirabegron group, respectively, which were significantly higher than those at the baseline. Furthermore, the changes in the Nocturia Quality of Life Questionnaire score 8 weeks after administration were 4.3 ± 16.5 and 7.7 ± 12.3, respectively. A statistical difference was seen only in the mirabegron group. Regarding the Nocturia Quality of Life Questionnaire subscores, oxybutynin patch and mirabegron significantly improved the Nocturia Quality of Life Questionnaire bother/concern subscore 4 and 8 weeks after administration, whereas the Nocturia Quality of Life Questionnaire sleep/energy subscore was not significantly improved in each period. Eight weeks after administration, 24-h frequency, 24-h urinary urgency and mean voided urine volume were improved in both groups statistically. CONCLUSIONS: The oxybutynin patch improves quality of life, focusing mainly on nocturia by improving the bother/concern subscores of the Nocturia Quality of Life Questionnaire in the short term.

Impact of low-dose tadalafil on adverse events after low-dose-rate brachytherapy for prostate cancer: A bi-center randomized open-label trial.

OBJECTIVE: To study the efficacy of phosphodiesterase-5 inhibitor tadalafil in attenuating adverse events after low-dose-rate brachytherapy for prostate cancer. METHODS: This was a randomized open-label trial, conducted at two institutions. Prostate cancer patients undergoing low-dose-rate brachytherapy were randomly assigned to receive tadalafil (study group) or tamsulosin (control group). The primary endpoint was International Prostate Symptom Score for subjective evaluation of lower urinary tract symptoms. Uroflowmetry, postvoid residual urine volume, and Sexual Health Inventory for Men score were the secondary endpoints. Each clinical variable was evaluated during a follow-up period of 1 year after low-dose-rate brachytherapy. RESULTS: A total of 107 patients were enrolled in this study, with a final total of 96 patients analyzed. The mean total International Prostate Symptom Score changes at 1, 3, 6, 9, and 12 months after low-dose-rate brachytherapy were +7.4, +7.1, +4.7, +1.5, and +0.8, respectively, in the tamsulosin group, and +8.5, +9.2, +6.4, +4.1, and +1.6, respectively, in the tadalafil group. There were no statistically significant differences in International Prostate Symptom Score with the exception of the score at 9-month follow-up. Moreover, there were no statistically significant differences in any of the uroflowmetry or postvoid residual urine volume findings. The Sexual Health Inventory for Men score in the tadalafil group was significantly higher than that in the tamsulosin group at 6, 9, and 12 months after low-dose-rate brachytherapy. CONCLUSIONS: Tadalafil could be an effective option for the management of lower urinary tract symptoms after low-dose-rate brachytherapy.

Vorticity in lower urinary tract can be assessed and associates with urinary tract morphology in men.

OBJECTIVES: The aim of this study is to develop a method to evaluate the fluid dynamics of urine flow in the lower urinary tract (LUT), especially that of vorticity. MATERIALS AND METHODS: This investigation included three sub-studies to demonstrate urine flow in the entire LUT. First, we attempted to observe vorticity generation in the urinary bladder during spontaneous voiding using transabdominal color Doppler ultrasonography (CDUS). Second, we performed transrectal CDUS to evaluate the vorticity of urine flow in the prostatic urethra. Patients with prostate cancer were enrolled before robotic surgery and divided into the vorticity and non-vorticity groups based on CDUS findings for comparisons of longitudinal urethral diameter and prostatic urethral angle. Third, the vorticity of the voided urine stream was observed using a high-speed video-camera. Micturition was done in a standing position while synchronously monitored for urine flow using uroflowmetry. RESULTS: Vorticity formation could be dynamically demonstrated in the urinary bladder and prostatic urethra using CDUS. The prostatic urethral angle of the vorticity group was more than that of the non-vorticity group. High-speed video recording could clearly capture vorticity and spiral shape generation in voided urine. The distance from the external urethral orifice to the first twist changed in accordance with urine flow rate. CONCLUSIONS: In a series of sub-studies, this investigation proved vorticity generation in the LUT and voided urine. Vorticity was detectable in the LUT and in voided urine using CDUS and a high-speed video-camera. Vorticity generation might be associated with urethral morphology.

Nicotine-induced hypoxia in rat urothelium deteriorates bladder storage functions.

AIMS: To measure the effects of nicotine on lower urinary tract symptoms (LUTS), bladder blood flow, and the urothelial markers hypoxia-inducible factor 1α (HIF1α), uroplakin III (UPIII), and aquaporin 3 (AQP3). METHODS: Ten-week-old female Sprague Dawley rats were subcutaneously injected with 2 mg/kg nicotine (n = 17) or vehicle (control, n = 18) twice daily for 13 days. Some nicotine-treated rats (n = 10) were injected daily with 1 mg/kg tadalafil for the last 6 days of nicotine treatment. One day before cystometry, the bladders of some nicotine-treated and control rats were instilled with 0.08% acetic acid. Urinary frequency and volume were measured 1 day after treatment. Blood flow in the bladder neck was measured, and the urothelia were immunochemically assayed for HIF1α, UPIII, and AQP3. RESULTS: Following acetic acid treatment, both voiding interval and micturition volume of the nicotine-treated rats were significantly lower than controls. Nicotine-treated rats had lower blood flow than controls, and the urothelial expression of HIF1α was higher than controls. Simultaneously, the expressions of UPIII and AQP3 were decreased. Tadalafil treatment increased bladder blood flow, and nicotine-treated rats had increased voiding interval and micturition volume. Further, the expression of HIF1α decreased, and both UPIII and AQP3 levels increased. CONCLUSIONS: Nicotine-treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. Changes in tissue markers in the nicotine-treated rats were consistent with hypoxia and loss of urothelial function. Restoration of blood flow reversed the nicotine effects. Nicotine may induce LUTS through reduced bladder blood flow and urothelial hypoxia.

Combined treatment with a ß3 -adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats.

AIMS: This study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the ß3 -adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). METHODS: Thirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then intravenously administered vehicle, 0.1 mg/kg solifenacin alone, 0.1 mg/kg mirabegron alone, or the combination of 0.1 mg/kg mirabegron and 0.1 mg/kg solifenacin (n = 8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 4 ± 2°C) for 40 min. Finally, the rats were returned to RT. After the cystometric investigations, the ß3 -ARs and M3 -MRs expressed within the urinary bladders were analyzed. RESULTS: Just after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M3 -MR and ß3 -AR mRNA. The tissue distribution of M3 -MRs was similar to that of the ß3 -ARs. CONCLUSIONS: This study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. © 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

Impact of ao-dake-humi, Japanese traditional bamboo foot stimulator, on lower urinary tract symptoms, constipation and hypersensitivity to cold: a single-arm prospective pilot study.

BACKGROUND: Ao-dake-humi is a traditional Japanese bamboo foot stimulator consisting of a half-pipe-shaped step made of bamboo used to stimulate the foot by stepping on it, and is commonly used to promote general health among the elderly in Japan. However, its efficacy has not been reported in the scientific literature. This study was performed to investigate the role of ao-dake-humi focusing on lower urinary tract symptoms (LUTS), constipation, and hypersensitivity to cold (HC). METHODS: Participants with LUTS, constipation, or HC were enrolled in this study. Ao-dake-humi was used twice a day for 28 days. Before and 28 days after starting ao-dake-humi use, international prostate symptom score (IPSS), quality-of-life (QoL) score, and overactive bladder symptom score (OABSS) were measured to evaluate the efficacy of ao-dake-humi on LUTS. To evaluate the objective efficacy of ao-dake-humi on LUTS, a frequency-volume chart (FVC) was plotted in LUTS patients for 3 days. A visual analogue scale (VAS) was used to evaluate the efficacy of ao-dake-humi on constipation (VAS-constipation) and HC (VAS-HC) in the participants with constipation or HC. RESULTS: A total of 24 participants were enrolled in this study. Twenty-one participants had LUTS, 11 had constipation, and 17 participants had HC. IPSS, especially storage-subscore, QoL score and OABSS, decreased significantly after use of ao-dake-humi. The use of ao-dake-humi increased maximal bladder capacity, resulting in a significant decrease in urinary frequency as determined from the FVC. In accordance with the results of VAS-constipation and VAS-HC, both constipation and HC were significantly relieved after ao-dake-humi use. CONCLUSION: The results of this prospective pilot study indicated that ao-dake-humi is safe and has therapeutic efficacy in cases of LUTS, constipation and HC. The possibility of using ao-dake-humi as physical neuromodulation therapy was shown in the management of LUTS, constipation and HC. TRIAL REGISTRATION: UMIN000019333 (UMIN-CTR, Registered October-15-2015) retrospectively registered.

Impact of dynamic transrectal ultrasonography on pelvic organ prolapse.

PURPOSE: We developed a new method to evaluate pelvic organ prolapse dynamically in patients in supine and standing positions using transrectal ultrasonography. We visualized the descent and prolapse of pelvic organs in real time using dynamic transrectal ultrasonography. The dynamic transrectal ultrasonography findings were compared with intraoperative findings. MATERIALS AND METHODS: A prospective analysis was performed including 31 women with symptomatic pelvic organ prolapse. Before surgical repair for pelvic organ prolapse, transrectal ultrasonography was performed by an operator separate from the surgeon, and the transrectal ultrasonography findings were compared with the intraoperative findings, focused on the diagnosis of pelvic organ prolapse. The patients were put on the fluoroscopic tilting table for passive postural change from supine to standing position. After injection of sonographic jelly into the vaginal lumen, the ultrasound probe was inserted into the rectum. With passive postural change from supine to standing position using the fluoroscopic tilting table, descent and prolapse of pelvic organs were dynamically evaluated in real time. RESULTS: Cystocele, uterine prolapse and rectocele were dynamically observed in this procedure. Morphological details of pelvic organ prolapse such as movement, sliding, eversion, descent, and looseness of vaginal wall and bladder wall were successfully demonstrated in most cases. Dynamic transrectal ultrasonography demonstrated a high sensitivity (85.0%), specificity (81.1%), and positive (77.3%) and negative (87.8%) predictive value. CONCLUSIONS: We successfully demonstrated morphological conditions and dynamic changes of pelvic organs during passive postural change using dynamic transrectal ultrasonography in real time. Dynamic transrectal ultrasonography can be a useful modality to visualize pelvic organ prolapse preoperatively.

Current and emerging drugs for interstitial cystitis/bladder pain syndrome (IC/BPS).

INTRODUCTION: Interstitial cystitis or bladder pain syndrome (IC/BPS) is a debilitating chronic disease characterized by suprapubic pain and lower urinary tract symptoms: however, the etiology is still unknown. Therefore, the long-lasting, effective treatments of IC/BPS are still not established, and the treatment is sometimes empirically selected depending on practitioners' experience and preference. AREA COVERED: In this review we focus on the current treatments, ongoing clinical trials, and several potential new drugs based on the results of basic and clinical research studies. First, we discuss the potential etiologies of IC/BPS that include altered barrier lining, afferent and/or central nervous system abnormalities, possible contribution of inflammation or infection and abnormal urothelial signaling. Then, the current therapies of IC/BPS, either systemic or local, are reviewed by critical evaluation of the efficacy and shortcomings of each treatment. Finally, based on proposed etiologies of the disease, potential emerging drugs and treatments are discussed. EXPERT OPINION: Current therapies often fail to control the symptoms of IC/BPS. Several interventions including sustained drug release and retaining techniques, and drugs that act on afferent neural pathways are emerging and may be promising. In addition, phenotyping of IC/BPS patients based on cystoscopic findings (e.g., Hunner vs. non-Hunner lesion) or patients' symptoms would be important for further investigation of IC/BPS etiology and the evaluation of efficacy of new treatments.

Alpha1 -adrenergic receptors mediate bladder overactivity induced by cold stress in rats with bladder outlet obstruction.

PURPOSE: To determine if alpha1 -adrenergic receptors (AR) mediate bladder overactivity induced by cold stress in rats with bladder outlet obstruction (BOO). MATERIALS AND METHODS: The urethras of 10-week-old female Sprague-Dawley rats were ligated to create BOO. After 4 weeks, cystometric investigations were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then given 0.3 mg/kg naftopidil (n = 6) or vehicle (n = 5) intravenously. Five minutes later, they were transferred to low temperature (LT, 4 ± 2°C), and the cystometric patterns were again recorded for 40 min. In BOO rats and in sham-operated rats (n = 8) the expression levels of alpha1A - and alpha1D -AR mRNAs and the presence of alpha1A - and alpha1D -AR immunoreactivity on calcitonin gene-related peptide (CGRP)-positive nerve cells were investigated. RESULTS: During LT exposure, the vehicle-treated BOO rats exhibited cold stress-induced bladder overactivity. In the naftopidil-treated rats, the increase of basal pressure and decreases of both voiding interval and bladder capacity induced by LT were significantly reduced compared to the vehicle-treated animals. In the bladders of BOO rats exposed to LT, the expression of alpha1D -AR mRNA was significantly higher than in sham-operated rats, and the immunoreactivity for alpha1D -ARs on the CGRP-positive nerve cells tended to be more pronounced. CONCLUSIONS: Alpha1 -ARs mediate part of the bladder overactivity induced by cold stress in rats with BOO. Cold stress increases the expression of alpha1D -AR mRNA and the immunoreactivity for alpha1D -ARs on the CGRP-positive nerve cells in BOO rats. Naftopidil partially inhibits the cold stress overactivity, suggesting that it is mediated, at least partially, through alpha1D/1A -ARs.

Usefulness of sonourethrography for penile abscess as a result of xanthogranulomatous granuloma in the corpus cavernosum of an adult: A case report.

A 75-year-old man presented with a 4-month history of a swollen and painful penis. Computed tomography showed a round-shaped mass measuring 3 × 2 cm in the corpus cavernosum. Percutaneous drainage of the penile mass was carried out and a course of antibiotics was prescribed. Viral, fungal and selective bacterial cultures were negative. Total penectomy and urethroperineal fistula formation were carried out because of penile pain. Histopathological diagnosis was xanthogranulomatous granuloma of the corpus cavernosum. Before surgery, sonourethrography was carried out under general anesthesia. Sonourethrography is an infrequently used modality to observe the male urethra under urinary micturition or injection of saline. We previously reported modified sonourethrography with retrograde jelly injection. In the present case, sonourethrography successfully showed the damaged and deformed urethra including the abscess cavity and fistula. Although xanthogranulomatous granuloma is rare, the findings reported here showed the usefulness of sonourethrography for morphological evaluation of the male urethra.

Transient receptor potential channel superfamily: Role in lower urinary tract function.

Lower urinary tract symptoms associated with neurogenic bladder and overactive bladder syndrome are mediated in part by members of the transient receptor potential channel superfamily. The best studied member of this superfamily is the vanilloid receptor. Other transient receptor potential channels, such as the melastatin receptor and the ankyrin receptor, are also active in the pathogenesis of lower urinary tract dysfunction. However, the detailed mechanisms by which the transient receptor potential channels contribute to lower urinary tract symptoms are still not clear, and the therapeutic benefits of modulating transient receptor potential channel activity have not been proved in the clinical setting. In the present review, to better understand the pathophysiology and therapeutic potential for lower urinary tract symptoms, we summarize the presence and role of different members of the transient receptor potential channel superfamily in the lower urinary tract.

[UNDIFFERENTIATED CARCINOMA OF THE URETER WITH FETAL CLINICAL COURSE: A CASE REPORT].

Undifferentiated carcinoma of ureter is rare neoplastic lesion, and the natural history of undifferentiated carcinoma of ureter has not been known well yet. We hereby presented an autopsy case of undifferentiated carcinoma of the ureter with rapid progression from the initial stage. A 62-year-old male visited the local urologist complaining of asymptomatic gross hematuria. Cystoscopy revealed the outflow of hematuria from the right ureteral orifice. Abdominal CT showed the right hydronephrosis with atrophic change of the renal parenchyma and the stenosis of upper ureter. He was referred to our hospital on suspicion of a right ureteral tumor. Magnetic resonance imaging and retrograde ureterography did not reveal a tumor in the right ureter. He complained of low back pain 4 months after the initial hematuria, and CT revealed the diffuse enlargement of the right kidney, swelling of the abdominal lymph nodes, and lung nodules. Renal biopsy was done, and only undifferentiated cells were revealed histopathologically without any specific findings to diagnose the primary organ. The tumor increased progressively, and he died about 6 months after the initial gross hematuria. Autopsy was performed, and urothelial carcinoma was found in the right ureter as the primary lesion. The ureteral tumor infiltrated to the right kidney, right adrenal gland, liver, duodenum, and pancreas with undifferentiation. Undifferentiated tumor cells were also found in distant metastatic lesion including the abdominal lymph nodes, left adrenal gland, liver, lung, pleura, and peritoneum.

Bladder afferent hyperexcitability in bladder pain syndrome/interstitial cystitis.

Bladder pain syndrome/interstitial cystitis is a disease with lower urinary tract symptoms, such as bladder pain and urinary frequency, which results in seriously impaired quality of life of patients. The extreme pain and urinary frequency are often difficult to treat. Although the etiology of bladder pain syndrome/interstitial cystitis is still not known, there is increasing evidence showing that afferent hyperexcitability as a result of neurogenic bladder inflammation and urothelial dysfunction is important to the pathophysiological basis of symptom development. Further investigation of the pathophysiology will lead to the effective treatment of patients with bladder pain syndrome/interstitial cystitis.

Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

OBJECTIVES: This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. METHODS: Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. RESULTS: In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. CONCLUSIONS: Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity.

[A case of advanced prostate fibrosarcoma that reacted well to chemotherapy].

Prostate fibrosarcoma is an extremely rare tumor for which complete excision has been the mainstay of treatment. Although chemotherapy has been attempted in cases with positive surgical margins and/or advanced stage disease, the effectiveness of this therapy has not been established. Herein, we report a case of advanced prostate fibrosarcoma that reacted well to chemotherapy. A 40-year-old man was referred for treatment of a large prostatic tumor with multiple lung, liver, and bone metastases. Needle biopsy of the prostate revealed that the tumor was a high-grade undifferentiated sarcoma. Chemotherapy with doxorubicin and ifosfamide was administered. After five courses of chemotherapy, the primary prostate tumor decreased markedly, and the lung and liver metastases almost disappeared. Radical cystoprostatectomy and ileal conduit formation were performed. Pathological diagnosis was fibrosarcoma. Another three courses of doxorubicin and ifosfamide therapy were performed, and doxorubicin was replaced by etoposide because the maximum dose of doxorubicin was reached. However, the effectiveness of the second-line therapy was poor, and the tumor progressed again. The patient died of lung metastasis 15 months later.