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.

Identification of hemodynamically compromised regions by means of cerebral blood volume mapping utilizing computed tomography perfusion imaging.

The aim of the study was to evaluate the potential role of computed tomography perfusion (CTP) imaging in identifying hemodynamically compromised regions in patients with occlusive cerebrovascular disease. Twelve patients diagnosed with either occlusion or severe stenosis of the internal carotid artery or the M1 portion of the middle cerebral artery underwent CTP imaging. The data was analyzed by an automated ROI-determining software. Patients were classified into two subgroups: an asymptomatic group consisting of three patients in whom perfusion pressure distal to the site of occlusion/stenosis (PPdis) could be maintained in spite of the arterial occlusion/stenosis, and a symptomatic group consisting of nine patients in whom PPdis could not be maintained enough to avoid watershed infarction. Four CTP-related parameters were independently compared between the two groups. Significant differences were determined using a two-sample t-test. When statistically significant differences were identified, cut-off points were calculated using ROC curves. Analysis revealed statistically significant differences between the asymptomatic and symptomatic subgroups only in the measure of relCBV (p=0.028). Higher relCBV values were observed in the symptomatic subgroup. ROC curve analysis revealed 1.059 to be the optimal relCBV cut-off value for distinguishing between the asymptomatic and symptomatic subgroups. The data revealed that, in patients whose PPdis is maintained, relCBV remains around 1.00. Conversely, in patients whose PPdis decreased, relCBV increased. From these findings, we conclude that elevation of relCBV as observed using CTP imaging accurately reflects the extent of compensatory vasodilatation involvement and can identify hemodynamically compromised regions.

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.

Modified sonourethrography assists urethral catheterization.

Sonourethrography (SUG) is an infrequently used modality to observe the male urethra. We modified SUG to examine the reasons for difficulty in urethral catheterization and to determine a safe approach to resolve these problems. Following retrograde urethral jelly injection, modified SUG (mSUG) was performed in male patients with difficulty in urethral catheterization. mSUG was performed using transcutaneous ultrasonography in patients for whom the catheter became lodged in the penile urethra. In other patients, mSUG was performed using transrectal ultrasonography. We divided the causes of difficult indwelling urethral catheterization into physiological and pathological conditions. With regard to physiological conditions, the urethral catheter became stuck in the bulbous portion, membranous urethra, and prostatic urethra. mSUG distinguished the problematic part of the urethra in real time, and it assisted in overcoming the problem. With regard to pathological conditions, urethral stricture after trauma or surgery was clearly demonstrated in the penile and prostatic portions of the urethra. As with physiological conditions, mSUG images assisted in navigating the catheter through the problematic pathological areas or demonstrated the need to abandon the catheterization. mSUG can visualize the male urethra clearly during urethral catheterization and provide real-time assistance with the procedure.

Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.

OBJECTIVE: To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats. METHODS: Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group). RESULTS: At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats. CONCLUSION: A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs.

Expression of 5-Hydroxytryptamine Receptors in Human Urinary Bladders with Benign Prostatic Hyperplasia.

INTRODUCTION: This study investigated the mRNA expression pattern and distribution of 5-hydroxytryptamine (5-HT) receptors 5-HT2A, 5-HT2B, 5-HT3A, 5-HT4, and 5-HT7 within the urothelium and detrusor of normal bladder tissue and in the urothelium of bladders from patients with benign prostatic hyperplasia (BPH). METHODS: Normal urinary bladder specimens were obtained from 13 patients undergoing radical cystectomy due to bladder cancer (normal group) and BPH specimens were obtained from 27 benign prostatic obstruction patients receiving transurethral prostatectomy or retropubic prostatectomy. Receptor subtype mRNA expression was determined by real-time reverse transcription polymerase chain reaction on urothelium, detrusor, and whole mucosal preparations. Receptor distribution was determined by immunohistochemistry. RESULTS: In normal tissues, expressions of 5-HT2B and 5-HT7 receptor mRNAs in the urothelium, detrusor, and whole mucosa were greater than the average expression for all receptor subtype mRNAs. 5-HT2B receptor protein was distributed in the apical urothelium and among the detrusor smooth muscle layers. In contrast, the 5-HT7 receptors were within the urothelium middle cell layers and detrusor smooth muscle cells. The expression pattern of each 5-HT receptor subtype mRNA within the BPH urothelium was similar to that in the normal urothelium. The expression level of 5-HT2A receptor mRNA in the BPH group was significantly lower than the normal group; however, the expressions of both 5-HT3A and 5-HT7 mRNAs were significantly higher. The expressions of both 5-HT2B and 5-HT4 mRNAs were not significantly different between the normal and BPH groups. CONCLUSION: In normal urinary bladders, the expressions of both 5-HT2B and 5-HT7 mRNAs were higher compared to the 5-HT2A, 5-HT3A, and 5-HT4 mRNAs. The distributions of 5-HT2B and 5-HT7 receptors were different in the urothelium and detrusor layers. The 5-HT3A and 5-HT7 receptor mRNAs in the BPH group were significantly higher compared to the normal urothelium, while the 5-HT2A mRNA was significantly lower. FUNDING: Asahi Kasei Pharma Corporation.

Hemodynamic stress distribution reflects ischemic clinical symptoms of patients with moyamoya disease.

OBJECTIVE: Currently, the probability of diagnosing asymptomatic moyamoya disease is increasing. In this study, we consider a less invasive method for predicting future ischemic symptoms in patients with moyamoya disease. METHODS: We reviewed cerebral blood flow (CBF)-related data obtained by xenon CT imaging (XeCT) in six patients with ischemic-type or asymptomatic moyamoya disease. The data were obtained as volume data using a 320-row CT, and applied to the automated region-of-interest-determining software (3DSRT) and converted to standardized images. Eight CBF-related parameters, including CBF value, cerebrovascular reserve capacity (CVRC), and hemodynamic distribution (hdSD), were compared between asymptomatic hemispheres and ischemic symptomatic hemispheres. A significant difference was determined by a two-sample t test. A difference with p<0.05 was considered significant. When statistically significant differences between parameters of asymptomatic hemispheres and ischemic symptomatic hemispheres were identified, cut-off points were calculated with receiver operating characteristic (ROC) curves. Change in the parameters before and after bypass surgery was also assessed. RESULTS: Of the eight CBF-related parameters evaluated, statistically significant differences between the asymptomatic hemispheres and ischemic hemispheres were observed in the CBF value of the MCA region (CBF-MCA), both at rest and after acetazolamide loading, and in the hdSD, also both at rest and after acetazolamide loading. Of the four statistically significant parameters, ROC analysis revealed that the hdSD at rest and CBF-MCA after acetazolamide loading were the most sensitive and specific parameters (threshold 1.2, sensitivity 1, specificity 1 for hdSD at rest, and threshold 26.44mL/100g/min, sensitivity 1, specificity 1 for CBF-MCA after acetazolamide loading). From the CBF data obtained both before and after surgery from the three patients who had undergone direct bypass surgeries, the hdSD was higher than the threshold of 1.2 before surgery but decreased to lower than the threshold of 1.2 after surgery. Ischemic symptoms also resolved after surgery. CONCLUSIONS: The data showed that hdSD at rest and CBF-MCA after acetazolamide loading reflects ischemic symptoms of patients with moyamoya disease. Thus, these parameters could be used as ischemic symptom markers for following patients with moyamoya disease. hdSD at rest is important because it is less invasive and can be performed without acetazolamide loading.

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.

Prediction of cerebrovascular reserve capacity by computed tomography perfusion using 320-row computed tomography.

BACKGROUND: Acetazolamide loading has been the "gold standard" for evaluating cerebrovascular reserve capacity (CVRC). However, life-threatening side effects of acetazolamide have recently been reported. The aim of the study was to identify alternative methods for evaluating CVRC. METHODS: We reviewed 6 patients who underwent both computed tomography perfusion (CTP) imaging and xenon CT (XeCT) imaging with and without acetazolamide loading during the same periods. The data were obtained as volume data using 320-row CT and applied to the automated region of interest-determining software and converted to standardized images. Correlations between CVRC and CTP parameters were analyzed by Pearson correlation coefficient analysis, and simple regression was used to assess the relationship between the data. When statistically significant, correlation between CVRC and any CTP data is identified, and cutoff points for CVRC 30% and 10% were calculated with receiver operating characteristic curves. RESULTS: Of 4 CTP parameters evaluated, statistically significant correlations were observed between time to peak (TTP) by CTP and CVRC (P < .0001, r = -.7228) calculated from XeCT. The regression line using CVRC as outcome variable (y) and using TTP as predictor variable (x) was y = -9.062x + 140.1. The cutoff value for the TTP for CVRC less than 10% was 12.56 seconds (sensitivity of 86% and specificity of 85%) and that for CVRC less than 30% was 9.34 seconds (sensitivity of 77% and specificity of 96%). CONCLUSIONS: TTP calculated from CTP data correlated well with the CVRC calculated from XeCT data. These results suggest that TTP calculated from CTP could be used to estimate CVRC in patients with occlusive cardiovascular disease.

Engineered bone marrow-derived cell sheets restore structure and function of radiation-injured rat urinary bladders.

Previously, we reported that implantation of isolated single bone marrow-derived cells into radiation-injured urinary bladders could restore structure and function. However, injections of isolated single cells had some limitations. Thus, in this study, we produced bone marrow-derived cell sheets in temperature-responsive culture dishes that release the monolayer sheets intact. We then determined whether the produced cell sheets could restore function to irradiated urinary bladders. Twenty female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2 gray once a week for 5 weeks. Bone marrow cells harvested from two male 17-week-old green fluorescence protein-transfected SD rats were placed in primary culture for 7 days. Bone marrow cell-derived outgrowths were harvested by enzymatic digestion and transferred into the atelocollagen-coated temperature-responsive culture dishes for 2 days. To harvest the secondarily cultured cells as monolayer sheets, a support membrane was put in each culture dish, and then the temperature was reduced to 20°C. Each released cell sheet was then patched onto the irradiated anterior bladder wall (n=10). As controls, cell-free sheets were similarly patched (n=10). After 4 weeks, transplanted cells were detected on the bladder walls. The cell sheet-transplanted bladders had smooth muscle layers and acetylcholinesterase-positive nerve fibers in proportions that were significantly larger than those of the control bladders. In addition, the cell sheet-transplanted bladders had reduced prolyl 4-hydroxylase beta (P4HB)-positive regions of collagen synthesis and apoptosis within the smooth muscle layers. In cystometric investigations, threshold pressures, voiding interval, micturition volume, and bladder capacity in the cell sheet-transplantation group were significantly higher than those in the control group. Residual volume of the cell sheet-transplantation group was significantly lower compared with the control. There were 24 growth factor mRNAs in the cell sheet-transplanted urinary bladders that were expressed greater than or equal to two-fold over the controls. In conclusion, cell sheet engineering has great potential to restore damaged urinary bladders.

Comparison of cerebral blood flow data obtained by computed tomography (CT) perfusion with that obtained by xenon CT using 320-row CT.

Cerebral blood flow (CBF) data obtained by computed tomography perfusion (CTP) imaging have been shown to be qualitative data rather than quantitative, in contrast with data obtained by other imaging methods, such as xenon CT (XeCT) imaging. Thus, interpatient comparisons of CBF values themselves obtained by CTP may be inaccurate. In this study, we have compared CBF ratios as well as CBF values obtained from CTP-CBF data to those obtained from XeCT-CBF data for the same patients to determine CTP-CBF parameters that can be used for interpatient comparisons. The data used in the present study were obtained as volume data using 320-row CT. The volume data were applied to an automated region of interest-determining software (3DSRT, version 3.5.2 ) and converted to 59 slices of 2 mm interval standardized images. In the present study, we reviewed 10 patients with occlusive cerebrovascular diseases (CVDs) undergoing both CTP and XeCT in the same period. Our study shows that ratios of CBF measurements, such as hemodynamic stress distribution (perforator-to-cortical flow ratio of middle cerebral artery [MCA] region) or the left/right ratio for the region of the MCA, calculated using CTP data have been shown to correlate well with the same ratios calculated using XeCT data. These results suggest that such CBF ratios could be useful for generating interpatient comparisons of CTP-CBF data obtained by 320-row CT among patients with occlusive CVD.

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.

[Study of the voxel-based specific regional analysis system for Alzheimer's disease imaging sequence after magnetic resonance apparatus replacement].

In our institute, an MR apparatus, MAGNETOM VISION (Siemens) was replaced by ECHELON Vega (HITACHI). Z-score data acquired by MPRAGE (VISION) was compared with those by radio frequency-spoiled steady-state acquisition with rewinded gradient echo (RSSG) and gradient echo inversion recovery (GEIR) (ECHELON). For this study, ten normal volunteers were recruited and their data ware obtained within two months using both apparatuses. In addition, the difference of the contrasts of the images of these apparatuses was compared. There was a significant difference between Z-scores of MPRAGE and RSSG while there was no difference between MPRAGE and GEIR. As for the contrast, data of MPRAGE were similar to those of GEIR. To compare Z-scores acquired with MAGNTOM VISION (Siemens), it seems appropriate to use GEIR in ECHELON Vega.

[Metachronous bilateral testicular cancer: report of two cases].

We report two cases of metachronous bilateral testicular tumors. In the first case (48 years old), and the second case (39 years old) the contralateral tumor developed 106 months and 63 months after the initial therapy, respectively. In both cases, the primary and the contralateral tumors were stage I seminomas. The patients underwent high inguinal orchiectomy and adjuvant retroperitoneal irradiation for the primary tumor, and only high inguinal orchiectomy for the contralateral tumor. There was no recurrence following the second operation in either case. In the second case, preoperative cryopreservation of the semen was performed for future artificial insemination. Long-term follow-up of contralateral testis is necessary for patients with testicular cancer, even if good prognosis is expected. The quality of life of the patients with bilateral testicular tumors should be maintained by preserving fertility and replacing androgen.

[A case of stone formation in the Mainz pouch using appendix as the efferent limb: a case report].

A large calculus (6.0 x 4.5 x 7.0 cm sized) in the continent urinary pouch was detected incidentally by computed tomography in a 7-year-old man with a gall bladder stone. He underwent a total cystectomy and Mainz pouch formation using appendix as the efferent limb for bladder cancer 7 years ago. Urine culture showed Proteus mirabilis and Escherichia coli, and urine pH was 8.5. The stone was removed successfully through a pouchotomy and composed mainly of struvite. The stone analysis was MAP; 88% and CaCO3; 12%. Convalescence was uneventful. This is the first case of in Mainz pouch using appendix as the efferent limb.