Postpubertal urodynamic and upper urinary tract changes in children with conservatively treated myelomeningocele.

PubMed

Almodhen, Fayez; Capolicchio, Jean Paul; Jednak, Roman; El Sherbiny, Mohamed

2007-10-01

We examined the urodynamic and upper urinary tract changes in children with myelomeningocele treated conservatively through puberty at our institution between 1980 and 2006. A total of 40 patients were exclusively treated conservatively with or without anticholinergics and/or clean intermittent catheterization through puberty at our institution. The records of 37 patients (17 males and 20 females) were available for review and constituted the subject matter for our study. The neurological lesion was sacral in 4 patients, lumbosacral in 5, thoracic in 12 and lumbar in 16. Clinical evaluations, radiological imaging studies of the upper urinary tract and urodynamic studies were repeated every 6 to 12 months. Data were collected and comparisons were made with respect to prepubertal (age 10 years) and postpubertal (15) continence status, urodynamic parameters and upper urinary tract changes. Children spontaneously achieving urinary continence postpubertally were examined in a similar fashion as a separate subgroup. Continence was defined as a dry interval of 4 hours or more. Of the 26 patients with urinary incontinence before puberty 12 (2 males and 10 females, 45%, p <0.003) achieved continence following puberty. Hydronephrosis remained stable in 4 patients, improved in 3 and was new onset in 3 (p >0.05). Vesicoureteral reflux persisted in 1 patient, resolved in 4 and was new onset in 1 (p >0.05). Total cystometric bladder capacity, maximum detrusor pressure and detrusor leak point pressure all increased significantly after puberty, from 277 +/- 82 to 487 +/- 140 ml, 45 +/- 17 to 54 +/- 20 cm H(2)O and 49 +/- 16 to 59 +/- 21 cm H2O, respectively. In patients achieving urinary continence following puberty total cystometric bladder capacity increased significantly from 284 +/- 58 to 473 +/- 93 ml (p <0.005). Maximum detrusor pressure and detrusor leak point pressure showed insignificant changes after puberty, increasing from 45 +/- 11 to 47 +/- 16 cm H2O and from 46 +/- 11 to 55 +/- 21 cm H2O, respectively. This study demonstrates that total cystometric bladder capacity, maximum detrusor pressure and detrusor leak point pressure increase significantly in patients with myelomeningocele following puberty. The increase in bladder capacity could be attributed to increasing bladder outlet resistance resulting from prostate gland enlargement in males and estrogenization in females. A significant number of patients spontaneously achieve continence at puberty, and continence becomes more likely when increased total cystometric bladder capacity is not associated with an increase in maximum detrusor pressure. Finally, no significant postpubertal upper urinary tract deterioration was observed in our series.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity.

PubMed

Gutiérrez-Martín, P; Vírseda-Chamorro, M; Salinas Casado, J; Gómez-Rodríguez, A; Esteban-Fuertes, M

2015-05-01

To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. The BTX-A significantly increased (p < .05) the cystomanometric bladder capacity, the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue. We observed a decrease that tended towards statistical significance (p < .1) of the maximum detrusor pressure and the maximum urine flow. Neither the bladder accommodation nor the urethral resistance index (bladder outlet obstruction index) varied significantly. The increase in vesical capacity was maintained in 50% of the sample for more than 32 months. Age, sex, anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

PubMed

Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

2016-08-01

The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

The enuretic episode--a complete micturition from a bladder with normal capacity? A critical reappraisal of the definition.

PubMed

Rasmussen, P V; Kirk, J; Rittig, S; Djurhuus, J C

1997-01-01

Fifty-five normal children, aged between 7 and 12 years, were hospitalised for four consecutive nights. On three of these nights, the subjects received 25 ml/kg body weight of fluid prior to bedtime. Such fluid-loading provoked 28 enuresis-like episodes in 17 children, most of which occurred during the first few hours of sleep. The incidence of these enuretic events decreased with increasing age, more boys than girls were affected, there was a statistically significant correlation between total enuresis volume and nocturia volume, and the micturition was frequently incomplete, leaving large volumes of residual urine in the bladder. It was concluded that if nocturnal urine production exceeds bladder capacity, enuresis may be provoked, even in children who do not normally wet the bed. Furthermore, the definition of nocturnal enuresis as a complete emptying of the bladder during sleep may need revision.

Ultrasound Thickness of Bladder Wall in Continent and Incontinent Women and Its Correlation with Cystometry

PubMed Central

Otsuki, Edney Norio; Oliveira, Emerson; Sartori, Marair Gracio Ferreira; Girão, Manoel João Batista Castelo; Jármy-Di Bella, Zsuzsanna Ilona Katalin

2014-01-01

Objective. To compare bladder wall thickness in two kinds of urinary incontinent women—stress urinary incontinence (SUI) and overactive bladder (OAB) with urodynamic detrusor overactivity (DO), and to compare them with continent patients by ultrasound, also, correlate with cystometric results in incontinent women. Methods. 91 women were divided into the following groups: continent (n = 31), SUI (n = 30), and DO (n = 30) groups after clinical evaluation and urodynamic test (only in incontinent women). Transvaginal ultrasound was performed to the bladder wall thickness (BWT) measurement. The mean of BWT was calculated and data were analyzed with ANOVA and Turkey's multiple comparison tests. Pearson's correlation coefficient (r) was used to compare two variables. Receiver operating characteristic (ROC) curve was performed to study BWT as a diagnostic parameter. Results. BWT in DO group was significantly higher than that in the other groups (P < 0.005). A moderate positive correlation was found between BWT and maximum bladder pressure during involuntary bladder contraction. There was no difference in BWT between SUI and continent groups. DO group had lower first desire to void and cystometric capacity. Maximum bladder pressure at detrusor contraction had a moderate positive correlation with BWT. The ROC revealed an area under the curve of 0.962 (95% CI, 0.90–1.01). Conclusions. DO patients have increased bladder wall thickness, lower first desire to void, and lower cystometric capacity. There was a moderate correlation between BWT and maximum bladder pressure during involuntary bladder contraction. PMID:25538959

Role of Bladder Hydrodistention and Intravesical Sodium Hyaluronate in the Treatment of Interstitial Cystitis.

PubMed

Yang, Jin-Yi; Wei, Wei; Lan, Yu-Long; Liu, Jun-Qiang; Wang, Hai-Bo; Li, Shao

2015-12-23

To evaluate the clinical efficacy of bladder hydrodistention and intravesical sodium hyaluronate in the treatment of interstitial cystitis (IC). Twenty-one patients with IC received intravesical sodium hyaluronate therapy under nerve block or intravenous anesthesia. Bladders were perfused with 100 cmH2O perfusion pressure and expanded for 10 min and were later injected with 40 mg/50 mL sodium hyaluronate through the catheter. After 1 h, the perfusion fluid was released. Perfusion was applied once per week, 4 to 6 times as a course of treatment. Under anesthesia, the average bladder capacity was 191.62 ± 88.67 mL, and after bladder expansion, the bladder capacity reached 425.33 ± 79.83 mL (P = .000). There were 2 suspected bladder ruptures after bladder expansion at 6.5 min and 7.2 min. After 10 min of bladder expansion, there were 19 cases of significantly gross hematuria. After treatment, the catheters of 17 patients were removed at 24 h; for the 2 cases of hematuria, catheters were removed at 72 h and for the 2 cases of suspected bladder rupture, catheters were removed after 4 days. After catheter removal, the pain threshold significantly decreased, and the maximum urinary output increased slightly. Compared with values before treatment, the day before the second injection of sodium hyaluronate, the frequency of urination decreased significantly (32.8 vs. 18.5 times/24 h), the maximum urinary output increased significantly (86.7 vs. 151.9 mL), the pain decreased significantly (8.7 vs. 3.0), and the O'Leary-Sant IC score and quality of life score were significantly decreased (30.0 vs. 17.0 and 5.9 vs. 2.4, respectively) (P = .000). Bladder hydrodistention under anesthesia for patients with severe intractable IC produces immediate effectiveness; sodium hyaluronic infusion can alleviate frequent urination and pain, and the efficacy was positively correlated with the duration of treatment.

Preclinical assessment of potential interactions between botulinum toxin and neuromodulation for bladder micturition reflex.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2015-06-09

While botulinum toxin A (BoNT-A) has become a more commonly used second-line treatment for patients with detrusor overactivity, it remains unknown whether the impacts of this therapy may persist to influence other therapies such as sacral neuromodulation. In this preclinical study we have evaluated urodynamic functions to intradetrusor injection of BoNT-A and the bladder inhibitory effects of spinal nerve stimulation (SNS) following BoNT-A treatment. Female rats were anesthetized with 3 % isoflurane. BoNT-A (2 units, 0.2 ml) or saline were injected into the detrusor. Rats then were housed for 2 days to 1 month before neuromodulation study. Monopolar electrodes were placed under each of the L6 spinal nerve bilaterally under urethane anesthesia. A bladder cannula was inserted via the urethra for saline infusion and intravesical pressure recording. Intradetrusor injection of BoNT-A for 1-2 weeks or 1 month significantly increased bladder capacity compared with saline injection (p < 0.05, two-way ANOVA). Following BoNT-A, SNS attenuated the frequency of bladder contractions, either eliminating bladder contractions or reducing the contraction frequency during electrical stimulation. Inhibition of the contraction frequency by SNS following BoNT-A treated rats was not different from that measured following saline injection. BoNT-A increased the bladder capacity, but compensating for additional saline infusion to the enlarged urinary bladder in BoNT-A pretreated rats, the bladder contractions induced by bladder filling were attenuated by SNS. BoNT-A did not alter the ability of SNS to inhibit bladder contraction following intradetrusor injection of BoNT-A for 2 days, 1-2 weeks or 1 month. These results support further pre-clinical and clinical studies to evaluate potential interactions or combination therapy with neuromodulation and intradetrusor BoNT-A therapeutic approaches.

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

PubMed

Greenland, J E; Hvistendahl, J J; Andersen, H; Jörgensen, T M; McMurray, G; Cortina-Borja, M; Brading, A F; Frøkiaer, J

2000-06-01

To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Measuring the success of combined intravesical dimethyl sulfoxide and triamcinolone for treatment of bladder pain syndrome/interstitial cystitis.

PubMed

Gafni-Kane, Adam; Botros, Sylvia M; Du, Hongyan; Sand, Robert I; Sand, Peter K

2013-02-01

The purpose of this study was to investigate change in bladder capacity as a measure of response to combined intravesical dimethyl sulfoxide (DMSO) and triamcinolone instillations for the treatment of newly diagnosed bladder pain syndrome/interstitial cystitis (BPS/IC). 141 newly diagnosed women were identified retrospectively. 79 were treated with weekly DMSO/triamcinolone instillations. Change in bladder capacity with bladder retrofill, daytime urinary frequency, nocturia episodes per night, and Likert scale symptom scores were reviewed. Wilcoxon signed-rank tests, Wilcoxon rank-sum tests, Spearman's rank correlations, COX regression analysis, and a Kaplan-Meier survival curve were performed. Significant changes (median (25(th)-percentile to 75(th)-percentile) were noted for bladder capacity (75 mL (25 to 130 mL), p < 0.0001), inter-void interval (0 hrs (0 to 1 hour), p < 0.0001), nocturia episodes per night (-1 (-2 to 0), p < 0.0001), and aggregate Likert symptom scores (-2 points (-5 to 0), p < 0.0001). Percent change in bladder capacity correlated positively with percent change in inter-void interval (p = 0.03) and negatively with percent changes in nocturia (p = 0.17) and symptom scores (p = 0.01). Women without detrusor overactivity (DO) had greater percent changes in capacity than women with DO (62.5 % vs. 16.5 %, p = 0.02). 61.3 % of patients were retreated with a 36 weeks median time to retreatment and no difference in time to retreatment based upon DO. Greater capacity was protective against retreatment (hazard ratio = 0.997 [95 % CI 0.994,0.999], p = 0.02). Percent change in bladder capacity is a useful objective measure of response to intravesical DMSO/triamcinolone for newly diagnosed BPS/IC. Clinical outcomes do not differ based upon presence of DO.

"Spiral-Cap" ileocystoplasty for bladder augmentation and ureteric reimplant.

PubMed

Sawant, S Ajit; Tamhankar, Ashwin Sunil; Kumar, Vikash; Prakash, W Pawar; Gaurav, V Kasat; Bansal, Sumit

2016-01-01

To demonstrate the new technique of Spiral-cap ileocystoplasty for bladder augmentation and simultaneous ureteric reimplant. Seven patients with small capacity bladder and simultaneous lower ureteric involvement operated in single tertiary care institute over the last 5 years were included in this study. Spiral-cap ileocystoplasty was used in all the patients for bladder augmentation. Proximal part of the same ileal loop was used in isoperistaltic manner for ureteric reimplantation. Distal end of this ileal loop was intussuscepted into the pouch to decrease the incidence of reflux. Detubularized distal portion of the loop was reconfigured in spiral manner to augment the native bladder. Patients were analyzed for upper tract changes, serum creatinine, bladder capacity, and requirement of clean intermittent self-catheterization in follow-up over 5 years. There was no evidence of any urinary or bowel leak in the postoperative period. Recovery was equivalent with those treated with other methods of bladder augmentation. Follow-up ultrasonography showed good capacity bladder. Upper tracts were well preserved in follow-up. Urinary bladder and lower ureter pathologies were addressed simultaneously. Spiral-cap ileocystoplasty is a useful technique in patients who require simultaneous bladder augmentation and ureteric reimplant.

Mechanisms of inhibitory action of TRK-130 (Naltalimide), a μ-opioid receptor partial agonist, on the micturition reflex.

PubMed

Fujimura, Morihiro; Izumimoto, Naoki; Kanie, Sayoko; Kobayashi, Ryosuke; Yoshikawa, Satoru; Momen, Shinobu; Hirakata, Mikito; Komagata, Toshikazu; Okanishi, Satoshi; Iwata, Masashi; Hashimoto, Tadatoshi; Doi, Takayuki; Yoshimura, Naoki; Kawai, Koji

2017-04-01

To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex. The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats. TRK-130 (0.001-0.01 mg/kg, iv) dose-dependently inhibited RBCs, which was dose-dependently antagonized by naloxone; however, the antagonism susceptibility was different from morphine (1 mg/kg, iv). The minimum effective dose (0.003 mg/kg) of TRK-130 remained similar in spinal cord-transected animals. TRK-130 (0.0025 mg/kg, iv) increased bladder capacity without changing the voiding efficiency, maximum flow rate, and intravesical pressure at the maximum flow rate, whereas oxybutynin (1 mg/kg, iv) increased the bladder capacity but affected the other parameters. TRK-130 (0.005 mg/kg, iv) did not produce significant changes on the bladder contractions induced by peripheral stimulation of the pelvic nerve, while oxybutynin (1 mg/kg, iv) significantly suppressed the bladder contractions. These results suggest that TRK-130 enhances the bladder storage function by modulating the afferent limb of the micturition reflex through µ-opioid receptors in the spinal cord. TRK-130 could be a more effective and safer therapeutic agent with a different fashion from antimuscarinics and conventional opioids for overactive bladder.

Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction

PubMed Central

Liu, Chong; Xu, Huan; Fu, Shi; Chen, Yanbo; Chen, Qi; Cai, Zhikang; Zhou, Juan; Wang, Zhong

2016-01-01

Purpose. We evaluated the effect of sulforaphane (SFN) treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO). Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each): the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results. We found that SFN treatment could prolong micturition interval and increase bladder capacity and bladder compliance. However, the peak voiding pressure was lower than BOO group. SFN treatment can ameliorate the increase of collagen fibers induced by obstruction. SFN treatment also increased the activity of SOD, GSH-Px, and CAT compared to the other groups. The level of bladder cell apoptosis was decreased in BOO rats with SFN treatment. Moreover, SFN could reduce the ratio of Bax/Bcl-2 expression. Furthermore, SFN could activate the Nrf2 expression with elevation of its target antioxidant proteins. Conclusions. The sulforaphane-mediated decrease of oxidative stress and activation of the Nrf2-ARE pathway may ameliorate bladder dysfunction caused by bladder outlet obstruction. PMID:27433291

Trypanosoma cruzi infection induced changes in the innervation, structure and function of the murine bladder.

PubMed

Boczko, Judd; Tar, Moses; Melman, Arnold; Jelicks, Linda A; Wittner, Murray; Factor, Stephen M; Zhao, Dazhi; Hafron, Jason; Weiss, Louis M; Tanowitz, Herbert B; Christ, George J

2005-05-01

The involvement of the lower urinary tract in chronic Chagas' disease has received little attention. Therefore, we investigated pathology and functional alterations in the bladder of Trypanosoma cruzi infected mice. CD1 mice were infected with 5 x 10 T. cruzi trypomastigotes of the Brazil strain of T. cruzi. At day 100 after infection bladder structure and function were examined by pathological evaluation, magnetic resonance imaging and cystometric studies. The bladder in infected mice weighed more and were large, dilated, deformed, friable and thin walled compared with control mice. Magnetic resonance imaging confirmed these observations. Inflammation, fibrosis and ganglionitis was observed. Cystometric studies revealed that baseline, threshold and micturition pressures were increased in infected mice. Bladder overactivity and decreased bladder compliance were also noted in infected mice. There were no detectable differences in bladder capacity, micturition volume or residual volume between infected and uninfected mice. Bladder abnormalities may be a more common clinical sequelae of T. cruzi infection than previously appreciated.

Urothelial Dysfunction and Chronic Inflammation are Associated With Increased Bladder Sensation in Patients With Chronic Renal Insufficiency.

PubMed

Cheng, Sheng-Fu; Jiang, Yuan-Hong; Kuo, Hann-Chorng

2018-01-01

Chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients usually have lower urinary tract symptoms, such as frequency and urgency. Additionally, they frequently suffer from urinary tract infections. This study investigated dysfunction and chronic inflammation of the bladder urothelium in ESRD/CKD patients. This study enrolled 27 patients with CKD (n=13) or ESRD (n=14) for urodynamic studies and bladder biopsies. Patients presented with detrusor underactivity (DU; n=8) or bladder oversensitivity (BO; n=19). Bladder biopsies were performed in these patients and in 20 controls. The bladder mucosa was examined for E-cadherin and zonula occludens-1 (ZO-1) expression, activated mast cell count (through tryptase staining), and urothelial apoptosis (through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling [TUNEL]). The urodynamic parameters were also compared with variables regarding urothelial dysfunction. The bladder mucosa samples of ESRD and CKD patients revealed significantly higher mast cell counts, more urothelial apoptosis, and lower levels of ZO-1 expression than the control samples. E-cadherin expression was significantly reduced in ESRD/CKD patients with DU, but not in ESRD/CKD patients with BO. Increased mast cell and apoptotic cell counts were also associated with ESRD/CKD with BO. Less expression of ZO-1 and E-cadherin was significantly associated with increased bladder sensation and a small bladder capacity. Bladder urothelial dysfunction and chronic inflammation were present to a noteworthy extent in patients with ESRD or CKD. Increased inflammation and defective barrier function were more notable in ESRD/CKD bladders with BO than in those with DU. The clinical characteristics of these patients may involve urothelial pathophysiology.

Role for pAKT in rat urinary bladder with cyclophosphamide (CYP)-induced cystitis

PubMed Central

Arms, Lauren

2011-01-01

AKT phosphorylation following peripheral nerve injury or inflammation may play a role in somatic pain processes and visceral inflammation. To examine such a role in micturition reflexes with bladder inflammation, we induced bladder inflammation in adult female Wistar rats (200–300 g) by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every third day for 10 days) time points. Western blot analyses of whole urinary bladders showed significant increases (P ≤ 0.01) in phosphorylated (p) AKT at all time points; however, the magnitude of AKT phosphorylation varied with duration of CYP treatment. Immunohistochemical analyses of pAKT immunoreactivity (pAKT-IR) in cryostat bladder sections demonstrated duration-dependent, significant (P ≤ 0.01) increases in pAKT-IR in both the urothelium and detrusor smooth muscle of CYP-inflamed bladders. Additionally, a suburothelial population of pAKT-IR macrophages (CD68-, MAC2-, and F4/80-positive) was present in chronic CYP-treated bladders. The functional role of pAKT in micturition was evaluated using open, conscious cystometry with continuous instillation of saline in conjunction with administration of an inhibitor of AKT phosphorylation, deguelin (1.0 μg/10 μl), or vehicle (1% DMSO in saline) in control (no inflammation) and CYP (48 h)-treated rats. Bladder capacity, void volume, and intercontraction void interval increased significantly (P ≤ 0.05) following intravesical instillation of deguelin in CYP (48 h)-treated rats. These results demonstrate increased AKT phosphorylation in the urinary bladder with urinary bladder inflammation and that blockade of AKT phosphorylation in the urothelium improves overall bladder function. PMID:21632956

The inhibitory effect of sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive bladder reflexes in cats.

PubMed

Wang, Zhaoxia; Liao, Limin; Deng, Han; Li, Xing; Chen, Guoqing

2018-05-01

To investigate the inhibitory effects of electrical stimulation of sacral dorsal root ganglion (DRG) on bladder activity under non-nociceptive and nociceptive bladder conditions in cats. 12 cats were divided into non-nociceptive and nociceptive groups. Saline was used to distend the bladder and induce non-nociceptive bladder activity, while acetic acid (AA, 0.25%) was used to induce nociceptive bladder overactivity, S1 or S2 DRG stimulation was applied via a pair of hook electrodes placed in the right S1 and S2 DRG. In both non-nociceptive and nociceptive groups, stimulation at 3 and 5 Hz significantly increased bladder capacity (BC) and no significantly different between the two frequencies. In non-nociceptive group, S1 DRG stimulation at 3 Hz was as effective (increasing BC to 139.7 ± 5.6 and 166.9 ± 12.21% of control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 129.2 ± 5.6 and 160.5 ± 13.3% of control). In nociceptive group, AA reduced the BC to 62.6 ± 11.7% of saline control. S1 DRG stimulation at 3 Hz was also as effective (increasing BC to 54.9 ± 5.5 and 61.9 ± 6.0% of saline control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 58.3 ± 3.7 and 65.6 ± 3.7% of control). This study showed the effective inhibition on bladder activity under both non-nociceptive and nociceptive conditions, suggesting the possibility of sacral DRG stimulation to treat bladder overactivity.

Ketamine-snorting associated cystitis.

PubMed

Chen, Chung-Hsien; Lee, Ming-Huei; Chen, Yi-Chang; Lin, Ming-Fong

2011-12-01

Ketamine hydrochloride, commonly used as a pediatric anesthetic agent, is an N-methyl-D-aspartic (NMDA) acid receptor antagonist with rapid onset and short duration of action. It produces a cataleptic-like state where the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. It has emerged as an increasingly popular choice among young drug users, especially within dance club venues. Cases of bladder dysfunction among recreational ketamine users were reported since Shahani et al first reported nine cases of ketamine-associated ulcerative cystitis in 2007. We report on four patients who had history of ketamine abuse, presenting with dysuria, fluctuating lower urinary tract symptoms (LUTS), lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis showed pyuria and microhematuria. Urine culture was sterile. Bladder ulceration with severe diffuse hemorrhage and low bladder capacity were noted under anesthetized cystoscopic examination. Transurethral bladder mucosa biopsy was consistent with chronic cystitis. Cessation of ketamine abuse was the milestone of treatment, followed by the administration of mucosal protective agents, such as pentosan polysulphate or hyaluronic acid. Suprapubic pain was improved in three patients during follow-up. However, the outcome of treatment depends on the severity of the disease process, similar to that of interstitial cystitis (IC). Copyright © 2011. Published by Elsevier B.V.

Identification of potential bladder cancer markers in urine by abundant-protein depletion coupled with quantitative proteomics.

PubMed

Chen, Chien-Lun; Lin, Tsung-Shih; Tsai, Cheng-Han; Wu, Chih-Ching; Chung, Ting; Chien, Kun-Yi; Wu, Maureen; Chang, Yu-Sun; Yu, Jau-Song; Chen, Yi-Ting

2013-06-24

In this study, we evaluated the reproducibility of abundant urine protein depletion by hexapeptide-based library beads and an antibody-based affinity column using the iTRAQ technique. The antibody-based affinity-depletion approach, which proved superior, was then applied in conjunction with iTRAQ to discover proteins that were differentially expressed between pooled urine samples from hernia and bladder cancer patients. Several proteins, including seven apolipoproteins, TIM, SAA4, and proEGF were further verified in 111 to 203 individual urine samples from patients with hernia, bladder cancer, or kidney cancer. Six apolipoproteins (APOA1, APOA2, APOB, APOC2, APOC3, and APOE) were able to differentiate bladder cancer from hernia. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. Additionally, the combination of SAA4 and ProEGF exhibited higher diagnostic capacity (AUC=0.80 and p<0.001) in discriminating bladder cancer from hernia than either marker alone. Using MetaCore software to interpret global changes of the urine proteome caused by bladder cancer, we found that the most notable alterations were in immune-response/alternative complement and blood-coagulation pathways. This study confirmed the clinical significance of the urine proteome in the development of non-invasive biomarkers for the detection of bladder cancer. In this study, we evaluated the reproducibility of abundant urine protein depletion by hexapeptide-based library beads and an antibody-based affinity column using the iTRAQ technique. The antibody-based affinity-depletion approach, which proved superior, was then applied in conjunction with iTRAQ to discover proteins that were differentially expressed between pooled urine samples from hernia and bladder cancer patients. Several proteins, including seven apolipoproteins, TIM, SAA4, and proEGF were further verified in 111 to 203 individual urine samples from patients with hernia, bladder cancer, or kidney cancer. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. Additionally, the combination of SAA4 and ProEGF exhibited higher diagnostic capacity in discriminating bladder cancer from hernia than either marker alone. A marker panel composed by two novel biomarker candidates, SAA4 and proEGF, was first discovered and verified successfully using Western blotting. To the best of our knowledge, the associations of urinary SAA4 and proEGF with bladder tumor and kidney cancer have not been mentioned before. In the present study, we discovered and verified SAA4 and proEGF as potential bladder cancer biomarker for the first time. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes

PubMed Central

Gonzalez, Eric J.; Peterson, Abbey; Malley, Susan; Daniel, Mitchel; Lambert, Daniel; Kosofsky, Michael; Vizzard, Margaret A.

2015-01-01

We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P ≤ 0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P ≤ 0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P ≤ 0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation. PMID:25973443

Effects of vitamin D analog on bladder function and sensory signaling in animal models of cystitis.

PubMed

Shapiro, Bennett; Redman, T Lawton; Zvara, Peter

2013-02-01

To measure the effects of nonhypercalcemic vitamin D receptor agonist elocalcitol on bladder function in rats with cyclophosphamide-induced cystitis and on bladder function and sensory nerve activity in a mouse with acetic acid-evoked bladder irritation. Female Wistar rats and male Balb/C mice were gavaged once daily with elocalcitol diluted in miglyol 812 (treatment group) or miglyol alone (control group). On experimental day 12, polyethylene tubing was implanted into the urinary bladder in all the animals. In the mice, a bipolar electrode was positioned under a single postganglionic bladder nerve. At 48 hours after surgery, bladder function was measured in awake, freely moving rats during bladder filling with 0.9% NaCl and both bladder function and sensory nerve activity was measured in awake, restrained mice during continuous intravesical infusion of 0.9% NaCl followed by 0.25% acetic acid. In rats, the treatment group showed a significant increase in bladder capacity and decrease in number of nonvoiding bladder contractions. In mice, the filling pressure during saline infusion was similar in both groups; however, during acetic acid infusion, the average filling pressure was significantly increased (47%) in the control group but not in the elocalcitol treatment group. The firing rate at filling pressure for the treatment group was 3.6-fold and 2.7-fold lower than that in the control group during the saline and acetic acid infusion, respectively. Oral treatment with elocalcitol suppressed signs of detrusor overactivity in both animal models and exerted strong suppressive effect on urinary bladder sensory signaling during filling in mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of intravesical Resiniferatoxin (RTX) on lower urinary tract symptoms, urodynamic parameters, and quality of life of patients with urodynamic increased bladder sensation.

PubMed

Apostolidis, Apostolos; Gonzales, Gwendoline E; Fowler, Clare J

2006-12-01

Intravesical resiniferatoxin (RTX) has been used with variable efficacy in the treatment of detrusor overactivity (DO). Patients with interstitial cystitis (IC) failed to benefit from this treatment, but a single placebo-controlled study in patients with non-IC painful bladders showed that RTX was effective in the short-term. We investigated the efficacy of intravesical RTX in patients with urgency and frequency due to increased bladder sensation. Patients with intractable urgency and frequency, with or without urgency incontinence or bladder pain/discomfort, and with no urodynamic evidence of DO were recruited. After a single intravesical instillation of 100ml 50 nM RTX solution, patients were followed at 1, 3, and 6 mo for changes in urodynamics, bladder diary, the King's Health Questionnaire (KHQ), and degree of bladder pain. Fifteen patients (mean age, 52.5 yr) were treated. RTX significantly improved maximum cystometric capacity, volume at first desire to void, mean micturition volume, 24-h frequency, and daytime frequency for up to 6 mo after treatment. The overall KHQ score improved at all time points, with sustained improvements in the Symptom Severity, Incontinence Impact, and Personal Relationships domains. A >50% decrease in pain was reported by five of seven patients with painful bladders at 1 mo, but only one of seven at 6 mo. In our small open-label study, a single administration of intravesical RTX in patients with frequency and urgency due to increased bladder sensation significantly improved lower urinary tract symptoms, urodynamic parameters, and quality of life for up to 6 mo.

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

PubMed Central

Guo, Michael; Chang, Phat; Hauke, Eric; Girard, Beatrice M.; Tooke, Katharine; Ojala, Jacqueline; Malley, Susan M.; Hsiang, Harrison; Vizzard, Margaret A.

2018-01-01

Changes in urinary bladder function and somatic sensation may be mediated, in part, by inflammatory changes in the urinary bladder including the expression of chemokines. Male and female C57BL/6 mice were treated with cyclophosphamide (CYP; 75 mg/kg, 200 mg/kg, i.p.) to induce bladder inflammation (4 h, 48 h, chronic). We characterized the expression of CXC chemokines (CXCL9, CXCL10 and CXCL11) in the urinary bladder and determined the effects of blockade of their common receptor, CXCR3, at the level urinary bladder on bladder function and somatic (hindpaw and pelvic) sensation. qRT-PCR and Enzyme-Linked Immunoassays (ELISAs) were used to determine mRNA and protein expression of CXCL9, CXCL10 and CXCL11 in urothelium and detrusor. In urothelium of female mice treated with CYP, CXCL9 and CXCL10 mRNA significantly (p ≤ 0.01) increased with CYP treatment whereas CXC mRNA expression in the detrusor exhibited both increases and decreases in expression with CYP treatment. CXC mRNA expression urothelium and detrusor of male mice was more variable with both significant (p ≤ 0.01) increases and decreases in expression depending on the specific CXC chemokine and CYP treatment. CXCL9 and CXCL10 protein expression was significantly (p ≤ 0.01) increased in the urinary bladder with 4 h CYP treatment in female mice whereas CXC protein expression in the urinary bladder of male mice did not exhibit an overall change in expression. CXCR3 blockade with intravesical instillation of AMG487 (5 mg/kg) significantly (p ≤ 0.01) increased bladder capacity, reduced voiding frequency and reduced non-voiding contractions in female mice treated with CYP (4 h, 48 h). CXCR3 blockade also reduced (p ≤ 0.01) hindpaw and pelvic sensitivity in female mice treated with CYP (4 h, 48 h). CXC chemokines may be novel targets for treating urinary bladder dysfunction and somatic sensitization resulting from urinary bladder inflammation. PMID:29681802

Morphometric partitioning of the respiratory surface area and diffusion capacity of the gills and swim bladder in juvenile Amazonian air-breathing fish, Arapaima gigas.

PubMed

Fernandes, Marisa Narciso; da Cruz, André Luis; da Costa, Oscar Tadeu Ferreira; Perry, Steven Franklin

2012-09-01

The gills and the respiratory swim bladders of juvenile specimens (mean body mass 100g) of the basal teleost Arapaima gigas (Cuvier 1829) were evaluated using stereological methods in vertical sections. The surface areas, harmonic mean barrier thicknesses and morphometric diffusing capacities for oxygen and carbon dioxide were estimated. The average respiratory surface area of the swim bladder (2173 cm² kg⁻¹) exceeded that of the gills (780 cm² kg⁻¹) by a factor of 2.79. Due to the extremely thin air-blood barrier in the swim bladder (harmonic mean 0.22 μm) and the much thicker water-blood barrier of the gills (9.61 μm), the morphometric diffusing capacity for oxygen and carbon dioxide was 88 times greater in the swim bladder than in the gills. These data clearly indicate the importance of the swim bladder, even in juvenile A. gigas that still engage in aquatic respiration. Because of the much greater diffusion constant of CO₂ than O₂ in water, the gills also remain important for CO₂ release. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bladder sensation measures and overactive bladder.

PubMed

Rapp, David E; Neil, Nancy J; Govier, Fred E; Kobashi, Kathleen C

2009-09-01

We performed a prospective multicomponent study to determine whether subjective and objective bladder sensation instruments may provide data on sensory dysfunction in patients with overactive bladder. We evaluated 70 prospectively enrolled patients with urodynamics and questionnaires on validated urgency (Urgency Perception Score), general overactive bladder (Urogenital Distress Inventory) and quality of life (Incontinence Impact Questionnaire). We first sought a correlation between sensory specific (Urgency Perception Score) and quality of life questionnaire scores. We then assessed a correlation between sensory questionnaire scores and urodynamic variables, exploring the hypothesis that certain urodynamic parameters may be bladder sensation measures. We evaluated 2 urodynamic derivatives (first sensation ratio and bladder urgency velocity) to increase sensory finding discrimination. We noted a moderate correlation between the Urgency Perception Score (0.56) and the Urogenital Distress Inventory (0.74) vs the Incontinence Impact Questionnaire (each p <0.01). A weak negative correlation was seen between Urgency Perception Score and bladder capacity (-0.25, p <0.05). No correlation was noted for the other urodynamics parameters. First sensation ratio and bladder urgency velocity statistically significantly correlated with the Urgency Perception Score despite the lesser or absent correlation associated with the individual components of these derivatives. Bladder sensation questionnaires may be valuable to identify patients with sensory dysfunction and provide additional data not obtained in generalized symptom questionnaires. Urodynamic variables correlated with bladder sensation questionnaire scores and may be an objective method to assess sensory dysfunction.

[Analysis for related factors of upper urinary tract deterioration in patients with spinal cord injury].

PubMed

Jing, Hua-fang; Liao, Li-min; Fu, Guang; Wu, Juan; Ju, Yan-he; Chen, Guo-qing

2014-08-18

To evaluate the related factors of upper urinary tract deterioration in spinal cord injured patients. Medical records of spinal cord injured patients from Jan.2002 to Sep.2009 were retrospectively reviewed. All the patients were divided into the upper urinary tract deterioration group and non-deterioration group according to the diagnostic criteria. Indexes such as demographic characteristic (gender, age), spinal cord injury information (cause, level, completeness), statuses of urinary tract system (bladder management, urine routine, urine culture, ultrasound, serum creatinine, fever caused by urinary tract infection) and urodynamics information(bladder compliance, bladder stability, bladder sensation, detrusor sphincter dyssynergia, detrusor leak point pressure, maximum cystometric capacity, relative safe bladder capacity, maximum flow rate, maximum urethra closure pressure) were compared between the two groups.Then Logistic regression analysis were performed. There was significantly difference between the two groups in spinal cord injury level(χ(2) = 8.840, P = 0.031),bladder management(χ(2) = 11.362, P = 0.045), urinary rutine(χ(2) = 17.983, P = 0.000), fever caused by urinary tract infection(χ(2)= 64.472, P = 0.000), bladder compliance(χ(2) = 6.531, P = 0.011), bladder sensation(χ(2) = 11.505, P = 0.009), maximum cystometric capacity(t = 2.209, P = 0.043), and detrusor-sphincter dyssynergia(χ(2) = 4.247, P = 0.039). The multiple-factor non-conditional Logistic regression analysis showed that bladder management (OR = 1.114, P = 0.006), fever caused by urinary tract infection(OR = 1.018,P = 0.000), bladder compliance (OR = 1.588, P = 0.040) and detrusor-sphincter dyssynergia(OR = 1.023, P = 0.034) were the key factors of upper urinary tract deterioration in spinal cord injured patients. Urinary tract infection, lower bladder compliance, detrusor-sphincter dyssynergia and unreasonable bladder management are the risk factors of upper urinary tract deterioration in spinal cord injured patients.

Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

PubMed

Qiao, Zhongwei; Xia, Chunmei; Shen, Shanwei; Corwin, Frank D; Liu, Miao; Guan, Ruijuan; Grider, John R; Qiao, Li-Ya

2014-01-01

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

Differential association for N-acetyltransferase 2 genotype and phenotype with bladder cancer risk in Chinese population.

PubMed

Quan, Lei; Chattopadhyay, Koushik; Nelson, Heather H; Chan, Kenneth K; Xiang, Yong-Bing; Zhang, Wei; Wang, Renwei; Gao, Yu-Tang; Yuan, Jian-Min

2016-06-28

N-acetyltransferase 2 (NAT2) is involved in both carcinogen detoxification through hepatic N-acetylation and carcinogen activation through local O-acetylation. NAT2 slow acetylation status is significantly associated with increased bladder cancer risk among European populations, but its association in Asian populations is inconclusive. NAT2 acetylation status was determined by both single nucleotide polymorphisms (SNPs) and caffeine metabolic ratio (CMR), in a population-based study of 494 bladder cancer patients and 507 control subjects in Shanghai, China. The CMR, a functional measure of hepatic N-acetylation, was significantly reduced in a dose-dependent manner among both cases and controls possessing the SNP-inferred NAT2 slow acetylation status (all P-values<5.0×10-10). The CMR-determined slow N-acetylation status (CMR<0.34) was significantly associated with a 50% increased risk of bladder cancer (odds ratio = 1.50, 95% confidence interval = 1.10-2.06) whereas the SNP-inferred slow acetylation statuses were significantly associated with an approximately 50% decreased risk of bladder cancer. The genotype-disease association was strengthened after the adjustment for CMR and was primarily observed among never smokers. The apparent differential associations for phenotypic and genetic measures of acetylation statuses with bladder cancer risk may reflect dual functions of NAT2 in bladder carcinogenesis because the former only measures the capacity of carcinogen detoxification pathway while the latter represents both carcinogen activation and detoxification pathways. Future studies are warranted to ascertain the specific role of N- and O-acetylation in bladder carcinogenesis, particularly in populations exposed to different types of bladder carcinogens.

Can recording only the day-time voided volumes predict bladder capacity?

PubMed

Cho, Won Yeol; Kim, Seong Cheol; Kim, Sun-Ouck; Park, Sungchan; Lee, Sang Don; Chung, Jae Min; Kim, Kyung Do; Moon, Du Geon; Kim, Young Sig; Kim, Jun Mo

2018-05-01

This study aimed to demonstrate a method to easily assess bladder capacity using knowledge of day-time voided volumes, which can be obtained even from patients with nocturnal enuresis where the first morning void cannot accurately predict the bladder capacity due to bladder emptying overnight. We evaluated 177 healthy children from 7 Korean medical centres entered the study between January 2008 and January 2009. Voided volumes measured for more than 48 hours were recorded in the frequency volume chart (FVC). Most voided volumes during day-time were showed between 30% and 80% of the maximal voided volume (MVV). The maximal voided volume during day-time (MVVDT) was significantly less than the MVV (179.5±71.1 mL vs. 227.0±79.2 mL, p<0.001). The correlation coefficients with the MVV were 0.801 for the estimated MVV using the MVVDT (MVVDT×1.25), which suggested a fairly strong relationship between the MVVDT×1.25 and the MVV. The MVV derived from the FVC excluding the FMV was less than if the FMV had been included. When an accurate first morning voided volume cannot be obtained, as in patients with nocturnal enuresis, calculating MVVDT×1.25 allows estimation of the bladder capacity in place of the MVV.

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PubMed

Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S

2015-04-01

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The effect of rectal distension on bladder function in patients with overactive bladder.

PubMed

Akl, Mohamed N; Jacob, Kristina; Klauschie, Jennifer; Crowell, Michael D; Kho, Rosanne M; Cornella, Jeffrey L

2012-04-01

To investigate the effect of rectal distension on bladder sensation volumes and the number of detrusor contractions in patients with overactive bladder (OAB) symptoms. A prospective randomized study included patients with OAB symptoms. Multichannel urodynamic studies were completed with and without rectal balloon distension. Bladder sensation volumes and detrusor contractions were compared. Twenty-six patients were included in the study. The mean age was 67 years and mean BMI was 28.3 kg/m(2) . Bladder sensation volumes were lower with rectal distention as follows: normal desire to void (139 ml SD, ±114 vs. 197 ml SD ±150, P = 0.01), strong desire to void (260 ml SD ±171 vs. 330 ml SD ±172, P = 0.01), and maximum cystometric capacity (326 ml SD ±183 vs. 403 ml SD ±180, P = 0.0001). There was no difference in the number of detrusor contractions or the bladder volume at which the first detrusor contraction had occurred with and without rectal distension. Rectal distention in patients with OAB symptoms significantly lowered bladder sensation volumes (normal desire, strong desire, and maximal capacity). Copyright © 2012 Wiley Periodicals, Inc.

Objective measurement of bladder sensation: use of a new patient-activated device and response to neuromodulation.

PubMed

Craggs, Michael D

2005-09-01

Detrusor overactivity is the primary objective focus of most investigations into the diagnosis and management of patients with urgency incontinence. Patients with an overactive bladder are characteristically troubled by subjective sensations of bladder fullness and urinary urgency, and frequently void at low bladder volumes attained before noticeable detrusor overactivity occurs. Bladder sensations are therefore crucial to understanding voiding patterns and symptoms, but little progress has been made in objectively describing the range of these sensations, and adequate information is lacking about their response to neuromodulation. Towards this end, a keypad 'urge score' device was designed to measure sensations during bladder filling. This patient-activated device gathers information about patient perceptions of bladder filling and the successive stages of increasing bladder sensation, without prompting or intervention by the investigator. The accuracy of the 'urge keypad' during filling cystometrography was validated in patients with urgency incontinence, and compared with data abstracted from patient voiding diaries. The device provides reliable and repeatable measures of different bladder sensations, with excellent, statistically significant consistency between bladder volumes and corresponding levels of sensation. Subsequently, it was shown that the sensation of urgency can be suppressed by neuromodulation in most patients tested; this suppression occurs with improvements in bladder capacity and voided volumes. It is therefore suggested that urodynamics with concurrent sensory evaluation may offer a more useful assessment tool for selecting those patients for therapies such as neuromodulation who present predominantly with the symptom of urgency.

Prerequisite for successful surgical outcome in urothelium lined seromuscular colocystoplasty.

PubMed

Jung, Hyun Jin; Lee, Hyeyoung; Im, Young Jae; Lee, Yong Seung; Hong, Chang Hee; Han, Sang Won

2012-04-01

Urothelium lined seromuscular colocystoplasty is an ideal method of augmentation cystoplasty that avoids various complications caused by the use of gastrointestinal segments. We reviewed the long-term outcomes using this technique at a single institution. We retrospectively analyzed 34 patients who underwent urothelium lined seromuscular colocystoplasty between January 1996 and December 2007. A total of 33 patients, excluding 1 who had previously undergone artificial urinary sphincter implantation, were included in the study. Changes in urodynamic parameters, duration of anticholinergic use, incontinence and surgical complications were analyzed. Mean±SD age at surgery was 10.0±5.7 years (range 3.0 to 26.0) and duration of followup was 6.0±2.3 years (2.7 to 13.4). A total of 17 patients (51.5%) underwent simultaneous anti-incontinence surgery and urothelium lined seromuscular colocystoplasty. Mean bladder capacity increased by a factor of 2.96 and mean percentage of expected bladder capacity for age increased by a factor of 1.96 postoperatively. Of patients who underwent anti-incontinence surgery 4 of 10 whose abdominal leak point pressure was less than 40 cm H2O required additional surgery, whereas none whose abdominal leak point pressure was 40 to 60 cm H2O required reoperation. Two of 16 patients who did not undergo anti-incontinence surgery eventually required continence surgery. A total of 13 patients (39.4%) were able to discontinue anticholinergics at 47.3 months postoperatively. There were no bladder perforations, bowel obstructions or metabolic abnormalities. Urothelium lined seromuscular colocystoplasty can be primarily considered in patients without prior bladder mucosal injury. Constant high bladder outlet pressure to facilitate adhesion of bladder mucosa and seromuscular patch is critical for the best results. We recommend abdominal leak point pressure 60 cm H2O or less as an indication for simultaneous anti-incontinence surgery and urothelium lined seromuscular colocystoplasty. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pharmacotherapy in Pediatric Neurogenic Bladder Intravesical Botulinum Toxin Type A

PubMed Central

Sager, Cristian; Burek, Carol; Durán, Victor; Corbetta, Juan Pablo; Weller, Santiago; Juan, Bortagaray; López, Juan Carlos

2012-01-01

When the neurogenic bladder is refractory to anticholinergics, botulinum toxin type A is used as an alternative. The neurotoxin type A reduces bladder pressure and increases its capacity and wall compliance. Additionally, it contributes to improving urinary continence and quality of life. This novel therapy is ambulatory with a low incidence of adverse effects. Due to its transitory effect, it is necessary to repeat the injections in order to sustain its therapeutic effect. In these review article we talk about Mechanism of Action, Indications, effects, administration and presentations of the Botulinum Neurotoxin Type A in pediatric patients. Also, we make references to controversial issues surrounding its use. A bibliographic search was done selecting articles and revisions from Pubmed. The key words used were botulinum toxin A, neurogenic bladder, and children. The search was limited to patients younger than 18 years of age and reports written in English in the past ten years. PMID:22720170

Expression and function of CCL2/CCR2 in rat micturition reflexes and somatic sensitivity with urinary bladder inflammation

PubMed Central

Arms, Lauren; Girard, Beatrice M.; Malley, Susan E.

2013-01-01

Chemokines are proinflammatory mediators of the immune response, and there is growing evidence for chemokine/receptor signaling involvement in pronociception. Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder-related with at least one urinary symptom. We have explored the expression and functional roles of CCL2 (monocyte chemoattractant protein-1) and its high-affinity receptor, CCR2, in micturition reflex function and somatic sensitivity in rats with urinary bladder inflammation induced by cyclophosphamide (CYP) treatment of varying duration (4 h, 48 h, chronic). Real-time quantitative RT-PCR, ELISAs, and immunohistochemistry demonstrated significant (P ≤ 0.01) increases in CCL2 and CCR2 expression in the urothelium and in Fast Blue-labeled bladder afferent neurons in lumbosacral dorsal root ganglia with CYP-induced cystitis. Intravesical infusion of RS504393 (5 μM), a specific CCR2 antagonist, reduced voiding frequency and increased bladder capacity and void volume in rats with CYP-induced cystitis (4 h), as determined with open outlet, conscious cystometry. In addition, CCR2 blockade, at the level of the urinary bladder, reduced referred somatic sensitivity of the hindpaw and pelvic region in rats with CYP treatment, as determined with von Frey filament testing. We provide evidence of functional roles for CCL2/CCR2 signaling at the level of the urinary bladder in reducing voiding frequency and somatic sensitivity following CYP-induced cystitis (4 h). These studies suggest that chemokines/receptors may be novel targets with therapeutic potential in the context of urinary bladder inflammation. PMID:23594826

Progressive vascular damage may lead to bladder underactivity in rats.

PubMed

Nomiya, Masanori; Yamaguchi, Osamu; Akaihata, Hidenori; Hata, Junya; Sawada, Norifumi; Kojima, Yoshiyuki; Andersson, Karl-Erik

2014-05-01

We assessed whether progressive vascular damage causes bladder underactivity in rats. Adult male Sprague Dawley® rats were divided into 4 groups. Controls received a regular diet and tap water. The L-NAME group received a 2% cholesterol diet and L-NAME (3 mg/ml) dissolved in drinking water. The arterial injury group underwent balloon endothelial injury of the common iliac arteries and received a 2% cholesterol diet and tap water after injury. The arterial injury/L-NAME group also received L-NAME dissolved in drinking water. At 8 weeks urodynamics were performed, bladder tissue was harvested for pharmacological studies, and the iliac arteries and bladders were histologically examined. Iliac arteries from the injury and injury/L-NAME groups showed neointimal formation and luminal occlusion but arteries from the L-NAME group did not. In the L-NAME and injury groups bladder capacity and voided volume were less than in controls. Conversely, in the injury/L-NAME group these cystometric parameters were significantly greater than in the other groups. Post-void residual volume in the injury/L-NAME group tended to increase compared with the other groups. Contractile responses of bladder strips to various stimuli in the L-NAME, injury and injury/L-NAME groups were significantly less than in controls and the lowest in the injury/L-NAME group. The injury and injury/L-NAME groups showed a significantly increased percent of collagen compared to controls. Pelvic arterial occlusive disease plus vascular endothelial dysfunction may cause progressive vascular damage resulting in bladder dysfunction that develops from bladder hyperactivity to bladder underactivity. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Adherence of urease-induced crystals to rat bladder epithelium.

PubMed

Grenabo, L; Hedelin, H; Pettersson, S

1988-01-01

Apart from urine supersaturation with respect to struvite and calcium phosphate caused by urease-producing microorganisms, retention of formed crystals in the urinary tract is necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat lining the urothelium in the adhesion of urease-induced crystals. Removal of this glycosaminoglycan-containing layer from rat bladders increased the adherence of struvite and calcium phosphate crystals 5-6 times compared to that in intact rat bladders. Heparin completely restored the antiadherence capacity while chondroitin sulphate had a very weak restorative effect and human urine had no restorative effect. These findings support the view that the mucous coat is of importance in preventing retention of urease-induced crystals.

Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice.

PubMed

Aboushwareb, Tamer; Zhou, Ge; Deng, Fang-Ming; Turner, Chanda; Andersson, Karl-Erik; Tar, Moses; Zhao, Weixin; Melman, Arnold; D'Agostino, Ralph; Sun, Tung-Tien; Christ, George J

2009-01-01

The effects of deleting genes encoding uroplakins II (UPII) and III (UPIIIa) on mouse bladder physiology/dysfunction were studied in male and female wild type and knockout (KO) mice. UPII, UPIIIa, and WT mice were catheterized using previously described techniques. Continuous cystometry was conducted in conscious, freely moving animals. Bladder strips were harvested after animal sacrifice and pharmacological studies and EFS were conducted in an organ chamber. Histological studies were also carried on with H&E staining to identify differences among the three mouse types. These studies have revealed numerous alterations, some of which were apparently gender-specific. Nonvoiding contractions were common in both UPII and UPIIIa KO mice, although more severe in the former. In particular, the increased bladder capacity, micturition pressure and demonstrable nonvoiding contractions observed in the male UPII KO's, were reminiscent of an obstruction-like syndrome accompanied by evidence of emerging bladder decompensation, as reflected by an increased residual volume. Pharmacological studies revealed a modest, gender-specific reduction in sensitivity of isolated detrusor strips from UPII KO female mice to carbachol-induced contractions. A similar reduction was observed in UPIIIa KO female mice. Histological investigation showed urothelial hyperplasia in both UPII KO and UPIIIa KO mice, although again, apparently more severe in the former. These results confirm and extend previous work to indicate that urothelial defects due to uroplakin deficiency are associated with significant alterations in bladder function and further highlight the importance of the urothelium to bladder physiology/dysfunction.

Chronobiology of micturition: putative role of the circadian clock.

PubMed

Negoro, Hiromitsu; Kanematsu, Akihiro; Yoshimura, Koji; Ogawa, Osamu

2013-09-01

Mammals urinate less frequently during the sleep period than the awake period. This is modulated by a triad of factors, including decreased arousal in the brain, a decreased urine production rate in the kidneys and increased functional bladder capacity during sleep. The circadian clock is genetic transcription-translation feedback machinery. It exists in most organs and cells, termed the peripheral clock, which is orchestrated by the central clock in the suprachiasmatic nucleus of the brain. We discuss the linkage between the day and night change in micturition frequency and the genetic rhythm maintained by the circadian clock system, focusing on the brain, kidney and bladder. We performed an inclusive review of the literature on the diurnal change in micturition frequency, urine volume, functional bladder capacity and urodynamics in humans and rodents, relating this to recent basic biological findings about the circadian clock. In humans various behavioral studies demonstrated a diurnal functional change in the kidney and bladder. Conversely, patients with nocturnal enuresis and nocturia showed impairment in this triad of factors. Rats and mice, which are nocturnal animals, also have a micturition frequency rhythm that is decreased during the day, which is the sleep phase for them. Mice with a genetically defective circadian clock system show impaired physiological rhythms in the triad of factors. The existence of the circadian clock has been proven in the brain, kidney and bladder, in which thousands of circadian oscillating genes exist. In the kidney they include genes involved in the regulation of water and major electrolytes. In the bladder they include connexin 43, a gene associated with the regulation of bladder capacity. Recent progress in molecular biology about the circadian clock provides an opportunity to investigate the genetic basis of the micturition rhythm or impairment of the rhythm in nocturnal enuresis and nocturia. If this approach is to be translated clinically, a strategy is to analyze and treat the triad of micturition factors as separate parts of 1 problem. The other way could be to cope with this triad of problems simultaneously, if possible, by treating the circadian physiological rhythm itself. The discoveries reviewed point toward further investigation of the micturition rhythm by basic and translational chronobiology. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Repeated onabotulinumtoxin-a injections provide better results than single injection in treatment of painful bladder syndrome.

PubMed

Kuo, Hann-Chorng

2013-01-01

Onabotulinumtoxin-A (BoNT-A) is effective for the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS). However, long-term follow-up does not show successful outcome after a single injection. To evaluate the efficacy and safety of repeated intravesical BoNT-A injections for treatment of IC/PBS and compare the success rates among patient groups receiving different injection numbers. Prospective interventional study. Tertiary medical center. Intravesical injection of 100 U of BoNT-A was performed in 81 patients every 6 months for up to 4 times or until patients' symptoms significantly improved. Patients who received a single injection served as active controls. Measured parameters included O'Leary-Sant symptom indexes (ICSI) and problem indexes (ICPI), visual analogue score (VAS) for pain, voiding diary variables, urodynamic parameters, maximal bladder capacity under anesthesia, glomerulation grade, and global response assessment. Multiple measurements and Kaplan-Meier analysis were used for comparison of consecutive data and success rates among groups. Among 81 patients, 20 received single injections, 19 received 2 injections, 12 received 3 injections, and 30 received 4 injections. The mean (± standard deviation) of ICSI, ICPI, total scores, VAS, functional bladder capacity, and daytime frequency all showed significant improvement after repeated BoNT-A treatment with different injections. Significantly better success rates were noted in patients who received 4 repeated injections (P = 0.0242) and 3 injections (P = 0.050), compared to those who received a single injection. However, there was no significant difference of long-term success rates among patients who received 2, 3, and 4 injections. Lack of placebo control group is the main limitation. Repeated intravesical BoNT-A injections were safe and effective for pain relief and they increased bladder capacity and provided a better long-term success rate than a single injection did for treatment of IC/PBS.

Alterations in Bladder Function Associated With Urothelial Defects in Uroplakin II and IIIa Knockout Mice

PubMed Central

Aboushwareb, Tamer; Zhou, Ge; Deng, Fang-Ming; Turner, Chanda; Andersson, Karl-Erik; Tar, Moses; Zhao, Weixin; Melman, Arnold; D’Agostino, Ralph; Sun, Tung-Tien; Christ, George J.

2014-01-01

Aims The effects of deleting genes encoding uroplakins II (UPII) and III (UPIIIa) on mouse bladder physiology/ dysfunction were studied in male and female wild type and knockout (KO) mice. Methods UPII, UPIIIa, and WT mice were catheterized using previously described techniques. Continuous cystometry was conducted in conscious, freely moving animals. Bladder strips were harvested after animal sacrifice and pharmacological studies and EFS were conducted in an organ chamber. Histological studies were also carried on with H&E staining to identify differences among the three mouse types. Results These studies have revealed numerous alterations, some of which were apparently gender-specific. Nonvoiding contractions were common in both UPII and UPIIIa KO mice, although more severe in the former. In particular, the increased bladder capacity, micturition pressure and demonstrable nonvoiding contractions observed in the male UPII KO’s, were reminiscent of an obstruction-like syndrome accompanied by evidence of emerging bladder decompensation, as reflected by an increased residual volume. Pharmacological studies revealed a modest, gender-specific reduction in sensitivity of isolated detrusor strips from UPII KO female mice to carbachol-induced contractions. A similar reduction was observed in UPIIIa KO female mice. Histological investigation showed urothelial hyperplasia in both UPII KO and UPIIIa KO mice, although again, apparently more severe in the former. Conclusions These results confirm and extend previous work to indicate that urothelial defects due to uroplakin deficiency are associated with significant alterations in bladder function and further highlight the importance of the urothelium to bladder physiology/dysfunction. PMID:19267388

The Photosynthesis, Na+/K+ Homeostasis and Osmotic Adjustment of Atriplex canescens in Response to Salinity

PubMed Central

Pan, Ya-Qing; Guo, Huan; Wang, Suo-Min; Zhao, Bingyu; Zhang, Jin-Lin; Ma, Qing; Yin, Hong-Ju; Bao, Ai-Ke

2016-01-01

Atriplex canescens (fourwing saltbush) is a C4 perennial fodder shrub with excellent resistance to salinity. However, the mechanisms underlying the salt tolerance in A. canescens are poorly understood. In this study, 5-weeks-old A. canescens seedlings were treated with various concentrations of external NaCl (0–400 mM). The results showed that the growth of A. canescens seedlings was significantly stimulated by moderate salinity (100 mM NaCl) and unaffected by high salinity (200 or 400 mM NaCl). Furthermore, A. canescens seedlings showed higher photosynthetic capacity under NaCl treatments (except for 100 mM NaCl treatment) with significant increases in net photosynthetic rate and water use efficiency. Under saline conditions, the A. canescens seedlings accumulated more Na+ in either plant tissues or salt bladders, and also retained relatively constant K+ in leaf tissues and bladders by enhancing the selective transport capacity for K+ over Na+ (ST value) from stem to leaf and from leaf to bladder. External NaCl treatments on A. canescens seedlings had no adverse impact on leaf relative water content, and this resulted from lower leaf osmotic potential under the salinity conditions. The contribution of Na+ to the leaf osmotic potential (Ψs) was sharply enhanced from 2% in control plants to 49% in plants subjected to 400 mM NaCl. However, the contribution of K+ to Ψs showed a significant decrease from 34% (control) to 9% under 400 mM NaCl. Interestingly, concentrations of betaine and free proline showed significant increase in the leaves of A. canescens seedlings, these compatible solutes presented up to 12% of contribution to Ψs under high salinity. These findings suggest that, under saline environments, A. canescens is able to enhance photosynthetic capacity, increase Na+ accumulation in tissues and salt bladders, maintain relative K+ homeostasis in leaves, and use inorganic ions and compatible solutes for osmotic adjustment which may contribute to the improvement of water status in plant. PMID:27379134

Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration: concept for effective treatment modality.

PubMed

Udo, Yukihiro; Nakao, Masahiro; Honjo, Hisashi; Ukimura, Osamu; Kawauchi, Akihiro; Kitakoji, Hiroshi; Miki, Tsuneharu

2011-03-01

• To determine the relationship between the number of nocturia and 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration as well as to assess the significance of these factors with respect to eliminating nocturnal voidings in individual patients with nocturia. • Among 532 participants who completed a 3-day bladder diary between April 2005 and December 2006, the diaries of 450 participants without 24-h polyuria were analyzed. • Clinical variables such as the number of daytime and night-time voids, 24-h urine volume, nocturnal polyuria index, daytime and night-time maximum voided volumes (MVV), night/day MVV ratio, sleep duration and proportion of night/day urine production rates were obtained from each diary. • Participants were classified into eight groups according to values of three factors: nocturnal MVV, proportion of night/day urine production rates and length of sleep duration. • Each group was divided into three subgroups: non-nocturics (number of nocturnal voidings is zero), mild nocturics (number of nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is two or more). • The data from non-nocturics with three normal factors were regarded as the normal control and compared with the variables of the other subgroups using Dunnett's method. • Variables that form the basis of classifying participants into eight groups and corresponding to abnormal factors of each group were statistically significant in all the subgroups of each group. • Furthermore, a significantly increased 24-h urine volume was found in severe nocturics of the group with three normal factors. • A significantly decreased 24-h urine volume was found in non-nocturics of groups with nocturnal polyuria, decreased bladder capacity and both long sleep duration and nocturnal polyuria. • A significantly increased nocturnal MVV and night/day MVV ratio were shown in non-nocturics and mild nocturics of the groups with nocturnal polyuria and both long sleep duration and nocturnal polyuria. • Because nocturia is a multifactorial disorder and closely related to four factors (i.e. 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration), the evaluation of all these factors appears to be clinically useful for determining the main contributing factor in patients with nocturia as well as the suitable treatment modality on an individual basis. • Physicians should take all these factors into consideration in the evaluation and treatment of nocturia. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

[Cystomanometric study of bladder sensation during sacral neuromodulation test].

PubMed

Leclers, François; Mourey, Eric; Galas, Jean Marie; Cormier, Luc; Mangin, Philippe

2005-04-01

Prospective clinical and urodynamic study evaluating modification of bladder sensation during sacral neuromodulation (SNM). 24 consecutive patients with non-neurological hyperactive bladder underwent an SNM test. Questioned about their symptoms before and during the test by the urinary handicap assessment scale, patients were divided into two groups: A (improved) and B (not improved). Group A consisted of patients obtaining 50% improvement of their symptoms with SNM followed by return of symptoms at the end of the test, while the other patients constituted group B. We then compared the cystomanometric results according to their clinical response. The mean age was 53 years: 10 patients with a good response constituted group A (n=10, i.e. 42%) and 14 patients with a poor response constituted group B (n=14, i.e. 58%). Clinically, in patients with a good response, SNM decreased urge incontinence by 100%, day-time frequency by 89% and protections by 55%. Urodynamic assessment in group A during the test demonstrated a significant increase of +23% of bladder capacity (p<0.01), +57% of the volume of onset of the first unstable contraction (p<0.004), +83% of bladder volume to the first urge to urinate BI (p<0.001) and +46% to urgency B3 (p<0.04). During SNM, cystometry revealed that 1 or 2 bladder filling volumes were increased at B1 and/or B3 in 100% of improved subjects. In contrast, 1 or 2 volumes decreased at B1 and/or B3 in 58% of non-improved subjects. No significant difference of intensity of unstable contractions was observed between the 2 groups during SNM (p=0.31). A significant correlation was observed between the two methods of clinical and urodynamic assessment. Our results suggest the use of the cystomanometric increase of bladder volume at B1 and B3 as selection criterion for candidates for SNM with non-neurological hyperactive bladder.

Effects of ageing and streptozotocin-induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder.

PubMed

Suadicani, Sylvia O; Urban-Maldonado, Marcia; Tar, Moses T; Melman, Arnold; Spray, David C

2009-06-01

To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X(1)R, and increase in P2X(7)R expression. There was decreased Cx43 and increased P2Y(4)R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X(1)R expression levels, and a positive correlation between bladder spontaneous activity and P2Y(4)R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y(2)R, P2X(4)R and increase in P2X(1)R expression in the corpora, and by a doubling in Cx43 and P2Y(2)R, and significant increase in P2Y(4)R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats.

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

PubMed Central

Noguera-Ortega, Estela; Blanco-Cabra, Núria; Rabanal, Rosa Maria; Sánchez-Chardi, Alejandro; Roldán, Mónica; Guallar-Garrido, Sandra; Torrents, Eduard; Luquin, Marina; Julián, Esther

2016-01-01

The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer. PMID:27265565

Measurement of DNA damage in rat urinary bladder transitional cells: improved selective harvest of transitional cells and detailed Comet assay protocols.

PubMed

Wang, Amy; Robertson, John L; Holladay, Steven D; Tennant, Alan H; Lengi, Andrea J; Ahmed, S Ansar; Huckle, William R; Kligerman, Andrew D

2007-12-01

Urinary bladder transitional epithelium is the main site of bladder cancer, and the use of transitional cells to study carcinogenesis/genotoxicity is recommended over the use of whole bladders. Because the transitional epithelium is only a small fraction of the whole bladder, the alkaline single cell gel electrophoresis assay (Comet assay), which requires only a small number of cells per sample, is especially suitable for measuring DNA damage in transitional cells. However, existed procedures of cell collection did not yield transitional cells with a high purity, and pooling of samples was needed for Comet assay. The goal of this study was to develop an optimized protocol to evaluate DNA damage in the urinary bladder transitional epithelium. This was achieved by an enzymatic stripping method (trypsin-EDTA incubation plus gentle scraping) to selectively harvest transitional cells from rat bladders, and the use of the alkaline Comet assay to detect DNA strand breaks, alkaline labile sites, and DNA-protein crosslinks. Step by step procedures are reported here. Cells collected from a single rat bladder were sufficient for multiple Comet assays. With this new protocol, increases in DNA damage were detected in transitional cells after in vitro exposure to the positive control agents, hydrogen peroxide or formaldehyde. Repair of the induced DNA damage occurred within 4h. This indicated the capacity for DNA repair was maintained in the harvested cells. The new protocol provides a simple and inexpensive method to detect various types of DNA damage and to measure DNA damage repair in urinary bladder transitional cells.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2015-06-18

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

Evidence of reduced bladder capacity during nighttime in children with monosymptomatic nocturnal enuresis.

PubMed

Borg, B; Kamperis, K; Olsen, L H; Rittig, S

2018-04-01

Bladder capacity in children with nocturnal enuresis is assessed by maximal voided volumes (MVV) obtained through daytime frequency volume (FV) charts. Although a degree of association has been demonstrated, daytime MVV does not consistently correspond with the nocturnal bladder capacity (NBC) in monosymptomatic nocturnal enuresis (MNE). It was hypothesized that isolated reduced NBC is a common phenomenon in children with nocturnal enuresis, despite normal daytime bladder function. The aim of this study was to evaluate NBC in children with MNE and normal daytime voided volumes. Specifically, it aimed to determine the prevalence and degree of reduced NBC when using nocturnal urine production (NUP) during wet nights as a surrogate estimate of NBC. Furthermore, it aimed to investigate the relationship between NBC and desmopressin response. Data from 103 children aged 5-15 years consecutively treated for MNE in a tertiary referral centre and with normal MVV on daytime FV charts were collected for this cohort study. Home recordings were completed for 2 weeks at baseline and during desmopressin dose titration. Estimated nocturnal bladder capacity (eNBC) was assessed separately each night as the total NUP causing a wet night. If NUP during a wet night was less than MVV, it was considered to be reduced eNBC during that particular night. Surprisingly, 82% (n = 84) of the children with MNE and normal daytime MVV experienced at least one wet night, with NUP below the daytime MVV indicative of a reduced eNBC. For 84 patients, mean percentage of wet nights with reduced eNBC (NUP below MVV) was 49% (SD ± 31). A total of 11% of children with frequently reduced eNBC (>40% of wet nights with reduced eNBC) responded to desmopressin (Summary Fig.). Of the children with frequently reduced NBC, 91% experienced wet nights, with NUP <65% of expected bladder capacity (EBC). A significant proportion of children with MNE and normal MVV during the daytime frequently experienced wet nights, with a NUP well below their MVV and even <65% of EBC. This indicated that bladder reservoir dysfunction during sleep is relatively common in MNE. This abnormality was not reflected on daytime recordings, and thus nighttime data with NUP must be collected. This phenomenon may explain treatment failure to desmopressin, despite adequate antidiuretic response. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Adipose-derived stem-cell-implanted poly(ϵ-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model.

PubMed

Zhou, Zhe; Yan, Hao; Liu, Yidong; Xiao, Dongdong; Li, Wei; Wang, Qiong; Zhao, Yang; Sun, Kang; Zhang, Ming; Lu, Mujun

2018-04-01

The study investigated the feasibility of seeding adipose-derived stem cells (ASCs) onto a poly(ϵ-caprolactone)/chitosan (PCL/CS) scaffold for bladder reconstruction using a rat model of bladder augmentation. In the experimental group, the autologous ASCs were seeded onto the PCL/CS scaffold for bladder augmentation. An unseeded scaffold was used for bladder augmentation as control group. The sham group was also set. 8 weeks after implantation, more densely smooth muscles were detected in the experimental group with a larger bladder capacity and more intensive blood vessels. Immunofluorescence staining demonstrated that some of the smooth muscle cells were transdifferentiated from the ASCs. Our findings indicated that ASC-seeded PCL/CS may be a potential scaffold for bladder tissue engineering.

Pudendal nerve stimulation and block by a wireless-controlled implantable stimulator in cats.

PubMed

Yang, Guangning; Wang, Jicheng; Shen, Bing; Roppolo, James R; de Groat, William C; Tai, Changfeng

2014-07-01

The study aims to determine the functionality of a wireless-controlled implantable stimulator designed for stimulation and block of the pudendal nerve. In five cats under α-chloralose anesthesia, the stimulator was implanted underneath the skin on the left side in the lower back along the sacral spine. Two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves in addition to one bipolar cuff electrode that was implanted on the left side central to the tripolar cuff electrode. The stimulator provided high-frequency (5-20 kHz) biphasic stimulation waveforms to the two tripolar electrodes and low-frequency (1-100 Hz) rectangular pulses to the bipolar electrode. Bladder and urethral pressures were measured to determine the effects of pudendal nerve stimulation (PNS) or block. The maximal (70-100 cmH2O) urethral pressure generated by 20-Hz PNS applied via the bipolar electrode was completely eliminated by the pudendal nerve block induced by the high-frequency stimulation (6-15 kHz, 6-10 V) applied via the two tripolar electrodes. In a partially filled bladder, 20-30 Hz PNS (2-8 V, 0.2 ms) but not 5 Hz stimulation applied via the bipolar electrode elicited a large sustained bladder contraction (45.9 ± 13.4 to 52.0 ± 22 cmH2O). During cystometry, the 5 Hz PNS significantly (p < 0.05) increased bladder capacity to 176.5 ± 27.1% of control capacity. The wireless-controlled implantable stimulator successfully generated the required waveforms for stimulation and block of pudendal nerve, which will be useful for restoring bladder functions after spinal cord injury. © 2013 International Neuromodulation Society.

Comparison of water and air charged transducer catheter pressures in the evaluation of cystometrogram and voiding pressure studies.

PubMed

McKinney, Timothy B; Babin, Elizabeth A; Ciolfi, Veronica; McKinney, Cynthia R; Shah, Nima

2018-04-01

Air-charged (AC) and water-perfused (WP) catheters have been evaluated for differences in measuring pressures for voiding dysfunction. Typically, a two-catheter system was used. We believe that simultaneous pressure measurements with AC and WP in a single catheter will provide analogous pressures for coughs, Valsalvas, and maximum pressures in voiding pressure studies (VPS). This IRB approved prospective study included 50 women over age 21. AC dual TDOC catheters were utilized. The water-filling channel served as the bladder filler and the water pressure readings. Patients were evaluated with empty bladders and at volumes of 50-100 mL, 200 mL, and maximum capacity with cough and Valsalva maneuvers. Comparative analysis was performed on maximum stress peak pressures. At maximum bladder capacity, VPS was done and maximum voiding pressure was recorded. Comparing coughs and Valsalva maneuvers pressures, there was significant increase in variability between AC and WP measurements with less than 50 mL volume (P < 0.001). Significant correlations were observed between AC and WP measurements for coughs and Valsalvas with bladder volume over 50 mL. Visual impression showed virtually identical tracings. Cough measurements had an average difference of 0.25 cmH 2 O (±8.81) and Valsalva measurements had an average difference of 3.15 cmH 2 O (±4.72). Thirty-eight women had usable maximum voiding pressure measurements and had a strong correlation. Cystometrogram and maximum voiding pressure measurements done with either water or air charged catheters will yield similarly accurate results and are comparable. Results suggest more variability at low bladder volumes <50 mL. © 2018 Wiley Periodicals, Inc.

Effectiveness of pelvic floor muscle training on symptoms and uroflowmetry parameters in female patients with overactive bladder.

PubMed

Kulaksizoğlu, Haluk; Akand, Murat; Çakmakçi, Evrim; Gül, Murat; Seçkin, Bedreddin

2015-01-01

To evaluate the effects of pelvic floor muscle training (PFMT) on symptoms of overactive bladder (OAB) as well as uroflowmetry parameters and functional bladder capacity. Fifty-nine female patients with OAB symptoms were included. Patients were assessed by SEAPI-QMM, uroflowmetry, and abdominal ultrasound. A specially designed PFMT program using a Pilates ball was generated for patients. The training period was 1-h sessions twice a week for 6 weeks and aerobic home exercises to be performed at home 4 or 5 times every other day. Following training, subjects were reevaluated for body mass index, SEAPI questionnaire, and uroflowmetry. Initial mean SEAPI score, mean maximum and average flow rates, and mean voided volume were 9.8 ± 7.2, 29.8 ± 16.4 mL/s, 16.3 ± 8.7 mL/s, and 211.6 ± 173.5 mL, respectively. After completion of the training program, SEAPI scores improved significantly to 3.4 ± 6.4 (P < 0.05). Maximum and average flow rate results did not show significant changes, whereas voided volume seemed to have improved in conjunction with patients' symptom scores (Pearson correlation coefficient: 0.86). According to. our results, we think that proper PFMT results in increase of functional bladder capacity as well as improvement in OAB symptoms and can be recommended as first-line therapy or in conjunction with medical therapy in severe cases.

[Nocturia in elderly patients].

PubMed

Kurenkov, A V; Petrov, S B

2010-01-01

This study demonstrates a comparative assessment of the causes of nocturia in young and elderly patients with overactive bladder (OAB). We used the database of 245 patients over 18 years (117 men, 128 women) with OAB (more than 8 micturition per day), with presence or absence of urgent urinary incontinence and nocturia (an average of 2.5 episodes per night). All the patients had to complete a diary within 3 days indicating the time of the urge to urinate, urine volume per micturition and sleep time (when the patient is actually asleep before waking time). These patients were divided by sex and also into three age groups: younger than 60 years, 61-69 years and over 70 years. A diary was used to determine the nocturia index, nocturnal polyuria index, index of nocturnal bladder capacity. The most obvious reason for nocturia in patients with OAB was the polyuria and reduced nocturnal bladder capacity, which are not dependent on age. In young patients (< or = 60 years) nocturia was the result of the decrease of nocturnal bladder capacity and was evaluated by IBC. For the patients older than 70 years, the most common cause of nocturia was nocturnal polyuria, which was estimated by the index of nocturnal polyuria.

Tissue engineering of the bladder--reality or myth? A systematic review.

PubMed

Sloff, Marije; Simaioforidis, Vasileios; de Vries, Rob; Oosterwijk, Egbert; Feitz, Wout

2014-10-01

We systematically reviewed preclinical studies in the literature to evaluate the potential of tissue engineering of the bladder. Study outcomes were compared to the available clinical evidence to assess the feasibility of tissue engineering for future clinical use. Preclinical studies of tissue engineering for bladder augmentation were identified through a systematic search of PubMed and Embase™ from January 1, 1980 to January 1, 2014. Primary studies in English were included if bladder reconstruction after partial cystectomy was performed using a tissue engineered biomaterial in any animal species, with cystometric bladder capacity as an outcome measure. Outcomes were compared to clinical studies available at http://www.clinicaltrials.gov and published clinical studies. A total of 28 preclinical studies are included, demonstrating remarkable heterogeneity in study characteristics and design. Studies in which preoperative bladder volumes were compared to postoperative volumes were considered the most clinically relevant (18 studies). Bladder augmentation through tissue engineering resulted in a normal bladder volume in healthy animals, with the influence of a cellular component being negligible. Furthermore, experiments in large animal models (pigs and dogs) approximated the desired bladder volume more accurately than in smaller species. The initial clinical experience was based on seemingly predictive healthy animal models with a promising outcome. Unfortunately these results were not substantiated in all clinical trials, revealing dissimilar outcomes in different clinical/disease backgrounds. Thus, the translational predictability of a model using healthy animals might be questioned. Through this systematic approach we present an unbiased overview of all published preclinical studies investigating the effect of bladder tissue engineering on cystometric bladder capacity. Preclinical research in healthy animals appears to show the feasibility of bladder augmentation by tissue engineering. However, in view of the disappointing clinical results based on healthy animal models new approaches should also be evaluated in preclinical models using dysfunctional/diseased bladders. This endeavor may aid in the development of clinically applicable tissue engineered bladder augmentation with satisfactory long-term outcome. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder overdistension with polyuria in a hypertensive rat model.

PubMed

Velasquez Flores, Monica; Mossa, Abubakr H; Cammisotto, Philippe; Campeau, Lysanne

2018-03-31

Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting. Male Dahl/SS rats, a hypertension model, received a high-salt or normal diet for 6 weeks. Twenty-four-hour water intake, micturition patterns, and blood pressures were recorded biweekly. Conscious cystometry was carried out at the end of this period. Bladders were collected to measure contractile force and for histological analysis. Paired t-tests were used to compare changes between Week 0 and Week 6 within each group. Unpaired t-tests were used for comparisons between groups for all parameters at Week 6. Six weeks of high-salt diet significantly increased water intake and total urine. Blood pressures and volume of urine per micturition was higher in rats on high-salt diet. Bladder overdistension in the high-salt diet group was confirmed by cystometry, shown by a significantly higher bladder capacity, and compliance. No difference in detrusor contractility was observed between both groups. Collagen content was significantly higher in the lamina propria of the high-salt group compared to the normal group, while the opposite was observed in the muscularis. Polyuria, in a hypertension context, leads to changes in bladder morphology and function. These findings help clarify the deleterious clinical impact of polyuria on voiding function, highlighting the variable consequences of bladder overdistension according to the underlying pathology. © 2018 Wiley Periodicals, Inc.

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study.

PubMed

Nishikawa, Nobuyuki; Yago, Rie; Yamazaki, Yuichiro; Negoro, Hiromitsu; Suzuki, Mari; Imamura, Masaaki; Toda, Yoshinobu; Tanabe, Kazunari; Ogawa, Osamu; Kanematsu, Akihiro

2015-01-21

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease. PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome). Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5-86.6%), median intravesical pressure at maximal capacity was 30 cmH2O (range 10-107 cmH2O), and median compliance was 3.93 ml/cmH2O (range 0.05-30.3 ml/cmH2O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases. Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.

Effects of ageing and streptozotocin–induced diabetes on connexin43 and P2 purinoceptor expression in the rat corpora cavernosa and urinary bladder

PubMed Central

Suadicani, Sylvia O.; Urban–Maldonado, Marcia; Tar, Moses T.; Melman, Arnold; Spray, David C.

2012-01-01

OBJECTIVE To investigate whether ageing and diabetes alter the expression of the gap junction protein connexin43 (Cx43) and of particular purinoceptor (P2R) subtypes in the corpus cavernosum and urinary bladder, and determine whether changes in expression of these proteins correlate with development of erectile and bladder dysfunction in diabetic and ageing rats. MATERIALS AND METHODS Erectile and bladder function of streptozotocin (STZ)-induced diabetic, insulin-treated and age-matched control Fischer-344 rats were evaluated 2, 4 and 8 months after diabetes induction by in vivo cystometry and cavernosometry. Corporal and bladder tissue were then isolated at each of these sample times and protein expression levels of Cx43 and of various P2R subtypes were determined by Western blotting. RESULTS In the corpora of control rats ageing was accompanied by a significant decrease in Cx43 and P2X1R, and increase in P2X7R expression. There was decreased Cx43 and increased P2Y4R expression in the ageing control rat bladder. There was a significant negative correlation between erectile capacity and P2X1R expression levels, and a positive correlation between bladder spontaneous activity and P2Y4R expression levels. There was already development of erectile dysfunction and bladder overactivity at 2 months after inducing diabetes, the earliest sample measured in the study. The development of these urogenital complications was accompanied by significant decreases in Cx43, P2Y2R, P2X4R and increase in P2X1R expression in the corpora, and by a doubling in Cx43 and P2Y2R, and significant increase in P2Y4R expression in the bladder. Changes in Cx43 and P2R expression were largely prevented by insulin therapy. CONCLUSION Ageing and diabetes mellitus markedly altered the expression of the gap junction protein Cx43 and of particular P2R subtypes in the rat penile corpora and urinary bladder. These changes in Cx43 and P2R expression provide the molecular substrate for altered gap junction and purinergic signalling in these tissues, and thus probably contribute to the early development of erectile dysfunction and higher detrusor activity in ageing and in diabetic rats. PMID:19154470

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats.

PubMed

Ungerer, Timothy D; Kim, Kyoungeun A; Daugherty, Stephanie L; Roppolo, James R; Tai, Changfeng; de Groat, William C

2016-11-01

The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C 6 ) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250μM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50-100μM), and the effects of nicotine were blocked by hexamethonium (1mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2mg/kg, subcutaneously) decreased PMC-AUC. 8-OH-DPAT (0.5mg/kg, s.c.), a 5-HT 1A receptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat. Copyright © 2016 Elsevier Inc. All rights reserved.

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience.

PubMed

Nagle, Anna S; Speich, John E; De Wachter, Stefan G; Ghamarian, Peter P; Le, David M; Colhoun, Andrew F; Ratz, Paul H; Barbee, Robert W; Klausner, Adam P

2017-06-01

The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0-100% scale) and standardized verbal sensory thresholds using a novel, touch-screen "sensation meter." 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity-sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way. © 2016 Wiley Periodicals, Inc.

Bladder control training in girls with lower urinary tract dysfunction.

PubMed

Amira, Peco-Antić; Dušan, Paripović; Gordana, Miloševski-Lomić; Sandra, Trojanović; Ivaniševic, Ivana

2013-01-01

To evaluate the efficacy of standard and biofeedback bladder control training (BCT) on the resolution of dysfunctional elimination syndrome (primary outcome), and on the reduction of urinary tract infections (UTI) and the use of medications such as antibacterial prophylaxis and/or anticholinergic/alpha-blockers (secondary outcome) in girls older than aged least 5 years. 72 girls, median age of 8 years (interquartile range, IQR 7-10) were subjected to standard BCT (cognitive, behavioural and constipation treatment) and 12 one-hour sessions of animated biofeedback using interactive computer games within 8 weeks. Fifty patients were reevaluated after median 11 (IQR, 6-17) months. Effectiveness of BCT was determined by reduction of dysfunctional voiding score (DVS), daytime urinary incontinence (DUI), constipation, UTI, nocturnal enuresis (NE), post void residual (PVR), and improvements in bladder capacity and uroflow/EMG patterns. BCT resulted in significant normalization of DUI, NE, constipation, bladder capacity, uroflow/EMG, while decrease of PVR didn't reach statistical significance. In addition, the incidence of UTI, antibacterial prophylaxis and medical urotherapy significantly decreased. There were no significant differences in DVS, DVI, NE, bladder capacity and voiding pattern at the end of the BCT and at the time of reevaluation. The success on BCT was supported by parenteral perception of the treatment response in 63.9% and full response in additional 15.3% of the patients. Combination of standard and biofeedback BCT improved dysfunctional elimination syndrome and decreased UTI with discontinuation of antibacterial prophylaxis and/or anticholinergic/alpha-blockers in the majority of the patients. Better training results are expected in patients with higher bladder wall thickness as well as in those with vesicoureteral reflux, while presence of nocturnal enuresis may be a negative predictor of the training effect.

Tibial nerve stimulation to inhibit the micturition reflex by an implantable wireless driver microstimulator in cats

PubMed Central

Li, Xing; Liao, Li-Min; Chen, Guo-Qing; Wang, Zhao-Xia; Lu, Tian-Ji; Deng, Han; Loeb, Gerald-E

2016-01-01

Abstract Background: Traditional tibial nerve stimulation (TNS) has been used to treat overactive bladder syndrome (OAB), but there are some shortcomings. Thus, a novel alternative is needed for the treatment of OAB. The study investigated the effects of a new type of tibial nerve microstimulator on the micturition reflex in cats. Methods: An implantable wireless driver microstimulator was implanted around the tibial nerve in 9 α-chloralose anesthetized cats. Cystometry was performed by infusing 0.9% normal saline (NS) or 0.25% acetic acid (AA) through a urethral catheter. Multiple cystometrograms were performed before, during, and after TNS to determine the inhibitory effect of the microstimulator on the micturition reflex. Results: TNS at 2 threshold (T) intensity significantly increased the bladder capacity (BC) during NS infusion. Bladder overactivity was irritated by the intravesical infusion of 0.25% AA, which significantly reduced the BC compared with the NS infusion. TNS at 2 T intensity suppressed AA-induced bladder overactivity and significantly increased the BC compared with the AA control. Conclusion: The implantable wireless driver tibial nerve microstimulator appears to be effective in inhibiting the micturition reflex during physiologic and pathologic conditions. The implantable wireless driver tibial nerve microstimulator could be used to treat OAB. PMID:27537576

The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice.

PubMed

Kadekawa, Katsumi; Majima, Tsuyoshi; Shimizu, Takahiro; Wada, Naoki; de Groat, William C; Kanai, Anthony J; Goto, Momokazu; Yoshiyama, Mitsuharu; Sugaya, Kimio; Yoshimura, Naoki

2017-09-01

We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1 ) spinal intact (SI)-control, 2 ) SI-capsaicin pretreatment (Cap), 3 ) SCI-control, and 4 ) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice. Copyright © 2017 the American Physiological Society.

Clinical radiobiology of stage T2-T3 bladder cancer.

PubMed

Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

2004-09-01

To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival (p = 0.087), and OTT did not reach statistical significance. The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

Genetic variation in the base excision repair pathway and bladder cancer risk.

PubMed

Figueroa, Jonine D; Malats, Núria; Real, Francisco X; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel; García-Closas, Montserrat

2007-04-01

Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.

Optimization of Neuromodulation for Bladder Control in a Rat Cystitis Model.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2016-01-01

In a bladder overactivity model of cystitis induced by intravesical infusion of acetic acid (a.a.), several parameters of spinal nerve stimulation (SNS) were optimized using continuous infusion cystometry. The optimal stimulation was further characterized through measurements of urodynamic function using single-fill cystometry. In anesthetized male rats, a cannula was placed into the bladder dome for saline or 0.3% a.a. infusion and intravesical pressure monitoring. For SNS, two teflon-coated stainless steel electrodes were placed bilaterally under each of the L6 spinal nerves, and current stimulation was controlled independently using two Grass stimulators. Stimulation of 1 Hz or 50 Hz at motor threshold (Tmot ) was ineffective for altering bladder activities, but 10-Hz SNS increased the infused volume (IV) in a stimulation intensity-dependent fashion (P < 0.01, mixed model repeated analysis). Pairwise comparisons of IV differences to each stimulation intensity show that IV during 1 × Tmot stimulation was significantly larger than 0 × Tmot (no stim, P = 0.001), while the IV during 2 × Tmot stimulation was significantly larger than other intensities tested (P < 0.01). The mean IV (±SEM) during 0 × Tmot (no stim), 0.5 × Tmot , 1 × Tmot , and 2 × Tmot were 0.23 ± 0.04 mL, 0.25 ± 0.03 mL, 0.26 ± 0.03 mL, and 0.40 ± 0.04 mL, respectively. In single-fill cystometry, 10-Hz SNS at 1 × Tmot and 2 × Tmot stimulation increased the IV, or voiding duration and threshold pressure. SNS did not produce significant effects on basal pressure and micturition pressure. SNS significantly attenuates hypersensitive micturition reflex; 10 Hz and high-intensity stimulation are mostly effective. Acute peripheral nerve activation increases the functional bladder capacity, which may be via mechanisms on the afferent arm of the bladder micturition reflex. © 2015 International Neuromodulation Society.

Expression and function of transforming growth factor-β isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis

PubMed Central

Gonzalez, Eric J.; Girard, Beatrice M.

2013-01-01

Numerous proinflammatory cytokines have been implicated in the reorganization of lower urinary tract function following cyclophosphamide (CYP)-induced cystitis. The present study investigated the functional profile of three pleiotropic transforming growth factor-β (TGF-β) isoforms and receptor (TβR) variants in the normal and inflamed (CYP-induced cystitis) rat urinary bladder. Our findings indicate that TGF-β (1, 2, and 3) and TβR (1, 2, and 3) transcript and protein expression were regulated to varying degrees in the urothelium or detrusor smooth muscle following intermediate (48 h; 150 mg/kg ip) or chronic (75 mg/kg ip; once every 3 days for 10 days), but not acute (4 h; 150 mg/kg ip), CYP-induced cystitis. Conscious, open-outlet cystometry was performed to determine whether aberrant TGF-β signaling contributes to urinary bladder dysfunction following intermediate (48 h) CYP-induced cystitis. TβR-1 inhibition with SB505124 (5 μM) significantly (p ≤ 0.001) decreased voiding frequency and increased bladder capacity (2.5-fold), void volume (2.6-fold), and intercontraction intervals (2.5-fold) in CYP-treated (48 h) rats. Taken together, these results provide evidence for 1) the involvement of TGF-β in lower urinary tract neuroplasticity following urinary bladder inflammation, 2) a functional role of TGF-β signaling in the afferent limb of the micturition reflex, and 3) urinary bladder TβR-1 as a viable target to reduce voiding frequency with cystitis. PMID:23926183

Effect of Shift Work on Nocturia.

PubMed

Kim, Jin Wook

2016-01-01

To identify the circadian sensitive component of nocturia by comparing nocturia in patients who voluntarily choose a disrupted circadian rhythm, that is, shift workers, with those who maintain normal day-night cycles. Between 2011 and 2013, a total of 1741 untreated patients, 1376 nonshift workers and 365 shift workers, were compared for nocturia indices based on frequency volume charts (FVCs). General linear model of 8-hour interval urine production and frequency were compared between FVCs of nonshift workers, FVCs of night-shift workers, and FVCs of day-shift workers. Nocturia frequency was increased in the night-shift workers (2.38 ± 1.44) compared with nonshift workers (2.18 ± 1.04) (P <.01). Whereas nocturnal polyuria index did not increase significantly (0.33 ± 0.19 for night-shift workers, 0.34 ± 0.13 for nonshift workers, P = .24), nocturnal bladder capacity index increased significantly (1.41 ± 1.06 for night-shift workers, 1.26 ± 0.92 for nonshift workers, P <.01). Eight-hour interval indices show that urine production changed with shift (P <.01), whereas voiding frequency remains unchanged despite shift changes (P = .35). Patients in alternating work shifts showed increased nocturia, especially during their night shift. These changes tended to be more associated with decreased nocturnal bladder capacity than increased nocturnal polyuria. Copyright © 2015 Elsevier Inc. All rights reserved.

Culturing of female bladder bacteria reveals an interconnected urogenital microbiota.

PubMed

Thomas-White, Krystal; Forster, Samuel C; Kumar, Nitin; Van Kuiken, Michelle; Putonti, Catherine; Stares, Mark D; Hilt, Evann E; Price, Travis K; Wolfe, Alan J; Lawley, Trevor D

2018-04-19

Metagenomic analyses have indicated that the female bladder harbors an indigenous microbiota. However, there are few cultured reference strains with sequenced genomes available for functional and experimental analyses. Here we isolate and genome-sequence 149 bacterial strains from catheterized urine of 77 women. This culture collection spans 78 species, representing approximately two thirds of the bacterial diversity within the sampled bladders, including Proteobacteria, Actinobacteria, and Firmicutes. Detailed genomic and functional comparison of the bladder microbiota to the gastrointestinal and vaginal microbiotas demonstrates similar vaginal and bladder microbiota, with functional capacities that are distinct from those observed in the gastrointestinal microbiota. Whole-genome phylogenetic analysis of bacterial strains isolated from the vagina and bladder in the same women identifies highly similar Escherichia coli, Streptococcus anginosus, Lactobacillus iners, and Lactobacillus crispatus, suggesting an interlinked female urogenital microbiota that is not only limited to pathogens but is also characteristic of health-associated commensals.

Hypertensive intracerebral hemorrhage due to autonomic dysreflexia in a young man with cervical cord injury.

PubMed

Sumiya, Tadashi

2013-06-01

The author reports the case of a 36 year old man with cervical cord injury in whom autonomic dysreflexia developed into intracerebral hemorrhage during inpatient rehabilitation. This patient showed complete quadriplegia (motor below C6 and sensory below C7) due to fracture of the 6th cervical vertebra. An indwelling urethral catheter had been inserted into the bladder for 3 months, diminishing bladder expansiveness. Bladder capacity decreased to 200 ml and the patient frequently experienced headaches whenever his bladder was full.To obtain smoother urine flow, a supra-pubic cystostomy was performed. The headaches were temporarily cured, but soon relapsed with extreme increases in blood pressure, representing typical symptoms of autonomic dysreflexia. However, no potential triggers were identified or removed, and lack of blood pressure management led to left putaminal hemorrhage. Despite operative treatment, the right upper extremity showed progressive increases in muscle tonus and finally formed a frozen shoulder with elbow flexion contracture. Two factors contributed to this serious complication: first, autonomic dysreflexia triggered by minor malfunction and/or irritation from the cystostomy catheter; and second, the medical staff lacked sufficient experience in and knowledge about the management of autonomic dysreflexia.It is of the utmost importance for medical staff engaging in rehabilitation of spinal patients to share information regarding triggers of autonomic dysreflexia and to be thorough in ensuring proper medical management.

Design and evaluation of potentiometric principles for bladder volume monitoring: a preliminary study.

PubMed

Chen, Shih-Ching; Hsieh, Tsung-Hsun; Fan, Wen-Jia; Lai, Chien-Hung; Chen, Chun-Lung; Wei, Wei-Feng; Peng, Chih-Wei

2015-06-01

Recent advances in microelectronics and wireless transmission technology have led to the development of various implantable sensors for real-time monitoring of bladder conditions. Although various sensing approaches for monitoring bladder conditions were reported, most such sensors have remained at the laboratory stage due to the existence of vital drawbacks. In the present study, we explored a new concept for monitoring the bladder capacity on the basis of potentiometric principles. A prototype of a potentiometer module was designed and fabricated and integrated with a commercial wireless transmission module and power unit. A series of in vitro pig bladder experiments was conducted to determine the best design parameters for implementing the prototype potentiometric device and to prove its feasibility. We successfully implemented the potentiometric module in a pig bladder model in vitro, and the error of the accuracy of bladder volume detection was <±3%. Although the proposed potentiometric device was built using a commercial wireless module, the design principles and animal experience gathered from this research can serve as a basis for developing new implantable bladder sensors in the future.

Effect of Botox injection at the bladder neck in boys with bladder dysfunction after valve ablation.

PubMed

Mokhless, Ibrahim; Zahran, Abdel-Rahman; Saad, Ashraf; Yehia, Mohamed; Youssif, Mohamed E

2014-10-01

After posterior urethral valve ablation, some boys are still have a hostile bladder. We conducted a prospective randomized study to determine if Botox injection at the bladder neck will help improve vesical dysfunction in this subgroup of boys or not. Twenty boys with history of posterior urethral valve ablation and severe bladder dysfunction with a mean age of 16 months were studied. Cases were further randomized into two groups. Group I (study group) had endoscopic injection of a single dose of 100 IU of Botox into the hypertrophied bladder neck at 3, 6, and 9 o'clock. Group II (control group) patients with the same parameters had urethroscopy to exclude residual valves. Both groups had the standard conservative treatment. Cases were followed after 6 months of initiating the management protocol. This includes laboratory studies (urine culture and sensitivity, blood urea nitrogen, serum creatinine), ultrasound of the urinary tract. Voiding cysto-urethrogram and urodynamic study (pressure flow study). There was no statistical difference in both groups regarding rate of urinary tract infection, improvement of hydronephrosis, resolution of vesico-ureteral reflux, creatinine level at the start or at the end of the study. Urodynamic parameters revealed an increase in cystometric capacity in both groups at the end of the study but without statistical difference. The mean voiding pressure reduced significantly in both groups but without statistical difference. Temporarily abolishing the effect of bladder neck by Botox injection does not seem to improve the outcome of those boys who had a severe voiding dysfunction after valve ablation. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The artificial somato-autonomic reflex arch does not improve lower urinary tract function in patients with spinal cord lesions.

PubMed

Rasmussen, Mikkel Mylius; Rawashdeh, Yazan F; Clemmensen, Dorte; Tankisi, Hatice; Fuglsang-Frederiksen, Anders; Krogh, Klaus; Christensen, Peter

2015-02-01

The artificial somato-autonomic reflex arch (Xiao procedure) was proposed as treatment for neurogenic bladder dysfunction. We investigated the effects of the procedure on lower urinary tract function. Seven and 3 patients with a median age of 46 years (range 19 to 64) had AIS A and B spinal cord injury, respectively. In these patients an anastomosis was created between the ventral (motor) part of L5 and the ventral part of the S2 root. Urodynamics were performed and a standard questionnaire was completed at baseline and 18 months postoperatively. Artificial reflex arch stimulation did not initiate voiding or increase bladder pressure. Maximum bladder capacity did not change significantly from baseline to followup (median 427.5 ml, range 168 to 581 vs 498.5, range 271 to 580, p = 0.09). Likewise, bladder compliance did not significantly differ at baseline and followup (median 16.9 ml/cm H2O, range 15.0 to 65.0 vs 25.1, range 17.5 to 50.0, p = 0.95). No difference was found in awareness of bladder emptying, incontinence episodes, bladder emptying method or medication use for neurogenic bladder dysfunction. The only statistically significant change was a decreased incidence of leakage at followup on urodynamics (p = 0.03). Postoperatively decreased genital sensation and erectile dysfunction developed in 1 patient and another experienced a minor cerebrovascular accident with no long-term complications. In contrast to earlier findings, creation of an artificial somato-autonomic reflex arch in patients with spinal cord injury had no clinically relevant effect on lower urinary tract function. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Obstructive Sleep Apnea in a Danish Population of Men and Women Aged 60-80 Years with Nocturia

PubMed Central

Bing, Mette Hornum; Jennum, Poul; Moller, Lars Alling; Mortensen, Svend; Lose, Gunnar

2012-01-01

Introduction and Hypothesis: The aim of the present study was in a case-control design to evaluate the association between nocturia and obstructive sleep apnea, in men and women who had nocturia ≥ 2 per night (nocturics) compared to those without nocturia (controls). Methods: Participants were randomly selected among respondents in a population study of 4000 elderly individuals. Nocturia was assessed using the validated Nocturia, Nocturnal Enuresis, and Sleep-interruption Questionnaire (NNES-Q). Nocturia (≥ 2 voids/night) or control (< 1 void/night) status was assessed by a 3-day frequency volume chart (FVC). Furthermore, all participants completed an overnight ambulatory polygraphic recording to identify obstructive sleep apnea (OSA). Results: Of 1111 eligible individuals, a total of 75 nocturics and 75 controls (13.5%) were included. Overall, the prevalence and severity of OSA among nocturics and controls was not significantly different. In a sub-analysis we found that 22 nocturics with OSA (69%) had nocturnal polyuria. This led to a significantly increased risk of having OSA (OR 2.8, 95% CI: 1.1-7.3, p < 0.05) when having nocturnal polyuria compared to other pathophysiological causes of nocturia (polyuria, low bladder capacity, a combination of nocturnal polyuria/low bladder capacity, and neither nocturnal polyuria/low bladder capacity). Conclusions: Nocturia twice or more was not significantly associated with OSA. However, nocturics with nocturnal polyuria had a significantly higher risk of having OSA than nocturics with other pathophysiologies. Citation: Bing MH; Jennum P; Moller LA; Mortensen S; Lose G. Obstructive sleep apnea in a danish population of men and women aged 60-80 years with nocturia. J Clin Sleep Med 2012;8(5):515-520. PMID:23066362

An alternative treatment modality in closing bladder exstrophy: use of rectus abdominus muscle flap--preliminary results in a rat model.

PubMed

Büyükünal, S N; Kaner, G; Celayir, S

1989-06-01

The aim of this study was to find a new alternate method for bladder exstrophies with small capacity and inelasticity, and to resolve complications of other bladder augmentation techniques. In 50 Wistar albino rats, a large bladder defect was created excising at least one half of their original bladder, keeping the peritrigonal zone intact. In each rat, a 2.5 x 1-cm inferiorly based rectus abdominus muscle flap was prepared from the lower abdominal quadrant. This flap was then rotated to cover the bladder defect. The inner layer formed by the peritoneum was sutured to the edges of the bladder defect by 6-0 separate sutures. The post-operative radiologic and scintigraphic examination of the urinary system done at different intervals showed no difference from that of normal rats. The only observed disadvantage of this technique was the formation of calculi in the bladder in 8/50 rats in the late post-operative period. Post-mortem histopathologic investigations performed at different intervals showed the inner layer of the flap to be completely covered by the transitional urinary epithelium of the bladder. We think this technique is easy to perform, non-time-consuming, and has a low complication rate. It may be useful in infants with small, noncompliant, inelastic bladder exstrophies.

Augmentation enterocystoplasty is effective in relieving refractory ketamine-related bladder pain.

PubMed

Chung, Shiu-Dong; Wang, Chung-Cheng; Kuo, Hann-Chorng

2014-11-01

To report our early results of augmentation enterocystoplasty (AE) for severe bladder pain associated with chronic ketamine cystitis (KC). We performed AE for 14 patients with refractory KC-related bladder pain, which is based on the criteria including severe bladder pain, urgency and frequency and/or upper urinary tract damage such as bilateral hydronephrosis, and contracted bladder. Every patient had been treated conservatively with medication or cystoscopic hydrodistention for at least 1 year before they had received surgical intervention. Video-urodynamic studies were obtained before AE and 3-6 months after surgery. Outcome measurements included visual analogue score (VAS) for pain, cystometric bladder capacity (CBC), maximum urinary flow rate (Qmax), post-void residual, and maximal detrusor pressure (Pdet). The patients' general satisfaction with regard to treatment outcome was also assessed by the Patient Perception of Bladder Condition (PPBC). A total of 4 men and 10 women underwent this procedure as indicated. The mean age was 26.7 (ranged 20-38) years old and the duration of ketamine abuse was 3.82 years (ranged 2-7). Contracted bladder was noted in all patients, hydronephrosis in nine and vesicoureteral reflux (VUR) in eight. At 3-6 months after AE, VAS was remarkably improved from baseline to the end-point (8.29 ± 1.54 vs. 2.14 ± 1.51, P < 0.0001), CBC increased from 50.9 ± 15.7 to 309.2 ± 58.0 ml (P < 0.0001), Qmax increased from 6.94 ± 3.60 to 15.2 ± 5.51 ml/sec (P < 0.0001) and Pdet reduced from 29.7 ± 16.0 to 17.9 ± 8.2 cmH2 O (P = 0.008). All patients reported marked improvement in PPBC from 6.0 to 1.4 ± 0.89 (P < 0.0001). All hydronephrosis disappeared and VUR was resolved in five patients after AE with ureteral reimplantation. This pilot study demonstrated that AE is effective in relieving refractory ketamine-related bladder pain and lower urinary tract symptoms. © 2013 Wiley Periodicals, Inc.

THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: a pilot prospective study.

PubMed

Maniscalco, Giorgia Teresa; Aponte, R; Bruzzese, D; Guarcello, G; Manzo, V; Napolitano, M; Moreggia, O; Chiariello, F; Florio, C

2018-01-01

Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple sclerosis (MS) patients and are mainly related to neurogenic overactive bladder (OAB). The aim of this observational study was to assess the effect of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by means of clinical and instrumental tools. Twenty-one MS patients were screened, and 15 cases have been evaluated. They underwent a specific clinical assessment (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first), bladder volume at the first desire (BVFD), leakage volume (LV), and post-void residual volume (PVR), before and after 4 weeks of THC/CBD administration. A complete neurological evaluation, including the assessment of their spasticity using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating scale (NRS), was performed at the same times. Mobility was evaluated through the 25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic findings after the end of treatment, PVR was significantly reduced (p = 0.016), while BVFD and CCmax were increased although the difference was not statistically significant. THC/CBD oromucosal spray has shown to be effective in improving overactive bladder symptoms in MS patients demonstrating a favorable impact on detrusor overactivity.

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men.

PubMed

Kamphuis, E T; Ionescu, T I; Kuipers, P W; de Gier, J; van Venrooij, G E; Boon, T A

1998-02-01

The aim of this study was to evaluate and compare the effects of spinal anesthesia with lidocaine and with bupivacaine on urinary bladder function in healthy men who were scheduled for minor orthopaedic surgical procedures. Twenty men were randomly allocated to receive either bupivacaine or lidocaine. Before spinal anesthesia, filling cystometry was performed with the patient in the supine position and a pressure flow study was done with the patient in the standing position. After operation, cystometric measurements were continued until the patient could void urine spontaneously. The levels of analgesia and of motor blockade were recorded. The urge to void disappeared immediately after injection of the local anesthetics. There was no difference in the duration of lower extremity motor blockade between bupivacaine and lidocaine. Detrusor blockade lasted significantly longer in the bupivacaine group (means +/- SD, 460 +/- 60 min) than in the lidocaine group (235 +/- 30 min). Total fluid intake and urine volume accumulated during the detrusor blockade were significantly higher in the bupivacaine group than in the lidocaine group. In the bupivacaine group, the total volume of accumulated urine (875 +/- 385 ml) was also significantly higher than cystometric bladder capacity (505 +/- 120 ml) with the risk of over distension of the bladder. Spontaneous voiding of urine did not occur until segmental sensory analgesia had regressed to the third sacral segment. Spinal anesthesia with lidocaine and with bupivacaine causes a clinically significant disturbance of bladder function due to interruption of the micturition reflex. The urge to void disappears quickly and bladder function remains impaired until the block has regressed to the third sacral segment in all patients. With long-acting local anesthetics, the volume of accumulated urine may exceed the cystometric bladder capacity. With respect to recovery of urinary bladder function, the use of short-acting local anesthetics for spinal anesthesia seems to be preferable.

Long-lasting, distinct changes in central opioid receptor and urinary bladder functions in models of schizophrenia in rats.

PubMed

Kekesi, Orsolya; Tuboly, Gabor; Szucs, Maria; Birkas, Erika; Morvay, Zita; Benedek, Gyorgy; Horvath, Gyongyi

2011-07-01

Ketamine treatments and social isolation of rats reflect certain features of schizophrenia, among them altered pain sensitivity. To study the underlying mechanisms of these phenomena, rats were either housed individually or grouped for 33 days after weaning, and treated with either ketamine or saline for 14 days. After one month re-socialization, the urinary bladder capacity by ultrasound examination in the anesthetized animals, and changes of μ-opioid receptors by saturation binding experiments using a specific μ-opioid agonist [(3)H]DAMGO were determined. G-protein signaling was investigated in DAMGO-stimulated [(35)S]GTPγS functional assays. Ketamine treatment significantly decreased the bladder volume and isolation decreased the receptor density in cortical membranes. Among all groups, the only change in binding affinity was an increase induced by social isolation in the cortex. G-protein signaling was significantly decreased by either ketamine or social isolation in this tissue. Ketamine treatment, but not housing, significantly increased μ-opioid receptor densities in hippocampal membranes. Both ketamine and isolation increased the efficacy, while the potency of signaling was decreased by any treatment. Ketamine increased the receptor density and G-protein activation; while isolation decreased the efficacy of G-protein signaling in hippocampal membranes. The changes in the co-treated group were similar to those of the isolated animals in most tests. The distinct changes of opioid receptor functioning in different areas of the CNS may, at least partially, explain the augmented nociceptive threshold and morphine potency observed in these animals. Changes in the relative urinary bladder suggest a detrusor hyperreflexia, another sign of schizophrenia. Copyright © 2011 Elsevier B.V. All rights reserved.

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition

PubMed Central

Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Introduction Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Methods Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Results Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Conclusion Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families. PMID:29494684

Neurogenic bladder findings in patients with Congenital Zika Syndrome: A novel condition.

PubMed

Costa Monteiro, Lucia Maria; Cruz, Glaura Nisya de Oliveira; Fontes, Juliana Marin; Saad Salles, Tania Regina Dias; Boechat, Marcia Cristina Bastos; Monteiro, Ana Carolina; Moreira, Maria Elizabeth Lopes

2018-01-01

Congenital Zika Syndrome (CZS) has been associated with microcephaly and other central nervous system abnormalities including areas that have been implicated in the control of the lower urinary tract. As such, this descriptive case series has aimed to investigate whether CZS is linked with neurogenic bladder. Identifying such an association is paramount in the effort to recognize CZS complications that have putative treatment options that could mitigate the impact of CZS in infected children. Following IRB approval, urological assessment was performed in all patients referred to our clinic between June 2016 and May 2017 who presented with confirmed CZS-associated microcephaly. The research protocol consisted of obtaining clinical history, laboratory tests, lower and upper urinary tract ultrasounds, as well as a diagnostic urodynamic evaluation. ZIKA virus infection was previously confirmed by maternal history and positive PCR in babies and mothers. Microcephaly and other central nervous system abnormalities were established based on neurological assessment and associated imaging of the central nervous system (CT head and/or Brain MRI). Twenty-two consecutive CZS patients were tested and confirmed to have neurogenic bladder. Of the 22 patients assessed, 21 presented with an overactive bladder combined with reduced bladder capacity and elevated detrusor filling pressures. Clinically significant increases in postvoid residual (PVR) were confirmed in 40% of cases while a urinary tract infection (UTI) was identified in 23% of cases. Neurogenic bladder, a known treatable health condition, was confirmed in 100% of patients tested in this study, most presenting with high-risk urodynamic patterns known to lead to renal damage when left untreated. Follow up studies are necessary to provide further insight onto long-term disease progression and to investigate the response to standard therapies for neurogenic bladder. Nonetheless, we emphasize the importance of proactive management of neurogenic bladder and prompt referral so as to help mitigate CZS disease burden for patients and their families.

Extravasation of the contrast media during voiding cystourethrography in a long-term spinal cord injury patient.

PubMed

Kovindha, A; Sivasomboon, C; Ovatakanont, P

2005-07-01

To present complications and pitfalls in voiding cystourethrography (VCUG) and introduce a guideline for performing VCUG in a long-term spinal cord injury (SCI) patient with neurogenic bladder dysfunction (NBD) and contracted bladder. A case report. Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand. We describe a chronic C(5) tetraplegic man with NBD and contracted bladder, who developed autonomic dysreflexia (AD), gross hematuria and extravasation of contrast median during VCUG. A foley catheter was retained after VCUG. AD was resolved and urine cleared after a week of continuous bladder irrigation. VCUG should be performed with caution in a long-term SCI patient with NBD and contracted bladder. Forceful pushing of the contrast media by the hand-injection method caused abrupt distention of the contracted bladder, damaged bladder mucosa and aggrevated AD. We suggest a guideline as follows: report bladder capacity and AD, if present, in an X-ray requisition form; use the gravity-drip method, stop the drip and drain the contrast media if a sudden headache and rising of blood pressure (BP) develop; observe urine colour, and report if bleeding or AD occurs.

Local anesthesia and hydro-distension to facilitate cystic calculus removal in horses.

PubMed

Russell, Tom; Pollock, Patrick J

2012-07-01

To report a technique for improving surgical access to the bladder for removal of cystic calculi in male horses. Retrospective case series. Geldings (8) with cystic calculi. After catheterization of the bladder through the penis, 100 mL 2% lidocaine hydrochloride solution was instilled. After 10 minutes, the bladder was distended with sterile, warmed Hartmann's solution to a pressure of ≈ 40 cm H(2) O, using gravity feed. This was left in place until abdominal access was gained at surgery, then the fluid siphoned off via the catheter. Calculi were 3-11 cm in diameter (median, 6 cm). Bladder capacity ranged from 1.4 to 2.5 L (median, 1.8 L). Exteriorization time from placing a hand in the abdomen to having the bladder in a surgically accessible position was <5 minutes. The described technique facilitates exteriorization of the bladder for removal of cystic calculi. Copyright 2012 by The American College of Veterinary Surgeons.

The modern staged repair of classic bladder exstrophy: a detailed postoperative management strategy for primary bladder closure.

PubMed

Stec, Andrew A; Baradaran, Nima; Schaeffer, Anthony; Gearhart, John P; Matthews, Ranjiv I

2012-10-01

Successful primary bladder closure of classic bladder exstrophy sets the stage for development of adequate bladder capacity and eventual voided continence. The postoperative pathway following primary bladder closure at the authors' institution is quantitatively and qualitatively detailed. Sixty-five consecutive newborns (47 male) undergoing primary closure of classic bladder exstrophy were identified and data were extracted relating to immediate postoperative care. Overall success rate was utilized to validate the pathway. Mean age at time of primary closure was 4.6 days and mean hospital stay was 35.8 days. Osteotomy was performed in 19 patients (mean age 8.8 days), and was not required in 39 infants (mean age 2.9 days). All patients were immobilized for 4 weeks. Tunneled epidural analgesia was employed in 61/65 patients. All patients had ureteral catheters and a suprapubic tube, along with a comprehensive antibiotic regimen. Postoperative total parenteral nutrition was commonly administered, and enteral feedings started around day 4.6. Our success rate of primary closure was 95.4%. A detailed and regimented plan for bladder drainage, immobilization, pain control, nutrition, antimicrobial prophylaxis, and adequate healing time is a cornerstone for the postoperative management of the primary closure of bladder exstrophy. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Does Reduction of Number of Intradetrusor Injection Sites of aboBoNTA (Dysport®) Impact Efficacy and Safety in a Rat Model of Neurogenic Detrusor Overactivity?

PubMed Central

Huynh Le Maux, Amélie; Pignol, Bernadette; Behr-Roussel, Delphine; Blachon, Jean-Luc; Chabrier, Pierre-Etienne; Compagnie, Sandrine; Picaut, Philippe; Bernabé, Jacques; Giuliano, François; Denys, Pierre

2015-01-01

Intradetrusor injections of Botulinum toxin A—currently onabotulinumtoxinA—is registered as a second-line treatment to treat neurogenic detrusor overactivity (NDO). The common clinical practice is 30 × 1 mL injections in the detrusor; however, protocols remain variable and standardization is warranted. The effect of reducing the number of injection sites of Dysport® abobotulinumtoxinA (aboBoNTA) was assessed in the spinal cord-injured rat (SCI). Nineteen days post-spinalization, female rats received intradetrusor injections of saline or aboBoNTA 22.5 U distributed among four or eight sites. Two days after injection, continuous cystometry was performed in conscious rats. Efficacy of aboBoNTA 22.5 U was assessed versus aggregated saline groups on clinically-relevant parameters: maximal pressure, bladder capacity, compliance, voiding efficiency, as well as amplitude, frequency, and volume threshold for nonvoiding contractions (NVC). AboBoNTA 22.5 U significantly decreased maximal pressure, without affecting voiding efficiency. Injected in four sites, aboBoNTA significantly increased bladder capacity and compliance while only the latter when in eight sites. AboBoNTA significantly reduced NVC frequency and amplitude. This preclinical investigation showed similar inhibiting effects of aboBoNTA despite the number of sites reduction. Further studies are warranted to optimize dosing schemes to improve the risk-benefit ratio of BoNTA-based treatment modalities for NDO and further idiopathic overactive bladder. PMID:26694464

Gastrocystoplasty and Hematuria-dysuria Syndrome. What Role Plays Helicobacter Pylori? Case Report and Literature Review

PubMed Central

Aponte, Hernán A.; Clavijo, Rafael A.; Quiroz, Yesica J.; Dallos, Diego F.; Ruiz, William N.; Ramirez-Troche, Nelson E.; Martin, Oscar Dario

2015-01-01

49 years male, who comes to the urology department, complaining of 8 months of lower abdominal pain, burning and oppressive type, of variable intensity reaching 9/10, which is occasionally exacerbated by urination, associated with intermittent gross hematuria, dysuria, refers no fever at any time. Patient with past medical history of bladder and right kidney Tuberculosis (TBC) 25 years ago, treated with a simple right nephrectomy and bladder augmentation with antrum segment of stomach, for low bladder capacity. Never showed any symptom during those 25 years lapsing time PMID:26793505

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience

PubMed Central

Nagle, Anna S.; Speich, John E.; De Wachter, Stefan G.; Ghamarian, Peter P.; Le, David M.; Colhoun, Andrew F.; Ratz, Paul H.; Barbee, Robert W.; Klausner, Adam P.

2016-01-01

AIMS The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0–100% scale) and standardized verbal sensory thresholds using a novel, touch-screen “sensation meter.” 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity–sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way. PMID:27654469

Urodynamic assessment of bladder and urethral function among men with lower urinary tract symptoms after radical prostatectomy: A comparison between men with and without urinary incontinence.

PubMed

Lee, Hansol; Kim, Ki Bom; Lee, Sangchul; Lee, Sang Wook; Kim, Myong; Cho, Sung Yong; Oh, Seung-June; Jeong, Seong Jin

2015-12-01

We compared bladder and urethral functions following radical prostatectomy (RP) between men with and without urinary incontinence (UI), using a large-scale database from SNU-experts-of-urodynamics-leading (SEOUL) Study Group. Since July 2004, we have prospectively collected data on urodynamics from 303 patients with lower urinary tract symptoms (LUTS) following RP at three affiliated hospitals of SEOUL Study Group. After excluding 35 patients with neurogenic abnormality, pelvic irradiation after surgery, or a history of surgery on the lower urinary tract, 268 men were evaluated. We compared the urodynamic findings between men who had LUTS with UI (postprostatectomy incontinence [PPI] group) and those who had LUTS without UI (non-PPI group). The mean age at an urodynamic study was 68.2 years. Overall, a reduced bladder compliance (≤20 mL/cmH2O) was shown in 27.2% of patients; and 31.3% patients had idiopathic detrusor overactivity. The patients in the PPI group were older (p=0.001) at an urodynamic study and had a lower maximum urethral closure pressure (MUCP) (p<0.001), as compared with those in the non-PPI group. Bladder capacity and detrusor pressure during voiding were also significantly lower in the PPI group. In the logistic regression, only MUCP and maximum cystometric capacity were identified as the related factor with the presence of PPI. In our study, significant number of patients with LUTS following RP showed a reduced bladder compliance and detrusor overactivity. PPI is associated with both impairment of the urethral closuring mechanism and bladder storage dysfunction.

Changes in surface structure and concanavalin A-binding capacity of urothelium in the mouse bladder after whole-body neutron irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodges, G.M.; Carr, K.E.; Hume, S.P.

A broad overview has been compiled of the literature on the effects of radiation on urinary bladder and on selected cell surface markers that may give information on the pathobiological status of the urinary bladder urothelium. Scanning electron microscopy and immunogold labelling have been used in this study which examines the early (6h to 12 day) radiation response of the mouse urinary bladder following whole-body neutron irradiation. Experimentally, after 5 Gy neutron irradiation, changes in the urothelium include surface morphological abnormalities and enhanced concanavalin A surface binding. These changes were most obvious 1 to 5 days post-irradiation, but lessened inmore » their extent from 5 to 12 days after treatment.« less

A clinical investigation of the mechanism of loxoprofen, a non-steroidal anti-inflammatory drug, for patients with nocturia.

PubMed

Araki, Tohru; Yokoyama, Teruhiko; Araki, Motoo; Furuya, Seiji

2008-12-01

We previously reported the effectiveness of loxoprofen sodium (loxoprofen), a non-steroidal anti-inflammatory drug, for patients with lower urinary tract symptoms (LUTS) complaining of nocturia. In this study, we explored the mechanism of loxoprofen in the treatment of nocturia. Fifty-six patients complaining of nocturia were enrolled. They took a single 60-mg tablet of loxoprofen at bedtime for 14 days. The effects of this treatment were assessed by bladder diaries. Nocturia improved (nocturia decreased >or=1 void/night) in 40 patients (71.4%). Nocturnal urine volume was reduced in 31 of 40 (77.5%) without nocturnal single-void volume increase. Nocturnal single-void volume increased in 4 of 40 (10.0%) without nocturnal urine volume reduction. Two of 40 (5.0%) demonstrated both nocturnal urine volume reduction and nocturnal single-void volume increase. Three (7.5%) were exceptions to the above. In conclusion, the main mechanism of loxoprofen is the reduction of nocturnal urine volume for the treatment of nocturia and the second mechanism is the increased bladder capacity.

Resveratrol improves urinary dysfunction in rats with chronic prostatitis and suppresses the activity of the stem cell factor/c-Kit signaling pathway.

PubMed

Yu, Yang; Jiang, Jiang; He, Yi; Wang, Wei; Shen, Chen; Yang, Bo

2017-08-01

Chronic prostatitis (CP) is a common urological disorder, with bladder voiding dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic compound isolated from numerous plants, with widely‑reported anti-inflammatory properties. The present study aimed to investigate whether resveratrol may improve overactive bladder in rats with CP and to investigate the underlying molecular mechanisms. Furthermore, the potential pharmacological synergy between resveratrol and solifenacin was also investigated as a potential treatment for CP. Following the successful establishment of a rat model of CP by subcutaneously injecting DPT vaccine, rats were treated with resveratrol or a combination of resveratrol + solifenacin. Bladder pressure and volume tests were performed to investigate the effect of resveratrol and solifenacin on urinary dysfunction in rats with chronic prostatitis. Western blot analysis and immunohistochemical staining were used to examine the expression of c‑Kit receptor, stem cell factor (SCF), AKT and phosphorylated‑AKT (p‑AKT) in the bladder tissue. The results of the bladder pressure and volume test indicated that the maximum capacity of the bladder, residual urine volume and maximum voiding pressure in the control group were 0.57 ml, 0.17 ml and 29.62 cm H2O, respectively. These values were increased by 71, 27 and 206% in rats in the CP group compared with the control group. Following treatment with resveratrol, the results in the resveratrol group were reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of western blot analysis, immunohistochemical staining and immunofluorescence labeling demonstrate that the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats in the CP group was 4.32, 6.13 and 6.31 times higher compared with the control group, respectively. Following treatment with resveratrol, protein expression was significantly reduced. However, no significant differences were observed between the protein expression of the SCF, c‑Kit and p‑AKT in the bladder between the resveratrol and combination groups. In conclusion, resveratrol may improve overactive bladder by downregulating the protein expression of SCF, c‑Kit and p‑AKT in the bladder of rats with CP. Furthermore, a combination of resveratrol and solifenacin may have potential pharmacological synergy as a treatment for patients with CP.

Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4–10) prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats

PubMed Central

Kullmann, F. Aura; Katofiasc, M.; Thor, K.B.; Marson, L.

2017-01-01

Purpose To determine feasibility of a novel therapeutic approach to drug-induced voiding after spinal cord injury (SCI) using a well-characterized, peptide, neurokinin 2 receptor (NK2 receptor) agonist, Lys5, MeLeu9, Nle10-NKA(4–10) (LMN-NKA). Methods Cystometry and colorectal pressure measurements were performed in urethane anesthetized, intact and acutely spinalized, female rats. Bladder pressure and voiding were monitored in response to intravenous LMN-NKA given with the bladder filled to 70% capacity. Results LMN-NKA (0.1–300 µg/kg) produced dose dependent, rapid (< 60 s), short duration (< 15 min) increases in bladder pressure. In intact rats, doses above 0.3–1 µg/kg induced urine release (voiding efficiency of ~ 70% at ≥ 1 µg/kg). In spinalized rats, urine release required higher doses (≥ 10 µg/kg) and was less efficient (30–50%). LMN-NKA (0.1–100 µg/kg) also produced dose dependent increases in colorectal pressure. No tachyphylaxis was observed, and the responses were blocked by an NK2 receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious cardiorespiratory effects were noted. Conclusions These results suggest that rapid-onset, short duration, drug-induced voiding is possible in acute spinal and intact rats with intravenous administration of an NK2 receptor agonist. Future challenges remain in regards to finding alternative routes of administration that produce clinically significant voiding, multiple times per day, in animal models of chronic SCI. PMID:27889808

Cluster analysis identifies three urodynamic patterns in patients with orthotopic neobladder reconstruction.

PubMed

Kim, Kwang Hyun; Yoon, Hyun Suk; Song, Wan; Choo, Hee Jung; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

2017-01-01

To classify patients with orthotopic neobladder based on urodynamic parameters using cluster analysis and to characterize the voiding function of each group. From January 2012 to November 2015, 142 patients with bladder cancer underwent radical cystectomy and Studer neobladder reconstruction at our institute. Of the 142 patients, 103 with complete urodynamic data and information on urinary functional outcomes were included in this study. K-means clustering was performed with urodynamic parameters which included maximal cystometric capacity, residual volume, maximal flow rate, compliance, and detrusor pressure at maximum flow rate. Three groups emerged by cluster analysis. Urodynamic parameters and urinary function outcomes were compared between three groups. Group 1 (n = 44) had ideal urodynamic parameters with a mean maximal bladder capacity of 513.3 ml and mean residual urine volume of 33.1 ml. Group 2 (n = 42) was characterized by small bladder capacity with low compliance. Patients in group 2 had higher rates of daytime incontinence and nighttime incontinence than patients in group 1. Group 3 (n = 17) was characterized by large residual urine volume with high compliance. When we examined gender differences in urodynamics and functional outcomes, residual urine volume and the rate of daytime incontinence were only marginally significant. However, females were significantly more likely to belong to group 2 or 3 (P = 0.003). In multivariate analysis to identify factors associated with group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017) and male gender (OR 7.57, P = 0.003) were identified as significant factors. While patients with ileal neobladder present with various voiding symptoms, three urodynamic patterns were identified by cluster analysis. Approximately half of patients had ideal urodynamic parameters. The other two groups were characterized by large residual urine and small capacity bladder with low compliance. Young age and male gender appear to have a favorable impact on urodynamic and voiding outcomes in patients undergoing orthotopic neobladder reconstruction.

Street ketamine-associated bladder dysfunction: an emerging health problem.

PubMed

Lee, Py; Ong, Ta; Chua, Cb; Lei, Ccm; Teh, Gc

2009-01-01

Ketamine is frequently abused nowadays as a recreational drug. Case reports are emerging since 2007 to describe a new clinical entity of severe bladder dysfunction associated with chronic abuse of street ketamine. Severe lower urinary tract symptoms of urinary frequency and urgency which are refractory to conventional treatment. Quality of life is adversely affected as a consequence. Chronic kidney disease will develop in advanced cases. Investigation findings: The urine is sterile on culture. Ultrasound will show reduced bladder capacity with thickened bladder wall. In advanced stage, hydronephrosis and renal impairment will develop. Patients should be advised to stop street ketamine use immediately. Anticholinergic medication could be tried to alleviate the symptoms. Refractory cases with dilatation of the upper urinary tract might need urinary diversion. Awareness of this new condition is essential in diagnosis. Early intervention offers better treatment outcome.

Biomarkers in bladder cancer: present status and perspectives.

PubMed

Kim, Wun-Jae; Park, Soongang; Kim, Yong-June

2007-03-27

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new bio-marker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.

Effects of fidarestat, an aldose reductase inhibitor, on nerve conduction velocity and bladder function in streptozotocin-treated female rats.

PubMed

Zotova, Elena G; Christ, George J; Zhao, Weixin; Tar, Moses; Kuppam, Srini D; Arezzo, Joseph C

2007-01-01

The effects of fidarestat, an aldose reductase inhibitor (ARI), were assessed on nerve conduction velocity (NCV) in somatic nerves and on multiple measures of bladder function in rats made hyperglycemic with streptozotocin (STZ) and in age-matched controls. Nerve conduction velocity was recorded at baseline and at 10, 20, 30, and 50 days after confirmation of the STZ-induced hyperglycemia in all rats (N=47); bladder function was assessed in a representative subset of rats (N=20) at Day 50. Caudal NCV was markedly slowed by STZ, and this effect was significantly reversed by fidarestat. The initial deficit and treatment-related improvement were especially evident for responses driven by high-frequency repetitive stimulation. Of the 11 parameters of bladder activity assessed, four measures-bladder capacity, micturition volume, micturition frequency, and bladder weight-were significantly different in the control and STZ-treated groups. These deficits were not affected by fidarestat. At Day 50, the induced deficits in bladder function were highly correlated with caudal NCV (r values ranging from 0.70 to 0.96; P values ranging from .02 to <.0001). These results suggested that fidarestat improved the slowing of somatic nerve NCV in hyperglycemic rats, but it was not effective in reversing associated bladder dysfunction, in spite of the highly significant correlation between these two diabetes-induced deficits. Possible explanations for this dissociation are discussed.

[Intra-detrusor injection of botulinumtoxin in patients with refractory overactive bladder].

PubMed

Krhut, J; Kopecký, J

2007-12-01

Symptoms of overactive bladder affect the quality of patients' life significantly. There is a standard treatment consisting in application of anticholinergics or possibly other conservative methods. This treatment fails at a certain part of patients however. While radical surgical therapy used to be offered to such patients in the past, the botulinumtoxin injection is available at present. The aim of the paper is to assess the efficacy and safety of this treatment method in own set of female patients with refractory overractive bladder. The set totals of 16 female patients with refractory overactive bladder. The average age in the set is 52.7 (38-69) years. Patients were treated by the application of botulinumtoxin in the period 6/2004-12/2006; the follow-up is 21.6 (6-36) months. In all cases the Dysport preparation in the dose 1000 UI was used for application. Botulinumtoxin has been applied during a short endoscopic procedure using a flexible needle into 40 points in the detrusor. Subjective satisfaction, data from voiding diaries, urodynamic parameters and the duration of effect persistence were evaluated. Subjective satisfaction with the treatment result was reached in 13 (81.3%) patients. In 12 (75.0%) patients the full continence was obtained. Average urinary bladder evacuation frequency decreased from 15.8/24 h to 5.5/24 h after the treatment, the number of urgency episodes decreased from 7.7/24 h to 0.8/24 h while average evacuated volume increased from 107.9 to 329.0 ml. The maximum cystometric capacity increased from 151.9 ml to 311.2 ml while maximum detrusor pressure decreased from 31.0 to 143 cm H2O at urodynamic assesment. The changes in all monitored parameters were statistically significant. The effect duration was 10.3 (6-13) months. No side effects of the application were registered during the treatment. The application of botulinumtoxin into detrusor is an effective and safe treatment method for refractory overactive bladder. Final standardization of the treatment by botulinumtoxin additional studies focused especially to the research of the relation among the dose, solution and clinical effect are necessary.

[Recommendations for the urodynamic examination in the investigation of non-neurological female urinary incontinence].

PubMed

Hermieu, Jean François

2007-11-01

INDICATIONS FOR URODYNAMIC ASSESSMENT IN WOMEN: Urodynamic assessment is not useful for the diagnosis of female urinary incontinence which remains a clinical diagnosis. Before any form of surgery for pure stress urinary incontinence, evaluation of bladder emptying by determination of maximum flow rate and residual urine is recommended. In the presence of pure stress urinary incontinence with no other associated clinical symptoms, a complete urodynamic assessment is not mandatory, but can be helpful to define the prognosis and inform the patient about her vesicosphincteric function. On the other hand, a complete urodynamic assessment is recommended to investigate complex or complicated urinary incontinence, mainly in the case of: history of surgery for urinary incontinence. urgency with or without urine leakage, severe urinary incontinence, voiding abnormalities, negative cough test, decreased bladder capacity, suspected obstruction or decreased bladder contractility, failure of first-line treatment. PATIENT PREPARATION: The patient should be thoroughly informed about the examination procedure and its possible consequences. The patient should be advised to attend the examination with a normal desire to urinate. Urodynamic assessment must not be performed in the presence of untreated urinary tract infection. Antibiotic prophylaxis is not recommended. UROFLOWMETRY: The flowmeter must be regularly calibrated and must be installed in a quiet room. Whenever possible, uroflowmetry should be performed before cystometry with a normal desire to urinate. The patient should be advised to urinate normally without straining and by staying as relaxed as possible. During voiding, all of the stream must enter the flowmeter. The main parameters recorded are Qmax (expressed in ml/s), the voided volume (expressed in ml), and the appearance of the curve. The examination must be interpreted manually without taking into account the automated interpretation. GUIDELINES CONCERNING CYSTOMETRY EQUIPMENT: A three pressure line configuration is recommended. Bladder filling must be performed with a sterile liquid; filling with gas is no longer recommended. Bladder filling is ideally performed by a pump ensuring a sufficiently slow flow rate to avoid modifying bladder behaviour (< 50 ml/min). It is essential to determine and check the volume infused into the bladder. When a peristaltic pump is used, the bladder filling catheter must be adapted to the pump. Water or electronic transducers can be used to measure bladder pressure. Balloon catheters filled with air appear to be sufficiently precise to perform pressure measurements in a manometric chamber (during cystometry) but not in a virtual cavity such as the urethra (during the urethral pressure profile). Measurement of abdominal pressure is recommended, either via the infusion catheter or preferably by a rectal balloon catheter. GUIDELINES ON THE PRACTICAL CONDITIONS OF CYSTOMETRY: The equipment must be regularly calibrated. Make sure that the bladder is empty before starting cystometry. Transducers are zeroed at the superior extremity of the pubic symphysis for infused transducers and at atmospheric pressure for electronic and air transducers. Tubings must be correctly connected without kinks, bubbles or leaks. The catheter must be selected according to its technical characteristics, particularly its pressure loss. After filling for one or two minutes, the patient is asked to cough to ensure a similar increase in both abdominal pressure and bladder pressure. The following parameters are recorded: baseline detrusor pressure, first desire to void, detrusor activity, bladder capacity and bladder compliance. Measurement of bladder pressure during voiding is used to confirm whether or not the bladder is contractile, assess obstruction in the case of low urine flow rate with high bladder pressure, and detect abdominal straining. Good test conditions must be ensured in order to obtain good quality voiding. In the case of incoherent results, the bladder should be re-filled after checking the equipment. MEASUREMENT AND INTERPRETATION OF URETHRAL PRESSURE: To obtain a reliable measurement of urethral pressure, it is recommended to: Define the normal values used. Use a catheter smaller than 12 F. Perform a circumferential measurement. Use a catheter with an infusion rate of 2 ml/min. Remove the catheter at a rate of 1 mm/s. Perform the examination in the seating or supine position with a half-full bladder after reducing any prolapse. Repeat the measurements. THE FOLLOWING ELEMENTS MUST BE TAKEN INTO ACCOUNT WHEN INTERPRETING AN URETHRAL PRESSURE PROFILE: The functional urethral length is neither a diagnostic criterion nor a prognostic criterion of urinary incontinence. The urethral pressure profile cannot be considered to be a useful test for the diagnosis of female urinary incontinence. However, in combination with clinical criteria, it is predictive of the results of female stress urinary incontinence surgical repair techniques. The pressure transmission ratio is neither a diagnostic criterion nor a prognostic criterion of urinary incontinence.

Urologic evaluation of urinary tract infection in pregnancy.

PubMed

Diokno, A C; Compton, A; Seski, J; Vinson, R

1986-01-01

Thirty-three antepartum patients with urinary tract infections underwent urologic evaluation as soon as the infection had been successfully treated. The evaluation included history of voiding habits, cystometry, urethral calibration and cystourethroscopy. A second phase of the urologic evaluation included an excretory urogram and repeat cystometry 10-12 weeks postpartum. Sixty percent had a history of infrequent voiding, and 90% of them had a bladder capacity greater than 450 mL. Forty-one percent of the patients had a normal bladder capacity (less than 450 mL), and 85% of this group did not have any history of infrequent voiding. The radiographic evaluation postpartum in 18 of 33 patients revealed major abnormalities in 50%. These abnormalities were seen as often and were as significant in women with asymptomatic bacteriuria as in those who presented with acute pyelonephritis. The results suggest that the large bladder seen in pregnant women may be secondary to the chronic, unphysiologic habit of infrequent voiding. Furthermore, this study reinforced the fact that most pregnant women with urinary tract infection have preexisting chronic bladder or renal abnormalities that predispose them to infection. Those at risk should be identified early through a careful history and urinalysis to determine which ones need urinary prophylaxis during pregnancy. Postpartum urologic investigation should be carried out to identify any structural or functional problems; understanding them is helpful in present and future management.

Cerebral control of the bladder in normal and urge-incontinent women

PubMed Central

Griffiths, Derek; Tadic, Stasa D.; Schaefer, Werner; Resnick, Neil M.

2007-01-01

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase. Conclusion: Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO). PMID:17574871

Nuclear fusion-independent smooth muscle differentiation of human adipose-derived stem cells induced by a smooth muscle environment.

PubMed

Zhang, Rong; Jack, Gregory S; Rao, Nagesh; Zuk, Patricia; Ignarro, Louis J; Wu, Benjamin; Rodríguez, Larissa V

2012-03-01

Human adipose-derived stem cells hASC have been isolated and were shown to have multilineage differentiation capacity. Although both plasticity and cell fusion have been suggested as mechanisms for cell differentiation in vivo, the effect of the local in vivo environment on the differentiation of adipose-derived stem cells has not been evaluated. We previously reported the in vitro capacity of smooth muscle differentiation of these cells. In this study, we evaluate the effect of an in vivo smooth muscle environment in the differentiation of hASC. We studied this by two experimental designs: (a) in vivo evaluation of smooth muscle differentiation of hASC injected into a smooth muscle environment and (b) in vitro evaluation of smooth muscle differentiation capacity of hASC exposed to bladder smooth muscle cells. Our results indicate a time-dependent differentiation of hASC into mature smooth muscle cells when these cells are injected into the smooth musculature of the urinary bladder. Similar findings were seen when the cells were cocultured in vitro with primary bladder smooth muscle cells. Chromosomal analysis demonstrated that microenvironment cues rather than nuclear fusion are responsible for this differentiation. We conclude that cell plasticity is present in hASCs, and their differentiation is accomplished in the absence of nuclear fusion. Copyright © 2011 AlphaMed Press.

Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature.

PubMed

Simsek, E; Simsek, T; Tekgül, S; Hosal, S; Seyrantepe, V; Aktan, G

2003-01-01

To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature. Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology. The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA(Leu) (UUR) A to G (nucleotide 3243) mutation. Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.

A Randomized Comparative Study Evaluating Various Cough Stress Tests and 24-Hour Pad Test with Urodynamics in the Diagnosis of Stress Urinary Incontinence.

PubMed

Henderson, Joseph W; Kane, Sarah M; Mangel, Jeffrey M; Kikano, Elias G; Garibay, Jorge A; Pollard, Robert R; Mahajan, Sangeeta T; Debanne, Sara M; Hijaz, Adonis K

2018-06-01

The cough stress test is a common and accepted tool to evaluate stress urinary incontinence but there is no agreement on how the test should be performed. We assessed the diagnostic ability of different cough stress tests performed when varying patient position and bladder volume using urodynamic stress urinary incontinence as the gold standard. The 24-hour pad test was also evaluated. We recruited women who presented to specialty outpatient clinics with the complaint of urinary incontinence and who were recommended to undergo urodynamic testing. A total of 140 patients were randomized to 4 cough stress test groups, including group 1-a comfortably full bladder, group 2-an empty bladder, group 3- a bladder infused with 200 cc saline and group 4-a bladder filled to half functional capacity. The sequence of standing and sitting was randomly assigned. The groups were compared by 1-way ANOVA or the generalized Fisher exact test. The κ statistic was used to evaluate agreement between the sitting and standing positions. The 95% CIs of sensitivity and specificity were calculated using the Wilson method. ROC analysis was done to evaluate the performance of the 24-hour pad test. The cough stress test performed with a bladder filled to half functional capacity was the best performing test with 83% sensitivity and 90% specificity. There was no statistically significant evidence that the sensitivity or specificity of 1 cough stress test differed from that of the others. The pad test had no significant predictive ability to diagnose urodynamic stress urinary incontinence (AUC 0.60, p = 0.08). Cough stress tests were accurate to diagnose urodynamic stress urinary incontinence. The 24-hour pad test was not predictive of urodynamic stress urinary incontinence and not helpful when used in conjunction with the cough stress test. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Paul-Yann; Lin, Yung-Lun; Huang, Chin-Chin

Epidemiological studies have revealed that exposure to an arsenic-contaminated environment correlates with the incidence of bladder cancer. Bladder cancer is highly recurrent after intravesical therapy, and most of the deaths from this disease are due to invasive metastasis. In our present study, the role of inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. This work provides the first evidence that inorganic arsenic in drinking water promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue damage, including the urothelium and submucosal layer. This damage to the bladder epithelium induced by BBN includes thickening of the submucosal layer, the loss of the glycosaminoglycanmore » layer and an increase in both the deoxyguanosine oxidation and cytosine methylation levels in the DNA. Further, when 10 ppm inorganic arsenic is combined with BBN, the number of bladder submucosal capillaries is increased. In addition, inorganic arsenic also increases the deoxyguanosine oxidation level, alters the cytosine methylation state, decreases the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and increases the protein expression of specific protein 1 (Sp1) in bladder tissues. In summary, our data reveal that inorganic arsenic in drinking water promotes the BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 8-hydroxy-2′-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein levels may be pre-neoplastic markers of bladder tumors. -- Highlights: ► The role of inorganic arsenic in bladder carcinogenesis is characterized in mice. ► We examine the changes in the histology and biochemistry of bladder tissues. ► Inorganic arsenic enhances BBN-induced DNA oxidation while decreases BBN-induced DNA methylation in the mouse bladder. ► Inorganic arsenic alters the activities of the anti-oxidant enzymes in the mouse bladder. ► Inorganic arsenic increases Sp1 while decreases NQO-1 protein expression in the mouse whole bladder.« less

Curcumin inhibits bladder cancer progression via regulation of β-catenin expression.

PubMed

Shi, Jing; Wang, Yunpeng; Jia, Zhuomin; Gao, Yu; Zhao, Chaofei; Yao, Yuanxin

2017-07-01

Bladder cancer has a considerable morbidity and mortality impact with particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic compound separated from turmeric to regulate tumor progression. However, the precise molecular mechanism by which curcumin inhibits the invasion and metastasis of bladder cancer cells is not fully elucidated. In this study, we investigate the effect of curcumin on the bladder cancer as well as possible mechanisms of curcumin. The expression of β-catenin was detected by quantitative real-time polymerase chain reaction and immunohistochemical analysis in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24 and 5637 cells were treated with different concentrations of curcumin. The cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The migration and invasion capacity of T24 and 5637 cells were measured by transwell assay. The effects of curcumin on expression levels of β-catenin and epithelial-mesenchymal transition marker were determined by western blotting. The β-catenin expression was significantly upregulated in bladder cancer tissues when compared with corresponding peri-tumor tissues. Furthermore, curcumin inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the migration and invasive ability of T24 and 5637 cells via regulating β-catenin expression and reversing epithelial-mesenchymal transition. Curcumin may be a new drug for bladder cancer.

Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring.

PubMed

Majerus, Steve J A; Garverick, Steven L; Suster, Michael A; Fletter, Paul C; Damaser, Margot S

2012-06-01

The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic bladder pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for bladder control. Neuromodulation in particular would benefit from a wireless bladder pressure sensor which could provide real-time pressure feedback to an implanted stimulator, resulting in greater bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μ A from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session.

Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring

PubMed Central

MAJERUS, STEVE J. A.; GARVERICK, STEVEN L.; SUSTER, MICHAEL A.; FLETTER, PAUL C.; DAMASER, MARGOT S.

2015-01-01

The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic bladder pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for bladder control. Neuromodulation in particular would benefit from a wireless bladder pressure sensor which could provide real-time pressure feedback to an implanted stimulator, resulting in greater bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μA from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session. PMID:26778926

1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

2010-01-01

Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

PubMed Central

Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron

2016-01-01

In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581

Spontaneously released substance P and bradykinin from isolated guinea-pig bladder.

PubMed

Saban, R; Franz, J; Bjorling, D E

1997-04-01

To investigate whether the isolated urinary bladder spontaneously releases substance P (SP) or bradykinin (BK), which can act as potent mediators of pain and inflammation of the urinary bladder, and whether peptidase inhibitors enhance peptide release. Urinary bladder segments (2 x 10 x 0.8-1 mm) were isolated from guinea pigs and studied in vitro; tissue contraction was assessed using force-displacement transducers and the release of peptides by specific enzyme immunoassays. In the absence of any exogenous agonists, the inhibition of neutral endopeptidase and angiotensin-converting enzyme by phosphoramidon and captopril, respectively, increased the frequency and magnitude of spontaneous motility of isolated bladder strips. Phosphoramidon increased the net release of SP-like immunoreactivity (SP-LI) and captopril increased the net release of SP-LI and BK-LI, concomitant with contraction. Peptide-LI was recovered primarily from bladder mucosa and to a lesser degree from detrusor smooth muscle. Similarly, peptidase inhibitors primarily affected the bladder mucosa; phosphoramidon induced a fourfold increase in SP-LI and captopril induced a significant increase of SP-LI and BK-LI from the mucosa. Tissues contracted in response to peptidase inhibitors in the presence of atropine and indomethacin, but contraction was reduced significantly by in vitro capsaicin desensitization or removal of bladder mucosa. BK stimulated SP-LI release from mucosa but not detrusor. SP stimulated increased BK-LI release from mucosa and detrusor. These findings indicate the basal release of peptide-like immunoreactivity by isolated bladder and further support the concept that peptidases located in the bladder mucosa are important in terminating the effects of endogenous peptides.

Botulinum-A toxin injection into the detrusor: a safe alternative in the treatment of children with myelomeningocele with detrusor hyperreflexia.

PubMed

Riccabona, Marcus; Koen, Mark; Schindler, Monica; Goedele, Beckers; Pycha, Armin; Lusuardi, Lukas; Bauer, Stuart B

2004-02-01

We prospectively evaluated the efficacy and durability of botulinum-A toxin in the treatment of detrusor hyperreflexia in children with myelomeningocele (MMC). This study involved 15 patients with MMC (10 male and 5 female, mean age 5.8 years), all nonresponders to orally and intravesically administered anticholinergic medication and all on clean intermittent catheterization. Pretreatment assessment included a videourodynamic evaluation, an incontinence score and a mercaptoacetyltriglycine-3 renal scan. We injected 10 U/kg to a maximum of 360 U of botulinum-A toxin into the detrusor at 25 to 40 sites, sparing the trigone. Followup lasted between 12 and 30 months. All children underwent a urodynamic reevaluation, an assessment of the bladder capacity and an incontinence score at 3, 9 and 12 months after the first injection. A second intravesical injection was administered after 12 months and followup repeated as in the first year. After the first injection treatment mean bladder reflex volume increased from 72.00 +/- 28.12 ml to 298 +/- 32.45 ml (mean +/- SD, p <0.001). Maximum detrusor pressure decreased from 78.76 +/- 23.14 cm H2O to 42.76 +/- 24.34 cm H2O (p <0.001). Maximum bladder capacity increased from 136.34 +/- 45.71 ml to 297.02 +/- 87.17 ml (p <0.001). Detrusor compliance increased from 18.29 +/- 27.19 ml/cm H2O to 51.17 +/- 38.17 ml/cm H2O (p <0.001). Of the 15 patients 13 became completely dry with CIC. The remaining 2 patients improved from score 3 to 1. Results after 9 months were similar to those obtained after 3 months. Mean durability of the effect of the drug was 10.5 months after the first as well as after the second intravesical injection. Botulinum-A toxin is a safe alternative in the management of detrusor hyperreflexia in children with MMC. The preliminary results regarding urodynamic parameters and continence have been promising.

Urinary incontinence in women

PubMed Central

Aoki, Yoshitaka; Brown, Heidi W.; Brubaker, Linda; Cornu, Jean Nicolas; Daly, J. Oliver; Cartwright, Rufus

2018-01-01

Urinary incontinence symptoms are highly prevalent among women, have a substantial effect on health-related quality of life and are associated with considerable personal and societal expenditure. Two main types are described: stress urinary incontinence, in which urine leaks in association with physical exertion, and urgency urinary incontinence, in which urine leaks in association with a sudden compelling desire to void. Women who experience both symptoms are considered as having mixed urinary incontinence. Research has revealed overlapping potential causes of incontinence, including dysfunction of the detrusor muscle or muscles of the pelvic floor, dysfunction of the neural controls of storage and voiding, and perturbation of the local environment within the bladder. A full diagnostic evaluation of urinary incontinence requires a medical history, physical examination, urinalysis, assessment of quality of life and, when initial treatments fail, invasive urodynamics. Interventions can include non-surgical options (such as lifestyle modifications, pelvic floor muscle training and drugs) and surgical options to support the urethra or increase bladder capacity. Future directions in research may increasingly target primary prevention through understanding of environmental and genetic risks for incontinence. PMID:28681849

Preventive Effect of Hydrogen Water on the Development of Detrusor Overactivity in a Rat Model of Bladder Outlet Obstruction.

PubMed

Miyazaki, Nozomu; Yamaguchi, Osamu; Nomiya, Masanori; Aikawa, Ken; Kimura, Junko

2016-03-01

Bladder ischemia and oxidative stress contribute to the pathogenesis of bladder dysfunction caused by bladder outlet obstruction. H2 reportedly acts as an effective antioxidant. We investigated whether oral ingestion of H2 water would have a beneficial effect on bladder function in a rat model of bladder outlet obstruction. H2 water was made by dissolving H2 gas in ordinary drinking water using a hydrogen water producing apparatus. The bladder outlet obstruction model was surgically induced in male rats. Rats with obstruction were fed H2 water or ordinary drinking water. On week 4 postoperatively cystometry was performed. Oxidative stress markers and the bladder nerve growth factor level were determined. Bladder tissues were processed for pharmacological studies and histological analysis. The micturition interval and micturition volume significantly decreased in obstructed rats given ordinary drinking water. These decreases were significantly suppressed by oral ingestion of H2 water. Increased post-void residual volume in obstructed rats was significantly reduced by H2 water. Obstruction led to a significant increase in bladder weight, oxidative stress markers and nerve growth factor. H2 water significantly suppressed these increases without affecting bladder weight. There was no significant difference in histological findings between rats with bladder obstruction given H2 water and ordinary drinking water. Decreased responses of detrusor muscle strips from obstructed bladders to KCl, carbachol and electrical field stimulation were reversed by H2 water ingestion. Results suggest that H2 water could ameliorate bladder dysfunction secondary to bladder outlet obstruction by attenuating oxidative stress. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Orthotopic bladder substitution in men revisited: identification of continence predictors.

PubMed

Koraitim, M M; Atta, M A; Foda, M K

2006-11-01

We determined the impact of the functional characteristics of the neobladder and urethral sphincter on continence results, and determined the most significant predictors of continence. A total of 88 male patients 29 to 70 years old underwent orthotopic bladder substitution with tubularized ileocecal segment (40) and detubularized sigmoid (25) or ileum (23). Uroflowmetry, cystometry and urethral pressure profilometry were performed at 13 to 36 months (mean 19) postoperatively. The correlation between urinary continence and 28 urodynamic variables was assessed. Parameters that correlated significantly with continence were entered into a multivariate analysis using a logistic regression model to determine the most significant predictors of continence. Maximum urethral closure pressure was the only parameter that showed a statistically significant correlation with diurnal continence. Nocturnal continence had not only a statistically significant positive correlation with maximum urethral closure pressure, but also statistically significant negative correlations with maximum contraction amplitude, and baseline pressure at mid and maximum capacity. Three of these 4 parameters, including maximum urethral closure pressure, maximum contraction amplitude and baseline pressure at mid capacity, proved to be significant predictors of continence on multivariate analysis. While daytime continence is determined by maximum urethral closure pressure, during the night it is the net result of 2 forces that have about equal influence but in opposite directions, that is maximum urethral closure pressure vs maximum contraction amplitude plus baseline pressure at mid capacity. Two equations were derived from the logistic regression model to predict the probability of continence after orthotopic bladder substitution, including Z1 (diurnal) = 0.605 + 0.0085 maximum urethral closure pressure and Z2 (nocturnal) = 0.841 + 0.01 [maximum urethral closure pressure - (maximum contraction amplitude + baseline pressure at mid capacity)].

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PubMed

Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E

2016-03-01

Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sensory feedback from the urethra evokes state-dependent lower urinary tract reflexes in rat.

PubMed

Danziger, Zachary C; Grill, Warren M

2017-08-15

The lower urinary tract is regulated by reflexes responsible for maintaining continence and producing efficient voiding. It is unclear how sensory information from the bladder and urethra engages differential, state-dependent reflexes to either maintain continence or promote voiding. Using a new in vivo experimental approach, we quantified how sensory information from the bladder and urethra are integrated to switch reflex responses to urethral sensory feedback from maintaining continence to producing voiding. The results demonstrate how sensory information regulates state-dependent reflexes in the lower urinary tract and contribute to our understanding of the pathophysiology of urinary retention and incontinence where sensory feedback may engage these reflexes inappropriately. Lower urinary tract reflexes are mediated by peripheral afferents from the bladder (primarily in the pelvic nerve) and the urethra (in the pudendal and pelvic nerves) to maintain continence or initiate micturition. If fluid enters the urethra at low bladder volumes, reflexes relax the bladder and evoke external urethral sphincter (EUS) contraction (guarding reflex) to maintain continence. Conversely, urethral flow at high bladder volumes, excites the bladder (micturition reflex) and relaxes the EUS (augmenting reflex). We conducted measurements in a urethane-anaesthetized in vivo rat preparation to characterize systematically the reflexes evoked by fluid flow through the urethra. We used a novel preparation to manipulate sensory feedback from the bladder and urethra independently by controlling bladder volume and urethral flow. We found a distinct bladder volume threshold (74% of bladder capacity) above which flow-evoked bladder contractions were 252% larger and evoked phasic EUS activation 2.6 times as often as responses below threshold, clearly demonstrating a discrete transition between continence (guarding) and micturition (augmenting) reflexes. Below this threshold urethral flow evoked tonic EUS activity, indicative of the guarding reflex, that was proportional to the urethral flow rate. These results demonstrate the complementary roles of sensory feedback from the bladder and urethra in regulating reflexes in the lower urinary tract that depend on the state of the bladder. Understanding the neural control of functional reflexes and how they are mediated by sensory information in the bladder and urethra will open new opportunities, especially in neuromodulation, to treat pathologies of the lower urinary tract. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

The use of water-soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle-invasive bladder cancer.

PubMed

Chatta, Dani; Cottrell, Lewis; Burnett, Bruce; Laverty, Garry; McConville, Christopher

2015-10-01

To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine. Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine. Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine. The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer. © 2015 Royal Pharmaceutical Society.

The inverse relationship between bladder and liver in 4-aminobiphenyl-induced DNA damage

PubMed Central

Stablewski, Aimee B.; Vouros, Paul; Zhang, Yuesheng

2015-01-01

Bladder cancer risk is significantly higher in men than in women. 4-Aminobiphenyl (ABP) is a major human bladder carcinogen from tobacco smoke and other sources. In mice, male bladder is more susceptible to ABP-induced carcinogenesis than female bladder, but ABP is more carcinogenic in the livers of female mice than of male mice. Here, we show that castration causes male mice to acquire female phenotype regarding susceptibility of bladder and liver to ABP. However, spaying has little impact on organ susceptibility to ABP. Liver UDP-glucuronosyltransferases (UGTs) are believed to protect liver against but sensitize bladder to ABP, as glucuronidation of ABP and its metabolites generally reduces their toxicity and promotes their elimination via urine, but the metabolites are labile in urine, delivering carcinogenic species to the bladder. Indeed, liver expression of ABP-metabolizing human UGT1A3 transgene in mice increases bladder susceptibility to ABP. However, ABP-specific liver UGT activity is significantly higher in wild-type female mice than in their male counterparts, and castration also significantly increases ABP-specific UGT activity in the liver. Taken together, our data suggest that androgen increases bladder susceptibility to ABP via liver, likely by modulating an ABP-metabolizing liver enzyme, but exclude UGT as an important mediator. PMID:25596734

The effectiveness of transcutaneous electrical neural stimulation therapy in patients with urinary incontinence resistant to initial medical treatment or biofeedback.

PubMed

Tugtepe, H; Thomas, D T; Ergun, R; Kalyoncu, A; Kaynak, A; Kastarli, C; Dagli, T E

2015-06-01

While there are many options for children with treatment refractory urinary incontinence, there is no single accepted method. This study's aim was to prospectively evaluate the effect of transcutaneous electrical nerve stimulation in children with urinary incontinence resistant to standard medical, urological therapy and/or biofeedback. This study was performed at a university hospital. For inclusion, patients >5 years of age first underwent evaluation with urinary ultrasonography, uroflow-electromyogram and voiding diaries. Treatment with biofeedback, alpha adrenergic blockers, anticholinergics and/or urotherapy was commenced according to uroflow-EMG and voiding diary findings. Patients with partial or no response to this standard therapy were then included in this study, performed between April 2012 and February 2014. Patients with anatomical or neurological causes for urinary incontinence were excluded. TENS was performed on S3 dermatome, every day for 3 months. Each session lasted 20 min with a frequency of 10 Hz and generated pulse of 350 μs. Intensity was determined by the child's sensitivity threshold. Medical treatment and urological therapy was continued during TENS. Uroflow parameters (voiding volume as percentage of expected bladder capacity, Qmax, Qave, flow and voiding time, postvoiding residual urine) and urinary system symptoms (presence of urinary tract infection, frequency, urge incontinence, fractionated voiding and constipation) were compared immediately before commencement and immediately after the completion of 3 months of TENS. Twenty-seven patients were included in this study (4 males, 23 females). Patients' average age was 7.2 years, 11 had overactive bladder and 16 had dysfunctional voiding. Comparison of urinary system symptoms and uroflow parameters before and after TENS are shown in Table. After 3 months of TENS; a statistically significant decrease was observed in the number of patients with frequency, urge incontinence, urinary tract infections and constipation. There was a decrease in the number of patients with fractionated voiding, although this change was not statistically significant. Similarly, for uroflow-EMG parameters; bladder capacity, Qmax, Qave and flow time increased while voiding time and PVR decreased. Changes seen in bladder capacity, Qmax and PVR were statically significant, while other changes were not. Patients' response rates after 3 months of TENS were; complete response in 70.4%, partial response in 22.2% and no response in 7.4%. This study has shown that transcutaneous electrical nerve stimulation is a promising treatment option for standard-treatment refractory children with urinary incontinence. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

PubMed Central

2011-01-01

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors. PMID:21507255

Electrical stimulation of anal sphincter or pudendal nerve improves anal sphincter pressure.

PubMed

Damaser, Margot S; Salcedo, Levilester; Wang, Guangjian; Zaszczurynski, Paul; Cruz, Michelle A; Butler, Robert S; Jiang, Hai-Hong; Zutshi, Massarat

2012-12-01

Stimulation of the pudendal nerve or the anal sphincter could provide therapeutic options for fecal incontinence with little involvement of other organs. The goal of this project was to assess the effects of pudendal nerve and anal sphincter stimulation on bladder and anal pressures. Ten virgin female Sprague Dawley rats were randomly allocated to control (n = 2), perianal stimulation (n = 4), and pudendal nerve stimulation (n = 4) groups. A monopolar electrode was hooked to the pudendal nerve or placed on the anal sphincter. Aballoon catheter was inserted into the anus to measure anal pressure, and a catheter was inserted into the bladder via the urethra to measure bladder pressure. Bladder and anal pressures were measured with different electrical stimulation parameters and different timing of electrical stimulation relative to spontaneous anal sphincter contractions. Increasing stimulation current had the most dramatic effect on both anal and bladder pressures. An immediate increase in anal pressure was observed when stimulating either the anal sphincter or the pudendal nerve at stimulation values of 1 mA or 2 mA. No increase in anal pressure was observed for lower current values. Bladder pressure increased at high current during anal sphincter stimulation, but not as much as during pudendal nerve stimulation. Increased bladder pressure during anal sphincter stimulation was due to contraction of the abdominal muscles. Electrical stimulation caused an increase in anal pressures with bladder involvement only at high current. These initial results suggest that electrical stimulation can increase anal sphincter pressure, enhancing continence control.

Use of donor bladder tissues for in vitro research.

PubMed

Garthwaite, Mary; Hinley, Jennifer; Cross, William; Warwick, Ruth M; Ambrose, Anita; Hardaker, Henry; Eardley, Ian; Southgate, Jennifer

2014-01-01

To evaluate deceased non-heart beating (DNHB) donors and deceased heart beating (DHB) brain-stem dead donors, as sources of viable urological tissue for use in biomedical research. To identify sources of viable human bladder tissue as an essential resource for cell biological research aimed at understanding human diseases of the bladder and for developing new tissue engineering and regenerative medicine strategies for bladder reconstruction. Typically, normal human urinary tract tissue is obtained from adult or paediatric surgical patients with benign urological conditions, but few surgical procedures yield useful quantities of healthy bladder tissue for research. Research ethics committee approval was obtained for collection of donor bladder tissue. Consent for DHB donors was undertaken by the Donor Transplant Coordinators. Tissue Donor Coordinators were responsible for consent for DNHB donors and the retrieval of bladders was coordinated through the National Blood Service Tissue Banking Service. All retrievals were performed by practicing urologists and care was taken to maintain sterility and to minimise bacterial contamination. Two bladders were retrieved from DNHB donors and four were retrieved from DHB donors. By histology, DNHB donor bladder tissue exhibited marked urothelial tissue damage and necrosis, with major loss or absence of urothelium. No cell cultures could be established from these specimens, as the urothelial cells were not viable in primary culture. Bladder urothelium from DHB donors was intact, but showed some damage, including loss of superficial cells and variable separation from the basement membrane. All four DHB bladder specimens yielded viable urothelial cells that attached in primary culture, but cell growth was slow to establish and cultures showed a limited capacity to form a functional barrier epithelium and a propensity to senesce early. We have shown that normal human bladder urothelial cell cultures can be established and serially propagated from DHB donor bladders. However, our study suggests that rapid post-mortem changes to the bladder affect the quality and viability of the urothelium, rendering tissue from DNHB donors an inadequate source for urothelial cell culture. Our experience is that whereas patients are willing to donate surgical tissue for research, there is a barrier to obtaining consent from next of kin for retrieved tissues to be used for research purposes. © 2013 The Authors. BJU International © 2013 BJU International.

Bladder augmentation using the gastrointestinal tract. Indication, follow up and complications.

PubMed

Escudero, R Molina; Patiño, G Escribano; Fernández, E Rodríguez; Gil, M J Cancho; García, E Lledó; Alonso, A Husillos; Piniés, G Ogaya; Sánchez, J Piñeiro; Fernández, C Hernández

2011-12-01

The purpose of bladder augmentation using the gastrointestinal tract is to create a low-pressure and high-capacity reservoir, permitting suitable continence and voiding, preserving the upper urinary tract. To analyze the indications, complications and results of our series of augmentation enterocystoplasties. We retrospectively reviewed patients undergoing augmentation enterocystoplasty in our department between 1997 and 2010, both included. The indications were: Interstitial cystitis, neurogenic bladder and inflammatory bladder retraction. In all cases a cystography, urethrocystoscopy, urodynamic study and studies of each condition. Bladder release is performed by means of medial laparotomy and an extraperitoneal approach with bivalve opening to the urethral orifices. The bladder augmentation is performed with a 15-20 cm segment of detubularized ileum obtained at 20 cm from the ileocecal valve; in cases of kidney failure, a 7-cm gastric body wedge is added. The bladder catheter was removed following cystogram after 15 days. Monitoring was performed by means of ultrasound with postvoid residual, blood analyses, urine culture and voiding diary. We performed a descriptive study of the demographic characteristics, postoperative complications according to the Clavien classification and in the long term. We included 24 patients, 19 women and 5 men with a mean age of 48.5 years and a median of 47 (21-77). Mean follow up was 7.5 years with a median of 8 (1-11). The indications were: 7 interstitial cystitis, 8 bladder retraction and 7 neurogenic bladder. There were no intraoperative complications. The postoperative complications were 3 Clavien I, 2 type II, 2 IIIA and 1 IIIB. In the long term, 3 patients presented urinary incontinence, 2 mild metabolic acidosis, 5 required self-catheterization, 6 bladder stones, 2 febrile urinary tract infections and 1 stricture of the anastomotic mouth. In three cases, an ileogastrocystoplasty was performed without hydroelectrolytic impairment or impairment of kidney function. In selected patients, augmentation enterocystoplasty constitutes an efficacious therapeutic option in the treatment of lower urinary tract dysfunction with scant morbidity and few complications.

Cytokine expression in patients with bladder pain syndrome/interstitial cystitis ESSIC type 3C.

PubMed

Logadottir, Yr; Delbro, Dick; Fall, Magnus; Gjertsson, Inger; Jirholt, Pernilla; Lindholm, Catharina; Peeker, Ralph

2014-11-01

Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls. Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count. IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C. Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Family history of cancer and the risk of bladder cancer: A case-control study from Italy.

PubMed

Turati, Federica; Bosetti, Cristina; Polesel, Jerry; Serraino, Diego; Montella, Maurizio; Libra, Massimo; Facchini, Gaetano; Ferraroni, Monica; Tavani, Alessandra; La Vecchia, Carlo; Negri, Eva

2017-06-01

A family history of bladder cancer has been associated with the risk of bladder cancer, but quantification of the excess risk in different populations is still a relevant issue. Further, the role of a family history of other cancers on the risk of bladder cancer remains unclear. We analyzed data from an Italian case-control study, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) were estimated through unconditional logistic regression models, adjusted for sex, age, study center, year of interview and further for education, smoking and sibling's number. The OR for family history of bladder cancer was 2.13 (95% confidence intervals (95%CIs) 1.02-4.49) from the model with partial adjustment, and 1.99 (95%CI 0.91-4.32) after additional adjustment for smoking and siblings' number, based on 23 cases (3.3%) and 11 controls (1.7%) with a family history of bladder cancer. The fully adjusted OR was 3.77 when the relative was diagnosed at age below 65years. Smokers with a family history of bladder cancer had a four-fold increased risk compared to non-smokers without a family history. Bladder cancer risk was significantly increased among subjects with a family history of hemolymphopoietic cancers (OR=2.97, 95%CI 1.35-6.55). Family history of cancer at other sites showed no significant association with bladder cancer risk. This study confirms an approximately two-fold increased risk of bladder cancer for family history of bladder cancer, and indicates a possible familial clustering of bladder cancer with cancers of the hemolymphopoietic system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder

PubMed Central

Pak, K. J.; Ostrom, R. S.; Matsui, M.

2010-01-01

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC50 value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 µM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M2 function is enhanced following streptozotocin treatment. PMID:20349044

Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder.

PubMed

Pak, K J; Ostrom, R S; Matsui, M; Ehlert, F J

2010-05-01

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg(-1)) 2-24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC(50) value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 microM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M(2) function is enhanced following streptozotocin treatment.

Cigarette smoke induced urocystic epithelial mesenchymal transition via MAPK pathways.

PubMed

Yu, Dexin; Geng, Hao; Liu, Zhiqi; Zhao, Li; Liang, Zhaofeng; Zhang, Zhiqiang; Xie, Dongdong; Wang, Yi; Zhang, Tao; Min, Jie; Zhong, Caiyun

2017-01-31

Cigarette smoke has been shown to be a major risk factor for bladder cancer. Epithelial-mesenchymal transition (EMT) is a crucial process in cancer development. The role of MAPK pathways in regulating cigarette smoke-triggered urocystic EMT remains to be elucidated. Human normal urothelial cells and BALB/c mice were used as in vitro and in vivo cigarette smoke exposure models. Exposure of human normal urothelial cells to cigarette smoke induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression, along with the activation of MAPK pathways. Moreover, we revealed that ERK1/2 and p38 inhibitors, but rather JNK inhibitor, effectively attenuated cigarette smoke-induced urocystic EMT. Importantly, the regulatory function of ERK1/2 and p38 pathways in cigarette smoke-triggered urocystic EMT was further confirmed in mice exposed to CS for 12 weeks. These findings could provide new insight into the molecular mechanisms of cigarette smoke-associated bladder cancer development as well as its potential intervention.

Resveratrol improves prostate fibrosis during progression of urinary dysfunction in chronic prostatitis.

PubMed

He, Yi; Zeng, Hui-Zhi; Yu, Yang; Zhang, Jia-Shu; Duan, Xingping; Zeng, Xiao-Na; Gong, Feng-Tao; Liu, Qi; Yang, Bo

2017-09-01

We investigated whether prostate fibrosis was associated with urinary dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary dysfunction and the underlying molecular mechanism. Rat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. Bladder pressure and volume tests investigated the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression level of C-kit/SCF and TGF-β/Wnt/β-catenin. Compared to the control group, the maximum capacity of the bladder, residual urine volume and maximum voiding pressure, the activity of C-kit/SCF and TGF-β/Wnt/β-catenin pathways were increased significantly in the CP group. Resveratrol treatment significantly improved these factors. CP induced significantly prostate fibrosis, which exhibits a close relationship with urinary dysfunction. Resveratrol improved fibrosis, which may be associated with the suppression of C-kit/SCF and TGF-β/Wnt/β-catenin pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

PubMed Central

Merrill, Liana; Malley, Susan

2013-01-01

Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

New Amniotic Membrane Based Biocomposite for Future Application in Reconstructive Urology

PubMed Central

Tworkiewicz, Jakub; Kowalczyk, Tomasz; van Breda, Shane V.; Tyloch, Dominik; Kloskowski, Tomasz; Bodnar, Magda; Skopinska-Wisniewska, Joanna; Marszałek, Andrzej; Frontczak-Baniewicz, Malgorzata; Kowalewski, Tomasz A.; Drewa, Tomasz

2016-01-01

Objective Due to the capacity of the amniotic membrane (Am) to support re-epithelisation and inhibit scar formation, Am has a potential to become a considerable asset for reconstructive urology i.e., reconstruction of ureters and urethrae. The application of Am in reconstructive urology is limited due to a poor mechanical characteristic. Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance, without affecting its unique bioactivity profile. This study evaluated biocomposite material composed of Am and nanofibers as a graft for urinary bladder augmentation in a rat model. Material and Methods Sandwich-structured biocomposite material was constructed from frozen Am and covered on both sides with two-layered membranes prepared from electrospun poly-(L-lactide-co-E-caprolactone) (PLCL). Wistar rats underwent hemicystectomy and bladder augmentation with the biocomposite material. Results Immunohistohemical analysis (hematoxylin and eosin [H&E], anti-smoothelin and Masson’s trichrome staining [TRI]) revealed effective regeneration of the urothelial and smooth muscle layers. Anti-smoothelin staining confirmed the presence of contractile smooth muscle within a new bladder wall. Sandwich-structured biocomposite graft material was designed to regenerate the urinary bladder wall, fulfilling the requirements for normal bladder tension, contraction, elasticity and compliance. Mechanical evaluation of regenerated bladder wall conducted based on Young’s elastic modulus reflected changes in the histological remodeling of the augmented part of the bladder. The structure of the biocomposite material made it possible to deliver an intact Am to the area for regeneration. An unmodified Am surface supported regeneration of the urinary bladder wall and the PLCL membranes did not disturb the regeneration process. Conclusions Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance without affecting its unique bioactivity profile. PMID:26766636

Sorafenib induces cathepsin B-mediated apoptosis of bladder cancer cells by regulating the Akt/PTEN pathway. The Akt inhibitor, perifosine, enhances the sorafenib-induced cytotoxicity against bladder cancer cells

PubMed Central

Amantini, Consuelo; Morelli, Maria Beatrice; Santoni, Matteo; Soriani, Alessandra; Cardinali, Claudio; Farfariello, Valerio; Eleuteri, Anna Maria; Bonfili, Laura; Mozzicafreddo, Matteo; Nabissi, Massimo; Cascinu, Stefano; Santoni, Giorgio

2015-01-01

Sorafenib, a tyrosine kinase inhibitor, has been demonstrated to exert anti-tumor effects. However, the molecular mechanisms underlying its effects on bladder cancer remain unknown. Here, we evaluated the mechanisms responsible for the sorafenib-induced anti-tumor effects on 5637 and T24 bladder cancer cells. We demonstrated that sorafenib reduces cell viability, stimulates lysosome permeabilization and induces apoptosis of bladder cancer cells. These effects are dependent by the activation of cathepsin B released from lysosomes. The sorafenib-increased cathepsin B activity induced the proteolysis of Bid into tBid that stimulates the intrinsic pathway of apoptosis characterized by mitochondrial membrane depolarization, oxygen radical generation and cytochrome c release. Moreover, we found that cathepsin B enzymatic activity, induced by sorafenib, is dependent on its dephosphorylation via PTEN activation and Akt inactivation. Pretreatment with orthovanadate rescued bladder cancer cells from apoptosis. In addition, the Akt inhibitor perifosine increased the sensitivity of bladder cancer cells to sorafenib-induced cytotoxicity. Overall, our results show that apoptotic cell death induced by sorafenib in bladder cancer cells is dependent on cathepsin B activity and involved PTEN and Akt signaling pathways. The Akt inhibitor perifosine increased the cytotoxic effects of sorafenib in bladder cancer cells. PMID:26097873

Mechanisms of Visceral Organ Crosstalk: Importance of Alterations in Permeability in Rodent Models

PubMed Central

Greenwood-Van Meerveld, B; Mohammadi, E; Tyler, K; Van Gordon, S; Parker, A; Towner, R; Hurst, R

2015-01-01

Purpose The pathophysiology of painful bladder syndrome (PBS) is poorly understood; however, there is evidence of female predominance and comorbidity with irritable bowel syndrome (IBS). Our hypothesis is that cross-sensitization between the bladder and colon is due to altered permeability in one organ affecting the other organ. Materials and methods Experiments were performed in anesthetized, ovariectomized (OVX) female rats. In separate groups, protamine sulfate was infused into the bladder or TNBS was infused into the colon, with untreated rats serving as controls. Both bladder and colonic tissue were harvested for all rats at 1, 3, and 5 days post-treatment. Permeability was assessed in vitro in Ussing chambers via measurements of transepithelial electrical resistance (TEER) and macromolecular flux of Fluorescein isothiocyanate (FITC)-4 dextran. Results Exposing the bladder to protamine sulfate induced a significant (p<0.05) decrease in bladder TEER and an increase in the translocation of FITC across the tissue compared to controls at 1 and 3 days. Colonic tissue from rats with enhanced bladder permeability exhibited a significant (p<0.05) decrease in TEER and increase in FITC when compared to untreated controls at all time points. Conversely, when colonic permeability was increased with TNBS, we observed an increase in bladder permeability in the absence of any changes to the bladder urothelium. Conclusions Changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may explain the overlapping symptomology of PBS and IBS. PMID:25776913

Long-term outcomes of intravesical dimethyl sulfoxide/heparin/hydrocortisone therapy for interstitial cystitis/bladder pain syndrome.

PubMed

Lim, Yik N; Dwyer, Peter; Murray, Christine; Karmakar, Debjyoti; Rosamilia, Anna; Thomas, Elizabeth

2017-07-01

For decades, intravesical dimethyl sulfoxide (DMSO) cocktail therapy has been used for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS), but little is known about its long-term efficacy. We aimed to assess the long-term efficacy of intravesical DMSO/heparin/hydrocortisone/bupivacaine therapy in patients with IC/BPS. Patients with IC/BPS from our institutions who underwent this therapy with >2 years follow-up were surveyed with O'Leary-Sant interstitial cystitis symptom and problem index questionnaires before and after therapy. Chart reviews and telephone surveys were then conducted to determine their posttherapy course. Of 68 eligible women, 55 (80.0%) with a median follow-up of 60 months (range 24-142) were surveyed. Their mean age at therapy onset was 44.8 years and their mean body mass index was 26.2 kg/m 2 . There were statistically significant improvements in O'Leary-Sant and pain scores of 23-47% at both 6 weeks and the end of the follow-up period. At the end of the follow-up period, 19 of the 55 women (34.5%) were cured (requiring no further treatment) and 12 (21.8%) were significantly improved (requiring only ongoing oral medication). Univariate and multivariate analyses showed that DMSO treatment failure was more likely in patients with pretreatment day-time urinary frequency more than 15 episodes per day (OR 1.41), nocturia more than two episodes per night (OR 2.47), maximum bladder diary voided volume <200 ml (OR 1.39) and bladder capacity under anaesthesia <500 ml (OR 1.6). At a median follow-up of 60 months, intravesical DMSO cocktail therapy appeared moderately effective for the treatment of IC/BPS. Treatment failure was more frequent in patients with pretreatment symptoms of reduced bladder capacity.

Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

PubMed

Lin, W-Y; Chang, P-J; Lin, Y-P; Wu, S-B; Chen, C-S; Levin, R M; Wei, Y-H

2012-02-01

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-β1 (TGF-β1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-β1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-β1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-β1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Effect of parathyroid hormone on transport by toad and turtle bladder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabatini, S.; Kurtzman, N.A.

1987-01-01

The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H/sub 2/O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H/sub 2/O and Na transport and H..mu.. secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H/sub 2/O flow and short-circuit current (SCC) after 60 min serosalmore » incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P < 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H/sup +/ secretion in turtle bladders. Both PTH and A23187 increased /sup 45/Ca uptake in toad bladder epithelial cells; only A23187 increased /sup 45/Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different.« less

Does increased urination frequency protect against bladder cancer?

PubMed

Silverman, Debra T; Alguacil, Juan; Rothman, Nathaniel; Real, Francisco X; Garcia-Closas, Montserrat; Cantor, Kenneth P; Malats, Nuria; Tardon, Adonina; Serra, Consol; Garcia-Closas, Reina; Carrato, Alfredo; Lloreta, Josep; Samanic, Claudine; Dosemeci, Mustafa; Kogevinas, Manolis

2008-10-01

Experimental studies suggest that increased urination frequency may reduce bladder cancer risk if carcinogens are present in the urine. Only 2 small studies of the effect of increased urination frequency on bladder cancer risk in humans have been conducted with conflicting results. Our purpose was to evaluate the effect of urination frequency on risk of bladder cancer in a large, multicenter case-control study. We analyzed data based on interviews conducted with 884 patients with newly diagnosed, bladder cancer and 996 controls from 1998 to 2001 in Spain. We observed a consistent, inverse trend in risk with increasing nighttime voiding frequency in both men (p = 0.0003) and women (p = 0.07); voiding at least 2 times per night was associated with a significant, 40-50% risk reduction. The protective effect of nocturia was apparent among study participants with low, moderate and high water consumption. The risk associated with cigarette smoking was reduced by nocturia. Compared with nonsmokers who did not urinate at night, current smokers who did not urinate at night had an OR of 7.0 (95% CI = 4.7-10.2), whereas those who voided at least twice per night had an OR of 3.3 (95% CI = 1.9-5.8) (p value for trend = 0.0005). Our findings suggest a strong protective effect of nocturia on bladder cancer risk, providing evidence in humans that bladder cancer risk is related to the contact time of the urothelium with carcinogens in urine. Increased urination frequency, coupled with possible dilution of the urine from increased water intake, may diminish the effect of urinary carcinogens on bladder cancer risk.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

PubMed

Hubscher, Charles H; Herrity, April N; Williams, Carolyn S; Montgomery, Lynnette R; Willhite, Andrea M; Angeli, Claudia A; Harkema, Susan J

2018-01-01

Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.

Use of botulinum toxin in individuals with neurogenic detrusor overactivity: State of the art review

PubMed Central

Linsenmeyer, Todd A.

2013-01-01

Background Botulinum neurotoxin (BoNT) injection into the bladder wall has been shown to be an effective alternative to anticholinergic (antimuscarinic) medications and more invasive surgery in those with multiple sclerosis and spinal cord injury with neurogenic detrusor overactivity (NDO) and urinary incontinence who are not tolerating anticholinergic medications. In August 2011, Botox® (onabotulinumtoxinA) received Food and Drug Administration (FDA) approval for this use. Clinically, intradetrusor injection of BoNT has been found to decrease urinary incontinence and improve quality of life. Its impact on urodynamic parameters is an increase in the maximum cystometric (bladder) capacity and decrease in the maximum detrusor pressures. The most common side effects are urinary tract infections and urinary retention. There have been rare reports and a black box warning of distant spread of BoNT. BoNT has gained popularity because of its effectiveness and long duration of action, relative ease of administration, easy learning curve, reproducibility of results on repeated administration, and low incidence of complications. Objective To discuss the structure and function, mechanisms of action, clinical and urodynamic studies, injection technique, potential beneficial and adverse effects, and potential areas of research of BoNT. Methods Literature search focused on botulinum toxin in MEDLINE/PubMed. Search terms included botulinum toxin, neurogenic bladder, NDO, botox bladder, botox spinal cord injury, botox, FDA, botox side effects. All papers identified were English language, full-text papers. In addition, English abstracts of non-English papers were noted. The reference list of identified articles was also searched for further papers. Conclusion Botulinum toxin is an alternative treatment for individuals with NDO who fail to tolerate anticholinergic medications. Its popularity has increased because of the literature, which has supported its effectiveness, safety, easy use and learning curve, reproducibility of results on repeated use, and recent FDA approval of Botox® (onabotulinumtoxinA). PMID:23941788

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

PubMed Central

Williams, Carolyn S.; Montgomery, Lynnette R.; Willhite, Andrea M.; Angeli, Claudia A.; Harkema, Susan J.

2018-01-01

Objective Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Study design Prospective cohort study; pilot trial with small sample size. Methods Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Results Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. Conclusions These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. Trial registration ClinicalTrials.gov NCT03036527 PMID:29385166

Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium.

PubMed

Carneiro, Inês; Timóteo, M Alexandrina; Silva, Isabel; Vieira, Cátia; Baldaia, Catarina; Ferreirinha, Fátima; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

2014-07-01

Despite the abundant expression of the UDP-sensitive P2Y6 receptor in urothelial cells and sub-urothelial myofibroblasts its role in the control of bladder function is not well understood. We compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [(3) H]-ACh overflow experiments. Instillation of UDP or PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions; an effect blocked by the P2Y6 receptor antagonist, MRS2578. Effects mediated by urothelial P2Y6 receptors required extrinsic neuronal circuitry as they were not detected in the isolated bladder. UDP-induced bladder hyperactvity was also prevented by blocking P2X3 and P2Y1 receptors, respectively, with A317491 and MRS2179 applied i.v.. UDP decreased [(3) H]-ACh release from stimulated bladder strips with urothelium, but not in its absence. Inhibitory effects of UDP were converted into facilitation by the P2Y1 receptor antagonist, MRS2179. The P2Y6 receptor agonist increased threefold ATP levels in the voided fluid. Activation of P2Y6 receptors increased the voiding frequency indirectly by releasing ATP from the urothelium and activation of P2X3 receptors on sub-urothelial nerve afferents. Bladder hyperactivity may be partly reversed following ATP hydrolysis to ADP by E-NTPDases, thereby decreasing ACh release from cholinergic nerves expressing P2Y1 receptors. © 2014 The British Pharmacological Society.

UTIs in patients with neurogenic bladder.

PubMed

Jahromi, Mona S; Mure, Amanda; Gomez, Christopher S

2014-09-01

Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy.

Regulation of IGF-1 but not TGF-β1 by NGF in the smooth muscle of the inflamed urinary bladder

PubMed Central

Zhang, Qing L.; Qiao, Li-Ya

2012-01-01

Intraperitoneal injection of cyclophosphamide (CYP) causes haemorrhagic cystitis with excess growth of muscular layer leading to bladder hypertrophy; this could be attributable to changes in the expression profiles of growth factors in the inflamed urinary bladder. The growth factors characterized in the current study include nerve growth factor (NGF), insulin-like growth factor (IGF)-1, and transforming growth factor (TGF)-β1. We found that following CYP injection for 8h and 48h, the mRNA levels of all three factors were increased in the inflamed bladder when compared to control. The level of NGF mRNA was mainly increased in the urothelium layer while the levels of IGF-1 mRNA and TGF-β1 mRNA were increased in the smooth muscle layer. The level of NGF high affinity receptor TrkA mRNA was also increased in both the urothelium and the smooth muscle layers during bladder inflammation. When we blocked NGF action with NGF neutralizing antibody in vivo, we found that the up-regulation of IGF-1 in the inflamed bladder was reversed while the up-regulation of TGF-β1 was not affected by NGF neutralization. The effect of NGF on regulating IGF-1 expression was further confirmed in bladder smooth muscle culture showing that exogenous NGF increased the mRNA level of IGF-1 after 30 min to 1h stimulation. These results suggest that bladder inflammation induced region-specific changes in the expression profiles of NGF, IGF-1 and TGF-β1. The up-regulation of NGF in the urothelium may have a role in affecting bladder smooth muscle cell physiology by regulating IGF-1 expression. PMID:22579999

Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse

PubMed Central

DeAngelis, Anthony; Kuchel, George A.

2012-01-01

The prevalence of urinary symptoms increases with age and is a significant source of distress, morbidity, and expense in the elderly. Recent evidence suggests that symptoms in the aged may result from sensory dysfunction, rather than abnormalities of detrusor performance. Therefore, we employed a pressure/flow multichannel urethane-anesthetized mouse cystometry model to test the hypothesis that in vivo detrusor performance does not degrade with aging. Secondarily, we sought to evaluate sensory responsiveness to volume using pressure-volume data generated during bladder filling. Cystometric data from 2-, 12-, 22-, and 26-mo-old female C57BL6 mice were compared. All 2- and 12-mo-old mice, 66% of 22-mo-old mice, and 50% of 26-mo-old mice responded to continuous bladder filling with periodic reflex voiding. Abdominal wall contraction with voiding had a minimal contribution to expulsive pressure, whereas compliance pressure was a significant contributor. Maximum bladder pressure, estimated detrusor pressure, detrusor impulse (pressure-time integral), as well as indices of detrusor power and work, did not decrease with aging. Bladder precontraction pressures decreased, compliance increased, and nonvoiding contraction counts did not change with increasing age. Intervoid intervals, per-void volumes, and voiding flow rates increased with age. Calculations approximating wall stress during filling suggested loss of bladder volume sensitivity with increasing age. We conclude that aging is associated with an impaired ability to respond to the challenge of continuous bladder filling with cyclic voiding, yet among responsive animals, voiding detrusor contraction strength does not degrade with aging in this murine model. Furthermore, indirect measures suggest that bladder volume sensitivity is diminished. Thus, changes in homeostatic reserve and peripheral and/or central sensory mechanisms may be important contributors to aging-associated changes in bladder function. PMID:22204955

Two differentially structured collagen scaffolds for potential urinary bladder augmentation: proof of concept study in a Göttingen minipig model.

PubMed

Leonhäuser, Dorothea; Stollenwerk, Katja; Seifarth, Volker; Zraik, Isabella M; Vogt, Michael; Srinivasan, Pramod K; Tolba, Rene H; Grosse, Joachim O

2017-01-04

The repair of urinary bladder tissue is a necessity for tissue loss due to cancer, trauma, or congenital abnormalities. Use of intestinal tissue is still the gold standard in the urological clinic, which leads to new problems and dysfunctions like mucus production, stone formation, and finally malignancies. Therefore, the use of artificial, biologically derived materials is a promising step towards the augmentation of this specialised tissue. The aim of this study was to investigate potential bladder wall repair by two collagen scaffold prototypes, OptiMaix 2D and 3D, naïve and seeded with autologous vesical cells, as potential bladder wall substitute material in a large animal model. Six Göttingen minipigs underwent cystoplastic surgery for tissue biopsy and cell isolation followed by implantation of unseeded scaffolds. Six weeks after the first operation, scaffolds seeded with the tissue cultured autologous urothelial and detrusor smooth muscle cells were implanted into the bladder together with additional unseeded scaffolds for comparison. Cystography and bladder ultrasound were performed to demonstrate structural integrity and as leakage test of the implantation sites. Eighteen, 22, and 32 weeks after the first operation, two minipigs respectively were sacrificed and the urinary tract was examined via different (immunohistochemical) staining procedures and the usage of two-photon laser scanning microscopy. Both collagen scaffold prototypes in vivo had good ingrowth capacity into the bladder wall including a quick lining with urothelial cells. The ingrowth of detrusor muscle tissue, along with the degradation of the scaffolds, could also be observed throughout the study period. We could show that the investigated collagen scaffolds OptiMaix 2D and 3D are a potential material for bladder wall substitution. The material has good biocompatible properties, shows a good cell growth of autologous cells in vitro, and a good integration into the present bladder tissue in vivo.

Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein synthesis pathway.

PubMed

Qiao, Li-Ya; Xia, Chunmei; Shen, Shanwei; Lee, Seong Ho; Ratz, Paul H; Fraser, Matthew O; Miner, Amy; Speich, John E; Lysiak, Jeffrey J; Steers, William D

2018-05-15

The present study aims to investigate the role of Akt in the regulation of urinary bladder organ hypertrophy caused by partial bladder outlet obstruction (pBOO). Male rats were surgically induced for pBOO. Real-time PCR and western blot were used to examine the levels of mRNA and protein. A phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to inhibit the activity of endogenous Akt. The urinary bladder developed hypertrophy at 2 weeks of pBOO. The protein but not mRNA levels of type I collagen and α-smooth muscle actin (αSMA) were increased in pBOO bladder when compared to sham control. The phosphorylation (activation) levels of Akt1 (p-Ser 473 ), mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E-BP1 were also increased in pBOO bladder. LY294002 treatment reduced the phosphorylation levels of Akt1 and 4E-BP1, and the protein levels of type I collagen and αSMA in pBOO bladder. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) were increased in pBOO bladder, and PCNA up-regulation occurred in urothelial not muscular layer. LY294002 treatment had no effect on the mRNA and protein levels of PCNA in pBOO bladder. LY294002 treatment partially reduced the bladder weight caused by pBOO. pBOO-induced urinary bladder hypertrophy is attributable to fibrosis, smooth muscle cellular hypertrophy, and urothelium cell hyper-proliferation. Akt1-mediated protein synthesis in pBOO bladder contributes to type I collagen and αSMA but not PCNA up-regulation. Target of Akt1 is necessary but not sufficient in treatment of urinary bladder hypertrophy following pBOO. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of imaging techniques in the diagnosis and follow-up of muscle-invasive bladder carcinoma.

PubMed

Mesa, A; Nava, E; Fernández Del Valle, A; Argüelles, B; Menéndez-Del Llano, R; Sal de Rellán, S

2017-10-10

Muscle-invasive bladder malignancies represent 20-30% of all bladder cancers. These patients require imaging tests to determine the regional and distant staging. To describe the role of various imaging tests in the diagnosis, staging and follow-up of muscle-invasive bladder cancer. To assess recent developments in radiology aimed at improving the sensitivity and specificity of local staging and treatment response. We conducted an updated literature review. Computed tomography and magnetic resonance imaging (MRI) are the tests of choice for performing proper staging prior to surgery. Computed tomography urography is currently the most widely used technique, although it has limitations in local staging. Ultrasonography still has a limited role. Recent developments in MRI have improved its capacity for local staging. MRI has been suggested as the test of choice for the follow-up, with promising results in assessing treatment response. Positron emission tomography could improve the detection of adenopathies and extrapelvic metastatic disease. Imaging tests are essential for the diagnosis, staging and follow-up of muscle-invasive bladder cancer. Recent technical developments represent important improvements in local staging and have opened the possibility of assessing treatment response. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

PubMed

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2013-03-01

Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

PubMed

Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; Graham, Gerry; O'Reilly, Barry A; McMahon, Stephen B

2016-08-01

Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating these genes in BPS is a potential treatment strategy. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The ultimate challenge of cloacal exstrophy.

PubMed

Schober, Justine M; Carmichael, Polly A; Hines, Melissa; Ransley, Philip G

2002-01-01

Our review addresses the various system abnormalities associated with cloacal exstrophy and revisits the question of gender assignment. Gender assignment decisions and psychological aspects of gender issues have become the "ultimate challenge." Exploration of gender identity, gender role behavior and sexual orientation has just begun. A comprehensive literature review was performed with all world literature regarding the current management of cloacal exstrophy. Research focused on management principles, outcomes and documentation of concurrent anomalies. We also describe original research evaluating gender identity in our own series of patients raised as girls to illustrate the challenge of treatment and augment the available literature, which is scant. Abnormalities of the vertebral column ranged from hemivertebra to myelomeningocele. With magnetic resonance imaging, the incidence of spinal dysraphism approached 100% and cord tethering was also more frequently recognized. For children with the short bowel syndrome, advances in antibiotic usage, and parenteral and enteral nutrition have increased the survival rate and reduced morbidity. A neurological component has been recognized for bladder function, bladder neck continence, lower extremity function and erectile capacity. Mitrofanoff-type reconstruction with bladder neck closure and continent catheterizable stoma dramatically increased continence. Diminutive or absent penis has been documented in 30% of males, and no documentation of paternity exists. The majority of females have bicornuate uterus. However, ovaries and tubes were generally normal. No reports of proven fertility exist. The strategy and timing of surgery relating to gender assignment remain controversial. A desperate need exists for research focusing on gender development and quality of life. Until that time, a cautious watchful approach may be most appropriate as our patients with cloacal exstrophy mature into adulthood.

Standard Approach to Urinary Bladder Endometriosis.

PubMed

Fernandes, Rodrigo Pinto; Centini, Gabriele; Afors, Karolina; Puga, Marco; Alves, Joao; Wattiez, Arnaud

2017-12-28

Urinary endometriosis accounts for 1% of all endometriosis where the bladder is the most affected organ. Although the laparoscopic removal of bladder endometriosis has been demonstrated to be effective in terms of symptom relief with a low recurrence rate, there is no standardized technique. Partial cystectomy allows the complete removal of the disease and is associated with low intra- and postoperative complications. Here we describe a stepwise approach to a rare case of a large endometriosis nodule affecting the trigone of the urinary bladder. Step-by-step video explanation of a large endometriotic nodule excision (Canadian Task Force classification III). IRCAD AMITS - Barretos | Hospital Pio XVI. The video was approved by the local institutional review board. A 31-year-old woman. Laparoscopic approach for bladder endometriosis. We present a case of a 31-year-old woman who complained of dysuria and hematuria with a bladder nodule of 3 cm affecting the bladder trigone. Laparoscopic complete excision of the nodule was performed. Laparoscopy began with full inspection of the pelvic and abdominal cavity. Vaginal examination under laparoscopic view helped to determinate the dimensions of the bladder nodule. Strategy consisted of bilateral dissection of the paravesical fossae and the identification of both uterine arteries and ureters. The bladder was slowly dissected from the uterine isthmus and was intentionally opened, thus helping the surgeons to identify the lateral and lower limits of the nodule and its proximity to both ureters. Bilateral double J stents were previously placed to guide the excision and further suture. Once the nodule was removed, the remaining wall consisted of the lower aspect of the trigone, both medial lower parts of the ureter, and the apex of the bladder. Suturing was performed in 2 steps. A simple monofilament interrupted suture was applied vertically at the lower wall between both ureters. The same technique was applied horizontally on the bladder dome. Pressure test demonstrated adequate correction. The patient was discharged 2 days later with a bladder catheter and double J stent. After 15 days, both indwelling catheter and ureteric stent were removed, and patient was submitted to a cystogram where no leakage was found. If a leakage had been found on the cystogram, the bladder should be allowed an additional week of continuous drainage. Early follow-up demonstrated a lower bladder capacity that was resolved within 6 months. After a 1-year follow-up the patient had no symptoms and demonstrated no recurrence. She is now 20 weeks pregnant with no need of assisted reproductive methods. The technique showed in the video demonstrates the feasibility of a laparoscopic approach for bladder endometriosis. Furthermore, the laparoscopic approach allowed the removal of the large nodule, reducing the risk of small bladder symptoms. Copyright © 2018. Published by Elsevier Inc.

Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring

PubMed Central

Lee, Wei-Chia; Tain, You-Lin; Wu, Kay L. H.; Leu, Steve; Chan, Julie Y. H.

2016-01-01

Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE. PMID:27703194

Maternal Fructose Exposure Programs Metabolic Syndrome-Associated Bladder Overactivity in Young Adult Offspring.

PubMed

Lee, Wei-Chia; Tain, You-Lin; Wu, Kay L H; Leu, Steve; Chan, Julie Y H

2016-10-05

Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M 2 -, M 3 -muscarinic and P2X 1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE.

A novel single compartment in vitro model for electrophysiological research using the perfluorocarbon FC-770.

PubMed

Choudhary, M; Clavica, F; van Mastrigt, R; van Asselt, E

2016-06-20

Electrophysiological studies of whole organ systems in vitro often require measurement of nerve activity and/or stimulation of the organ via the associated nerves. Currently two-compartment setups are used for such studies. These setups are complicated and require two fluids in two separate compartments and stretching the nerve across one chamber to the other, which may damage the nerves. We aimed at developing a simple single compartment setup by testing the electrophysiological properties of FC-770 (a perfluorocarbon) for in vitro recording of bladder afferent nerve activity and electrical stimulation of the bladder. Perflurocarbons are especially suitable for such a setup because of their high oxygen carrying capacity and insulating properties. In male Wistar rats, afferent nerve activity was recorded from postganglionic branches of the pelvic nerve in vitro, in situ and in vivo. The bladder was stimulated electrically via the efferent nerves. Organ viability was monitored by recording spontaneous contractions of the bladder. Additionally, histological examinations were done to test the effect of FC-770 on the bladder tissue. Afferent nerve activity was successfully recorded in a total of 11 rats. The bladders were stimulated electrically and high amplitude contractions were evoked. Histological examinations and monitoring of spontaneous contractions showed that FC-770 maintained organ viability and did not cause damage to the tissue. We have shown that FC-770 enables a simple, one compartment in vitro alternative for the generally used two compartment setups for whole organ electrophysiological studies.

Salt adaptation in Bufo bufo

PubMed Central

Ferreira, H. G.; Jesus, C. H.

1973-01-01

1. The capacity of adaptation of toads (Bufo bufo) to environments of high salinity was studied and the relative importance of skin, kidney and urinary bladder in controlling the balance of water and salt was assessed. 2. Toads were kept in NaCl solutions of 20, 50, 110, 150 and 220 mM and studied in their fourth week of adaptation. A group of animals considered as `control' was kept in wet soil with free access to water. Plasma, ureter urine, and bladder and colon contents were analysed for sodium, potassium, chloride and osmolality, and total body sodium and water were determined. Absorption of water and 22Na through the skin, and water flow and sodium excretion through the ureter, of intact animals was studied. Hydrosmotic water transport through the isolated urinary bladder of `control' and adapted animals was determined. The effects of pitressin and aldosterone on the water and sodium balance are described. 3. The survival rates of toads kept in saline concentrations up to 150 mM were identical to that of `control' animals, but half of the animals kept in 220 mM died within 4 weeks. 4. There is a linear correlation between the sodium concentrations and osmolality of plasma and of the external media. 5. The sodium concentration in colon contents rose with rising external concentrations, up to values higher than the values in plasma. 6. Sodium concentrations and osmolalities of ureter and bladder urine increased in adapted animals, the values for bladder urine becoming much higher than those for ureter urine in animals adapted to 110, 150 and 220 mM. 7. Total body water, as a percentage of total weight was kept within very narrow limits, although the total body sodium increased with adaptation. 8. Absorption of water through the skin for the same osmotic gradients was smaller in adapted than in `control' animals. 9. The ureteral output of water of toads adapted to 110 and 150 mM-NaCl was larger than the water absorption through the skin. 10. Skin absorption of sodium was lower in animals adapted to concentrated saline solutions than in `control' animals. 11. Sodium output by the ureter was identical to skin absorption in `control' animals adapted to 20, 50 and 110 mM-NaCl but was higher in animals adapted to 150 mM-NaCl. 12. Aldosterone increased the absorption of sodium in `control' and adapted toads, but at all dose levels absorption by control was greater than by adapted animals. 13. The stimulation of water absorption by vasopressin in vivo or in isolated bladders was not modified in animals adapted to high salinities. PMID:4633911

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

PubMed Central

Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

2017-01-01

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

Social stress in mice induces voiding dysfunction and bladder wall remodeling

PubMed Central

Chang, Andy; Butler, Stephan; Sliwoski, Joanna; Valentino, Rita; Canning, Douglas

2009-01-01

Several studies have anecdotally reported the occurrence of altered urinary voiding patterns in rodents exposed to social stress. A recent study characterized the urodynamic and central changes in a rat model of social defeat. Here, we describe a similar voiding phenotype induced in mice by social stress and in addition we describe potential molecular mechanisms underlying the resulting bladder wall remodeling. The mechanism leading to the altered voiding habits and underlying bladder phenotype may be relevant to the human syndrome of dysfunctional voiding which is thought to have a psychological component. To better characterize and investigate social stress-induced bladder wall hypertrophy, FVB mice (6 wk old) were randomized to either social stress or control manipulation. The stress involved repeated cycles of a 1-h direct exposure to a larger aggressive C57Bl6 breeder mouse followed by a 23-h period of barrier separation over 4 wk. Social stress resulted in altered urinary voiding patterns suggestive of urinary retention and increased bladder mass. In vivo cystometry revealed an increased volume at micturition with no change in the voiding pressure. Examination of these bladders revealed increased nuclear expression of the transcription factors MEF-2 and NFAT, as well as increased expression of the myosin heavy chain B isoform mRNA. BrdU uptake was increased within the urothelium and lamina propria layers in the social stress group. We conclude that social stress induces urinary retention that ultimately leads to shifts in transcription factors, alterations in myosin heavy chain isoform expression, and increases in DNA synthesis that mediate bladder wall remodeling. Social stress-induced bladder dysfunction in rodents may provide insight into the underlying mechanisms and potential treatment of dysfunctional voiding in humans. PMID:19587139

Comparison of Coregistration Accuracy of Pelvic Structures Between Sequential and Simultaneous Imaging During Hybrid PET/MRI in Patients with Bladder Cancer.

PubMed

Rosenkrantz, Andrew B; Balar, Arjun V; Huang, William C; Jackson, Kimberly; Friedman, Kent P

2015-08-01

The aim of this study was to compare coregistration of the bladder wall, bladder masses, and pelvic lymph nodes between sequential and simultaneous PET and MRI acquisitions obtained during hybrid (18)F-FDG PET/MRI performed using a diuresis protocol in bladder cancer patients. Six bladder cancer patients underwent (18)F-FDG hybrid PET/MRI, including IV Lasix administration and oral hydration, before imaging to achieve bladder clearance. Axial T2-weighted imaging (T2WI) was obtained approximately 40 minutes before PET ("sequential") and concurrently with PET ("simultaneous"). Three-dimensional spatial coordinates of the bladder wall, bladder masses, and pelvic lymph nodes were recorded for PET and T2WI. Distances between these locations on PET and T2WI sequences were computed and used to compare in-plane (x-y plane) and through-plane (z-axis) misregistration relative to PET between T2WI acquisitions. The bladder increased in volume between T2WI acquisitions (sequential, 176 [139] mL; simultaneous, 255 [146] mL). Four patients exhibited a bladder mass, all with increased activity (SUV, 9.5-38.4). Seven pelvic lymph nodes in 4 patients showed increased activity (SUV, 2.2-9.9). The bladder wall exhibited substantially less misregistration relative to PET for simultaneous, compared with sequential, acquisitions in in-plane (2.8 [3.1] mm vs 7.4 [9.1] mm) and through-plane (1.7 [2.2] mm vs 5.7 [9.6] mm) dimensions. Bladder masses exhibited slightly decreased misregistration for simultaneous, compared with sequential, acquisitions in in-plane (2.2 [1.4] mm vs 2.6 [1.9] mm) and through-plane (0.0 [0.0] mm vs 0.3 [0.8] mm) dimensions. FDG-avid lymph nodes exhibited slightly decreased in-plane misregistration (1.1 [0.8] mm vs 2.5 [0.6] mm), although identical through-plane misregistration (4.0 [1.9] mm vs 4.0 [2.8] mm). Using hybrid PET/MRI, simultaneous imaging substantially improved bladder wall coregistration and slightly improved coregistration of bladder masses and pelvic lymph nodes.

Ontogeny and morphometrics of the gills and swim bladder of air-breathing striped catfish Pangasianodon hypophthalmus.

PubMed

Phuong, Le My; Huong, Do Thi Thanh; Malte, Hans; Nyengaard, Jens Randel; Bayley, Mark

2018-02-01

The air-breathing fish Pangasianodon hypophthalmus has been shown to have highly plastic branchial surfaces whose area (SA) increases with temperature and aquatic hypoxia. This modulation occurs through development of inter-lamellar cell mass (ILCM). Paradoxically, in conditions where this fish has been shown capable of covering its entire aerobic scope from the water phase, it has been shown to have a very small branchial SA. To address this paradox, we measured the SA, harmonic mean diffusion distance (τ h ) and calculated the anatomic diffusion factor (ADF) of the branchial and swim bladder surfaces in fish ranging from 3 to 1900 g at 27°C in normoxia. Since the lamellae were distinguishable from the ILCM, we measured the actual SA as well as the potential SA if ILCM were lost. As a result of low τ h , P. hypophthalmus has a high capacity for branchial oxygen uptake with or without ILCM. Actual and potential gill ADF were 361 and 1002 cm 2  µm -1  kg -1 , respectively, for a 100 g fish and the ADF of the swim bladder was found to be 308 cm 2  µm -1  kg -1 By swimming fish to exhaustion at different temperatures, we show that modulation of this SA is rapid, indicating that the apparent paradox between previous studies is eliminated. Regression analysis of log-log plots of respiratory SA in relation to body mass shows that the gill scales with mass similarly to the SA in active water-breathing fish, whereas the swim bladder scales with mass more like the mammalian lung does. This fish presents a combination of respiratory surfaces not previously seen in air-breathing fish. © 2018. Published by The Company of Biologists Ltd.

Colon pouch (Mainz III) for continent urinary diversion.

PubMed

Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Liatsikos, Evangelos N; Sakelaropoulos, George; Rödder, Kilian; Hohenfellner, Rudolph; Fisch, Margit

2007-06-01

To evaluate the use of a continent cutaneous pouch made exclusively of colon (Mainz pouch III), as excellent results with the Mainz pouch III in irradiated patients suggested that the indication for this type of urinary diversion could be extended. The outcome of 24 patients with continent cutaneous urinary diversions using colon segments (Mainz pouch III) was investigated retrospectively. Overall, 22 of the patients had a malignant disease and two a benign disease; 16 had a hysterectomy and pelvic exenteration for gynaecological tumours; two men with a rhabdomyosarcoma of the prostate had a radical cystoprostatectomy; one woman had pelvic exenteration for bladder cancer; one man had a simultaneous rectum resection due to infiltrating rectal cancer, and another a left nephrectomy with cystectomy for concomitant kidney and bladder tumour. Benign indications were hyper-reflexive bladder after polytrauma and two cases of neurogenic bladder dysfunction. Eighteen patients had radiotherapy (32-48 Gy) before the urinary diversion. The mean (range) follow-up was 35 (12-65) months. The mean pouch capacity was 293.8 mL. Three patients died during the follow-up (two from disease progression and one suicide); 20 patients were fully continent, four with reduced pouch capacity (<300 mL) had slight incontinence and are wearing a protective pad (band-aid at the umbilicus). All patients use intermittent self-catheterization (mean catheterization frequency 6.8/day, range 6-12). Complications related to the pouch were one outlet stenosis that required revision. Postoperative pouchograms showed asymptomatic reflux in four patients. None of the patients developed metabolic acidosis or diarrhoea. The Mainz pouch III is an alternative to other types of continent urinary diversion.

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

PubMed Central

2012-01-01

Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain. PMID:23249422

A porcine model of bladder outlet obstruction incorporating radio-telemetered cystometry.

PubMed

Shaw, Matthew B; Herndon, Claude D; Cain, Mark P; Rink, Richard C; Kaefer, Martin

2007-07-01

To present a novel porcine model of bladder outlet obstruction (BOO) with a standardized bladder outlet resistance and real-time ambulatory radio-telemetered cystometry, as BOO is a common condition with many causes in both adults and children, with significant morbidity and occasional mortality, but attempts to model this condition in many animal models have the fundamental problem of standardising the degree of outlet resistance. BOO was created in nine castrated male pigs by dividing the mid-urethra; outflow was allowed through an implanted bladder drainage catheter containing a resistance valve, allowing urine to flow across the valve only when a set pressure differential was generated across the valve. An implantable radio-telemetered pressure sensor monitored the pressure within the bladder and abdominal cavity, and relayed this information to a remote computer. Four control pigs had an occluded bladder drainage catheter and pressure sensor placed, but were allowed to void normally through the native urethra. Intra-vesical pressure was monitored by telemetry, while the resistance valve was increased weekly, beginning with 2 cmH2O and ultimately reaching 10 cmH2O. The pigs were assessed using conventional cystometry under anaesthesia before death, and samples conserved in formalin for haematoxylin and eosin staining. The pigs had radio-telemetered cystometry for a median of 26 days. All telemetry implants functioned well for the duration of the experiment, but one pig developed a urethral fistula and was excluded from the study. With BOO the bladder mass index (bladder mass/body mass x 10 000) increased from 9.7 to 20 (P = 0.004), with a significant degree of hypertrophy of the detrusor smooth muscle bundles. Obstructed bladders were significantly less compliant than control bladders (8.3 vs 22.1 mL/cmH2O, P = 0.03). Telemetric cystometry showed that there was no statistically significance difference in mean bladder pressure between obstructed and control pigs (4.8 vs 6.7 cmH2O, P = 0.7), but that each void was longer in the pigs with BOO. This new model of BOO provides a method of reliably and precisely defining the bladder outlet resistance; it induces the changes classically seen with BOO, including increased bladder mass, increased smooth muscle bundle size and decreased compliance.

Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering.

PubMed

Horst, Maya; Milleret, Vincent; Noetzli, Sarah; Gobet, Rita; Sulser, Tullio; Eberli, Daniel

2017-04-01

Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol ® ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 658-667, 2017. © 2015 Wiley Periodicals, Inc.

Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2–Dependent Bladder Cancer Cell Migration and Invasion

PubMed Central

Gupta, Sounak; Hau, Andrew M.; Al-Ahmadie, Hikmat A.; Harwalkar, Jyoti; Shoskes, Aaron C.; Elson, Paul; Beach, Jordan R.; Hussey, George S.; Schiemann, William P.; Egelhoff, Thomas T.; Howe, Philip H.; Hansel, Donna E.

2017-01-01

Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed Vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. Inhibition of TGF-β receptor I using SB431542 ablated TGF-β–induced migration and invasion. A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced. Our results suggest that TGF-β can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladder cancers. PMID:26988652

Mechanisms of reflex bladder activation by pudendal afferents

PubMed Central

Woock, John P.; Yoo, Paul B.

2011-01-01

Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a β-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by −25% to −39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder contractions following administration of hexamethonium bromide confirmed that contractions were generated by pelvic efferent activation via the pelvic ganglion. These findings indicate that pudendal afferent stimulation evokes bladder contractions through convergence with pelvic afferents to increase pelvic efferent activity. PMID:21068196

Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium

PubMed Central

Carneiro, Inês; Timóteo, M Alexandrina; Silva, Isabel; Vieira, Cátia; Baldaia, Catarina; Ferreirinha, Fátima; Silva-Ramos, Miguel; Correia-de-Sá, Paulo

2014-01-01

BACKGROUND AND PURPOSE Despite the abundant expression of the UDP-sensitive P2Y6 receptor in urothelial cells and sub-urothelial myofibroblasts its role in the control of bladder function is not well understood. EXPERIMENTAL APPROACH We compared the effects of UDP and of the selective P2Y6 receptor agonist, PSB0474, on bladder urodynamics in anaesthetized rats; the voided fluid was tested for ATP bioluminescence. The isolated urinary bladder was used for in vitro myographic recordings and [3H]-ACh overflow experiments. KEY RESULTS Instillation of UDP or PSB0474 into the bladder increased the voiding frequency (VF) without affecting the amplitude (A) and the duration (Δt) of bladder contractions; an effect blocked by the P2Y6 receptor antagonist, MRS2578. Effects mediated by urothelial P2Y6 receptors required extrinsic neuronal circuitry as they were not detected in the isolated bladder. UDP-induced bladder hyperactvity was also prevented by blocking P2X3 and P2Y1 receptors, respectively, with A317491 and MRS2179 applied i.v.. UDP decreased [3H]-ACh release from stimulated bladder strips with urothelium, but not in its absence. Inhibitory effects of UDP were converted into facilitation by the P2Y1 receptor antagonist, MRS2179. The P2Y6 receptor agonist increased threefold ATP levels in the voided fluid. CONCLUSIONS AND IMPLICATIONS Activation of P2Y6 receptors increased the voiding frequency indirectly by releasing ATP from the urothelium and activation of P2X3 receptors on sub-urothelial nerve afferents. Bladder hyperactivity may be partly reversed following ATP hydrolysis to ADP by E-NTPDases, thereby decreasing ACh release from cholinergic nerves expressing P2Y1 receptors. PMID:24697602

Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness.

PubMed

Ekman, Mari; Bhattachariya, Anirban; Dahan, Diana; Uvelius, Bengt; Albinsson, Sebastian; Swärd, Karl

2013-01-01

Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower urinary tract and increases bladder stiffness. Here we tested the hypothesis that miR-29 is repressed in the bladder in outlet obstruction and that this has an impact on protein synthesis and matrix remodeling leading to increased bladder stiffness. c-Myc, NF-κB and SMAD3, all of which repress miR-29, were activated in the rat detrusor following partial bladder outlet obstruction but at different times. c-Myc and NF-κB activation occurred early after obstruction, and SMAD3 phosphorylation increased later, with a significant elevation at 6 weeks. c-Myc, NF-κB and SMAD3 activation, respectively, correlated with repression of miR-29b and miR-29c at 10 days of obstruction and with repression of miR-29c at 6 weeks. An mRNA microarray analysis showed that the reduction of miR-29 following outlet obstruction was associated with increased levels of miR-29 target mRNAs, including mRNAs for tropoelastin, the matricellular protein Sparc and collagen IV. Outlet obstruction increased protein levels of eight out of eight examined miR-29 targets, including tropoelastin and Sparc. Transfection of human bladder smooth muscle cells with antimiR-29c and miR-29c mimic caused reciprocal changes in target protein levels in vitro. Tamoxifen inducible and smooth muscle-specific deletion of Dicer in mice reduced miR-29 expression and increased tropoelastin and the thickness of the basal lamina surrounding smooth muscle cells in the bladder. It also increased detrusor stiffness independent of outlet obstruction. Taken together, our study supports a model where the combined repressive influences of c-Myc, NF-κB and SMAD3 reduce miR-29 in bladder outlet obstruction, and where the resulting drop in miR-29 contributes to matrix remodeling and altered passive mechanical properties of the detrusor.

Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis.

PubMed

Zhu, Zongheng; Zhang, Jinshan; Jiang, Wei; Zhang, Xianjue; Li, Youkong; Xu, Xiaoming

2015-01-01

It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer. The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis. The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11-1.55). The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer.

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

PubMed

Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

2017-06-01

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Artificial sweeteners and absence of bladder cancer risk in Copenhagen.

PubMed

Møller-Jensen, O; Knudsen, J B; Sørensen, B L; Clemmesen, J

1983-11-15

During the years 1979 to 1981 a population-based case-control study of bladder cancer including papillomas was performed in Greater Copenhagen. After exclusions some 388 patients (290 males; 98 females) and an age- and sex-matched group of 787 controls (592 males; 195 females) remained for analysis. Controls were selected at random from the general population of the study area. All persons were interviewed concerning use of artificial sweeteners in addition to their exposure to a number of other known or suspected risk factors for bladder cancer. Fifty-five male bladder cancer patients (19.4%) and 150 controls (25.7%) had at some time used artificial sweeteners regularly. Among females 27.1% of cases and 25.9% of controls regularly used sweeteners. In neither sex was the relative risk significantly increased in users compared with non-users of artificial sweeteners. The relative risk of 0.78 in the two sexes combined was not significantly different from 1.0 (95% C.I.: 0.58-1.05). There was no indication of a regular increase in risk with increasing daily consumption of table-top sweeteners nor was there any indication of an increase in risk with a duration of regular use of artificial sweeteners. Taking into account a possible latency period between first regular use and bladder cancer development did not change the finding of an absence of association between use of artificial sweeteners and the risk of bladder cancer. Neither saccharine nor cyclamate users had an increased risk of bladder cancer. This population-based case-control investigation provides further evidence that it is highly unlikely that the consumption of artificial sweeteners has contributed to current bladder cancer rates in man.

Roles of Polyuria and Hyperglycemia on Bladder Dysfunction in Diabetes

PubMed Central

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2014-01-01

Purpose Diabetes mellitus (DM) causes diabetic bladder dysfunction (DBD). We aimed to identify the pathogenic roles of polyuria and hyperglycemia on DBD in rats. Materials and Methods Seventy-two female Sprague-Dawley rats were divided: age-matched controls (control), sham urinary diversion (sham), urinary diversion (UD), streptozotocin-induced diabetes after sham UD (DM), streptozotocin-induced diabetes after UD (UD+DM), and 5% sucrose-induced diuresis after sham UD (DIU). UD was performed by ureterovaginostomy 10d before DM induction. Animals were evaluated 20 wks after DM or diuresis induction. We measured 24-hr drinking and voiding volumes and cystometry (CMG). Bladders were harvested for quantification of smooth muscle, urothelium, and collagen. We measured nitrotyrosine and manganese superoxide dismutase (MnSOD) in bladder. Results Diabetes and diuresis caused increases in drinking volume, voiding volume and bladder weight. Bladder weights decreased in the UD and UD+DM groups. Intercontractile intervals, voided volume, and compliance increased in the DIU and DM groups, decreased in the UD, and further decreased in the UD+DM group. The total cross-sectional tissue, smooth muscle and urothelium areas increased in the DIU and DM groups, and decreased in the UD and UD+DM groups. As percentages of total tissue area, collagen decreased in the DIU and DM groups, and increased in the UD and UD+DM groups, and smooth muscle and urothelium decreased in the UD and UD+DM groups. Nitrotyrosine and MnSOD increased in DM and UD+DM rats. Conclusions Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may play a pathogenic role in late stage DBD. PMID:22999997

Is It Safe to Reduce Water Intake in the Overactive Bladder Population? A Systematic Review.

PubMed

Wood, Lauren N; Markowitz, Melissa A; Parameshwar, Pooja S; Hannemann, Alex J; Ogawa, Shellee L; Anger, Jennifer T; Eilber, Karyn S

2018-03-01

Overactive bladder imposes a significant socioeconomic burden on the health care system. It is a commonly held belief that increased fluid intake (8 glasses of water per day) is beneficial for health. However, increased fluid intake exacerbates overactive bladder symptoms. Thus, it is imperative that clinicians appropriately educate patients for whom increased water intake may be detrimental (women with overactive bladder), in contrast to patients with comorbidities that necessitate increased water intake (nephrolithiasis). We systematically reviewed the literature to determine the potential health advantages of increased water intake and identify specific subpopulations that need increased hydration. We systematically reviewed published articles from 1972 through 2017 on PubMed® and the Cochrane Library. The data were reviewed independently by 2 individuals. Studies were included if they explored water intake in relation to the risk of a particular disease. Level 1 evidence supported increased fluid intake in patients with nephrolithiasis. There was no available evidence to support increased fluid intake in patients with cardiovascular disease, constipation, venous thromboembolism, headaches, cognitive function or bladder cancer. Dehydration may exacerbate some conditions, specifically chronic constipation and headache intensity. Increased fluid intake may have a role in preventing stroke recurrence but not in preventing primary stroke. The available reviewed literature suggests no benefit to drinking 8 glasses of water per day in patients without nephrolithiasis. Also, excess fluid intake can exacerbate symptoms of overactive bladder. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Nocturnal enuresis in children].

PubMed

Hjälmås, K

1998-01-01

After allergic disorders, nocturnal enuresis is the most common chronic childhood condition. Recent research has yielded abundant new knowledge about the condition, especially about its aetiology and pathophysiology, and the psychological consequences. A hereditary background has been substantiated by the identification in genetic linkage studies of areas in chromosomes 12 and 13 that are manifestly associated with bedwetting, though genotype expression in the phenotype appears to be complex and heterogeneous. Pathophysiologically, findings in current intensive research suggest three interactive factors to be involved: (i) relative nocturnal polyuria, due to insufficient antidiuretic hormone release during sleep in pre-teenagers, and due to renal tubular dysfunction in adolescents and adults; (ii) reduced nocturnal bladder capacity, especially in the 33 per cent of cases which do not respond to desmopressin treatment; and (iii) the patient's inability to waken in response to signals from a full bladder. Recent findings have also confirmed previous reports that with very few exceptions bedwetting is not caused by psychological factors. On the contrary, the condition causes psychological problems manifested in reduced self-esteem, shame and guilt, though self-esteem is restored by successful treatment. Active treatment should be started as soon as the child is ready to receive it, the main options being an enuresis alarm, desmopressin, or a combination of the two. If reduced bladder capacity is suspected, treatment with a detrusor relaxant should be included.

Evaluation and treatment of enuresis.

PubMed

Ramakrishnan, Kalyanakrishnan

2008-08-15

Enuresis is defined as repeated, spontaneous voiding of urine during sleep in a child five years or older. It affects 5 to 7 million children in the United States. Primary nocturnal enuresis is caused by a disparity between bladder capacity and nocturnal urine production and failure of the child to awaken in response to a full bladder. Less commonly, enuresis is secondary to a medical, psychological, or behavioral problem. A diagnosis usually can be made with a history focusing on enuresis and a physical examination followed by urinalysis. Imaging and urodynamic studies generally are not needed unless specifically indicated (e.g., to exclude suspected neurologic or urologic disease). Primary nocturnal enuresis almost always resolves spontaneously over time. Treatment should be delayed until the child is able and willing to adhere to the treatment program; medications are rarely indicated in children younger than seven years. If the condition is not distressing to the child, treatment is not needed. However, parents should be reassured about their child's physical and emotional health and counseled about eliminating guilt, shame, and punishment. Enuresis alarms are effective in children with primary nocturnal enuresis and should be considered for older, motivated children from cooperative families when behavioral measures are unsuccessful. Desmopressin is most effective in children with nocturnal polyuria and normal bladder capacity. Patients respond to desmopressin more quickly than to alarm systems. Combined treatment is effective for resistant cases.

Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty.

PubMed

Tu, Duong D; Chung, Yeun Goo; Gil, Eun Seok; Seth, Abhishek; Franck, Debra; Cristofaro, Vivian; Sullivan, Maryrose P; Di Vizio, Dolores; Gomez, Pablo; Adam, Rosalyn M; Kaplan, David L; Estrada, Carlos R; Mauney, Joshua R

2013-11-01

Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6 × 6 cm(2)) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded nonsurgical control gains (144%) encountered due to animal growth.In addition, animals augmented with both matrix configurations displayed increases in bladder compliance over pre-operative levels(Group 1: 357%; Group 2: 338%) similar to growth-related elevations observed in non-surgical controls (354%) [corrected]. Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair. © 2013 Elsevier Ltd. All rights reserved.

Is sensory urgency part of the same spectrum of bladder dysfunction as detrusor overactivity?

PubMed

Haylen, Bernard T; Chetty, Naven; Logan, Vanessa; Schulz, Serena; Verity, Louise; Law, Matthew; Zhou, Jialun

2007-02-01

It has been suggested that the urogynecological diagnosis of sensory urgency is an early form of detrusor overactivity and may be just earlier in the spectrum of disease. The former term is generally defined as increased perceived bladder sensation during filling, a low first desire to void and low bladder capacity in the absence of recorded urinary tract infection (UTI) or detrusor overactivity. The aims of this study are to determine the prevalence and associations of sensory urgency in comparison with detrusor overactivity, and whether sensory urgency is shown to be in the same spectrum of bladder dysfunction as detrusor overactivity. Five hundred and ninety-two women attending for an initial urogynecological/urodynamic assessment took part in this prospective study. In addition to a full clinical assessment, all women underwent free uroflowmetry, residual urine volume measurement (by vaginal ultrasound) and multichannel filling and voiding cystometry. Data were separated into those having (1) sensory urgency or (2) detrusor overactivity. Apart from prevalence figures, comparative associations were sought for (3) age; (4) parity; (5) presenting symptoms; (6) presence of at least one (medically) documented UTI in the previous 12 months; (7) two or more (recurrent) documented UTIs in the previous 12 months; (8) prior hysterectomy; (9) prior continence surgery; (10) menopause; (11) menopause and HRT use; (12) sign of clinical stress leakage; (13) retroverted uterus; (14) anterior vaginal wall prolapse; (15) uterine prolapse; (16) posterior vaginal wall prolapse; (17) apical vaginal prolapse; (18, 19) maximum, average urine flow rate (MUFR, AUFR) centiles, Liverpool Nomograms; (20) median residual urine volume (RUV) in milliliters; (21, 22) voiding difficulty: VD1,VD2 (MUFR, AUFR under 10th centile Liverpool Nomogram and/or RUV >30 ml); (23) diagnosis of urodynamic stress incontinence and (24) diagnosis of uterine and/or vaginal prolapse (grade >0). The prevalence of sensory urgency was 13%. The only differences in the clinical and urodynamic profiles of it and detrusor overactivity were (1) significantly increased prevalence of the symptom of urge incontinence and (2) (by definition) abnormal detrusor contractions during filling cystometry in women with detrusor overactivity. Overall, sensory urgency and detrusor overactivity appear to be part of the same spectrum of bladder dysfunction.

Hexavalent Chromium Induces Chromosome Instability in Human Urothelial Cells

PubMed Central

Wise, Sandra S.; Holmes, Amie L.; Liou, Louis; Adam, Rosalyn M.; Wise, John Pierce

2016-01-01

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of Cr(VI) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Hexavalent chromium (Cr(VI)) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer specifically and may be a mechanism for metal-induced bladder cancer in general. PMID:26908176

Downregulation of glutathione S-transferase M1 protein in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced mouse bladder carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, Jing-Jing; Dai, Yuan-Chang; Lin, Yung-Lun

2014-09-15

Bladder cancer is highly recurrent following specific transurethral resection and intravesical chemotherapy, which has prompted continuing efforts to develop novel therapeutic agents and early-stage diagnostic tools. Specific changes in protein expression can provide a diagnostic marker. In our present study, we investigated changes in protein expression during urothelial carcinogenesis. The carcinogen BBN was used to induce mouse bladder tumor formation. Mouse bladder mucosa proteins were collected and analyzed by 2D electrophoresis from 6 to 20 weeks after commencing continuous BBN treatment. By histological examination, the connective layer of the submucosa showed gradual thickening and the number of submucosal capillaries graduallymore » increased after BBN treatment. At 12-weeks after the start of BBN treatment, the urothelia became moderately dysplastic and tumors arose after 20-weeks of treatment. These induced bladder lesions included carcinoma in situ and connective tissue invasive cancer. In protein 2D analysis, the sequentially downregulated proteins from 6 to 20 weeks included GSTM1, L-lactate dehydrogenase B chain, keratin 8, keratin 18 and major urinary proteins 2 and 11/8. In contrast, the sequentially upregulated proteins identified were GSTO1, keratin 15 and myosin light polypeptide 6. Western blotting confirmed that GSTM1 and NQO-1 were decreased, while GSTO1 and Sp1 were increased, after BBN treatment. In human bladder cancer cells, 5-aza-2′-deoxycytidine increased the GSTM1 mRNA and protein expression. These data suggest that the downregulation of GSTM1 in the urothelia is a biomarker of bladder carcinogenesis and that this may be mediated by DNA CpG methylation. - Highlights: • GSTM1 and NQO-1 proteins decreased in the mouse bladder mucosa after BBN treatment. • BBN induced GSTO1 and Sp1 protein expression in the mouse bladder mucosa. • 5-Aza-2′-deoxycytidine increased GSTM1 mRNA and protein in human bladder cancer cell. • GSTM1 downregulation in the urothelia may be a biomarker of bladder carcinogenesis.« less

Nanotechnology in bladder cancer: current state of development and clinical practice

PubMed Central

Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc; Pan, Chong-Xian

2015-01-01

Nanotechnology is being developed for the diagnosis and treatment of both nonmyoinvasive bladder cancer (NMIBC) and invasive bladder cancer. The diagnostic applications of nanotechnology in NMIBC mainly focus on tumor identification during endoscopy to increase complete resection of bladder cancer while nanotechnology to capture malignant cells or their components continues to be developed. The therapeutic applications of nanotechnology in NMIBC are to reformulate biological and cytotoxic agents for intravesical instillation, combine both diagnostic and therapeutic application in one nanoformulation. In invasive and advanced bladder cancer, magnetic resonance imaging with supraparamagnetic iron oxide nanoparticles can improve the sensitivity and specificity in detecting small metastasis to lymph nodes. Nanoformulation of cytotoxic agents can potentially decrease the toxicity while increasing efficacy. PMID:25929573

Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy

PubMed Central

Patterson, Karl; Arya, Lovleen; Bottomley, Sarah; Morgan, Susan; Cox, Angela; Catto, James; Bryant, Helen E.

2016-01-01

RECQ helicases are a family of enzymes with both over lapping and unique functions. Functional autosomal recessive loss of three members of the family BLM, WRN and RECQL4, results in hereditary human syndromes characterized by cancer predisposition and premature aging, but despite the finding that RECQL5 deficient mice are cancer prone, no such link has been made to human RECQL5. Here we demonstrate that human urothelial carcinoma of the bladder (UCC) has increased expression of RECQL5 compared to normal bladder tissue and that increasing RECQL5 expression can drive proliferation of normal bladder cells and is associated with poor prognosis. Further, by expressing a helicase dead RECQL5 and by depleting bladder cancer cells of RECQL5 we show that inhibition of RECQL5 activity has potential as a new target for treatment of UCC. PMID:27764811

The urodynamic evaluation of neuromodulation in patients with voiding dysfunction.

PubMed

Everaert, K; Plancke, H; Lefevere, F; Oosterlinck, W

1997-05-01

To determine which patients with voiding dysfunction might be suitable for treatment with neuromodulation, using urodynamics to obtain an objective measure of improvement and to illustrate the effect of neuromodulation on voiding dysfunction. Patients were selected for implantation of a neuroprosthesis using a urodynamic evaluation before and during subchronic stimulation; 27 such patients (four men and 23 women, mean age 33 years, SD 15) were evaluated. Of the 27 patients, the 17 who responded well to neuromodulation all had hypocontractile detrusors and sphincter hypertonicity; sphincter relaxation during micturition was impaired. The urodynamic evaluation showed that these patients were not obstructed. Of 10 patients with spastic pelvic floor syndrome, nine responded well to the treatment. Those not responding to neuromodulation had mainly acontractile detrusors. The ideal candidates for neuromodulation are those patients with a spastic pelvic floor syndrome or with a hypocontractile detrusor, in combination with sphincter instability, and impaired sphincter relaxation. An increase of bladder contractility, enhancement of sphincter relaxation and decrease in bladder capacity and residual urine are the most important features of the response.

Efficacy of bladder neck incision on urodynamic abnormalities in patients with posterior urethral valves.

PubMed

Sarin, Yogesh K; Sinha, Shalini

2013-04-01

This study aims to study the efficacy of simultaneous endoscopic bladder neck incision (BNI) and primary endoscopic valve incision (PEVI) in patients with posterior urethral valves (PUV). Nine PUV patients underwent PEVI and BNI over a year. They were compared to nine comparable historical controls that had undergone only PEVI. Trends in renal function tests, urodynamics and changes in the upper urinary tracts were evaluated after 3 months during which no pharmacotherapy was given. The incidence of bladder dysfunction in the two groups was similar-55.5 % in case group and 66.6 % in control group. Hypocompliant, high-pressure bladder was the predominant cystometric finding in both groups. Three patients in the case group and two patients in the control group had high end infusion pressure (EIP) with poor compliance. Detrusor overactivity (DOA) was seen in 23.1 % patients in the case group as compared to 55.5 % patients in the control group (P = 0.3348). Five patients in both groups were later started on anticholinergics due to raised EIP, small capacity bladder and/or DOA. Although BNI should theoretically improve the outcome of PUV patients, the current pilot study failed to demonstrate any significant difference. A larger sample size and longer follow-up are required to prove or disprove its efficacy.

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

PubMed

Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

2010-08-01

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

Cerebral control of the lower urinary tract: How age-related changes might predispose to urge incontinence

PubMed Central

Griffiths, D.; Tadic, S.D.; Schaefer, W.; Resnick, N.M.

2009-01-01

Loss of bladder control (urge incontinence) is common in elderly; the cause is usually unknown. Functional imaging has revealed the brain network controlling responses to bladder filling. Age-related changes in this network might predispose to urge incontinence. We sought such changes in 10 continent, healthy women aged 30 – 79 years who underwent fMRI while fluid (20 ml) was repeatedly infused into and withdrawn from the bladder. Data were collected in 4 measurement blocks with progressively increasing bladder volumes and were analyzed by SPM2, using the contrast infuse-withdraw to quantify response to bladder infusion. Effective connectivity was examined by physiophysiological interaction (PhPI; see interpretation in Supplementary Material), with right insula (RI) and dorsal anterior cingulate cortex (dACC) as seed regions. Dependence on age and bladder volume (=block number) was assessed. Bladder infusion evoked expected activations. Activation decreased with age in bilateral insula and dACC. PhPI revealed connectivity with RI and dACC in regions that included bilateral putamen and R pontine micturition center. Interaction (connectivity) tended to increase with age in regions including L insula, L paracentral lobule and PAG. Consistent with a special role in maintaining continence, medial prefrontal cortex (mPFC) showed a trend to deactivation on bladder infusion that became more prominent in old age, and a trend to negative interaction (connectivity) that weakened significantly with age. Thus, with increasing age, weaker signals in the bladder control network as a whole and/or changes in mPFC function or connecting pathways may be responsible for the development of urge incontinence. PMID:19427909

Effects of stimulation of muscarinic receptors on bladder afferent nerves in the in vitro bladder-pelvic afferent nerve preparation of the rat.

PubMed

Yu, Yongbei; de Groat, William C

2010-11-18

Effects of a muscarinic receptor agonist oxotremorine-M (oxo-M) on bladder afferent nerve (BAN) activity were studied in an in vitro bladder-pelvic nerve preparation. Distension of the bladder induced rhythmic bladder contractions that were accompanied by multiunit afferent firing. Intravesical administration of 25 and 50 μM oxo-M significantly increased afferent firing from 41 ± 2 spikes/s to 51 ± 4 spikes/s and 60.5 ± 5 spikes/s, respectively, but did not change the maximum amplitude of spontaneous bladder contractions. The afferent nerve firing induced by isotonic distension of the bladder (10-40 cmH(2)O) was increased 22-100% by intravesical administration of 50 μM oxo-M. Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Oxo-M significantly decreased the voltage threshold by 40% (p<0.05) and increased by 157% (p<0.05) the area of the AP evoked at a submaximal stimulus intensity. These effects were blocked by intravesical injection of 5 μM atropine methyl nitrate (AMN). Intravesical administration of 5 μM AMN alone did not alter BAN firing or the amplitude of bladder contractions. The facilitatory effects induced by oxo-M on BAN activity were also suppressed (p<0.05) by intravesical administration of 2',3'-0-trinitrophenyl-ATP (TNP-ATP) (30 μM). In preparations pretreated with capsaicin (125 mg/kg, s.c.) the facilitatory effects of 50 μM oxo-M on BAN activity were absent. These results suggest that activation of muscarinic receptors facilitates mechano-sensitive, capsaicin-sensitive BAN activity in part by mechanisms involving purinergic receptors located near the luminal surface of the bladder and ATP release which presumably occurs in the urothelium. Copyright © 2010 Elsevier B.V. All rights reserved.

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

PubMed Central

Childs, M. Adam; Mynderse, Lance A.; Rangel, Laureano J.; Wilson, Torrence M.; Lingeman, James E.; Krambeck, Amy E.

2013-01-01

Purpose Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. Materials and Methods Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. Results Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). Conclusions In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis. PMID:23159588

[Investigation of urinary management after removal of indwelling urethral catheters in a general hospital: associations between bedridden state and impaired bladder emptying].

PubMed

Tsuchiyama, Katsuki; Ueki, Osamu; Minami, Hidero; Kawaguchi, Kouhei; Aoki, Yoshitaka; Yokoyama, Osamu

2010-06-01

In this study we investigated the influences of decreased levels of activities of daily living (ADL), especially in bedridden patients,on lower urinary tract dysfunction and urinary management during hospital care. All 1,106 non-urological inpatients (896 non-bedridden patients and 210 bedridden patients) with an indwelling urethral catheter treated at Noto General Hospital between April 2006 and October 2009 were retrospectively evaluated. Maximum bladder capacity and post-void residual urine volume (PVR) were evaluated with uroflowmetry or voiding cystourethrography at the time the catheter was removed. Clean intermittent catheterization (CIC) and drug administration were performed for patients who had a PVR of 100 ml or more. Bedridden patients required urinary interventions at a higher rate than did non-bedridden patients (bedridden : 29.0%,non-bedridden : 17.6%). Although indwelling urethral catheters were reinserted in 13 patients in the bedridden group and 16 patients in the non-bedridden group,many patients in both groups could be free from the catheter. Our results indicate that patients with low ADL are vulnerable to impaired bladder emptying,and early diagnosis of impaired bladder emptying and active urinary management are required to solve their urinary problems.

ATP during early bladder stretch is important for urgency in detrusor overactivity patients.

PubMed

Cheng, Y; Mansfield, K J; Allen, W; Chess-Williams, R; Burcher, E; Moore, K H

2014-01-01

ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤ 200 mL) than in those with higher FDV (> 200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid.

Clinical characteristics of bladder cancer in patients with spinal cord injury: the experience from a single centre.

PubMed

Böthig, Ralf; Kurze, Ines; Fiebag, Kai; Kaufmann, Albert; Schöps, Wolfgang; Kadhum, Thura; Zellner, Michael; Golka, Klaus

2017-06-01

Life expectancy for people with spinal cord injury has shown a marked increase due to modern advances in treatment methods and in neuro-urology. However, since life expectancy of people with paralysis increases, the risk of developing of urinary bladder cancer is gaining importance. Single-centre retrospective evaluation of patient data with spinal cord injuries and proven urinary bladder cancer and summary of the literature. Between 1998 and 2014, 24 (3 female, 21 male) out of a total of 6599 patients with spinal cord injury were diagnosed with bladder cancer. The average age at bladder cancer diagnosis was 57.67 years, which is well below the average for bladder cancer cases in the general population (male: 73, female: 77). All but one patient had a latency period between the onset of the spinal paralysis and tumour diagnosis of more than 10 years. The median latency was 29.83 years. The median survival for these patients was 11.5 months. Of the 24 patients, 19 (79%) had muscle invasive bladder cancer at ≥T2 at the time of diagnosis. The type of neurogenic bladder (neurogenic detrusor overactivity or acontractility) and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients. The significantly younger age at onset and the frequency of invasive tumours at diagnosis indicate that spinal cord injury influences bladder cancer risk and prognosis as well. Early detection of bladder cancer in patients with spinal cord injury remains a challenge.

Acute and Chronic Deficits in the Urinary Bladder after Spinal Contusion Injury in the Adult Rat

PubMed Central

Herrera, Juan J.; Haywood-Watson, Ricky J.L.

2010-01-01

Abstract Traumatic spinal cord injury (SCI) permanently alters bladder function in humans. Hematuria and cystitis occur in both human SCI as well as in rodent models of SCI. Others have reported early SCI-dependent disruption to bladder uroepithelial integrity that results in increased permeability to urine and urine-borne substances. This can result in cystitis, or inflammation of the bladder, an ongoing pathological condition present throughout the chronic phase of SCI in humans. The goals of our study were twofold: (1) to begin to examine the inflammatory and molecular changes that occur within the bladder uroepithelium using a clinically-relevant spinal contusion model of injury, and (2) to assess whether these alterations continue into the chronic phase of SCI. Rats received either moderate SCI or sham surgery. Urine was collected from SCI and sham subjects over 7 days or at 7 months to assess levels of excreted proteins. Inflammation in the bladder wall was assessed via biochemical and immunohistochemical methods. Bladder tight junction proteins, mediators of uroepithelial integrity, were also measured in both the acute and chronic phases of SCI. Urine protein and hemoglobin levels rapidly increase following SCI. An SCI-dependent elevation in numbers of neutrophils within the bladder wall peaked at 48 h. Bladder tight junction proteins demonstrate a rapid but transient decrease as early as 2 h post-SCI. Surprisingly, elevated levels of urine proteins and significant deficits in bladder tight junction proteins could be detected in chronic SCI, suggesting that early pathological changes to the bladder may continue throughout the chronic phase of injury. PMID:19891526

Transforming Growth Factor-β Is an Upstream Regulator of Mammalian Target of Rapamycin Complex 2-Dependent Bladder Cancer Cell Migration and Invasion.

PubMed

Gupta, Sounak; Hau, Andrew M; Al-Ahmadie, Hikmat A; Harwalkar, Jyoti; Shoskes, Aaron C; Elson, Paul; Beach, Jordan R; Hussey, George S; Schiemann, William P; Egelhoff, Thomas T; Howe, Philip H; Hansel, Donna E

2016-05-01

Our prior work identified the mammalian target of rapamycin complex 2 (mTORC2) as a key regulator of bladder cancer cell migration and invasion, although upstream growth factor mediators of this pathway in bladder cancer have not been well delineated. We tested whether transforming growth factor (TGF)-β, which can function as a promotility factor in bladder cancer cells, could regulate mTORC2-dependent bladder cancer cell motility and invasion. In human bladder cancers, the highest levels of phosphorylated SMAD2, a TGF-β signaling intermediate, were present in high-grade invasive bladder cancers and associated with more frequent recurrence and decreased disease-specific survival. Increased expression of TGF-β isoforms, receptors, and signaling components was detected in invasive high-grade bladder cancer cells that expressed Vimentin and lacked E-cadherin. Application of TGF-β induced phosphorylation of the Ser473 residue of AKT, a selective target of mTORC2, in a SMAD2- and SMAD4-independent manner and increased bladder cancer cell migration in a modified scratch wound assay and invasion through Matrigel. Inhibition of TGF-β receptor I using SB431542 ablated TGF-β-induced migration and invasion. A similar effect was seen when Rictor, a key mTORC2 component, was selectively silenced. Our results suggest that TGF-β can induce bladder cancer cell invasion via mTORC2 signaling, which may be applicable in most bladder cancers. Copyright © 2016. Published by Elsevier Inc.

Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

NASA Astrophysics Data System (ADS)

Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

2011-02-01

Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction.

PubMed

Shiina, Kazuhiro; Hayashida, Ken-Ichiro; Ishikawa, Kazuo; Kawatani, Masahito

2016-01-01

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.

Evidence of bladder oversensitivity in the absence of an infection in premenopausal women with a history of recurrent urinary tract infections.

PubMed

Arya, Lily A; Northington, Gina M; Asfaw, Tirsit; Harvie, Heidi; Malykhina, Anna

2012-07-01

Study Type - Prevalence (case control) Level of Evidence 4. What's known on the subject? and What does the study add? Urinary tract infections (UTIs) have been implicated in the aetiology of interstitial cystitis/painful bladder syndrome (IC/PBS). Prior studies have described symptoms and laboratory tests suggestive of UTI at the onset of IC/PBS as well as a significant history of childhood recurrent UTIs. However, the mechanism by which recurrent UTIs contribute to the development of IC/PBS is not clear. Our study shows that women with recurrent UTI suffer from bladder oversensitivity. Our findings have useful clinical implications. Women with bladder oversensitivity complain of urinary frequency which is often misdiagnosed as an infection and treated with unnecessary antibiotics. Additionally, there are no effective therapies for bladder oversensitivity. Therefore, women with recurrent UTI should undergo prompt evaluation and treatment of episodes of infection to prevent the development of bladder oversensitivity. Our findings also provide a possible mechanism for the development of IC/PBS. Whether women with recurrent UTI are at increased risk for developing IC/PBS in the future will need to be confirmed in future studies. • To compare the mean voided volume and bladder sensation during filling cystometry in women with a history of recurrent urinary tract infection (UTI) and controls. • This was a case-control study including adult women seen in the urogynaecology clinic. • The cases were 49 women with at least three documented positive urine cultures >105 colonies/mL in the previous 12 months and no active infection at the time of data collection. • Controls were 53 women with stress urinary incontinence and no history of recurrent UTI or coexistent urge urinary incontinence. • We compared bladder diary variables and filling cystometry data in the absence of an active infection. • There was no significant difference in the median age, parity and body mass index of women with a history of recurrent UTI and controls. • The median number of voids per day and median number of voids per litre of fluid intake was significantly greater in women with recurrent UTI than controls (12 vs 7 voids/day and 6 vs 4 voids/L, P= 0.005 and P= 0.004 respectively). • The median average voided volume was significantly lower in women with recurrent UTI than controls (155 vs 195 mL, P= 0.008). • On filling cystometry, median volumes of strong desire to void and maximum cystometric capacity were significantly lower in women with recurrent UTI than controls (all P < 0.05). • In the absence of an infection, premenopausal women with a history of recurrent UTI have significantly greater urinary frequency, lower average voided volume and a lower threshold of bladder sensitivity than controls. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity.

PubMed

Van Meel, Tom David; De Wachter, Stefan; Wyndaele, Jean Jacques

2010-03-01

The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects. (c) 2009 Wiley-Liss, Inc.

Apoptotic effect of the selective PPARβ/δ agonist GW501516 in invasive bladder cancer cells.

PubMed

Péchery, Adeline; Fauconnet, Sylvie; Bittard, Hugues; Lascombe, Isabelle

2016-11-01

GW501516 is a selective and high-affinity synthetic agonist of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). This molecule promoted the inhibition of proliferation and apoptosis in few cancer cell lines, but its anticancer action has never been investigated in bladder tumor cells. Thus, this study was undertaken to determine whether GW501516 had antiproliferative and/or apoptotic effects on RT4 and T24 urothelial cancer cells and to explore the molecular mechanisms involved. Our results indicated that, in RT4 cells (derived from a low-grade papillary tumor), GW501516 did not induce cell death. On the other hand, in T24 cells (derived from an undifferentiated high-grade carcinoma), this PPARβ/δ agonist induced cytotoxic effects including cell morphological changes, a decrease of cell viability, a G2/M cell cycle arrest, and the cell death as evidenced by the increase of the sub-G1 cell population. Furthermore, GW501516 triggered T24 cell apoptosis in a caspase-dependent manner including both extrinsic and intrinsic apoptotic pathways through Bid cleavage. In addition, the drug led to an increase of the Bax/Bcl-2 ratio, a mitochondrial dysfunction associated with the dissipation of ΔΨm, and the release of cytochrome c from the mitochondria to the cytosol. GW501516 induced also ROS generation which was not responsible for T24 cell death since NAC did not rescue cells upon PPARβ/δ agonist exposure. For the first time, our data highlight the capacity of GW501516 to induce apoptosis in invasive bladder cancer cells. This molecule could be relevant as a therapeutic drug for high-grade urothelial cancers.

Nocturia: current status and future perspectives.

PubMed

Van Kerrebroeck, Philip

2011-10-01

Nocturia is a bothersome and highly prevalent condition characterized by the need to wake to void at night. Nocturia is equally common in men and women, and although its prevalence increases with age, a significant proportion of younger people are also affected. Nocturia leads to fragmentation of sleep and consequently to a serious decline in daytime functioning and in quality of life and health. Its impact should not be underestimated by clinicians and therefore a review on nocturia is timely and relevant. Traditionally, nocturia is regarded as a symptom of benign prostatic enlargement and/or overactive bladder syndrome, with treatment therefore directed toward increasing the capacity of the bladder to hold urine. Such treatments have proven ineffective in many patients because nocturnal polyuria, an overproduction of urine at night, has been found to be present in the majority of patients. Nocturia can be attributed to some underlying pathological factors but it can also be a distinct clinical entity with specific pathogenesis. Frequency-volume charts are recommended for routine use in clinical practice, to determine whether nocturia is a result of excessive urine production at night, or of small voided volumes due to bladder problems, or a combination of these factors. Desmopressin, a synthetic analogue of the antidiuretic hormone, should be considered in patients with nocturia where nocturnal polyuria is present. Contrary to popular and medical misconception nocturia is an important condition leading to general morbidity and with serious impact on overall quality of life and health. We advise clinicians to pay attention to nocturia and diagnostics should be offered. Treatment modalities are available and have to be discussed with the patient. (C) 2011 Lippincott Williams & Wilkins, Inc.

Comparative analysis of the pressure profilometry of vesicocutaneous continent catheterizable conduits between patients with and without rectus abdominis neosphincter (Yachia principle).

PubMed

Rondon, Atila; Leslie, Bruno; Arcuri, Leonardo Javier; Ortiz, Valdemar; Macedo, Antonio

2015-09-01

To assess whether crossing rectus abdominis muscle strips, as proposed by Yachia, would change urinary catheterizable conduit's pressure profilometry, in static and dynamic conditions. Non-randomized selection of 20 continent patients that underwent Macedo's ileum-based reservoir, 10 including Yachia's technique (Study Group) and 10 without this mechanism of continence (Control Group). Demographics and cystometric data were assessed. Conduit's pressure profilometry was obtained by infusing saline through a multichannel catheter, at rest and during Valsalva maneuver. We assessed the pressure: (a) in the bladder; (b) in conduit's proximal segment; and (c) in conduit's distal segment, which is presumably the abdominal wall and crossed muscle strips site. Mean age at surgery was 6.1 years in the Control Group and 7.7 years in the Study Group. There was no statistically significant difference between groups regarding maximum cystometric bladder capacity and leakage point pressure. At rest, the pressure profilometry showed similar results between groups in all segments analyzed. During Valsalva maneuver, pressure profilometry showed similar results between groups in bladder and conduit's proximal segment pressure. In this condition, conduit's distal segment pressure in the Study Group (Mean = 72.9 and Peak = 128.7 cmH2 O) was significantly greater (P < 0.05) than conduit's distal segment pressure in the Control Group (Mean = 48.3 and Peak = 65.1 cmH2 O). Crossing muscle strips over the conduit significantly increases the pressure in its distal segment during contraction of the rectus abdominis muscle, which can be important in moments of sudden increase in abdominal pressure in order to keep continence. © 2014 Wiley Periodicals, Inc.

The emerging role of the androgen receptor in bladder cancer.

PubMed

Lombard, Alan P; Mudryj, Maria

2015-10-01

Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease. © 2015 Society for Endocrinology.

The Impact of Increased Bladder Blood Flow on Storage Symptoms after Holmium Laser Enucleation of the Prostate

PubMed Central

Ide, Hisamitsu; Aoki, Hiroaki; Muto, Satoru; Yamaguchi, Raizo; Tsujimura, Akira; Horie, Shigeo

2015-01-01

In order to investigate how holmium laser enucleation of the prostate (HoLEP) improves urinary storage symptoms, we assessed blood flow in the urinary bladder mucosa of patients with benign prostatic hyperplasia (BPH) before and after laser surgery. Seventy-four consecutive patients with BPH (median age 69 years, range; 53–88) underwent HoLEP at our institution and are included in this study. We prospectively assessed the International Prostate Symptom Score (IPSS), IPSS-QOL Score, the Overactive Bladder Symptom Score (OABSS), uroflowmetry, and blood flow in the urinary bladder, before and after surgery. Blood flow in the bladder mucosa was measured using the OMEGA FLOW (OMEGAWAVE, Tokyo, Japan) laser Doppler flowmeter. The median volume of the enucleated adenomas was 45.0 g (range: 25.0 to 83.2). The median IPSS improved significantly from 20 (range: 6–35) to 3 (0–22) (p<0.001; Wilcoxon signed-rank test), as did the storage symptoms score, which decreased from 13 (2–20) to 3 (1–8) (p<0.001). Median bladder blood flow increased at the trigone from 9.57±0.83 ml/sec to 17.60±1.08 ml/sec. Multiple regression analysis for the improved storage symptom score eliminated all explanatory variables except increased bladder perfusion. The data suggest that HoLEP improves blood flow in the bladder mucosa, which independently leads to the improvement of storage symptoms. PMID:26090819

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats

PubMed Central

Chiang, Bing-Juin; Chen, Tien-Wen; Chung, Shiu-Dong; Lee, Way-Zen; Chien, Chiang-Ting

2017-01-01

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction. PMID:29285288

Factors influencing bladder stone formation in patients with spinal cord injury.

PubMed

Favazza, Terry; Midha, Meena; Martin, Jessicca; Grob, B Mayer

2004-01-01

Bladder stones that form in patients with spinal cord injury (SCI) can cause significant morbidity. This study sought to analyze factors associated with bladder stone formation to determine which patients might be at increased risk to develop bladder stones. A review of 56 SCI patients treated for bladder calculi over a 10-year period at a single institution was performed. These patients were compared with a control population of general SCI patients known to be stone free. The factors compared were patient age, duration of injury, level of injury, completeness of injury, method of bladder management, and the presence of documented urinary tract infections with urease-producing organisms. All patients with stones were male and had a median age of 58.5 years. The median level of injury was C6, the median time since injury was 21 years, 66% had complete injuries, 68% managed their bladders with indwelling catheters or suprapubic tubes, and 83% had a history of infections with urease-producing organisms. When compared with the control group, patients forming bladder stones were older (P = 0.03), were more likely to have indwelling catheters (P < 0.0001), had a history of infections with urease-producing organisms (P = 0.04), and had complete injuries (P = 0.018). This information can be used to identify patients who have an increased risk of bladder stones and measures can be taken to reduce their incidence and morbidity.

Urothelium update: how the bladder mucosa measures bladder filling.

PubMed

Janssen, D A W; Schalken, J A; Heesakkers, J P F A

2017-06-01

This review critically evaluates the evidence on mechanoreceptors and pathways in the bladder urothelium that are involved in normal bladder filling signalling. Evidence from in vitro and in vivo studies on (i) signalling pathways like the adenosine triphosphate pathway, cholinergic pathway and nitric oxide and adrenergic pathway, and (ii) different urothelial receptors that are involved in bladder filling signalling like purinergic receptors, sodium channels and TRP channels will be evaluated. Other potential pathways and receptors will also be discussed. Bladder filling results in continuous changes in bladder wall stretch and exposure to urine. Both barrier and afferent signalling functions in the urothelium are constantly adapting to cope with these dynamics. Current evidence shows that the bladder mucosa hosts essential pathways and receptors that mediate bladder filling signalling. Intracellular calcium ion increase is a dominant factor in this signalling process. However, there is still no complete understanding how interacting receptors and pathways create a bladder filling signal. Currently, there are still novel receptors investigated that could also be participating in bladder filling signalling. Normal bladder filling sensation is dependent on multiple interacting mechanoreceptors and signalling pathways. Research efforts need to focus on how these pathways and receptors interact to fully understand normal bladder filling signalling. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Hexavalent chromium induces chromosome instability in human urothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wise, Sandra S.; Holmes, Amie L.; Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damagemore » in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.« less

Overactive and Underactive Bladder Dysfunction is Reflected by Alterations in Urothelial ATP and NO Release

PubMed Central

Munoz, Alvaro; Smith, Christopher P.; Boone, Timothy B.; Somogyi, George T.

2011-01-01

ATP and NO are released from the urothelium in the bladder. Detrusor Overactivity (DO) following spinal cord injury results in higher ATP and lower NO release from the bladder urothelium. Our aim was to study the relationship between ATP and NO release in 1) early diabetic bladders, an overactive bladder model; and 2) in “diuretic” bladders, an underactive bladder model. To induce diabetes mellitus female rats received 65 mg/kg streptozocin (i.v.). To induce chronic diuresis rats were fed with 5% sucrose. At 28 days, in vivo open cystometry was performed. Bladder wash was collected to analyze the amount of ATP and NO released into the bladder lumen. For in vitro analysis of ATP and NO release, a Ussing chamber was utilized and hypoosmotic Krebs was perfused on the urothelial side of the chamber. ATP was analyzed with luminometry or HPLC-fluorometry while NO was measured with a Sievers NO-analyzer. In vivo ATP release was increased in diabetic bladders and unchanged in diuretic bladders. In vitro release from the urothelium followed the same pattern. NO release was unchanged both in vitro and in vivo in overactive bladders whereas it was enhanced in underactive bladders. We found that the ratio of ATP/NO, representing sensory transmission in the bladder, was high in overactive and low in underactive bladder dysfunction. In summary, ATP release has a positive correlation while NO release has a negative correlation with the bladder contraction frequency. The urinary ATP/NO ratio may be a clinically relevant biomarker to characterize the extent of bladder dysfunction. PMID:21145365

Urologic Management of Spina Bifida

ERIC Educational Resources Information Center

Clayton, Douglass B.; Brock, John W., III; Joseph, David B.

2010-01-01

The urologist plays an important role in the multidisciplinary team of physicians who provide care for patients with spina bifida. We review common strategies for managing the urinary tract in these patients. The primary objective in all phases of life is protecting kidney function by minimizing bladder hostility and establishing a good capacity,…

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

PubMed Central

Hertting, Olof; Holm, Åsa; Lüthje, Petra; Brauner, Hanna; Dyrdak, Robert; Jonasson, Aino Fianu; Wiklund, Peter; Chromek, Milan; Brauner, Annelie

2010-01-01

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI. PMID:21179490

Positive feedback loop for cystitis cystica: the effect of recurrent urinary tract infection on the number of bladder wall mucosa nodules.

PubMed

Vrljicak, Kristina; Turudić, Daniel; Bambir, Ivan; Gradiski, Ivan Pavao; Spajić, Borislav; Batinić, Danica; Topalović-Grković, Marija; Spajić, Marija; Batinić, Danko; Milosević, Danko

2013-12-01

The main purpose of this study was to demonstrate positive feedback loop between bladder wall nodules (nodules being one of the key diagnostic factors), bladder wall thickness, and recurrent urinary tract infections. Cystitis cystica was diagnosed in 115 prepubertal girls (mean age 7.79 +/- 3.05 years) by optic examination of bladder mucosal nodules and by ultrasonographic measurement of bladder wall thickness. Bladder wall thickness increased with the frequency of recurrent urinary tract infections as well as with the number of nodules on bladder wall mucosa (3.52 +/- 0.522 mm < or = 5 nodules vs. 4.42 +/- 0.429 mm 6-10 nodules vs. 5.20 +/- 0.610 mm > 10 nodules, respectively). Study results suggested that early control of urinary tract infections by chemoprophylaxis could prevent higher grades of bladder wall mucosal changes and consequently shorten the length of chemoprophylaxis.

Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.

PubMed

Nakai, Yasushi; Tatsumi, Yoshihiro; Miyake, Makito; Anai, Satoshi; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2016-03-01

The mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells. Western blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis. The expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p=0.04). The expression of peptide transporter 1 (p<0.01, R=0.39), heme oxygenase-1 (p<0.01, R=0.33), and ferrochelatase (p<0.01, R=0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p=0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology. The expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Hongxue; Department of Urology, Hospital of Xinjiang Production and Construction Corps, Urumqi 830002; Li, Xuechao

Antisense non-coding RNA in the INK4 locus (ANRIL) is a member of long non-coding RNAs and has been reported to be dysregulated in several human cancers. However, the role of ANRIL in bladder cancer remains unclear. This present study aimed to investigate whether and how ANRIL involved in bladder cancer. Our results showed up-regulation of ANRIL in bladder cancer tissues versus the corresponding adjacent non-tumor tissues. To explore the specific mechanisms, ANRIL was silenced by small interfering RNA or short hairpin RNA transfection in human bladder cancer T24 and EJ cells. Knockdown of ANRIL repressed cell proliferation and increased cellmore » apoptosis, along with decreased expression of Bcl-2 and increased expressions of Bax, cytoplasmic cytochrome c and Smac and cleaved caspase-9, caspase-3 and PARP. However, no change of cleaved caspase-8 level was observed. Furthermore, in vivo experiment confirmed that knockdown of ANRIL inhibited tumorigenic ability of EJ cells in nude mice. Meanwhile, in accordance with in vitro study, knockdown of ANRIL inhibited expression of Bcl-2 and up-regulated expressions of Bax and cleaved caspase-9, but did not affect cleaved caspase-8 level. In conclusion, we first report that ANRIL possibly serves as an oncogene in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic apoptosis pathway. - Highlights: • We first report the role of ANRIL in bladder cancer. • ANRIL is obviously up-regulated in bladder cancer tissues. • ANRIL regulates bladder cancer cell proliferation and cell apoptosis through the intrinsic pathway.« less

[Physiotherapy in Women with Overactive Bladder].

PubMed

Henscher, U; Tholen, R; Kirschner-Hermanns, R

2016-08-01

As regards treatment for overactive bladder, physiotherapeutic interventions can be seen as an alternative to drug treatment. Targeted pelvic floor and bladder training is used to decrease the number of voids and the incontinence episodes or to increase the average voided volume in women with overactive bladder (3 systematic reviews with evidence level 1/1a).An additional option to treat women with overactive bladder is to use functional electrical stimulation and magnetic stimulation.2 systematic reviews 1 2 and 2 RCTs 3 4 reveal a low level of evidence (2 studies with level 2/2b) for the use of electrical stimulation (transcutaneous, vaginal or transanal) to reduce incontinence episodes and the number of voids and to increase the average voided volume. The trial from Yamanishi et al. (2014) shows that magnetic stimulation has a positive effect 5. Further studies are needed to evaluate the benefit of conservative treatment procedures for overactive bladder. © Georg Thieme Verlag KG Stuttgart · New York.

Urinary tract infections and reduced risk of bladder cancer in Los Angeles.

PubMed

Jiang, X; Castelao, J E; Groshen, S; Cortessis, V K; Shibata, D; Conti, D V; Yuan, J-M; Pike, M C; Gago-Dominguez, M

2009-03-10

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case-control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.

Botulinum toxin A for the Treatment of Overactive Bladder.

PubMed

Hsieh, Po-Fan; Chiu, Hung-Chieh; Chen, Kuan-Chieh; Chang, Chao-Hsiang; Chou, Eric Chieh-Lung

2016-02-29

The standard treatment for overactive bladder starts with patient education and behavior therapies, followed by antimuscarinic agents. For patients with urgency urinary incontinence refractory to antimuscarinic therapy, currently both American Urological Association (AUA) and European Association of Urology (EAU) guidelines suggested that intravesical injection of botulinum toxin A should be offered. The mechanism of botulinum toxin A includes inhibition of vesicular release of neurotransmitters and the axonal expression of capsaicin and purinergic receptors in the suburothelium, as well as attenuation of central sensitization. Multiple randomized, placebo-controlled trials demonstrated that botulinum toxin A to be an effective treatment for patients with refractory idiopathic or neurogenic detrusor overactivity. The urinary incontinence episodes, maximum cystometric capacity, and maximum detrusor pressure were improved greater by botulinum toxin A compared to placebo. The adverse effects of botulinum toxin A, such as urinary retention and urinary tract infection, were primarily localized to the lower urinary tract. Therefore, botulinum toxin A offers an effective treatment option for patients with refractory overactive bladder.

[A patient with high creatinine levels but no renal failure: reversed autodialysis in a patient with a ruptured bladder].

PubMed

Raeymaeckers, Steven; Tosi, Maurizio; Van Bael, Kobe; Brussaard, Carola; De Mey, Johan

2016-01-01

In case of a ruptured bladder with urine leakage into the peritoneal cavity 'reversed autodialysis' can occur, in which urea and creatinine diffuse back into the bloodstream via the peritoneum. This causes clinical signs of pseudorenal failure, with raised concentrations of creatinine and urea. The urea/creatinine ratio does not change. A 34-year-old female patient experienced increasing abdominal pain 3 days after laparoscopic myomectomy. Acute renal failure was suspected because of increased serum concentrations of creatinine and urea, but no cause could be found. There was a build-up of fluid in the abdominal cavity, which proved to be urine originating from an iatrogenic rupture of the bladder. Serum levels normalised following repair of the rupture. If serum creatinine levels rise rapidly following abdominal surgery or blunt abdominal trauma the bladder should be examined for possible perforation, particularly if the abdominal dimension increases. A ruptured bladder leading to pseudorenal failure is an indication for rapid surgical intervention.

Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria.

PubMed

Hudson, M A; Ritchey, J K; Catalona, W J; Brown, E J; Ratliff, T L

1990-07-01

Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P less than 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P less than 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P less than 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG.

Current management of overactive bladder.

PubMed

Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

2008-10-01

The concept of overactive bladder has helped us address the problem of urgency and urge incontinence from a symptomatic perspective. In this review, we provide a critical summary of clinically relevant recent publications, focusing in particular on advances in our understanding of assessment methods and therapeutic interventions for overactive bladder in women. According to current definitions, the prevalence of overactive bladder in western nations is now estimated as 13.0%. Although the prevalence increases with age, the symptoms of overactive bladder may follow a relapsing and remitting course. There has been a proliferation of validated symptom and quality of life measures and increasing sophistication in the analysis of bladder diaries. The role of urodynamics in the evaluation of urgency remains uncertain, with many trials showing limited benefit as a preoperative investigation. Fluid restriction and bladder retraining remain important first-line interventions. Many new anticholinergic medications have been licensed, with limited benefits compared with existing preparations. Intravesical botulinum toxin has become a popular alternative for patients who fail oral therapies. Although there have been few important therapeutic innovations, recent publications have led to greater sophistication in assessment methods and a clearer understanding of the role of existing interventions.

Occupational Bladder Cancer in a 4,4′-Methylenebis(2-chloroaniline) (MBOCA)-Exposed Worker

PubMed Central

Liu, Chiu-Shong; Liou, Saou-Hsing; Loh, Ching-Hui; Yu, Yi-Chun; Uang, Shi-Nian; Shih, Tung-Sheng; Chen, Hong-I

2005-01-01

A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria about five times per night for 2 months. He was a nonsmoker and denied a history of any other bladder carcinogen exposure except for occasional pesticide application during agricultural work. Intravenous urogram imaging showed a mass occupying half of the bladder capacity. Cystoscopy revealed a mass over the left dome of the bladder. Cystoscopic biopsy revealed a grade 3 invasive transitional cell carcinoma with marked necrosis. From 1987 until hospital admission in 2001, the patient had worked in a company that produced the 4,4′-methylenebis(2-chloroaniline) (MBOCA) curing agent. He did not wear any personal protective equipment during work. Ambient air MBOCA levels in the purification process area (0.23–0.41 mg/m3) exceeded the U.S. Occupational Safety and Health Administration’s permissible exposure level. Urinary MBOCA levels (267.9–15701.1 μg/g creatinine) far exceeded the California Occupational Safety and Health Administration’s reference value of 100 μg/L. This patient worked in the purification process with occupational exposure to MBOCA for 14 years. According to the environmental and biologic monitoring data and latency period, and excluding other potential bladder carcinogen exposure, this worker was diagnosed as having occupational bladder cancer due to high exposure to MBOCA through inhalation or dermal absorption in the purification area. This case finding supports that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent workers from MBOCA exposure. PMID:15929884

OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.

PubMed

Collins, Valerie M; Daly, Donna M; Liaskos, Marina; McKay, Neil G; Sellers, Donna; Chapple, Christopher; Grundy, David

2013-11-01

To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium. Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve activity was analysed to classify the single afferent units responding to physiological (low-threshold [LT] afferent <15 mmHg) and supra-physiological (high-threshold [HT] afferent >15 mmHg) distension pressures. Bladder distension evoked reproducible pressure-dependent increases in afferent nerve firing. After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated. OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release. These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves. © 2013 The Authors. BJU International © 2013 BJU International.

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels

PubMed Central

Malysz, John; Afeli, Serge A. Y.; Provence, Aaron

2013-01-01

Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca2+-activated K+ (BK) channels or L-type voltage-dependent Ca2+ channels (VDCCs), major regulators of DSM excitability and contractility, are targets for EtOH by patch-clamp electrophysiology (conventional and perforated whole cell and excised patch single channel) and isometric tension recordings using guinea pig DSM cells and isolated tissue strips, respectively. EtOH at 0.3% vol/vol (∼50 mM) enhanced whole cell BK currents at +30 mV and above, determined by the selective BK channel blocker paxilline. In excised patches recorded at +40 mV and ∼300 nM intracellular Ca2+ concentration ([Ca2+]), EtOH (0.1–0.3%) affected single BK channels (mean conductance ∼210 pS and blocked by paxilline) by increasing the open channel probability, number of open channel events, and open dwell-time constants. The amplitude of single BK channel currents and unitary conductance were not altered by EtOH. Conversely, at ∼10 μM but not ∼2 μM intracellular [Ca2+], EtOH (0.3%) decreased the single BK channel activity. EtOH (0.3%) affected transient BK currents (TBKCs) by either increasing frequency or decreasing amplitude, depending on the basal level of TBKC frequency. In isolated DSM strips, EtOH (0.1–1%) reduced the amplitude and muscle force of spontaneous phasic contractions. The EtOH-induced DSM relaxation, except at 1%, was attenuated by paxilline. EtOH (1%) inhibited L-type VDCC currents in DSM cells. In summary, we reveal the involvement of BK channels and L-type VDCCs in mediating EtOH-induced urinary bladder relaxation accommodating alcohol-induced diuresis. PMID:24153429

Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Majewski, Wojciech, E-mail: wmajewski1@poczta.onet.p; Wesolowska, Iwona; Urbanczyk, Hubert

2009-12-01

Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanningmore » during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to <95% of the prescribed dose. The dose distribution in the rectum and intestines was better with a 'partially empty' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm{sup 3} for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm{sup 3} for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder filling during RT could influence the dose distribution in the bladder and intestines. The dose distribution in the rectum and bowel was slightly better with a 'partially empty' than with a 'full' bladder.« less

Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

NASA Astrophysics Data System (ADS)

Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

2016-10-01

Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Malley, Susan E; Vizzard, Margaret A

2011-02-01

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency, and results in increased referred somatic hypersensitivity. Additional NGF-mediated pleiotropic changes might contribute to the increased voiding frequency and pelvic hypersensitivity observed in these transgenic mice, such as modulation of other growth factor/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific uroplakin II promoter. In the present study, we examined NGF, brain-derived neurotrophic factor (BDNF), and associated receptor [p75(NTR), tyrosine kinase (Trk)A, TrkB] transcript and protein expression in urothelium and detrusor smooth muscle of NGF-overexpressing (OE) and littermate wild-type mice, using real-time quantitative reverse transcription-polymerase chain reaction, ELISAs, and semiquantitation of immunohistochemistry. We focused on these growth factor/receptors given the established roles of NGF/TrkA, NGF/p75(NTR), and BDNF/TrkB systems in bladder function. Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA, and TrkB protein expression was significantly (P ≤ 0.01) reduced and p75(NTR) protein expression was significantly (P ≤ 0.01) increased in urinary bladder of NGF-OE mice. The NGF-OE-induced changes in neurotrophic factor/receptor expression in urinary bladder may represent compensatory changes to reduce voiding frequency in the NGF-OE mouse.

A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells.

PubMed

Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

2015-10-13

Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect.

A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells

PubMed Central

Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

2015-01-01

Reactive oxygen species (ROS) and cellular oxidant stress are regulators of cancer cells. The alteration of redox status, which is induced by increased generation of ROS, results in increased vulnerability to oxidative stress. The aim of this study is to investigate the influence of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, C13H16N6O8) on proliferation and apoptosis in bladder cancer cells and explored possible ROS-related mechanisms. Our results indicated that JS-K could suppress bladder cancer cell proliferation in a concentration- and time-dependent manner and induce apoptosis and ROS accumulation in a concentration-dependent manner. With increasing concentrations of JS-K, expression of proteins that are involved in cell apoptosis increased in a concentration-dependent manner. Additionally, the antioxidant N-acetylcysteine (NAC) reversed JS-K-induced cell apoptosis; conversely, the prooxidant oxidized glutathione (GSSG) exacerbated JS-K-induced cell apoptosis. Furthermore, we found that nitrites, which were generated from the oxidation of JS-K-released NO, induced apoptosis in bladder cancer cells to a lower extent through the ROS-related pathway. In addition, JS-K was shown to enhance the chemo-sensitivity of doxorubicin in bladder cancer cells. Taken together, the data suggest that JS-K-released NO induces bladder cancer cell apoptosis by increasing ROS levels, and nitrites resulting from oxidation of NO have a continuous apoptosis-inducing effect. PMID:26458509

The concept of peripheral modulation of bladder sensation

PubMed Central

Eastham, Jane E; Gillespie, James I

2013-01-01

It is recognized that, as the bladder fills, there is a corresponding increase in sensation. This awareness of the volume in the bladder is then used in a complex decision making process to determine if there is a need to void. It is also part of everyday experience that, when the bladder is full and sensations strong, these sensations can be suppressed and the desire to void postponed. The obvious explanation for such altered perceptions is that they occur centrally. However, this may not be the only mechanism. There are data to suggest that descending neural influences and local factors might regulate the sensitivity of the systems within the bladder wall generating afferent activity. Specifically, evidence is accumulating to suggest that the motor-sensory system within the bladder wall is influenced in this way. The motor-sensory system, first described over 100 years ago, appears to be a key component in the afferent outflow, the afferent “noise,” generated within the bladder wall. However, the presence and possible importance of this complex system in the generation of bladder sensation has been overlooked in recent years. As the bladder fills the motor activity increases, driven by cholinergic inputs and modulated, possibly, by sympathetic inputs. In this way information on bladder volume can be transmitted to the CNS. It can be argued that the ability to alter the sensitivity of the mechanisms generating the motor component of this motor-sensory system represents a possible indirect way to influence afferent activity and so the perception of bladder volume centrally. Furthermore, it is emerging that the apparent modulation of sensation by drugs to alleviate the symptoms of overactive bladder (OAB), the anti-cholinergics and the new generation of drugs the β3 sympathomimetics, may be the result of their ability to modulate the motor component of the motor sensory system. The possibility of controlling sensation, physiologically and pharmacologically, by influencing afferent firing at its point of origin is a “new” concept in bladder physiology. It is one that deserves careful consideration as it might have wider implications for our understanding of bladder pathology and in the development of new therapeutic drugs. In this overview, evidence for the concept peripheral modulation of bladder afferent outflow is explored. PMID:23917648

Non-alcoholic beverages and risk of bladder cancer in Uruguay

PubMed Central

De Stefani, Eduardo; Boffetta, Paolo; Deneo-Pellegrini, Hugo; Correa, Pelayo; Ronco, Alvaro L; Brennan, Paul; Ferro, Gilles; Acosta, Giselle; Mendilaharsu, María

2007-01-01

Background Bladder cancer is the fourth most frequent malignancy among Uruguayan men. A previous study from Uruguay suggested a high risk of bladder cancer associated with maté drinking. We conducted an additional case-control study in order to further explore the role of non-alcoholic beverages in bladder carcinogenesis. Methods In the time period 1996–2000, 255 incident cases with transitional cell carcinoma of the bladder and 501 patients treated in the same hospitals and in the same time period were frequency matched on age, sex, and residence. Both cases and controls were face-to-face interviewed on occupation, tobacco smoking, alcohol drinking and intake of maté, coffee, tea, and soft drinks. Statistical analysis was carried out by unconditional multiple logistic regression. Results Ever maté drinking was positively associated with bladder cancer (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2–3.9) and the risk increased for increasing duration and amount of maté drinking. Both coffee and tea were strongly associated with bladder cancer risk (OR for coffee drinking 1.6, 95% CI 1.2–2.3; OR for tea drinking 2.3, 95% CI 1.5–3.4). These results were confirmed in a separate analysis of never-smokers. Conclusion Our results suggest that drinking of maté, coffee and tea may be risk factors for bladder carcinoma in Uruguay. PMID:17394632

CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jiajia; Zhu, Xi; Zhang, Jie, E-mail: zhangjiebjmu@163.com

2014-03-28

Highlights: • We first demonstrated CXCL5 is highly expressed in human bladder tumor tissues and cells. • CXCL5 knockdown inhibits proliferation, migration and promotes apoptosis in T24 cells. • CXCL5 knockdown inhibits Snail, PI3K-AKT and ERK1/2 signaling pathways in T24 cells. • CXCL5 is critical for bladder tumor growth and progression. - Abstract: CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCRmore » and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.« less

MicroRNA-137 Upregulation Increases Bladder Cancer Cell Proliferation and Invasion by Targeting PAQR3

PubMed Central

Xia, Shunyao; Jin, Chengjun; Yin, Huaifu; Zhao, Weiming; Wu, Qiong

2014-01-01

There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3′-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer. PMID:25330156

Development of upper tract stones in patients with congenital neurogenic bladder.

PubMed

Stephany, Heidi A; Clayton, Douglass B; Tanaka, Stacy T; Thomas, John C; Pope, John C; Brock, John W; Adams, Mark C

2014-02-01

Patients with neurogenic bladder are at increased risk of developing upper tract stones. We hypothesized that patients with lower urinary tract stone disease are at greater risk of developing upper tract stones. We performed a 10-year retrospective case-control study of patients with neurogenic bladder to determine the association between bladder and upper tract stones. Independent risk factors for upper tract stones were assessed. Cases and controls were matched 1:1. Univariable analysis was performed by Fisher's exact test and the Mann-Whitney U test. Multivariable logistic regression was performed. 52 cases and controls were identified. Cases were significantly more likely to be non-ambulatory, have bowel-urinary tract interposition, thoracic level dysraphism, and history of bladder stones. On multivariable analysis, independent predictors of stone formation were male sex (OR 2.82; p = 0.02), dysraphism involving the thoracic spine (OR 3.37; p = 0.014) bowel-urinary tract interposition (OR 2.611; p = 0.038), and a history of bladder stones (OR 3.57; p = 0.015). Patients with neurogenic bladder are at increased risk for upper tract stones. The presence of bladder stones may herald the development of upper tract stones. The predictors of stone disease identified should guide prospective studies to better understand the natural history of upper tract stone development in this population. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Expression and diagnosis of transient receptor potential vanilloid1 in urothelium of patients with overactive bladder.

PubMed

Zhang, H Y; Chu, J F; Li, P; Li, N; Lv, Z H

2015-01-01

This study was carried out to test expression of transient receptor potential vanilloid1 (TRPV1) in urothelium of female patients with overactive bladder (OAB) and explore clinical significance of TRPV1 in diagnosing female OAB. TRPV1 expression in urothelium of female OAB patients (n=21) and healthy females (n=9) was detected using Strept Avidin-Biotin Complex (SABC), an immunohistochemical method and image analysis system. Relative content of TRPV1 was expressed by average optical density (AOD) and was analyzed through data of urodynamics. Compared to TRPV1 expression in urothelium of healthy females (AOD 0.3658 ± 0.1009), TRPV1 expression in OAB patients was much higher (AOD 0.4834 ± 0.1252) and the difference was significant P less than 0.05. Observation and comparison in clinic of urodynamic parameters of female patients and healthy females revealed that the former had lower indexes with remarkable differences (P less than 0.05) such as Qmax, first desire volume (FDV), strong desire volume (SDV), maximum cyst capacity (MCC) and bladder compliance (BC). Thus high expression of TRPV1 in urothelium of female OAB patients is closely correlated to OAB occurrence, showing great importance of improved bladder sensitivity in female OAB occurrence mechanism.

Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

PubMed

Averbeck, Marcio A; De Lima, Nelson G; Motta, Gabriela A; Beltrao, Lauro F; Abboud Filho, Nury J; Rigotti, Clarice P; Dos Santos, William N; Dos Santos, Steven K J; Da Silva, Luis F B; Rhoden, Ernani L

2018-03-01

To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery. From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics. Bladder biopsies were obtained during open prostatectomy for determination of collagen content (sirius red-picric acid stain; polarized light analysis). Collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with preoperative parameters was investigated. The level of significance was P < 0.05. Thirty-eight consecutive patients were included in this pilot study. Mean age was 66.36 ± 6.44 years and mean IPSS was 11.05 ± 8.72 points. Men diagnosed with diabetes mellitus (DM2) were found to have higher collagen content in the bladder wall when compared to non-diabetic patients (17.71 ± 6.82% vs 12.46 ± 5.2%, respectively; P = 0.024). Reduced bladder compliance was also marker for higher collagen content (P = 0.042). Bladder outlet obstruction (BOO) was not a predictor of increased collagen deposition in the bladder wall (P = 0.75). Patients with PVR ≥ 200 mL showed a higher collagen to smooth muscle ratio in the bladder wall (P = 0.036). DM2 and urodynamic parameters, such as increased PVR and reduced bladder compliance, were associated with higher collagen content in the bladder wall of men with LUTS. © 2017 Wiley Periodicals, Inc.

The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

PubMed

Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

2017-08-01

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

Sex-dependent expression of TRPV1 in bladder arterioles

PubMed Central

Phan, Thieu X.; Ton, Hoai T.; Chen, Yue; Basha, Maureen E.

2016-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1PLAP-nlacZ) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15–40 μm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca2+ in ∼15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions. PMID:27654891

Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant

PubMed Central

Carreón, Tania; Hein, Misty J; Hanley, Kevin W; Viet, Susan M; Ruder, Avima M

2015-01-01

Background An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation. Methods Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking. Results Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence. Conclusions Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits. PMID:24368697

Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PubMed

Smith, Norm D; Prasad, Sandip M; Patel, Amit R; Weiner, Adam B; Pariser, Joseph J; Razmaria, Aria; Maene, Chieko; Schuble, Todd; Pierce, Brandon; Steinberg, Gary D

2016-02-01

We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

HOW DOES ADDING AND REMOVING LIQUID FROM SOCKET BLADDERS AFFECT RESIDUAL LIMB FLUID VOLUME?

PubMed Central

Sanders, JE; Cagle, JC; Harrison, DS; Myers, TR; Allyn, KJ

2015-01-01

Adding and removing liquid from socket bladders is a means for people with limb loss to accommodate residual limb volume change. Nineteen people with trans-tibial amputation using their regular prosthetic socket fitted with fluid bladders on the inside socket surface underwent cycles of bladder liquid addition and removal. In each cycle, subjects sat, stood, and walked for 90s with bladder liquid added and then sat, stood, and walking for 90s again with the bladder liquid removed. The amount of bladder liquid added was increased in each cycle. Bioimpedance analysis was implemented to measure residual limb fluid volume. Results showed that the preferred bladder liquid volume was 16.8 mL (s.d.8.4), corresponding to 1.7% (s.d.0.8%) of the average socket volume between the bioimpedance voltage-sensing electrodes. Limb fluid volume driven out of the residual limb when bladder liquid was added was typically not recovered upon subsequent bladder liquid removal. Fifteen of nineteen subjects experienced a gradual limb fluid volume loss over the test session. Care should be taken when implementing adjustable socket technologies in people with limb amputation. Reducing socket volume may accentuate limb fluid volume loss. PMID:24203546

Effects of increased Kindlin-2 expression in bladder cancer stromal fibroblasts.

PubMed

Wu, Jitao; Yu, Cuicui; Cai, Li; Lu, Youyi; Jiang, Lei; Liu, Chu; Li, Yongwei; Feng, Fan; Gao, Zhenli; Zhu, Zhe; Yu, Shengqiang; Yuan, Hejia; Cui, Yuanshan

2017-08-01

Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression ( p < 0.01). Multivariate analysis revealed that high Kindlin-2 expression leads to poor prognosis in bladder cancer. Using cancer-associated fibroblasts (CAFs) isolated from human bladder cancer tissue, we observed that Kindlin-2 knockdown decreased CAFs activation, resulting in decreased expression of α-smooth muscle actin (α-SMA) and the extracellular matrix protein fibronectin. Kindlin-2 suppression also reduced CAF-induced bladder cancer cell migration and invasion. Moreover, we found that Kindlin-2 activates CAFs and promotes the invasiveness of bladder cancer cells by stimulating TGF-β-induced epithelial-mesenchymal transition. These results support targeting Kindlin-2 and the corresponding activated CAFs in bladder cancer therapy.

[Nitric oxide pathway and female lower urinary tract. Physiological and pathophysiological role].

PubMed

Gamé, X; Rischmann, P; Arnal, J-F; Malavaud, B

2013-09-01

The aim was to review the literature on nitric oxide and female lower urinary tract. A literature review through the PubMed library until December, 31 2012 was carried out using the following keywords: lower urinary tract, bladder, urethra, nervous central system, innervation, female, women, nitric oxide, phosphodiesterase, bladder outlet obstruction, urinary incontinence, overactive bladder, urinary tract infection. Two nitric oxide synthase isoforms, the neuronal (nNOS) and the endothelial (eNOS), are constitutively expressed in the lower urinary tract. Nevertheless, nNOS is mainly expressed in the bladder neck and the urethra. In the bladder, NO modulates the afferent neurons activity. In pathological condition, inducible NOS expression induces an increase in detrusor contractility and bladder wall thickness and eNOS facilitates Escherichia coli bladder wall invasion inducing recurrent urinary tract infections. In the urethra, NO play a major role in smooth muscle cells relaxation. The NO pathway plays a major role in the female lower urinary tract physiology and physiopathology. While it acts mainly on bladder outlet, in pathological condition, it is involved in bladder dysfunction occurrence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Bladder volume-dependent excitatory and inhibitory influence of lumbosacral dorsal and ventral roots on bladder activity in rats

PubMed Central

Sugaya, Kimio; de Groat, William C.

2011-01-01

This study was undertaken to examine the role of the afferent and efferent pathways of the lumbosacral spinal nerve roots in the tonic control of bladder activity. Changes of isovolumetric bladder activity were recorded in 21 sympathectomized female rats under urethane anesthesia following transection of the dorsal (DRT) and ventral (VRT) lumbosacral spinal roots, and after intraperitoneal administration of hexamethonium. DRT altered the baseline intravesical pressure in a bladder volume-dependent manner in each animal. The percent change of baseline pressure after VRT following DRT was also dependent upon bladder volume. The percent change of baseline pressure after VRT alone was similarly dependent on bladder volume, but not after VRT followed by DRT. The percent change of baseline intravesical pressure (y)(−9 to +8 cm H2O, −56 to +46%) after DRT and VRT depended upon bladder volume (x)(y = 44.7 x −40.4) in all rats. Hexamethonium increased the amplitude of small myogenic bladder contractions after DRT and VRT. In conclusion, the bladder is tonically excited or inhibited by a local reflex pathway and by a parasympathetic reflex pathway that depends on connections with the lumbosacral spinal cord and the pelvic nerves. Both reflex mechanisms are influenced by bladder volume. PMID:17878597

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-12-01

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Manipulating the extracellular matrix: an animal model of the bladder pain syndrome.

PubMed

Offiah, Ifeoma; Didangelos, Athanasios; OʼReilly, Barry A; McMahon, Stephen B

2017-01-01

Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.

Implantable Bladder Sensors: A Methodological Review

PubMed Central

Dakurah, Mathias Naangmenkpeong; Koo, Chiwan; Choi, Wonseok; Joung, Yeun-Ho

2015-01-01

The loss of urinary bladder control/sensation, also known as urinary incontinence (UI), is a common clinical problem in autistic children, diabetics, and the elderly. UI not only causes discomfort for patients but may also lead to kidney failure, infections, and even death. The increase of bladder urine volume/pressure above normal ranges without sensation of UI patients necessitates the need for bladder sensors. Currently, a catheter-based sensor is introduced directly through the urethra into the bladder to measure pressure variations. Unfortunately, this method is inaccurate because measurement is affected by disturbances in catheter lines as well as delays in response time owing to the inertia of urine inside the bladder. Moreover, this technique can cause infection during prolonged use; hence, it is only suitable for short-term measurement. Development of discrete wireless implantable sensors to measure bladder volume/pressure would allow for long-term monitoring within the bladder, while maintaining the patient’s quality of life. With the recent advances in microfabrication, the size of implantable bladder sensors has been significantly reduced. However, microfabricated sensors face hostility from the bladder environment and require surgical intervention for implantation inside the bladder. Here, we explore the various types of implantable bladder sensors and current efforts to solve issues like hermeticity, biocompatibility, drift, telemetry, power, and compatibility issues with popular imaging tools such as computed tomography and magnetic resonance imaging. We also discuss some possible improvements/emerging trends in the design of an implantable bladder sensor. PMID:26620894

Bacillus Calmette-Guérin enhances production and secretion of type IV collagenases in peripheral blood mononuclear cells.

PubMed

Kageyama, Y; Kawakami, S; Fujii, Y; Kihara, K; Oshima, H

1997-03-01

Intravesical administration of bacillus Calmette-Guérin (BCG) is an effective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whether BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Production and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography, western blot analysis, and northern blot analysis. Invasion of bladder cancer cells was also examined using reconstituted basement membrane (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the production and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PBMCs may account in part for the effect.

Bladder cancer and occupation: a case-control study in northern Italy.

PubMed Central

Porru, S; Aulenti, V; Donato, F; Boffetta, P; Fazioli, R; Cosciani Cunico, S; Alessio, L

1996-01-01

OBJECTIVES--A hospital based case-control study was conducted between 1992 and 1993 in the province of Brescia, a highly industrialised area in northern Italy, to evaluate occupational risk factors of bladder cancer. METHODS--The study evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80 women) and 579 controls affected by urological non-neoplastic diseases (397 men, 182 women). Lifetime occupational history, smoking and drinking habits, and sociodemographic characteristics were recorded by means of a structured questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking, alcohol and coffee consumption, education, and place of residence. RESULTS--A significant (P < 0.05) increase of risk of bladder cancer were found in men for labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI) 1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9). Increased risks, although not significant, were found for various other occupations and industries such as machinery mechanics, metal processers and polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased risk with increasing duration of employment was found. CONCLUSIONS--Occupational exposures seem to contribute to bladder cancer risk in the area under study. PMID:8563860

Association Between N-acetyltransferase 2 Polymorphism and Bladder Cancer Risk: Results From Studies of the Past Decade and a Meta-Analysis.

PubMed

Wu, Haoran; Wang, Xugang; Zhang, Liang; Mo, Naixin; Lv, Zhong

2016-04-01

Numerous studies have identified that the slow acetylation status of N-acetyltransferase 2 (NAT2) is associated with an elevated bladder cancer risk. However, the results remain inconclusive. The aim of our study was to evaluate the effect of NAT2 acetylation status in patients with bladder cancer. Electronic databases were searched to retrieve related studies published in the past decade. The pooled odds ratio (OR) with its 95% confidence interval (CI) was used to calculate the strength of this relationship. Overall, a total of 18 studies were selected for the analysis, which included 4473 bladder cancer cases and 7204 matched controls. Our result showed that the NAT2 slow acetylation phenotypes were significantly associated with an increased risk of bladder cancer compared with the rapid phenotypes (OR, 1.56; 95% CI, 1.33-1.82; P < .00001) in a random-effect model. This significant association was also found in a subgroup analysis of ethnicity (P < .05). Furthermore, the NAT2 slow phenotypes also significantly increased the risk of bladder cancer in smokers (OR, 0.75; 95% CI, 0.62-0.90; P = .002). However, no correlation was found between the combined effect of NAT2 slow phenotypes and gender with bladder cancer risk (OR, 0.89; 95% CI, 0.28-2.78; P = .84). In conclusion, our results suggest that the NAT2 slow acetylator, in particular, the NAT2 slow acetylator combined with smoking, are associated with an increased bladder cancer risk. Future well-designed studies with large populations and more ethnicities are needed to clarify this association further. Copyright © 2016 Elsevier Inc. All rights reserved.

Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Ning; Thanan, Raynoo; Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie

Highlights: {yields} Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. {yields} iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. {yields} 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. {yields} Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-{kappa}B (NF-{kappa}B) and induciblemore » nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-{kappa}B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-{kappa}B activation, leading to tumor development.« less

Functional and molecular characterization of kinin B1 and B 2 receptors in human bladder cancer: implication of the PI3Kγ pathway.

PubMed

Sgnaolin, V; Pereira, T C B; Bogo, M R; Zanin, R; Battastini, A M O; Morrone, F B; Campos, M M

2013-08-01

Kinins and their receptors have been recently implicated in cancer. Using functional and molecular approaches, we investigated the relevance of kinin B1 and B2 receptors in bladder cancer. Functional studies were conducted using bladder cancer cell lines, and human biopsies were employed for molecular studies. Both B1 des-Arg(9)-BK and B2 BK receptor agonists stimulated the proliferation of grade 3-derived T24 bladder cancer cells. Furthermore, treatment with B1 and B2 receptor antagonists (SSR240612 and HOE140) markedly inhibited the proliferation of T24 cells. Only higher concentrations of BK increased the proliferation of the grade 1 bladder cancer cell line RT4, while des-Arg(9)-BK completely failed to induce its proliferation. Real-time PCR revealed that the mRNA expression of kinin receptors, particularly B1 receptors, was increased in T24 cells relative to RT4 cells. Data from bladder cancer human biopsies revealed that B1 receptor expression was increased in all tumor samples and under conditions of chronic inflammation. We also show novel evidence demonstrating that the pharmacological inhibition of PI3Kγ (phosphatidylinositol 3-kinase) with AS252424, concentration-dependently reduced T24 cell proliferation induced by BK or des-Arg(9)-BK. Finally, the incubation of T24 cells with kinin agonists led to a marked activation of the PI3K/AKT and ERK 1/2 signaling pathways, whereas p38 MAP kinase remained unaffected. Kinin receptors, especially B1 receptors, appear to be implicated in bladder cancer progression. It is tempting to suggest that selective kinin antagonists might represent potential alternative therapies for bladder cancer.

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence.

PubMed

Saint-Jacques, Nathalie; Parker, Louise; Brown, Patrick; Dummer, Trevor Jb

2014-06-02

Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2-4.1]; 4.2 [2.1-6.3] and; 5.8 [2.9-8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35-4.0], 2.3 [0.59-6.4], and 3.1 [0.80-8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial.

Immediate postoperative complications of combined penetrating rectal and bladder injuries.

PubMed

Crispen, Paul L; Kansas, Bryan T; Pieri, Paola G; Fisher, Carol; Gaughan, John P; Pathak, Abhijit S; Mydlo, Jack H; Goldberg, Amy J

2007-02-01

Combined penetrating trauma involving the rectum and bladder has been associated with increased postoperative morbidity. Specific complications resulting from these injuries include colovesical fistula, urinoma, and abscess formation. A retrospective review of Temple University Hospital trauma database was performed. Patients were categorized by having an isolated rectal (n = 29), isolated bladder (n = 16), or combined injury (n = 24). Records were reviewed for sex, age, site of injury, location of rectal and bladder injuries, operative intervention, fistula formation, urinoma formation, abscess formation, time to urinary catheter removal, length of intensive care unit stay, and length of hospital stay. Patient sex and age did not differ significantly between groups, nor was there a significant difference in location of rectal injury between groups. Presacral drainage was utilized in all patients with extraperitoneal injuries. Fecal diversion was performed in all patients, except two with intraperitoneal rectal injuries. Omental flap interposition between rectal and bladder injuries was utilized in one patient. No significant difference was noted in immediate postoperative complications between groups including fistula, urinoma, and abscess formation. However, all cases of colovesical fistula (n = 2) and urinoma (n = 2) formation were noted in those patients with rectal and posterior bladder injuries. Combined rectal and bladder injuries were not associated with an increase in immediate postoperative complications compared with isolated rectal and bladder injuries. However, postoperative fistula and urinoma formation occurred only in patients with a combined rectal and posterior bladder injury. Consequently, these patients may benefit from omental flap interposition between injuries to decrease fistula and urinoma formation.

Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

PubMed

Liss, Michael A; White, Martha; Natarajan, Loki; Parsons, J Kellogg

2017-06-01

The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as "did no exercise" vs. "light, moderate, or vigorous exercise in ≥ 10-minute bouts"), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than "no exercise". Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. Published by Elsevier Inc.

Trends in the survival of patients diagnosed with kidney or urinary bladder cancer in the Nordic countries 1964-2003 followed up to the end of 2006.

PubMed

Engholm, Gerda; Hakulinen, Timo; Gislum, Mette; Tryggvadóttir, Laufey; Klint, Asa; Bray, Freddie; Storm, Hans H

2010-06-01

Previous studies have shown systematic differences between the Nordic Countries in population-based relative survival following a kidney or urinary bladder cancer diagnosis. Comparison of bladder cancer over time and between Nordic registries is complicated by variable coding practices with respect to the inclusion of in situ cases with invasive tumours. Five-year relative survival of patients with urinary cancer diagnosed in the Nordic countries 1964-2003 and followed up for death through 2006 was studied and contrasted with developments in incidence and mortality. The survival following bladder cancer was higher than for kidney cancer and highest for men. Survival increased over the years in all countries, more for kidney cancer than bladder cancer. For Danish kidney cancer patients, the rate of increase over all the years has been lower than in the other countries, especially among women, resulting in a survival in Denmark some 10-20% points lower than elsewhere in 1999-2003. Danish bladder cancer patient survival was in the last period 4% points lower among men and 10% points lower among women than in the other Nordic countries. The differences were mainly found in the first year following diagnosis, where a higher excess mortality in Denmark was observed. Survival decreased with higher age at diagnosis. The increasing 5-year relative survival in all the Nordic countries for both kidney and bladder cancer are promising, but for kidney cancer a higher percentage detected coincidentally during an imaging investigation for other diseases could play a role. Denmark had the lowest survival, despite their known practice of including benign conditions with invasive bladder cancers. The lower Danish survival after kidney and bladder cancer in the first year after diagnosis could be due to later diagnosis on average, a higher co-morbidity from smoking-related diseases, and perhaps, less adequate cancer treatment and management in Denmark.

Aging and recurrent urinary tract infections are associated with bladder dysfunction in type 2 diabetes.

PubMed

Lin, Tzu-Li; Chen, Gin-Den; Chen, Yi-Ching; Huang, Chien-Ning; Ng, Soo-Cheen

2012-09-01

The objective of this study was to demonstrate the diversity of urodynamic findings and temporal effects on bladder dysfunction in diabetes as well as to evaluate the predisposing factors that attenuate the storage and voiding function of diabetic women. In this prospective study, 181 women with type 2 diabetes mellitus (DM) and lower urinary tract dysfunction underwent complete urogynecological evaluations and urodynamic studies. The patients' histories of DM and the treatment agents used were documented from chart records and interviews. The urodynamic diagnoses were recategorized into two groups for comparison, namely overactive detrusor (detrusor overactivity and/or increased bladder sensation as well as mixed incontinence) and voiding dysfunction (detrusor hyperactivity with insufficient contractility and detrusor underactivity with poor voiding efficiency) in order to evaluate the temporal effect of DM on diabetic bladder dysfunction. The development of bladder dysfunction showed a trend involving time-dependent progression, beginning with storage problems (i.e. advancing from urodynamic stress incontinence to detrusor overactivity and/or increased bladder sensation) and eventually led to impaired voiding function. The duration of DM relative to the urodynamic diagnoses of these women was longer in women with voiding dysfunction (6.8 ± 2.8 years with urodynamic stress incontinence, 7.3 ± 6.5 years with detrusor overactivity and/or increased bladder sensation, and 10.4 ± 8.3 years with women with voiding dysfunction). Notwithstanding these findings, stepwise logistic regression analysis indicated that age and recurrent urinary tract infections were the two independent factors associated with developing voiding dysfunction. The urodynamic study revealed a temporal effect on bladder function, and women with diabetic voiding dysfunction were found to have had a longer duration of DM than women with an overactive detrusor. However, aging and recurrent urinary tract infections are the two independent factors that contribute to impaired voiding function and diabetic bladder dysfunction. Copyright © 2012. Published by Elsevier B.V.

Maximum Neutral Buoyancy Depth of Juvenile Chinook Salmon: Implications for Survival during Hydroturbine Passage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pflugrath, Brett D.; Brown, Richard S.; Carlson, Thomas J.

This study investigated the maximum depth at which juvenile Chinook salmon Oncorhynchus tshawytscha can acclimate by attaining neutral buoyancy. Depth of neutral buoyancy is dependent upon the volume of gas within the swim bladder, which greatly influences the occurrence of injuries to fish passing through hydroturbines. We used two methods to obtain maximum swim bladder volumes that were transformed into depth estimations - the increased excess mass test (IEMT) and the swim bladder rupture test (SBRT). In the IEMT, weights were surgically added to the fishes exterior, requiring the fish to increase swim bladder volume in order to remain neutrallymore » buoyant. SBRT entailed removing and artificially increasing swim bladder volume through decompression. From these tests, we estimate the maximum acclimation depth for juvenile Chinook salmon is a median of 6.7m (range = 4.6-11.6 m). These findings have important implications to survival estimates, studies using tags, hydropower operations, and survival of juvenile salmon that pass through large Kaplan turbines typical of those found within the Columbia and Snake River hydropower system.« less

Evaluation of oxidative stress status and antioxidant capacity in patients with painful bladder syndrome/interstitial cystitis: preliminary results of a randomised study.

PubMed

Ener, Kemal; Keske, Murat; Aldemir, Mustafa; Özcan, Muhammet Fuat; Okulu, Emrah; Özayar, Asım; Ergin, Merve; Doluoğlu, Ömer Gökhan; Çakmak, Serdar; Erel, Özcan

2015-08-01

This study aimed to investigate oxidative stress in etiopathogenesis by analyzing serum total antioxidant capacity (TAC), total oxidant status (TOS), binding capacity of exogenous cobalt to human albumin (IMA), serum advanced oxidation protein products (AOPP), paraoxonase (PON), arylesterase, IgE, and C-reactive protein (CRP) in bladder pain syndrome/interstitial cystitis (BPS/IC). The study included 16 female patients diagnosed with BPS/IC and 25 healthy female subjects forming the control group. A bladder biopsy was performed on all patients in the BPS/IC group by carrying out cystoscopy with hydrodistention under general anesthesia. The results of serum TAC, TOS, IMA, AOPP, PON, arylesterase, IgE, and CRP of the subjects in both groups were compared. The mean age of the 16 female patients in the BPS/IC group was 43.6 ± 14.5 years, and the mean age of the 25 healthy subjects in the control group was 42.0 ± 10.3 years. According to the criteria of International Society for the Study of Interstitial Cystitis (ESSIC), eight patients were classified as Type 2A, three patients as Type 2B, four patients as Type 2C, and one patient as Type 3C. In the BPS/IC group, while TAC was found significantly lower than in the control group, IMA, IgE, and CRP were found significantly higher (P < 0.05). When binary logistic regression analysis was performed, the created model was determined to have 81.3 % sensitivity and 80 % specifity. In the etiology of BPS/IC, mechanism of oxidative damage comes into prominence. In the diagnosis of BPS/IC, IgE, CRP, and TAC are not specific markers when used separately; however, a higher specifity and sensitivity could be reached when used jointly in the suspected patients.

Comparison of cost determination of both resource consumption accounting and time-driven activity-based costing systems in a healthcare setting.

PubMed

Özyapıcı, Hasan; Tanış, Veyis Naci

2017-05-01

Objective The aim of the present study was to explore the differences between resource consumption accounting (RCA) and time-driven activity-based costing (TDABC) systems in determining the costs of services of a healthcare setting. Methods A case study was conducted to calculate the unit costs of open and laparoscopic gall bladder surgeries using TDABC and RCA. Results The RCA system assigns a higher cost both to open and laparoscopic gall bladder surgeries than TDABC. The total cost of unused capacity under the TDABC system is also double that in RCA. Conclusion Unlike TDABC, RCA calculates lower costs for unused capacities but higher costs for products or services in a healthcare setting in which fixed costs make up a high proportion of total costs. What is known about the topic? TDABC is a revision of the activity-based costing (ABC) system. RCA is also a new costing system that includes both the theoretical advantages of ABC and the practical advantages of German costing. However, little is known about the differences arising from application of TDABC and RCA. What does this paper add? There is no study comparing both TDABC and RCA in a single case study based on a real-world healthcare setting. Thus, the present study fills this gap in the literature and it is unique in the sense that it is the first case study comparing TDABC and RCA for open and laparoscopic gall bladder surgeries in a healthcare setting. What are the implications for practitioners? This study provides several interesting results for managers and cost accounting researchers. Thus, it will contribute to the spread of RCA studies in healthcare settings. It will also help the implementers of TDABC to revise data concerning the cost of unused capacity. In addition, by separating costs into fixed and variable, the paper will help managers to create a blended (combined) system that can improve both short- and long-term decisions.

Exercise Decreases and Smoking Increases Bladder Cancer Mortality

PubMed Central

Liss, Michael A.; White, Martha; Natarajan, Loki; Parsons, J. Kellogg

2018-01-01

Modifiable lifestyle factors play an important role regarding the development and outcomes in solid tumors. Whereas smoking has been attributed to bladder cancer and cessation leads to better outcome, we show that exercise may provide similar benefits regarding bladder cancer mortality Background The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. Patients and Methods We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as “did no exercise” vs. “light, moderate, or vigorous exercise in ≥ 10-minute bouts”), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Results Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HRadj], 0.53; 95% confidence interval [CI], 0.29–0.96; P = .038) to die of bladder cancer than “no exercise”. Compared with never-smokers, current (HRadj, 4.24; 95% CI, 1.89–9.65; P = .001) and former (HRadj, 2.95; 95% CI, 1.50–5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Conclusion Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. PMID:28007367

Altered Redox Status Accompanies Progression to Metastatic Human Bladder Cancer

PubMed Central

Hempel, Nadine; Ye, Hanqing; Abessia, Bryan; Mian, Badar; Melendez, J. Andres

2009-01-01

The role of reactive oxygen species (ROS) in bladder cancer progression remains an unexplored field. Expression levels of enzymes regulating ROS levels are often altered in cancer. Search of publicly available micro-array data reveals that expression of mitochondrial manganese superoxide dismutase (Sod2), responsible for the conversion of superoxide (O2-.) to hydrogen peroxide (H2O2), is consistently increased in high grade and advanced stage bladder tumors. Here we aim to identify the role of Sod2 expression and ROS in bladder cancer. Using an in vitro human bladder tumor model we monitored the redox state of both non-metastatic (253J) and highly metastatic (253J B-V) bladder tumor cell lines. 253J B-V cells displayed significantly higher Sod2 protein and activity levels compared to their parental 253J cell line. The increase in Sod2 expression was accompanied by a significant decrease in catalase activity, resulting in a net increase in H2O2 production in the 253J B-V line. Expression of pro-metastatic and –angiogenic factors, matrix metalloproteinase 9 (MMP-9) and vascular endothelial derived growth factor (VEGF), respectively, were similarly upregulated in the metastatic line. Expression of both MMP-9 and VEGF were shown to be H2O2-dependent, as removal of H2O2 by overexpression of catalase attenuated their expression. Similarly, expression of catalase effectively reduced the clonogenic activity of 253J B-V cells. These findings indicate that metastatic bladder cancer cells display an altered antioxidant expression profile, resulting in a net increase in ROS production, which leads to the induction of redox-sensitive pro-tumorigenic and pro-metastatic genes such as VEGF and MMP-9. PMID:18930813

Bladder cancer and occupational exposure to diesel and gasoline engine emissions among Canadian men.

PubMed

Latifovic, Lidija; Villeneuve, Paul J; Parent, Marie-Élise; Johnson, Kenneth C; Kachuri, Linda; Harris, Shelley A

2015-12-01

The International Agency for Research on Cancer has classified diesel exhaust as a carcinogen based on lung cancer evidence; however, few studies have investigated the effect of engine emissions on bladder cancer. The purpose of this study was to investigate the association between occupational exposure to diesel and gasoline emissions and bladder cancer in men using data from the Canadian National Enhanced Cancer Surveillance System; a population-based case-control study. This analysis included 658 bladder cancer cases and 1360 controls with information on lifetime occupational histories and a large number of possible cancer risk factors. A job-exposure matrix for engine emissions was supplemented by expert review to assign values for each job across three dimensions of exposure: concentration, frequency, and reliability. Odds ratios (OR) and their corresponding 95% confidence intervals were estimated using logistic regression. Relative to unexposed, men ever exposed to high concentrations of diesel emissions were at an increased risk of bladder cancer (OR = 1.64, 0.87-3.08), but this result was not significant, and those with >10 years of exposure to diesel emissions at high concentrations had a greater than twofold increase in risk (OR = 2.45, 1.04-5.74). Increased risk of bladder cancer was also observed with >30% of work time exposed to gasoline engine emissions (OR = 1.59, 1.04-2.43) relative to the unexposed, but only among men that had never been exposed to diesel emissions. Taken together, our findings support the hypothesis that exposure to high concentrations of diesel engine emissions may increase the risk of bladder cancer. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Host-Pathogen Checkpoints and Population Bottlenecks in Persistent and Intracellular Uropathogenic E. coli Bladder Infection

PubMed Central

Hannan, Thomas J.; Totsika, Makrina; Mansfield, Kylie J.; Moore, Kate H.; Schembri, Mark A.; Hultgren, Scott J.

2013-01-01

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multi-drug resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic E. coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the Quiescent Intracellular Reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection: QIR, ASB, or chronic cystitis, is determined within the first 24 hours of infection and constitutes a putative host-pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies. PMID:22404313

l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats.

PubMed

Tsai, Wen-Hsin; Wu, Chung-Hsin; Yu, Hong-Jeng; Chien, Chiang-Ting

2017-02-01

Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy-mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. l-Theanine dose-dependently depressed H 2 O 2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP-induced bladder hyperactivity via the inhibition of proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis, and autophagy. Neurourol. Urodynam. 36:297-307, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

PubMed

Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

2016-07-01

Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. ©2016 American Association for Cancer Research.

Primary nocturnal enuresis in children. Background and treatment.

PubMed

Wille, S

1994-01-01

The aim of the present studies was to investigate background factors and treatment in children with monosymptomatic primary nocturnal enuresis. The study material comprised enuretics, former enuretics and controls from the municipal community of Falkenberg on the west coast of Sweden. Whenever possible all investigations were made with the children staying in their own home environment. Different background factors have been suspected as being causative: sleep disturbances, behavioural or psychological disturbances, small bladder capacity, increased night diuresis and an insufficient production of the antidiuretic hormone during sleep. These factors have been investigated in these studies. The treatment of enuresis has been dominated by the alarm and antidiuretic treatment with DDAVP. Primary nocturnal monosymptomatic enuresis is a common problem in childhood. In this study the prevalence among 392 seven year old children was 7.3%. A prior history of enuresis was found in 65% of families of the enuretics compared to 25% in controls. The enuretic children showed no statistically significant differences in behavioural or psychological problems compared to non-enuretic children. Enuretic children were described as heavy sleepers by their parents and a wake-up test performed at home showed that they were statistically significantly harder to arouse than the controls. Children with nocturnal enuresis, former enuretics and controls did not differ in social or behavioural traits in an interview study. No signs of symptom substitution was found when enuresis was resolved. Enuretic children had a normal bladder capacity and no statistically significant difference was found compared to controls and former enuretics. The enuretic children showed a normal calcium-creatinine quota in the urine. Former enuretic children showed a significantly enhanced calcium/creatinine quota compared to enuretics and controls. Enuretic children had a statistically significant lower morning plasma level of the anti diuretic hormone vasopressin than non-enuretic children. Enuretic children were treated for 12 weeks with DDAVP or the alarm. DDAVP treated patients had a more rapid effect compared with alarm treated patients. Alarm treated children had a lower relapse frequency. Enuretic children were treated in a randomised, double blind, double dummy, cross over, placebo-controlled study with DDAVP 20 micrograms intranasally by a single dose pipette or 200 micrograms orally as a tablet. Both methods were equally effective in controlling enuresis, but significantly superior to placebo. Enuretic children are normal, well adjusted children with a normal bladder capacity, a high level of arousal threshold, and a low morning level of plasma vasopressin. The alarm and DDAVP are equally effective in treating enuresis.(ABSTRACT TRUNCATED AT 400 WORDS)

[Prevalence and characterization of overactive bladder detected in a population in Madrid with self-administered OAB-V3 questionnaire in Primary Care].

PubMed

Angulo, Javier C; Calderín, María P; Fernández, Yolanda; González, Miriam; Gómez, Esther; Herreros, Maria B; Peñasco, Purificación; Zapatero, Manuela; Dorado, Juan F

2018-02-01

Determining the prevalence of symptoms suggestive of overactive bladder (OAB) in a Spanish population and evaluate the impact of these symptoms on well-being and labour productivity in this population. Transversal study. Primary health care, Madrid, Spain. Males and females >30 years. Classification by primary care physicians with the Overactive Bladder Awareness Tool abbreviated version (OAB-V3). Subjects with score ≥3 and a similarly balanced control population with score <3 were clinically investigated. History, physical examination, urinalysis, sonography, general well-being scale and the questionnaires PPBC, OAB-q y WPAI-SHP. A total 923 subjects were screened, of which 209 (22.6%), 35% males and 65% females, had probable OAB. Age distribution increased from 11.1% in 4th decade to 44.4% in 9th decade. Kappa coefficient between suspected OAB and definite diagnosis was .83. The area under ROC curve for diagnosis based on OAB-V3 questionnaire and the presence of perceived bother and coping strategies was 92%. Subjects classified by score ≥3 had worse well-being, higher PPBC score and worse parameters on total OAB-q and transformed scores for each OAB-q subscale (P<.0001). In these subjects labour productivity was not affected (P=.14) but the capacity to perform regular activities was (P<.0001). OAB-V3 is a simple questionnaire to screen OAB with good predictive accuracy in a primary care setting and reveals important implications on health related quality of life issues. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The effects of juvenile capsaicin desensitization in rats: behavioral impairments.

PubMed

Petrovszki, Zita; Adam, Gábor; Kekesi, Gabriella; Tuboly, Gábor; Morvay, Zita; Nagy, Endre; Benedek, György; Horvath, Gyöngyi

2014-02-10

Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional and histological bladder damage in mice after photodynamic therapy: the influence of sensitiser dose and time of administration.

PubMed Central

Stewart, F. A.; Oussoren, Y.

1993-01-01

The bladders of anaesthetised mice were illuminated with red laser light (630 nm) at intervals of 1 day to 4 weeks after i.p. administration of Photofrin. Light was delivered intravesically by inserting a fibre optic, with a diffusing bulb tip, into the centre of fluid filled bladders. A single light dose of 11.3 J cm-2 applies 1 day after 10 mg kg-1 Photofrin caused a severe acute response, with increased urination frequency (five to seven times control) and hematuria. Recovery was good, however, and by 10 weeks only a mild (approximately two-fold) increase in frequency remained. There was no reduction in the amount of acute bladder damage or in the rate of healing when the interval between Photofrin and light was increased from 1 to 7 days but a 2 to 3 week interval lead to a significant reduction in damage. For an interval of 4 weeks there was only a mild (less than two-fold) increase in urination frequency during the first week. A drug dose of 2.5 mg kg-1 given 1 day before illumination caused transient haematuria but no increase in urination frequency. Doses of 5, 7.5 or 10 mg kg-1 all caused photosensitisation and the amount of bladder damage was drug dose dependent. The bladder seems to be well able to recover from severe acute damage induced by PDT. Occasional incidences of pyelonephritis were seen, however, suggesting that urinary tract infection during the acute period may lead to permanent renal damage. Images Figure 5 PMID:8398691

The effect of prolapse repair on urinary flow rates and the relationship to changes in the ultrasound appearance of the bladder neck.

PubMed

Duckett, Jonathan; Chakani, Dorothy

2013-12-01

To assess whether specific changes in bladder neck morphology, caused by an anterior repair operation, are associated with resolution of overactive bladder and improved urinary flow rates. Sixty-four women with urgency documented on the urgency perception scale (UPS) underwent an anterior repair. Their preoperative flow studies were compared to those 8 weeks postoperatively. Flow rates were compared in those women who reported improved or cured urgency to those who reported no effect. Resolution of urgency was correlated with the change in bladder neck angulation (posterior urethrovesical angle-PUA). 55% (35/64) women reported no urgency after the anterior repair. A further 19% (12/64) were improved and 26% (17/64) were no better. Patients who were cured or improved showed a significant increase in their flow rates after surgery (mean flow=15 before and 17.6 ml/s after) (Mann-Whitney p=0.04). There was a significant change (increase in the PUA angle/straightening of the angle between the bladder and urethra) from a mean value of 123 degrees (SD 49.3) preoperatively to a mean value of 146.8 (SD 29.2) post operatively (p<0.001). Despite an increase in PUA, this was not correlated with an increase in the maximum flow rate centile (p=0.45, r=0.10). An anterior repair results in increased maximum urinary flow rates but this does not correlate to changes in the appearance of the bladder neck. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

BROMINATED TRIHALOMETHANE (BrTHM) TOXICITY IN HUMAN BLADDER CELL LINES

EPA Science Inventory

Epidemiology studies have consistently found that greater exposure to drinking water disinfection byproducts (DBPs) is associated with an increased risk for bladder cancer. In 2010, Cantor et al. (Environ. Health Perspect. 118: 1545) reported that this increased risk was depende...

N-acetyltransferase 2 gene polymorphism as a biomarker for susceptibility to bladder cancer in Bangladeshi population.

PubMed

Hosen, Md Bayejid; Islam, Jahidul; Salam, Md Abdus; Islam, Md Fakhrul; Hawlader, M Zakir Hossain; Kabir, Yearul

2015-03-01

To investigate the association between the three most common single nucleotide polymorphisms of the N-acetyltransferase 2 gene together with cigarette smoking and the risk of developing bladder cancer and its aggressiveness. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genomic DNA was extracted from peripheral white blood cells and N-acetyltransferase 2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods. Bladder cancer risk was estimated as odds ratio and 95% confidence interval using binary logistic regression models adjusting for age and gender. Overall, N-acetyltransferase 2 slow genotypes were associated with bladder cancer risk (odds ratio=4.45; 95% confidence interval=2.26-8.77). The cigarette smokers with slow genotypes were found to have a sixfold increased risk to develop bladder cancer (odds ratio=6.05; 95% confidence interval=2.23-15.82). Patients with slow acetylating genotypes were more prone to develop high-grade (odds ratio=6.63; 95% confidence interval=1.15-38.13; P<0.05) and invasive (odds ratio=10.6; 95% confidence interval=1.00-111.5; P=0.05) tumor. N-acetyltransferase 2 slow genotype together with tobacco smoking increases bladder cancer risk. Patients with N-acetyltransferase 2 slow genotypes were more likely to develop a high-grade and invasive tumor. N-acetyltransferase 2 slow genotype is an important genetic determinant for bladder cancer in Bangladesh population. © 2014 Wiley Publishing Asia Pty Ltd.

Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

PubMed

Oyama, Tatsuya; Homan, Takashi; Kyotani, Junko; Oka, Michiko

2012-02-15

Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that μ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity. Copyright © 2011 Elsevier B.V. All rights reserved.

Magnetic Fluid Hyperthermia for Bladder Cancer: A Preclinical Dosimetry Study

PubMed Central

Oliveira, Tiago R.; Stauffer, Paul R.; Lee, Chen-Ting; Landon, Chelsea D.; Etienne, Wiguins; Ashcraft, Kathleen A.; McNerny, Katie L.; Mashal, Alireza; Nouls, John; Maccarini, Paolo F.; Beyer, Wayne F.; Inman, Brant; Dewhirst, Mark W.

2014-01-01

Purpose This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with Magnetic Fluid Hyperthermia (MFH), performed by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. Materials and Methods The bladders of twenty-five female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42°C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fiberoptic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterization method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. Results Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1°C/min to a steady-state of 42°C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. Conclusion These data demonstrate that our MFH system with magnetite-based nanoparticles provide well-localized heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues. PMID:24050253

Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

PubMed

Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

2017-07-27

The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

How should bladder sensation be measured? ICI-RS 2011.

PubMed

De Wachter, S; Smith, Philip P; Smith, P; Tannenbaum, C; Van Koeveringe, G; Drake, M; Wyndaele, J J; Chapple, C

2012-03-01

Disturbed bladder sensations, or in broader terms, sensory dysfunctions are increasingly recognized as key elements in the origin and manifestation of symptom syndromes of urinary dysfunction. Adequate assessment of bladder sensation is crucial to improve our understanding of the pathophysiology and treatment of urinary dysfunction. This manuscript summarizes the discussions of a think tank on "How to measure bladder sensation" held at the ICI-RS meeting in 2011. Based upon literature reviews on bladder sensation presented at the think tank in the ICI-RS meeting, discussions evolved which were summarized in the ICI-RS report. Different physicians/researchers further elaborated on this report, which is presented in this manuscript. Bladder sensations are not merely the result of bladder distension. Other factors inside the bladder or bladder wall: central processing and/or cognitive manipulation may play an important role. Current methods to measure sensations such as urodynamics, voiding diaries, forced diuresis, electrical stimulation and brain imaging are likely sub-optimal as they only consider part of these factors in isolation. Different methods to measure bladder sensations have been described and are used in clinical practice. Current methods only address part of the parameters responsible for the generation and perception of urinary sensations. Further focused research is required, and several recommendations are provided. Copyright © 2012 Wiley Periodicals, Inc.

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

PubMed Central

Peh, Wendy Yen Xian; Mogan, Roshini; Thow, Xin Yuan; Chua, Soo Min; Rusly, Astrid; Thakor, Nitish V.; Yen, Shih-Cheng

2018-01-01

The disruption of coordination between smooth muscle contraction in the bladder and the relaxation of the external urethral sphincter (EUS) striated muscle is a common issue in dysfunctional bladders. It is a significant challenge to overcome for neuromodulation approaches to restore bladder control. Bladder-sphincter dyssynergia leads to undesirably high bladder pressures, and poor voiding outcomes, which can pose life-threatening secondary complications. Mixed pelvic nerves are potential peripheral targets for stimulation to treat dysfunctional bladders, but typical electrical stimulation of pelvic nerves activates both the parasympathetic efferent pathway to excite the bladder, as well as the sensory afferent pathway that causes unwanted sphincter contractions. Thus, a novel pelvic nerve stimulation paradigm is required. In anesthetized female rats, we combined a low frequency (10 Hz) stimulation to evoke bladder contraction, and a more proximal 20 kHz stimulation of the pelvic nerve to block afferent activation, in order to produce micturition with reduced bladder-sphincter dyssynergia. Increasing the phase width of low frequency stimulation from 150 to 300 μs alone was able to improve voiding outcome significantly. However, low frequency stimulation of pelvic nerves alone evoked short latency (19.9–20.5 ms) dyssynergic EUS responses, which were abolished with a non-reversible proximal central pelvic nerve cut. We demonstrated that a proximal 20 kHz stimulation of pelvic nerves generated brief onset effects at lower current amplitudes, and was able to either partially or fully block the short latency EUS responses depending on the ratio of the blocking to stimulation current. Our results indicate that ratios >10 increased the efficacy of blocking EUS contractions. Importantly, we also demonstrated for the first time that this combined low and high frequency stimulation approach produced graded control of the bladder, while reversibly blocking afferent signals that elicited dyssynergic EUS contractions, thus improving voiding by 40.5 ± 12.3%. Our findings support advancing pelvic nerves as a suitable neuromodulation target for treating bladder dysfunction, and demonstrate the feasibility of an alternative method to non-reversible nerve transection and sub-optimal intermittent stimulation methods to reduce dyssynergia. PMID:29618971

Nocturia in men is a chaotic condition dominated by nocturnal polyuria.

PubMed

Fujimura, Tetsuya; Yamada, Yuta; Sugihara, Toru; Azuma, Takeshi; Suzuki, Motofumi; Fukuhara, Hiroshi; Nakagawa, Tohru; Kume, Haruki; Igawa, Yasuhiko; Homma, Yukio

2015-05-01

To characterize nocturia in men based on frequency volume chart data and symptom profiles assessed using the Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires. The Core Lower Urinary Tract Symptom Score and Athens Insomnia Scale questionnaires were administered to 299 consecutive treatment naïve men with nocturia (≥one time per night). Frequency volume chart data were recorded for 2 days. Correlations between nocturia and clinical characteristics including symptom scores, clinical diagnosis, Charlson Comorbidity Index, estimated glomerular filtration rate, uroflowmetry and prostate volume were analyzed. Patients were divided into five groups: one time (n = 36), two times (n = 65), three times (n = 85), four times (n = 78) and five times (n = 34) of nocturia. Age, prevalence or severity of chronic kidney disease, hyperlipidemia, low bladder capacity, nocturnal polyuria, urgency, bladder pain and sleep disorders were significantly correlated with the severity of nocturia. The Spearman correlation analysis identified eight possible independent factors for nocturia: age, estimated glomerular filtration rate, urgency, bladder pain, sleep quality, sleepiness during the day, average voided volume and nocturnal volume divided by body weight. Logistic regression analysis showed that nocturnal volume divided by body weight was the strongest factor of nocturia, and ≥7, 9 and 9.7 mL/kg were practical cut-off values of three, four and five times per night of nocturia, respectively. Nocturia in men is a chaotic condition dominated by nocturnal polyuria, and related to multiple factors including age, renal function, urgency, bladder pain, insomnia and bladder volume. © 2015 The Japanese Urological Association.

Standards of the Polish Ultrasound Society - update. Ultrasound examination of the kidneys, ureters and urinary bladder.

PubMed

Tyloch, Janusz F; Woźniak, Magdalena Maria; Wieczorek, Andrzej Paweł

2013-09-01

The paper presents the principles of performing proper ultrasound examinations of the urinary tract. The following are discussed: preparation of patients, type of optimal apparatus, technique of examination and conditions which its description should fulfill. Urinary track examination in adults and in children constitutes an integral part of each abdominal examination. Such examinations should be performed with fasting patients or several hours after the last meal, with filled urinary bladder. Ultrasound examinations in children and infants are performed using transducers with the frequency of 5.0-9.0 MHz and in adults - with the frequency of 2.0-6.0 MHz. Doppler options are desirable since they improve diagnostic capacity of sonography in terms of differentiation between renal focal lesions. Renal examinations are performed with the patients in the supine position. The right kidney is examined in the right hypochondriac region using the liver as the ultrasound "window." The left kidney is examined in the left hypochondriac region, preferably in the posterior axillary line. Ultrasound examinations of the upper segment of the ureters are performed after renal examination when the pelvicalyceal system is dilated. A condition necessary for a proper examination of the perivesical portion of the ureter is full urinary bladder. The scans of the urinary bladder are performed in transverse, longitudinal and oblique planes when the bladder is filled. The description should include patient's personal details, details of the referring unit, of the unit in which the examination is performed, examining physician's details, type of ultrasound apparatus and transducers as well as the description proper.

Afferent Nerve Regulation of Bladder Function in Health and Disease

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2012-01-01

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

Tunneling nanotubes promote intercellular mitochondria transfer followed by increased invasiveness in bladder cancer cells

PubMed Central

Lu, Jinjin; Zheng, Xiufen; Li, Fan; Yu, Yang; Chen, Zhong; Liu, Zheng; Wang, Zhihua; Xu, Hua; Yang, Weimin

2017-01-01

Intercellular transfer of organelles via tunneling nanotubes (TNTs) is a novel means of cell-to-cell communication. Here we demonstrate the existence of TNTs between co-cultured RT4 and T24 bladder cancer cells using light microscopy, fluorescence imaging, and scanning electron microscopy (SEM). Spontaneous unidirectional transfer of mitochondria from T24 to RT4 cells was detected using fluorescence imaging and flow cytometry. The distribution of mitochondria migrated from T24 cells was in good agreement with the original mitochondria in RT4 cells, which may imply mitochondrial fusion. We detected cytoskeleton reconstruction in RT4-Mito-T24 cells by observing F-actin redistribution. Akt, mTOR, and their downstream mediators were activated and increased. The resultant increase in the invasiveness of bladder cancer cells was detected in vitro and in vivo. These data indicate that TNTs promote intercellular mitochondrial transfer between heterogeneous cells, followed by an increase in the invasiveness of bladder cancer cells. PMID:28107184

[Comparative Study on Evaluating the Bladder Volume between BladderScan BVI9400 and Ultrasound System iU22].

PubMed

Luo, Huanli; Wang, Ying; Li, Fang; Ling, Yun; Yang, Dingyi; Jin, Fu

2015-07-01

To evaluate the accuracy of the latest BladderScan BVI9400 on measuring bladder volume. Two bladder phantoms were selected for investigating the accuracy of BVI9400. 341 patients with the iU22 ultrasound examinations were followed by BVI 9400. The difference and correlation between BVI9400 and iU22 were contrastively analyzed. The relative difference between results from BVI9400 and phantom volume was 2.5% and 1.36%. There was a strong correlation for patients between BVI9400 and iU22 (R = 0.96, P < 0.001). The relative difference between BVI9400 and iU22 decreased with the increasing of bladder volume and had no significant difference with patient's gender (P > 0.1). BladderScan BVI9400 had the ability of high accuracy and good stability of measured data. In view of quick and conveniences, BVI9400 could be as auxiliary equipment on pelvic tumor to evaluate whether the bladder volume during fractional radiotherapy was consistency with that during CT positioning.

Intravesical antineoplastic therapy following transurethral resection of bladder tumors: nursing implications from the operating room to discharge.

PubMed

Washburn, Donna J

2007-08-01

An aging population and latent effects from exposure to carcinogens will likely augment the current trend of increased incidence of urinary bladder cancer. Intravesical antineoplastic therapy is a common treatment for urinary bladder cancer. Transurethral resection of bladder tumors often is followed immediately by the instillation of an antineoplastic agent in the operating room or postanesthesia care unit. Oncology nurses, who have a unique knowledge of safe handling and patient care, can improve staff safety and patient outcomes in several areas of healthcare organizations, as well as reduce the mortality and morbidity of urinary bladder cancer by learning more about the disease and intravesical antineoplastic therapy.

Neural control of Substance P-induced upregulation and release of macrophage migration inhibitory factor in the rat bladder

PubMed Central

Vera, Pedro L.; Wang, Xihai; Meyer-Siegler, Katherine L.

2009-01-01

OBJECTIVE Macrophage migration inhibitory factor (MIF) is increased in the intraluminal fluid after experimental inflammation and mediates pro-inflammatory effects on the bladder. We examined the contribution of nerve activity and of specific neurotransmitter systems on the mechanism of MIF release from the bladder during inflammation. MATERIALS & METHODS Male Sprague-Dawley rats were anesthetized, bladders were emptied and filled with saline. Rats received saline (s.c.; control; 0.1 ml/100 g bodyweight) or substance P (40 μg/kg in saline; s.c.; 0.1 ml/100 g bodyweight) and also received hexamethonium (50 mg/kg;i.p.; in saline; 0.1 ml/100 g body weight); intravesical lidocaine (2%; 0.3 ml), atropine (3 mg/kg in saline; i.v.; 0.1 ml/100 g body weight), propranolol (3 mg/kg in saline; i.v.; 0.1 ml/100 g body weight) or phentolamine (10 mg/kg in saline; i.v.; 0.1 ml/100 g body weight). After of 1 hour, the intravesical fluid was removed and the bladder was excised. MIF levels in the intraluminal fluid were measured by ELISA and Western-blotting. MIF expression in bladder homogenates was examined using RT-PCR. RESULTS Either intravesical lidocaine or ganglionic blockage with hexamethonium prevented Substance P-induced MIF release. In addition, pretreatment with atropine and phentolamine, but not propranolol, also prevented MIF release. MIF upregulation in the bladder, while increased with Substance P treatment, was only prevented by intravesical lidocaine. CONCLUSION Substance P-induced MIF release in the bladder is mediated through nerve activation. Post-ganglionic parasympathetic (via muscarinic receptors) and sympathetic (via alpha-adrenergic receptors) fibers mediate MIF release while activation of bladder afferent nerve terminals upregulate MIF. PMID:18499160

Occupational exposure to pesticides and bladder cancer risk.

PubMed

Koutros, Stella; Silverman, Debra T; Alavanja, Michael Cr; Andreotti, Gabriella; Lerro, Catherine C; Heltshe, Sonya; Lynch, Charles F; Sandler, Dale P; Blair, Aaron; Beane Freeman, Laura E

2016-06-01

In the developed world, occupational exposures are a leading cause of bladder cancer. A few studies have suggested a link between pesticide exposures among agricultural populations and bladder cancer. We used data from the Agricultural Health Study, a prospective cohort study which includes 57 310 pesticide applicators with detailed information on pesticide use, to evaluate the association between pesticides and bladder cancer. We used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) to estimate the association between each of 65 pesticides and 321 incident bladder cancer cases which accrued over the course of follow-up (1993-2011), adjusting for lifestyle and demographic and non-pesticide farm-related exposures, including those previously linked to bladder cancer. We conducted additional analyses stratified by smoking status (never, former, current). We observed associations with bladder cancer risk for two imidazolinone herbicides, imazethapyr and imazaquin, which are aromatic amines. Ever use of imazaquin (RR = 1.54, 95% CI: 1.05, 2.26) was associated with increased risk whereas the excess risk among users of imazethapyr was evident among never smokers (RR in highest quartile vs non-exposed = 3.03, 95% CI: 1.46, 6.29, P-interaction = 0.005). We also observed increased risks overall and among never smokers for use of several chlorinated pesticides including chlorophenoxy herbicides and organochlorine insecticides. Several associations between specific pesticides and bladder cancer risk were observed, many of which were stronger among never smokers, suggesting that possible risk factors for bladder cancer may be more readily detectable in those unexposed to potent risk factors like tobacco smoke. Published by Oxford University Press on behalf of the International Epidemiological Association 2015. This work is written by US Government employees and is in the public domain in the US.

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PubMed

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

PubMed

Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

2018-05-15

To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hyperexcitability of bladder afferent neurons associated with reduction of Kv1.4 α-subunit in rats with spinal cord injury.

PubMed

Takahashi, Ryosuke; Yoshizawa, Tsuyoshi; Yunoki, Takakazu; Tyagi, Pradeep; Naito, Seiji; de Groat, William C; Yoshimura, Naoki

2013-12-01

To clarify the functional and molecular mechanisms inducing hyperexcitability of C-fiber bladder afferent pathways after spinal cord injury we examined changes in the electrophysiological properties of bladder afferent neurons, focusing especially on voltage-gated K channels. Freshly dissociated L6-S1 dorsal root ganglion neurons were prepared from female spinal intact and spinal transected (T9-T10 transection) Sprague Dawley® rats. Whole cell patch clamp recordings were performed on individual bladder afferent neurons. Kv1.2 and Kv1.4 α-subunit expression levels were also evaluated by immunohistochemical and real-time polymerase chain reaction methods. Capsaicin sensitive bladder afferent neurons from spinal transected rats showed increased cell excitability, as evidenced by lower spike activation thresholds and a tonic firing pattern. The peak density of transient A-type K+ currents in capsaicin sensitive bladder afferent neurons from spinal transected rats was significantly less than that from spinal intact rats. Also, the KA current inactivation curve was displaced to more hyperpolarized levels after spinal transection. The protein and mRNA expression of Kv1.4 α-subunits, which can form transient A-type K+ channels, was decreased in bladder afferent neurons after spinal transection. Results indicate that the excitability of capsaicin sensitive C-fiber bladder afferent neurons is increased in association with reductions in transient A-type K+ current density and Kv1.4 α-subunit expression in injured rats. Thus, the Kv1.4 α-subunit could be a molecular target for treating overactive bladder due to neurogenic detrusor overactivity. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Glucocorticoid receptor beta increases migration of human bladder cancer cells.

PubMed

McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

2016-05-10

Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3' untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3'UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

Association between the high risk occupations and bladder cancer in Iran: a case-control study.

PubMed

Khoubi, Jamshid; Pourabdian, Siamak; Mohebbi, Iraj; Tajvidi, Mina; Zaroorian, Omid; Giahi, Omid

2013-04-01

The objective of this work was to identify the high-risk occupations in Iran and to re-inspect occupations that were related to bladder cancer. In the study, 300 patients suffering from bladder cancer and 500 control individuals were interviewed. Demographic information, occupational history, and history of exposure to chemical compounds such as aromatic amines for each participant were collected. ORs and 95% CIs were calculated using unconditional logistic regression for each occupation. There was a significantly increased risk of bladder cancer among truck and bus drivers (OR = 11.3), skilled agricultural, forestry and fishery workers (OR = 6.0), metal industry workers (OR = 6.0), domestic housekeepers (OR = 5.9), and construction workers (OR = 3.8). The study showed a strong correlation between truck and bus drivers, skilled agricultural, forestry and fishery workers, metal industry workers, domestic housekeepers, as well as construction workers and the increased risk of bladder cancer in these occupations.

Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways

PubMed Central

Pan, Xiao-Qing; Gonzalez, Jessica A.; Chang, Shaohua; Chacko, Samuel; Wein, Alan J.; Malykhina, Anna P.

2010-01-01

Clinical data provides evidence of high level of co-morbidity among genitourinary and gastrointestinal disorders characterized by chronic pelvic pain. The objective of this study was to test the hypothesis that colonic inflammation can impact the function of the urinary bladder via activation of TRPV1 signaling pathways followed by alterations in gene and protein expression of Substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory neurons and in the bladder. Inflammation was induced by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS, 12.5 mg/kg) and desensitization of TRPV1 receptors was evoked by intracolonic resiniferatoxin (RTX, 10−7 M). mRNA and protein concentrations of CGRP and SP were measured at 3, 5 and 30 days. RTX instillation in the colon caused 3-fold up-regulation of SP mRNA in the urinary bladder at day 5 (n=7, p≤0.05) followed by 35-fold increase at day 30 (n=5, p≤0.05). Likewise, TNBS colitis triggered 15.8-fold up-regulation of SP mRNA one month after TNBS (n=5, p≤0.05). Desensitization of colonic TRPV1 receptors prior to TNBS abolished SP increase in the urinary bladder. RTX led to 4.3-fold increase of CGRP mRNA at day 5 (n=7, p≤0.05 to control) in the bladder followed by 28-fold increase at day 30 post-RTX (n=4, p≤0.05). Colitis did not alter CGRP concentration during acute phase, however, at day 30 mRNA level was increased by 17.8±6.9 fold (n=5, p≤0.05) in parallel with 4-fold increase in CGRP protein (n=5, p≤0.01) in the detrusor. Protein concentration of CGRP in the spinal cord was diminished by 45–65% (p≤0.05) during colitis. RTX pretreatment did not affect CGRP concentration in the urinary bladder, however, caused a reduction in CGRP release from lumbosacral DRG neurons during acute phase (3 and 5 days post-TNBS). Our results clearly demonstrate that colonic inflammation triggers the release of pro-inflammatory neuropeptides SP and CGRP in the urinary bladder via activation of TRPV1 signaling mechanisms enunciating the neurogenic nature of pelvic organ cross-sensitization. PMID:20501335

Analyzing the effects of instillation volume on intravesical delivery using biphasic solute transport in a deformable geometry.

PubMed

Smith, Sean G; Griffith, Boyce E; Zaharoff, David A

2018-04-05

Ailments of the bladder are often treated via intravesical delivery-direct application of therapeutic into the bladder through a catheter. This technique is employed hundreds of thousands of times every year, but protocol development has largely been limited to empirical determination. Furthermore, the numerical analyses of intravesical delivery performed to date have been restricted to static geometries and have not accounted for bladder deformation. This study uses a finite element analysis approach with biphasic solute transport to investigate several parameters pertinent to intravesical delivery including solute concentration, solute transport properties and instillation volume. The volume of instillation was found to have a substantial impact on the exposure of solute to the deeper muscle layers of the bladder, which are typically more difficult to reach. Indeed, increasing the instillation volume from 50-100 ml raised the muscle solute exposure as a percentage of overall bladder exposure from 60-70% with higher levels achieved for larger instillation volumes. Similar increases were not seen for changes in solute concentration or solute transport properties. These results indicate the role that instillation volume may play in targeting particular layers of the bladder during an intravesical delivery.

Association between N-Acetyltransferase 2 Polymorphism and Bladder Cancer Risk: a Meta-Analysis in a Single Ethnic Group.

PubMed

Xu, Wan-Jiang; Wen, Li-Ping; Jiang, Xiang-Xin; Ye, Li-Yin; Meng, Fan-Hua; Guan, Sheng; Qian, Ying-Jun; Wei, Jing-Feng

2017-02-01

Many studies have evaluated the correlation between N-acetyltransferase 2 (NAT2) slow acetylation genotype and bladder cancer risk. However, the results are inconsistent and remain to be confirmed in each ethnic group. To assess the effects of NAT2 acetylation status on the risk of bladder cancer in the Chinese population, a meta-analysis was performed. Studies were identified using PubMed and Chinese databases through February 2016. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). This meta-analysis included 10 studies with 896 bladder cancer cases and 1188 controls. In the overall analysis, NAT2 slow acetylation phenotype was significantly associated with an increased risk of bladder cancer in the Chinese population (OR = 1.68, 95% CI = 1.11 - 2.53). In the subgroup analyses by geographic areas and sources of controls, significant risk was found in Mainland China (OR = 1.83, 95% CI = 1.04 - 3.20) and hospitalbased studies (OR = 1.74, 95% CI = 1.27 - 2.38), but not in Taiwan China. This meta-analysis suggested that the NAT2 slow acetylation genotype is associated with an increased bladder cancer risk in Chinese individuals.

Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up.

PubMed

Pira, Enrico; Piolatto, Giorgio; Negri, Eva; Romano, Canzio; Boffetta, Paolo; Lipworth, Loren; McLaughlin, Joseph K; La Vecchia, Carlo

2010-07-21

We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure.

Effect of quercetin on tachykinin-induced plasma extravasation in rat urinary bladder.

PubMed

Wille, P R; Ribeiro-do-Valle, R M; Simões, C M; Gabilan, N H; Nicolau, M

2001-08-01

The effect of quercetin on substance P-induced plasma extravasation in rat urinary bladder and its modulation by endogenous peptidases in conscious rats was studied. Plasma protein extravasation (PE) was assayed by measurement of extravasated Evans blue dye (microg/g dry tissue). Intravenous injection of substance P (SP, 10 nmol/kg) significantly increased PE in the urinary bladder. PE evoked by SP was increased significantly by quercetin (20 mg/kg, p.o.) pretreatment in the urinary bladder (73.5 +/- 4.9 to 152.2 +/- 9.9). Pretreatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor (10 nmol/kg, i.v.), or with phosphoramidon, a neutral endopeptidase (NEP) inhibitor (2.5 micromol/kg, i.v.) also potentiated the SP-induced PE in urinary bladder, 286.2 +/- 20.4 and 323.3 +/- 34.0, respectively. Quercetin did not show any effect on neurokinin-A (NKA, 10 nmol/kg, i.v.) -induced plasma extravasation. The present study demonstrates that quercetin potentiates the PE induced by substance P in the urinary bladder. These effects suggest that this flavonoid might cause inhibition of NEP and/or ACE. Copyright 2001 John Wiley & Sons, Ltd.

[Physics of materials and female stress urinary continence: New concepts: I) Elasticity under bladder].

PubMed

Guerquin, B

2015-09-01

Improving the understanding of the adaptation to stress of urinary continence. A transversal analysis between physics of materials and the female anatomy. Laws of physics of the materials and of their viscoelastic behavior are applied to the anatomy of the anterior vaginal wall. The anterior vaginal wall may be divided into two segments of different viscoelastic behavior, the vertical segment below the urethra and the horizontal segment below the bladder. If the urethra gets crushed on the first segment according to the hammock theory, the crushing of the bladder on the second segment is, on the other hand, damped by its important elasticity. The importance of this elasticity evokes an unknown function: damping under the bladder that moderates and delays the increase of intravesical pressure. This damping function below the bladder is increased in the cystocele, which is therefore a continence factor; on the other hand, it is impaired in obesity, which is therefore a factor of SUI. It is necessary to include in the theory of stress continence, the notion of a damping function below the bladder. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Making Epidermal Bladder Cells Bigger: Developmental- and Salinity-Induced Endopolyploidy in a Model Halophyte.

PubMed

Barkla, Bronwyn J; Rhodes, Timothy; Tran, Kieu-Nga T; Wijesinghege, Chathura; Larkin, John C; Dassanayake, Maheshi

2018-06-01

Endopolyploidy occurs when DNA replication takes place without subsequent mitotic nuclear division, resulting in cell-specific ploidy levels within tissues. In plants, endopolyploidy plays an important role in sustaining growth and development, but only a few studies have demonstrated a role in abiotic stress response. In this study, we investigated the function of ploidy level and nuclear and cell size in leaf expansion throughout development and tracked cell type-specific ploidy in the halophyte Mesembryanthemum crystallinum In addition to developmental endopolyploidy, we examined the effects of salinity stress on ploidy level. We focused specifically on epidermal bladder cells (EBC), which are modified balloon-like trichomes, due to their large size and role in salt accumulation. Our results demonstrate that ploidy increases as the leaves expand in a similar manner for each leaf type, and ploidy levels up to 512C were recorded for nuclei in EBC of leaves of adult plants. Salt treatment led to a significant increase in ploidy levels in the EBC, and these cells showed spatially related differences in their ploidy and nuclear and cell size depending on the positions on the leaf and stem surface. Transcriptome analysis highlighted salinity-induced changes in genes involved in DNA replication, cell cycle, endoreduplication, and trichome development in EBC. The increase in cell size and ploidy observed in M. crystallinum under salinity stress may contribute to salt tolerance by increasing the storage capacity for sodium sequestration brought about by higher metabolic activity driving rapid cell enlargement in the leaf tissue and EBC. © 2018 American Society of Plant Biologists. All rights reserved.

Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

PubMed

Lina, B A; Rutten, A A; Woutersen, R A

1993-12-01

A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

Prevalence and psychosocial correlates of symptoms suggestive of painful bladder syndrome: results from the Boston area community health survey.

PubMed

Link, Carol L; Pulliam, Samantha J; Hanno, Philip M; Hall, Susan A; Eggers, Paul W; Kusek, John W; McKinlay, John B

2008-08-01

We estimated the prevalence of symptoms suggestive of painful bladder syndrome defined as pain increasing as the bladder fills and/or pain relieved by urination for at least 3 months, and its association with sociodemographics (gender, age, race/ethnicity and socioeconomic status), lifestyle (smoking, alcohol consumption, physical activity) and psychosocial variables (sexual, physical, emotional abuse experienced as a child or as an adult, worry, trouble paying for basics, depression). The data used come from the Boston Area Community Health Survey, an epidemiological study of 5,506 randomly selected adults 30 to 79 years old of 3 race/ethnic groups (black, Hispanic, white). The overall prevalence of symptoms suggestive of painful bladder syndrome was 2% (1.3% in men and 2.6% in women) with increased prevalence in middle-aged adults and those of lower socioeconomic status. Symptoms suggestive of painful bladder syndrome were more common in those who experienced abuse, in those who were worried about someone close to them and in those who were having trouble paying for basics. This pattern held even after adjusting for depression. Painful bladder syndrome is associated with a number of lifestyle and psychosocial correlates. This suggests that the treatment of patients with painful bladder syndrome (physical symptoms) may benefit from a multifaceted approach of combining medical, psychological and cognitive treatment.

Chloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis.

PubMed

Lin, Yi-Chia; Lin, Ji-Fan; Wen, Sheng-I; Yang, Shan-Che; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

2017-05-01

Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer. Copyright © 2017. Published by Elsevier Taiwan.

Differential Expression of Renal Outer Medullary K+ Channel and Voltage-gated K+ Channel 7.1 in Bladder Urothelium of Patients With Interstitial Cystitis/Painful Bladder Syndrome.

PubMed

Lee, Jane-Dar; Lee, Ming-Huei; Yang, Wen-Kai; Wang, Kuan-Lin; Lee, Tsung-Han

2017-03-01

To investigate the changes including expression and localization of 2 potassium channels, renal outer medullary K + channel (ROMK) and voltage-gated K + channel 7.1 (KCNQ1), after increased urinary potassium leakage in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). The study group included 24 patients with IC/PBS and a control group consisting of 12 volunteers without any IC/PBS symptoms. Bladder biopsies were taken from both groups. We determined the protein expression and distribution of potassium channels using immunoblotting, immunohistochemistry, and immunofluorescent staining under confocal laser microscopy. The results revealed that ROMK was predominantly expressed in apical cells of the bladder urothelium at significantly higher levels (3.3-fold) in the study group than in the control group. In contrast, KCNQ1 was expressed in the basolateral membrane according to confocal microscopy results and did not significantly differ between groups. Our data showed that the abundance of ROMK protein in apical cells was increased in the IC/PBS group, whereas KCNQ1, which was distributed in the basolateral membrane of the bladder urothelium, showed similar abundance between groups. These results suggest that upregulation of the ROMK channel in apical cells might permit avid potassium flux into the bladder lumen to maintain intracellular K + homeostasis in the dysfunctional urothelium. Copyright © 2016 Elsevier Inc. All rights reserved.

Systematic Review of Studies Reporting Positive Surgical Margins After Bladder Neck Sparing Radical Prostatectomy.

PubMed

Bellangino, Mariangela; Verrill, Clare; Leslie, Tom; Bell, Richard W; Hamdy, Freddie C; Lamb, Alastair D

2017-11-07

Bladder neck preservation (BNP) during radical prostatectomy (RP) has been proposed as a method to improve early recovery of urinary continence after radical prostatectomy. However, there is concern over a possible increase in the risk of positive surgical margins and prostate cancer recurrence rate. A recent systematic review and meta-analysis reported improved early recovery and overall long-term urinary continence without compromising oncologic control. The aim of our study was to perform a critical review of the literature to assess the impact on bladder neck and base margins after bladder neck sparing radical prostatectomy. We carried out a systematic review of the literature using Pubmed, Scopus and Cochrane library databases in May 2017 using medical subject headings and free-text protocol according to PRISMA guidelines. We used the following search terms: bladder neck preservation, prostate cancer, radical prostatectomy and surgical margins. Studies focusing on positive surgical margins (PSM) in bladder neck sparing RP pertinent to the objective of this review were included. Overall, we found 15 relevant studies reporting overall and site-specific positive surgical margins rate after bladder neck sparing radical prostatectomy. This included two RCTs, seven prospective comparative studies, two retrospective comparative studies and four case series. All studies were published between 1993 and 2015 with sample sizes ranging between 50 and 1067. Surgical approaches included open, laparoscopic and robot-assisted radical prostatectomy. The overall and base-specific PSM rates ranged between 7-36% and 0-16.3%, respectively. Mean base PSM was 4.9% in those patients where bladder neck sparing was performed, but only 1.85% in those without sparing. Bladder neck preservation during radical prostatectomy may increase base-positive margins. Further studies are needed to better investigate the impact of this technique on oncological outcomes. A future paradigm could include modification of intended approach to bladder neck dissection when anterior base lesions are identified on pre-operative MRI.

[Efficacy and problems of bladder volume measurement using portable three dimensional ultrasound scanning device--in particular, on measuring bladder volume lower than 100ml].

PubMed

Oh-Oka, Hitoshi; Nose, Ryuichiro

2005-09-01

Using a portable three dimensional ultrasound scanning device (The Bladder Scan BVI6100, Diagnostic Ultrasound Corporation), we examined measured values of bladder volume, especially focusing on volume lower than 100 ml. A total of 100 patients (male: 66, female: 34) were enrolled in the study. We made a comparison study between the measured value (the average of three measurements of bladder urine volume after a trial in male and female modes) using BVI6100, and the actual measured value of the sample obtained by urethral catheterization in each patient. We examined the factors which could increase the error rate. We also introduced the effective techniques to reduce measurement errors. The actual measured values in all patients correlated well with the average value of three measurements after a trial in a male mode of the BVI6100. The correlation coefficient was 0.887, the error rate was--4.6 +/- 24.5%, and the average coefficient of variation was 15.2. It was observed that the measurement result using the BVI6100 is influenced by patient side factors (extracted edges between bladder wall and urine, thickened bladder wall, irregular bladder wall, flattened rate of bladder, mistaking prostate for bladder in male, mistaking bladder for uterus in a female mode, etc.) or examiner side factors (angle between BVI and abdominal wall, compatibility between abdominal wall and ultrasound probe, controlling deflection while using probe, etc). When appropriate patients are chosen and proper measurement is performed, BVI6100 provides significantly higher accuracy in determining bladder volume, compared with existing abdominal ultrasound methods. BVI6100 is a convenient and extremely effective device also for the measurement of bladder urine over 100 ml.

Brain responses to bladder filling in older women without urgency incontinence.

PubMed

Tadic, Stasa D; Tannenbaum, Cara; Resnick, Neil M; Griffiths, Derek

2013-06-01

To investigate normal brain responses to bladder filling, especially when there is little or no sensation as in much of daily life. We performed an functional magnetic resonance imaging (fMRI) study of brain responses to bladder filling in normal female subjects, evoked by infusion and withdrawal of fluid in and out of the bladder. Using the contrast (infusion-withdrawal), we imaged brain activity at small bladder volumes with weak filling sensation and also with full bladder and strong desire to void. Eleven women, average age 65 years (range: 60-71 years) were included. With full bladder and strong desire to void, filling provoked a well-known pattern of activation near the right insula and (as a trend) in the dorsal anterior cingulate cortex and supplementary motor area. There was no significant deactivation. With small bladder volume filling provoked widespread apparent deactivation and no significant activation. Apparent deactivation was associated with increased fMRI signal during withdrawal rather than decrease during infusion, suggesting artifact. A correction for global changes in cerebral blood flow eliminated it and revealed significant subcortical activation, although none in frontal or parietal cortex. In older women with normal bladder function, infusion into an already full bladder resulted in strong sensation and brain activation near the insula and in the dorsal anterior cingulate/supplementary motor complex. With near-empty bladder and little sensation, the situation during much of daily life, these cortical areas were not detectably activated, but activation in midbrain and parahippocampal regions presumably indicated unconscious monitoring of ascending bladder signals. Copyright © 2013 Wiley Periodicals, Inc.

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence

PubMed Central

2014-01-01

Background Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Methods Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Results Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2–4.1]; 4.2 [2.1–6.3] and; 5.8 [2.9–8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35–4.0], 2.3 [0.59–6.4], and 3.1 [0.80–8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Conclusion Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial. PMID:24889821

Comparisons of urodynamic findings and voiding habits in patients with concomitant benign prostatic hyperplasia and detrusor overactivity presenting with or without the symptom of urgency.

PubMed

Tong, Yat-Ching

2007-01-01

The urodynamic findings and voiding habits in patients with concomitant clinical benign prostatic hyperplasia (BPH) and detrusor overactivity (DO) presenting with or without the symptom of urgency were compared. 84 BPH patients with an urodynamic diagnosis of DO by conventional cystometry were included in the study. The patients were grouped according to the presence or absence of the symptom of urgency. The urodynamic findings, urinary diary and clinical information were analyzed. Among the 84 BPH-DO patients, 52 reported the symptom of urgency while 32 did not. There were no significant differences in mean age, International Prostate Symptom Score and flow rate between the two groups. Patients without urgency had a higher incidence of terminal DO and abnormal bladder sensation. The occurrence of unfelt phasic DO was also significantly higher in this group. Sphincter electromyography showed conscious and subconscious sphincter contractions associated with DO. The urinary diary showed lower 24-hour urinary output, smaller bladder functional capacity and average voided volume in the BPH-DO patients without urgency. BPH patients with DO may neglect the symptom of urgency due to abnormal bladder sensation, or negate the symptom by subconscious sphincter contraction to abort the overactivity. Some may avoid the symptom by drinking less fluid and emptying the bladder at a smaller volume. Copyright 2007 S. Karger AG, Basel.

Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea.

PubMed

Joung, Jae Young; Lim, Jiwon; Oh, Chang-Mo; Jung, Kyu-Won; Cho, Hyunsoon; Kim, Sung Han; Seo, Ho Kyung; Park, Weon Seo; Chung, Jinsoo; Lee, Kang Hyun; Won, Young-Joo

2017-07-01

This descriptive study assessed the current trends in the incidence of urological cancers and patient survival in Korea. In this nationwide retrospective observational study based on the data from the Korea National Cancer Incidence Database (KNCIDB), this study analyzed the age-standardized incidence rates (ASRs) and annual percentage changes (APCs) of kidney, bladder, prostate, testicular, and penile cancers as well as cancer of the renal pelvis and ureter between 1999 and 2012. The relative survival rates (RSRs) were calculated for urological cancer patients diagnosed between 1993 and 2012 from the KNCIDB data. Prostate cancer was diagnosed in 66,812 individuals followed by bladder (41,549) and kidney (36,836) cancers. The overall ASR (18.26 per 100,000) increased with age because of the higher ASRs of bladder and prostate cancers in the elderly. The ASR for kidney cancer was highest in the 40-59-year-old group, whereas testicular cancer occurred most frequently before the age of 40. The incidence of most urological cancers increased (overall APC, 6.39%; p < 0.001), except for penile (APC, -2.01%; p=0.05) and bladder (APC, -0.40%; p=0.25) cancers. The overall survival increased steadily (5-year RSR, 66.4% in 1993-1995 vs. 84.2% in 2008-2012; p < 0.001), particularly for prostate (by 34.10%) and kidney (by 16.30%) cancers, but not for renal pelvis and ureter cancers (-7.20%). The most common urological cancer in Korea was prostate cancer followed by bladder and kidney cancers. The incidence of most urological cancers, except for penile and bladder cancers, increased. Survival also increased, particularly for prostate and kidney cancers.

Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity

PubMed Central

Anderson, U A; Carson, C; Johnston, L; Joshi, S; Gurney, A M; McCloskey, K D

2013-01-01

Background and Purpose The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. Experimental Approach KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. Key Results KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. Conclusions and Implications These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder. PMID:23586426

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence.

PubMed

Chen, Yule; Zhu, Guodong; Wu, Kaijie; Gao, Yang; Zeng, Jin; Shi, Qi; Guo, Peng; Wang, Xinyang; Chang, Luke S; Li, Lei; He, Dalin

2016-04-01

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.

Impact of Dose to the Bladder Trigone on Long-Term Urinary Function After High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E.

2014-02-01

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose–volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients. Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose–volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analysesmore » were done by the Kaplan-Meier method and Cox proportional hazard models, respectively. Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19). Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity.« less

Occupational risks for bladder cancer among men in Sweden.

PubMed

Malker, H S; McLaughlin, J K; Silverman, D T; Ericsson, J L; Stone, B J; Weiner, J A; Malker, B K; Blot, W J

1987-12-15

With the use of the Swedish Cancer-Environment Registry, census data on employment in 1960 were linked with registry data on bladder cancer during 1961-79. This hypothesis-generating study revealed for the first time associations between bladder cancer and employment in pulp and fiberboard manufacturing, in rope and twine making, and work as a dental technician. Statistically significant increases in risk were also found for several occupations previously associated with bladder cancer, including barbers and beauticians, artistic painters, toolmakers and machinists, and physicians, and employment in butcher shops, industrial chemical making, apparel manufacturing, and plumbing. Etiologic inferences cannot be made from this investigation, but the findings from this large national resource provide further clues to the occupational determinants of bladder cancer.

Effect of bladder augmentation on VP shunt failure rates in spina bifida.

PubMed

Gonzalez, Dani O; Cooper, Jennifer N; McLeod, Daryl J

2017-12-11

Most patients with spina bifida require ventriculoperitoneal (VP) shunt placement. Some also require bladder augmentation, which may increase the risk of VP shunt malfunction and/or failure. The aim of this study was to assess whether bladder augmentation affects the rate of VP shunt failure in this population. Using the Pediatric Health Information System, we studied patients with spina bifida born between 1992 and 2014 who underwent VP shunt placement. Using conditional logistic regression, we compared age- and hospital-matched patients who did and did not undergo a bladder augmentation to determine their difference in rates of VP shunt failure. There were 4192 patients with spina bifida who underwent both surgical closure and VP shunt placement. Of these, 203 patients with bladder augmentation could be matched to 593 patients without bladder augmentation. VP shunt failure occurred within 2 years in 7.7% of patients, the majority of whom were in the group who underwent bladder augmentation (87%). After adjusting for confounders, undergoing bladder augmentation was independently associated with VP shunt failure (HR: 33.5, 95% CI: 13.15-85.44, p< 0.001). Bladder augmentation appears to be associated with VP shunt failure. Additional studies are necessary to better define this relationship and identify risk-reduction techniques.

Effect of drying and frying conditions on physical and chemical characteristics of fish maw from swim bladder of seabass (Lates calcarifer).

PubMed

Sinthusamran, Sittichoke; Benjakul, Soottawat

2015-12-01

Swim bladder is generated as a by-product during evisceration. It has been used for the production of fish maw, in which several processing parameters determine the characteristics or quality of the resulting fish maw. The present study aimed to investigate the characteristics of fish maws from seabass swim bladder as influenced by drying and frying conditions. The expansion ratio and oil uptake content of fish maw increased as the moisture content of swim bladder increased (P < 0.05). Nevertheless, the expansion ratio of fish maw decreased when the moisture content was higher than 150 g kg(-1) . The L*-value decreased, whilst the a*- and b*-values of fish maw increased with increasing moisture content. When pre-frying and frying temperatures increased, the expansion ratio of fish maw increased (P < 0.05). However, the expansion ratio decreased when the frying was performed at a temperature higher than 200 °C. The oil uptake contents of fish maw with frying temperatures of 180 and 200 °C were in the range of 451.06-578.06 g kg(-1) , whereas the lower contents (378.60-417.17 g kg(-1) ) were found in those having frying temperatures of 220-240 °C. Hardness of fish maw decreased but no changes in fracturability were observed with increasing pre-frying temperature when subsequent frying was carried out 200 °C. Drying temperatures, moisture content, pre-frying and frying temperatures were the factors influencing the characteristics and properties of fish maws from seabass swim bladder. Fish maw could be prepared by pre-frying swim bladder, dried at 60 °C to obtain 150 g kg(-1) moisture content, at 110 °C for 5 min, followed by frying at 200 °C for 20 s. © 2014 Society of Chemical Industry.

Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

PubMed

Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

2017-01-01

Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

Bladder cancer mortality trends and patterns in Córdoba, Argentina (1986-2006).

PubMed

Pou, Sonia Alejandra; Osella, Alberto Ruben; Diaz, Maria Del Pilar

2011-03-01

Bladder cancer is common worldwide and the fourth most commonly diagnosed malignancy in men in Argentina. To describe bladder cancer mortality trends in Córdoba (1986-2006), considering the effect of age, period, and cohort, and to estimate the effect of arsenic exposure on bladder cancer, and its interaction with sex, while controlling by smoking habits and space and time variation of the rates. A joinpoint regression was performed to compute the estimated annual percentage changes (EAPC) of the age-standardized mortality rates (ASMR) in an adult population from Córdoba, Argentina. A Poisson model was fitted to estimate the effect of age, period, and cohort. The influence of gender, tobacco smoking (using lung cancer ASMR as surrogate), and arsenic in drinking water was examined using a hierarchical model. A favorable trend (1986-2006) in bladder cancer ASMR in both sexes was found: EAPC of -2.54 in men and -1.69 in women. There was a decreasing trend in relative risk (RR) for cohorts born in 1931 or after. The multilevel model showed an increasing risk for each increase in lung cancer ASMR unit (RR = 1.001) and a biological interaction between sex and arsenic exposure. RR was higher among men exposed to increasing As-exposure categories (RR male low exposure 3.14, RR male intermediate exposure 4.03, RR male high exposure 4.71 versus female low exposure). A non-random space-time distribution of the rates was observed. There has been a decreasing trend in ASMR for bladder cancer in Córdoba. This study confirms that bladder cancer is associated with age, gender, smoking habit, and exposure to arsenic. Moreover, an effect measure modification between exposure to arsenic and sex was found.

Radical cystectomy with W-shaped orthotopic ileal neobladder constructed with non-absorbable titanium staples-long term follow-up.

PubMed

Kravchick, Sergey; Lobik, Leonid; Paz, Adrian; Stepnov, Eugeny; Ben-Dor, David; Cytron, Shmuel

2013-01-01

We retrospectively assessed our experience with the W-shaped orthotopic ileal pouch, which was constructed with non-absorbable titanium staples. For these purpose, we discuss the results of bladder capacity, urinary continence and early and long-term postoperative complications. We included in the study 17 patients who underwent radical cystoprostatectomy followed by construction of an orthotopic W-shaped ileal pouch between October 2000 and November 2009. A 65-70 cm segment of ileum was isolated and prearranged into a W-configuration, leaving two 10 cm intact segments on both sides of the ileal fragment. In our technique we entirely anatomized all adjacent limbs in order to create a sphere-shaped pouch. The ureters were directly anastomized to both intact segments of the ileal division. All our patients underwent pouchscopy 6 months after operation and annually. Mean operative time for neobladder reconstruction and ureteral anastomoses was 87 ± 7.67 minutes. In one patient a leak from the ileo-ileal anastomosis was confirmed on the 3rd day after operation. In 2 cases unilateral stricture of the ureteral-neobladder anastomosis was documented. Staple lines were mostly covered with ileal mucosa after 6 months. The mean functional bladder capacity was 340 ± 27.6 mL and 375 ± 43.4 mL at 6 and 12 months, respectively. First-year daytime and nighttime continence was good and acceptable in 90% and 78% of patients, while it increased to 95% during the 2nd year. The long term follow-up shows that non-absorbable titanium staples can be safely used for creation of an orthotopic ileal neobladder. However, these data should be further validated in a larger series of patients.

Importance of contraction history on muscle force of porcine urinary bladder smooth muscle.

PubMed

Menzel, Robin; Böl, Markus; Siebert, Tobias

2017-02-01

The purpose of this study was to provide a comprehensive dataset of porcine urinary bladder smooth muscle properties. Particularly, the history dependence of force production, namely force depression (FD) following shortening and force enhancement (FE) following stretch, was analysed. During active micturition, the circumference of the urinary bladder changes enormously. Thus, FD might be an important phenomenon during smooth muscle contraction. Electrically stimulated, intact urinary bladder strips from pigs (n = 10) were suspended in an aerated-filled organ bath, and different isometric, isotonic, and isokinetic contraction protocols were performed to determine the force-length and the force-velocity relation. FD and FE were assessed in concentric and eccentric contractions with different ramp lengths and ramp velocities. Bladder smooth muscles exhibit considerable amounts of FD and FE. The amount of FD increased significantly with ramp length, while FE did not change. However, FE and FD were independent of ramp velocity. The results imply that smooth muscle bladder strips exhibit similar muscle properties and history-dependent behaviour compared to striated muscles. The provided dataset of muscle properties is important for bladder modelling as well as for the analyses and interpretation of dynamic bladder filling and voiding.

Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin.

PubMed

Ito, Yoshihiko; Kashiwabara, Michishi; Yoshida, Akira; Hikiyama, Eriko; Onoue, Satomi; Yamada, Shizuo

2016-01-01

Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.

Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells.

PubMed

Wen, Wu; Li, Jingying; Wang, Longwang; Xing, Yifei; Li, Xuechao; Ruan, Hailong; Xi, Xiaoqing; Xiong, Jianhua; Kuang, Renrui

2017-08-18

The neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) plays a pivotal oncogenic role in various types of human cancers. However, the function of NEDD4 in bladder cancer has not been fully investigated. In the present study, we aim to explore whether NEDD4 governs cell proliferation, apoptosis, migration, and invasion in bladder cancer cells. Our results showed that downregulation of NEDD4 suppressed cell proliferation in bladder cancer cells. Moreover, we found that inhibition of NEDD4 significantly induced cell apoptosis. Furthermore, downregulation of NEDD4 retarded cell migration and invasion. Notably, overexpression of NEDD4 enhanced cell growth and inhibited apoptosis. Consistently, upregulation of NEDD4 promoted cell migration and invasion in bladder cancer cells. Mechanically, our Western blotting results revealed that downregulation of NEDD4 activated PTEN and inhibited Notch-1 expression, whereas upregulation of NEDD4 reduced PTEN level and increased Notch-1 level in bladder cancer cells. Our findings indicated that NEDD4 exerts its oncogenic function partly due to regulation of PTEN and Notch-1 in bladder cancer cells. These results further revealed that targeting NEDD4 could be a useful approach for the treatment of bladder cancer.

Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

PubMed

Aydin, H; Ercan, F; Cetinel, S; San, T

2001-08-01

This morphological study aims to investigate the effects of defibrotide, a deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or, either protamine sulfate (bladder injury group) or protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in phosphate buffered solution. The morphology of the urinary bladder was investigated using light and electron microscopy. The number of mast cells in the mucosa, mucosal alterations, intercellular junctions, surface topography and the glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal surface were evaluated. In the bladder injury group, ulcerated areas, irregularity of the GAG layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and dilatations in the intercellular spaces in the urothelium were observed. In the bladder injury+defibrotide group a relatively normal urothelial topography, GAG layer and a few mast cells in the mucosa, some dilatations between the intercellular areas, less uniform microvilli, regular perinuclear cistern and tight junctions were observed. These results show that defibrotide can inhibit PS induced bladder damage.

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

PubMed

Cho, Young-Man; Hasumura, Mai; Imai, Toshio; Takami, Shigeaki; Nishikawa, Akiyoshi; Ogawa, Kumiko

2017-07-01

Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg -1 body weight day -1 ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg -1 body weight day -1 ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg -1 body weight day -1 ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer.

PubMed

Lee, Jun Taik; Lee, Sang Don; Lee, Jeong Zoo; Chung, Moon Kee; Ha, Hong Koo

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10(-2) and 1.99×10(-2) in benign bladder tissue and 1.39×10(-2) and 2.32×10(-2) in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets.

SU-E-J-83: CBCT Based Rectum and Bladder Dose Tracking in the Prostate Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Z; Wang, J; Yang, Z

2015-06-15

Purpose: The aim of this study is to monitor the volume changes of bladder and rectum and evaluate the dosimetric changes of bladder and rectum using daily cone-beam CT for prostate radiotherapy. Methods: The data of this study were obtained from 12 patients, totally 222 CBCTs. All the volume of the bladder and the rectum on the CBCT were normalized to the bladder and the rectum on their own original CT to monitory the volume changes. To evaluate dose delivered to the OARs, volumes that receive 70Gy (V70Gy), 60Gy, 50Gy, 40Gy and 30Gy are calculated for the bladder and themore » rectum, V20Gy and V10Gy for rectum additionally. And the deviation of the mean dose to the bladder and the rectum are also chosen as the evaluation parameter. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19. Results: The results show that the variances of the normalize volume of the bladder and the rectum are 0.15–0.58 and 0.13–0.50. The variances of V70Gy, V60Gy, V50Gy, V40Gy and V30Gy of bladder are bigger than rectum for 11 patients. The linear regression analysis indicated a negative correlation between the volume and the mean dose of the bladder (p < 0.05). A 10% increase in bladder volume will cause 5.1% (±4.3%) reduction in mean dose. Conclusion: The bladder volume change is more significant than that for rectum for the prostate cancer patient. The volume changes of rectum are not significant except air gap in the rectum. Bladder volume varies will cause significant dose change. The bladder volume monitoring before fractional treatment delivery would be crucial for accuracy dose delivery.« less

Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

DTIC Science & Technology

2007-02-01

bladder and the rectum are overprotected while the PTV coverage is undesirably reduced. On the other hand, if their maximum dose is increased and/or...B, the bladder and rectum were overprotected with undesirably low PTV coverage (84.54%). The reduction of their weighting factor increased PTV

Portable bladder ultrasound: an evidence-based analysis.

PubMed

2006-01-01

The aim of this review was to assess the clinical utility of portable bladder ultrasound. TARGET POPULATION AND CONDITION Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device's hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario's complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort.

Portable Bladder Ultrasound

PubMed Central

2006-01-01

Executive Summary Objective The aim of this review was to assess the clinical utility of portable bladder ultrasound. Clinical Need: Target Population and Condition Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. The Technology Being Reviewed Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. Review Strategy To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Summary of Findings Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device’s hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. Economic Analysis An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Considerations for Policy Development Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario’s complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort. PMID:23074481

Traditional Foley drainage systems--do they drain the bladder?

PubMed

Garcia, Maurice M; Gulati, Shelly; Liepmann, Dorian; Stackhouse, G Bennett; Greene, Kirsten; Stoller, Marshall L

2007-01-01

Foley catheters are assumed to drain the bladder to completion. Drainage characteristics of Foley catheter systems are poorly understood. To investigate unrecognized retained urine with Foley catheter drainage systems, bladder volumes of hospitalized patients were measured with bladder scan ultrasound volumetrics. Additionally, an in vitro bench top mock bladder and urinary catheter system was developed to understand the etiology of such residual volumes. A novel drainage tube design that optimizes indwelling catheter drainage was also designed. Bedside bladder ultrasound volumetric studies were performed on patients hospitalized in ward and intensive care unit. If residual urine was identified the drainage tubing was manipulated to facilitate drainage. An ex vivo bladder-urinary catheter model was designed to measure flow rates and pressures within the drainage tubing of a traditional and a novel drainage tube system. A total of 75 patients in the intensive care unit underwent bladder ultrasound volumetrics. Mean residual volume was 96 ml (range 4 to 290). In 75 patients on the hospital ward mean residual volume was 136 ml (range 22 to 647). In the experimental model we found that for every 1 cm in curl height, obstruction pressure increased by 1 cm H2O within the artificial bladder. In contrast, the novel spiral-shaped drainage tube demonstrated rapid (0.5 cc per second), continuous and complete (100%) reservoir drainage in all trials. Traditional Foley catheter drainage systems evacuate the bladder suboptimally. Outflow obstruction is caused by air-locks that develop within curled redundant drainage tubing segments. The novel drainage tubing design eliminates gravity dependent curls and associated air-locks, optimizes flow, and minimizes residual bladder urine.

Residence in Proximity of a Coal-Oil-Fired Thermal Power Plant and Risk of Lung and Bladder Cancer in North-Eastern Italy. A Population-Based Study: 1995-2009.

PubMed

Collarile, Paolo; Bidoli, Ettore; Barbone, Fabio; Zanier, Loris; Del Zotto, Stefania; Fuser, Simonetta; Stel, Fulvio; Panato, Chiara; Gallai, Irene; Serraino, Diego

2017-07-31

This study investigated the risk of lung and bladder cancers in people residing in proximity of a coal-oil-fired thermal power plant in an area of north-eastern Italy, covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter, and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged ≥75 years significantly increased risks of lung and bladder cancers were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to a high exposure to SO2. Acknowledging the limitations of our study, in particular that we did not have information regarding cigarette smoking habits, the findings of this study indicate that air pollution exposure may have had a role with regard to the risk of lung and bladder cancers limited to women aged ≥75 years. Such increased risk warrants further analytical investigations.

Bladder control, urgency, and urge incontinence: evidence from functional brain imaging.

PubMed

Griffiths, Derek; Tadic, Stasa D

2008-01-01

To review brain imaging studies of bladder control in subjects with normal control and urge incontinence; to define a simple model of supraspinal bladder control; and to propose a neural correlate of urgency and possible origins of urge incontinence. Review of published reports of brain imaging relevant to urine storage, and secondary analyses of our own recent observations. In a simple model of normal urine storage, bladder and urethral afferents received in the periaqueductal gray (PAG) are mapped in the insula, forming the basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and control; the prefrontal cortex makes voiding decisions. The net result, as the bladder fills, is inhibition of the pontine micturition center (PMC) and of voiding, together with gradual increase in insular response, corresponding to increasing desire to void. In urge-incontinent subjects, brain responses differ. At large bladder volumes and strong sensation, but without detrusor overactivity (DO), most cortical responses become exaggerated, especially in ACG. This may be both a learned reaction to previous incontinence episodes and the neural correlate of urgency. The neural signature of DO itself seems to be prefrontal deactivation. Possible causes of urge incontinence include dysfunction of prefrontal cortex or limbic system, suggested by weak responses and/or deactivation, as well as abnormal afferent signals or re-emergence of infantile reflexes. Bladder control depends on an extensive network of brain regions. Dysfunction in various parts may contribute to urge incontinence, suggesting that there are different phenotypes requiring different treatments. (c) 2007 Wiley-Liss, Inc.

Overactive bladder symptom severity, bother, help-seeking behavior, and quality of life in patients with type 2 diabetes: a path analysis.

PubMed

Xu, Dongjuan; Zhao, Meng; Huang, Liqun; Wang, Kefang

2018-01-02

This study aimed to investigate the relationships among overactive bladder (OAB) symptom severity, bother, help-seeking behavior, and quality of life (QOL) in patients with type 2 diabetes. A total of 127 diabetic patients, aged at least 18 years, with overactive bladder from a hospital in Shandong Province, China, were recruited for this study. Symptom severity, bother, and quality of life were assessed using the Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and Overactive Bladder Questionnaire Short Form (OAB-q SF), respectively. Help-seeking behavior was assessed by asking patients whether they consulted health care professionals or received treatment for their bladder problems. A two-step path analysis was performed to analyze the data. OAB symptom severity was directly associated with lower levels of QOL, and the strength of this association was no longer significant when taking bother and help-seeking behavior into account. Bother increased with OAB symptom severity, and patients with bothersome OAB tended to have lower levels of QOL. Moreover, bother increased help-seeking behavior; however, patients who sought help tended to have lower levels of QOL. Our findings highlight the role of bother and help-seeking behavior in the relationship between OAB symptom severity and QOL. To improve a patient's QOL, health care providers should focus not only on symptom bother but also on dysfunctional help-seeking patterns.

Intravesical PAC1 Receptor Antagonist, PACAP(6–38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice

PubMed Central

Girard, Beatrice M.; Malley, Susan E.; Mathews, Morgan M.; May, Victor

2017-01-01

Chronic NGF overexpression (OE) in the urothelium, achieved through the use of a highly urothelium-specific uroplakin II promoter, stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency and non-voiding contractions, and referred somatic sensitivity. Additional NGF-mediated pleiotropic changes might contribute to increased voiding frequency and pelvic hypersensitivity in NGF-OE mice such as neuropeptide/receptor systems including PACAP(Adcyap1) and PAC1 receptor (Adcyap1r1). Given the presence of PAC1-immunoreactive fibers and the expression of PAC1 receptor expression in bladder tissues, and PACAP-facilitated detrusor contraction, whether PACAP/receptor signaling contributes to increased voiding frequency and somatic sensitivity was evaluated in NGF-OE mice. Intravesical administration of the PAC1 receptor antagonist, PACAP(6–38) (300 nM), significantly (p ≤ 0.01) increased intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP(6–38) also decreased baseline bladder pressure in NGF-OE mice. PACAP(6–38) had no effects on bladder function in WT mice. Intravesical administration of PACAP(6–38) (300 nM) significantly (p ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in WT mice. PACAP/receptor signaling contributes to the increased voiding frequency and pelvic sensitivity observed in NGF-OE mice. PMID:27146136

Spectroscopic analysis of bladder cancer tissues using Fourier transform infrared spectroscopy

NASA Astrophysics Data System (ADS)

Al-Muslet, Nafie A.; Ali, Essam E.

2012-03-01

Bladder cancer is one of the most common cancers in Africa. It takes several days to reach a diagnosis using histological examinations of specimens obtained by endoscope, which increases the medical expense. Recently, spectroscopic analysis of bladder cancer tissues has received considerable attention as a diagnosis technique due to its sensitivity to biochemical variations in the samples. This study investigated the use of Fourier transform infrared (FTIR) spectroscopy to analyze a number of bladder cancer tissues. Twenty-two samples were collected from 11 patients diagnosed with bladder cancer from different hospitals without any pretreatment. From each patient two samples were collected, one normal and another cancerous. FTIR spectrometer was used to differentiate between normal and cancerous bladder tissues via changes in spectra of these samples. The investigations detected obvious changes in the bands of proteins (1650, 1550 cm-1), lipids (2925, 2850 cm-1), and nucleic acid (1080, 1236 cm-1). The results show that FTIR spectroscopy is promising as a rapid, accurate, nondestructive, and easy to use alternative method for identification and diagnosis of bladder cancer tissues.

Continence outcomes in patients undergoing robotic assisted laparoscopic mitrofanoff appendicovesicostomy.

PubMed

Wille, Mark A; Zagaja, Gregory P; Shalhav, Arieh L; Gundeti, Mohan S

2011-04-01

Continent catheterizable channels for emptying the bladder are typically performed via an open surgical approach. We present our surgical approach and initial outcomes with specific attention to continence for robotic assisted laparoscopic Mitrofanoff appendicovesicostomy formation. Between February 2008 and April 2010, 13 patients were considered for robotic assisted laparoscopic Mitrofanoff appendicovesicostomy and 11 underwent the procedure (2 open conversions). Five patients underwent enterocystoplasty with appendicovesicostomy and 6 underwent isolated appendicovesicostomy. The appendicovesicostomy anastomosis was performed on the anterior (without augmentation) or posterior (with augmentation) bladder wall and the stoma was brought to the umbilical site or right lower quadrant. Detrusor backing (4 cm) was ensured except in 1 patient (number 5). Mean patient age at surgery was 10.4 years (range 5 to 14). Mean estimated blood loss was 61.8 cc. Mean operative time for isolated appendicovesicostomy was 347 minutes and there were no intraoperative complications. Incontinence through the stoma developed in 1 patient with inadequate detrusor backing (less than 4 cm), which resolved with dextranomer/hyaluronic acid injection into the appendicovesicostomy anastomosis. This patient had resolution of incontinence with an increase in bladder capacity to 300 cc. Three patients required skin flap revision for cutaneous scarring. To date all patients are catheterizing without difficulty and are continent. Median followup was 20 months (range 3 to 29). We are encouraged by our preliminary experience with the robotic assisted laparoscopic Mitrofanoff appendicovesicostomy continent urinary diversion with or without ileocystoplasty. Early in the experience we emphasize the importance of 4 cm of detrusor backing to maintain stomal continence. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The different roles of opioid receptors in the inhibitory effects induced by sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive conditions in cats.

PubMed

Wang, Zhaoxia; Liao, Limin; Deng, Han; Li, Xing; Chen, Guoqing; Liao, Xiwen

2018-06-04

To examine the roles of opioid receptors in the inhibition of nociceptive and nonnociceptive bladder reflexes by sacral dorsal root ganglion (DRG) stimulation in cats. Hook electrodes were placed in the right S1 and S2 DRG of cats. The bladders were infused with physiologic saline or 0.25% acetic acid (AA). Naloxone (0.1, 0.3, and 1 mg/kg), an opioid receptor antagonist, was administered intravenously. S1 or S2 DRG stimulation was applied before and after administering the drug. Multiple cystometrograms were performed to determine the effects of DRG stimulation and opioid receptors on the micturition reflex under nociceptive and non-nociceptive conditions. AA significantly (P < 0.01) reduced bladder capacity (BC). DRG stimulation at threshold (T) and 1.5 T significantly increased BC of the saline control under nociceptive and non-nociceptive conditions. When saline was infused, naloxone (0.1-1 mg/kg) significantly (P < 0.01) reduced BC; however, naloxone did not change BC during AA irritation. During saline infusion, naloxone (0.3 and 1 mg/kg) partly blocked S1 DRG stimulation-induced inhibition but had only a slight effect on S2 DRG stimulation. During AA infusion, naloxone (0.3 and 1 mg/kg) only partially blocked S1 DRG stimulation at T intensity but not during 1.5 T stimulation. However, no doses of naloxone significantly affected S2 DRG stimulation. Opioid receptors play a role in sacral DRG stimulation on non-nociceptive condition but are not involved in the inhibitory effect of stimulation in nociceptive conditions. © 2018 Wiley Periodicals, Inc.

Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer

PubMed Central

Yuan, Jian-Min; Chan, Kenneth K.; Coetzee, Gerhard A.; Castelao, J.Esteban; Watson, Mary A.; Bell, Douglas A.; Wang, Renwei; Yu, Mimi C.

2008-01-01

Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual’s susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case–control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19–48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19–1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12–1.81) and 1.71 (1.25–2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12–3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. PMID:18544563

Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

PubMed Central

Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

2011-01-01

Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

Increased Expression of Interleukin-6 Family Members and Receptors in Urinary Bladder with Cyclophosphamide-Induced Bladder Inflammation in Female Rats

PubMed Central

Girard, Beatrice M.; Cheppudira, Bopaiah P.; Malley, Susan E.; Schutz, Kristin C.; May, Victor; Vizzard, Margaret A.

2011-01-01

Recent studies suggest that janus-activated kinases–signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, members of the interleukin (IL)-6 family of cytokines including, leukemia inhibitory factor (LIF), IL-6, and ciliary neurotrophic factor (CNTF) and associated receptors, IL-6 receptor (R) α, LIFR, and gp130 were examined in the urinary bladder in control and CYP-treated rats. Cytokine and receptor transcript and protein expression and distribution were determined in urinary bladder after CYP-induced cystitis using quantitative, real-time polymerase chain reaction (Q-PCR), western blotting, and immunohistochemistry. Acute (4 h; 150 mg/kg; i.p.), intermediate (48 h; 150 mg/kg; i.p.), or chronic (75 mg/kg; i.p., once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Q-PCR analyses revealed significant (p ≤ 0.01) CYP duration- and tissue- (e.g., urothelium, detrusor) dependent increases in LIF, IL-6, IL-6Rα, LIFR, and gp130 mRNA expression. Western blotting demonstrated significant (p ≤ 0.01) increases in IL-6, LIF, and gp130 protein expression in whole urinary bladder with CYP treatment. CYP-induced cystitis significantly (p ≤ 0.01) increased LIF-immunoreactivity (IR) in urothelium, detrusor, and suburothelial plexus whereas increased gp130-IR was only observed in urothelium and detrusor. These studies suggest that IL-6 and LIF may be potential upstream chemical mediators that activate JAK/STAT signaling in urinary bladder pathways. PMID:21373362

Type 2 Diabetes and TZDs (Thiazolidinediones)

MedlinePlus

... suggest that pioglitazone may increase the risk of bladder cancer, but this has not been proven. Even if ... you have a personal or family history of bladder cancer. If you have type 2 diabetes and want ...

Bladder outlet obstruction (BOO) in men with castration-resistant prostate cancer.

PubMed

Rom, Maximilian; Waldert, Matthias; Schatzl, Georg; Swietek, Natalia; Shariat, Shahrokh F; Klatte, Tobias

2014-07-01

To evaluate the frequency of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in patients with castration-resistant prostate cancer (CRPC) and lower urinary tract symptoms (LUTS). Our prospective urodynamics database was queried. Inclusion criteria were CRPC and an International Prostate Symptom Score (IPSS) ≥ 20. Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS. Twenty-one patients were identified. Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement (BPE). The median age of patients in the CRPC group was 74 years, and the median prostate-specific antigen (PSA) level at the time of the urodynamic study was 90 ng/mL. According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed. DO was seen in 12 patients (57%). Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities (P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028). This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO. LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity. A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates. Larger prospective studies are needed to confirm our findings. © 2013 The Authors. BJU International © 2013 BJU International.

Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

PubMed

Yoshizawa, Tsuyoshi; Hayashi, Yukio; Yoshida, Akira; Yoshida, Shohei; Ito, Yoshihiko; Yamaguchi, Kenya; Yamada, Shizuo; Takahashi, Satoru

2018-03-01

To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P 2 X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P 2 X receptor were measured by a radioreceptor assay using [N-methyl- 3 H] scopolamine methyl chloride ([ 3 H]NMS) and α,β-methylene-ATP (2,8- 3 H) tetrasodium salt ([ 3 H]α,β-MeATP). In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [ 3 H]NMS and [ 3 H]α,β-MeATP was concurrently increased in the bladder from diabetic rats. Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P 2 X receptors in STZ-induced diabetic rats.

Effects of St John's wort and its active constituents, hypericin and hyperforin, on isolated rat urinary bladder.

PubMed

Valeri, Aurora; Capasso, Raffaele; Valoti, Massimo; Pessina, Federica

2012-12-01

To investigate the effect of St John's wort (SJW) and its active constituents hypericin and hyperforin on detrusor smooth muscle contractility and their possible neuroprotective role against ischaemic-like conditions, which could arise during overactive bladder disease. In whole bladders, intrinsic nerves underwent electrical field stimulation (EFS). The effect of drugs on the contractile response and its recovery in reperfusion phase (R) was monitored at different concentrations during 1 or 2 h of anoxia-glucopenia (A-G) and the first 30 min of R. The effects of the drugs were also investigated on rat detrusor muscle strips contracted with carbachol, KCl and electrically. SJW has spasmolytic activity, which increases with increasing concentration and it worsens the damage induced by A-G/R on rat urinary bladder. Hypericin and hyperforin had no effect during ischemic-like conditions but they both exert a dual modulation of rat detrusor strips contraction. At high micromolar concentrations they showed a relaxing effect, but at submicromolar range hypericin increased the plasma membrane depolarisation and hyperforin showed a stimulatory effect on the cholinergic system. The results of our study showed that SJW and its constituents could modulate urinary bladder contractility and even worsen A-G/R injury. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Lack of Promoting Effects of α‐Linolenic, Linoleic or Palmitic Acid on Urinary Bladder Carcinogenesis in Rats

PubMed Central

Mori, Satoru; Chen, Tianxin; Murai, Takashi; Fukushima, Shoji

1995-01-01

Potential promoting effects of α‐linolenic, linoleic and palmitic acids were investigated in a two‐stage urinary bladder carcinogenesis model. In experiment 1, male F344 rats were given 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosainine (BBN) in their drinking water for 4 weeks and then basal diet containing 10%α‐linolenic, 10% linoleic or 10% palmitic acid along with 0.2% butylated hydroxyanisole (BHA) as an antioxidant for 24 weeks. The development of tumors in the urinary bladder was not increased by treatment with any of the fatty acids. In experiment 2, male F344 rats were given 10%α‐linolenic, 10% linoleic or 10% palmitic acid along with 0.2% BHA in their diet for 8 weeks without prior BBN treatment. The administration of fatty acids was not associated with any increase in the 5‐bromo‐2′‐deoxyuridine labeling index of the urinary bladder epithelium. Serum and/or urine fatty acid Ievels increased in the cases of α‐linolenic and linoleic acid treatments, but not with palmitic acid. Under the present experimental conditions neither the two polyunsaturated nor the one saturated fatty acid exerted any promoting effect on urinary bladder carcinogenesis. PMID:7622416

The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

PubMed Central

Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine D.; Tang, Wei; Porter-Gill, Patricia; Chatterjee, Nilanjan; Scott-Johnson, Alexandra; Garcia-Closas, Montserrat; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B.; Karagas, Margaret R.; Tarway, McAnthony; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A.; Kida, Masatoshi; Monawar Hosain, GM; Malats, Nuria; Kogevinas, Manolis; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, Reina; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald L.; Grubb, Robert L.; Black, Amanda; Landi, Maria T.; Caporaso, Neil E.; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquita, H. Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Govannucci, Edward; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M.; Jacobs, Eric J.; Diver, W. Ryan; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J.; Cortessis, Victoria K.; Conti, David V.; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Haiman, Christopher A.; Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Grossman, H. Barton; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph; Chanock, Stephen J.; Hewitt, Stephen M.; Silverman, Debra T.; Rothman, Nathaniel; Prokunina-Olsson, Ludmila

2014-01-01

A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell cycle protein. We performed genetic fine mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r2≥0.7) associated with increased bladder cancer risk. From this group we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWAS, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele odds ratio (OR) =1.18 (95%CI=1.09-1.27, p=4.67×10−5 vs. OR =1.01 (95%CI=0.93-1.10, p=0.79) for non-aggressive disease, with p=0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (p=0.013) and, independently, with each rs7257330-A risk allele (ptrend=0.024). Over-expression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E over-expression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. PMID:25320178

Acute Urinary Obstruction in a Tetraplegic Patient from Misplacement of Catheter in Urethra.

PubMed

Vaidyanathan, Subramanian; Singh, Gurpreet; Hughes, Peter L; Soni, Bakul M

2016-01-01

A male tetraplegic patient attended accident and emergency with a blocked catheter; on removing the catheter, he passed bloody urine. After three unsuccessful attempts were made to insert a catheter by nursing staff, a junior doctor inserted a three-way Foley catheter with a 30-mL balloon but inflated the balloon with 10 mL of water to commence the bladder irrigation. The creatinine level was mostly 19 µmol/L (range: 0-135 µmol/L) but increased to 46 µmol/L on day 7. Computerized tomography urogram revealed that the bilateral hydronephrosis with hydroureter was extended down to urinary bladder, the bladder was distended, prostatic urethra was dilated and filled with urine, and although the balloon of Foley catheter was not seen in the bladder, the tip of the catheter was seen lying in the urethra. Following the re-catheterization, the creatinine level decreased to 21 µmol/L. A follow-up ultrasound scan revealed no evidence of hydronephrosis in both kidneys. Flexible cystoscopy revealed inflamed bladder mucosa, catheter reaction, and tiny stones. There was no bladder tumor. This case report concludes that the cause of bilateral hydronephrosis, hydroureter, and distended bladder was inadequate drainage of urinary bladder as the Foley balloon that was under-filled slipped into the urethra resulting in an obstruction to urine flow. Urethral catheterization in tetraplegic patients should be performed by senior, experienced staff in order to avoid trauma and incorrect positioning. Tetraplegic subjects with decreased muscle mass have low creatinine level. Increase in creatinine level (>1.5 times the basal level) indicates acute kidney injury, although peak creatinine level may still be within laboratory reference range. While scanning the urinary tract of spinal cord injury patients with indwelling urinary catheter, if Foley balloon is not seen within the bladder, urethra should be scanned to locate the Foley balloon.

A Murine Model of Inflammatory Bladder Disease: Cathelicidin Peptide Induced Bladder Inflammation and Treatment With Sulfated Polysaccharides

PubMed Central

Oottamasathien, Siam; Jia, Wanjian; McCoard, Lindsi; Slack, Sean; Zhang, Jianxing; Skardal, Aleksander; Job, Kathleen; Kennedy, Thomas P.; Dull, Randal O.; Prestwich, Glenn D.

2013-01-01

Purpose Studies show that LL-37 is a naturally occurring urinary defensin peptide that is up-regulated during urinary tract infections. Although normal urinary LL-37 levels are antimicrobial, we propose that increased LL-37 may trigger bladder inflammation. We further suggest that anti-inflammatory sulfated polysaccharides known as semi-synthetic glycosaminoglycan ether compounds can treat/prevent LL-37 mediated bladder inflammation. Materials and Methods C57BL/6 mice were catheterized/instilled with LL-37 (320 μM at 150 μl) for 45 minutes. Animals were sacrificed at 12 and 24 hours, and tissues were examined using hematoxylin and eosin. Separate experiments were performed for myeloperoxidase to quantify inflammation. GM-1111 semi-synthetic glycosaminoglycan ether treatments involved instillation of 10 mg/ml for 45 minutes directly before or after LL-37. Tissues were harvested at 24 hours. To compare semi-synthetic glycosaminoglycan ether efficacy experiments were performed using 10 mg/ml heparin. Finally, tissue localization of semi-synthetic glycosaminoglycan ether was examined using a fluorescent GM-1111-Alexa Fluor® 633 conjugate. Results Profound bladder inflammation developed after LL-37. Greater tissue inflammation occurred after 24 hours compared to that at 12 hours. Myeloperoxidase assays revealed a 21 and 61-fold increase at 12 and 24 hours, respectively. Semi-synthetic glycosaminoglycan ether treatment after LL-37 showed mild attenuation of inflammation with myeloperoxidase 2.5-fold below that of untreated bladders. Semi-synthetic glycosaminoglycan ether treatment before LL-37 demonstrated almost complete attenuation of inflammation. Myeloperoxidase results mirrored those in controls. In heparin treated bladders minimal attenuation of inflammation occurred. Finally, instillation of GM-1111-Alexa Fluor 633 revealed urothelial coating, significant tissue penetration and binding to endovasculature. Conclusions We developed what is to our knowledge a new model of inflammatory bladder disease by challenge with the naturally occurring urinary peptide LL-37. We also noted that a new class of anti-inflammatory sulfated polysaccharides prevents and mitigates bladder inflammation. PMID:21855919

Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: pathological implications in diagnosis.

PubMed

Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G; Horn, Adam J; Lele, Subodh M; Theodorescu, Dan; Batra, Surinder K

2014-01-01

Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

PubMed

Anderson, Beverley

2018-05-10

Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

A voxel-based finite element model for the prediction of bladder deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chai Xiangfei; Herk, Marcel van; Hulshof, Maarten C. C. M.

2012-01-15

Purpose: A finite element (FE) bladder model was previously developed to predict bladder deformation caused by bladder filling change. However, two factors prevent a wide application of FE models: (1) the labor required to construct a FE model with high quality mesh and (2) long computation time needed to construct the FE model and solve the FE equations. In this work, we address these issues by constructing a low-resolution voxel-based FE bladder model directly from the binary segmentation images and compare the accuracy and computational efficiency of the voxel-based model used to simulate bladder deformation with those of a classicalmore » FE model with a tetrahedral mesh. Methods: For ten healthy volunteers, a series of MRI scans of the pelvic region was recorded at regular intervals of 10 min over 1 h. For this series of scans, the bladder volume gradually increased while rectal volume remained constant. All pelvic structures were defined from a reference image for each volunteer, including bladder wall, small bowel, prostate (male), uterus (female), rectum, pelvic bone, spine, and the rest of the body. Four separate FE models were constructed from these structures: one with a tetrahedral mesh (used in previous study), one with a uniform hexahedral mesh, one with a nonuniform hexahedral mesh, and one with a low-resolution nonuniform hexahedral mesh. Appropriate material properties were assigned to all structures and uniform pressure was applied to the inner bladder wall to simulate bladder deformation from urine inflow. Performance of the hexahedral meshes was evaluated against the performance of the standard tetrahedral mesh by comparing the accuracy of bladder shape prediction and computational efficiency. Results: FE model with a hexahedral mesh can be quickly and automatically constructed. No substantial differences were observed between the simulation results of the tetrahedral mesh and hexahedral meshes (<1% difference in mean dice similarity coefficient to manual contours and <0.02 cm difference in mean standard deviation of residual errors). The average equation solving time (without manual intervention) for the first two types of hexahedral meshes increased to 2.3 h and 2.6 h compared to the 1.1 h needed for the tetrahedral mesh, however, the low-resolution nonuniform hexahedral mesh dramatically decreased the equation solving time to 3 min without reducing accuracy. Conclusions: Voxel-based mesh generation allows fast, automatic, and robust creation of finite element bladder models directly from binary segmentation images without user intervention. Even the low-resolution voxel-based hexahedral mesh yields comparable accuracy in bladder shape prediction and more than 20 times faster in computational speed compared to the tetrahedral mesh. This approach makes it more feasible and accessible to apply FE method to model bladder deformation in adaptive radiotherapy.« less

Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic Treatment.

PubMed

Tarcan, Tufan; Akbal, Cem; Sekerci, Cağri A; Top, Tuncay; Simşek, Ferruh

2014-04-01

This was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization. The study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia. Thirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated. Onabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.

Does sacral pulsed electromagnetic field therapy have a better effect than transcutaneous electrical nerve stimulation in patients with neurogenic overactive bladder?

PubMed

Fergany, Lamyaa A; Shaker, Husain; Arafa, Magdy; Elbadry, Mohamed S

2017-06-01

To compare the effectiveness of pulsed electromagnetic field therapy (PEMFT) and transcutaneous electrical nerve stimulation (TENS) on neurogenic overactive bladder dysfunction (OAB) in patients with spinal cord injury (SCI). In all, 80 patients [50 men and 30 women, with a mean (SD) age of 40.15 (8.76) years] with neurogenic OAB secondary to suprasacral SCI were included. They underwent urodynamic studies (UDS) before and after treatment. Patients were divided into two equal groups: Group A, comprised 40 patients who received 20 min of TENS (10 Hz with a 700 s generated pulse), three times per week for 20 sessions; Group B, comprised 40 patients who received PEMFT (15 Hz with 50% intensity output for 5 s/min for 20 min), three times per week for 20 sessions. In Group B, there was a significant increase in the maximum cystometric capacity ( P  < 0.001), volume at first uninhibited detrusor contraction ( P  < 0.002), and maximum urinary flow rate ( P  < 0.02). The UDS showed that the effects of PEMFT in patients with neurogenic OAB secondary to suprasacral SCI was better than TENS for inducing an inhibitory effect on neurogenic detrusor overactivity.

Target sequencing and CRISPR/Cas editing reveal simultaneous loss of UTX and UTY in urothelial bladder cancer.

PubMed

Ahn, Jinwoo; Kim, Kwang Hyun; Park, Sanghui; Ahn, Young-Ho; Kim, Ha Young; Yoon, Hana; Lee, Ji Hyun; Bang, Duhee; Lee, Dong Hyeon

2016-09-27

UTX is a histone demethylase gene located on the X chromosome and is a frequently mutated gene in urothelial bladder cancer (UBC). UTY is a paralog of UTX located on the Y chromosome. We performed target capture sequencing on 128 genes in 40 non-metastatic UBC patients. UTX was the most frequently mutated gene (30%, 12/40). Of the genetic alterations identified, 75% were truncating mutations. UTY copy number loss was detected in 8 male patients (22.8%, 8/35). Of the 9 male patients with UTX mutations, 6 also had copy number loss (66.7%). To evaluate the functional roles of UTX and UTY in tumor progression, we designed UTX and UTY single knockout and UTX-UTY double knockout experiments using a CRISPR/Cas9 lentiviral system, and compared the proliferative capacities of two UBC cell lines in vitro. Single UTX or UTY knockout increased cell proliferation as compared to UTX-UTY wild-type cells. UTX-UTY double knockout cells exhibited greater proliferation than single knockout cells. These findings suggest both UTX and UTY function as dose-dependent suppressors of UBC development. While UTX escapes X chromosome inactivation in females, UTY may function as a male homologue of UTX, which could compensate for dosage imbalances.

Use of Flexible Cystoscopy to Insert a Foley Catheter over a Guide Wire in Spinal Cord Injury Patients: Special Precautions to be Observed.

PubMed

Vaidyanathan, Subramanian; Soni, Bakul; Singh, Gurpreet; Hughes, Peter; Oo, Tun

2011-01-01

When urethral catheterisation is difficult or impossible in spinal cord injury patients, flexible cystoscopy and urethral catheterisation over a guide wire can be performed on the bedside, thus obviating the need for emergency suprapubic cystostomy. Spinal cord injury patients, who undergo flexible cystoscopy and urethral catheterisation over a guide wire, may develop potentially serious complications. (1) Persons with lesion above T-6 are susceptible to develop autonomic dysreflexia during cystoscopy and urethral catheterisation over a guide wire; nifedipine 5-10 milligrams may be administered sublingually just prior to the procedure to prevent autonomic dysreflexia. (2) Spinal cord injury patients are at increased risk for getting urine infections as compared to able-bodied individuals. Therefore, antibiotics should be given to patients who get haematuria or urethral bleeding following urethral catheterisation over a guide wire. (3) Some spinal cord injury patients may have a small capacity bladder; in these patients, the guide wire, which is introduced into the urinary bladder, may fold upon itself with the tip of guide wire entering the urethra. If this complication is not recognised and a catheter is inserted over the guide wire, the Foley catheter will then be misplaced in urethra despite using cystoscopy and guide wire.

Use of Flexible Cystoscopy to Insert a Foley Catheter over a Guide Wire in Spinal Cord Injury Patients: Special Precautions to be Observed

PubMed Central

Vaidyanathan, Subramanian; Soni, Bakul; Singh, Gurpreet; Hughes, Peter; Oo, Tun

2011-01-01

When urethral catheterisation is difficult or impossible in spinal cord injury patients, flexible cystoscopy and urethral catheterisation over a guide wire can be performed on the bedside, thus obviating the need for emergency suprapubic cystostomy. Spinal cord injury patients, who undergo flexible cystoscopy and urethral catheterisation over a guide wire, may develop potentially serious complications. (1) Persons with lesion above T-6 are susceptible to develop autonomic dysreflexia during cystoscopy and urethral catheterisation over a guide wire; nifedipine 5–10 milligrams may be administered sublingually just prior to the procedure to prevent autonomic dysreflexia. (2) Spinal cord injury patients are at increased risk for getting urine infections as compared to able-bodied individuals. Therefore, antibiotics should be given to patients who get haematuria or urethral bleeding following urethral catheterisation over a guide wire. (3) Some spinal cord injury patients may have a small capacity bladder; in these patients, the guide wire, which is introduced into the urinary bladder, may fold upon itself with the tip of guide wire entering the urethra. If this complication is not recognised and a catheter is inserted over the guide wire, the Foley catheter will then be misplaced in urethra despite using cystoscopy and guide wire. PMID:22110492

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis

PubMed Central

Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-01-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I–II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919–0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments. PMID:29616090

Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis.

PubMed

Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

2018-04-01

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments.

Dimethylarsinic acid in drinking water changed the morphology but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats

EPA Science Inventory

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In laboratory animals, it is dimethylarsinic acid [DMA(V)], a major arsenic metabolite in the urine of inorganic arsenic-exposed people, that increases transitional cell carcinoma, namely in F344 r...

The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Bladder Cancer Cells.

PubMed

Orywal, Karolina; Jelski, Wojciech; Werel, Tadeusz; Szmitkowski, Maciej

2018-01-02

The aim of this study was to determine the differences in the activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase (ALDH) in normal and cancerous bladder cells. Class III, IV of ADH and total ADH activity were measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method. Significantly higher total activity of ADH was found in both, low-grade and high-grade bladder cancer, in comparison to healthy tissues. The increased activity of total ADH in bladder cancer cells may be the cause of metabolic disorders in cancer cells, which may intensify carcinogenesis.

The location of pain and urgency sensations during cystometry.

PubMed

Veit-Rubin, Nikolaus; Cartwright, Rufus; Esmail, Alisha; Digesu, G Alessandro; Fernando, Ruwan; Khullar, Vikram

2017-03-01

The relationship between bladder pain and urinary urgency sensations is poorly understood. We analyzed the relationship between locations and intensities of urgency and pain sensations felt during filling cystometry. Participants completed the King's Health Questionnaire (KHQ) to indicate presence of bladder pain or urgency. During cystometry, participants scored the intensity of urgency and pain, both in the suprapubic and the urethral region, on a VAS scale of 0-10 at a baseline, at first desire, normal desire, strong desire to void, and at maximum cystometric capacity during filling. We allocated the participants to six groups; those reporting urgency or not, pain or not, both symptoms and neither. Friedman's Test was used to ascertain if all scores increased significantly, the Wilcoxon Signed Rank Test was used to demonstrate the difference between scores, and agreement for findings during cystometry was tested with Mann-Whitney U. A total of 68 women participated; 38 participants reported pain, 57 reported urgency, and 33 reported both symptoms. Pain and urgency scores significantly increased during cystometry (P < 0.0001). For participants reporting pain, suprapubic pain was rated significantly higher than urethral pain. Participants reporting both symptoms, felt more urgency than pain, and again pain more suprapubically than urethrally. Participants reporting only urgency scored suprapubic and urethral urgency similarly at all desires. Pain and urgency are well differentiated sensations and are felt at different locations although pain is seemingly easier localized. Neurourol. Urodynam. 36:620-625, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Photoacoustic cystography using handheld dual modal clinical ultrasound photoacoustic imaging system

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Periyasamy, Vijitha; Austria, Dienzo Rhonnie; Pramanik, Manojit

2018-02-01

Vesicoureteral reflux is the abnormal flow of urine from your bladder back up the tubes (ureters) that connect your kidneys to your bladder. Normally, urine flows only down from your kidneys to your bladder. Vesicoureteral reflux is usually diagnosed in infants and children. The disorder increases the risk of urinary tract infections, which, if left untreated, can lead to kidney damage. X-Ray cystography is used currently to diagnose this condition which uses ionising radiation, making it harmful for patients. In this work we demonstrate the feasibility of imaging the urinary bladder using a handheld clinical ultrasound and photoacoustic dual modal imaging system in small animals (rats). Additionally, we demonstrate imaging vesicoureteral reflux using bladder mimicking phantoms. Urinary bladder imaging is done with the help of contrast agents like black ink and gold nanoparticles which have high optical absorption at 1064 nm. Imaging up to 2 cm was demonstrated with this system. Imaging was done at a framerate of 5 frames per second.

Egg consumption and risk of bladder cancer: a meta-analysis.

PubMed

Li, Fei; Zhou, You; Hu, Rui-ting; Hou, Li-na; Du, Yue-Jun; Zhang, Xin-ji; Olkkonen, Vesa M; Tan, Wan-long

2013-01-01

The findings of epidemiologic studies on the association between egg consumption and bladder cancer risk remain conflicting. We conducted a meta-analysis to clarify the potential association between egg consumption and bladder cancer risk. Four cohort studies and 9 case-control studies in the PubMed database through February 2012 were identified on egg consumption and risk of bladder cancer involving 2715 cases and 184,727 participants. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest compared with the lowest category of egg consumption. In addition, we performed stratified analyses and sensitivity and dose-response analyses to examine the association. Overall, no significant association was observed between egg consumption and bladder cancer (SRRE = 1.11 95% CI: 0.90-1.35). However, increased risk of bladder cancer was detected in North/South America (SRRE = 1.40 95% CI: 1.05-1.86) and, moreover, fried egg intake positively associated with bladder cancer as well (SRRE = 2.04, 95% CI: 1.41-2.95). In conclusion, our findings suggest no significant association between egg consumption and bladder cancer risk, except for a possible positive relationship with the intake of fried eggs based on the limited number of studies. Additional studies, especially large prospective cohort studies, are warranted to confirm these findings.

Evaluation of associations between lifetime exposure to drinking water disinfection by-products and bladder cancer in dogs.

PubMed

Backer, Lorraine C; Coss, Angela M; Wolkin, Amy F; Flanders, W Dana; Reif, John S

2008-06-01

To assess the risk of bladder cancer in dogs from exposure to drinking water disinfection by-products and determine whether dogs could serve as sentinels for human bladder cancer associated with such exposures. Case-control study. 100 dogs with cancer of the urinary bladder and 100 control dogs. Case and control dogs were frequency-matched by age (within 2 years) and sex. Owners of dogs enrolled provided verbal informed consent and were interviewed by telephone. The telephone questionnaire included a complete residence history for each dog. Each dog's total exposure history to trihalomethanes was reconstructed from its residence history and corresponding drinking water utility company data. No association was detected between increasing years of exposure to chlorinated drinking water and risk of bladder cancer. Dogs with bladder cancer were exposed to higher total trihalomethanes concentrations than control dogs; however, the difference was not significant. Although humans and their dogs live in the same household, the activity patterns of dogs may lead to lower exposures to household tap water. Thus, although exposure to disinfection by-products in tap water may be a risk factor for human bladder cancer, this may not be true for canine bladder cancer at the concentrations at which dogs are exposed.

Increased expression of GGN promotes tumorigenesis in bladder cancer and is correlated with poor prognosis.

PubMed

Wang, Wentao; Li, Changfu; Chen, Yongsheng; Teng, Lichen; Cao, Yan; Xu, Yongpeng; Pan, Hongxin; An, Ruihua

2018-04-30

Bladder cancer has shown great challenge for people's life. Traditional therapeutics against bladder cancer including surgery could not bring much benefit for patients, particularly for the late stage patients. So it is necessary to keep in mind why and how bladder cancer cells survive in our body. In this study, we explored the function and the molecular mechanism of GGN gene in bladder cancer. GGN was shown to be expressed at a high level in bladder cancer tissues compared to the control and was associated with the unsatisfactory survival rate of patients. GGN was also expressed abundantly in bladder cancer cell lines such as T24, 5637 and BIU87. Then GGN was knocked down in 5637 cells and T24 cells at both RNA and protein level. In accordance, aberrant growth and proliferation were demonstrated in bladder cancer cells. The ability of migration and invasion of bladder cancer cells was also inhibited. The in vivo data further proved that the xenograft tumor growth was dramatically suppressed by GGN knockdown. Then we demonstrated that the level of IκB, bax and truncated caspase3 was upregulated after GGN was knocked down in 5637 cells. In contrast, expression level of NFκB, IKK, c-Myc, cyclin D1 and Bcl-2 was reduced. Further, the phosphorylation level of IκB was also downregulated. These data suggest that NFκB/caspase3-mediated apoptosis signaling was regulated by GGN. Conclusively, GGN played a tumor-promoting role in bladder cancer through regulation of NFκB/caspase3-mediated apoptosis signaling. This study provides a new clue for the treatment of patients with bladder cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

PubMed Central

Van Gordon, Samuel; Tyler, Karl; Kropp, Bradley; Towner, Rheal; Lin, HsuehKung; Marentette, John O.; McHowat, Jane; Mohammedi, Ehsan; Greenwood-Van Meerveld, Beverley

2016-01-01

Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 ± 1.1 vs. 2.6 ± 1.1 vs 1.2 ± 0.5 and 1.01 ± 0.7 kΩ·cm2 in the PS-treated and ChABC-treated rat bladders (P = 0.0016 and P = 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. PMID:26911855

Contouring and Constraining Bowel on a Full-Bladder Computed Tomography Scan May Not Reflect Treatment Bowel Position and Dose Certainty in Gynecologic External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaparpalvi, Ravindra, E-mail: ryaparpa@montefiore.org; Mehta, Keyur J.; Bernstein, Michael B.

Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined.more » Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm{sup 3}. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm{sup 3} (range, 74.3-251.4 cm{sup 3}). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm{sup 3}; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV{sub B}owel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient.« less

Image-Based 3D Treatment Planning for Vaginal Cylinder Brachytherapy: Dosimetric Effects of Bladder Filling on Organs at Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hung, Jennifer; Shen Sui; De Los Santos, Jennifer F.

2012-07-01

Purpose: To investigate the dosimetric effects of bladder filling on organs at risk (OARs) using three-dimensional image-based treatment planning for vaginal cylinder brachytherapy. Methods and Materials: Twelve patients with endometrial or cervical cancer underwent postoperative high-dose rate vaginal cylinder brachytherapy. For three-dimensional planning, patients were simulated by computed tomography with an indwelling catheter in place (empty bladder) and with 180 mL of sterile water instilled into the bladder (full bladder). The bladder, rectum, sigmoid, and small bowel (OARs) were contoured, and a prescription dose was generated for 10 to 35 Gy in 2 to 5 fractions at the surface ormore » at 5 mm depth. For each OAR, the volume dose was defined by use of two different criteria: the minimum dose value in a 2.0-cc volume receiving the highest dose (D{sub 2cc}) and the dose received by 50% of the OAR volume (D{sub 50%}). International Commission on Radiation Units and Measurements (ICRU) bladder and rectum point doses were calculated for comparison. The cylinder-to-bowel distance was measured using the shortest distance from the cylinder apex to the contoured sigmoid or small bowel. Statistical analyses were performed with paired t tests. Results: Mean bladder and rectum D{sub 2cc} values were lower than their respective ICRU doses. However, differences between D{sub 2cc} and ICRU doses were small. Empty vs. full bladder did not significantly affect the mean cylinder-to-bowel distance (0.72 vs. 0.92 cm, p = 0.08). In contrast, bladder distention had appreciable effects on bladder and small bowel volume dosimetry. With a full bladder, the mean small bowel D{sub 2cc} significantly decreased from 677 to 408 cGy (p = 0.004); the mean bladder D{sub 2cc} did not increase significantly (1,179 cGy vs. 1,246 cGy, p = 0.11). Bladder distention decreased the mean D{sub 50%} for both the bladder (441 vs. 279 cGy, p = 0.001) and the small bowel (168 vs. 132 cGy, p = 0.001). Rectum and sigmoid volume doses were not affected by bladder filling. Conclusions: In high-dose rate vaginal cylinder brachytherapy, treatment with a distended bladder preferentially reduces high dose to the small bowel around the vaginal cuff without a significant change in dose to the bladder, rectum, or sigmoid.« less

Simplifying the diagnosis of 4 common voiding conditions using uroflow/electromyography, electromyography lag time and voiding history.

PubMed

Van Batavia, Jason P; Combs, Andrew J; Hyun, Grace; Bayer, Agnes; Medina-Kreppein, Daisy; Schlussel, Richard N; Glassberg, Kenneth I

2011-10-01

Noninvasive uroflowmetry with simultaneous electromyography is useful to triage cases of lower urinary tract symptoms into 4 urodynamically defined conditions, especially when incorporating short and long electromyography lag times in the analysis. We determined the prevalence of these 4 conditions at a single referral institution and the usefulness of uroflowmetry with simultaneous electromyography and electromyography lag time to confirm the diagnosis, guide treatment and monitor response. We retrospectively reviewed the records of 100 consecutive normal children who presented with persistent lower urinary tract symptoms, underwent uroflowmetry with electromyography as part of the initial evaluation and were diagnosed with 1 of 4 conditions based on certain uroflowmetry/electromyography features. The conditions included 1) dysfunctional voiding--active pelvic floor electromyography during voiding with or without staccato flow, 2a) idiopathic detrusor overactivity disorder-A--a quiet pelvic floor during voiding and shortened lag time (less than 2 seconds), 2b) idiopathic detrusor overactivity disorder-B--a quiet pelvic floor with a normal lag time, 3) detrusor underutilization disorder--volitionally deferred voiding with expanded bladder capacity but a quiet pelvic floor, and 4) primary bladder neck dysfunction--prolonged lag time (greater than 6 seconds) and a depressed, right shifted uroflowmetry curve with a quiet pelvic floor during voiding. Treatment was tailored to the underlying condition in each patient. The group consisted of 50 males and 50 females with a mean age of 8 years (range 3 to 18). Dysfunctional voiding was more common in females (p <0.05) while idiopathic detrusor overactivity disorder-B and primary bladder neck dysfunction were more common in males (p <0.01). With treatment uroflowmetry parameters normalized for all types. Electromyography lag time increased in idiopathic detrusor overactivity disorder-A cases and decreased in primary bladder neck dysfunction cases. Noninvasive uroflowmetry with simultaneous electromyography offers an excellent alternative to invasive urodynamics to diagnose 4 urodynamically defined conditions. It identifies the most appropriate therapy for the specific condition and objectively monitors the treatment response. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Urologic complications of major genitourinary reconstruction in the exstrophy-epispadias complex.

PubMed

Inouye, Brian M; Shah, Bhavik B; Massanyi, Eric Z; Di Carlo, Heather N; Kern, Adam J; Tourchi, Ali; Baradaran, Nima; Stewart, Dylan; Gearhart, John P

2014-08-01

To present the authors' experiences with urologic complications associated with various techniques used to create a continent stoma (CS), augmentation cystoplasty (AC), and neobladder in the exstrophy-epispadias complex (EEC) population. Retrospective review of medical records of patients who underwent CS with or without bladder augmentation were identified from an institutional review board-approved database of 1208 EEC patients. Surgical indications, tissue type, length of hospital stay, age, preoperative bladder capacity, prior genitourinary surgeries, postoperative urological complications, and continence status were reviewed. Among the EEC patients reviewed, 133 underwent CS (80 male, 53 female). Mean follow-up time after initial continent stoma was 5.31 years (range: 6 months to 20 years). Appendix and tapered ileum were the primary bowel segments used for the continent channel and stoma in the EEC population. The most common stomal complications in this population were stenosis, incontinence, and prolapse. Seventy-nine percent of EEC CS patients underwent AC primarily done with sigmoid colon or ileum. Eleven patients (8%) underwent neobladder creation with either colon or a combination of colon and ileum. Bladder calculi, vesicocutaneous fistula, and pyelonephritis were the most common non-stomal complications. Stomal ischemia was significantly increased in Monti ileovesicostomy compared to Mitrofanoff appendicovesicostomy in classic bladder exstrophy patients (p = 0.036). Furthermore, pyelonephritis was more than twice as likely in colonic neobladder than all other reservoir tissue types in the same cohort (OR = 2.53, 95% CI: 1.762-3.301, p < 0.001). To the best of the authors' knowledge, this is the largest study examining catheterizable stomas in the exstrophy population. While Mitrofanoff appendicovesicostomy is preferred to Monti ileovesicostomy because it is technically less challenging, it may also confer a lower rate of stomal ischemia. Furthermore, even though ileum or colon can be used in AC with equally low complication rates, practitioners must be wary of potential urologic complications that should be primarily managed by an experienced reconstructive surgeon. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG

PubMed Central

2011-01-01

Background This work tests the hypothesis that increased levels of vascular endothelial growth factor (VEGF) observed during bladder inflammation modulates nerve plasticity. Methods Chronic inflammation was induced by intravesical instillations of Bacillus Calmette-Guérin (BCG) into the urinary bladder and the density of nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) or pan-neuronal marker PGP9.5 was used to quantify alterations in peripheral nerve plasticity. Some mice were treated with B20, a VEGF neutralizing antibody to reduce the participation of VEGF. Additional mice were treated systemically with antibodies engineered to specifically block the binding of VEGF to NRP1 (anti-NRP1B) and NRP2 (NRP2B), or the binding of semaphorins to NRP1 (anti-NRP1 A) to diminish activity of axon guidance molecules such as neuropilins (NRPs) and semaphorins (SEMAs). To confirm that VEGF is capable of inducing inflammation and neuronal plasticity, another group of mice was instilled with recombinant VEGF165 or VEGF121 into the urinary bladder. Results The major finding of this work was that chronic BCG instillation resulted in inflammation and an overwhelming increase in both PGP9.5 and TRPV1 immunoreactivity, primarily in the sub-urothelium of the urinary bladder. Treatment of mice with anti-VEGF neutralizing antibody (B20) abolished the effect of BCG on inflammation and nerve density. NRP1A and NRP1B antibodies, known to reduce BCG-induced inflammation, failed to block BCG-induced increase in nerve fibers. However, the NRP2B antibody dramatically potentiated the effects of BCG in increasing PGP9.5-, TRPV1-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactivity (IR). Finally, instillation of VEGF121 or VEGF165 into the mouse bladder recapitulated the effects of BCG and resulted in a significant inflammation and increase in nerve density. Conclusions For the first time, evidence is being presented supporting that chronic BCG instillation into the mouse bladder promotes a significant increase in peripheral nerve density that was mimicked by VEGF instillation. Effects of BCG were abolished by pre-treatment with neutralizing VEGF antibody. The present results implicate the VEGF pathway as a key modulator of inflammation and nerve plasticity, introduces a new animal model for investigation of VEGF-induced nerve plasticity, and suggests putative mechanisms underlying this phenomenon. PMID:22059553

Do neural tube defects lead to structural alterations in the human bladder?

PubMed

Pazos, Helena M F; Lobo, Márcio Luiz de P; Costa, Waldemar S; Sampaio, Francisco J B; Cardoso, Luis Eduardo M; Favorito, Luciano Alves

2011-05-01

Anencephaly is the most severe neural tube defect in human fetuses. The objective of this paper is to analyze the structure of the bladder in anencephalic human fetuses. We studied 40 bladders of normal human fetuses (20 male and 20 female, aged 14 to 23 WPC) and 12 bladders of anencephalic fetuses (5 male and 7 female, aged 18 to 22 WPC). The bladders were removed and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in sections. Data were expressed as volumetric density (Vv-%). The images were captured with Olympus BX51 microscopy and Olympus DP70 camera. The stereological analysis was done using the software Image Pro and Image J. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p<0.05). We observed a significant increase (p<0.0001) in the Vv of collagen in the bladders of anencephalic fetuses (69.71%) when compared to normal fetuses (52.74%), and a significant decrease (p<0.0001) in the Vv of smooth muscle cells in the bladders of anencephalic fetuses (23.96%) when compared to normal fetuses (38.35%). The biochemical analyses showed a higher concentration of total collagen in the bladders of anencephalic fetuses (37354 µg/mg) when compared to normal fetuses (48117 µg/mg, p<0.02). The structural alterations of the bladder found in this study may suggest the existence of functional alterations in the bladder of anencephalic human fetuses.

Electrical pelvic floor stimulation in the management of urinary incontinence due to neuropathic overactive bladder.

PubMed

Ishigooka, M; Hashimoto, T; Izumiya, K; Katoh, T; Yaguchi, H; Nakada, T; Handa, Y; Hoshimiya, N

1993-01-01

Electrical pelvic floor stimulation employing a portable functional electrical stimulation system with percutaneously indwelling electrodes was carried out to improve detrusor urinary incontinence. Cyclic stimulation using negative going pulse trains of 20 Hz was applied 3 to 6 times daily to the bilateral pudendal nerves distributing to the pelvic floor muscles for the purpose of strengthening these muscles, including the urethral sphincter, and simultaneously, suppressing detrusor overactivity and increasing cystometric capacity. Electrical training for 4-8 weeks resulted in an improvement of urinary incontinence in five of six patients. In two of six cases incontinence had subjectively disappeared. Urodynamic investigations demonstrated an increase in detrusor reflex threshold and less tendency for abortive detrusor contraction. No apparent complications were encountered during these periods. This procedure appears to be efficient for the management of patients with detrusor incontinence who respond poorly to conservative therapies.

[The onset mechanism of nocturia in the elderly and the possibility of ramelteon].

PubMed

Shimizu, Nobutaka

2013-06-01

Nocturia causes sleep disorder and affects not only the fall of QOL but also the increase of falling and bone fracture risk, and life convalescence. Therefore, among the elderly who are particularly likely to fall down, it is necessary to pay attention to them to prevent them from falling down, in addition to their treatment for nocturia. On the other hand, it is also necessary to be careful for insomnia which the prevalence rate rises by aging, because of their sleep getting divided by nocturia. In the examination at our hospital, by the dosage of ramelteon to the insomniac patients complicated with nocturia, the increase of night bladder capacity and the decrease in number of urination times during night were accepted with improvement in insomnia. In addition, adverse event was not accepted. From now on, we regard ramelteon as one of the new treatment choices for insomniac patients complicated with nocturia.

Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

PubMed Central

Teschke, K; Morgan, M S; Checkoway, H; Franklin, G; Spinelli, J J; van Belle, G; Weiss, N S

1997-01-01

OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners). PMID:9245952

The effect of Pokemon on bladder cancer epithelial-mesenchymal transition.

PubMed

Guo, Changcheng; Zhu, Kai; Sun, Wei; Yang, Bin; Gu, Wenyu; Luo, Jun; Peng, Bo; Zheng, Junhua

2014-01-24

This study aimed at detecting Pokemon expression in bladder cancer cell and investigating the relationship between Pokemon and epithelial-mesenchymal transition. Furthermore, we investigated the functions of Pokemon in the carcinogenesis and development of bladder cancer. This study was also designed to observe the inhibitory effects of siRNA expression vector on Pokemon in bladder cancer cell. The siRNA expression vectors which were constructed to express a short hairpin RNA against Pokemon were transfected to the bladder cancer cells T24 with a liposome. Levels of Pokemon, E-cadherin and β-catenin mRNA and protein were examined by real-time quantitative-fluorescent PCR and Western blot analysis, respectively. The effects of Pokemon silencing on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay. Pokemon was strongly inhibited by siRNA treatment, especially siRNA3 treatment group, as it was reflected by Western blot and real-time PCR. The gene and protein of E-cadherin expression level showed increased markedly after Pokemon was inhibited by RNA interference. While there were no differences in the levels of gene and protein of β-catenin among five groups. The bladder cancer cell after Pokemon siRNA interference showed a significantly reduced wound-closing efficiency at 6, 12 and 24h. Our findings suggest Pokemon may inhibit the expression of E-cadherin. The low expression of E-cadherin lead to increasing the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Copyright © 2013 Elsevier Inc. All rights reserved.

Spinal mechanism of micturition reflex inhibition by naftopidil in rats.

PubMed

Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

2014-10-29

We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Development of Neurogenic Detrusor Overactivity (NDO)

PubMed Central

Frias, Bárbara; Santos, João; Morgado, Marlene; Sousa, Mónica Mendes; Gray, Susannah M.Y.; McCloskey, Karen D.; Allen, Shelley; Cruz, Francisco

2015-01-01

Neurogenic detrusor overactivity (NDO) is a well known consequence of spinal cord injury (SCI), recognizable after spinal shock, during which the bladder is areflexic. NDO emergence and maintenance depend on profound plastic changes of the spinal neuronal pathways regulating bladder function. It is well known that neurotrophins (NTs) are major regulators of such changes. NGF is the best-studied NT in the bladder and its role in NDO has already been established. Another very abundant neurotrophin is BDNF. Despite being shown that, acting at the spinal cord level, BDNF is a key mediator of bladder dysfunction and pain during cystitis, it is presently unclear if it is also important for NDO. This study aimed to clarify this issue. Results obtained pinpoint BDNF as an important regulator of NDO appearance and maintenance. Spinal BDNF expression increased in a time-dependent manner together with NDO emergence. In chronic SCI rats, BDNF sequestration improved bladder function, indicating that, at later stages, BDNF contributes NDO maintenance. During spinal shock, BDNF sequestration resulted in early development of bladder hyperactivity, accompanied by increased axonal growth of calcitonin gene-related peptide-labeled fibers in the dorsal horn. Chronic BDNF administration inhibited the emergence of NDO, together with reduction of axonal growth, suggesting that BDNF may have a crucial role in bladder function after SCI via inhibition of neuronal sprouting. These findings highlight the role of BDNF in NDO and may provide a significant contribution to create more efficient therapies to manage SCI patients. PMID:25653370

On the nature of bladder sensation: the concept of sensory modulation.

PubMed

De Wachter, S G; Heeringa, R; van Koeveringe, G A; Gillespie, J I

2011-09-01

Going to the toilet is an essential everyday event. Normally, we do not give much thought to the sensations and factors that trigger voiding behavior: we just go. For many people, this apparently simple task is complicated and dominates their life. They have strong sensations and sudden desires to void, often resulting in incontinence. It is therefore important that we understand the origins for this functional change and identify means to alleviate it. Literature survey. A considerable body of work has focused on this problem and ideas and concepts on the nature of bladder sensations are embedded in the literature. In this paper we argue the necessity to return to first principles and a re-examination of the problem. We explore the use of focus groups to identify relevant bladder sensation and what triggers 'bladder' behavior. We argue that there are differences in what can be described as 'introspective bladder sensations' and the sensations reported immediately before a void, 'void sensations'. Finally, we propose an alternative model describing how peripheral information generating 'introspective sensations' and 'void sensations' might be different but interrelated sensations. By exploring such ideas and identifying such complexity it is our intention to stimulate debate and generate further research in the field in order to understand better the physiology of bladder sensation and the pathology of increased urge, frequency and incontinence. Review of the literature on bladder sensation and the established ideas suggests that we might be missing something and the problem of normal and increased sensation and of urgency may be much more complex. Copyright © 2011 Wiley-Liss, Inc.

Effects of social support, hope and resilience on quality of life among Chinese bladder cancer patients: a cross-sectional study.

PubMed

Li, Meng-Yao; Yang, Yi-Long; Liu, Li; Wang, Lie

2016-05-06

Improvement of quality of life has been one of goals in health care for people living with bladder cancer. Meanwhile, positive psycho-social variables in oncology field have increasingly received attention. However, the assessment of quality of life of bladder cancer patients and the integrative effects of positive psycho-social variables has limited reporting. The aim of this study was to assess quality of life as well as the integrative effects of social support, hope and resilience on quality of life among Chinese bladder cancer patients. A cross-sectional study was conducted at the First Hospital of China Medical University in Liaoning Province, China. A total of 365 bladder cancer patients eligible for this study completed questionnaires on demographic variables, FACT-BL, Perceived Social Support Scale, Adult Hope Scale, and Resilience Scale-14 during July 2013 to July 2014. The average score of FACT-BL was 87.60 ± 16.27 (Mean ± SD). Hierarchical regression analyses indicated that social support, hope and resilience as a whole accounted for 30.3 % variance of quality of life. Under standardized estimate (β) sequence, social support, hope and resilience significantly and positively associated with quality of life, respectively. Quality of life for bladder cancer patients was at a low level in China, which should receive more attention in Chinese medical institutions. More importantly, efforts to increase social support, hope and resilience might be useful to support the quality of life among Chinese bladder cancer patients.

Disruption of the FA/BRCA pathway in bladder cancer.

PubMed

Neveling, K; Kalb, R; Florl, A R; Herterich, S; Friedl, R; Hoehn, H; Hader, C; Hartmann, F H; Nanda, I; Steinlein, C; Schmid, M; Tonnies, H; Hurst, C D; Knowles, M A; Hanenberg, H; Schulz, W A; Schindler, D

2007-01-01

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression. Copyright (c) 2007 S. Karger AG, Basel.

Expression analysis and clinical significance of CXCL16/CXCR6 in patients with bladder cancer

PubMed Central

LEE, JUN TAIK; LEE, SANG DON; LEE, JEONG ZOO; CHUNG, MOON KEE; HA, HONG KOO

2013-01-01

The interactions between chemokines and their receptors are closely involved in the progression and metastasis of cancer. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in bladder cancer progression. To evaluate this hypothesis, the expression levels of CXCL16 and CXCR6 were evaluated in 160 patients, including 155 patients with bladder cancer and 5 patients with benign bladder disease. The tissues were analyzed by immunohistochemical (IHC) staining and real-time reverse-transcription polymerase chain reaction. We compared the expression of CXCL16/CXCR6 in bladder cancer and benign bladder disease. The expression of CXCR6 was increased in patients with bladder cancer compared with benign bladder disease in RT-PCR. The mRNA expression levels of CXCL16 and CXCR6 were 1.75×10−2 and 1.99×10−2 in benign bladder tissue and 1.39×10−2 and 2.32×10−2 in bladder cancer tissue, respectively. In IHC staining, the expression of CXCL16/CXCR6 in bladder cancer tissues was higher compared with benign bladder tissues. On multivariate analysis, the IHC staining of CXCL16 was correlated with the 2004 WHO grade and lymphovascular invasion (P=0.021 and P=0.011, respectively). CXCR6 was correlated with the 1973 WHO grade (P=0.001), 2004 WHO grade (P<0.001), pathological T stage (P=0.002) and perineural invasion (P=0.031). However, Cox regression analysis revealed that the expression of CXCL16 and CXCR6 was not correlated with cancer recurrence and cancer-specific survival (P=0.142 and P=0.324, respectively). The expression of CXCL16/CXCR6 was higher in bladder cancer compared to benign disease and correlated with aggressive cancer behavior. Based on our results, the CXCL16/CXCR6 axis appears to be important in the progression of bladder cancer. Thus, CXCL16 and CXCR6 serve as potential therapeutic targets. PMID:23255926

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

PubMed Central

Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

2017-01-01

Abstract Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case–control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case–control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93–3.47; P = 1.87 × 10−10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10–2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers. PMID:29028944

Personal use of hair dyes and the risk of bladder cancer: results of a meta-analysis.

PubMed Central

Huncharek, Michael; Kupelnick, Bruce

2005-01-01

OBJECTIVE: This study examined the methodology of observational studies that explored an association between personal use of hair dye products and the risk of bladder cancer. METHODS: Data were pooled from epidemiological studies using a general variance-based meta-analytic method that employed confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of bladder cancer development associated with use of hair dye products vs. non-use. Sensitivity analyses were performed to explain any observed statistical heterogeneity and to explore the influence of specific study characteristics of the summary estimate of effect. RESULTS: Initially combining homogenous data from six case-control and one cohort study yielded a non-significant RR of 1.01 (0.92, 1.11), suggesting no association between hair dye use and bladder cancer development. Sensitivity analyses examining the influence of hair dye type, color, and study design on this suspected association showed that uncontrolled confounding and design limitations contributed to a spurious non-significant summary RR. The sensitivity analyses yielded statistically significant RRs ranging from 1.22 (1.11, 1.51) to 1.50 (1.30, 1.98), indicating that personal use of hair dye products increases bladder cancer risk by 22% to 50% vs. non-use. CONCLUSION: The available epidemiological data suggest an association between personal use of hair dye products and increased risk of bladder cancer. PMID:15736329

The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

PubMed Central

Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

2013-01-01

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

PubMed

de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

The Potential Role of Polymethyl Methacrylate as a New Packaging Material for the Implantable Medical Device in the Bladder

PubMed Central

Kim, Su Jin; Choi, Bumkyoo; Kim, Kang Sup; Bae, Woong Jin; Hong, Sung Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Kim, Sae Woong

2015-01-01

Polydimethylsiloxane (PDMS) is used in implantable medical devices; however, PDMS is not a completely biocompatible material for electronic medical devices in the bladder. To identify novel biocompatible materials for intravesical implanted medical devices, we evaluated the biocompatibility of polymethyl methacrylate (PMMA) by analyzing changes in the levels of macrophages, macrophage migratory inhibitory factor (MIF), and inflammatory cytokines in the bladder. A ball-shaped metal coated with PMMA or PDMS was implanted into the bladders of rats, and after intravesical implantation, the inflammatory changes induced by the foreign body reaction were evaluated. In the early period after implantation, increased macrophage activity and MIF in the urothelium of the bladder were observed. However, significantly decreased macrophage activity and MIF in the bladder were observed after implantation with PMMA- or PDMS-coated metal in the later period. In addition, significantly decreased inflammatory cytokines such as IL-1β, IL-6, and TNF-α were observed with time. Based on these results, we suggest that MIF plays a role in the foreign body reaction and in the biocompatible packaging with PMMA for the implanted medical devices in the bladder. PMID:25705692

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor.

PubMed

Kim, Su-Jin; Lee, Dong-Sup; Kim, In-Gul; Sohn, Dong-Wan; Park, Jung-Yul; Choi, Bum-Kyoo; Kim, Sae-Woong

2012-03-01

As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real-time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene-C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene-C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene-C can be used as safe coating materials for the implantable bladder volume sensor reported previously. Copyright © 2012. Published by Elsevier B.V.

A Review on the Relationship between SGLT2 Inhibitors and Cancer

PubMed Central

Lin, Hao-Wen; Tseng, Chin-Hsiao

2014-01-01

Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2) inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance). This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted. PMID:25254045

Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination

PubMed Central

Zhang, Yuesheng

2013-01-01

Allyl isothiocyanate (AITC) occurs in cruciferous vegetables that are commonly consumed by humans and has been shown to inhibit urinary bladder cancer growth and progression in previous preclinical studies. However, AITC does not significantly modulate cyclooxygenase-2 (Cox-2), whose oncogenic activity has been well documented in bladder cancer and other cancers. Celecoxib is a selective Cox-2 inhibitor and has been widely used for treatment of several diseases. Celecoxib has also been evaluated in bladder cancer patients, but its efficacy against bladder cancer as a single agent remains unclear. In a syngeneic rat model of orthotopic bladder cancer, treatment of the animals with the combination of AITC and celecoxib at low dose levels (AITC at 1mg/kg and celecoxib at 10mg/kg) led to increased or perhaps synergistic inhibition of bladder cancer growth and muscle invasion, compared with each agent used alone. The combination regime was also more effective than each single agent in inhibiting microvessel formation and stimulating microvessel maturation in the tumor tissues. The anticancer efficacy of the combination regime was associated with depletion of prostaglandin E2, a key downstream signaling molecule of Cox-2, caspase activation and downregulation of vascular endothelial growth factor in the tumor tissues. These data show that AITC and celecoxib complement each other for inhibition of bladder cancer and provide a novel combination approach for potential use for prevention or treatment of human bladder cancer. PMID:23946495

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

PubMed Central

Lin, Wei-Ching; Chen, Jeon-Hor

2015-01-01

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care. PMID:26055180

Rapamycin attenuates bladder hypertrophy during long-term outlet obstruction in vivo: tissue, matrix and mechanistic insights.

PubMed

Schröder, Annette; Kirwan, Tyler P; Jiang, Jia-Xin; Aitken, Karen J; Bägli, Darius J

2013-06-01

Previous molecular studies showed that the mTOR inhibitor rapamycin prevents bladder smooth muscle hypertrophy in vitro. We investigated the effect of rapamycin treatment in vivo on bladder smooth muscle hypertrophy in a rat model of partial bladder outlet obstruction. A total of 48 female Sprague-Dawley® rats underwent partial bladder outlet obstruction and received daily subcutaneous injections of rapamycin (1 mg/kg) or vehicle commencing 2 weeks postoperatively. A total of 36 rats underwent sham surgery and received rapamycin or vehicle. Rats were sacrificed 3, 6 and 12 weeks after surgery. Before sacrifice, voiding was observed in a metabolic cage for 24 hours. Bladder-to-body weight in gm bladder weight per kg body weight and post-void residual urine were assessed. We evaluated Col1a1, Col3a1, Eln and Mmp7 mRNA expression and histology. Two-factor ANOVA and the post hoc t test were applied. Bladder outlet obstruction caused a significant increase in bladder weight in all obstructed groups. Three weeks postoperatively (1 week of treatment) there was no difference in the bladder-to-body weight ratio in the obstructed group. However, at 6 and 12 weeks (4 and 10 weeks of treatment, respectively) the bladder-to-body weight ratio of rats with obstruction plus rapamycin was significantly lower than that of rats with obstruction plus vehicle. Post-void residual urine volume after 6 and 12 weeks of obstruction was lower in obstructed rats with rapamycin compared to that in obstructed rats with vehicle. Rapamycin decreased the obstruction induced expression of Col1a1, Col3a1, Eln and Mmp7. Rapamycin prevents mechanically induced hypertrophy in cardiovascular smooth muscle. In vivo mTOR inhibition may attenuate obstruction induced detrusor hypertrophy and help preserve bladder function. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

Cancer.gov

Researchers in the United Kingdom have found that adding chemotherapy to radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

Orthotopic AY-27 rat bladder urothelial cell carcinoma model presented an elevated methemoglobin proportion in the increased total hemoglobin content when evaluated in vivo by single-fiber reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Sun, Tengfei; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.; Piao, Daqing

2017-02-01

In vivo single-fiber reflectance spectroscopy (SfRS) was performed on an orthotopic AY-27 rat bladder urothelial cell carcinoma model to explore potential spectroscopic features revealing neoplastic changes. AY-27 bladder tumor cells were intravesically instilled in four rats and allowed to implant and grow for one week, with two additional rats as the control. A total of 107 SfRS measurements were taken from 27 sites on two control bladders and 80 from four AY-27 treated bladders. The spectral profiles obtained from AY-27 treated bladders revealed various levels of a methemoglobin (MetHb) characteristic spectral feature around 635nm. A multisegment spectral analysis method estimated concentrations of five chromophore compositions including oxyhemoglobin, deoxyhemoglobin, MetHb, lipid and water. The total hemoglobin concentration ([HbT]), the MetHb proportion in the total hemoglobin and the lipid volume content showed possible correlations. The 80 measurements from the AY-27 treated bladders could separate to three sub-sets according to the MetHb proportion. Specifically, 72 were in subset 1 with low proportion (5.3%<[MetHb]<7%), 6 in subset 2 with moderate proportion (7%<[MetHb]<30%), and 2 in subset 3 with significant proportion (>30%). When grouped according to [MetHB], the [HbT] increased from 368 μM of subset 1 to 488 μM of subset 2 to 541 μM of subset 3, in comparison to the 285 μM of the control. The increased total hemoglobin and the elevation of MetHb proportion may signify angiogenesis and degradation in hemoglobin oxygen-transport. Additionally, the lipid volume content decreased from 2.58% in the control to <0.2% in the tumor groups, indicating disruption of subepithelium tissue architecture.

Comparison of sensation-related voiding patterns between continent and incontinent women: a study with a 3-day sensation-related bladder diary (SR-BD).

PubMed

Naoemova, Irina; De Wachter, Stefan; Wyndaele, Jean-Jacques

2008-01-01

To describe and compare voiding patterns on a 3-day sensation-related bladder diary (SR-BD) in women with urinary incontinence (UI) and healthy volunteers. A total of 251 women (224 incontinent patients and 27 healthy volunteers) who recorded a 3-day SR-BD and underwent standard cystometry participated in the study. Parameters from the 3-day SR-BD were compared between incontinent patients and healthy volunteers. Compared to continent women, all groups of incontinent women noted a significantly higher 24 hr voiding frequency, a greater voiding frequency per liter diuresis, a smaller mean voided volume for different degrees of bladder sensation with more voids made with higher intensity of desire to void. The smallest mean voided volumes for different degrees of desire to void and the highest voiding frequency per liter diuresis were observed in the urge incontinence group. There were different sensation-related voiding patterns on the 3-day SR-BD from incontinent women and healthy volunteers. All incontinence groups had increased bladder sensation compared to healthy volunteers. The most severe increase of bladder sensation was observed in the patients with urgency incontinence. (c) 2007 Wiley-Liss, Inc.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.

PubMed

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R; Guterres, Silvia S; Collares, Tiago; Seixas, Fabiana Kömmling

2017-01-01

Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

PubMed Central

Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R.; Guterres, Silvia S.; Collares, Tiago; Seixas, Fabiana Kömmling

2018-01-01

Mycobacterium bovis bacillus Calmette–Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer. PMID:29379438

Effect of spinal anaesthesia on the lower urinary tract in continent women.

PubMed

Haeusler, G; Sam, C; Chiari, A; Tempfer, C; Hanzal, E; Koelbl, H

1998-01-01

To evaluate the effect of spinal anaesthesia on the bladder neck position and the urethral closure function in the resting state and during clinical stress test in healthy, continent women. Controlled clinical trial. Department of Gynaecology and Obstetrics, Vienna University Medical School. Fourteen continent women, of which seven were nulliparous and seven parous, underwent minor gynaecological procedures under spinal anaesthesia. Urodynamics and ultrasound investigations were performed before and during spinal anaesthesia. Changes in the bladder neck position and the urethral closure function before and during spinal anaesthesia. Bladder neck position was found to be lower and more posterior during spinal anaesthesia as compared with pre-operative assessment. The posterior urethrovesical angle increased significantly both at rest and during maximum straining. We observed a significant increase in bladder compliance, and all parameters of the urethral pressure profile decreased significantly. While none of the nulliparous women had a positive clinical stress test during spinal anaesthesia, 4/7 parous women demonstrated leakage (Fisher's exact test, P = 0.003). Blockage of nerve supply to the pelvic floor muscles in continent women is associated with a significant loss of support of the bladder neck region confirming the theory of an active mechanism of muscular elements providing continence.

Superficial bladder cancer.

PubMed Central

Hall, R. R.

1994-01-01

Bladder cancer is almost certainly a product of the industrial revolution and the cigarette smoking that has accompanied it. Exposure to a chemical bladder carcinogen such as beta naphthylamine, benzidine, or 4-diphenylaniline can be proved in only a small proportion of patients and only a handful obtain industrial diseases benefit after developing "Prescribed Industrial Disease C23." None the less, the continued use of known carcinogenic substances in British industry for many years after their identification, the wide range of industries with a known or suspected increased risk of bladder cancer, and our ignorance of the carcinogenic potential of many materials used in current manufacturing should be a cause for continuing concern. Images p912-a PMID:8173377

Does the valve regulated release of urine from the bladder decrease encrustation and blockage of indwelling catheters by crystalline proteus mirabilis biofilms?

PubMed

Sabbuba, N A; Stickler, D J; Long, M J; Dong, Z; Short, T D; Feneley, R J C

2005-01-01

We tested whether valve regulated, intermittent flow of urine from catheterized bladders decreases catheter encrustation. Laboratory models of the catheterized bladder were infected with Proteus mirabilis. Urine was allowed to drain continuously through the catheters or regulated by valves to drain intermittently at predetermined intervals. The time that catheters required to become blocked was recorded and encrustation was visualized by scanning electron microscopy. When a manual valve was used to drain urine from the bladder at 2-hour intervals 4 times during the day, catheters required significantly longer to become blocked than those on continuous drainage (mean 62.6 vs 35.9 hours, p = 0.039). A similar 1.7-fold increase occurred when urine was drained at 4-hour intervals 3 times daily. Experiments with an automatic valve in which urine was released at 2 or 4-hour intervals through the day and night also showed a significant increase in mean time to blockage compared with continuous drainage (p = 0.001). Scanning electron microscopy confirmed that crystalline biofilm was less extensive on valve regulated catheters. Valve regulated, intermittent flow of urine through catheters increases the time that catheters require to become blocked with crystalline biofilm. The most beneficial effect was recorded when urine was released from the bladder at 4-hour intervals throughout the day and night by an automatic valve.

A Double Blind, Randomized Study of Safety and Efficacy of OnabotulinumtoxinA (OnaBoNT A) versus Oral Oxybutynin in SCI Patients with NDO (11 09 10 04)

DTIC Science & Technology

2017-10-01

Overactive bladder is a condition resulting from disruption of the normal micturition process. It is a syndrome complex characterized by urinary...from our pilot study in patients with another model of bladder dysfunction (i.e. interstitial cystitis/painful bladder syndrome (IC/PBS)) implanted...increased risk with exposure to ONAboNT-A including diagnosed myasthenia gravis, Eaton-Lambert syndrome or amyotrophic lateral sclerosis. 17

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Laboratory practical to study the differential innervation pathways of urinary tract smooth muscle.

PubMed

Rembetski, Benjamin E; Cobine, Caroline A; Drumm, Bernard T

2018-06-01

In the mammalian lower urinary tract, there is a reciprocal relationship between the contractile state of the bladder and urethra. As the bladder fills with urine, it remains relaxed to accommodate increases in volume, while the urethra remains contracted to prevent leakage of urine from the bladder to the exterior. Disruptions to the normal contractile state of the bladder and urethra can lead to abnormal micturition patterns and urinary incontinence. While both the bladder and urethra are smooth-muscle organs, they are differentially contracted by input from cholinergic and sympathetic nerves, respectively. The laboratory practical described here provides an experiential approach to understanding the anatomy of the lower urinary tract. Several key factors in urinary tract physiology are outlined, e.g., the bladder is contracted by activation of the parasympathetic pathway via cholinergic stimulation on muscarinic receptors, whereas the urethra is contracted by activation of the sympathetic pathway via adrenergic stimulation on α 1 -adrenoceptors. This is achieved by measuring the force generated by bladder and urethra smooth muscle to demonstrate that acetylcholine contracts the smooth muscle of the bladder, whereas adrenergic agonists contract the urethral smooth muscle. An inhibition of these effects is also demonstrated by application of the muscarinic receptor antagonist atropine and the α 1 -adrenergic receptor blocker phentolamine. A list of suggested techniques and exam questions to evaluate student understanding on this topic is also provided.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Kuiqing; Chen, Xu; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120

Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinasemore » p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.« less

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single-Balloon Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Kiyohito, E-mail: rad105@poh.osaka-med.ac.jp; Yamamoto, Kazuhiro, E-mail: rad043@poh.osaka-med.ac.jp; Nakai, Go, E-mail: rad091@poh.osaka-med.ac.jp

2016-06-15

PurposeApproximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI).Materials and MethodsFifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access.more » A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow.ResultsOne-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold).ConclusionThe amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response.« less

Down-regulation of annexin A1 in the urothelium decreases cell survival after bacterial toxin exposure.

PubMed

Monastyrskaya, Katia; Babiychuk, Eduard B; Draeger, Annette; Burkhard, Fiona C

2013-07-01

We examined the role of annexins in bladder urothelium. We characterized expression and distribution in normal bladders, biopsies from patients with bladder pain syndrome, cultured human urothelium and urothelial TEU-2 cells. Annexin expression in bladder layers was analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunofluorescence. We assessed cell survival after exposure to the pore forming bacterial toxin streptolysin O by microscopy and alamarBlue® assay. Bladder dome biopsies were obtained from 8 asymptomatic controls and 28 patients with symptoms of bladder pain syndrome. Annexin A1, A2, A5 and A6 were differentially distributed in bladder layers. Annexin A6 was abundant in detrusor smooth muscle and low in urothelium, while annexin A1 was the highest in urothelium. Annexin A2 was localized to the lateral membrane of umbrella cells but excluded from tight junctions. TEU-2 cell differentiation caused up-regulation of annexin A1 and A2 and down-regulation of annexin A6 mRNA. Mature urothelium dedifferentiation during culture caused the opposite effect, decreasing annexin A1 and increasing annexin A6. Annexin A2 influenced TEU-2 cell epithelial permeability. siRNA mediated knockdown of annexin A1 in TEU-2 cells caused significantly decreased cell survival after streptolysin O exposure. Annexin A1 was significantly reduced in biopsies from patients with bladder pain syndrome. Several annexins are expressed in human bladder and TEU-2 cells, in which levels are regulated during urothelial differentiation. Annexin A1 down-regulation in patients with bladder pain syndrome might decrease cell survival and contribute to compromised urothelial function. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model.

PubMed

Wang, Hung-Jen; Lee, Wei-Chia; Tyagi, Pradeep; Huang, Chao-Cheng; Chuang, Yao-Chi

2017-08-01

Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model. Control and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm 2 ) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting. CYP-induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812). CYP-induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity. © 2016 Wiley Periodicals, Inc.

Urinary tract infection-like symptom is associated with worse bladder cancer outcomes in the Medicare population: Implications for sex disparities.

PubMed

Richards, Kyle A; Ham, Sandra; Cohn, Joshua A; Steinberg, Gary D

2016-01-01

To determine the time to bladder cancer diagnosis from initial infection-like symptoms and its impact on cancer outcomes. Using Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥ 66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes. The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥ pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70-2.55) and men (odds ratio 1.71, 95% confidence interval 1.49-1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10-1.71, and hazard ratio 1.47, 95% confidence interval 1.28-1.69) compared with women with hematuria. Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes. © 2015 The Japanese Urological Association.

Intrafraction Bladder Motion in Radiation Therapy Estimated From Pretreatment and Posttreatment Volumetric Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foroudi, Farshad, E-mail: farshad.foroudi@petermac.org; Pham, Daniel; Bressel, Mathias

2013-05-01

Purpose: The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Methods and Materials: Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatmentmore » and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. Results: The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Conclusion: Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.« less

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer.

PubMed

Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

2016-12-01

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer.

PubMed

Lu, Yan; Liu, Pengyuan; Van den Bergh, Francoise; Zellmer, Victoria; James, Michael; Wen, Weidong; Grubbs, Clinton J; Lubet, Ronald A; You, Ming

2012-02-01

The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10(-8) and r = 0.73, P = 1.50 × 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. ©2011 AACR.

Modulating the internalization of bacille Calmette-Guérin by cathelicidin in bladder cancer cells.

PubMed

Choi, Se Young; Kim, Soon-Ja; Chi, Byung Hoon; Kwon, Jong Kyou; Chang, In Ho

2015-04-01

To confirm the role of cathelicidin (LL-37) in the internalization of bacille Calmette-Guérin (BCG) into bladder cancer cells. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction analysis evaluated the changes in protein and messenger ribonucleic acid (RNA) expression with BCG incubation after LL-37 pretreatment in 5637 and T24 human bladder cancer cells. The internalization rate was evaluated by a double immunofluorescence assay, and confocal microscopy confirmed the function of LL-37 in BCG internalization. We also investigated the difference in internalization rates and cell viability between LL-37, anti-LL-37 antibody, and LL-37 plus anti-LL-37 antibody. The levels of LL-37 increased after BCG exposure in bladder cancer cells in dose- and time-dependent manners. Increasing LL-37 levels using recombinant LL-37 protein further dose dependently decreased BCG internalization in both cell lines. The internalization rates of BCG after LL-37 instillation were lower compared with the controls, and the internalization rate of BCG after anti-LL-37 antibody instillation was significantly higher compared with the controls in both cell lines (P <.05). Viability of LL-37 plus BCG group was higher compared with the BCG-alone group. The anti-LL-37 antibody plus BCG group had decreased cell viability compared with the BCG-alone group in both cell lines. Bladder cancer cells produce cathelicidin when infected with BCG and upregulate cathelicidin to defend against BCG by inhibiting its internalization. Blocking the action of cathelicidin may increase the internalization and effectiveness of BCG in reducing bladder cancer cell proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

PubMed

Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

2016-04-01

Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS. Copyright © 2016 the American Physiological Society.

Doing More for More: Unintended Consequences of Financial Incentives for Oncology Specialty Care.

PubMed

O'Neil, Brock; Graves, Amy J; Barocas, Daniel A; Chang, Sam S; Penson, David F; Resnick, Matthew J

2016-02-01

Specialty care remains a significant contributor to health care spending but largely unaddressed in novel payment models aimed at promoting value-based delivery. Bladder cancer, chiefly managed by subspecialists, is among the most costly. In 2005, Centers for Medicare and Medicaid Services (CMS) dramatically increased physician payment for office-based interventions for bladder cancer to shift care from higher cost facilities, but the impact is unknown. This study evaluated the effect of financial incentives on patterns of fee-for-service (FFS) bladder cancer care. Data from a 5% sample of Medicare beneficiaries from 2001-2013 were evaluated using interrupted time-series analysis with segmented regression. Primary outcomes were the effects of CMS fee modifications on utilization and site of service for procedures associated with the diagnosis and treatment of bladder cancer. Rates of related bladder cancer procedures that were not affected by the fee change were concurrent controls. Finally, the effect of payment changes on both diagnostic yield and need for redundant procedures were studied. All statistical tests were two-sided. Utilization of clinic-based procedures increased by 644% (95% confidence interval [CI] = 584% to 704%) after the fee change, but without reciprocal decline in facility-based procedures. Procedures unaffected by the fee incentive remained unchanged throughout the study period. Diagnostic yield decreased by 17.0% (95% CI = 12.7% to 21.3%), and use of redundant office-based procedures increased by 76.0% (95% CI = 59% to 93%). Financial incentives in bladder cancer care have unintended and costly consequences in the current FFS environment. The observed price sensitivity is likely to remain a major issue in novel payment models failing to incorporate procedure-based specialty physicians. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Opposite effects of tamoxifen on metabolic syndrome-induced bladder and prostate alterations: a role for GPR30/GPER?

PubMed

Comeglio, P; Morelli, A; Cellai, I; Vignozzi, L; Sarchielli, E; Filippi, S; Maneschi, E; Corcetto, F; Corno, C; Gacci, M; Vannelli, G B; Maggi, M

2014-01-01

BPH and LUTS have been associated to obesity, hypogonadism, and metabolic syndrome (MetS). MetS-induced prostate and bladder alterations, including inflammation and tissue remodeling, have been related to a low-testosterone and high-estrogen milieu. In addition to ERs, GPR30/GPER is able to mediate several estrogenic non-genomic actions. Supplementing a subgroup of MetS rabbits with tamoxifen, we analyzed the in vivo effects on MetS-induced prostate and bladder alterations. The effects of selective ER/GPER ligands and GPER silencing on prostate inflammation were also studied in vitro using hBPH cells. ERα, ERβ, and PR expression was upregulated in MetS bladder, where tamoxifen decreased ERα and PR expression, further stimulating ERβ. In addition, tamoxifen-dosing decreased MetS-induced overexpression of inflammatory and tissue remodeling genes. In prostate, sex steroid receptors, pro-inflammatory and pro-fibrotic genes were upregulated in MetS. However, tamoxifen did not affect them and even increased COX-2. In hBPH cells, 17β-estradiol increased IL-8 secretion, an effect blunted by co-treatment with GPER antagonist G15 but not by ER antagonist ICI 182,780, which further increased it. GPER agonist G1 dose-dependently (IC50  = 1.6 nM) induced IL-8 secretion. In vitro analysis demonstrated that GPER silencing reverted these stimulatory effects. GPER can be considered the main mediator of estrogen action in prostate, whereas in bladder the mechanism appears to rely on ERα, as indicated by in vivo experiments with tamoxifen dosing. Limiting the effects of the MetS-induced estrogen action via GPER could offer new perspectives in the management of BPH/LUTS, whereas tamoxifen dosing showed potential benefits in bladder. © 2013 Wiley Periodicals, Inc.

Auxotrophic recombinant Mycobacterium bovis BCG overexpressing Ag85B enhances cytotoxicity on superficial bladder cancer cells in vitro.

PubMed

Begnini, Karine Rech; Rizzi, Caroline; Campos, Vinicius Farias; Borsuk, Sibele; Schultze, Eduarda; Yurgel, Virginia Campello; Nedel, Fernanda; Dellagostin, Odir Antônio; Collares, Tiago; Seixas, Fabiana Kömmling

2013-02-01

BCG therapy remains at the forefront of immunotherapy for treating patients with superficial bladder cancer. The high incidence of local side effects and the presence of non-responder diseases have led to efforts to improve the therapy. Hence, we proposed that an auxotrophic recombinant BCG strain overexpressing Ag85B (BCG ∆leuD/Ag85B), could enhance the cytotoxicity to the human bladder carcinoma cell line 5637. The rBCG was generated using an expression plasmid encoding the mycobacterial antigen Ag85B to transform a BCG ∆leuD strain. The inhibitory effect of BCG ∆leuD/Ag85B on 5637 cells was determined by the MTT method, morphology observation and a LIVE/DEAD assay. Gene expression profiles for apoptotic, cell cycle-related and oxidative stress-related genes were investigated by qRT-PCR. Bax, bcl-2 and p53 induction by BCG ∆leuD/Ag85B treatment was evaluated by Western blotting. BCG ∆leuD/Ag85B revealed a superior cytotoxicity effect compared to the control strains used in this study. The results showed that the expression level of pro-apoptotic and cell cycle-related genes increased after BCG ∆leuD/Ag85B treatment, whereas the mRNA levels of anti-apoptotic genes decreased. Interestingly, BCG ∆leuD/Ag85B also increased the mRNA level of antioxidant enzymes in the bladder cancer cell line. Bax and p53 proteins levels increased following treatment. In conclusion, these results suggest that treatment with BCG ∆leuD/Ag85B enhances cytotoxicity for superficial bladder cancer cells in vitro. Therefore, rBCG therapy may have potential benefits in the treatment of bladder cancer.

Risk of transitional-cell carcinoma of the bladder in first- and second-generation immigrants to Sweden.

PubMed

Mousavi, Seyed Mohsen; Sundquist, Jan; Hemminki, Kari

2010-07-01

Environmental risk factors, particularly tobacco smoking, are important for transitional-cell carcinoma of the bladder. Studies in migrants may provide valuable insight into the environmental and genetic etiology of cancer. The nationwide Swedish Family-Cancer Database was used to calculate standardized incidence ratios (SIRs) for transitional-cell carcinoma among the immigrants compared with native Swedes. SIRs for lung cancer were also calculated as a proxy for smoking prevalence. Significantly decreased risks of bladder cancer were observed for male (SIR=0.89) and female (0.71) Finns and male East Asian (0.39) first-generation immigrants. Male immigrants from many countries showed increased risks, ranging from 1.18 to 2.29. Only female immigrants from Denmark (1.40) and Norway (1.27) had increased risks. The risks for bladder and lung cancers correlated, except for Finnish and Iranian men. The sons of immigrants born in high-risk countries had an increased SIR (1.51) whereas the daughters of immigrants born in low-risk countries had a decreased risk (0.32). The risk in the second-generation immigrants born in Sweden was equal to that of natives. In conclusion, the observed bladder cancer risks in the first-generation immigrants, the changes in risks in the second-generation immigrants, and the covariation of the risk patterns of bladder and lung cancers suggested a main contribution by tobacco smoking. The exceptional patterns among the Finns and Iranians may point to the existence of modifying factors. The changes in incidence in second-generation immigrants, yet based on small case numbers, lend little support to the involvement of genetic factors.

Novel bifunctional anthracycline and nitrosourea chemotherapy for human bladder cancer: analysis in a preclinical survival model.

PubMed

Glaves, D; Murray, M K; Raghavan, D

1996-08-01

A hybrid drug [N-2-chloroethylnitrosoureidodaunorubicin (AD312)] that combines structural and functional features of both anthracyclines and nitrosoureas was evaluated in a preclinical survival model of human bladder cancer. To measure the therapeutic activity of AD312, UCRU-BL13 transitional cell carcinoma cells were grown as xenografts in nude mice, and tumor growth rates were compared after i.v. administration of the drug at three dose levels. AD312 treatment at 45 and 60 mg/kg achieved 7-10-fold inhibition of tumor growth and increased host survival by 156 and 249%, respectively. Doses of 60 mg/kg showed optimal therapeutic efficacy, with sustained tumor growth inhibition, an over 2-fold increase in life span, and 40% of mice tumor free ("cured") at 120 days. Tumors were unresponsive to maximum tolerated doses of doxorubicin, a standard anthracycline used as a single agent and in combination therapies for bladder cancer. 1,3-Bis-[2-chloroethyl]-1-nitrosourea was used as a control for the apparently enhanced response of human tumors in murine hosts to nitrosoureas. 1, 3-Bis-[2-chloroethyl]-1-nitrosourea administered in three injections of 20 mg/kg did not cure mice but temporarily inhibited tumor growth by 70% and prolonged survival by 55%; its activity in this model suggests that it may be included in the repertoire of alkylating agents currently used for treatment of bladder cancers. AD312 showed increased antitumor activity with less toxicity than doxorubicin, and its bifunctional properties provide the opportunity for simultaneous treatment of individual cancer cells with two cytotoxic modalities as well as treatment of heterogeneous populations typical of bladder cancers. This novel cytotoxic drug cured doxorubicin-refractory disease and should be investigated for the clinical management of bladder cancer.

[miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway].

PubMed

Li, Xiaohui; Han, Xingtao; Yang, Jinhui; Sun, Jiantao; Wei, Pengtao

2017-10-01

Objective To observe the effect of microRNA-503-5p (miR-503-5p) on the growth of T24 and EJ bladder cancer cells, and explore the possible molecular mechanism. Methods The miR-504-5p mimics or miR-NC was transfected into T24 and EJ cells. The target gene of miR-503-5p was predicted by bioinformatics. The expressions of E2F transcription factor 3 (E2F3) mRNA and Rb/E2F signaling pathway mRNA were detected by the real-time quantitative PCR (qPCR). The expressions of Rb/E2F signal pathway proteins E2F3, cyclin E, CDK2, Rb and p-Rb were detected by Western blotting. The cell cycle of bladder cancer cell lines was determined by flow cytometry. MTT assay and plate cloning assay were performed to observe the proliferation ability of bladder cancer cells. Results After miR-503-5p mimics transfection, the expression of miR-503-5p in bladder cancer cells significantly increased. The increased expression of miR-503-5p significantly reduced the expressions of E2F3 mRNA and Rb/E2F signaling pathway mRNA in bladder cancer cells. What's more, the expressions of Rb/E2F signal pathway proteins were down-regulated. The bladder cancer cells were arrested in G0/G1 phase, and their growth was significantly inhibited by miR-503-5p. Conclusion The miR-503-5p over-expression can inhibit the growth of bladder cancer cell lines T24 and EJ by down-regulating the expression of the Rb/E2F signaling pathway.

SU-E-T-491: Influence of Applicator Dimensions On Doses to Bladder, Rectum and Sigmoid in HDR Brachytherapy for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumane, V; Rhome, R; Yuan, Y

2015-06-15

Purpose: To study the influence of dimensions of the tandem and ring applicator on bladder D2cc, rectum D2cc and sigmoid D2cc in HDR treatment planning for cervical cancer. Methods: 53 plans from 13 patients treated at our institution with the tandem and ring applicator were retrospectively reviewed. Prescription doses were one of the following: 8 Gy x 3, 7 Gy x 4 and 5.5 Gy x 5. Doses to the D2ccs of the bladder, rectum and the sigmoid were recorded. These doses were normalized to their relative prescriptions doses. Correlations between the normalized bladder D2cc, rectum D2cc and sigmoid D2ccmore » were investigated and linear regression models were developed to study the dependence of these doses on the ring diameter and the applicator angle. Results: Normalized doses to the D2cc of the bladder, rectum and sigmoid showed statistically significant correlation (P < 0.05) to the applicator angle. Significant correlation was also noted for the normalized D2cc of the rectum and the sigmoid with the ring diameter. The normalized bladder D2cc was found to decrease with applicator angle on an average by 22.65% ± 4.43% while the same for the rectum and sigmoid were found to increase on an average by 14.43% ± 1.65% and 14.01% ± 1.42% respectively. Both the rectum and sigmoid D2cc reduced with increasing ring diameter by 12.93% ± 1.95% and 11.27% ± 1.79%. No correlation was observed between the normalized bladder D2cc and the ring diameter. Conclusion: Preliminary regression models developed in this study can potentially aid in the choice of the appropriate applicator angle and ring diameter for tandem and ring implant so as to optimize doses to the bladder, rectum and sigmoid.« less

The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration.

PubMed

Snow-Lisy, Devon C; Diaz, Edward C; Bury, Matthew I; Fuller, Natalie J; Hannick, Jessica H; Ahmad, Nida; Sharma, Arun K

2015-01-01

Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an alternate means to achieve functional bladder regeneration.

Altered Expression of Transmembrane Mucins, MUC1 and MUC4, in Bladder Cancer: Pathological Implications in Diagnosis

PubMed Central

Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G.; Horn, Adam J.; Lele, Subodh M.; Theodorescu, Dan; Batra, Surinder K.

2014-01-01

Purpose Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma. PMID:24671186

An improved distance-to-dose correlation for predicting bladder and rectum dose-volumes in knowledge-based VMAT planning for prostate cancer

NASA Astrophysics Data System (ADS)

Wall, Phillip D. H.; Carver, Robert L.; Fontenot, Jonas D.

2018-01-01

The overlap volume histogram (OVH) is an anatomical metric commonly used to quantify the geometric relationship between an organ at risk (OAR) and target volume when predicting expected dose-volumes in knowledge-based planning (KBP). This work investigated the influence of additional variables contributing to variations in the assumed linear DVH-OVH correlation for the bladder and rectum in VMAT plans of prostate patients, with the goal of increasing prediction accuracy and achievability of knowledge-based planning methods. VMAT plans were retrospectively generated for 124 prostate patients using multi-criteria optimization. DVHs quantified patient dosimetric data while OVHs quantified patient anatomical information. The DVH-OVH correlations were calculated for fractional bladder and rectum volumes of 30, 50, 65, and 80%. Correlations between potential influencing factors and dose were quantified using the Pearson product-moment correlation coefficient (R). Factors analyzed included the derivative of the OVH, prescribed dose, PTV volume, bladder volume, rectum volume, and in-field OAR volume. Out of the selected factors, only the in-field bladder volume (mean R  =  0.86) showed a strong correlation with bladder doses. Similarly, only the in-field rectal volume (mean R  =  0.76) showed a strong correlation with rectal doses. Therefore, an OVH formalism accounting for in-field OAR volumes was developed to determine the extent to which it improved the DVH-OVH correlation. Including the in-field factor improved the DVH-OVH correlation, with the mean R values over the fractional volumes studied improving from  -0.79 to  -0.85 and  -0.82 to  -0.86 for the bladder and rectum, respectively. A re-planning study was performed on 31 randomly selected database patients to verify the increased accuracy of KBP dose predictions by accounting for bladder and rectum volume within treatment fields. The in-field OVH led to significantly more precise and fewer unachievable KBP predictions, especially for lower bladder and rectum dose-volumes.

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Hong, Jin Ki; Jang, Ja Yun; An, Jieun; Lee, Kyu-Sung; Kang, Tong Mook; Shin, Hyun Joon; Suh, Jun-Kyo Francis

2017-01-01

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

PubMed

Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

2017-02-01

Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study.

PubMed

Ferrucci, Leah M; Sinha, Rashmi; Ward, Mary H; Graubard, Barry I; Hollenbeck, Albert R; Kilfoy, Briseis A; Schatzkin, Arthur; Michaud, Dominique S; Cross, Amanda J

2010-09-15

Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer. During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; P(trend) = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; P(trend) = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; P(trend) = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; P(trend) = .11). These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis. © 2010 American Cancer Society.

Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells.

PubMed

Adam, Rosalyn M; Eaton, Samuel H; Estrada, Carlos; Nimgaonkar, Ashish; Shih, Shu-Ching; Smith, Lois E H; Kohane, Isaac S; Bägli, Darius; Freeman, Michael R

2004-12-15

Application of mechanical stimuli has been shown to alter gene expression in bladder smooth muscle cells (SMC). To date, only a limited number of "stretch-responsive" genes in this cell type have been reported. We employed oligonucleotide arrays to identify stretch-sensitive genes in primary culture human bladder SMC subjected to repetitive mechanical stimulation for 4 h. Differential gene expression between stretched and nonstretched cells was assessed using Significance Analysis of Microarrays (SAM). Expression of 20 out of 11,731 expressed genes ( approximately 0.17%) was altered >2-fold following stretch, with 19 genes induced and one gene (FGF-9) repressed. Using real-time RT-PCR, we tested independently the responsiveness of 15 genes to stretch and to platelet-derived growth factor-BB (PDGF-BB), another hypertrophic stimulus for bladder SMC. In response to both stimuli, expression of 13 genes increased, 1 gene (FGF-9) decreased, and 1 gene was unchanged. Six transcripts (HB-EGF, BMP-2, COX-2, LIF, PAR-2, and FGF-9) were evaluated using an ex vivo rat model of bladder distension. HB-EGF, BMP-2, COX-2, LIF, and PAR-2 increased with bladder stretch ex vivo, whereas FGF-9 decreased, consistent with expression changes observed in vitro. In silico analysis of microarray data using the FIRED algorithm identified c-jun, AP-1, ATF-2, and neurofibromin-1 (NF-1) as potential transcriptional mediators of stretch signals. Furthermore, the promoters of 9 of 13 stretch-responsive genes contained AP-1 binding sites. These observations identify stretch as a highly selective regulator of gene expression in bladder SMC. Moreover, they suggest that mechanical and growth factor signals converge on common transcriptional regulators that include members of the AP-1 family.

A Randomized Pilot Trial of Dietary Modification for the Chemoprevention of Non-invasive Bladder Cancer: The Dietary Intervention in Bladder Cancer Study (DIBS)

PubMed Central

Parsons, J. Kellogg; Pierce, John P.; Natarajan, Loki; Newman, Vicky A.; Barbier, Leslie; Mohler, James; Rock, Cheryl L.; Heath, Dennis D.; Guru, Khurshid; Jameson, Michael B.; Li, Hongying; Mirheydar, Hossein; Holmes, Michael A.; Marshall, James

2013-01-01

Epidemiological data suggest robust associations of high vegetable intake with decreased risks of bladder cancer incidence and mortality, but translational prevention studies have yet to be performed. We designed and tested a novel intervention to increase vegetable intake in patients with non-invasive bladder cancer. We randomized 48 patients aged 50 to 80 years with biopsy-proven non-invasive (Ta, T1, or carcinoma in situ) urothelial cell carcinoma to telephone- and Skype-based dietary counseling or a control condition that provided print materials only. The intervention behavioral goals promoted 7 daily vegetable servings, with at least 2 of these as cruciferous vegetables. Outcome variables were self-reported diet and plasma carotenoid and 24-hour urinary isothiocyanate (ITC) concentrations. We used 2-sample t-tests to assess between-group differences at 6-month follow-up. After 6 months, intervention patients had higher daily intakes of vegetable juice (p=0.02), total vegetables (p=0.02), and cruciferous vegetables (p=0.07); lower daily intakes of energy (p=0.007), (p=0.002) and energy from fat (p=0.06); and higher plasma alpha-carotene concentrations (p=0.03). Self-reported cruciferous vegetable intake correlated with urinary ITC concentrations at baseline (p<0.001) and at 6 months (p=0.03). Although urinary ITC concentrations increased in the intervention group and decreased in the control group, these changes did not attain between-group significance (p=0.32). In patients with non-invasive bladder cancer, our novel intervention induced diet changes associated with protective effects against bladder cancer. These data demonstrate the feasibility of implementing therapeutic dietary modifications to prevent recurrent and progressive bladder cancer. PMID:23867158

Extracellular UDP enhances P2X-mediated bladder smooth muscle contractility via P2Y6 activation of the phospholipase C/inositol trisphosphate pathway

PubMed Central

Yu, Weiqun; Sun, Xiaofeng; Robson, Simon C.; Hill, Warren G.

2013-01-01

Bladder dysfunction characterized by abnormal bladder smooth muscle (BSM) contractions is pivotal to the disease process in overactive bladder, urge incontinence, and spinal cord injury. Purinergic signaling comprises one key pathway in modulating BSM contractility, but molecular mechanisms remain unclear. Here we demonstrate, using myography, that activation of P2Y6 by either UDP or a specific agonist (MRS 2693) induced a sustained increase in BSM tone (up to 2 mN) in a concentration-dependent manner. Notably, activation of P2Y6 enhanced ATP-mediated BSM contractile force by up to 45%, indicating synergistic interactions between P2X and P2Y signaling. P2Y6-activated responses were abolished by phospholipase C (PLC) and inositol trisphosphate (IP3) receptor antagonists U73122 and xestospongin C, demonstrating involvement of the PLC/IP3 signal pathway. Mice null for Entpd1, an ectonucleotidase on BSM, demonstrated increased force generation on P2Y6 activation (150%). Thus, in vivo perturbations to purinergic signaling resulted in altered P2Y6 activity and bladder contractility. We conclude that UDP, acting on P2Y6, regulates BSM tone and in doing so selectively maximizes P2X1-mediated contraction forces. This novel neurotransmitter pathway may play an important role in urinary voiding disorders characterized by abnormal bladder motility.—Yu, W., Sun, X., Robson, S. C., Hill, W. G. Extracellular UDP enhances P2X-mediated bladder smooth muscle contractility via P2Y6 activation of the phospholipase C/inositol trisphosphate pathway. PMID:23362118

Variations of thickness of trigonal muscle layer in different age and sex.

PubMed

Sultana, J; Khalil, M; Sultana, S Z; Mannan, S; Choudhury, S; Ara, A; Sumi, M S; Farzana, T; Sultana, R; Tania, A H

2014-10-01

This cross sectional descriptive study was to measure the thickness of muscular layer in trigone of the urinary bladder and to establish the difference between sexes of different age groups in Bangladeshi cadaver. A total 60 human urinary bladders were collected by purposive sampling from May 2013 to October 2013. Among them from male 43 and from female 17 were collected from Bangladeshi cadavers of age ranging from 01 to 60 years, from autopsy laboratory of the Department of Forensic Medicine of Mymensingh Medical College, Mymensingh. The thickness of muscular layer in trigone of the urinary bladder was measured and significant differences of the value between age and sex groups were observed. The mean±SD thickness of muscular layer of trigone of the urinary bladder was 318.59±93.15μm in age Group A (01 to 20 years), 633.25±79.79μm in age Group B (21 to 40 years), and 352.50±116.15μm in age Group C (41 to 60 years). The mean difference of muscular layer of the trigone of the urinary bladder between age Groups A&B, B&C was statistically highly significant, where p=0.001. In statistical analysis, differences between age groups were calculated by using one way ANOVA test. The present study revealed that the value of thickness of muscular layer in trigone of the urinary bladder was increased with the increase of age and it was declined to a low level in the late age. The mean value of muscular layer of the trigone of the urinary bladder was higher in male than that of in female of Group A, B & C.

Menthol Inhibits Detrusor Contractility Independently of TRPM8 Activation

PubMed Central

Ramos-Filho, Antonio Celso Saragossa; Shah, Ajay; Augusto, Taize Machado; Barbosa, Guilherme Oliveira; Leiria, Luiz Osorio; de Carvalho, Hernandes Faustino; Antunes, Edson; Grant, Andrew Douglas

2014-01-01

Agonists such as icilin and menthol can activate the cool temperature-sensitive ion channel TRPM8. However, biological responses to menthol may occur independently of TRPM8 activation. In the rodent urinary bladder, menthol facilitates the micturition reflex but inhibits muscarinic contractions of the detrusor smooth muscle. The site(s) of TRPM8 expression in the bladder are controversial. In this study we investigated the regulation of bladder contractility in vitro by menthol. Bladder strips from wild type and TRPM8 knockout male mice (25–30 g) were dissected free and mounted in organ baths. Isometric contractions to carbachol (1 nM–30 µM), CaCl2 (1 µM to 100 mM) and electrical field stimulation (EFS; 8, 16, 32 Hz) were measured. Strips from both groups contracted similarly in response to both carbachol and EFS. Menthol (300 µM) or nifedipine (1 µM) inhibited carbachol and EFS-induced contractions in both wild type and TRPM8 knockout bladder strips. Incubation with the sodium channel blocker tetrodotoxin (1 µM), replacement of extracellular sodium with the impermeant cation N-Methyl-D-Glucamine, incubation with a cocktail of potassium channel inhibitors (100 nM charybdotoxin, 1 µM apamin, 10 µM glibenclamide and 1 µM tetraethylammonium) or removal of the urothelium did not affect the inhibitory actions of menthol. Contraction to CaCl2 was markedly inhibited by either menthol or nifedipine. In cultured bladder smooth muscle cells, menthol or nifedipine abrogated the carbachol or KCl-induced increases in [Ca2+]i. Intravesical administration of menthol increased voiding frequency while decreasing peak voiding pressure. We conclude that menthol inhibits muscarinic bladder contractions through blockade of L-type calcium channels, independently of TRPM8 activation. PMID:25375115

Epidemiologic survey of bladder cancer in greater New Orleans.

PubMed

Sullivan, J W

1982-08-01

Primary ancestry of the patients and controls in this study was not statistically different but the Jewish population had a significantly increased incidence of bladder cancer. Over-all, a significantly greater number of patients smoked filtered cigarettes, began drinking artificially sweetened beverages at an earlier age, drank artificially sweetened beverages for a greater number of years, consumed a greater number of glasses of artificially sweetened beverages weekly and related a history of urinary tract infections. A significantly increased incidence of bladder cancer was noted in individuals employed by certain types of companies, by certain job titles and by certain job material handled. Analysis of the data failed to show any significant difference in years of consumption of coffee, amount of various types of coffee or tea consumed, consumption of various nonalcoholic and alcoholic beverages, including source of drinking water, use of hair dye, incidence of diabetes mellitus, family history of urinary cancer and a history of pelvic irradiation or bladder stones.

Cancer among farmers in central Italy.

PubMed

Forastiere, F; Quercia, A; Miceli, M; Settimi, L; Terenzoni, B; Rapiti, E; Faustini, A; Borgia, P; Cavariani, F; Perucci, C A

1993-12-01

This case-referent study evaluated cancer risks among farmers in central Italy. Cancer cases (N = 1674, 17 sites) were selected from all deceased men aged 35-80 years; a random sample of 480 decedents formed the reference series. Farmers had a decreased risk of lung and bladder cancer and melanoma and nonsignificant excess risks for stomach, rectal, kidney, and nonmelanoma skin cancer. Stomach and kidney cancer were significantly increased among the farmers with > 10 years' experience, and stomach, rectal, and pancreatic cancer were increased among licensed pesticide users with > 10 years' experience. Possible relationships emerged between specific crops and cancer: fruit and colon and bladder cancer, wheat and prostate cancer, olives and kidney cancer, and potato and kidney cancer. The results regarding stomach, pancreatic, lung, bladder, and prostate cancer and melanoma congrue with earlier results. The kidney cancer excess, the association of colon and bladder cancer with orchard farming, and the excess of rectal cancer among licensed farmers are new and unexpected findings.

[Spinal cord injury with neurogenic lower urinary tract dysfunction as a potential risk factor for bladder carcinoma].

PubMed

Böthig, Ralf; Fiebag, Kai; Kowald, Birgitt; Hirschfeld, Sven; Thietje, Roland; Kurze, Ines; Schöps, Wolfgang; Böhme, Holger; Kaufmann, Albert; Zellner, Michael; Kadhum, Thura; Golka, Klaus

2018-05-29

 Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population?  Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer.  Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months).  The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between paralysis and tumour disease seems to be a decisive risk parameter.The type of neurogenic bladder dysfunction and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients.Early detection of bladder cancer in patients with spinal cord injury remains a challenge. © Georg Thieme Verlag KG Stuttgart · New York.

G-protection mechanisms afforded by the anti-G suit abdominal bladder with and without pressure breathing.

PubMed

Eiken, Ola; Bergsten, Eddie; Grönkvist, Mikael

2011-10-01

G protection afforded by the abdominal bladder of a pneumatic anti-G suit is usually attributed to counteraction of G-induced caudad displacement of the heart and pooling of blood in the abdominal veins. The study examined whether the abdominal bladder might provide G protection also via other mechanisms. Each subject was exposed to +Gz loads while sitting relaxed, wearing a full-coverage anti-G suit modified to permit separate pressurization of the abdominal and leg bladders. In two experimental series (N = 8, N = 14), subjects were breathing at positive airway pressure (PPB); in a third series, five subjects were breathing at atmospheric airway pressure. Intrathoracic pressures were estimated by use of esophageal catheters. During PPB at high G loads, intrathoracic pressure was higher with than without the pressurized abdominal bladder. In 7 of the 14 subjects, basilar intrathoracic pressure exceeded airway pressure during PPB when the abdominal bladder was pressurized. The mean arterial pressure response at high G loads was higher in this subset of subjects (55 +/- 23 mmHg) than in the subjects in whom airway pressure exceeded intrathoracic pressure (41 +/- 27 mmHg). Without PPB at increased G load, the intrathoracic pressure gradient was higher with than without the pressurized abdominal bladder. During PPB, the abdominal bladder acts as an airway counterpressure, thereby facilitating pressure transmission from the airways to the thorax and hence improving G protection. It also appears that in several individuals, pressure may be transmitted from the abdominal bladder to the thorax and heart.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

PubMed

Krech, Eugen; Selinski, Silvia; Blaszkewicz, Meinolf; Bürger, Hannah; Kadhum, Thura; Hengstler, Jan G; Truss, Michael C; Golka, Klaus

2017-01-01

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

PubMed

Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

2018-01-01

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somogyi, G.T.; de Groat, W.C.

Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activationmore » of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.« less

THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

PubMed

Kehinde, E O; Al-Maghrebi, M; Anim, J T; Kapila, K; George, S S; Al-Juwaiser, A; Memon, A

2013-01-01

To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. Prospective study Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

Bladder Smooth Muscle Cells Differentiation from Dental Pulp Stem Cells: Future Potential for Bladder Tissue Engineering

PubMed Central

Song, Bing; Jiang, Wenkai; Alraies, Amr; Liu, Qian; Gudla, Vijay; Oni, Julia; Wei, Xiaoqing; Sloan, Alastair; Ni, Longxing; Agarwal, Meena

2016-01-01

Dental pulp stem cells (DPSCs) are multipotent cells capable of differentiating into multiple cell lines, thus providing an alternative source of cell for tissue engineering. Smooth muscle cell (SMC) regeneration is a crucial step in tissue engineering of the urinary bladder. It is known that DPSCs have the potential to differentiate into a smooth muscle phenotype in vitro with differentiation agents. However, most of these studies are focused on the vascular SMCs. The optimal approaches to induce human DPSCs to differentiate into bladder SMCs are still under investigation. We demonstrate in this study the ability of human DPSCs to differentiate into bladder SMCs in a growth environment containing bladder SMCs-conditioned medium with the addition of the transforming growth factor beta 1 (TGF-β1). After 14 days of exposure to this medium, the gene and protein expression of SMC-specific marker (α-SMA, desmin, and calponin) increased over time. In particular, myosin was present in differentiated cells after 11 days of induction, which indicated that the cells differentiated into the mature SMCs. These data suggested that human DPSCs could be used as an alternative and less invasive source of stem cells for smooth muscle regeneration, a technology that has applications for bladder tissue engineering. PMID:26880982

Genome-wide association studies in bladder cancer: first results and potential relevance.

PubMed

Kiemeney, Lambertus A; Grotenhuis, Anne J; Vermeulen, Sita H; Wu, Xifeng

2009-09-01

The role of genetic susceptibility in the development of urinary bladder cancer is unclear, as it is in many other types of cancer. Since 2007, however, an innovative research approach (i.e. genome-wide association studies or GWASs) has led to the identification of numerous genomic loci that harbor susceptibility factors for one or more cancer sites. All GWASs have been published in high-impact journals and the strengths of the design are acknowledged by all experts, but there is criticism about the relevance of the results. Late 2008, the first GWAS in bladder cancer was published. In this review, the principles of GWASs are explained, as well as their strengths and limitations. The study in bladder cancer among 4000 cases and 38,000 controls identified three new susceptibility loci at 8q24, 3q28, and 5p15 that increase the risk of bladder cancer by 22, 19, and 16%, respectively. The results of two other GWASs in bladder cancer are expected to appear this year. Joint analysis of the three studies will probably identify additional susceptibility loci. The results of bladder cancer GWASs may point the way to yet unknown disease mechanisms. So far, the findings are not sufficiently discriminative for risk predictions to be used in clinical care or public health.

Bladder cancer and smoking. Part 3: influence of perceptions and beliefs.

PubMed

Anderson, Beverley; Naish, Wendy

This is the third of a four-part series on bladder cancer and smoking. Part one examined the risks factors for bladder cancer, emphasizing that although there are many risk factors, smoking is the main predisposing factor for the disease. Part two presented an overview of bladder cancer, including diagnosis and management of the disease. Part three seeks to determine the extent to which people's concept of what constitutes good health is influenced by their perceptions and beliefs. It then looks at whether educational support, specifically health promotion and health education, are effective in increasing the individual's awareness of the dangers of smoking for their health, and consequently in changing existing behaviours or dissuading them from becoming future smokers.

Foods and risk of bladder cancer: a case-control study in Uruguay.

PubMed

Balbi, J C; Larrinaga, M T; De Stefani, E; Mendilaharsu, M; Ronco, A L; Boffetta, P; Brennan, P

2001-10-01

A case-control study on 144 cases of transitional cell bladder carcinoma and 576 hospitalized controls was conducted in Montevideo, Uruguay. Barbecued meat, salted meat and fried eggs were associated with significant increased risks of bladder cancer (odds ratio (OR) for high intake of salted meat 4.04, 95% confidence interval (CI) 2.24-7.27). On the other hand, all fruits, cooked vegetables, potatoes and cheese were associated with inverse associations (OR for high consumption of potatoes 0.38, 95% CI 0.23-0.64). The associations with salted and barbecued meat suggest that the way of preserving or cooking meat play a role in bladder carcinogenesis. More precisely, N-nitroso compounds and heterocyclic amines could be involved in this process.

Optimal bladder filling during high-dose-rate intracavitary brachytherapy for cervical cancer: a dosimetric study

PubMed Central

Shetty, Saurabha; Majumder, Dipanjan; Adurkar, Pranjal; Swamidas, Jamema; Engineer, Reena; Chopra, Supriya; Shrivastava, Shyamkishore

2017-01-01

Purpose The aim of this study is to compare 3D dose volume histogram (DVH) parameters of bladder and other organs at risk with different bladder filling protocol during high-dose-rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer, and to find optimized bladder volume. Material and methods This dosimetric study was completed with 21 patients who underwent HDR-ICBT with computed tomography/magnetic resonance compatible applicator as a routine treatment. Computed tomography planning was done for each patient with bladder emptied (series 1), after 50 ml (series 2), and 100 ml (series 3) bladder filling with a saline infusion through the bladder catheter. Contouring was done on the Eclipse Planning System. 7 Gy to point A was prescribed with the standard loading patterns. Various 3D DVH parameters including 0.1 cc, 1 cc, 2 cc doses and mean doses to the OAR’s were noted. Paired t-test was performed. Results The mean (± SD) bladder volume was 64.5 (± 25) cc, 116.2 (± 28) cc, and 172.9 (± 29) cc, for series 1, 2, and 3, respectively. The 0.1 cm3,1 cm3, 2 cm3 mean bladder doses for series 1, series 2, and series 3 were 9.28 ± 2.27 Gy, 7.38 ± 1.72 Gy, 6.58 ± 1.58 Gy; 9.39 ± 2.28 Gy, 7.85 ± 1.85 Gy, 7.05 ± 1.59 Gy, and 10.09 ± 2.46 Gy, 8.33 ± 1.75 Gy, 7.6 ± 1.55 Gy, respectively. However, there was a trend towards higher bladder doses in series 3. Similarly, for small bowel dose 0.1 cm3, 1 cm3, and 2 cm3 in series 1, 2, and 3 were 5.44 ± 2.2 Gy, 4.41 ± 1.84 Gy, 4 ± 1.69 Gy; 4.57 ± 2.89 Gy, 3.78 ± 2.21 Gy, 3.35 ± 2.02 Gy, and 4.09 ± 2.38 Gy, 3.26 ± 1.8 Gy, 3.05 ± 1.58 Gy. Significant increase in small bowel dose in empty bladder (series 1) compared to full bladder (series 3) (p = 0.03) was noted. However, the rectal and sigmoid doses were not significantly affected with either series. Conclusions Bladder filling protocol with 50 ml and 100 ml was well tolerated and achieved a reasonably reproducible bladder volume during cervical brachytherapy. In our analysis so far, there is no significant impact of bladder filling on DVH parameters, although larger bladders tend to have higher doses. Small bowel doses are lesser with higher bladder volumes. Further evaluation and validation are necessary. PMID:28533798

Serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat.

PubMed

Tu, Hongjian; Cao, Nailong; Gu, Baojun; Si, Jiemin; Chen, Zhong; Andersson, Karl-Erik

2015-07-01

To examine the effects of the serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) on micturition in rats with diabetes mellitus (DM). Female Sprague-Dawley rats (n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram (CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v. Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume (PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation (HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes. The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5-HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

[Advances in clinical study of nocturia].

PubMed

Guan, Zhi-chen

2010-08-18

Nocturia is one of the most common reasons for interrupted sleep in general adult population. The condition affects both men and women, with an incidence that increases dramatically with age. Nocturia has a negative impact on quality of life, affecting both morbidity and mortality. International Continence Society (ICS) issued a report of terminology standardization in 2002, in which nocturia is defined as waking during the night at least once to urinate. Nocturia is a common complaint in elderly population. Although most cases of nocturia are assumed to be caused by urologic problems, the interacting effects of aging and sleep on renal and urinary function, in fact, cause nocturia in the elderly. Effective diagnosis of the condition is dependent on a clear understanding of its underlying etiology. Multiple factors may cause nocturia, such as behavioral or environmental factors and pathologic conditions. In general, the causes of nocturia fall into three categories: diurnal polyuria, nocturnal polyuria, and low bladder capacity. Careful evaluation of medications and underlying medical conditions is essential for the proper management of nocturia. A voiding diary is necessary to diagnose the syndrome of nocturnal polyuria, which is a common cause of nocturia. Addressing any underlying conditions that contribute to nocturia is the first step in treating the condition. Lifestyle and behavioral changes may provide benefit in some individuals, but for many cases, pharmacotherapy is the best option. Antimuscarinic agents are first-line therapies for overactive bladder and are often used in the management of nocturia. Current treatment options also include desmopressin, a synthetic analog of arginine vasopressin, which can increase urinary osmolality and decrease total urinary volume. The desmopressin therefore increases the length of time until the first nocturnal void and decreases the number of nocturnal voids, the NUV voided, and the percentage of urine voided at night.

Comparison of urodynamic volume measurements using room and body temperature saline: a double-blinded randomized crossover study design.

PubMed

Gehrich, Alan Paul; Hill, Micah J; McWilliams, Grant D E; Larsen, Wilma; McCartin, Tamarin

2012-01-01

Urodynamic studies, routinely performed in women with lower urinary tract symptoms, have a large impact on clinical decision making. Unfortunately, these studies are insensitive in reproducing idiopathic detrusor overactivity (IDO). We set out to examine whether serial cystometry with different distending fluid temperatures could better reproduce symptoms. Eighty-six women were enrolled in a double-blinded, randomized, crossover study. Two cystometries were performed in series, starting with either body temperature fluid (BTF) or room temperature fluid (RTF) and then repeating cystometry with the other temperature fluid. Primary outcomes included first sensation, first urge, and maximum cystometric capacity. Secondary outcomes included subjective sensation of bladder discomfort and the incidence of IDO. In aggregate, the temperature of the fluid did not affect volumes of bladder sensation. There were no differences in self-reported bladder irritation or IDO between the different temperature fluids. There was a significant carryover effect with BTF. BTF administered first reached sensory thresholds at lower volumes than when it was administered second after RTF. Room temperature fluid cystometry showed no statistical difference in volume between first fill and second fill. Idiopathic detrusor overactivity contractions were seen in 9% of studies and were not affected by period or temperature. These data suggest that BTF and RTF independently do not affect bladder sensory thresholds. The periodicity in combination with varying fluid temperature is of greater impact. This study documents that changes in temperature of the distending fluid from BTF to RTF or vice versa likely do not provoke IDO contractions.

ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes--a possible sensory mechanism?

PubMed Central

Ferguson, D R; Kennedy, I; Burton, T J

1997-01-01

1. The responses of rabbit urinary bladder to hydrostatic pressure changes and to electrical stimulation have been investigated using both the Ussing chamber and a superfusion apparatus. These experiments enabled us to monitor changes in both ionic transport across the tissue and cellular ATP release from it. 2. The urinary bladder of the rabbit maintains an electrical potential difference across its wall as a result largely of active sodium transport from the urinary (mucosal) to the serosal surface. 3. Small hydrostatic pressure differences produced by removal of bathing fluid from one side of the tissue caused reproducible changes in both potential difference and short-circuit current. The magnitude of these changes increases as the volume of fluid removed increases. 3. Amiloride on the mucosal (urinary), but not the serosal, surface of the membrane reduces the transepithelial potential difference and short-circuit current with an IC50 of 300 nM. Amiloride reduces the size of, but does not abolish, transepithelial potential changes caused by alterations in hydrostatic pressure. 4. Field electrical stimulation of strips of bladder tissue produces a reproducible release of ATP. Such release was demonstrated to occur largely from urothelial cells and is apparently non-vesicular as it increases in the absence of calcium and is not abolished by tetrodotoxin. 5. It is proposed that ATP is released from the urothelium as a sensory mediator for the degree of distension of the rabbit urinary bladder and other sensory modalities. PMID:9423189

Urothelium muscarinic activation phosphorylates CBSSer227 via cGMP/PKG pathway causing human bladder relaxation through H2S production

PubMed Central

d’Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Fusco, Ferdinando; Russo, Annapina; Pagliara, Valentina; Tramontano, Teresa; Donnarumma, Erminia; Mirone, Vincenzo; Cirino, Giuseppe; Russo, Giulia; Sorrentino, Raffaella

2016-01-01

The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser227 following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders. PMID:27509878

Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway causing human bladder relaxation through H2S production.

PubMed

d'Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Fusco, Ferdinando; Russo, Annapina; Pagliara, Valentina; Tramontano, Teresa; Donnarumma, Erminia; Mirone, Vincenzo; Cirino, Giuseppe; Russo, Giulia; Sorrentino, Raffaella

2016-08-11

The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders.

Dimethylarsinic acid in drinking water changed the morphology of urinary bladder but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats.

PubMed

Wang, Amy; Wolf, Douglas C; Sen, Banalata; Knapp, Geremy W; Holladay, Steven D; Huckle, William R; Caceci, Thomas; Robertson, John L

2009-06-01

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.

Stress and coping of parents of young children diagnosed with bladder exstrophy.

PubMed

Mednick, Lauren; Gargollo, Patricio; Oliva, Melisa; Grant, Rosemary; Borer, Joseph

2009-03-01

Previous studies have examined the psychological impact that living with bladder exstrophy has on patients. However, little is known about how parents of children diagnosed with this condition are affected. We examine how parents caring for children diagnosed with bladder exstrophy are impacted. An increased understanding of the stressors these parents face may lead to the development of appropriate parenting interventions, which may ultimately affect psychosocial and health outcomes in the child. All parents of children 10 years and younger treated for bladder exstrophy at our institution were selected from a centralized database. A total of 20 parents (65% of the eligible population) completed standardized questionnaires assessing pediatric specific parenting stress (Pediatric Inventory for Parents) and coping (Ways of Coping Questionnaire). Parents identified several common stressors (eg worrying about the long-term impact of the illness, helping the child with his/her hygiene needs) and overall reported using adaptive ways of coping (ie planful problem solving, seeking social support, positive reappraisal). However, when they experienced increased stress they reported using more nonadaptive ways of coping (ie escape/avoidance and distancing). Overall the findings of our study suggest that parents of children diagnosed with bladder exstrophy experience a significant amount of stress. In fact, parents in our study indicated experiencing similar frequency and difficulty of stress compared to parents of the same aged children diagnosed with type 1 diabetes. Increased stress can have negative consequences for parents and children. Future directions and implications of these findings are discussed.

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model.

PubMed

Sasaki, Noboru; Ishi, Kazuhiro; Kudo, Nobuki; Nakayama, Shouta M M; Nakamura, Kensuke; Morishita, Keitaro; Ohta, Hiroshi; Ishizuka, Mayumi; Takiguchi, Mitsuyoshi

2017-01-01

Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.

The Patient Burden of Bladder Outlet Obstruction after Prostate Cancer Treatment.

PubMed

Liberman, Daniel; Jarosek, Stephanie; Virnig, Beth A; Chu, Haitao; Elliott, Sean P

2016-05-01

Bladder outlet obstruction after prostate cancer therapy imposes a significant burden on health and quality of life in men. Our objective was to describe the burden of bladder outlet obstruction after prostate cancer therapy by detailing the type of procedures performed and how often those procedures were repeated in men with recurrent bladder outlet obstruction. Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1992 to 2007 with followup through 2009 we identified 12,676 men who underwent at least 1 bladder outlet obstruction procedure after prostate cancer therapy, including external beam radiotherapy in 3,994, brachytherapy in 1,485, brachytherapy plus external beam radiotherapy in 1,847, radical prostatectomy in 4,736, radical prostatectomy plus external beam radiotherapy in 369 and cryotherapy in 245. Histogram, incidence rates and Cox proportional hazards models with repeat events analysis were done to describe the burden of repeat bladder outlet obstruction treatments stratified by prostate cancer therapy type. We describe the type of bladder outlet obstruction surgery grouped by level of invasiveness. At a median followup of 8.8 years 44.6% of men underwent 2 or more bladder outlet obstruction procedures. Compared to men who underwent radical prostatectomy those treated with brachytherapy and brachytherapy plus external beam radiotherapy were at increased adjusted risk for repeat bladder outlet obstruction treatment (HR 1.2 and 1.32, respectively, each p <0.05). After stricture incision the men treated with radical prostatectomy or radical prostatectomy plus external beam radiotherapy were most likely to undergo dilation at a rate of 34.7% to 35.0%. Stricture resection/ablation was more common after brachytherapy, external beam radiotherapy or brachytherapy plus external beam radiotherapy at a rate of 28.9% to 41.2%. Almost half of the men with bladder outlet obstruction after prostate cancer therapy undergo more than 1 procedure. Furthermore men with bladder outlet obstruction after radiotherapy undergo more invasive endoscopic therapies and are at higher risk for multiple treatments than men with bladder outlet obstruction after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

An investigation of the basic physics of irrigation in urology and the role of automated pump irrigation in cystoscopy.

PubMed

Chang, Dwayne; Manecksha, Rustom P; Syrrakos, Konstantinos; Lawrentschuk, Nathan

2012-01-01

To investigate the effects of height, external pressure, and bladder fullness on the flow rate in continuous, non-continuous cystoscopy and the automated irrigation fluid pumping system (AIFPS). Each experiment had two 2-litre 0.9% saline bags connected to a continuous, non-continuous cystoscope or AIFPS via irrigation tubing. Other equipment included height-adjustable drip poles, uroflowmetry devices, and model bladders. In Experiment 1, saline bags were elevated to measure the increment in flow rate. In Experiment 2, saline bags were placed under external pressures to evaluate the effect on flow rate. In Experiment 3, flow rate changes in response to variable bladder fullness were measured. Elevating saline bags caused an increase in flow rates, however the increment slowed down beyond a height of 80 cm. Increase in external pressure on saline bags elevated flow rates, but inconsistently. A fuller bladder led to a decrease in flow rates. In all experiments, the AIFPS posted consistent flow rates. Traditional irrigation systems were susceptible to changes in height of irrigation solution, external pressure application, and bladder fullness thus creating inconsistent flow rates. The AIFPS produced consistent flow rates and was not affected by any of the factors investigated in the study.

Activation of RAS family genes in urothelial carcinoma.

PubMed

Boulalas, I; Zaravinos, A; Karyotis, I; Delakas, D; Spandidos, D A

2009-05-01

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.

The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.

PubMed

Cheng, Hai-Ling Margaret; Loai, Yasir; Beaumont, Marine; Farhat, Walid A

2010-08-01

Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM-based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue-engineering and regeneration. Measured MR relaxation times (T(1), T(2)) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T(2) components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid.

[Post-traumatic complication of trans-appendiceal cystostomy: urinary peritonitis].

PubMed

Landry, J L; Dubois, R; Chaffange, P; Pelizzo, G; Dodat, H

2001-04-01

Two children who had undergone a transappendicular urinary diversion (type Mitrofanoff) developed bladder rupture, one following abdominal trauma, 4 months after the operation and the other following traumatic self-catheterization at 4 years. The clinical history and standard radiological examinations (ultrasonography, cystography) confirmed the diagnosis of urinary peritonitis. Emergency surgical repair was possible in both cases with an uneventful postoperative course. This serious and rare complication requires emergency surgery and justifies rigorous selection of children suitable for this type of diversion giving preference to increased bladder neck resistance over bladder neck closure.

Accelerated onset of the vesicovesical reflex in postnatal NGF-OE mice and the role of neuropeptides

PubMed Central

Girard, Beatrice; Peterson, Abbey; Malley, Susan; Vizzard, Margaret A.

2016-01-01

The mechanisms underlying the postnatal maturation of micturition from a somatovesical to a vesicovesical reflex are not known but may involve neuropeptides in the lower urinary tract. A transgenic mouse model with chronic urothelial overexpression (OE) of NGF exhibited increased voiding frequency, increased number of non-voiding contractions, altered morphology and hyperinnervation of the urinary bladder by peptidergic (e.g., Sub P and CGRP) nerve fibers in the adult. In early postnatal and adult NGF-OE mice we have now examined: (1) micturition onset using filter paper void assays and open-outlet, continuous fill, conscious cystometry; (2) innervation and neurochemical coding of the suburothelial plexus of the urinary bladder using immunohistochemistry and semi-quantitative image analyses; (3) neuropeptide protein and transcript expression in urinary bladder of postnatal and adult NGF-OE mice using Q-PCR and ELISAs and (4) the effects of intravesical instillation of a neurokinin (NK)-1 receptor antagonist on bladder function in postnatal and adult NGF-OE mice using conscious cystometry. Postnatal NGF-OE mice exhibit age-dependent (R2= 0.996–0.998; p ≤ 0.01) increases in Sub and CGRP expression in the urothelium and significantly (p ≤ 0.01) increased peptidergic hyperinnervation of the suburothelial nerve plexus. By as early as P7, NGF-OE mice exhibit a vesicovesical reflex in response to intravesical instillation of saline whereas littermate WT mice require perigenital stimulation to elicit a micturition reflex until P13 when vesicovesical reflexes are first observed. Intravesical instillation of a NK-1 receptor antagonist, netupitant (0.1 μg/ml), significantly (p ≤ 0.01) increased void volume and the interval between micturition events with no effects on bladder pressure (baseline, threshold, peak) in postnatal NGF-OE mice; effects on WT mice were few. NGF-induced pleiotropic effects on neuropeptide (e.g., Sub P) expression in the urinary bladder contribute to the maturation of the micturition reflex and are excitatory to the micturition reflex in postnatal NGF-OE mice. These studies provide insight into the mechanisms that contribute to the postnatal development of the micturition reflex. PMID:27342083

Vasculogenic mimicry in bladder cancer and its association with the aberrant expression of ZEB1

PubMed Central

Li, Baimou; Mao, Xiaopeng; Wang, Hua; Su, Guanyu; Mo, Chengqiang; Cao, Kaiyuan; Qiu, Shaopeng

2018-01-01

The aim of the present study was to investigate the associations between vasculogenic mimicry (VM) and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer. VM structure and ZEB1 expression were analyzed by cluster of differentiation 34/periodic acid Schiff (PAS) double staining and immunohistochemical staining in 135 specimens from patients with bladder cancer, and a further 12 specimens from normal bladder tissues. Three-dimensional (3-D) culture was used to detect VM formation in the bladder transitional cancer cell lines UM-UC-3 and J82, and the immortalized human bladder epithelium cell line SV-HUC-1 in vitro. ZEB1 expression in these cell lines was compared by reverse transcription-quantitative polymerase chain reaction and western blot assays. In addition, small interfering RNA was used to inhibit ZEB1 in UM-UC-3 and J82 cells, followed by 3-D culturing of treated cell lines. As a result, VM was observed in 31.1% of specimens from bladder cancer tissues, and cases with high ZEB1 expression accounted for 60.0% of patients with bladder cancer. In addition, ZEB1 expression was closely associated with VM (r=0.189; P<0.05), and also increased as the grade and stage of the tumor developed. In an in vitro assay, UM-UC-3 and J82 cells exhibited VM formation, however, SV-HUC-1 did not. Furthermore, VM-forming cancer cell lines UM-UC-3 and J82 exhibited higher ZEB1 expression. Notably, VM formation was inhibited following knockdown of ZEB1. In conclusion, ZEB1 may be associated with VM in bladder cancer and serve an important role in the process of VM formation. However, its detailed mechanism requires further study. PMID:29552157

Swim bladder function and buoyancy control in pink snapper (Pagrus auratus) and mulloway (Argyrosomus japonicus).

PubMed

Stewart, John; Hughes, Julian M

2014-04-01

Physoclist fish are able to regulate their buoyancy by secreting gas into their hydrostatic organ, the swim bladder, as they descend through the water column and by resorbing gas from their swim bladder as they ascend. Physoclists are restricted in their vertical movements due to increases in swim bladder gas volume that occur as a result of a reduction in hydrostatic pressure, causing fish to become positively buoyant and risking swim bladder rupture. Buoyancy control, rates of swim bladder gas exchange and restrictions to vertical movements are little understood in marine teleosts. We used custom-built hyperbaric chambers and laboratory experiments to examine these aspects of physiology for two important fishing target species in southern Australia, pink snapper (Pagrus auratus) and mulloway (Argyrosomus japonicus). The swim bladders of pink snapper and mulloway averaged 4.2 and 4.9 % of their total body volumes, respectively. The density of pink snapper was not significantly different to the density of seawater (1.026 g/ml), whereas mulloway were significantly denser than seawater. Pink snapper secreted gas into their swim bladders at a rate of 0.027 ± 0.005 ml/kg/min (mean ± SE), almost 4 times faster than mulloway (0.007 ± 0.001 ml/kg/min). Rates of swim bladder gas resorption were 11 and 6 times faster than the rates of gas secretion for pink snapper and mulloway, respectively. Pink snapper resorbed swim bladder gas at a rate of 0.309 ± 0.069 ml/kg/min, 7 times faster than mulloway (0.044 ± 0.009 ml/kg/min). Rates of gas exchange were not affected by water pressure or water temperature over the ranges examined in either species. Pink snapper were able to acclimate to changes in hydrostatic pressure reasonably quickly when compared to other marine teleosts, taking approximately 27 h to refill their swim bladders from empty. Mulloway were able to acclimate at a much slower rate, taking approximately 99 h to refill their swim bladders. We estimated that the swim bladders of pink snapper and mulloway ruptured after decreases in ~2.5 and 2.75 times the hydrostatic pressure to which the fish were acclimated, respectively. Differences in buoyancy, gas exchange rates, limitations to vertical movements and acclimation times between the two species are discussed in terms of their differing behaviour and ecology.

Problems arising in the diagnosis of primary ovarian transitional cell carcinoma after the occurrence of a transitional cell carcinoma of the bladder: a report of a difficult case and a critical review of literature.

PubMed

Raspollini, Maria Rosaria; Paglierani, Milena; Taddei, Gian Luigi

2009-03-01

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer that morphologically resembles a TCC of the bladder. The most frequent metastases to ovaries come from the gastrointestinal tract and from breast carcinoma, but metastatic TCCs from the urinary tract to the ovary have been reported. TCC of the bladder is the sixth most common cancer in European and North American countries and its incidence has been increasing. We recently observed a woman, who previously had undergone endoscopic resection of a TCC of the bladder. She was affected by an ovarian bilateral tumor with features of malignant transitional cell tumor, characterized by papillae with multilayered transitional epithelium infiltrating the ovarian stroma. In this study, we showed the utility of WT1 and a panel of immunohistochemical markers in the difficult differential diagnosis between bladder and ovarian TCC.

Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen.

PubMed

Huang, Weiren; Chen, Yuanbin; Liu, Yuchen; Zhang, Qiaoxia; Yu, Zhou; Mou, Lisha; Wu, Hanwei; Zhao, Li; Long, Ting; Qin, Danian; Gui, Yaoting

2015-01-01

Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB) is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1) were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis.

PubMed

Guerriero, S; Ajossa, S; Minguez, J A; Jurado, M; Mais, V; Melis, G B; Alcazar, J L

2015-11-01

To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of endometriosis in the uterosacral ligaments (USL), rectovaginal septum (RVS), vagina and bladder in patients with clinical suspicion of deep infiltrating endometriosis (DIE). An extensive search was performed in MEDLINE (PubMed) and EMBASE for studies published between January 1989 and December 2014. Studies were considered eligible if they reported on the use of TVS for the preoperative detection of endometriosis in the USL, RVS, vagina and bladder in women with clinical suspicion of DIE using the surgical data as a reference standard. Study quality was assessed using the PRISMA guidelines and QUADAS-2 tool. Of the 801 citations identified, 11 studies (n = 1583) were considered eligible and were included in the meta-analysis. For detection of endometriosis in the USL, the overall pooled sensitivity and specificity of TVS were 53% (95%CI, 35-70%) and 93% (95%CI, 83-97%), respectively. The pretest probability of USL endometriosis was 54%, which increased to 90% when suspicion of endometriosis was present after TVS examination. For detection of endometriosis in the RVS, the overall pooled sensitivity and specificity were 49% (95%CI, 36-62%) and 98% (95%CI, 95-99%), respectively. The pretest probability of RVS endometriosis was 24%, which increased to 89% when suspicion of endometriosis was present after TVS examination. For detection of vaginal endometriosis, the overall pooled sensitivity and specificity were 58% (95%CI, 40-74%) and 96% (95%CI, 87-99%), respectively. The pretest probability of vaginal endometriosis was 17%, which increased to 76% when suspicion of endometriosis was present after TVS assessment. Substantial heterogeneity was found for sensitivity and specificity for all these locations. For detection of bladder endometriosis, the overall pooled sensitivity and specificity were 62% (95%CI, 40-80%) and 100% (95%CI, 97-100%), respectively. Moderate heterogeneity was found for sensitivity and specificity for bladder endometriosis. The pretest probability of bladder endometriosis was 5%, which increased to 92% when suspicion of endometriosis was present after TVS assessment. Overall diagnostic performance of TVS for detecting DIE in uterosacral ligaments, rectovaginal septum, vagina and bladder is fair with high specificity. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction

PubMed Central

Kiss, Bernhard; Moltzahn, Felix; Keller, Irene; Rehrauer, Hubert; Fournier, Catharine Aquino; Burkhard, Fiona C.

2017-01-01

Bladder outlet obstruction (BOO) induces significant organ remodeling, leading to lower urinary tract symptoms accompanied by urodynamic changes in bladder function. Here, we report mRNA and miRNA transcriptome sequencing of bladder samples from human patients with different urodynamically defined states of BOO. Patients’ miRNA and mRNA expression profiles correlated with urodynamic findings. Validation of RNA sequencing results in an independent patient cohort identified combinations of 3 mRNAs (NRXN3, BMP7, UPK1A) and 3 miRNAs (miR-103a-3p, miR-10a-5p, miR-199a-3p) sufficient to discriminate between bladder functional states. All BOO patients shared cytokine and immune response pathways, TGF-β and NO signaling pathways, and hypertrophic PI3K/AKT signaling pathways. AP-1 and NFkB were dominant transcription factors, and TNF-α was the top upstream regulator. Integrated miRNA-mRNA expression analysis identified pathways and molecules targeted by differentially expressed miRNAs. Molecular changes in BOO suggest an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states. PMID:28138557

[Bladder rupture caused by spontaneous perforation of an infected urachal cyst].

PubMed

Maruschke, M; Kreutzer, H J; Seiter, H

2003-06-01

Anomalies of the fetal urachus are rare. Normally, the postnatal urachus presents as a fibrous band extending from the bladder to the umbilicus. Urachal cysts may occur in postnatal life. Spontaneous perforation of urachal cysts is a very rare condition, which clinically may not be distinguishable from other acute abdominal conditions. We report a case of a 63-year-old male with a history of recurrent urinary tract infections and a bladder rupture caused by a spontaneous perforation of an infected urachal cyst. The symptomatology showed abdominal rigidity and pain, a palpable mass in the lower abdomen, and hematuria. Laboratory findings showed leukocytosis and an increased CRP level. The bladder rupture was confirmed by cystography. Bacteriologic examination identified Proteus vulgaris, Corynebacterium species, and Klebsiella pneumoniae. Most of the published cases in the literature report about intraperitoneal perforation of infected urachal cysts. In the present case, we found a spontaneous perforation of an infected urachal cyst leading to an extraperitoneal bladder rupture with an extraperitoneal limitation of the infection. The definitive therapy was complete surgical excision including a cuff of the bladder, drainage, and systemic broad-spectrum and local application of antibiotics. The further course was uneventful.

Overactive bladder – 18 years – part I

PubMed Central

Truzzi, Jose Carlos; Gomes, Cristiano Mendes; Bezerra, Carlos A.; Plata, Ivan Mauricio; Campos, Jose; Garrido, Gustavo Luis; Almeida, Fernando G.; Averbeck, Marcio Augusto; Fornari, Alexandre; Salazar, Anibal; Dell'Oro, Arturo; Cintra, Caio; Sacomani, Carlos Alberto Ricetto; Tapia, Juan Pablo; Brambila, Eduardo; Longo, Emilio Miguel; Rocha, Flavio Trigo; Coutinho, Francisco; Favre, Gabriel; Garcia, José Antonio; Castaño, Juan; Reyes, Miguel; Leyton, Rodrigo Eugenio; Ferreira, Ruiter Silva; Duran, Sergio; López, Vanda; Reges, Ricardo

2016-01-01

ABSTRACT Abstract: Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals – including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years. PMID:27176184

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

ClinicalTrials.gov

2018-03-20

Bladder Cancer; Bladder Neoplasm; Bladder Tumors; Cancer of Bladder; Cancer of the Bladder; Malignant Tumor of Urinary Bladder; Neoplasms, Bladder; Urinary Bladder Cancer; Carcinoma in Situ of Bladder; Papillary Carcinoma of Bladder (Diagnosis); BCG-Unresponsive Bladder Cancer

[Efficacy of Botulinum-A toxin injection into bladder to treat neurogenic incontinence in patients with spinal cord injury: comparison of two doses].

PubMed

Fu, Guang; Wu, Juan; Cong, Huiling; Zha, Lihua; Li, Dong; Ju, Yanhe; Chen, Guoqing; Xiong, Zhongsheng; Liao, Limin

2015-12-19

To evaluate the efficacy of Botulinum-A toxin injection into bladder to treat neurogenic incontinence in patients with spinal cord injury and compare effectiveness of two different doses (200 U and 300 U). Between January 2009 and October 2014, A total of 60 adult patients with spinal cord injury above the sacral (mean age, 32 years; male 56, female 4) were selected in Beijing Bo'ai Hospital of China Rehabilitation Research Center. All the patients kept voiding diary and underwent urodynamic examination before operation. All the patients were allocated with a random number table into 200 U Botulinum-A toxin injection group or 300 U group (both n=30). In the 200 U group, 200 U of Botulinum-A toxin were dissolved in 10 ml of normal saline, which was injected into 20 different sites (0.5 ml for each site) of bladder wall, including 10 outside the bladder trigone and the remaining 10 inside trigone. In the 300 U group, 300 U of Botulinum-A toxin were dissolved in 15 ml of normal saline, which was injected into 30 different sites (0.5 ml for each site) in bladder outside of the bladder trigone using a flexible cystoscopic needle. The evaluation of the effects and follow-up included voiding diary, urodynamic testing and observation of adverse and toxic effects. At baseline, mean urinary incontinence frequencies were (15.2±3.2) episodes/day and (16.2±2.9) episodes/day in 200 U and 300 U group, which reduced to (2.9±1.2) episodes/day and (2.5±1.4) episodes/day, respectively in week 4 (P<0.05). However, continence rate was not significantly different between the two dose groups [63% (19/30) vs 70% (21/30), P>0.05]. The effect of botulinum-A toxin started to be observed from the 1(st) posttreatment week on average. Obvious improvements in maximum cystometric capacity, end-filling maximum detrusor pressure, and bladder compliance were observed at week 4 as shown by urodynamics (all P<0.05), but with no significant difference between the 200 U and 300 U groups. In the follow-up period of (6.3±1.2) months, no toxic or adverse effects were observed after injection in the two groups. The regimen of Botulinum-A toxin 200 U injection involving trigone of the bladder can achieve a short-term effect comparable with that of the standard 300 U injection excluding trigone. It may be an effective and safe treatment for neurogenic incontinence in spinal cord injury patients.

Nocturnal polyuria and decreased serum testosterone: is there an association in men with lower urinary tract symptoms?

PubMed

Kim, Jin Wook; Oh, Mi Mi; Yoon, Cheol Yong; Bae, Jae Hyun; Kim, Je Jong; Moon, Du Geon

2014-05-01

To investigate the putative association between nocturia and decreased serum testosterone in men with lower urinary tract symptoms. Frequency volume charts and serum testosterone levels of patients visiting the outpatient clinic for lower urinary tract symptoms were collected and analyzed. Age, prostate volume, body mass index and the presence of comorbidities were accounted for. Frequency volume charts were analyzed for pathophysiological components of nocturnal polyuria, global polyuria, decreased nocturnal bladder capacity and increased frequency to identify associated risks. Frequency volume charts were also used to chart 8-h changes of volume, frequency and capacity to identify time diurnal interactions with risk factors based on serum testosterone levels. A total of 2180 patients were enrolled in the study. Multivariate analysis showed testosterone decreased 0.142 ng/mL for every increase in nocturia, independent of other factors. Logistic regression analysis showed a significant difference between pathophysiological components. Decreased testosterone was shown to carry a significant independent risk for overall nocturia (odds ratio 1.60, 95% confidence interval 1.013-2.527, P = 0.044), and particularly nocturnal polyuria (odds ratio 1.934, 95% confidence interval 1.001-3.737, P = 0.027). Repeated measurement models showed patients with serum testosterone below 2.50 ng/mL to have a paradoxical increase in nocturnal urine volume at night. Nocturia, especially nocturnal polyuria, is associated with decreased serum testosterone. Patients with low serum testosterone show increased nocturnal urine output. © 2013 The Japanese Urological Association.

Male bladder cancer risk and occupational exposure according to a job-exposure matrix-a case-control study in British Columbia, Canada.

PubMed

Richardson, Kathryn; Band, Pierre R; Astrakianakis, George; Le, Nhu D

2007-12-01

The authors investigated the risk of bladder cancer in association with exposure to over 12 000 occupational chemical agents, complex mixtures, and other substances (hereafter referred to as chemical agents). Adult males diagnosed with cancer between 1983 and 1990 in British Columbia, Canada, were surveyed. Detailed occupational histories and confounding information was provided by a self-administered questionnaire. Cancer controls were matched to bladder cancer cases, resulting in 1062 cases and 8057 controls for the analysis. An extensive United-States-based job-exposure matrix was applied to estimate cumulative exposure to occupational chemical agents. Odds ratios for bladder cancer due to exposure to chemical agents were estimated via conditional logistic regression analyses, adjusted for important confounders. A significantly (P<0.05) increased risk was detected for ever exposure to 635 chemical agents, and 341 chemical agents exhibited a significantly increasing dose-response relationship. Adjustment for multiple comparisons resulted in a subset of 29 chemical agents that continued to show significant results. A principal components analysis classified these 29 chemical agents into five independent groups, distinguished mainly by job. Exposures to these chemical agents were largely due to employment in the logging and construction industries and occupations involving motor vehicles. Consistent results were observed for bladder carcinogens reported in the literature. This study suggests that several specific chemical agents were significantly associated with the risk of bladder cancer. The chemical agents were mainly derivatives or combustion products of fossil fuels. The results corroborate important findings from the literature and document a risk for specific chemical agents not previously reported.

Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways

PubMed Central

Kanika, Nirmala; Chang, Jinsook; Tong, Yuehong; Tiplitsky, Scott; Lin, Juan; Yohannes, Elizabeth; Tar, Moses; Chance, Mark; Christ, George J.; Melman, Arnold; Davies, Kelvin

2010-01-01

Objectives To investigate the role that oxidative stress plays in the development of diabetic cystopathy. Materials and methods Comparative gene expression in the bladder of non-diabetic and streptozotocin (STZ)-induced 2-month-old diabetic rats was carried out using microarray analysis. Evidence of oxidative stress was investigated in the bladder by analyzing glutathione S-transferase activity, lipid peroxidation, and carbonylation and nitrosylation of proteins. The activity of protein degradation pathways was assessed using western blot analysis. Results Analysis of global gene expression showed that detrusor smooth muscle tissue of STZ-induced diabetes undergoes significant enrichment in targets involved in the production or regulation of reactive oxygen species (P = 1.27 × 10−10). The microarray analysis was confirmed by showing that markers of oxidative stress were all significantly increased in the diabetic bladder. It was hypothesized that the sequelae to oxidative stress would be increased protein damage and apoptosis. This was confirmed by showing that two key proteins involved in protein degradation (Nedd4 and LC3B) were greatly up-regulated in diabetic bladders compared to controls by 12.2 ± 0.76 and 4.4 ± 1.0-fold, respectively, and the apoptosis inducing protein, BAX, was up-regulated by 6.76 ± 0.76-fold. Conclusions Overall, the findings obtained in the present study add to the growing body of evidence showing that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways that may contribute to a deterioration in bladder function. PMID:21518418

Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk

PubMed Central

Pattison, Jillian M.; Posternak, Valeriya; Cole, Michael D.

2016-01-01

It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear since it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development. Implications A polymorphic KLF5 binding site near the CCNE1 gene explains genetic risk identified through genome wide association studies. PMID:27514407

Central control of visceral pain and urinary tract function.

PubMed

Lovick, Thelma A

2016-10-01

Afferent input from Aδ and C-fibres innervating the urinary bladder are processed differently by the brain, and have different roles in signaling bladder sensation. Aδ fibres that signal bladder filling activate a spino-bulbo-spinal loop, which relays in the midbrain periaqueductal grey (PAG) and pontine micturition centre (PMC). The excitability of this circuitry is regulated by tonic GABAergic inhibitory processes. In humans and socialised animals micturition is normally under volitional control and influenced by a host of psychosocial factors. Higher nervous decision-making in a social context to 'go now' or 'do not go' probably resides in frontal cortical areas, which act as a central control switch for micturition. Exposure to psychosocial stress can have profoundly disruptive influence on the process and lead to maladaptive changes in the bladder. During sleeping the voiding reflex threshold appears to be reset to a higher level to promote urinary continence. Under physiological conditions C-fibre bladder afferents are normally silent but are activated in inflammatory bladder states and by intense distending pressure. Following prolonged stimulation visceral nociceptors sensitise, leading to a lowered threshold and heightened sensitivity. In addition, sensitization may occur within the central pain processing circuitry, which outlasts the original nociceptive insult. Visceral nociception may also be influenced by genetic and environmental influences. A period of chronic stress can produce increased sensitivity to visceral pain that lasts for months. Adverse early life events can produce even longer lasting epigenetic changes, which increase the individual's susceptibility to developing visceral pain states in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of non-rigid point-set registration methods using a porcine bladder pelvic phantom

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Spadinger, Ingrid

2016-01-01

The problem of accurate dose accumulation in fractionated radiotherapy treatment for highly deformable organs, such as bladder, has garnered increasing interest over the past few years. However, more research is required in order to find a robust and efficient solution and to increase the accuracy over the current methods. The purpose of this study was to evaluate the feasibility and accuracy of utilizing non-rigid (affine or deformable) point-set registration in accumulating dose in bladder of different sizes and shapes. A pelvic phantom was built to house an ex vivo porcine bladder with fiducial landmarks adhered onto its surface. Four different volume fillings of the bladder were used (90, 180, 360 and 480 cc). The performance of MATLAB implementations of five different methods were compared, in aligning the bladder contour point-sets. The approaches evaluated were coherent point drift (CPD), gaussian mixture model, shape context, thin-plate spline robust point matching (TPS-RPM) and finite iterative closest point (ICP-finite). The evaluation metrics included registration runtime, target registration error (TRE), root-mean-square error (RMS) and Hausdorff distance (HD). The reference (source) dataset was alternated through all four points-sets, in order to study the effect of reference volume on the registration outcomes. While all deformable algorithms provided reasonable registration results, CPD provided the best TRE values (6.4 mm), and TPS-RPM yielded the best mean RMS and HD values (1.4 and 6.8 mm, respectively). ICP-finite was the fastest technique and TPS-RPM, the slowest.

Effects of age and hypertension on α1-adrenoceptors in the major source arteries of the rat bladder and penis.

PubMed

Yono, Makoto; Tanaka, Takanori; Tsuji, Shigeki; Irie, Shin; Sakata, Yukikuni; Otani, Masayuki; Yoshida, Masaki; Latifpour, Jamshid

2011-11-16

α(1)-Adrenoceptors regulate blood pressure, regional vascular resistance and tissue blood flow. As aging and hypertension may impact pelvic arterial blood flow resulting in bladder and penile dysfunction, we investigated effects of age and hypertension on α(1)-adrenoceptors in the major source arteries of the rat bladder and penis. Using radioligand receptor binding, real-time reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent microsphere infusion techniques, we compared 3 and 22-month-old male Fischer rats, and male normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Twenty-two-month-old rats and SHRs had significantly higher total α(1)-adrenoceptor density in the internal iliac artery and lower blood flow to the bladder and penis than 3-month-old and WKY rats, respectively. RT-PCR data showed an age and hypertension related increase in the expression of α(1B)-adrenoceptor mRNA in the internal iliac, vesical and internal pudendal arteries and a switch from α(1A) predominance in 3-month-old and WKY rats to α(1B)>α(1A) in 22-month-old rats and SHRs. Our data indicate the presence of age and hypertension related alterations in vascular α(1)-adrenoceptor subtype distribution and in blood flow to the rat bladder and penis. These findings suggest that pharmacological blockade of the vascular α(1B)-adrenoceptor, which could increase pelvic blood flow, may contribute to the improvement of bladder and penile dysfunctions in animal models for aging and hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras.

PubMed

Ehrhardt, Annette; Wang, Bin; Yung, Andrew C; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W

2015-01-01

Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras-/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly 'layered' with age in Mras-/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras-/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras-/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras-/- males were increased, and Mras-/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras-/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice.

Urinary Retention, Incontinence, and Dysregulation of Muscarinic Receptors in Male Mice Lacking Mras

PubMed Central

Ehrhardt, Annette; Wang, Bin; Yung, Andrew C.; Wang, Yanni; Kozlowski, Piotr; van Breemen, Cornelis; Schrader, John W.

2015-01-01

Here we show that male, but not female mice lacking expression of the GTPase M-Ras developed urinary retention with distention of the bladder that exacerbated with age but occurred in the absence of obvious anatomical outlet obstruction. There were changes in detrusor morphology in Mras -/- males: Smooth muscle tissue, which exhibited a compact organization in WT mice, appeared disorganized and became increasingly ‘layered’ with age in Mras -/- males, but was not fibrotic. Bladder tissue near the apex of bladders of Mras -/- males exhibited hypercontractility in response to the cholinergic agonist carbachol in in vitro, while responses in Mras -/- females were normal. In addition, spontaneous phasic contractions of detrusors from Mras -/- males were increased, and Mras -/- males exhibited urinary incontinence. We found that expression of the muscarinic M2 and M3 receptors that mediate the cholinergic contractile stimuli of the detrusor muscle was dysregulated in both Mras -/- males and females, although only males exhibited a urinary phenotype. Elevated expression of M2R in young males lacking M-Ras and failure to upregulate M3R with age resulted in significantly lower ratios of M3R/M2R expression that correlated with the bladder abnormalities. Our data suggests that M-Ras and M3R are functionally linked and that M-Ras is an important regulator of male bladder control in mice. Our observations also support the notion that bladder control is sexually dimorphic and is regulated through mechanisms that are largely independent of acetylcholine signaling in female mice. PMID:26516777

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

PubMed

Saito, Motoaki; Shimizu, Shogo; Ohmasa, Fumiya; Oikawa, Ryo; Tsounapi, Panagiota; Dimitriadis, Fotios; Kinoshita, Yukako; Satoh, Keisuke

2013-04-01

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. 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. 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. 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. Copyright © 2012 Wiley Periodicals, Inc.

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.