Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-injured Rat Bladders.

PubMed

Imamura, Tetsuya; Shimamura, Mitsuru; Ogawa, Teruyuki; Minagawa, Tomonori; Nagai, Takashi; Silwal Gautam, Sudha; Ishizuka, Osamu

2018-05-08

The ability to repair damaged urinary bladders through the application of bone marrow-derived cells is in the earliest stages of development. We investigated the application of bone marrow-derived cells to repair radiation-injured bladders. We used a three-dimensional (3D) bioprinting robot system to biofabricate bone marrow-derived cell structures. We then determined if the biofabricated structures could restore the tissues and functions of radiation-injured bladders. The bladders of female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2-Gy once a week for 5 weeks. Adherent and proliferating bone marrow-derived cells harvested from the femurs of male 17-week-old green fluorescence protein-transfected Tg-SD rats were cultured in collagen-coated flasks. Bone marrow-derived cell spheroids were formed in 96-well plates. Three layers of spheroids were assembled by the bioprinter onto a 9x9 microneedle array. The assembled spheroids were perfusion cultured for 7 days, and then the microneedle array was removed. Two weeks after the last radiation treatment, the biofabricated structures were transplanted into an incision on the anterior wall of the bladders (n=10). Control rats received the same surgery but without the biofabricated structures (sham-structure, n=12). At 2 and 4 weeks after surgery, the sham-structure control bladder tissues exhibited disorganized smooth muscle layers, decreased nerve cells, and significant fibrosis with increased presence of fibrosis-marker P4HB-positive cells and hypoxia-marker HIF1α-positive cells. The transplanted structures survived within the recipient tissues, and blood vessels extended within them from the recipient tissues. The bone marrow-derived cells in the structures differentiated into smooth muscle cells and formed smooth muscle clusters. The recipient tissues near the transplanted structures had distinct smooth muscle layers and reconstructed nerve cells, and only minimal fibrosis with decreased presence of P4HB- and HIF1α-positive cells. At 4 weeks after surgery, the sham-structure control rats exhibited significant urinary frequency symptoms with irregular and short voiding intervals, and low micturition volumes. In contrast, the structure-transplanted rats had regular micturition with longer voiding intervals and higher micturition volumes compared to the control rats. Further, the residual volume of the structure-transplanted rats was lower than for the controls. Therefore, transplantation of biofabricated bone marrow-derived cell structures reconstructed functional bladders.

MiR-133 modulates TGF-β1-induced bladder smooth muscle cell hypertrophic and fibrotic response: implication for a role of microRNA in bladder wall remodeling caused by bladder outlet obstruction.

PubMed

Duan, Liu Jian; Qi, Jun; Kong, Xiang Jie; Huang, Tao; Qian, Xiao Qiang; Xu, Ding; Liang, Jun Hao; Kang, Jian

2015-02-01

Bladder outlet obstruction (BOO) evokes urinary bladder wall remodeling significantly, including the phenotype shift of bladder smooth muscle cells (BSMCs) where transforming growth factor-beta1 (TGF-β1) plays a pivotal role given the emerging function of modulating cellular phenotype. miR-133 plays a role in cardiac and muscle remodeling, however, little is known about its roles in TGF-β1-induced BSMC hypertrophic and fibrotic response. Here, we verified BOO induced bladder wall remodeling and TGF-β1 expression mainly located in bladder endothelium. Furthermore, we uncovered miR-133a/b expression profile in BOO rats, and then explored its regulated effects on BSMCs' phenotypic shift. Our study found that miR-133 became down-regulated during rat bladder remodeling. Next, we sought to examine whether the expression of miR-133 was down-regulated in primary BSMCs in response to TGF-β1 stimulation and whether forced overexpression of miR-133 could regulate profibrotic TGF-β signaling. We found that stimulation of BSMCs with exogenous TGF-β1 of increasing concentrations resulted in a dose-dependent decrease of miR-133a/b levels and transfection with miR-133 mimics attenuated TGF-β1-induced α-smooth muscle actin, extracellular matrix subtypes and fibrotic growth factor expression, whereas it upregulated high molecular weight caldesmon expression compared with the negative control. Also, downregulation of p-Smad3, not p-Smad2 by miR-133 was detected. Additionally, miR-133 overexpression suppressed TGF-β1-induced BSMC hypertrophy and proliferation through influencing cell cycle distribution. Bioinformatics analyses predicted that connective tissue growth factor (CTGF) was the potential target of miR-133, and then binding to the 3'-untranslated region of CTGF was validated by luciferase reporter assay. These results reveal a novel regulator for miR-133 to modulate TGF-β1-induced BSMC phenotypic changes by targeting CTGF through the TGF-β-Smad3 signaling pathway. A novel antifibrotic functional role for miR-133 is presented which may represent a potential target for diagnostic and therapeutic strategies in bladder fibrosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Estimation of bladder wall location in ultrasound images.

PubMed

Topper, A K; Jernigan, M E

1991-05-01

A method of automatically estimating the location of the bladder wall in ultrasound images is proposed. Obtaining this estimate is intended to be the first stage in the development of an automatic bladder volume calculation system. The first step in the bladder wall estimation scheme involves globally processing the images using standard image processing techniques to highlight the bladder wall. Separate processing sequences are required to highlight the anterior bladder wall and the posterior bladder wall. The sequence to highlight the anterior bladder wall involves Gaussian smoothing and second differencing followed by zero-crossing detection. Median filtering followed by thresholding and gradient detection is used to highlight as much of the rest of the bladder wall as was visible in the original images. Then a 'bladder wall follower'--a line follower with rules based on the characteristics of ultrasound imaging and the anatomy involved--is applied to the processed images to estimate the bladder wall location by following the portions of the bladder wall which are highlighted and filling in the missing segments. The results achieved using this scheme are presented.

Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-β1.

PubMed

Wang, Junpeng; Chen, Yang; Gu, Di; Zhang, Guihao; Chen, Jiawei; Zhao, Jie; Wu, Peng

2017-10-01

Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). Sprague-Dawley rats were randomly distributed into four groups, which received saline, ketamine, ketamine combined with a TGF-β receptor inhibitor (SB-505124) for 16 wk, or 12 wk of ketamine and 4 wk of abstinence. In addition, the profibrotic effect of ketamine was confirmed in SV-40 immortalized human uroepithelial (SV-HUC-1) cells. The ketamine-treated rats displayed voiding dysfunction and decreased bladder compliance. Bladder fibrosis was accompanied by the appearance of a certain number of cells expressing both epithelial and mesenchymal markers, indicating that epithelial cells might undergo EMT upon ketamine administration. Meanwhile, the expression level of TGF-β1 was significantly upregulated in the urothelium of bladders in ketamine-treated rats. Treatment of SV-HUC-1 cells with ketamine increased the expression of TGF-β1 and EMT-inducing transcription factors, resulting in the downregulation of E-cadherin and upregulation of fibronectin and α-smooth muscle actin. Administration of SB-505124 inhibited EMT and fibrosis both in vitro and vivo. In addition, withdrawal from ketamine did not lead to recovery of bladder urinary function or decreased fibrosis. Taken together, our study shows for the first time that EMT might contribute to bladder fibrosis in KC. TGF-β1 may have an important role in bladder fibrogenesis via an EMT mechanism. Copyright © 2017 the American Physiological Society.

Normal reference values for bladder wall thickness on CT in a healthy population.

PubMed

Fananapazir, Ghaneh; Kitich, Aleksandar; Lamba, Ramit; Stewart, Susan L; Corwin, Michael T

2018-02-01

To determine normal bladder wall thickness on CT in patients without bladder disease. Four hundred and nineteen patients presenting for trauma with normal CTs of the abdomen and pelvis were included in our retrospective study. Bladder wall thickness was assessed, and bladder volume was measured using both the ellipsoid formula and an automated technique. Patient age, gender, and body mass index were recorded. Linear regression models were created to account for bladder volume, age, gender, and body mass index, and the multiple correlation coefficient with bladder wall thickness was computed. Bladder volume and bladder wall thickness were log-transformed to achieve approximate normality and homogeneity of variance. Variables that did not contribute substantively to the model were excluded, and a parsimonious model was created and the multiple correlation coefficient was calculated. Expected bladder wall thickness was estimated for different bladder volumes, and 1.96 standard deviation above expected provided the upper limit of normal on the log scale. Age, gender, and bladder volume were associated with bladder wall thickness (p = 0.049, 0.024, and < 0.001, respectively). The linear regression model had an R 2 of 0.52. Age and gender were negligible in contribution to the model, and a parsimonious model using only volume was created for both the ellipsoid and automated volumes (R 2  = 0.52 and 0.51, respectively). Bladder wall thickness correlates with bladder wall volume. The study provides reference bladder wall thicknesses on CT utilizing both the ellipsoid formula and automated bladder volumes.

Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

PubMed Central

Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

2013-01-01

Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

Computer-aided detection of bladder wall thickening in CT urography (CTU)

NASA Astrophysics Data System (ADS)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon Z.; Gordon, Marshall N.; Samala, Ravi K.

2018-02-01

We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). Bladder wall thickening is a manifestation of bladder cancer and its detection is more challenging than the detection of bladder masses. We first segmented the inner and outer bladder walls using our method that combined deep-learning convolutional neural network with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensity-projection-based method. The non-contrast region was smoothed and gray level threshold was applied to the contrast and non-contrast regions separately to extract the bladder wall and potential lesions. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify regions of wall thickening candidates. Volume-based features of the wall thickening candidates were analyzed with linear discriminant analysis (LDA) to differentiate bladder wall thickenings from false positives. A data set of 112 patients, 87 with wall thickening and 25 with normal bladders, was collected retrospectively with IRB approval, and split into independent training and test sets. Of the 57 training cases, 44 had bladder wall thickening and 13 were normal. Of the 55 test cases, 43 had wall thickening and 12 were normal. The LDA classifier was trained with the training set and evaluated with the test set. FROC analysis showed that the system achieved sensitivities of 93.2% and 88.4% for the training and test sets, respectively, at 0.5 FPs/case.

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.

A pilot study on bladder wall thickness at different filling stages

NASA Astrophysics Data System (ADS)

Zhang, Xi; Liu, Yang; Li, Baojuan; Zhang, Guopeng; Liang, Zhengrong; Lu, Hongbing

2015-03-01

The ever-growing death rate and the high recurrence of bladder cancer make the early detection and appropriate followup procedure of bladder cancer attract more attention. Compare to optical cystoscopy, image-based studies have revealed its potentials in non-invasive observations of the abnormities of bladder recently, in which MR imaging turns out to be a better choice for bladder evaluation due to its non-ionizing and high contrast between urine and wall tissue. Recent studies indicate that bladder wall thickness tends to be a good indicator for detecting bladder wall abnormalities. However, it is difficult to quantitatively compare wall thickness of the same subject at different filling stages or among different subjects. In order to explore thickness variations at different bladder filling stages, in this study, we preliminarily investigate the relationship between bladder wall thickness and bladder volume based on a MRI database composed of 40 datasets acquired from 10 subjects at different filling stages, using a pipeline for thickness measurement and analysis proposed in our previous work. The Student's t-test indicated that there was no significant different on wall thickness between the male group and the female group. The Pearson correlation analysis result indicated that negative correlation with a correlation coefficient of -0.8517 existed between the wall thickness and bladder volume, and the correlation was significant(p <0.01). The corresponding linear regression equation was then estimated by the unary linear regression. Compared to the absolute value of wall thickness, the z-score of wall thickness would be more appropriate to reflect the thickness variations. For possible abnormality detection of a bladder based on wall thickness, the intra-subject and inter-subject thickness variation should be considered.

[Study on different responses of rats' small intestine mucous membrane and bladder transitional epithelium in the same carcinogenic urine environment].

PubMed

Wu, B; Pan, C; Song, G

2001-10-25

To preliminarily verify the tentative idea of replacement of bladder transitional epithelium with small intestine mucous membrane to prevent recurrence of carcinoma of bladder. A certain segment of small intestine was transplanted to the urinary bladder of the same body in 17 rats. Then N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) was used to induce carcinoma of bladder. BBN was used to 11 control rats that did not undergo operation. Bladder carcinoma failed to be found in the transplanted small intestine mucous membrane in all experimental rats except one. After stimulation of BBN, carcinoma of urinary bladder occurred in all rats' bladder transitional epithelium. 1) The carcinogenic substances in the urine of rats suffering from BBN-induced bladder carcinoma are carcinogenic only to bladder transitional epithelium and have no effect on small intestine epithelium. 2) Bladder transitional epithelium may be more sensitive to the urine carcinogenic substances and easier to be cancerized than small intestine epithelium. 3) The tentative idea of substitution of small intestine mucous membrane for bladder transitional epithelium to prevent the recurrence of bladder carcinoma is worth further studying.

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.

The effect of dietary administration of Disperse Blue 1 on the urinary system of the Fischer 344 rat.

PubMed

Burnett, C M; Squire, R A

1986-04-01

Disperse Blue 1 (containing 50% lignosulphonate dispersants) was fed to Fischer 344 rats at dietary levels of 0.01 and 0.1% for 19 months and at 1.0% for 6 months. Fischer 344 rats were also given the dye by gavage at 1 g/kg for 1-3 days or in the diet at 0.5 or 1% for 4 days, and corresponding dietary levels of the colouring without dispersant were also fed for 4 days. Bladders and kidneys were examined after the 1-4 day treatments, in animals dying or killed from month 6 to termination (19 months) in the chronic study and in those killed at wk 5, 9 and 17. At the latter three times, autoradiography following injection of tritiated thymidine showed increased DNA synthesis in the urothelium of high-dose rats, but no other increased labelling in any group. Bladder lesions were seen only at the 1.0% level, epithelial erosion with adhering dye particles being seen by day 4, calculi and hyperplasia by wk 5 and squamous metaplasia by wk 9. The calculi contained more dye in males than in females and more calcium in females. By month 6, dye particles were embedded in the bladder wall, with some evidence of histiocyte accumulation in their vicinity. Two papillomas and one carcinoma, but no leiomyosarcomas, were diagnosed. The earliest tumours, two papillomas, were detected at wk 17. Tumour incidence following surgical removal of calculus was about double that in rats not subjected to surgery and the incidence of normal bladders at month 19 was higher in the latter group. Compound-related effects in the kidneys--inflammation, pelvic epithelial hyperplasia and tubular degeneration and regeneration with interstitial fibrosis--were seen only in the high-dose group. Dye present in the tubules and renal pelvis persisted in many rats for a year after cessation of treatment.

Suprapubic Bladder Catheterization of Male Spinal-Cord–Injured Sprague–Dawley Rats

PubMed Central

Robinson, Mary A; Herron, Alan J; Goodwin, Bradford S; Grill, Raymond J

2012-01-01

The rat spinal-cord–injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine. PMID:22330872

The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin-induced Diabetic Rats.

PubMed

Evcim, Atiye Sinem; Micili, Serap Cilaker; Karaman, Meral; Erbil, Guven; Guneli, Ensari; Gidener, Sedef; Gumustekin, Mukaddes

2015-06-01

This study was designed to determine the role of the small GTPase Rac1 on carbachol-induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study groups were composed of control, diabetic and insulin-treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes-related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose-dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin-treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh-induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes-related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effects of aniracetam on bladder overactivity in rats with cerebral infarction.

PubMed

Nakada, Y; Yokoyama, O; Komatsu, K; Kodama, K; Yotsuyanagi, S; Niikura, S; Nagasaka, Y; Namiki, M

2000-06-01

Aniracetam has been used to improve the mental condition of patients with cerebrovascular disease. Previous studies have demonstrated that aniracetam activates the residual functions of cholinergic neurons in damaged brain areas. In this study, the effects of aniracetam on bladder overactivity after left middle cerebral artery occlusion were assessed through oral or i.c.v. administration in sham-operated and cerebral infarcted rats. Oral administration of aniracetam (100 and 300 mg/kg) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but had no effect on bladder capacity in sham-operated rats. Intracerebroventricular administration of aniracetam (0.25 and 2.5 microg/rat) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but not in sham-operated rats. Aniracetam had no significant effect on bladder contraction pressure or micturition threshold pressure in either sham-operated or cerebral infarcted rats. Furthermore, i.c.v. administration of atropine (1 microg/rat), a muscarinic acetylcholine receptor antagonist, completely inhibited the enhancing effects of aniracetam on bladder capacity in cerebral infarcted rats. The effects of aniracetam on bladder overactivity are thought to be mediated in part by activation of cholinergic inhibitory mechanisms in the brain. These results indicate that aniracetam may improve the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

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.

Influence of gender and the oestrous cycle on in vitro contractile responses of the rat urinary bladder to cholinergic stimulation

PubMed Central

Longhurst, Penelope A; Levendusky, Mark

2000-01-01

Experiments were done to determine the influence of gender and the oestrous cycle on rat urinary bladder contractility in response to cholinergic stimulation. Bladder strips from female rats responded to high frequency stimulation with smaller contractile responses than did strips from males, and to low concentrations of carbachol with greater responses. The decreased responsiveness of bladder strips from female rats to electrical field stimulation can be primarily attributed to the rats in the oestrous stage of the oestrous cycle. Bladder strips from female rats in all stages of the oestrous cycle were more sensitive to carbachol than those from males, but there were no differences in sensitivity to electrical field stimulation. The contractile responses of strips from both male and female rats to carbachol were antagonized by muscarinic antagonists with the following rank order of affinity (pA2) estimates: 4-DAMP>>pirenzepine>methoctramine, suggesting that the receptor mediating contraction was the M3 subtype. There were no differences in pA2 values between bladder strips from male and female rats. The data indicate that responsiveness of bladder strips to electrical field stimulation and carbachol is altered in female rats in the oestrous stage of the oestrous cycle. Furthermore, gender influences the sensitivity of rat bladder to muscarinic stimulation. PMID:10991909

A unified EM approach to bladder wall segmentation with coupled level-set constraints

PubMed Central

Han, Hao; Li, Lihong; Duan, Chaijie; Zhang, Hao; Zhao, Yang; Liang, Zhengrong

2013-01-01

Magnetic resonance (MR) imaging-based virtual cystoscopy (VCys), as a non-invasive, safe and cost-effective technique, has shown its promising virtue for early diagnosis and recurrence management of bladder carcinoma. One primary goal of VCys is to identify bladder lesions with abnormal bladder wall thickness, and consequently a precise segmentation of the inner and outer borders of the wall is required. In this paper, we propose a unified expectation-maximization (EM) approach to the maximum-a-posteriori (MAP) solution of bladder wall segmentation, by integrating a novel adaptive Markov random field (AMRF) model and the coupled level-set (CLS) information into the prior term. The proposed approach is applied to the segmentation of T1-weighted MR images, where the wall is enhanced while the urine and surrounding soft tissues are suppressed. By introducing scale-adaptive neighborhoods as well as adaptive weights into the conventional MRF model, the AMRF model takes into account the local information more accurately. In order to mitigate the influence of image artifacts adjacent to the bladder wall and to preserve the continuity of the wall surface, we apply geometrical constraints on the wall using our previously developed CLS method. This paper not only evaluates the robustness of the presented approach against the known ground truth of simulated digital phantoms, but further compares its performance with our previous CLS approach via both volunteer and patient studies. Statistical analysis on experts’ scores of the segmented borders from both approaches demonstrates that our new scheme is more effective in extracting the bladder wall. Based on the wall thickness calibrated from the segmented single-layer borders, a three-dimensional virtual bladder model can be constructed and the wall thickness can be mapped on to the model, where the bladder lesions will be eventually detected via experts’ visualization and/or computer-aided detection. PMID:24001932

[Biodegradable catheters for fistula prevention in hypospadias. Experimental preliminary study].

PubMed

Ramos, J L; Aldazabal, P; Zuza, E; Sarasúa, J R; Arrieta, A; Villanueva, A; Eizaguirre, I

2013-04-01

Continuous technical innovations are not enough to resolve the high incidence of fistula after hypospadias repair. A urethral catheter-tutor made of reabsorbable polymeric biomaterial (RPB) which could be left in situ long enough could reduce the complications. To investigate in an animal model differents RPB to be used in urology. CRL Wistar rats, males, divided into 5 equal groups according to the used polymers: polylactide; lactic-coprolactone copolymer; lactic-glycolic copolymer; simulated; control silicones. Three individuals were sacrificed per group at 4th, 10th and 16th week. In all animals (exceptuating the simulated group), biomaterial was fixed to the bladder wall bylaparotomy. Animals remained in individual housing and kept under daily control of hematuria during the first 15 days and weekly weight and urine control for pH and lactate. After being slaughtered, remaining polymer was collected for chemical analysis and bladder tissue for hystologic study. There was no mortality, hematuria nor other clinical signs. The bladder wall showed a mild foreign body reaction. The values of lactate and pH in urine did not reach toxic levels. Lactic-glycolic was totally reabsorbed by the 10th week and had the lowest degree of calcification. Polylactide and lactic-coprolactone remained intact. The model of urinary bladder has proven useful for studying the degradation of bioresorbable polymers. The analyzed polymers have spent long time to be reabsorbed, so we will have to study new others.

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

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

DTIC Science & Technology

2014-01-01

thickness abdominal wall defects. Tissue Eng 12, 1929, 2006. 7. Gamba, P.G., Conconi, M.T., Lo Piccolo, R., Zara , G., Spi nazzi, R., and Parnigotto... Zara , G., Sabatti, M., Marzaro, M., et al. Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue engineering approach to

Location-dependent correlation between tissue structure and the mechanical behaviour of the urinary bladder.

PubMed

Morales-Orcajo, Enrique; Siebert, Tobias; Böl, Markus

2018-05-25

The mechanical properties of the urinary bladder wall are important to understand its filling-voiding cycle in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. The present study aimed to assess the regional differences in the mechanical properties and microstructure of the urinary bladder wall. Ninety (n=90) samples of porcine urinary bladder wall (ten samples from nine different locations) were mechanically and histologically analysed. Half of the samples (n=45) were equibiaxially tested within physiological conditions, and the other half, matching the sample location of the mechanical tests, was frozen, cryosectioned, and stained with Picro-Sirius red to differentiate smooth muscle cells, extracellular matrix, and fat. The bladder wall shows a non-linear stress-stretch relationship with hysteresis and softening effects. Regional differences were found in the mechanical response and in the microstructure. The trigone region presents higher peak stresses and thinner muscularis layer compared to the rest of the bladder. Furthermore, the ventral side of the bladder presents anisotropic characteristics, whereas the dorsal side features perfect isotropic behaviour. This response matches the smooth muscle fibre bundle orientation within the tunica muscularis. This layer, comprising approximately 78% of the wall thickness, is composed of two fibre bundle arrangements that are cross-oriented, one with respect to the other, varying the angle between them across the organ. That is, the ventral side presents a 60°/120° cross-orientation structure, while the muscle bundles were oriented perpendicular in the dorsal side. In the present study, we demonstrate that the mechanical properties and the microstructure of the urinary bladder wall are heterogeneous across the organ. The mechanical properties and the microstructure of the urinary bladder wall within nine specific locations matching explicitly the mechanical and structural variations have been examined. On the one hand, the results of this study contribute to the understanding of bladder mechanics and thus to their functional understanding of bladder filling and voiding. On the other hand, they are relevant to the fields of constitutive formulation of bladder tissue, whole bladder mechanics, and bladder-derived scaffolds i.e., tissue-engineering grafts. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

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.

[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.

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.

Nerve growth factor release from the urothelium increases via activation of bladder C-fiber in rats with cerebral infarction.

PubMed

Yokokawa, Ryusei; Akino, Hironobu; Ito, Hideaki; Zha, Xinmin; Yokoyama, Osamu

2017-08-01

There are some reports that bladder C-fibers are partially involved in detrusor overactivity in patients with brain lesions. We investigated the contribution of bladder C-fiber to decreased bladder capacity in rats with cerebral infarction. Cerebral infarction was induced under halothane anesthesia by left middle cerebral artery occlusion with 4-0 nylon thread in female Sprague-Dawley rats. Intramural amounts of ATP and prostaglandin E 2 , in vivo and in vitro ATP, NGF, and prostaglandin E 2 release from the distended bladder urothelium, and changes in mRNA expressions of sensor molecules and receptors were monitored 6 h after the occlusion. Cystometry was performed in rats with or without resiniferatoxin pretreatment. Overexpression of sensor molecule, transient receptor potential vanilloid-type channel 1, acid-sensing ion channel 2, purinergic receptors P2X 3 , and M 2 /M 3 muscarinic receptors was found in the bladder. These changes were accompanied by increases in ATP and NGF release from the urothelium. In contrast, when bladder C-fibers were desensitized by resiniferatoxin, no increase in NGF release from the urothelium was found either in vivo or in vitro. There was no difference in the percentage decrease in bladder capacity between cerebral infarction rats pretreated with resiniferatoxin and cerebral infarction rats without pretreatment. Results indicate that expression of sensor molecules in the bladder is altered by distant infarction in the brain. ATP and NGF release from the urothelium also increased. NGF release was related to activation of bladder C-fibers. Bladder C-fibers might not contribute much to decreased bladder capacity caused by cerebral infarction. © 2016 Wiley Periodicals, 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.

Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model.

PubMed

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

2014-04-01

We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Radiation absorbed dose to bladder walls from positron emitters in the bladder content.

PubMed

Powell, G F; Chen, C T

1987-01-01

A method to calculate absorbed doses at depths in the walls of a static spherical bladder from a positron emitter in the bladder content has been developed. The beta ray dose component is calculated for a spherical model by employing the solutions to the integration of Loevinger and Bochkarev point source functions over line segments and a line segment source array technique. The gamma ray dose is determined using the specific gamma ray constant. As an example, absorbed radiation doses to the bladder walls from F-18 in the bladder content are presented for static spherical bladder models having radii of 2.0 and 3.5 cm, respectively. Experiments with ultra-thin thermoluminescent dosimeters (TLD's) were performed to verify the results of the calculations. Good agreement between TLD measurements and calculations was obtained.

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

Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats

PubMed Central

Merrill, Liana

2014-01-01

Individuals with functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) often report symptom (e.g., urinary frequency) worsening due to stress. One member of the transient receptor potential ion channel vanilloid family, TRPV4, has recently been implicated in urinary bladder dysfunction disorders including OAB and IC/BPS. These studies address the role of TRPV4 in stress-induced bladder dysfunction using an animal model of stress in male rats. To induce stress, rats were exposed to 7 days of repeated variate stress (RVS). Quantitative PCR data demonstrated significant (P ≤ 0.01) increases in TRPV4 transcript levels in urothelium but not detrusor smooth muscle. Western blot analyses of split urinary bladders (i.e., urothelium and detrusor) showed significant (P ≤ 0.01) increases in TRPV4 protein expression levels in urothelial tissues but not detrusor smooth muscle. We previously showed that RVS produces bladder dysfunction characterized by decreased bladder capacity and increased voiding frequency. The functional role of TRPV4 in RVS-induced bladder dysfunction was evaluated using continuous, open outlet intravesical infusion of saline in conjunction with administration of a TRPV4 agonist, GSK1016790A (3 μM), a TRPV4 antagonist, HC067047 (1 μM), or vehicle (0.1% DMSO in saline) in control and RVS-treated rats. Bladder capacity, void volume, and intercontraction interval significantly decreased following intravesical instillation of GSK1016790A in control rats and significantly (P ≤ 0.01) increased following administration of HC067047 in RVS-treated rats. These results demonstrate increased TRPV4 expression in the urothelium following RVS and that TRPV4 blockade ameliorates RVS-induced bladder dysfunction consistent with the role of TRPV4 as a promising target for bladder function disorders. PMID:24965792

A Convex Hull-Based New Metric for Quantification of Bladder Wall Irregularity in Pediatric Patients With Congenital Anomalies of the Kidney and Urinary Tract.

PubMed

Stember, Joseph N; Newhouse, Jeffrey; Behr, Gerald; Alam, Shumyle

2017-11-01

Early identification and quantification of bladder damage in pediatric patients with congenital anomalies of the kidney and urinary tract (CAKUT) is crucial to guiding effective treatment and may affect the eventual clinical outcome, including progression of renal disease. We have developed a novel approach based on the convex hull to calculate bladder wall trabecularity in pediatric patients with CAKUT. The objective of this study was to test whether our approach can accurately predict bladder wall irregularity. Twenty pediatric patients, half with renal compromise and CAKUT and half with normal renal function, were evaluated. We applied the convex hull approach to calculate T, a metric proposed to reflect the degree of trabeculation/bladder wall irregularity, in this set of patients. The average T value was roughly 3 times higher for diseased than healthy patients (0.14 [95% confidence interval, 0.10-0.17] versus 0.05 [95% confidence interval, 0.03-0.07] for normal bladders). This disparity was statistically significant (P < .01). We have demonstrated that a convex hull-based procedure can measure bladder wall irregularity. Because bladder damage is a reversible precursor to irreversible renal parenchymal damage, applying such a measure to at-risk pediatric patients can help guide prompt interventions to avert disease progression. © 2017 by the American Institute of Ultrasound in Medicine.

Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats

PubMed Central

Salas, Nilson A.; Somogyi, George T.; Gangitano, David A.; Boone, Timothy B.; Smith, Christopher P.

2009-01-01

Neurally intact (NI) rats and chronic spinal cord injured (SCI) rats were studied to determine how activation of mechanosensory or cholinergic receptors in the bladder urothelium evokes ATP release from afferent terminals in the bladder as well as in the spinal cord. Spinal cord transection was performed at the T9-T10 level 2–3 weeks prior to the experiment and a microdialysis fiber was inserted in the L6-S1 lumbosacral spinal cord. Mechanically evoked (i.e. 10cm/w bladder pressure) ATP release into the bladder lumen was approximately 6.5 fold higher in SCI compared to NI rats (p<0.05). Intravesical carbachol (CCh) induced a significantly greater release of ATP in the bladder from SCI as compared to NI rats (3424.32 ± 1255.57 vs. 613.74 ± 470.44 pmol/ml, respectively, p<0.05). However, ATP release in NI or SCI rats to intravesical CCh was not affected by the muscarinic antagonist atropine (Atr). Spinal release of ATP to bladder stimulation with 10cm/w pressure was 5-fold higher in SCI compared to NI rats (p<0.05). CCh also induced a significantly greater release of spinal ATP in SCI rats compared to controls (4.3 ± 0.9 vs. 0.90 ± 0.15 pmol, p < 0.05). Surprisingly, the percent inhibitory effect of Atr on CCh-induced ATP release was significantly less in SCI as compared to NI rats (49% vs. 89%, respectively). SCI induces a dramatic increase in intravesical pressure and cholinergic receptor evoked bladder and spinal ATP release. Muscarinic receptors do not mediate intravesical CCh induced ATP release into the bladder lumen in NI or SCI rats. In NI rats sensory muscarinic receptors are the predominant mechanism by which CCh induces ATP release from primary afferents within the lumbosacral spinal cord. Following SCI, however, nicotinic or purinergic receptor mechanisms become active, as evidenced by the fact that Atr was only partially effective in inhibiting CCh-induced spinal ATP release. PMID:17067723

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

PubMed Central

Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Suguro, Mayuko; Kawabe, Mayumi; Furukawa, Fumio; Nagano, Kasuke; Fukushima, Shoji

2013-01-01

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses. PMID:24526807

An ex vivo investigation into the transurothelial permeability and bladder wall distribution of the nonsteroidal anti-inflammatory ketorolac.

PubMed

Williams, Nicholas A; Bowen, Jenna L; Al-Jayyoussi, Ghaith; Gumbleton, Mark; Allender, Chris J; Li, Jamie; Harrah, Tim; Raja, Aditya; Joshi, Hrishi B

2014-03-03

Transurothelial drug delivery continues to be an attractive treatment option for a range of urological conditions; however, dosing regimens remain largely empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory ketorolac has been shown to significantly reduce ureteral stent-related pain. While this latest development provides an opportunity for advancing the management of stent-related pain, clinical translation will undoubtedly require an understanding of the rate and extent of delivery of ketorolac into the bladder wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and bladder wall distribution of ketorolac. The subsequent application of a pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (Kp) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp = 2.63 × 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and 21 μg g(-1) were achieved in the urothelium, lamina propria and detrusor respectively. An average concentration of 87 μg g(-1) was achieved across the whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo values for Kp and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations. When dilution of the drug solution with urine and vascular clearance were taken into account, a reduced ketorolac concentration of 37 μg g(-1) across the whole bladder wall was predicted. These studies reveal crucial information about the urothelium's permeability to agents such as ketorolac and the concentrations achievable in the bladder wall. It would appear that levels of ketorolac delivered to the bladder wall intravesically would be sufficient to provide an anti-inflammatory effect. The combination of such ex vivo data and PK modeling provides an insight into the likelihood of achieving clinically relevant concentrations of drug following intravesical administration.

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.

α-Information Based Registration of Dynamic Scans for Magnetic Resonance Cystography

PubMed Central

Han, Hao; Lin, Qin; Li, Lihong; Duan, Chaijie; Lu, Hongbing; Li, Haifang; Yan, Zengmin; Fitzgerald, John

2015-01-01

To continue our effort on developing magnetic resonance (MR) cystography, we introduce a novel non–rigid 3D registration method to compensate for bladder wall motion and deformation in dynamic MR scans, which are impaired by relatively low signal–to–noise ratio in each time frame. The registration method is developed on the similarity measure of α–information, which has the potential of achieving higher registration accuracy than the commonly-used mutual information (MI) measure for either mono-modality or multi-modality image registration. The α–information metric was also demonstrated to be superior to both the mean squares and the cross-correlation metrics in multi-modality scenarios. The proposed α–registration method was applied for bladder motion compensation via real patient studies, and its effect to the automatic and accurate segmentation of bladder wall was also evaluated. Compared with the prevailing MI-based image registration approach, the presented α–information based registration was more effective to capture the bladder wall motion and deformation, which ensured the success of the following bladder wall segmentation to achieve the goal of evaluating the entire bladder wall for detection and diagnosis of abnormality. PMID:26087506

An animal model to study lower urinary tract symptoms and erectile dysfunction: the hyperlipidaemic rat.

PubMed

Rahman, Nadeem U; Phonsombat, Surat; Bochinski, Derek; Carrion, Rafael E; Nunes, Lora; Lue, Tom F

2007-09-01

To present evidence that rats fed a high-fat diet could serve as a useful animal model to study both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), as recent epidemiological studies have shown a strong association between LUTS and ED but the physiological basis behind this relationship is unknown. In all, 24 male Sprague-Dawley rats were divided into two groups: nine controls were fed a 'normal' diet and 15 were fed a high-fat diet (hyperlipidaemic rats). After 6 months all the rats had bladder and erectile functions evaluated using awake cystometry and cavernosal nerve electrostimulation, respectively. After the functional studies were completed, the penis, prostate and bladder were collected for immunohistochemical analysis. The hyperlipidaemic rats had significantly higher serum cholesterol and low-density lipoprotein than the controls (P < 0.05). The hyperlipidaemic rats also had significantly worse erectile function (P = 0.004) and developed more bladder overactivity (P = 0.004) than the controls. In the hyperlipidaemic rats there was significant muscle hypertrophy in the peri-urethral lobe of the prostate (P < 0.001) and in the bladder (P < 0.05). There was also greater P2X(1) (purinoceptor) staining as well as other molecular changes in the bladder of the hyperlipidaemic rats. In this hyperlipidaemic rat model three abnormalities were consistently detected: prostatic enlargement, bladder overactivity, and ED. This rat model could be a useful research tool for understanding the common causes of LUTS and ED, as well as facilitating the development of preventive measures and better therapies to treat both conditions.

Morphologic study of three collagen materials for body wall repair.

PubMed

Soiderer, Emily E; Lantz, Gary C; Kazacos, Evelyn A; Hodde, Jason P; Wiegand, Ryan E

2004-05-15

The search for ideal prostheses for body wall repair continues. Synthetic materials such as polypropylene mesh (PPM) are associated with healing complications. A porcine-derived collagen-based material (CBM), small intestinal submucosa (SIS), has been studied for body wall repair. Renal capsule matrix (RCM) and urinary bladder submucosa (UBS) are CBMs not previously evaluated in this application. This is the first implant study using RCM. Full-thickness muscle/fascia ventral abdominal wall defects were repaired with SIS, RCM, UBS, and PPM in rats with omentum and omentectomy. A random complete block design was used to allot implant type to each of 96 rats. Healing was evaluated at 4 and 8 weeks. Adhesion tenacity and surface area were scored. Implant site dimensions were measured at implantation and necropsy. Inflammation, vascularization, and fibrosis were histopathologically scored. Data were compared by analysis of variance (P < 0.05). PPM produced a granulomatous foreign body response in contrast to the organized healing of CBM implants. CBM mean scores were lower than PPM scores for adhesion tenacity, surface area, and inflammation at each follow-up time for rats with omentums (P < 0.02). The CBMs had less tenacity and inflammation than PPM at each follow-up time in omentectomy groups (P < 0.008). Wound contraction was greater for PPM (P < 0.0001) for all rats. RCM and UBS were similar to SIS invoking reduced inflammation, adhesion, and contraction compared to PPM. The fibrotic response to PPM was unique and more intense compared to CBMs. These CBM implants appear morphologically acceptable and warrant continued investigation.

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

EPA Science Inventory

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder.

PubMed Central

Hall, J. M.; Flowers, J. M.; Morton, I. K.

1992-01-01

1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1282072

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

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.

Fetal stomach and gallbladder in contact with the bladder wall is a common ultrasound sign of stomach-down left congenital diaphragmatic hernia.

PubMed

Morgan, Tara A; Basta, Amaya; Filly, Roy A

2017-01-01

The aim of this study was to identify sonographic (US) findings that can assist in prenatal diagnosis of stomach-down left congenital diaphragmatic hernia (CDH), specifically related to positioning of the abdominal contents including the stomach, bladder, and gallbladder. All US examinations with a postnatally confirmed diagnosis of stomach-down left CDH over a 13-year period were retrospectively reviewed for abnormal position of the abdominal contents, including whether the fetal stomach was in contact with the urinary bladder. Normal fetuses that underwent comprehensive US surveys were similarly evaluated for comparison in a 2:1 ratio. Twenty-two fetuses with stomach-down left CDH were identified in a cohort of 278 fetuses with left CDH. In 15/22 (68.2%) cases of stomach-down left CDH, the bladder and stomach walls were in contact. Contact of the fetal gallbladder with the fetal bladder wall was also observed and was present even more commonly (17/22 cases [77.3%]). There was no case of either the stomach or gallbladder in contact with the bladder wall in the normal fetal cohort (n = 44). Recognition of the fetal stomach and/or gallbladder in contact with the bladder wall can help in the detection of stomach-down left CDH. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:8-13, 2017. © 2016 Wiley Periodicals, Inc.

Urothelial acetylcholine involvement in ATP-induced contractile responses of the rat urinary bladder.

PubMed

Stenqvist, Johanna; Winder, Michael; Carlsson, Thomas; Aronsson, Patrik; Tobin, Gunnar

2017-08-15

Both acetylcholine and adenosine 5'-triphosphate (ATP) are released from the urothelium. In in vivo experiments ATP has been shown to evoke contractile responses that are significantly reduced by atropine. Currently, we aimed to examine the cholinergic part of the ATP-evoked contractile response of normal and inflamed (cyclophosphamide-treated rats) bladders. A whole bladder preparation that enabled drug administration either outside or inside the urinary bladder was used. The responses were examined in bladders from control and cyclophosphamide-treated rats that were either intact or urothelium-denuded. The expression of choline acetyltransferase and carnitine acetyltransferase were examined by Western blotting of normal and inflamed bladders. Methacholine evoked larger contractions when administered to the outside of the bladder in comparison to instillation. For ATP, an opposite trend emerged. While atropine substantially reduced the ATP-induced responses at internal administration (7.4±1.1 and 3.7±0.9 mN at 10 -3 M; n=13; P<0.001), it had no effect when administered outside the bladder. The removal of the urothelium caused a similar reduction of the responses to internal administration of ATP as caused by atropine. In cyclophosphamide-treated rats, neither atropine nor urothelium-denudation had any effect on the ATP-evoked responses. No changes in the expressions of the acetylcholine synthesising enzymes were observed. The current study shows that ATP induces a release of urothelial acetylcholine that contributes to the purinergic contractile response in the rat urinary bladder. This atropine-sensitive part of the purinergic contractile response is absent in the inflamed bladder. This may be one pathological mechanism involved in bladder dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

PubMed Central

Saitoh, Chikashi; Yokoyama, Hitoshi; Chancellor, Michael B.; de Groat, William C.; Yoshimura, Naoki

2009-01-01

Aims Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (ip) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats. Methods Female Sprague-Dawley rats were used. Cystitis was induced by ip injection of CYP (100 and 200mg/kg) or intravesical instillation of acetone (10, 30 and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an evans blue (EB) dye leakage technique. Results CYP (100mg/kg, ip) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200mg/kg, ip) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected. Conclusions These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity. PMID:19618450

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.

Characteristics of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction.

PubMed

Aizawa, Naoki; Ichihara, Koji; Fukuhara, Hiroshi; Fujimura, Tetsuya; Andersson, Karl-Erik; Homma, Yukio; Igawa, Yasuhiko

2017-08-09

We investigated the characteristics of bladder mechanosensitive single-unit afferent activities (SAAs) in rats with a bladder outlet obstruction (BOO) and their relationship with bladder microcontractions. Male Wistar rats were divided into Sham and BOO groups. Four or 10 days after the surgery, rats were anesthetized with urethane. The SAAs of Aδ- or C-fibers from the L6 dorsal roots were recorded during bladder filling. The BOO group showed a higher number of microcontractions and lower SAAs of Aδ-fibers compared with those of the Sham group. These findings were significant at day 10 post-operatively. In contrast, SAAs of C-fibers were not significantly different between the groups at either day 4 or 10. In the BOO group at day 10, the SAAs of both Aδ- and C-fibers at the "ascending" phase of microcontractions were significantly higher than those at the other phases (descending or stationary), and a similar tendency was also observed at day 4. Taken together, during bladder filling, the bladder mechanosensitive SAAs of Aδ-fibers were attenuated, but SAAs of both Aδ- and C-fibers were intermittently enhanced by propagation of microcontractions.

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.

Effects of streptozotocin-induced diabetes on bladder and erectile (dys)function in the same rat in vivo.

PubMed

Christ, George J; Hsieh, Yi; Zhao, Weixin; Schenk, Gregory; Venkateswarlu, Karicheti; Wang, Hong-Zhan; Tar, Moses T; Melman, Arnold

2006-05-01

To establish the methods, feasibility and utility of evaluating the impact of diabetes on bladder and erectile function in the same rat, as more than half of diabetic patients have bladder dysfunction, and half of diabetic men have erectile dysfunction, but the severity of coincident disease has not been rigorously assessed. In all, 16 F-344 rats had diabetes induced by streptozotocin (STZ), and were divided into insulin-treated (five) and untreated (11), and compared with age-matched controls (10), all assessed in parallel. All STZ rats were diabetic for 8-11 weeks. Cystometric studies were conducted on all rats, with cavernosometric studies conducted on a subset of rats. There were insulin-reversible increases in the following cystometric variables; bladder weight, bladder capacity, micturition volume, residual volume, micturition pressure and spontaneous activity (P < 0.05, in all, one-way analysis of variance, anova). Cavernosometry showed a diabetes-related, insulin-reversible decline in the cavernosal nerve-stimulated intracavernosal pressure (ICP) response at all levels of current stimulation (P < 0.05, in all one-way anova). Plotting erectile capacity (i.e. ICP) against bladder capacity showed no correlation between the extent of the decline in erectile capacity and the magnitude of the increase in bladder capacity. These studies extend previous work to indicate that the extent of diabetes-related bladder and erectile dysfunction can vary in the same rat. As such, these findings highlight the importance of evaluating the impact of diabetes on multiple organ systems in the lower urinary tract. Future studies using this model system should lead to a better understanding of the initiation, development, progression and coincidence of these common diabetic complications.

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.

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.

Effects of saw palmetto extract on micturition reflex of rats and its autonomic receptor binding activity.

PubMed

Oki, Tomomi; Suzuki, Mayumi; Nishioka, Yasuhiko; Yasuda, Akio; Umegaki, Keizo; Yamada, Shizuo

2005-04-01

We examined the effects of saw palmetto extract (SPE) on the rat micturition reflex and on autonomic receptors in the lower urinary tract. The effect of SPE was examined on cystometrograms of anesthetized rats induced by intravesical infusion of saline or 0.1% acetic acid. SHR/NDmc-cp (cp/cp) rats received repeat oral administration of SPE and nighttime urodynamic function was determined. The autonomic receptor binding activity of SPE in the rat bladder and prostate was examined by radioligand binding assay. Intraduodenal administration of SPE (60 mg/kg) in anesthetized rat cystometry caused a significant increase in the micturition interval, micturition volume and bladder capacity during intravesical saline infusion. Also, similar administration of SPE at doses of 12 and 20 mg/kg significantly reversed the shortened micturition interval as well as the decreased micturition volume and bladder capacity due to 0.1% acetic acid infusion in a dose dependent manner. In conscious SHR/NDmc-cp (cp/cp) rats repeat oral administration of SPE (6 mg/kg daily) constantly increased the micturition interval and concomitantly decreased voiding frequency. SPE inhibited specific binding of [H]NMS ([N-methyl-H]scopolamine methyl chloride) (bladder) and [H]prazosin (prostate) with IC50 values of 46.1 and 183 microg/ml, respectively. SPE significantly alleviates urodynamic symptoms in hyperactive rat bladders by increasing bladder capacity and subsequently prolonging the micturition interval. Our data may support the clinical efficacy of SPE for the treatment of lower urinary tract symptoms.

AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome.

PubMed

Lashinger, Erin S R; Steiginga, Matthew S; Hieble, J Paul; Leon, Lisa A; Gardner, Scott D; Nagilla, Rakesh; Davenport, Elizabeth A; Hoffman, Bryan E; Laping, Nicholas J; Su, Xin

2008-09-01

The activation of the TRPM8 channel, a member of the large class of TRP ion channels, has been reported to be involved in overactive bladder and painful bladder syndrome, although an endogenous activator has not been identified. In this study, N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride salt (AMTB) was evaluated as a TRPM8 channel blocker and used as a tool to evaluate the effects of this class of ion channel blocker on volume-induced bladder contraction and nociceptive reflex responses to noxious bladder distension in the rat. AMTB inhibits icilin-induced TRPM8 channel activation as measured in a Ca(2+) influx assay, with a pIC(50) of 6.23. In the anesthetized rat, intravenous administration of AMTB (3 mg/kg) decreased the frequency of volume-induced bladder contractions, without reducing the amplitude of contraction. The nociceptive response was measured by analyzing both visceromotor reflex (VMR) and cardiovascular (pressor) responses to urinary bladder distension (UBD) under 1% isoflurane. AMTB (10 mg/kg) significantly attenuated reflex responses to noxious UBD to 5.42 and 56.51% of the maximal VMR response and pressor response, respectively. The ID50 value on VMR response was 2.42 +/- 0.46 mg/kg. These results demonstrate that TRPM8 channel blocker can act on the bladder afferent pathway to attenuate the bladder micturition reflex and nociceptive reflex responses in the rat. Targeting TRPM8 channel may provide a new therapeutic opportunity for overactive bladder and painful bladder syndrome.

Circulating inhibitor of ouabain-insensitive cation transport in malignantrenal hypertension

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

Simon, G.

1986-03-01

The role of circulating humoral agents in the pathogenesis of vascular wall Na depletion in malignant hypertension (MHT) was investigated. Plasma was collected from 33 male F344 rats with malignant one-kidney, one clip HT and 22 normotensive control rats. MHT developed spontaneously and was characterized by inactivity, weight loss, edema, anemia or hemoconcentration, hyperkalemia, and renal insufficiency. For bioassay, monolayers of quiescent vascular smooth muscle cells from F344 rats were incubated in deproteinized or whole plasma for measurement of /sup 86/Rb uptake with or without 2 mM ouabain or 1 mM furosemide. Compared to controls, ouabain-insensitive /sup 86/Rb uptake wasmore » reduced from 8.2 +- 2.0 nmol/mg protein min/sup -1/ (mean +- SD) to 5.2 +- 1.4 in deproteinized plasma (p < 0.01, N = 12) and from 6.6 +- 1.9 to 4.0 +- 0.3 in whole plasma (p < 0.05, N=5) of rats with MHT, due in part to a reduction in furosemide-sensitive uptake (p < 0.01, N = 6). There were no differences in ouabain-sensitive /sup 86/Rb uptake of cells between groups. In rats with MHT the increased Na content of the aorta that characterizes benign one-kidney, one clip HT was reversed, and bladder wall Na content was reduced (p < 0.001, N = 9). In MHT, a furosemide-like, ouabain-insensitive cation transport inhibitor in blood and urine may be the cause of vascular wall Na loss and of natriuresis that triggers the syndrome.« less

Chronic cystitis with ossification of the bladder wall in a 6-month-old German shepherd dog

PubMed Central

Zotti, Alessandro; Fant, Pierluigi; De Zan, Gabrita; Mollo, Antonio; Busetto, Roberto

2007-01-01

Ossification of the bladder wall, detected radiographically as a nonhomogeneous radiopaque area in the cranioventral part of the bladder in a puppy, is reported. We speculate that chronic inflammation due to the presence of uroliths in the lumen may have stimulated a metaplastic transformation of the cells. PMID:17966335

Dietary phytoestrogens maintain contractile responses to carbachol with age in the female rat isolated bladder.

PubMed

Owen, Suzzanne J; Rose'Meyer, Roselyn B; Massa, Helen M

2011-08-15

Development of urinary incontinence, for many women, occurs following menopause. Dietary phytoestrogens consumed over the long term may affect the contractile function and maintenance of the urinary bladder in post menopausal women. This study examined the muscarinic receptor mediated contractile responses in the rat isolated bladder in response to ovariectomy and long term dietary phytoestrogen consumption. Ovariectomised or sham-operated female Wistar rats (8 weeks) were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. Bladders were dissected from rats at 12, 24 and 52 weeks of age and placed in 25 ml organ baths filled with McEwans solution. The contractile response to carbachol, in 12 week old female rats did not change as a result of dietary phytoestrogens or ovariectomy (P>0.05). At 24 weeks of age, detrusor muscle strip responses to carbachol from non-soy fed ovariectomised rats were attenuated (P<0.05). At 52 weeks, bladder detrusor strip responses to carbachol were reduced in all treatment groups with the exception of the soy-fed sham operated rats. These results suggest an age-related reduction in the contractile response of the detrusor to the muscarinic receptor agonist carbachol, which may be prevented by long term dietary phytoestrogen intake. Copyright © 2011 Elsevier Inc. All rights reserved.

A placebo-controlled efficacy study of the intravesical immunomodulators TMX-101 and TMX-202 in an orthotopic bladder cancer rat model.

PubMed

Falke, Johannes; Hulsbergen-van de Kaa, Christina A; Maj, Roberto; Oosterwijk, Egbert; Witjes, J Alfred

2018-05-16

TMX-101 and TMX-202 are formulations of toll-like receptor 7 (TLR-7) agonists, under investigation for the treatment of urothelial carcinoma. Our goal was to evaluate the efficacy of intravesical instillations of TMX-101 or TMX-202 in an orthotopic bladder cancer rat model. Four groups of 14 rats received an instillation with isogenic AY-27 tumor cells on day 0, starting tumor development. On day 2 and 5, the rats were treated with an intravesical instillation of TMX-101 0.1%, TMX-202 0.38%, vehicle solution or NaCl. On day 12 the rats were sacrificed and the bladders were evaluated histopathologically. No signs of toxicity were seen. The number of tumor-positive rats was 11 of 14 (79%) in the vehicle control group and in the NaCl control group, versus 9 of 14 (64%) in the TMX-101-treated group, and 8 of 14 (57%) in the TMX-20-treated group. The difference between tumor-bearing rats in the treated and control groups was not significant (p = 0.12). Bladder weight was significantly lower for TMX-202-treated rats compared to vehicle (p = 0.005). TMX-101 and TMX-202 are TLR-7 agonists with antitumor activity. Treatment with TMX-101 and TMX-202 resulted in less tumor-bearing rats compared to vehicle or saline control groups, although not statistically significant. In this aggressive bladder cancer model, a lower number of tumor-positive rats after treatment with TLR-7 agonists indicates activity for the treatment of non-muscle invasive bladder cancer.

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.

Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

PubMed

Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

2017-12-01

With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

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

Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, bradykinin and angiotensin in guinea pig, hamster and rat urinary bladders.

PubMed

Rouissi, N; Nantel, F; Drapeau, G; Rhaleb, N E; Dion, S; Regoli, D

1990-01-01

Neurokinins, bradykinin and angiotensins were tested in isolated urinary bladder of the guinea pig, the hamster and the rat, in the absence and in presence of a variety of peptidase inhibitors in order to establish if peptide degradation interferes with the bladder contractions elicited by the three types of peptides. Indeed, the effects of neurokinins, bradykinin and angiotensin I in the guinea pig bladder were significantly enhanced by captopril (4.6 x 10(-6) mol/l), chymostatin (1 mg/l), phosphoramidon (4.6 x 10(-6) mol/l) and thiorphan (1.0 x 10(-6) mol/l), while only captopril was found to potentiate the effects of the same peptides in the rat bladder. The four peptidase inhibitors, as well as bacitracin were found to modify the responses of the hamster urinary bladder to one or another or to all three groups of peptides and to DiMeC7. The present results suggest that the urinary bladders of various species have different types of active proteolytic enzymes: only the angiotensin-converting enzyme appears to be present in the rat bladder, while the same enzyme and possibly two additional endopeptidases interfere with the myotropic effects of neurokinins, kinins and angiotensins in the guinea pig and the hamster bladder.

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.

Neuromodulation in a rat model of the bladder micturition reflex

PubMed Central

Nickles, Angela; Nelson, Dwight E.

2012-01-01

A rat model of bladder reflex contraction (BRC) was used to determine the optimal frequency and intensity of spinal nerve (SN) stimulation to produce neuromodulation of bladder activity and to assess the therapeutic mechanisms of this neuromodulation. In anesthetized female rats (urethane 1.2 g/kg ip), a wire electrode was used to produce bilateral stimulation of the L6 SN. A cannula was placed into the bladder via the urethra, and the urethra was ligated to ensure an isovolumetric bladder. Saline infusion induced BRC. Electrical stimulation of the SN produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. Ten-herz stimulation produced maximal inhibition; lower and higher stimulation frequency produced less attenuation of BRC. Attenuation of bladder contraction frequency was directly proportional to the current intensity. At 10 Hz, stimulation using motor threshold pulses (Tmot) produced a delayed inhibition of the frequency of bladder contractions to 34 ± 11% of control. Maximal bladder inhibition appeared at 10 min poststimulation. High current intensity at 0.6 mA (∼6 * Tmot) abolished bladder contraction during stimulation, and the inhibition was sustained for 10 min poststimulation (prolonged inhibition). Furthermore, in rats pretreated with capsaicin (125 mg/kg sc), stimulation produced a stronger inhibition of BRC. The inhibitory effects on bladder contraction may be mediated by both afferent and efferent mechanisms. Lower intensities of stimulation may activate large, fast-conducting fibers and actions through the afferent limb of the micturition reflex arc in SN neuromodulation. Higher intensities may additionally act through the efferent limb. PMID:22049401

Biomarkers in lower urinary tract symptoms/overactive bladder: a critical overview.

PubMed

Antunes-Lopes, Tiago; Cruz, Célia D; Cruz, Francisco; Sievert, Karl D

2014-07-01

Biomarkers constitute objectively measurable characteristics that can be evaluated as indicators of physiological and pathogenic processes and might be used as diagnostic, prognostic or predictive tools in clinical care. This review examines the availability of biomarkers to treat the dynamic and complex symptoms of overactive bladder (OAB). OAB biomarkers may contribute to reveal the origin of storage symptoms in otherwise healthy individuals. The research encompassing the changes that occur in the bladder or in the peripheral (and central) nervous system might be determined through blood or urinary molecules (neurotrophins, ATP, prostaglandins, C-reactive protein and cytokines) or the measurement of events occurring in the bladder wall (bladder wall or detrusor wall thickness, oxyhemoglobin and deoxyhemoglobin concentration). These biomarkers might contribute to a better understanding of the pathophysiologic mechanisms underlying OAB. The word biomarker to name all the parameters described above, from bladder wall thickness to urinary molecules, has been introduced to call the attention to a field wherein objective noninvasive parameters were nonexistent. OAB treatment based on a biomarker, in comparison to the treatment based on a diagnosis made from a careful history and exclusion of urinary tract infection, is not supported by current literature.

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

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.

Effects of shielded or unshielded laser and electrohydraulic lithotripsy on rabbit bladder.

PubMed

Bhatta, K M; Rosen, D I; Flotte, T J; Dretler, S P; Nishioka, N S

1990-04-01

The pulsed dye laser and electrohydraulic lithotriptor (EHL) are both effective devices for fragmenting urinary and biliary calculi. Both fragment stones by producing a plasma-mediated shockwave. Recently, a plasma shield consisting of a hollow spring and a metal end cap has been described for use with the laser and EHL devices in an attempt to minimize tissue damage without adversely affecting stone fragmentation rates. The tissue effects produced by a pulsed dye laser and an EHL device with and without plasma shields were examined and compared using rabbit urinary bladders. If blood was present, the unshielded laser perforated the bladder wall in two pulses. However, in the absence of blood, over 100 pulses were needed for the laser to perforate the bladder. A mean of six pulses were required to perforate the bladder wall with a shielded laser. The unshielded EHL perforated the bladder wall in two pulses, whereas, the shielded EHL required a mean of 35 pulses. Microscopically, areas of exposure revealed hemorrhage and tissue ablation. We conclude that all devices examined can produce significant tissue damage when discharged directly onto bladder epithelium.

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

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

Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder.

PubMed

Downie, J W; Armour, J A

1992-11-01

The relationship between vesical mechanoreceptor field dimensions and afferent nerve activity recorded in pelvic plexus nerve filaments was examined in chloralose-anesthetized cats. Orthogonal receptor field dimensions were monitored with piezoelectric ultrasonic crystals. Reflexly generated bladder contractile activity made measurements difficult, therefore data were collected from cats subjected to actual sacral rhizotomy. Afferent activity was episodic and was initiated at different pressure and receptor field dimension thresholds. Maximum afferent activity did not correlate with maximum volume or pressure. Furthermore, activity was not linearly related to intravesical pressure, receptor field dimensions, or calculated wall tension. Pressure-length hysteresis of the receptor fields occurred. The responses of identified afferent units and their associated receptor field dimensions to brief contractions elicited by the ganglion stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (2.5-20 micrograms i.a.), studied under constant volume or constant pressure conditions, are compatible with bladder mechanoreceptors behaving as tension receptors. Because activity generated by bladder mechanoreceptors did not correlate in a simple fashion with intravesical pressure or receptor field dimensions, it is concluded that such receptors are influenced by the viscoelastic properties of the bladder wall. Furthermore, as a result of the heterogeneity of the bladder wall, receptor field tension appears to offer a more precise relationship with the activity of bladder wall mechanoreceptors than does intravesical pressure.

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

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.

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

METABOLISM AND DNA ADDUCT FORMATION OF 2-ACETYLAMINOFLUORENE BY BLADDER EXPLANTS FROM HUMAN, DOG, MONKEY, HAMSTER AND RAT

EPA Science Inventory

It is concluded that bladder explants of the human, dog, monkey, hamster, and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF. Neither the overall binding of AAF to bladder DNA, nor the fo...

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.

Effects of Moderate Alcohol Intake in the Bladder of the Otsuka Long Evans Tokushima Fatty Diabetic Rats.

PubMed

Bae, Woong Jin; Choi, Yong Sun; Kim, Su Jin; Cho, Hyuk Jin; Hong, Sung Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Kim, Dai Jin; Lee, Ji Youl

2015-09-01

Diabetes is related with a number of cystopathic complications. However, there have been no studies about the influence of alcohol consumption in the bladder of type 2 diabetes. Thus, we investigated the effect of moderate alcohol intake in the bladder of the Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rat. The non-diabetic Long-Evans Tokushima Otsuka (LETO, n=14) and the OLETF control group (n=14) were fed an isocaloric diet; the LETO (n=14) and the OLETF ethanol group (n=14) were fed 36% ethanol 7 g/kg/day. After ten weeks, muscarinic receptors, RhoGEFs, myogenic change, and the level of oxidative stress were evaluated. Moderate alcohol intake significantly decreased excessive muscarinic receptor and Rho kinase expressions in the OLETF rats compared with the LETO rats. In addition, iNOS and collagen expression were not changed in the OLETF rats in spite of alcohol consumption. Superoxide dismutase levels, which is involved in antioxidant defense, in the LETO rats were significantly decreased after alcohol consumption, however those in the OLETF rats were similar. Moderate alcohol consumption reduces the oxidative stress, and may prevent molecular and pathologic changes of the bladder of rats with type 2 diabetes.

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

Autonomic innervation of the muscles in the wall of the bladder and proximal urethra of male rats.

PubMed Central

Watanabe, H; Yamamoto, T Y

1979-01-01

The muscular coat of the body of the rat bladder is innervated almost exclusively by cholinergic endings:adrenergic endings are rare. In the inner longitudinal muscle layer of the proximal urethra, 53% of 310 autonomic nerve endings observed in close relation to the smooth muscle cells were adrenergic and the remaining 47% cholinergic. The middle circular muscle layer of the proximal urethra was innervated predominantly by adrenergic endings: in this layer 86% of the total of 335 endings examined wre regarded as adrenergic. A similar predominantly adrenergic innervation was noted in the outer longitudinal layer of the proximal urethra. A number of striated muscle fibres arose from the outermost striated muscle layer of the proximal urethra and intruded deeply into the outer and middle smooth muscle layers. These intruding striated muscle fibres also received direct autonomic (mostly adrenergic) innervation. The significance of these findings in relation to the physiology of the lower urinary tracts is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:489473

Hemangiopericytoma arising from the wall of the urinary bladder.

PubMed

Kibar, Y; Uzar, A I; Erdemir, F; Ozcan, A; Coban, H; Seckin, B

2006-01-01

Hemangiopericytoma (HPC) arising from within the urinary bladder is exceptionally rare. A 45-year-old man having the symptoms of left groin pain, vague suprapubic discomfort and frequency was admitted to our clinic. Pelvic tomography revealed a tumor in the bladder wall measuring 4 x 3 cm and was not clearly distinct from the lower abdominal wall. Partial cystectomy was performed and the histopathological examination confirmed the hemangiopericytoma. Three thousand rad exterior beam irradiation was performed after operation. Partial cystectomy and adjuvant radiotherapy may be a simple and effective alternative operation for the patient with HPC.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

PubMed

Zvara, P; Sahi, S; Hassouna, M M

1998-08-01

To develop an animal model to examine the pathophysiology by which S3 sacral root electrostimulation alters the micturition reflex in patients with bladder hyper-reflexia. Chronic sacral nerve root electrostimulation was applied to spinally transected rats; 21 animals were divided into four groups. The spinal cord was completely transected at the T10-11 level and stainless-steel electrodes implanted into the sacral foramen in 17 animals; these animals were subsequently divided into two groups (1 and 2). Six rats in group 1 underwent sacral root elctrostimulation for 2 h/day and five in group 2 for 6 h/day, for 21 days. The sham group (group 3, six rats) received no stimulation and four rats were used as healthy controls (group 4). Voiding frequency was recorded and each animal was evaluated cystometrically at the end of the stimulation period. The results were compared with the sham and control groups. Spinal cord transection resulted in bladder areflexia and complete urinary retention; 7-9 days after the injury, the bladder recovered its activity. Twenty-one days after transection all animals had evidence of uninhibited bladder contractions. The mean (SD) hourly frequency of urination was 0.66 (0.18) in healthy controls, 0.83 (0.21) in group 1, 0.87 (0.34) in group 2 and 1.1 (0.31) in group 3. There was a significant decrease in eh cystometric signs of bladder hyper-reflexia in groups 1 and 2 when compared with group 3. This work reports and initial study showing that chronic electrostimulation of sacral nerve roots can reduce the signs of bladder hyper-reflexia in the spinally injured rat. To our knowledge, this is the first report describing the rat as an animal model to determine the effects of chronic electrostimulation on the micturition reflex.

Inhibitory effects of silodosin on the bladder mechanosensitive afferent activities and their relation with bladder myogenic contractions in male rats with bladder outlet obstruction.

PubMed

Aizawa, Naoki; Watanabe, Daiji; Fukuhara, Hiroshi; Fujimura, Tetsuya; Kume, Haruki; Homma, Yukio; Igawa, Yasuhiko

2018-03-06

We investigated the effects of silodosin, an α1A-adrenoceptor (AR) antagonist, on bladder function, especially on non-voiding contractions (NVCs), in a male rat model of bladder outlet obstruction (BOO) by evaluating cystometry (CMG) findings and bladder mechanosensitive single-unit afferent activities (SAAs), related with microcontractions, which may be similar with NVCs and to be of myogenic origin, in the rat model. BOO was created by partial ligation of the posterior urethra. At 4 days after surgery for BOO, an osmotic pump filled with silodosin (0.12 mg/kg/day) or its vehicle was subcutaneously implanted. At 10 days after surgery, CMG and SAAs measurements were taken under conscious and urethane-anesthetized conditions, respectively. The SAAs of Aδ- and C-fibers, which were identified by electrical stimulation of the pelvic nerve and by bladder distention, and intravesical pressure were recorded during constant bladder-filling with saline. Microcontractions were divided into three phases: "ascending," "descending," and "stationary." The silodosin-treated group showed a smaller number of NVCs in CMG measurements and lower SAAs of both Aδ- and C-fibers than the vehicle-treated group during bladder-filling. Moreover, in the vehicle-treated groups, the SAAs of both fibers for the ascending phase of microcontractions were significantly higher than those for the other two phases. On the contrary, no significant change was found between any of these three phases in the silodosin-treated group. The present results suggest that silodosin inhibits the SAAs of mechanosensitive Aδ- and C-fibers at least partly due to suppressing myogenic bladder contractions in male BOO rats. © 2018 Wiley Periodicals, Inc.

Tadalafil attenuates hypotonicity-induced Ca2+ influx via TRPV2 and TRPV4 in primary rat bladder urothelial cell cultures.

PubMed

Dong, Xiao; Nakagomi, Hiroshi; Miyamoto, Tatsuya; Ihara, Tatsuya; Kira, Satoru; Sawada, Norifumi; Mitsui, Takahiko; Takeda, Masayuki

2018-03-22

To investigate the localization of phosphodiesterase 5 (PDE5) and the molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in signal transduction in the bladder urothelium. PDE5 expression in rat bladder tissues and cultured primary rat bladder urothelial cells was evaluated using immunochemistry and western blot assays. Ca 2+ influx in cells exposed to isotonic solution, hypotonic solution, a selective transient receptor potential vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10 µM tadalafil was evaluated using calcium imaging techniques. We also evaluated stretch-induced changes in ATP concentration in the mouse bladder in the presence or absence of 100 µM tadalafil. Immunochemistry and western blot analyses demonstrated that PDE5 is abundantly expressed in the bladder urothelium and in primary rat urothelial cells. Ca 2+ influx induced by hypotonic stimulation, GSK1016790A, or cannabidiol was significantly inhibited by tadalafil, whereas ATP-induced Ca 2+ influx was unaffected by tadalafil. PIP2 did not induce Ca2+ influx. ATP release in tadalafil-pretreated bladders significantly decreased compared to control bladders. Tadalafil attenuates Ca 2+ influx via TRPV4 and TRPV2, and inhibits ATP release in the bladder urothelium. These findings indicate that tadalafil functions as an inhibitor of urothelial signal transduction. © 2018 Wiley Periodicals, Inc.

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.

Transcutaneous electrical nerve stimulation (TENS) improves the diabetic cytopathy (DCP) via up-regulation of CGRP and cAMP.

PubMed

Ding, Liucheng; Song, Tao; Yi, Chaoran; Huang, Yi; Yu, Wen; Ling, Lin; Dai, Yutian; Wei, Zhongqing

2013-01-01

The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS) on the diabetic cytopathy (DCP) in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM)/TENS group (n=15), DM group (n=15) and control group (n=15). The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min) for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP) was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG) in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.

Spontaneous puerperal extraperitoneal bladder wall rupture in young woman with diagnostic dilemma

PubMed Central

Sabat, Debabrat Kumar; Panigrahi, Pradeep Kumar; Sahoo, Ranjan Kumar; Acharya, Mousumi; Sahu, Mahesh Ch

2015-01-01

A young female presented with an acute abdominal pain and oliguria for 1 week following normal vaginal delivery. No history of hematuria was present. Patient was having lochia rubra. Sealed uterine rupture was suspected clinically. Initial ultrasound of the patient showed distended urinary bladder containing Foley catheter ballon with clamping of Foley catheter and particulate ascites. Abdominal paracentesis revealed hemorrhagic fluid. Contrast-enhanced computed tomography of abdomen revealed ascites, distended urinary bladder and no extraluminal contrast extravasation in delayed scan. As patient condition deteriorated, repeat ultrasound guided abdominal paracentesis was done which revealed transudative peritoneal collection with distended bladder. Cystoscopy revealed urinary bladder ruptures with exudate sealing the rupture site. Exploratory laparotomy was done and a diagnosis of extraperitoneal bladder rupture was confirmed. The rent was repaired in layers. She was put on continuous bladder drainage for 3 weeks followed by bladder training. It presented in a unique way as there was hemorrhagic peritoneal tap, no macroscopic hematuria and urinary bladder was distended in spite of urinary bladder wall rupture which delayed the diagnosis and treatment. Complete emptying of urinary bladder before second stage of labor and during postpartum period with perineal repair is mandatory to prevent urinary bladder rupture. PMID:26985426

Spontaneous puerperal extraperitoneal bladder wall rupture in young woman with diagnostic dilemma.

PubMed

Sabat, Debabrat Kumar; Panigrahi, Pradeep Kumar; Sahoo, Ranjan Kumar; Acharya, Mousumi; Sahu, Mahesh Ch

2015-01-01

A young female presented with an acute abdominal pain and oliguria for 1 week following normal vaginal delivery. No history of hematuria was present. Patient was having lochia rubra. Sealed uterine rupture was suspected clinically. Initial ultrasound of the patient showed distended urinary bladder containing Foley catheter ballon with clamping of Foley catheter and particulate ascites. Abdominal paracentesis revealed hemorrhagic fluid. Contrast-enhanced computed tomography of abdomen revealed ascites, distended urinary bladder and no extraluminal contrast extravasation in delayed scan. As patient condition deteriorated, repeat ultrasound guided abdominal paracentesis was done which revealed transudative peritoneal collection with distended bladder. Cystoscopy revealed urinary bladder ruptures with exudate sealing the rupture site. Exploratory laparotomy was done and a diagnosis of extraperitoneal bladder rupture was confirmed. The rent was repaired in layers. She was put on continuous bladder drainage for 3 weeks followed by bladder training. It presented in a unique way as there was hemorrhagic peritoneal tap, no macroscopic hematuria and urinary bladder was distended in spite of urinary bladder wall rupture which delayed the diagnosis and treatment. Complete emptying of urinary bladder before second stage of labor and during postpartum period with perineal repair is mandatory to prevent urinary bladder rupture.

Evaluation of two techniques of partial urethral obstruction in the male rat model of bladder outlet obstruction.

PubMed

Melman, Arnold; Tar, Moses; Boczko, Judd; Christ, George; Leung, Albert C; Zhao, Weixin; Russell, Robert G

2005-11-01

To perform a comparison to determine which of two methods of partial urethral ligation produces the most consistent outcome and fewest side effects. Such a study has not been previously reported. Partial urethral ligation is a means of causing reproducible bladder outlet obstruction. In the male rat model, partial urethral obstruction can be performed either by perineal incision and bulbous urethral ligation or retropubic incision and midprostatic obstruction. Fifteen male Sprague-Dawley rats were studied. Five were selected for bulbous urethral obstruction through a perineal incision, five for midprostatic obstruction using a retropubic approach, and five for a sham operation through a perineal incision. The operative time was shorter and morbidity lower with the perineal approach compared with the retropubic approach. Inflammation or infection, or both, were seen in the prostate, bladder, proximal urethra, ureters, and kidneys in the rats in which a midprostatic obstruction was performed. The proximal urethra and prostate were mildly inflamed in those rats that underwent bulbous obstruction. Sham-operated rats exhibited mild prostatitis only. The perineal approach to the bulbous urethra is the method of choice for creating a partial urethral obstruction model of bladder outlet obstruction in the male rat.

Significance of Random Bladder Biopsies in Non-Muscle Invasive Bladder Cancer

PubMed Central

Kumano, Masafumi; Miyake, Hideaki; Nakano, Yuzo; Fujisawa, Masato

2013-01-01

Background/Aims To evaluate retrospectively the clinical outcome of random bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC) undergoing transurethral resection (TUR). Patients and Method This study included 234 consecutive patients with NMIBC who underwent random biopsies from normal-appearing urothelium of the bladder, including the anterior wall, posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra, during TUR. Result Thirty-seven patients (15.8%) were diagnosed by random biopsies as having urothelial cancer. Among several factors available prior to TUR, preoperative urinary cytology appeared to be independently related to the detection of urothelial cancer in random biopsies on multivariate analysis. Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8% positive predictive value and 89.3% negative predictive value for predicting the findings of the random biopsies. Conclusion Biopsies of normal-appearing urothelium resulted in the additional detection of urothelial cancer in a definite proportion of NMIBC patients, and it remains difficult to find a reliable alternative to random biopsies. Collectively, these findings suggest that it would be beneficial to perform random biopsies as part of the routine management of NMIBC. PMID:24917759

Fenoterol functionally activates the β₃-adrenoceptor in human urinary bladder, comparison with rat and mouse: implications for drug discovery.

PubMed

Palea, Stefano; Rekik, Moèz; Rouget, Céline; Camparo, Philippe; Botto, Henri; Rischmann, Pascal; Lluel, Philippe; Westfall, Timothy D

2012-09-05

Fenoterol has been reported to be a potent and selective β(2)-adrenoceptor agonist and is currently used clinically to treat asthma. Electrical field stimulation (EFS) of isolated urinary bladder mimics the voiding contraction by stimulating parasympathetic nerves, resulting in neurogenic contractions. To determine if stimulation of β(2)-adrenoceptors can inhibit this response, fenoterol was tested against EFS-induced contractions in human isolated urinary bladder and compared with mouse and rat. Bladder strips were mounted in organ baths and reproducible contractions induced by EFS. Fenoterol was added cumulatively in the presence of the β(2)-adrenoceptor antagonist ICI118551 or the β(3)-adrenoceptor antagonist L-748337. Fenoterol inhibited neurogenic contractions in all three species in a concentration-dependent manner with pEC(50) values of 6.66 ± 0.11, 6.86 ± 0.06 and 5.71 ± 0.1 in human, mouse and rat respectively. In human bladder strips ICI118551 (100 nM) did not affect responses to fenoterol, while L-748337 (0.3-3 μM) produced rightward shifts of the concentration-response curves with a pA(2) value of 8.10. In mouse bladder strips ICI118551 (30 nM) blocked the inhibitory effect of fenoterol (pA(2)=8.80), while L-748337 (10 μM) inhibited the response with a pA(2) of 5.79. In rat bladder ICI118551 (30 nM) was without effect, while L-748,337 (10 μM) inhibited the response to fenoterol with a pA(2) of 5.40. From these results it is clear that fenoterol potently activates β(3)-adrenoceptors in human isolated urinary bladder to inhibit EFS-induced contractions. Fenoterol also activates β(3)-adrenoceptors in rat, but β(2)-adrenoceptors in mouse bladder to inhibit EFS-induced contractions. Copyright © 2012 Elsevier B.V. All rights reserved.

Muscarinic receptor subtypes involved in urothelium-derived relaxatory effects in the inflamed rat urinary bladder.

PubMed

Andersson, M; Aronsson, P; Doufish, D; Lampert, A; Tobin, G

2012-09-25

Functional studies have shown altered cholinergic mechanisms in the inflamed bladder, which partly depend on muscarinic receptor-induced release of nitric oxide (NO). The current study aimed to characterize which muscarinic receptor subtypes that are involved in the regulation of the nitrergic effects in the bladder cholinergic response during cystitis. For this purpose, in vitro examinations of carbachol-evoked contractions of inflamed and normal bladder preparations were performed. The effects of antagonists with different selectivity for the receptor subtypes were assessed on intact and urothelium-denuded bladder preparations. In preparations from cyclophosphamide (CYP; in order to induce cystitis) pre-treated rats, the response to carbachol was about 75% of that of normal preparations. Removal of the urothelium or administration of a nitric oxide synthase inhibitor re-established the responses in the inflamed preparations. Administration of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) inhibited the carbachol-induced contractile responses of preparations from CYP pre-treated rats less potently than controls. Pirenzepine and p-fluoro-hexahydro-sila-diphenidol (pFHHSiD) affected the carbachol-induced contractile responses to similar extents in preparations of CYP pre-treated and control rats. However, the Schild slopes for the three antagonists were all significantly different from unity in the preparations from CYP pre-treated rats. Again, L-NNA or removal of the urothelium eliminated any difference compared to normal preparations. This study confirms that muscarinic receptor stimulation in the inflamed rat urinary bladder induces urothelial release of NO, which counteracts detrusor contraction. Copyright © 2012 Elsevier B.V. All rights reserved.

Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

PubMed

Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

2014-01-01

Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.

Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

PubMed

Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

2015-11-01

Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women. Copyright © 2013 John Wiley & Sons, Ltd.

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

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

PubMed

Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

2016-11-01

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA V ) is a major urinary metabolite of sodium arsenite (iAs III ) and induces urinary bladder cancers in rats. DMA V and iAs III are negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMA V and iAs III in rat urinary bladder epithelium and liver using gpt delta F344 rats. Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0, 92mg/L DMA V , or 87mg/L iAs III (each 50mg/L As) for 13weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations are identified in the red/gam genes by Spi - selection (Spi - assay). Results of the gpt and Spi - assays showed that DMA V and iAs III had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMA V and iAs III are not mutagenic in urinary bladder epithelium or liver in rats. Copyright © 2016. Published by Elsevier B.V.

A microangiographic study of the effect of hyperthermia on the rabbit bladder

NASA Technical Reports Server (NTRS)

Hietala, S. O.; Howells, R.; Hazra, I. A.

1978-01-01

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury

PubMed Central

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

2011-01-01

The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T9–T10 spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine. The endpoints of the study were: (1) percent NANC contraction that was unmasked by the muscarinic antagonist 4-DAMP, and (2) P2X purinergic contraction that was evoked by α,β–methylene ATP. NANC contraction accounted for 78.5% of the neurally evoked contraction in SCI bladders. When SCI bladder strips were treated with carbachol (10 µM) prior to 4-DAMP (500 nM), the percent NANC contraction decreased dramatically to only 13.1% of the neurally evoked contraction (p=0.041). This was accompanied by a substantial decrease in α,β–methylene ATP evoked P2X contraction, and desensitization of purinergic receptors (the ratio of subsequent over initial P2X contraction decreased from 97.2% to 42.1%, p=0.0017). Sequential activation of the cholinergic receptors with carbachol (or with muscarine in neurally intact bladders) and unmasking of the NANC response with 4-DAMP switched the neurally evoked bladder contraction from predominantly NANC to predominantly cholinergic. We conclude that activation of muscarinic receptors (with carbachol or muscarine) blocks NANC and purinergic contractions in neurally intact or in SCI rat bladders. The carbachol-induced inhibition of the NANC contraction is expressed more in SCI bladders compared to neurally intact bladders. Along with receptor plasticity, this change in bladder function may involve P2X-independent mechanisms. PMID:21689735

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.

Wall structure and material properties cause viscous damping of swimbladder sounds in the oyster toadfish Opsanus tau

PubMed Central

King, Terrence L.; Ali, Heba; Sidker, Nehan; Cameron, Timothy M.

2016-01-01

Despite rapid damping, fish swimbladders have been modelled as underwater resonant bubbles. Recent data suggest that swimbladders of sound-producing fishes use a forced rather than a resonant response to produce sound. The reason for this discrepancy has not been formally addressed, and we demonstrate, for the first time, that the structure of the swimbladder wall will affect vibratory behaviour. Using the oyster toadfish Opsanus tau, we find regional differences in bladder thickness, directionality of collagen layers (anisotropic bladder wall structure), material properties that differ between circular and longitudinal directions (stress, strain and Young's modulus), high water content (80%) of the bladder wall and a 300-fold increase in the modulus of dried tissue. Therefore, the swimbladder wall is a viscoelastic structure that serves to damp vibrations and impart directionality, preventing the expression of resonance. PMID:27798293

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

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

Effect of Dietary Treatment with Dimethylarsinous Acid (DMAIII) on the Urinary Bladder Epithelium of Arsenic (+3 Oxidation State) Methyltransferase (As3mt) Knockout and C57BL/6 Wild Type Female Mice

EPA Science Inventory

Abstract Chronic exposure to inorganic arsenic (iAs) is carcinogenic to the human urinary bladder. It produces urothelial cytotoxicity and proliferation in rats and mice. DMAv, a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the...

[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.

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

Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.

PubMed

Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk

2014-04-01

The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.

Water avoidance stress induces frequency through cyclooxygenase-2 expression: a bladder rat model.

PubMed

Yamamoto, Keisuke; Takao, Tetsuya; Nakayama, Jiro; Kiuchi, Hiroshi; Okuda, Hidenobu; Fukuhara, Shinichiro; Yoshioka, Iwao; Matsuoka, Yasuhiro; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

2012-02-01

Water avoidance stress is a potent psychological stressor and it is associated with visceral hyperalgesia, which shows degeneration of the urothelial layer mimicking interstitial cystitis. Cyclooxygenase-2 inhibitors have been recognized to ameliorate frequency both in clinical and experimental settings. We investigated the voiding pattern and cyclooxygenase-2 expression in a rat bladder model of water avoidance stress. After being subjected to water avoidance stress or a sham procedure, rats underwent metabolic cage analysis and cystometrography. Real time reverse transcription polymerase chain reaction was carried out to examine cyclooxygenase-2 messenger ribonucleic acid in bladders of rats. Protein expression of cyclooxygenase-2 was analyzed with immunohistochemistry and western blotting. Furthermore, the effects of the cyclooxygenase-2 inhibitor, etodolac, were investigated by carrying out cystometrography, immunohistochemistry and western blotting. Metabolic cage analysis and cystometrography showed significantly shorter intervals and less volume of voiding in water avoidance stress rats. Significantly higher expression of cyclooxygenase-2 messenger ribonucleic acid was verified by reverse transcription polymerase chain reaction. Immunohistochemistry and western blotting showed significantly higher cyclooxygenase-2 protein levels in water avoidance stress bladders. Furthermore, immunohistochemistry showed high cyclooxygenase-2 expression exclusively in smooth muscle cells. All water avoidance stress-induced changes were reduced by cyclooxygenase-2 inhibitor pretreatment. Chronic stress might cause frequency through cyclooxygenase-2 gene upregulation in bladder smooth muscle cells. Further study of cyclooxygenase-2 in the water avoidance stress bladder might provide novel therapeutic modalities for interstitial cystitis. © 2011 The Japanese Urological Association.

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

PubMed

Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

2011-01-01

Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

Distribution of cocaine and amphetamine regulated transcript in ureters and urinary bladder of hypertensive rats.

PubMed

Janiuk, I; Kasacka, I

2013-01-01

Cocaine and amphetamine regulated transcript (CART), a neuropeptide of the central and peripheral nervous system plays an essential role in maintaining body homeostasis by regulating body temperature, orexia, digestive motility and blood pressure. Very few studies describe the relationship of hyperten¬sion with CART. Therefore, the present research was undertaken to identify, locate and determine the number of CART-immunopositive neuroendocrine cells (NE) and structures in the urinary bladder and ureter of rats with experimentally induced nephrogenic hypertension. The experiments were conducted on 20 Wistar rats in which hypertension was experimentally induced by applying a clamp on the left renal artery based on the two kidney, one clip experimental model (2K1C). After 6 weeks, fragments of the ureters and urinary bladder were sampled from rats with permanent hypertension. Immunohisto¬chemical analyses revealed a salient effect of renovascular hypertension on the neuroendocrine system of rat ureters and urinary bladder. Differences in the number of neuroendocrine cells and in the density of CART-positive structures were identified between the hypertensive and normotensive (control) rats. Hypertension greatly increased the number of NE cells and the density of CART- immunoreactive (IR) structures in the analysed urinary system organs.

The inhibitory effect of vitamin E on cigarette smoke-induced oxidative damage to the rat urothelium: can it prevent transitional cell carcinoma?

PubMed

Onol, Fikret Fatih; Demir, Aslan; Temiz, Yusuf; Yüksel, Meral; Eren, Funda; Türkeri, Levent N

2007-01-01

We aimed to detect reactive oxygen species (ROS) and assess subsequent carcinogenesis in terms of cellular proliferation in the bladder and kidney epithelial tissues of rats exposed to cigarette smoke (CS), and to investigate the changes following vitamin E treatment. Twenty-four male Sprague-Dawley rats were divided into 3 groups: group 1 was kept intact; group 2 was subjected to CS exposure for 8 weeks, and group 3 received intraperitoneal vitamin E injections (200 mg/kg/week) for 8 weeks in addition to CS exposure. Histological examination and Ki67 antigen expression measurements were made from bladder and renal pelvic tissue sections. Luminol-amplified chemiluminescence was used to measure ROS levels. All results were compared using a one-way ANOVA test. In CS-exposed rats, light microscopy of renal and bladder tissues revealed nonspecific epithelial changes; however, Ki67 expression was significantly increased in bladder tissues compared to other groups (17.5 +/- 4.7, 35 +/- 2.9 and 18.7 +/- 5.1% in groups 1, 2 and 3, respectively, p < 0.05). Chemiluminescence levels in bladder and renal tissues were also significantly higher in the CS-exposed animals (78.1 +/- 11.4, 148 +/- 13.3, 97.8 +/- 6.1 rlu/mg for the bladder, and 99.8 +/- 12.2, 176.1 +/- 27.9, 67.1 +/- 9 rlu/mg, for renal pelvic tissues, respectively, p < 0.05). Vitamin E can alleviate CS-induced oxidative damage in rat bladder and kidney epithelium suggesting a potential role for vitamin E in the prevention of CS-mediated carcinogenesis. 2007 S. Karger AG, Basel

The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder.

PubMed

Gevaert, Thomas; Ridder, Dirk De; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Aa, Frank Van Der; Pintelon, Isabel; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Neuhaus, Jochen

2017-06-01

The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT + ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody-related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin-1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT + cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT + ICC are present in bladder. In this perspective, functional concepts of KIT + ICC being involved in sensory and/or motor aspects of bladder physiology should be revised. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer

NASA Astrophysics Data System (ADS)

Virani, Needa A.; Davis, Carole; McKernan, Patrick; Hauser, Paul; Hurst, Robert E.; Slaton, Joel; Silvy, Ricardo P.; Resasco, Daniel E.; Harrison, Roger G.

2018-01-01

Bladder cancer has a 60%-70% recurrence rate most likely due to any residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0.1 mg SWCNT per kg body weight) followed 24 h later by a short 30 s treatment with a 360° near-infrared light that heats only the bound nanotubes. The energy density of the treatment was 50 J cm-2, and the power density that this treatment corresponds to is 1.7 W cm-2, which is relatively low. Nanotubes are specifically targeted to the tumour via the interaction of annexin V (AV) and phosphatidylserine, which is normally internalised on healthy tissue but externalised on tumours and the tumour vasculature. SWCNTs are conjugated to AV, which binds specifically to bladder cancer cells as confirmed in vitro and in vivo. Due to this specific localisation, NIR light can be used to heat the tumour while conserving the healthy bladder wall. In a short-term efficacy study in mice with orthotopic MB49 murine bladder tumours treated with the SWCNT-AV conjugate and NIR light, no tumours were visible on the bladder wall 24 h after NIR light treatment, and there was no damage to the bladder. In a separate survival study in mice with the same type of orthotopic tumours, there was a 50% cure rate at 116 days when the study was ended. At 116 days, no treatment toxicity was observed, and no nanotubes were detected in the clearance organs or bladder.

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.

Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis.

PubMed

Liang, Simin; Li, Jie; Gou, Xin; Chen, Daihui

2016-01-01

Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E-binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. © The Author(s) 2016.

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.

Evaluation of pressor and visceromotor reflex responses to bladder distension in urethane anesthetized rats.

PubMed

Blatt, Lauren K; Lashinger, Erin S R; Laping, Nicholas J; Su, Xin

2009-01-01

We tested cardiovascular and visceromotor reflex (VMR) responses to urinary bladder distension (UBD) in urethane anesthetized rats to see if it can replicate the response pattern and the inhibition of bladder nociceptive transmission by analgesics seen in isoflurane anesthetized animals. Female Sprague-Dawley rats under 3% isoflurane anesthesia were acutely instrumented with jugular venous, carotid arterial, and bladder cannulas for drug administration, blood pressure (BP) measurement, and bladder distension, respectively. Needle electrodes were placed directly into the abdominal musculature to measure myoelectrical activity subsequent to phasic UBD (30 sec in 3 min intervals). A cardiovascular response (pressor) and a VMR response (a contraction of abdominal and hind limb musculature) to UBD were evaluated in urethane (1.2 g/kg, i.v.) or isoflurane (1%) anesthetized rats. Pressor and VMR responses to noxious UBD (60 mmHg) were generated under both anesthesics. The thresholds of stimulus response functions for both pressor and VMR responses were not affected by either anesthesics. However, the magnitude of the maximal pressor response was significantly reduced in urethane anesthesia. The analgesics, morphine, and mexiletine, significantly inhibited the VMR response to noxious UBD under both anesthetics, but the intensities of the inhibition from both analgesics under urethane anesthesia were much lower than under isoflurane anesthesia (ID50: 2.07 mg/kg vs. 0.88 mg/kg for morphine, >10 mg/kg vs. 0.47 mg/kg for mexiletine). The rat urinary bladder distension model in urethane anesthetized rats demonstrates a blunted maximal pressor response and a reduced inhibition of visceral nociceptive transmission by analgesics. Neurourol. Urodynam. 28:442-446, 2009. (c) 2008 Wiley-Liss, Inc.

Bladder necrosis: 'A man without a bladder'.

PubMed

Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

2018-02-17

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intraperitoneally placed Foley catheter via verumontanum initially presenting as a bladder rupture.

PubMed

Raheem, Omer A; Jeong, Young Beom

2011-09-01

Since urethral Foley catheterization is usually easy and safe, serious complications related to this procedure have been rarely reported. Herein, we describe a case of intraperitoneally placed urethral catheter via verumontanum presenting as intraperitoneal bladder perforation in a chronically debilitated elderly patient. A 82-yr-old male patient was admitted with symptoms of hematuria, lower abdominal pain after traumatic Foley catheterization. The retrograde cystography showed findings of intraperitoneal bladder perforation, but emergency laparotomy with intraoperative urethrocystoscopy revealed a tunnel-like false passage extending from the verumontanum into the rectovesical pouch between the posterior wall of the bladder and the anterior wall of the rectum with no bladder injury. The patient was treated with simple closure of the perforated rectovesical pouch and a placement of suprapubic cystostomy tube.

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.

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

PubMed

Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

2014-01-01

Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

Impact of the radiotherapy technique on the correlation between dose-volume histograms of the bladder wall defined on MRI imaging and dose-volume/surface histograms in prostate cancer patients

NASA Astrophysics Data System (ADS)

Maggio, Angelo; Carillo, Viviana; Cozzarini, Cesare; Perna, Lucia; Rancati, Tiziana; Valdagni, Riccardo; Gabriele, Pietro; Fiorino, Claudio

2013-04-01

The aim of this study was to evaluate the correlation between the ‘true’ absolute and relative dose-volume histograms (DVHs) of the bladder wall, dose-wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose-surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose-volume/surface histogram. Correlation was quantified for selected dose-volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD < 5%): DVH5 showed the best agreement. The correlation was slightly better for absolute (R = 0.80-0.94) compared to relative (R = 0.66-0.92) histograms. The DSH was also found to be highly correlated with the DWH, although slightly higher deviations were generally found. The DVH was not a good surrogate of the DWH (R < 0.7 for most of parameters). When comparing the two treatment techniques, more pronounced differences between relative histograms were seen for IMRT with respect to 3DCRT (p < 0.0001).

New clinical trial open for patients with muscle-invasive bladder cancer | Center for Cancer Research

Cancer.gov

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which the tumor invades deep into the musculature of the bladder wall, making it more likely to spread to other parts of the body. Standard treatment involves cisplatin-based chemotherapy followed by radical cystectomy, which is surgery to remove the bladder and nearby organs. However, many patients

Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

PubMed Central

Nett, Jeniel E.; Brooks, Erin G.; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen

2014-01-01

Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract. PMID:25183731

Effect of glycine on recovery of bladder smooth muscle contractility after acute urinary retention in rats.

PubMed

Hong, Sung K; Son, Hwancheol; Kim, Soo W; Oh, Seung-June; Choi, Hwang

2005-12-01

To investigate the effects of glycine on the recovery of bladder smooth muscle contractility after acute urinary retention. Bladder overdistension was induced in Sprague-Dawley rats by an infusion of saline (twice the threshold volume), maintained for 2 h. From 15 min before emptying of the bladder until 2 h after, saline or glycine solution was infused i.v. At 30 min, 2 h and 1 week after bladder emptying, samples of bladder tissue were taken for muscle strip study, malondialdehyde (MDA) assay, ATP assay, Western blotting for apoptosis-related molecules (Bcl-2, Bax, Caspase-3), and histological analysis including terminal deoxynucleotidyl transferase-mediated nick-end labelling staining. The results were compared among normal control, saline-treated and glycine-treated rats. In the glycine-treated group, muscle strip contractile responses induced by electrical-field stimulation and carbachol were both significantly greater at 1 week after bladder emptying than in the saline-treated group. The results of the ATP assay appeared to correspond with those of the muscle strip study. The saline-treated group had significantly higher MDA levels at 30 min after bladder emptying than the glycine-treated group. At 2 h after bladder emptying, there was significantly more apoptosis and greater leukocyte infiltration in the saline-treated group than in the glycine-treated group. While pro-apoptotic Bax and caspase-3 were down-regulated, Bcl-2 was up-regulated in the glycine-treated group. Glycine infusions might improve the contractile responses of bladder smooth muscle after acute urinary retention by reducing oxidative damage and apoptosis.

Pharmacologic evaluation of pressor and visceromotor reflex responses to bladder distension.

PubMed

Su, Xin; Riedel, Erin S; Leon, Lisa A; Laping, Nicholas J

2008-01-01

Several mechanisms that are involved in acute rat bladder nociception were examined. The nociceptive response was measured by analyzing both cardiovascular and visceromotor reflex responses to urinary bladder distension. The contributions of micro-opioid receptor, kappa-opioid receptor, sodium channels, muscarinic receptors, and cyclooxygenase, were explored with morphine, U50,488, mexiletine, oxybutynin, and naproxen, respectively. Female Sprague-Dawley rats were acutely instrumented with jugular venous, carotid arterial, and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectrical activity subsequent to repeated phasic urinary bladder distension (60 mmHg for 20 sec in 3 min intervals) under 1% isoflurane. Drugs were administered by i.v. bolus injection 2 min prior to distension. The analgesics morphine (ID50 0.69 mg/kg), U50,488 (1.34 mg/kg), and mexiletine (2.60 mg/kg) significantly inhibited the visceromotor reflex response to noxious urinary bladder distension. Oxybutynin also attenuated reflex responses to noxious urinary bladder distension to 41% of the maximal pressor response and 32% of the control visceromotor reflex response (3.01 and 5.05 mg/kg), respectively, indicating a role of muscarinic receptors in bladder nociception. Naproxen did not attenuate the pressor response, but moderately inhibited visceromotor reflex to 45% of control at 30 mg/kg (P < 0.05). Current results using the rat urinary bladder distension model are consistent with previous research demonstrating a role of the analgesics (morphine, U50,488, and mexiletine) in the inhibition of visceral nociceptive transmission. The utility of the reflex responses to urinary bladder distension may provide a method useful to examine mechanisms which target the bladder sensory pathway. (c) 2007 Wiley-Liss, Inc.

Aldehyde dehydrogenase induction in arsenic-exposed rat bladder epithelium.

PubMed

Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin

2016-01-01

Arsenic is widely distributed in the environment. Many human cancers, including urothelial carcinoma (UC), show a dose-dependent relationship with arsenic exposure in the south-west coast of Taiwan (also known as the blackfoot disease (BFD) areas). However, the molecular mechanisms of arsenic-mediated UC carcinogenesis has not yet been defined. In vivo study, the rat bladder epithelium were exposed with arsenic for 48 h. The proteins were extracted from untreated and arsenic-treated rat bladder cells and utilized two-dimensional gel electrophoresis and mass spectrometry. Selected peptides were extracted from the gel and identified by quadrupole-time of flight (Q-TOF) Ultima-Micromass spectra. The significantly difference expression of proteins in arsenic-treated groups as compared with untreated groups was confirmed by immunohistochemistry (IHC) and western blotting. We found that thirteen proteins were down-regulated and nine proteins were up-regulated in arsenic-treated rat bladder cells when compared with untreated groups. The IHC and western blotting results confirmed that aldehyde dehydrogenase (ALDH) protein was up-regulated in arsenic-treated rat bladder epithelium. Expression of ALDH protein was significantly higher in UC patients from BFD areas than those from non-BFD areas using IHC (p=0.018). In conclusion, the ALDH protein expression could be used as molecular markers for arsenic-induced transformation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Quantitative elasticity measurement of urinary bladder wall using laser-induced surface acoustic waves.

PubMed

Li, Chunhui; Guan, Guangying; Zhang, Fan; Song, Shaozhen; Wang, Ruikang K; Huang, Zhihong; Nabi, Ghulam

2014-12-01

The maintenance of urinary bladder elasticity is essential to its functions, including the storage and voiding phases of the micturition cycle. The bladder stiffness can be changed by various pathophysiological conditions. Quantitative measurement of bladder elasticity is an essential step toward understanding various urinary bladder disease processes and improving patient care. As a nondestructive, and noncontact method, laser-induced surface acoustic waves (SAWs) can accurately characterize the elastic properties of different layers of organs such as the urinary bladder. This initial investigation evaluates the feasibility of a noncontact, all-optical method of generating and measuring the elasticity of the urinary bladder. Quantitative elasticity measurements of ex vivo porcine urinary bladder were made using the laser-induced SAW technique. A pulsed laser was used to excite SAWs that propagated on the bladder wall surface. A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system remotely recorded the SAWs, from which the elasticity properties of different layers of the bladder were estimated. During the experiments, series of measurements were performed under five precisely controlled bladder volumes using water to estimate changes in the elasticity in relation to various urinary bladder contents. The results, validated by optical coherence elastography, show that the laser-induced SAW technique combined with PhS-OCT can be a feasible method of quantitative estimation of biomechanical properties.

Recovery, growth and development of Macroorchis spinulosus in albino rats

PubMed Central

Woo, Ho-Chun; Chai, Jong-Yil

2003-01-01

The developmental features, growth and organogenesis of Macroorchis spinulosus were observed in albino rats. Globular and thick walled metacercariae, possessed a stylet, Y-shaped excretory bladder and extracecal testes. In albino rats, M. spinulosus showed habitat shifting. The majority of M. spinulosus reside in the jejunum for the first four days post infection (p.i.) and migrate to the duodenum at the later stage of infection. M. spinulosus grew rapidly during the first four days and reached full maturity at 14 days p.i. and later reduced in size. The ovary was separated from the genital primodium at one day p.i. The seminal vesicle appeared on the third day and divided into two sacs on the fourth day p.i. and intrauterine eggs and sperm mass were produced on the fourth day. Organogenesis and enlargement of reproductive organs governed the growth of M. spinulosus. The similarity of related species of the genus Macroorchis to M. spinulosus was discussed in consideration to developmental features. PMID:12666727

Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

PubMed

Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

2013-01-30

Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign prostatic hyperplasia may be due, in part, to the blockade of the 5-HT(2A) and 5-HT(2B) receptors in the bladder. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Hydrostatic pressure and muscarinic receptors are involved in the release of inflammatory cytokines in human bladder smooth muscle cells.

PubMed

Liang, Zhou; Xin, Wei; Qiang, Liu; Xiang, Cai; Bang-Hua, Liao; Jin, Yang; De-Yi, Luo; Hong, Li; Kun-Jie, Wang

2017-06-01

Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H 2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 μM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO. © 2016 Wiley Periodicals, Inc.

Muscarinic and alpha 1-adrenergic receptor binding characteristics of saw palmetto extract in rat lower urinary tract.

PubMed

Suzuki, Mayumi; Oki, Tomomi; Sugiyama, Tomomi; Umegaki, Keizo; Uchida, Shinya; Yamada, Shizuo

2007-06-01

To elucidate the in vitro and ex vivo effects of saw palmetto extract (SPE) on autonomic receptors in the rat lower urinary tract. The in vitro binding affinities for alpha 1-adrenergic, muscarinic, and purinergic receptors in the rat prostate and bladder were measured by radioligand binding assays. Rats received vehicle or SPE (0.6 to 60 mg/kg/day) orally for 4 weeks, and alpha 1-adrenergic and muscarinic receptor binding in tissues of these rats were measured. Saw palmetto extract inhibited specific binding of [3H]prazosin and [N-methyl-3H]scopolamine methyl chloride (NMS) but not alpha, beta-methylene adenosine triphosphate [2,8-(3)H]tetrasodium salt in the rat prostate and bladder. The binding activity of SPE for muscarinic receptors was four times greater than that for alpha 1-adrenergic receptors. Scatchard analysis revealed that SPE significantly reduced the maximal number of binding sites (Bmax) for each radioligand in the prostate and bladder under in vitro condition. Repeated oral administration of SPE to rats brought about significant alteration in Bmax for prostatic [3H]prazosin binding and for bladder [3H]NMS binding. Such alteration by SPE was selective to the receptors in the lower urinary tract. Saw palmetto extract exerts significant binding activity on autonomic receptors in the lower urinary tract under in vitro and in vivo conditions.

Biochemical and pathological changes in the male rat kidney and bladder following exposure to continuous 900-MHz electromagnetic field on postnatal days 22-59^.

PubMed

Türedi, Sibel; Kerimoğlu, Gökçen; Mercantepe, Tolga; Odacı, Ersan

2017-09-01

To investigate the effect on male rat kidney and bladder tissues of exposure to 900-megahertz (MHz) electromagnetic field (EMF) applied on postnatal days 22-59, inclusive. Twenty-four male Sprague Dawley rats, aged 21 days, were used. These were divided equally into one of three groups, control (CG), sham (SG) or EMF (EMFG). CG was not exposed to any procedure. SG rats were kept inside a cage, without being exposed to the effect of EMF, for 1 h a day on postnatal days 22-59, inclusive. EMFG rats were exposed to continuous 900-MHz EMF for 1 h a day under the same conditions as those for the SG rats. Rats were sacrificed on postnatal day 60, and the kidney and bladder tissues were removed. Tissues were stained with hematoxylin and eosin (H&E) and Masson trichrome for histomorphological evaluation. The TUNEL method was used to assess apoptosis. Transmission electron microscopy (TEM) was also used for the kidney tissue. Oxidant/antioxidant parameters were studied in terms of biochemical values. The findings showed that tissue malondialdehyde increased in EMFG compared to CG and SG in both kidney (p = 0.004 and p = 0.004, respectively) and bladder tissue (p = 0.004, p = 0.006, respectively), while catalase and glutathione levels decreased compared to CG (p = 0.004; p = 0.004, respectively) and SG (p = 0.004; p = 0.004, respectively). In the EMF group, pathologies such as dilatation and vacuolization in the distal and proximal tubules, degeneration in glomeruli and an increase in cells tending to apoptosis were observed in kidney tissue. In bladder tissue, degeneration in the transitional epithelium and stromal irregularity and an increase in cells tending to apoptosis were observed in EMFG. Additionally, EMFG samples exhibited glomerular capillary degeneration with capillary basement membranes under TEM. We conclude that continuous exposure to the effect of 900-MHz EMF for 1 h a day on postnatal days 22-59, inclusive, causes an increase in oxidative stress and various pathological changes in male rat kidney and bladder tissues.

Multilayered disease-mimicking bladder phantom with realistic surface topology for optical coherence tomography

NASA Astrophysics Data System (ADS)

Smith, Gennifer T.; Lurie, Kristen L.; Khan, Saara A.; Liao, Joseph C.; Ellerbee, Audrey K.

2014-03-01

Optical coherence tomography (OCT) has shown potential as a complementary modality to white light cystoscopy (WLC), the gold standard for imaging bladder cancer. OCT can visualize sub-surface details of the bladder wall, which enables it to stage cancers and detect tumors that are otherwise invisible to WLC. Currently, OCT systems have too slow a speed and too small a field of view for comprehensive bladder imaging, which limits its clinical utility. Validation and feasibility testing of technological refinements aimed to provide faster imaging and wider fields of view necessitates a realistic bladder phantom. We present a novel process to fabricate the first such phantom that mimics both the optical and morphological properties of layers of the healthy and pathologic bladder wall as they characteristically appear with OCT. The healthy regions of the silicone-based phantom comprises three layers: the urothelium, lamina propria and muscularis propria, each containing an appropriate concentration of titanium dioxide to mimic its distinct scattering properties. As well, the layers each possess a unique surface appearance imposed by a textured mold. Within this phantom, pathologic tissue-mimicking regions are created by thickening specific layers or creating inclusions that disrupt the layered appearance of the bladder wall, as is characteristic of bladder carcinomas. This phantom can help to evaluate the efficacy of new OCT systems and software for tumor localization. Moreover, the procedure we have developed is highly generalizable for the creation of OCT-relevant, multi-layer phantoms for tissues that incorporate diseased states characterized by the loss of layered structures.

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.

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.

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.

Urodynamic measurements reflect physiological bladder function in rats.

PubMed

Schneider, Marc P; Sartori, Andrea M; Tampé, Juliane; Moors, Selina; Engmann, Anne K; Ineichen, Benjamin V; Hofer, Anna-Sophie; Schwab, Martin E; Kessler, Thomas M

2018-04-01

Our objective was to investigate and compare bladder function in rats assessed by metabolic cage and by urodynamic measurements in fully awake animals. Bladder function of female Lewis rats was investigated in naïve animals by metabolic cage at baseline, 14-16 days after bladder catheter and external urethral sphincter electromyography electrode implantation in fully awake animals by urodynamics, and again by metabolic cage. Investigating the same animals (n = 8), voided volume, average flow, and duration of voiding were similar (P > 0.05) in naïve animals measured by metabolic cage and after catheter implantation by urodynamic measurements and by metabolic cage. In naïve animals measured by metabolic cage, voided volumes were significantly different in the light (resting phase) versus the dark (active phase) part of the 24 h cycle (mean difference 0.14 mL, 21%, P = 0.004, n = 27). Lower urinary tract function assessed by metabolic cage or by urodynamic meaurements in fully awake rats was indistinguishable. Thus, catheter implantation did not significantly change physiological bladder function. This shows that urodynamic measurements in awake animals are an appropriate approach to study lower urinary tract function in health and disease in animal models, directly paralleling the human diagnostic procedures. © 2017 Wiley Periodicals, Inc.

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.

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

A Novel Vesicoscopic Bladder Wall Suture Fixation Technique to Aid Endoscopic Vesicostomy Button Insertion

PubMed Central

Adam, Ahmed; Sookram, Jayveer

2018-01-01

Background To describe a novel bladder fixation technique for use during endoscopic vesicostomy button insertion. Methods After standard cystoscopic visualization of the bladder, a standard 18 G intravenous cannula was inserted into the bladder. A non-absorbable suture thread was placed through this intravenous cannula under cystoscopic vision. The proximal end of the suture was then removed using standard ureteroscopic grasping forceps (3 Fr) through another needle (15 G) inserted next to the initial puncture site (following a path at 30 degrees from the initial puncture tract) into the bladder. The suture ends were brought out of the bladder and tied at the skin level, 2 cm from the intended vesicostomy site. Sutures were removed on the second postoperative day. Results This fixation technique allows for adequate fixation of the bladder dome to the anterior abdominal wall. These sutures also have less potential for cutaneous scarring and pain. No complications were reported. Conclusion This simple fixation technique is easily performed using materials found in every urology suite. It also avoids the skills required with other previously reported fixation suture techniques, and can also be utilized for bladder fixation in cases of vesicoscopic laparoscopic or robotic assisted laparoscopic procedures. PMID:29692696

Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium.

PubMed

Hanna-Mitchell, Ann T; Wolf-Johnston, Amanda S; Barrick, Stacey R; Kanai, Anthony J; Chancellor, Michael B; de Groat, William C; Birder, Lori A

2015-01-01

Botulinum neurotoxin serotype A (BoNT/A) has emerged as an effective treatment of urinary bladder overactivity. Intravesical lipotoxin (BoNT/A delivery using liposomes), which may target the urothelium, is effective in blocking acetic acid induced hyperactivity in animals. The objective of this study was to assess the possible site of toxin action within the urothelium. We examined expression of the toxin receptor (SV2) and its cleavage targets (SNAP-25 and SNAP-23) within urothelium as well as effects of the toxin on mechanically evoked release of ATP from cultured rat urothelial cells. ATP release was measured using the luciferin-luciferase assay; we examined expression of SNAP-23 and -25 in urothelial cells and mucosa of rat and human bladders. BoNT/A (1.5 U; 1-3 hr) blocked hypotonic evoked release of urothelial ATP, without affecting morphology. The expression of protein targets for BoNT/A binding (SV2) was detected in human and rat bladder mucosa and catalytic action (SNAP-23, -25) in urothelial cells and mucosa (differed in intensity) from rat and human bladder. Incubation of cultured (rat) urothelial cells with BoNT/A decreased expression levels of both SNAP-23 (44%) and SNAP-25 (80%). Our findings reveal that the bladder urothelium expresses the intracellular targets and the binding protein for cellular uptake of BoNT/A; and that the toxin is able to suppress the levels of these targets as well as hypotonic-evoked ATP release. These data raise the possibility that intravesical treatment with BoNT/A suppresses bladder reflex and sensory mechanisms by affecting a number of urothelial functions including release of transmitters. © 2013 Wiley Periodicals, Inc.

COMPARISON OF GENE EXPRESSION IN KIDNEY AND URINARY BLADDER FROM RATS TREATED WITH DIMETHYLARSINIC ACID

EPA Science Inventory

Arsenic is widespread in the environment and a human carcinogen. A major metabolite of inorganic arsenic (iAs) in most species, including humans, is dimethylarsinic acid (DMA), which is also used as a pesticide. Unlike iAs, DMA induces urinary bladder tumors in rats. DMA is belie...

Transcriptional profile of diurnon-induces toxicity on the urinary bladder of male wistar rats to inform mode of action

EPA Science Inventory

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that induces rat urinary bladder urothelial tumors at high dietary levels (2500 ppm). The specific mode of action and molecular alterations triggered by diuron, however, have not been clarified. Th...

[PATHOGENICALLY INDUCED APOPTOSIS CAUSED BY HYPOXIC EFFECTS IN THE URINARY SYSTEM ORGANS OF FETUSES AND NEWBORNS (EXPERIMENTAL STUDY)].

PubMed

Myroshnychenko, M; Sherstiuk, S; Zubova, Y; Nakonechna, S

2017-09-01

The purpose of the study was to identify the characteristics of apoptosis in the kidneys, ureters and bladder of fetuses and newborns in the modeling of chronic intrauterine hypoxia, acute postnatal hypoxia and mixed hypoxia. An experiment was conducted on WAG rats for modeling high altitude hypoxia. Experimental animals were divided into four groups: I - control - fetuses and newborns from healthy rats; II - modeling of chronic intrauterine hypoxia; III - modeling of acute postnatal hypoxia; IV - modeling of mixed hypoxia. The material of the study was the tissue of the kidneys, ureters and bladder of fetuses and newborns. In group I in the kidneys of fetuses the mean value of the number of p53-positive cells was 7.83±0.31, newborns - 5.40±0.28; in the ureters and bladder of fetuses - 5.77±0.29 and 6.97±0.32, newborns - 3.58±0.21 and 5.36±0.28. In the kidneys in group II the mean value of the number of p53-expressing cells in fetuses was 1.43±0.50, in newborns - 21.72±0.58; in group III in newborns - 15.03±0.63; in group IV in newborns - 33.33±0.72. The mean value of the number of p53-expressing cells in the ureters and bladder in group II in fetuses was 13.17±0.49 and 11.83±0.43, in newborns - 16.24±0.37 and 15.38±0.37; in group III in newborns - 7.25±0.27 and 8.68±0.32; in group IV in newborns - 19.63±0.31and 21.03±0.40. As the result of the study it was found that experimental hypoxia induced apoptotic processes in the kidneys, ureters and bladder of fetuses and newborns, the severity of which was moderate in the modeling of acute postnatal hypoxia, expressed in the modeling of chronic intrauterine hypoxia and strongly expressed in the modeling of mixed hypoxia. Under the influence of acute postnatal hypoxia, chronic intrauterine hypoxia and mixed hypoxia in the ureters and bladder of fetuses and newborns p53-positive cells were located evenly in all layers of the wall of these organs, whereas in the kidneys p53-positive cells prevailed in the tubular component. In the modeling of chronic intrauterine hypoxia apoptotic processes in the kidneys, ureters and bladder increased in newborns in comparison with fetuses.

Experimental investigations on intracavity sonography. Part 2: Alteration of imaging by artificial alterations in the wall of isolated porcine urinary bladders.

PubMed

Jaeger, N; Vahlensieck, W

1986-01-01

Because the determination of the depth of urinary bladder tumors by means of intracavity sonography depends on several factors (tumor size, reflection behavior of the tumor etc.), we checked the imaging of this diagnostic technique in the isolated porcine urinary bladder under various experimental conditions. Different tissues of defined size were fixed on the inner or outer surface of the bladder wall; both the bladder mucosa and the foreign tissue were damaged thermally or by incision. The importance of a limited depth of sound penetration or of a sound shadow depending on the characteristics of the tissue under investigation was revealed; tissue types could not be distinguished unequivocally by the reflection pattern; above all, a sonographic diagnosis of the tumor was not possible in the presence of histo-pathologically detectable tissue changes due to thermal damage.

Characterization of bombesin receptors in peripheral contractile organs.

PubMed Central

Rouissi, N.; Rhaleb, N. E.; Nantel, F.; Dion, S.; Drapeau, G.; Regoli, D.

1991-01-01

1 Guinea-pig and rat urinary bladders, rat stomach and the guinea-pig gall bladder, four isolated organs that show high sensitivity to bombesin, were used to characterize bombesin receptors in peripheral organs. 2 The order of potency of agonists was determined with several naturally occurring peptides of the bombesin series, namely bombesin (BBS), litorin (Lit), neuromedin B (NMB), the gastrin-releasing peptide (GRP 18-27), neuromedin C (NMC) and with some bombesin fragments. It was found that bombesin, neuromedin C, litorin and two bombesin fragments, BBS (6-14) and AcBBS (6-14) had similar activities in the four preparations, while neuromedin B and [Phe6]-neuromedin C were more active on the rat urinary bladder than on the other tissues. 3 The order of potency of agonists determined in the rat urinary bladder was as follows: BBS = NMB greater than Lit greater than NMC greater than [Phe6]NMC = GRP and it was found to be different from that observed in the other preparations: BBS greater than GRP = Lit greater than or equal to NMC much greater than NMB greater than [Phe6]NMC, suggesting the existence of two different bombesin receptors, BBS1 and BBS2. 4 This interpretation was convalidated by the finding that bombesin antagonists, namely Ac.GRP(20-26)OCH3 and Ac.GRP(20-26)OC2H5 reduced or blocked the effects of bombesin-related peptides on BBS2 receptor systems while being completely inactive on the rat urinary bladder (BBS1 system). PMID:1652341

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

Tissue-mimicking bladder wall phantoms for evaluating acoustic radiation force-optical coherence elastography systems.

PubMed

Ejofodomi, O'tega A; Zderic, Vesna; Zara, Jason M

2010-04-01

Acoustic radiation force-optical coherence elastography (ARF-OCE) systems are novel imaging systems that have the potential to simultaneously quantify and characterize the optical and mechanical properties of in vivo tissues. This article presents the construction of bladder wall phantoms for use in ARF-OCE systems. Mechanical, acoustic, and optical properties are reported and compared to published values for the urinary bladder. The phantom consisted of 0.2000 +/- 0.0089 and 6.0000 +/- 0.2830 microm polystyrene microspheres (Polysciences Inc., Warrington, PA, Catalog Nos. 07304 and 07312), 7.5 +/- 1.5 microm copolymer microspheres composed of acrylonitrile and vinylidene chloride, (Expancel, Duluth, GA, Catalog No. 461 DU 20), and bovine serum albumin within a gelatin matrix. Young's modulus was measured by successive compression of the phantom and obtaining the slope of the resulting force-displacement data. Acoustic measurements were performed using the transmission method. The phantoms were submerged in a water bath and placed between transmitting and receiving 13 mm diameter unfocused transducers operating at a frequency of 3.5 MHz. A MATLAB algorithm to extract the optical scattering coefficient from optical coherence tomography (OCT) images of the phantom was used. The phantoms possess a Young's modulus of 17.12 +/- 2.72 kPa, a mass density of 1.05 +/- 0.02 g/cm3, an acoustic attenuation coefficient of 0.66 +/- 0.08 dB/cm/MHz, a speed of sound of 1591 +/- 8.76 m/s, and an optical scattering coefficient of 1.80 +/- 0.23 mm(-1). Ultrasound and OCT images of the bladder wall phantom are presented. A material that mimics the mechanical, optical, and acoustic properties of healthy bladder wall has been developed. This tissue-mimicking bladder wall phantom was developed as a control tool to investigate the feasibility of using ARF-OCE to detect the mechanical and optical changes that may be indicative of the onset or development of cancer in the urinary bladder. By following the methods used in this article, phantoms matching the optical, acoustic, and mechanical properties of other biological tissues can also be constructed.

PPAR alpha and PPAR gamma coactivation rapidly induces Egr-1 in the nuclei of the dorsal and ventral urinary bladder and kidney pelvis urothelium of rats.

PubMed

Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer; Southgate, Jennifer; Bartels, Annette; Brünner, Nils; Oleksiewicz, Martin B

2009-12-01

To facilitate studies of the rat bladder carcinogenicity of dual-acting PPAR alpha+gamma agonists, we previously identified the Egr-1 transcription factor as a candidate carcinogenicity biomarker and developed rat models based on coadministration of commercially available specific PPAR alpha and PPAR gamma agonists. Immunohistochemistry for Egr-1 with a rabbit monoclonal antibody demonstrated that male vehicle-treated rats exhibited minimal urothelial expression and specifically, no nuclear signal. In contrast, Egr-1 was induced in the nuclei of bladder, as well as kidney pelvis, urothelia within one day (2 doses) of oral dosing of rats with a combination of 8 mg/kg rosiglitazone and 200 mg/kg fenofibrate (specific PPAR gamma and PPAR alpha agonists, respectively). These findings were confirmed by Western blotting using a different Egr-1 antibody. Egr-1 was induced to similar levels in the dorsal and ventral bladder urothelium, arguing against involvement of urinary solids. Egr-1 induction sometimes occurred in a localized fashion, indicating physiological microheterogeneity in the urothelium. The rapid kinetics supported that Egr-1 induction occurred as a result of pharmacological activation of PPAR alpha and PPAR gamma, which are coexpressed at high levels in the rat urothelium. Finally, our demonstration of a nuclear localization supports that the Egr-1 induced by PPAR alpha and PPAR gamma coactivation in the rat urothelium may be biologically active.

Computed tomography findings of human polyomavirus BK (BKV)-associated cystitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Schulze, M; Beck, R; Igney, A; Vogel, M; Maksimovic, O; Claussen, C D; Faul, C; Horger, M

2008-12-01

Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and increased mucosal enhancement. These findings are not specific for BKV cystitis, but awareness of this differential diagnosis should help in the early diagnosis and correct management of this infectious complication.

DEVELOPMENT OF A NOVEL METHOD FOR ANALYSIS OF TRANSCRIPTIONAL CHANGES IN TRANSITIONAL EPITHELIUM FROM URINARY BLADDERS OF RATS EXPOSED TO DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

Development of a Novel Method for Analysis of Transcriptional Changes in Transitional Epithelium from Urinary Bladders of Rats Exposed to Drinking Water Disinfection By- products.

Epidemiologic studies in human populations that drink chemically disinfected drinking wa...

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.

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

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.

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.

Primary Bladder Neurofibroma: A Rare Case with Clinical Implications and Diagnostic Challenges.

PubMed

Umakanthan, Srikanth; Naik, Ramadas; Bukelo, Maryann Margaret; Rai, Sharada; Prabhu, Laxman

2015-09-01

Neurofibroma of the genito-urinary tract is rare. Urinary bladder is the commonest organ involved in cases of urinary tract involvement. Patients present early in life and there is male preponderance. We discuss here a case of primary neurofibroma of the urinary bladder in a 52-year-male presenting with haematuria, irritative bladder symptoms and pelvic mass. Cystoscopy showed a swelling in the left lateral wall. A transurethral biopsy revealed neurofibroma of the urinary bladder. Immunohistochemical studies confirmed the diagnosis.

Primary Bladder Neurofibroma: A Rare Case with Clinical Implications and Diagnostic Challenges

PubMed Central

Naik, Ramadas; Bukelo, Maryann Margaret; Rai, Sharada; Prabhu, Laxman

2015-01-01

Neurofibroma of the genito-urinary tract is rare. Urinary bladder is the commonest organ involved in cases of urinary tract involvement. Patients present early in life and there is male preponderance. We discuss here a case of primary neurofibroma of the urinary bladder in a 52-year-male presenting with haematuria, irritative bladder symptoms and pelvic mass. Cystoscopy showed a swelling in the left lateral wall. A transurethral biopsy revealed neurofibroma of the urinary bladder. Immunohistochemical studies confirmed the diagnosis. PMID:26500913

Localization of hypericin-induced fluorescence after Hypericum perforatum polar fraction instillation in normal rat urinary bladder

NASA Astrophysics Data System (ADS)

Stavropoulos, Nikos E.; Skalkos, Dimitris; Tsimaris, Ioannis; Kalogeras, D.; Nseyo, Unyime O.; Batistatou, A.; Agnantis, N. J.

2005-04-01

The photodynamic action of the Hypericum perforatum L. extract, mainly its polar methanolic fraction (PMF) has recently been substantiated by our group. The herb contains a number of naphthodianthrones - photosensitizers mainly hypericin and pseudohypericin. The concentration of hypericins in PMF was found to be 1.37 %. The distribution of hypericins fluorescence in sections of normal rat bladder tissues after the intravesical instillation of the polar methanolic fraction of hypericum (PMF) was studied by the use of fluorescence microscopy. PMF was dissolved in normal saline containing 0.5 μg/ml concentration of hypericins, and was then instilled in rat bladder for 15, 30, 60 and 120 minutes respectively. PMF solutions were withdrawn, bladders were rinsed through the catheter with normal saline and rats were sacrificed. Bladders were then removed, cut open and immediately mounted in medium, and immersed in liquid nitrogen. Two consecutive 3-μm frozen sections were cut with a cryostat. The first section was examined by fluorescence microscopy and the second section was stained with hematoxylin and eosin. For fluorescence imaging the filter set used included a 535/50 nm bandpass excitation filter and a 610/75 nm emission filter. Fluorescence images were acquired and documented using photography. Fluorescene could be detected in bladder samples after only 15 minutes of instillation with the above described solution. The urothelium / muscle fluorescence ratio ranged from 5/1 to 11/1 in various sites of the samples examined. No fluorescence originating from the muscle could be detected. PMF should be further studied towards the direction of its use in photodynamic therapy.

Ex vivo culture of tumor cells from N-methyl-N-nitrosourea-induced bladder cancer in rats: Development of organoids and an immortalized cell line.

PubMed

Yoshida, Takahiro; Kates, Max; Sopko, Nikolai A; Liu, Xiaopu; Singh, Alok K; Bishai, William R; Joice, Gregory; McConkey, David J; Bivalacqua, Trinity J

2018-04-01

We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them. Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay. Primary tumor cells were successfully prepared as multicellular spheroids from MNU-induced bladder tumors. The differentiation marker expression patterns observed in the original tumors were largely retained in the spheroids. We succeeded in establishing a cell line from the spheroids and named it T-MNU-1. Although basal markers (CK14 and CK5) were enriched in T-MNU-1 compared to the spheroids, T-MNU-1 expressed both luminal and basal markers. T-MNU-1 was able to migrate through a transwell. Tumor cells in MNU-induced bladder tumors were successfully cultured ex vivo as organoids, and an immortalized cell line was also established from them. The ex vivo models offer a platform that enables analysis of intrinsic characteristics of tumor cells excluding influence of microenvironment in MNU-induced bladder tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

[Plastic closure of a bladder wall defect by use of a pedicled auto-alloplastic prosthesis in experiments].

PubMed

Sedlarik, K; Stanulla, H; Samohýl, J

1975-01-01

The problems of substituting larger areas of the bladder wall are not definitely solved. Experiments on implantation of auto-allografts resulted in complications, which prevented correct epithelization of the interior surface, due to ischemia. In successful experiments on 34 rabbits, the authors obtained sufficient blood supply of the implantate and re-epithelization of the graft's interior surface in a two-stage operation.

Macroscopic Hematuria due to Placenta Percreta: Report of Two Cases and Short Review

PubMed Central

Garas, Antonios; Sveronis, George; Nidimos, Asterios; Gkorezi, Irondiana; Alevra, Zoi; Oeconomou, Athanasios; Zachos, Ioannis

2017-01-01

Herein we present two cases of pregnant women with placenta percreta and severe hematuria during the 24th and 35th weeks of pregnancy, respectively. A timely sonographic diagnosis was feasible in the first case and cesarean section was performed during the 29th week. During the operation, the placenta was invading the bladder wall and concomitant hysterectomy with cystotomy and bladder wall reconstruction was performed. The second case presented in our emergency department with vaginal bleeding during the 35th weeks of pregnancy. She underwent an emergency cesarean section with uterine preservation, cystotomy, and bladder reconstruction. PMID:28698813

Virtual 3D bladder reconstruction for augmented medical records from white light cystoscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lurie, Kristen L.; Zlatev, Dimitar V.; Angst, Roland; Liao, Joseph C.; Ellerbee, Audrey K.

2016-02-01

Bladder cancer has a high recurrence rate that necessitates lifelong surveillance to detect mucosal lesions. Examination with white light cystoscopy (WLC), the standard of care, is inherently subjective and data storage limited to clinical notes, diagrams, and still images. A visual history of the bladder wall can enhance clinical and surgical management. To address this clinical need, we developed a tool to transform in vivo WLC videos into virtual 3-dimensional (3D) bladder models using advanced computer vision techniques. WLC videos from rigid cystoscopies (1280 x 720 pixels) were recorded at 30 Hz followed by immediate camera calibration to control for image distortions. Video data were fed into an automated structure-from-motion algorithm that generated a 3D point cloud followed by a 3D mesh to approximate the bladder surface. The highest quality cystoscopic images were projected onto the approximated bladder surface to generate a virtual 3D bladder reconstruction. In intraoperative WLC videos from 36 patients undergoing transurethral resection of suspected bladder tumors, optimal reconstruction was achieved from frames depicting well-focused vasculature, when the bladder was maintained at constant volume with minimal debris, and when regions of the bladder wall were imaged multiple times. A significant innovation of this work is the ability to perform the reconstruction using video from a clinical procedure collected with standard equipment, thereby facilitating rapid clinical translation, application to other forms of endoscopy and new opportunities for longitudinal studies of cancer recurrence.

Bladder accumulated dose in image-guided high-dose-rate brachytherapy for locally advanced cervical cancer and its relation to urinary toxicity

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Gaudet, Marc; Aquino-Parsons, Christina; Spadinger, Ingrid

2016-12-01

The purpose of this study was to estimate locally accumulated dose to the bladder in multi-fraction high-dose-date (HDR) image-guided intracavitary brachytherapy (IG-ICBT) for cervical cancer, and study the locally-accumulated dose parameters as predictors of late urinary toxicity. A retrospective study of 60 cervical cancer patients who received five HDR IG-ICBT sessions was performed. The bladder outer and inner surfaces were segmented for all sessions and a bladder-wall contour point-set was created in MATLAB. The bladder-wall point-sets for each patient were registered using a deformable point-set registration toolbox called coherent point drift (CPD), and the fraction doses were accumulated. Various dosimetric and volumetric parameters were calculated using the registered doses, including r{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} (minimum dose to the most exposed n-cm3 volume of bladder wall), r V n Gy (wall volume receiving at least m Gy), and r\\text{EQD}{{2}n \\text{c{{\\text{m}}\\text{3}}}} (minimum equivalent biologically weighted dose to the most exposed n-cm3 of bladder wall), where n  =  1/2/5/10 and m  =  3/5/10. Minimum dose to contiguous 1 and 2 cm3 hot-spot volumes was also calculated. The unregistered dose volume histogram (DVH)-summed equivalent of r{{\\text{D}}n \\text{c{{\\text{m}}3}}} and r\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} parameters (i.e. s{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} and s\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} ) were determined for comparison. Late urinary toxicity was assessed using the LENT-SOMA scale, with toxicity Grade 0-1 categorized as Controls and Grade 2-4 as Cases. A two-sample t-test was used to identify the differences between the means of Control and Case groups for all parameters. A binomial logistic regression was also performed between the registered dose parameters and toxicity grouping. Seventeen patients were in the Case and 43 patients in the Control group. Contiguous values were on average 16 and 18% smaller than parameters for 1 and 2 cm3 volumes, respectively. Contiguous values were on average 26 and 27% smaller than parameters. The only statistically significant finding for Case versus Control based on both methods of analysis was observed for r V3 Gy (p  =  0.01). DVH-summed parameters based on unregistered structure volumes overestimated the bladder dose in our patients, particularly when contiguous high dose volumes were considered. The bladder-wall volume receiving at least 3 Gy of accumulated dose may be a parameter of interest in further investigations of Grade 2+  urinary toxicity.

Tissue engineering of urinary bladder - current state of art and future perspectives.

PubMed

Adamowicz, Jan; Kowalczyk, Tomasz; Drewa, Tomasz

2013-01-01

Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary blad- der based on tissue engineering methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells. Numerous studies to develop a substitute for the native urinary bladder wall us- ing the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application. Before tissue engineering techniques could be recognize as effective and safe for patients, more research stud- ies performed on large animal models and with long follow-up are needed to carry on in the future.

Sci—Thur AM: YIS - 11: Estimation of Bladder-Wall Cumulative Dose in Multi-Fraction Image-Based Gynaecological Brachytherapy Using Deformable Point Set Registration

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

Zakariaee, R; Brown, C J; Hamarneh, G

2014-08-15

Dosimetric parameters based on dose-volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high-dose-rate (HDR) brachytherapy fractions ofmore » 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3-dimensional point clouds constituting the “bladder wall”. A point-set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non-rigidly transform the bladder-wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT-SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.« less

Hydration status affects urea transport across rat urothelia.

PubMed

Spector, David A; Deng, Jie; Stewart, Kerry J

2011-12-01

Although mammalian urinary tract epithelium (urothelium) is generally considered impermeable to water and solutes, recent data suggest that urine constituents may be reabsorbed during urinary tract transit and storage. To study water and solute transport across the urothelium in an in vivo rat model, we instilled urine (obtained during various rat hydration conditions) into isolated in situ rat bladders and, after a 1-h dwell, retrieved the urine and measured the differences in urine volume and concentration and total quantity of urine urea nitrogen and creatinine between instilled and retrieved urine in rat groups differing by hydration status. Although urine volume did not change >1.9% in any group, concentration (and quantity) of urine urea nitrogen in retrieved urine fell significantly (indicating reabsorption of urea across bladder urothelia), by a mean of 18% (489 mg/dl, from an instilled 2,658 mg/dl) in rats receiving ad libitum water and by a mean of 39% (2,544 mg/dl, from an instilled 6,204 mg/dl) in water-deprived rats, but did not change (an increase of 15 mg/dl, P = not significant, from an instilled 300 mg/dl) in a water-loaded rat group. Two separate factors affected urea nitrogen reabsorption rates, a urinary factor related to hydration status, likely the concentration of urea nitrogen in the instilled urine, and a bladder factor(s), also dependent on the animal's state of hydration. Urine creatinine was also absorbed during the bladder dwell, and hydration group effects on the concentration and quantity of creatinine reabsorbed were qualitatively similar to the hydration group effect on urea transport. These findings support the notion(s) that urinary constituents may undergo transport across urinary tract epithelia, that such transport may be physiologically regulated, and that urine is modified during transit and storage through the urinary tract.

IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

EPA Science Inventory

Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

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

The protective effect of Moringa oleifera leaves against cyclophosphamide-induced urinary bladder toxicity in rats.

PubMed

Taha, Nevine R; Amin, Hanan Ali; Sultan, Asrar A

2015-02-01

Cyclophosphamide (CP), an alkylating antineoplastic agent is widely used in the treatment of solid tumors and B-cell malignant disease. It is known to cause urinary bladder damage due to inducing oxidative stress. Moringa oleifera (Mof) is commonly known as drumstick tree. Moringa leaves have been reported to be a rich source of β-carotene, protein, vitamin C, calcium, and potassium. It acts as a good source of natural antioxidants; due to the presence of various types of antioxidant compounds such as ascorbic acid, flavonoids, phenolics and carotenoids. The aim of this work was to test the possible antioxidant protective effects of M. oleifera leaves against CP induced urinary bladder toxicity in rats. Female Wister albino rats were divided into 4 groups. Group I served as control, received orally normal saline, group II received a single dose CP 100mg/kg intraperitoneally, group III and VI both received orally hydroethanolic extract of Mof; 500 mg/kg and 1000 mg/kg respectively daily for a week, 1h before and 4h after CP administration. Rats were sacrificed 24h after CP injection. The bladder was removed, sectioned, and subjected to light, transition electron microscopic studies, and biochemical studies (measuring the parameter of lipid peroxidation; malondialdehyde along with the activities of the antioxidant enzyme reduced glutathione). The bladders of CP treated rats showed ulcered mucosa, edematous, hemorrhagic, and fibrotic submucosa by light microscopy. Ultrastructure observation showed; losing large areas of uroepithelium, extended intercellular gaps, junction complexes were affected as well as damage of mitochondria in the form of swelling and destruction of cristae. Biochemical analysis showed significant elevation of malondialdhyde, while reduced glutathione activity was significantly lowered. From the results obtained in this work, we can say that Moringa leaves play an important role in ameliorating and protecting the bladder from CP toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats.

PubMed

Aizawa, Naoki; Wakamatsu, Daisuke; Kida, Jun; Otsuki, Takeya; Saito, Yasuho; Matsuya, Hidekazu; Homma, Yukio; Igawa, Yasuhiko

2017-02-01

Kv7 voltage-gated potassium channels have been suggested to modulate mechano-afferent transduction and nociception in the bladder. We investigated the effects of retigabine, a Kv7 channel activator, on rhythmic bladder contractions (RBCs), and single-unit afferent activities (SAAs) of the primary bladder mechanosensitive afferent nerve fibers in urethane-anesthetized rats. In addition, the effects of pretreatment with retigabine on the nociceptive behaviors provoked by an intravesical instillation of resiniferatoxin (RTX) were evaluated in the conscious condition. Female Sprague-Dawley rats were used. Under urethane anesthesia, saline was instilled into the bladder until RBCs were induced reproducibly. Then, the effects of intravenous, cumulative administrations of retigabine (0.1-3 mg/kg) or vehicle (saline) on RBCs were assessed. In separate animals, SAAs of Aδ- and C-fibers were identified by electrical stimulation of the pelvic nerve and by bladder distention with saline. After baseline recording, vehicle or retigabine (0.01-1 mg/kg) was administered intravenously and further recordings were performed. Under pretreatment with vehicle or retigabine (3 mg/kg intraperitoneally), the frequencies of lower abdominal licking and freezing were counted and scored as the bladder nociceptive behaviors induced by intravesical RTX instillation (3 µM, 0.3 ml). Retigabine dose-dependently decreased both the frequency and the amplitude of RBCs and SAAs of both Aδ- and C-fibers. The effect on RBCs was more potent on the frequency than the amplitude. Retigabine inhibited the RTX-induced abdominal licking, but not freezing. Kv7 channels are likely to be implicated in inhibition of bladder mechano- and nociceptive sensory transduction. Neurourol. Urodynam. 36:280-285, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Longitudinal studies of time-dependent changes in both bladder and erectile function after streptozotocin-induced diabetes in Fischer 344 male rats.

PubMed

Melman, Arnold; Zotova, Elena; Kim, Mimi; Arezzo, Joseph; Davies, Kelvin; DiSanto, Michael; Tar, Moses

2009-11-01

To provide sensitive physiological endpoints for the onset and long-term progression of deficits induced by diabetes mellitus (DM) in bladder and erectile function in male rats, and to evaluate parallel changes in urogenital and nerve function induced by hyperglycaemia over a protracted period as a model for chronic deficits in patients with diabetes. The study comprised in 877 male, 3-month-old, Fischer 344 rats; 666 were injected intraperitoneally with 35 mg/kg streptozotocin (STZ) and divided into insulin-treated and untreated diabetic groups. The rats were studied over 8 months and measurements made of both erectile and bladder function, as well as nerve conduction studies over the duration of the study. There was an early (first month) abnormality of both erectile and bladder function that persisted through the 8 months of the study. The erectile dysfunction was manifest as reduced intracavernous pressure/blood pressure ratio, and the bladder dysfunction as a persistent increase in detrusor overactivity with no detrusor decompensation. Insulin treatment prevented or modified the abnormality in each organ. Hyperglycaemia caused a progressive decrease in caudal nerve conduction velocity. The mean digital sensory and tibial motor nerve conduction velocity did not deteriorate over time. Correlation measurements of nerve and organ function were not consistent. The results of this extensive long-term study show early and profound effects of hyperglycaemia on the smooth muscle of the penis and bladder, that were persistent and stable in surviving rats over the 8 months. The physiological changes did not correlate well with neurological measurements of those organs. Significantly, diverse smooth-muscle cellular and subcellular events antedated the measured neurological manifestations of the hyperglycaemia by several months. Although autonomic diabetic neuropathy is a primary life-threatening complication of long-term diabetes in humans, this rat model of STZ-induced diabetes showed that the rapid onset of physiological manifestations was based on many molecular changes in the smooth muscle cells in this model of type 1 DM.

Bladder Monitor

NASA Technical Reports Server (NTRS)

1993-01-01

Diagnostic Ultrasound Corporation's Bladder Scan Monitor continuously records and monitors bladder fullness and alerts the wearer or caretaker when voiding is required. The sensor is held against the lower abdomen by a belt and connected to the monitor by a cable. The sensor obtains bladder volume data from sound waves reflecting off the bladder wall. The device was developed by Langley Research Center, the Ames Research Center and the NASA Technology Applications Team. It utilizes Langley's advanced ultrasound technology. It is licensed to the ARC for medical applications, and sublicensed to Diagnostics Ultrasound. Central monitoring systems are planned for the future.

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

Inhibition of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine in rats by green tea.

PubMed

Sato, D

1999-02-01

Recently, the anticarcinogenic effects of green tea have been studied in sites other than the urinary tract. The present study examined the inhibition by green tea of vesical tumors induced in rats by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In the first series of experiments, 0.05% BBN was added to the drinking water of rats and remained present for 5 weeks. In one experiment, six groups of animals received either tap water, green tea, matcha, hojicha, oolong tea or black tea from week 6. In a second experiment, three groups of rats received either tap water, green tea extract or powdered green tea mixed into a pellet diet from week 6. In a third experiment, five groups of rats were fed a pellet diet with addition of either 0, 0.15, 1.5 or 3.0% powdered green tea from week 6. All rats were killed and examined at 40 weeks. Green tea, particularly green tea leaves, dose-dependently inhibited the growth of BBN-induced urinary bladder tumors when given after the carcinogen. Green tea may inhibit bladder tumor growth.

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.

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

Construction of Extended 3D Field of Views of the Internal Bladder Wall Surface: A Proof of Concept

NASA Astrophysics Data System (ADS)

Ben-Hamadou, Achraf; Daul, Christian; Soussen, Charles

2016-09-01

3D extended field of views (FOVs) of the internal bladder wall facilitate lesion diagnosis, patient follow-up and treatment traceability. In this paper, we propose a 3D image mosaicing algorithm guided by 2D cystoscopic video-image registration for obtaining textured FOV mosaics. In this feasibility study, the registration makes use of data from a 3D cystoscope prototype providing, in addition to each small FOV image, some 3D points located on the surface. This proof of concept shows that textured surfaces can be constructed with minimally modified cystoscopes. The potential of the method is demonstrated on numerical and real phantoms reproducing various surface shapes. Pig and human bladder textures are superimposed on phantoms with known shape and dimensions. These data allow for quantitative assessment of the 3D mosaicing algorithm based on the registration of images simulating bladder textures.

Evaluation of the rat bladder-derived relaxant factor by coaxial bioassay system.

PubMed

Bozkurt, Turgut Emrah; Sahin-Erdemli, Inci

2004-07-14

The release of bladder-derived relaxant factor in a coaxial bioassay system and the effects of reactive oxygen species were studied. After precontraction with phenylephrine (10(-6)-3x10(-6)) or 50 mM K+, acetylcholine (10(-8)-10(-3) M) induced relaxation in rat anococcygeus muscle mounted within rat bladder in a tissue bath. This relaxation was not altered by the removal of the urothelium or incubation with tetrodotoxin (10(-6) M). However, bupivacaine (10(-4) M) and lidocaine (3 x 10(-4) M) inhibited this response after raising the pH of the nutrient solution to 7.8, and oxybuprocaine (10(-4) M) exerted inhibitory effect at both physiological pH (7.4) and at pH 7.8. Exposure to electrolysis-generated reactive oxygen species or incubation with hydrogen peroxide and pyrogallol did not alter the acetylcholine response. Present results indicate that the bladder-derived relaxant factor does not behave like endothelium-derived hyperpolarizing factor, but its release may be associated with tetrodotoxin-resistant Na+ channels, which are probably in the neurons of the bladder rather than in the urothelium or detrusor muscle. Furthermore, reactive oxygen species do not interact with this relaxing factor, the exact nature and the physiological importance of which, however, remains to be established.

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

Vaginal prolapse with urinary bladder incarceration and consecutive irreducible rectal prolapse in a dog.

PubMed

Ober, Ciprian-Andrei; Peștean, Cosmin Petru; Bel, Lucia Victoria; Taulescu, Marian; Cătoi, Cornel; Bogdan, Sidonia; Milgram, Joshua; Schwarz, Guenter; Oana, Liviu Ioan

2016-09-22

True vaginal prolapse is a rare condition in dogs and it is occasionally observed in animals with constipation, dystocia, or forced separation during breeding. If a true prolapse occurs, the bladder, the uterine body and/or distal part of the colon, may be present in the prolapse. A 2-year-old intact non pregnant Central Asian Shepherd dog in moderate condition, was presented for a true vaginal and rectal prolapse. The prolapses were confirmed by physical examination and ultrasonography. Herniation of the urinary bladder was identified within the vaginal prolapse. The necrotic vaginal wall was resected, the urinary bladder was reduced surgically and fixed to the right abdominal wall to prevent recurrence. Rectal resection and anastomosis was necessary to correct the rectal prolapse. Recurrence of the prolapses was not observed and the dog recovered completely after the surgical treatment. In our opinion, extreme tenesmus arising from constipation may have predisposed to the vaginal prolapse with bladder incarceration and secondarily to rectal prolapse. In the young female dog, true vaginal prolapse with secondary involvement of the urinary bladder and irreducible rectal prolapse is an exceptionally rare condition.

[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.

[Contribution of ultrasound signs for the prenatal diagnosis of posterior urethral valves: Experience of 3years at the maternity of the Bicêtre Hospital].

PubMed

Roy, S; Colmant, C; Cordier, A-G; Sénat, M-V

2016-05-01

Posterior urethral valves (PUV) are the most common cause of renal impairment in boys during early childhood. The aim of this study was to evaluate the value of ultrasound (US) criteria currently used to diagnose PUV. From 2009 to 2012, 31 patients were referred to the Bicêtre Hospital after detection of fetal bilateral hydronephrosis in male fetus. The ultrasound criteria were bladder dilation, thick-walled bladder, urethral dilation ("keyhole sign"), and amniotic fluid volume. Patients were divided in two groups: suspected or not to have PUV. US diagnosis of PUV was done in 18 fetuses and confirmed in 14 new borns, one of them without prenatal diagnosis. Sensitivity and specificity of US scan were 92.8 and 66.7%. The likelihood ratio (LHR) was 4.8 for a thick-walled bladder, 4.2 for oligohydramnios, 3.6 for the "keyhole sign", 2.4 for bladder dilation and 1.6 for ureteral dilation. The first four signs were combined in four fetuses, all of them with PUV. US scan is a very sensitive exam for the diagnosis of PUV but with a low specificity. A thick-walled bladder seems to have a better diagnostic performance than the "keyhole sign". Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Adenocarcinoma arising in urinary bladder endocervicosis.

PubMed

Nakaguro, Masato; Tsuzuki, Toyonori; Shimada, Satoko; Taki, Tetsuro; Tsuchiyama, Mari; Kitamura, Atsuko; Suzuki, Yasuhiko; Nakano, Yojiro; Ono, Kenzo

2016-02-01

Endocervicosis is a rare benign condition characterized by the presence of endocervical-type mucinous glands. Urinary bladder endocervicosis forms an elevated lesion in the posterior wall of the urinary bladder and is sometimes misdiagnosed as a malignant tumor clinically and pathologically. Herein we describe the first case of adenocarcinoma arising in urinary bladder endocervicosis. The patient, a 58-year-old woman, presented with asymptomatic hematuria. Cystoscopy revealed a nodular mass measuring 4 cm in diameter in the posterior wall, and total cystectomy was performed. Histology revealed that the elevated lesion of the bladder wall was composed of haphazard proliferation of cystic glands lined by benign endocervical-type epithelium. An adenocarcinoma arose at the center of this endocervicosis. Mucin histochemistry revealed the presence of sulfomucin in both the endocervicosis and adenocarcinoma components. Immunohistochemically, the endocervicosis was positive for cytokeratin (CK) 7, AE1/AE3, CAM5.2, HBME1, CA19-9, and estrogen receptor (ER), and negative for CK20, CDX2, progesterone receptor (PR), MUC5AC, and β-catenin. The adenocarcinoma showed similar immunohistochemical results, except for loss of ER expression and a slight increase in the ratio of Ki-67-positive cells. This case indicates that endocervicosis, known as a benign lesion, harbors the possibility of malignant transformation. © 2016 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

DIMETHYLARSINIC ACID ALTERS EXPRESSION OF OXIDATIVE STRESS AND DNA REPAIR GENES IN A DOSE DEPENDENT MANNER IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS.

EPA Science Inventory

Dose-dependent alteration of oxidative stress and DNA repair gene expression by Dimethylarsinic acid [DMA(V)] in transitional epithelium of urinary bladder from female F344 rats.
Arsenic (As) is a major concern as millions of people are at risk from drinking arsenic contaminat...

Effects of Saw Palmetto Extract on Urodynamic Parameters, Bladder Muscarinic and Purinergic Receptors and Urinary Cytokines in Rats with Cyclophosphamide-Induced Cystitis.

PubMed

Nasrin, Sweety; Masuda, Eiji; Kugaya, Haruna; Osano, Ayaka; Ito, Yoshihiko; Yamada, Shizuo

2014-01-01

To clarify the effect of saw palmetto extract (SPE), a phytotherapeutic agent, on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cystitis induced by cyclophosphamide (CYP). Saw palmetto extract (60 mg/kg per day) was administered orally twice a day for 7 days to rats. The urodynamic parameters in CYP (150 mg/kg i.p.)-treated rats were monitored by a cystometric method under anesthesia. The muscarinic and purinergic receptors in the bladder and submaxillary gland were measured by radioreceptor assays using [N-methyl-(3) H] scopolamine chloride([(3) H]NMS) and αβ-methylene-ATP [2,8-(3) H] tetrasodium salt ([(3) H]αβ-MeATP), respectively. Urinary cytokines (interleukin-1β [IL-1β], IL-6 and L-17) were measured with enzyme linked immunosorbent assay kits. Micturition interval and micturition volume were significantly decreased and the frequency of micturition and basal pressure were significantly increased in the CYP-treated rats compared with sham-operated rats. Orally administered SPE significantly increased the micturition interval and micturition volume and decreased the frequency of micturition and basal pressure. The maximal number of sites (Bmax ) for the specific binding of [(3) H]NMS and [(3) H]αβ-MeATP was significantly decreased in the bladder. The decrease in receptors was attenuated by repeated treatment with SPE. An elevation in urinary cytokine (IL-1β and IL-17) levels were seen, and this increase was effectively suppressed by SPE treatment. Saw palmetto extract attenuates the alteration of urodynamic parameters, pharmacologically relevant receptors, and urinary cytokines in CYP-treated rats. Therefore, SPE may be a potential therapeutic agent for improving the clinical symptoms of cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

Role of M2 and M3 muscarinic acetylcholine receptor subtypes in activation of bladder afferent pathways in spinal cord injured rats.

PubMed

Matsumoto, Yoshihiro; Miyazato, Minoru; Yokoyama, Hitoshi; Kita, Masafumi; Hirao, Yoshihiko; Chancellor, Michael B; Yoshimura, Naoki

2012-05-01

To evaluate the role of M2 and M3 muscarinic acetylcholine receptor (mAChR) subtypes in the activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI). Adult female Sprague-Dawley rats were spinalized at the T9 level. Continuous cystometry was performed under awake conditions 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-methiodide), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine), and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into the mucosa and detrusor, and the M2 and M3 mAChR mRNA expression in the mucosa was determined using real-time quantitative polymerase chain reaction. At 2 and 4 weeks after SCI, intravesical administration of a nonselective mAChR agonist (25 μM oxotremorine-methiodide) increased the area under the curve of nonvoiding contractions, although the intercontraction interval of voiding contractions and maximal voiding pressure did not change. This effect was blocked by atropine and methoctramine (10 μM) but not by darifenacin (50 μM). However, mAChR antagonists alone (10-50 μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in the mucosa of SCI rats compared with that in normal rats. Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity might not be involved in the emergence of detrusor overactivity in SCI. Copyright © 2012 Elsevier Inc. All rights reserved.

Herpes simplex virus vector-mediated gene delivery of glutamic acid decarboxylase reduces detrusor overactivity in spinal cord injured rats

PubMed Central

Miyazato, Minoru; Sugaya, Kimio; Goins, William F.; Goss, James R.; Chancellor, Michael B.; de Groat, William C.; Glorioso, Joseph C.; Yoshimura, Naoki

2010-01-01

We examined whether replication-defective herpes simplex virus (HSV) vectors encoding the 67 Kd form of the glutamic acid decarboxylase (GAD67) gene product, the gamma-aminobutyric acid (GABA) synthesis enzyme, can suppress detrusor overactivity (DO) in spinal cord injury (SCI) rats. One week after spinalization, HSV vectors expressing GAD and green fluorescent protein (GFP) (HSV-GAD) were injected into the bladder wall. SCI rats without HSV injection (HSV-untreated) and those injected with lacZ-encoding reporter gene HSV vectors (HSV-LacZ) were used as controls. Three weeks after viral injection, continuous cystometry was performed under awake conditions in all three groups. In the HSV-GAD group, the number and amplitude of non-voiding contractions (NVCs) were significantly decreased (40–45% and 38–40%, respectively) along with an increase in voiding efficiency, compared with HSV-untreated and HSV-LacZ groups, but micturition pressure was not different among the three groups. Intrathecal application of bicuculline partly reversed the decreased number and amplitude of NVCs, and decreased voiding efficiency in the HSV-GAD group. In the HSV-GAD group, GAD67 mRNA and protein levels were significantly increased in L6-S1 dorsal root ganglia (DRG) compared with the HSV-LacZ group while 57% of DRG cells were GFP-positive, and these neurons showed increased GAD67-like immunoreactivity compared with the HSV-LacZ group. These results indicate that GAD gene therapy effectively suppresses DO following SCI predominantly via activation of spinal GABAA receptors. Thus, HSV-based GAD gene transfer to bladder afferent pathways may represent a novel approach for the treatment of neurogenic DO. PMID:19225548

Computer-aided detection of bladder masses in CT urography (CTU)

NASA Astrophysics Data System (ADS)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Samala, Ravi K.

2017-03-01

We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). We have previously developed methods for detection of bladder masses within the contrast-enhanced and the non-contrastenhanced regions of the bladder individually. In this study, we investigated methods for detection of bladder masses within the entire bladder. The bladder was segmented using our method that combined deep-learning convolutional neural network with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensity-projection-based method. The non-contrast region was smoothed and gray level threshold was applied to the contrast and non-contrast regions separately to extract the bladder wall and potential masses. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify lesion candidates in a prescreening step. The candidates were mapped back to the 3D CT volume and segmented using our auto-initialized cascaded level set (AI-CALS) segmentation method. Twenty-seven morphological features were extracted for each candidate. A data set of 57 patients with 71 biopsy-proven bladder lesions was used, which was split into independent training and test sets: 42 training cases with 52 lesions, and 15 test cases with 19 lesions. Using the training set, feature selection was performed and a linear discriminant (LDA) classifier was designed to merge the selected features for classification of bladder lesions and false positives. The trained classifier was evaluated with the test set. FROC analysis showed that the system achieved a sensitivity of 86.5% at 3.3 FPs/case for the training set, and 84.2% at 3.7 FPs/case for the test set.

Dietary protein affects urea transport across rat urothelia.

PubMed

Spector, David A; Deng, Jie; Stewart, Kerry J

2012-10-01

Recent evidence suggests that regulated solute transport occurs across mammalian lower urinary tract epithelia (urothelia). To study the effects of dietary protein on net urothelial transport of urea, creatinine, and water, we used an in vivo rat bladder model designed to mimic physiological conditions. We placed groups of rats on 3-wk diets differing only by protein content (40, 18, 6, and 2%) and instilled 0.3 ml of collected urine in the isolated bladder of anesthetized rats. After 1 h dwell, retrieved urine volumes were unchanged, but mean urea nitrogen (UN) and creatinine concentrations fell 17 and 4%, respectively, indicating transurothelial urea and creatinine reabsorption. The fall in UN (but not creatinine) concentration was greatest in high protein (40%) rats, 584 mg/dl, and progressively less in rats receiving lower protein content: 18% diet, 224 mg/dl; 6% diet, 135 mg/dl; and 2% diet, 87 mg/dl. The quantity of urea reabsorbed was directly related to a urine factor, likely the concentration of urea in the instilled urine. In contrast, the percentage of instilled urea reabsorbed was greater in the two dietary groups receiving the lowest protein (26 and 23%) than in those receiving higher protein (11 and 9%), suggesting the possibility that a bladder/urothelial factor, also affected by dietary protein, may have altered bladder permeability. These findings demonstrate significant regulated urea transport across the urothelium, resulting in alteration of urine excreted by the kidneys, and add to the growing evidence that the lower urinary tract may play an unappreciated role in mammalian solute homeostasis.

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

Transcriptomic dose-and-time-course indicators of early key events in a cytotoxicity-mediated mode of action for rodent urinary bladder tumorigenesis

EPA Science Inventory

TRANSCRIPTOMIC DOSE- AND TIME-COURSE INDICATORS OF EARLY KEY EVENTS IN A CYTOTOXICITY-MEDIATED MODE OF ACTION FOR RODENT URINARY BLADDER TUMORIGENESISDiuron is a substituted urea compound used globally as an herbicide. Urinary bladder tumors were induced in rats after chronic die...

Effects of Estrogen Receptor β Stimulation in a Rat Model of Non-Bacterial Prostatic Inflammation

PubMed Central

Mizoguchi, Shinsuke; Mori, Kenichi; Wang, Zhou; Liu, Teresa; Funahashi, Yasuhito; Sato, Fuminori; DeFranco, Donald B.; Yoshimura, Naoki; Mimata, Hiromitsu

2017-01-01

BACKGROUND There is increasing evidence showing that chronic non-bacterial prostatic inflammation is involved in the pathogenesis of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS). It has also been reported that estrogen receptor β (ERβ) could have an immunoprotective role in prostatic tissue. Therefore, we investigated the effect of ERβ-activation on not only prostatic inflammation, but also bladder overactive conditions in a rat model with nonbacterial prostatic inflammation. METHODS Male Sprague-Dawley rats (8 weeks, n = 15) were divided into three groups: sham-saline group (n = 5), formalin-vehicle group (n = 5), and formalin-treatment group (n = 5). The sham-saline group had sham operation and 50 μl normal saline injected into each ventral lobe of the prostate. The formalin-vehicle group had 50 μl 5% formalin injection into bilateral ventral lobes of the prostate. The formalin-treatment group was treated with 3α-Adiol (a selective ERβ agonist precursor) at a dose of 3 mg/kg daily from 2 days before induction of prostatic inflammation, whereas formalin-vehicle rats received vehicle (olive oil). In each group, conscious cystometry was performed on day 28 after intraprostatic formalin injection or sham treatment. After cystometry, the bladder and prostate were harvested for evaluation of mRNA expression and histological analysis. RESULTS In cystometric investigation, the mean number of non-voiding contractions was significantly greater and voiding intervals were significantly shorter in formalin-vehicle rats than those in sham-saline rats (P < 0.05). In RT-qPCR analysis, mRNA expression of NGF, P2X2, and TRPA1 receptors was significantly increased in the bladder mucosa, and mRNA expression of TNF-α, iNOS and COX2 in the ventral lobes of prostate was significantly increased in formalin-vehicle rats compared with sham-saline rats (P < 0.05). In addition, relative mRNA expression ratio of ERβ to ERα (ERβ/ERα) in the ventral lobes of prostate was significantly decreased in formalin-vehicle rats compared with sham-saline rats (P < 0.05). These changes were ameliorated by 3α-Adiol administration in formalin-treatment rats. CONCLUSIONS These results indicate that ERβ activation by 3α-Adiol administration, which normalized the ERβ/ERα expression ratio in the prostate, can improve not only prostatic inflammation, but also bladder overactivity. Therefore, ERβ agonists might be useful for treating irritative bladder symptoms in patients with symptomatic BPH associated with prostatic inflammation. PMID:28181685

Anti-NGF Local Therapy for Autonomic Dysreflexia in Spinal Cord Injury

DTIC Science & Technology

2013-10-01

growth factor in the urothelium of sham treated rats, which was decreased 5 by antisense treatment (Fig. 4A) and (5) increased nerve growth...sensitization. B Figure 4. A: Antisense OND mediated suppression of acetic acid (AA) induced NGF protein expression in urothelium . AA exposure...upregulation in the bladder urothelium of SCI rats  Detection of hyperexcitability of bladder afferent neurons due to the reduction of A-type K+ channel

Peritoneal mucinous cystadenocarcinoma of probable urachal origin: a challenging diagnosis

PubMed Central

Gore, D M; Bloch, S; Waller, W; Cohen, P

2006-01-01

This report describes the case of a mucinous cystadenocarcinoma of probable urachal origin that presented with mass effect, precipitating deep venous thrombosis and pulmonary embolism. The patient presented with acute symptoms of leg swelling, pain and dyspnoea, and a vague awareness of lower abdominal distension. Computer tomography showed a cystic mass closely related to the anterior abdominal wall and the superior aspect of the bladder. A 1500 cm3 cyst adherent to the dome of the urinary bladder was resected on laparotomy. Partial cystectomy was not carried out in the belief that the cyst represented a benign lesion. Subsequent imaging has shown cystic changes in the anterior bladder wall, and the patient has been referred for partial cystectomy. PMID:17021133

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.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Fluorescein angiography of the bladder: technique and relevance to bladder cancer and interstitial cystitis patients.

PubMed

Zimmern, P E; Laub, D; Leach, G E

1995-07-01

Fluorescein angiography has been used in the study of bleeding vessels, neovascularity, tumors and ischemic tissues in a variety of disorders. This pilot study was designed to evaluate the feasibility, safety and relevance of this interesting technology for the evaluation of bladder wall vessels in patients with interstitial cystitis and bladder cancer. Five patients with National Institutes of Health defined interstitial cystitis symptoms and 10 with bladder cancer were studied during cytoscopy while they were under general anesthesia. A yellow-green barrier filter (520 nm.) was placed over the cystoscope eyepiece and a blue exciter filter (465 nm.) was attached to the light source. Patients received a 5 ml. bolus of 10% fluorescein intravenously. After hydrodistension, glomerulations in interstitial cystitis patients were more prominent with fluorescein angiography and occurred in the venule phase. Areas of papillary transitional cell tumor and carcinoma in situ developed a brilliant yellow-green fluorescence. Adjacent normal urothelium was nonfluorescent and provided a contrasting dark background facilitating the detection of all lesions. No allergic reaction or other adverse effect related to the fluorescein injection was observed. These unique observations in a limited number of patients suggest that fluorescein angiography of the bladder is a safe and simple procedure. This preliminary report underscores the relevance of fluorescein angiography in the detection of bladder tumor and offers a new approach to the evaluation of bladder wall vessels in interstitial cystitis patients.

The morphological regeneration and functional restoration of bladder defects by a novel scaffold and adipose-derived stem cells in a rat augmentation model.

PubMed

Wang, Qiong; Xiao, Dong-Dong; Yan, Hao; Zhao, Yang; Fu, Shi; Zhou, Juan; Wang, Zhong; Zhou, Zhe; Zhang, Ming; Lu, Mu-Jun

2017-06-24

Due to the multilineage differentiation ability and paracrine role of adipose-derived stem cells (ASCs) for bladder defect repair, various scaffolds have been applied in combination with ASCs to promote bladder regeneration and restore bladder function. However, the low survival rate of ASCs and the difficulty of promoting bladder functional recovery are still unsolved. To explore these problems, we investigated the feasibility of a novel scaffold seeded with ASCs in a rat model of bladder augmentation. A novel autologous myofibroblast (AM)-silk fibroin (SF) scaffold was harvested after subcutaneously prefabricating the bladder acellular matrix grafts (BAMG) and SF by removing the BAMG. The AM-SF scaffolds were then seeded with ASCs (AM-SF-ASCs). Fifty percent supratrigonal cystectomies were performed followed by augmenting the cystectomized defects with AM-SF scaffolds or AM-SF-ASCs. The histological and functional assessments of bladders were performed 2, 4, and 12 weeks after surgery while the ASCs were tracked in vivo. For bladder tissue regeneration, immunofluorescence analysis revealed that AM-SF-ASCs (the experimental group) promoted better morphological regeneration of the urothelium, vessels, bladder smooth muscle, and nerve than AM-SF scaffolds (the control group). Regarding functional restoration, the AM-SF-ASC group exhibited higher bladder compliance and relatively normal micturition pattern compared to the AM-SF group. In addition, a certain number of surviving ASCs could be found in vivo 12 weeks after implantation, and some of them had differentiated into smooth muscle cells. The AM-SF scaffolds with ASCs could rapidly promote bladder morphological regeneration and improved bladder urinary function. In addition, the bag-shaped structure of the AM-SF scaffold can improve the survival of ASCs for at least 12 weeks. This strategy of AM-SF-ASCs has a potential to repair large-scale bladder defects in the clinic in the future.

Induction of hyperplasia in the bladder epithelium of rats by a dietary excess of acid or base: implications for toxicity/carcinogenicity testing.

PubMed

de Groot, A P; Feron, V J; Immel, H R

1988-05-01

In previous studies we observed an increased incidence of hyperplasia in the epithelium of the urinary bladder of rats fed cereal-based stock diet supplemented with 6% monosodium glutamate (MSG) for 3 months. Hyperplasia was not enhanced, however, when 6% MSG was fed in a purified casein diet. Further studies have been conducted to identify the dietary factor that caused the different response with the two diets. Feeding MSG had a marked alkalizing effect on the urine. Rats fed purified diet produced urine of higher acidity than did those fed stock diet, a finding attributed to the greater excess of base in the stock diet. When diets with a considerable excess of cations were fed, urinary pH showed a characteristic pattern of widely differing values during a 24-hr period, with high values (pH greater than or equal to 8] for several hours of darkness, when food intake was high, declining during the day to a minimum at the end of the light period. Hyperplasia of the bladder epithelium was induced not only by feeding MSG, but also by feeding 5% of the alkalizing salt KHCO3, both in purified diet and in stock diet. The epithelial response to an alkalizing substance was prevented by simultaneous feeding of the acidifying salt NH4Cl. These findings indicate that the bladder changes induced by MSG are attributable to its alkalizing properties rather than to MSG per se. Moderate to severe hyperplasia of the bladder epithelium was induced also by feeding 5% NH4Cl in purified diet, a procedure accompanied by a further lowering of urinary pH. These findings showed that hyperplasia of the bladder epithelium of rats can be induced both by acidifying and by alkalizing the urine through manipulation of the acid-base balance of the basal diet. There is thus a possibility that, in carcinogenicity studies, administration of compounds to rats in the form of a salt may lead to erroneous conclusions.

Oral erlotinib, but not rapamycin, causes modest acceleration of bladder and hindlimb recovery from spinal cord injury in rats.

PubMed

Kjell, J; Pernold, K; Olson, L; Abrams, M B

2014-03-01

Erlotinib and Rapamycin are both in clinical use and experimental inhibition of their respective molecular targets, EGFR and mTORC1, has improved recovery from spinal cord injury. Our aim was to determine if daily Erlotinib or Rapamycin treatment started directly after spinal contusion injury in rats improves locomotion function or recovery of bladder function. Stockholm, Sweden. Rats were subjected to contusion injuries and treated during the acute phase with either Erlotinib or Rapamycin. Recovery of bladder function was monitored by measuring residual urine volume and hindlimb locomotion assessed by open-field observations using the BBB rating scale as well as by automated registration of gait parameters. Body weights were monitored. To determine whether Erlotinib and Rapamycin inhibit the same signaling pathway, a cell culture system and western blots were used. Erlotinib accelerated locomotor recovery and slightly improved bladder recovery; however, we found no long-term improvements of locomotor function. Rapamycin did neither improved locomotor function nor bladder recovery. In vitro studies confirmed that Erlotinib and Rapamycin both inhibit the EGFR-mTORC1 signaling pathway. We conclude that none of these two drug regimes improved long-term functional outcome in our current model of spinal cord injury. Nevertheless, oral treatment with Erlotinib may offer modest temporary advantages, whereas treatment with Rapamycin does not.

LYMPHOEPITHELIOMA-LIKE CARCINOMA OF THE URINARY BLADDER ASSOCIATED WITH SCHISTOSOMIASIS: A CASE REPORT AND REVIEW OF LITERATURE.

PubMed

Mina, Samir N; Antonios, Sanaa N

2015-08-01

Lymphoepithelioma-like carcinoma is an undifferentiated carcinoma with histological features similar to undifferentiated, non-keratinizing carcinoma of the nasopharynx. Lymphoepithelioma-like carcinoma of the urinary bladder is uncommon with a reported. incidence of 0.4% -1.3% of all bladder cancers. This case describes an 80 years old Egyptian male patient presented with recurrent hematuria and necroturia. Cystoscopy revealed a tumor involving the left lateral and the posterior wall of the urinary bladder. The patient underwent transurethral resection of the bladder tumor. Pathological examination showed muscle invasive lymphoepithelioma-like carcinoma associated with schistosomiasis of the urinary bladder. To the best of our knowledge the association of schistosomiasis with lymphoepithelioma-like bladder cancer was not described in the literature before this case report.

Expression of brain derived-neurotrophic factor and granulocyte-colony stimulating factor in the urothelium: relation with voiding function.

PubMed

Yuk, Seung Mo; Shin, Ju Hyun; Song, Ki Hak; Na, Yong Gil; Lim, Jae Sung; Sul, Chong Koo

2015-05-08

We designed this experiment to elucidate the relationship between the expression of brain derived-neurotrophic factor (BDNF), the expression of granulocyte-colony stimulating factor (G-CSF), and the development of overactive bladder (OAB). In our previous study, the urothelium was observed to be more than a simple mechanosensory receptor and was found to be a potential therapeutic target for OAB. Moreover, neuregulin-1 and BDNF were found to be potential new biomarkers of OAB. Here, we investigated the relationship between changes in the voiding pattern and the expression of BDNF and G-CSF in the urothelium and evaluated the effects of 5-hydroxymethyl tolterodine (5-HMT) on rats with bladder outlet obstruction (BOO). A total of 100 Sprague-Dawley rats were divided into the following groups: 20 control rats; 40 BOO rats; and 40 BOO rats administered 5-HMT (0.1 mg/kg). After BOO was induced for 4 weeks, the rats were assessed by cystometrography. The changes in BDNF and G-CSF expression were examined in both separated urothelial tissues and in cultured urothelial cells by reverse transcription polymerase chain reaction (RT-PCR). BOO rats showed increased non-voiding activity [NVA; (number/10 voidings)] and bladder weight and decreased micturition volume (MV), micturition interval (MI), and micturition time (MT) relative to the controls. Moreover, the 5-HMT administration rats showed decreased NVA and bladder weight and increased MV and MI in comparison to the BOO rats. BDNF and G-CSF expression was increased in BOO rats and decreased following 5-HMT administration. In this model, voiding dysfunction developed as a result of BOO. As a therapeutic agent for OAB, the administration of 5-HMT improved the voiding dysfunction. BDNF and G-CSF might modulate voiding patterns through micturition pathways and might be involved only in the urothelium. Moreover, the expression of both genes in the urothelium might be related to voiding dysfunction in OAB patients. Thus, the urothelium has an important role in the manifestation of voiding symptoms.

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.

Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Low Energy Shock Waves.

PubMed

Chuang, Yao-Chi; Huang, Tung-Liang; Tyagi, Pradeep; Huang, Chao-Cheng

2016-08-01

We investigated the feasibility of using low energy shock waves for intravesical botulinum toxin A delivery. We also evaluated its efficacy for acetic acid induced bladder hyperactivity in rats. In study 1 magnetic resonance imaging with intravesical administration of Gd-DTPA (Gd-diethylenetriamine pentaacetic acid) contrast medium was performed to visualize increased bladder urothelial permeability after low energy shock waves. In study 2 saline (1 ml) or botulinum toxin A (20 U/1 ml saline) was administered in the bladder with or without low energy shock waves (300 pulses at 0.12 mJ/mm(2)) and retained for 1 hour on day 1. Continuous cystometrograms were performed on day 8 by filling the bladder with saline followed by 0.3% acetic acid. The bladder was harvested for histology, and SNAP-25, SNAP-23 and COX-2 expression by Western blot or immunostaining. Magnetic resonance imaging established bladder urothelial leakage of Gd-DTPA after low energy shock waves, which was not seen in controls. The intercontraction interval was decreased 71.9%, 72.6% and 70.6% after intravesical instillation of acetic acid in saline, saline plus low energy shock wave and botulinum toxin A pretreated rats, respectively. However, rats that received botulinum toxin A plus low energy shock waves showed a significantly reduced response (48.6% decreased intercontraction interval) to acetic acid instillation without compromising voiding function. Rats pretreated with botulinum toxin A plus low energy shock waves showed a decreased inflammatory reaction (p <0.05), and decreased expression of SNAP-23 (p <0.05), SNAP-25 (p = 0.061) and COX-2 (p <0.05) compared with the control group. Low energy shock waves increased urothelial permeability, facilitated intravesical botulinum toxin A delivery and blocked acetic acid induced hyperactive bladder. These results support low energy shock waves as a promising method to deliver botulinum toxin A without the need for injection. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Saw palmetto is an indirectly acting sympathomimetic in the rat-isolated prostate gland.

PubMed

Cao, Nga; Haynes, John M; Ventura, Sabatino

2006-02-01

To investigate whether saw palmetto that inhibits alpha1-adrenoceptor binding in vitro affects contractility of the rat prostate gland. The effects of a commercially available saw palmetto extract were examined on the contractility of rat-isolated prostate glands. The extract was tested in the presence and absence of phentolamine, prazosin, yohimbine, propranolol, hexamethonium, cocaine, desipramine, nifedipine, guanethidine, atropine, and alpha,beta-methylene ATP to evaluate the mechanism of action. Isolated preparations of rat vas deferens and bladder were used for comparison. Unexpectedly, saw palmetto extract caused contractions of the rat prostate gland that could be attenuated by prazosin, phentolamine, nifedipine, guanethidine, cocaine, and desipramine but not by any of the other pharmacological tools. Similar contractile effects were observed in rat-isolated vas deferens preparations but not in rat-isolated bladder preparations. In the rat prostate gland, saw palmetto extract causes indirect alpha1-adrenoceptor-mediated contractions via the release of noradrenaline from sympathetic neurons. Copyright 2005 Wiley-Liss, Inc.

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

Single Versus Customized Treatment Planning for Image-guided High-Dose-Rate Brachytherapy for Cervical Cancer: Dosimetric Comparison and Predicting Factor for Organs at Risk Overdose With Single Plan Approach

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

Chi, Alexander; Gao Mingcheng; Sinacore, James

2009-09-01

Purpose: To compare the dose distribution between customized planning (CP) and adopting a single plan (SP) in multifractionated high-dose-rate brachytherapy and to establish predictors for the necessity of CP in a given patient. Methods and Materials: A total of 50 computed tomography-based plans for 10 patients were evaluated. Each patient had received 6 Gy for five fractions. The clinical target volume and organs at risk (i.e., rectum, bladder, sigmoid, and small bowel) were delineated on each computed tomography scan. For the SP approach, the same dwell position and time was used for all fractions. For the CP approach, the dwellmore » position and time were reoptimized for each fraction. Applicator position variation was determined by measuring the distance between the posterior bladder wall and the tandem at the level of the vaginal fornices. Results: The organs at risk D{sub 2cc} (dose to 2 cc volume) was increased with the SP approach. The dose variation was statistically similar between the tandem and ring and tandem and ovoid groups. The bladder D{sub 2cc} dose was 81.95-105.42 Gy{sub 2} for CP and 82.11-122.49 Gy{sub 2} for SP. In 5 of the 10 patients, the bladder would have been significantly overdosed with the SP approach. The variation of the posterior bladder wall distance from that in the first fraction was correlated with the increase in the bladder D{sub 2cc} (SP/CP), with a correlation coefficient of -0.59. Conclusion: Our results support the use of CP instead of the SP approach to help avoid a significant overdose to the bladder. This is especially true for a decrease in the posterior wall distance of {>=}0.5 cm compared with that in the first fraction.« less

CT in the diagnosis of enterovesical fistulae

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

Goldman, S.M.; Fishman, E.K.; Gatewood, O.M.B.

1985-06-01

Enterovesical fistulae are difficult to demonstrate by conventional radiographic methods. Computed tomography (CT), a sensitive, noninvasive method of documenting the presence of such fistulae, is unique in its ability to outline the extravesical component of the primary disease process. Twenty enterovesical fistulae identified by CT were caused by diverticulitis (nine), carcinoma of the rectosigmoid (two), Crohn disease (three), gynecologic tumors (two), bladder cancer (one), cecal carcinoma (one), prostatic neoplasia (one), and appendiceal abscess (one). The CT findings included intravesical air (90%), passage of orally or rectally administered contrast medium into the bladder (20%), focal bladder-wall thickening (90%), thickening of adjacentmore » bowel wall (85%), and an extraluminal mass that often contained air (75%). CT proved to be an important new method in the diagnosis of enterovesical fistulae.« less

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

Bladder welding in rats using controlled temperature CO2 laser system.

PubMed

Lobik, L; Ravid, A; Nissenkorn, I; Kariv, N; Bernheim, J; Katzir, A

1999-05-01

Laser tissue welding has potential advantages over conventional suture closure of surgical wounds. It is a noncontact technique that introduces no foreign body and limits the possibility of infections and complications. The closure could be immediately watertight and the procedure may be less traumatic, faster and easier. In spite of these positives laser welding has not yet been approved for wide use. The problem in the clinical implementation of this technique arises from the difficulty in defining the conditions under which a highly reliable weld is formed. We have assumed that the successful welding of tissues depends on the ability to monitor and control the surface temperature during the procedure, thereby avoiding underheating or overheating. The purpose of this work was to develop a laser system for reliable welding of urinary tract tissues under good temperature control. We have developed a "smart" laser system that is capable of a dual role: transmitting CO2 laser power for tissue heating, and noncontact (radiometric) temperature monitoring and control. Bladder opening (cystotomy) was performed in 38 rats. Thirty-three animals underwent laser welding. In 5 rats (control group) the bladder wound was closed with one layer of continuous 6-0 dexon sutures. Reliable welding was obtained when the surface temperature was kept at 71 + 5C. Quality of weld was controlled immediately after operation. The rats were sacrificed on days 2, 10 and 30 for histological study. Bladder closure using the laser welding system was successful in 31/33 (94%) animals. Histological examination revealed an excellent welding and healing of the tissue. Efficiency of laser welding of urinary bladder in rats was confirmed by high survival rate and quality of scar that was demonstrated by clinical and histological examinations. In the future, optimal laser welding conditions will be studied in larger animals, using CO2 lasers and other lasers, with deeper radiation penetration into tissues.

Ba-Wei-Die-Huang-Wan (Hachimi-jio-gan) can ameliorate cyclophosphamide-induced ongoing bladder overactivity and acidic adenosine triphosphate solution-induced hyperactivity on rats prestimulated bladder.

PubMed

Lee, Wei-Chia; Wu, Chia-Ching; Chuang, Yao-Chi; Tain, You-Lin; Chiang, Po-Hui

2016-05-26

Ba-Wei-Die-Huang-Wan (BWDHW) is the traditional Chinese medicine formula containing eight ingredients, namely Rehmannia glutinosa (Gaetn.) DC., root, steamed & dried; Cornus officinalis Siebold & Zucc., fructus, dried; Dioscorea oppositifolia L., root, dried; Alisma plantago-aquatica, subsp. orientale (Sam.) Sam., tuber, dried; Poria cocos (Fr.) Wolf., sclerotium, dried; Paeonia×suffruticosa Andrews, bark, dried; Cinnamomum cassia (Nees & T.Nees) J. Presl, bark, dried; Aconitum carmichaeli Debeaux, lateral root, dried & processed. It has been used for diabetes and urinary frequency treatments. We investigate effects of BWDHW on cyclophosphamide (CYP)-induced ongoing bladder overactivity and acidic adenosine triphosphate (ATP) solution-induced hyperactivity on rat's prestimulated bladder. Female Wistar rats were injected with intraperitoneal CYP (100mg/kg) or saline respectively. Rats were treated with BWDHW (90mg/kg/day) or vehicle for the next five days. After treatments animals were evaluated both in metabolic cage model and then by cystometry. Acidic ATP solution (5mM, pH 3.3) was instilled to provoke bladder hyperactivity. Bladder mucosa and muscle proteins were assessed by Western blotting. As compared to the controls, the CYP group showed significantly decreased mean cystometric intercontractile interval and increased micturition frequency, whereas the CYP/BWDWH group did not. The CYP group had significant protein overexpression in mucosal M2, M3, P2X2, and P2X3 receptors as well as detrusor M2 and M3 receptors. However, the CYP/BWDWH group had insignificant changes from controls. In the provoking test, the control/BWDHW and CYP/BWDHW groups were less affected by acidic ATP stimulation of intercontractile interval changes than the control group. Compared to the control group, the control/BWDHW group showed significantly lower mucosal P2X3 protein expression and the CYP group showed significant mucosal TRPV1 protein upregulation after the provoking test. BWDHW treatment can ameliorate CYP-induced ongoing bladder overactivity and suppress mucosal P2X2, P2X3, M2, and M3 receptor protein overexpression, as well as detrusor M2 and M3 receptor protein overexpression. BWDHW pretreatment can reduce acidic ATP solution-provoked hyperactivity by preventing TRPV1 receptor overexpression in CYP-treated bladder mucosa and inhibiting P2X3 receptor overexpression in naïve bladder mucosa. Copyright © 2016. Published by Elsevier Ireland Ltd.

Preconditioning methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model

PubMed Central

MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI

2014-01-01

Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition. PMID:24649309

Demonstration of muscarinic and nicotinic receptor binding activities of distigmine to treat detrusor underactivity.

PubMed

Harada, Taketsugu; Fushimi, Kazumi; Kato, Aya; Ito, Yoshihiko; Nishijima, Saori; Sugaya, Kimio; Yamada, Shizuo

2010-01-01

The present study was undertaken to examine whether distigmine, a therapeutic agent used to treat detrusor underactivity, binds directly to muscarinic and nicotinic receptors. We used radioreceptor binding assays and compared the effects of distigmine with those of neostigmine and donepedil. The inhibitory effect of distigmine on the blood acetylcholinesterase (AChE) activity was significantly weaker than that of neostigmine. Distigmine, neostigmine, and donepezil competed for specific binding sites of [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS ) and [(3)H]oxotremorine-M in the bladder, submaxillary gland and cerebral cortex of rats in a concentration-dependent manner, indicating significant binding activity of muscarinic receptors. Distigmine displayed significantly higher affinity for binding sites of [(3)H]oxotremorine-M compared with those of [(3)H]NMS as revealed by large ratios of its K(i) value for [(3)H]NMS to that for [(3)H]oxotremorine-M, suggesting that it has preferential affinity for agonist sites of muscarinic receptors. Distigmine seemed to bind to the agonist sites of muscarinic receptors in a competitive manner. Repeated oral administration of distigmine caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]NMS in the bladder and submaxillary gland but not cerebral cortex. Distigmine also bound to nicotinic receptors in the rat cerebral cortex. In conclusion, distigmine shows direct binding to muscarinic receptors in the rat bladder, and repeated oral administration of distigmine causes downregulation of muscarinic receptors in the rat bladder. The observed direct interaction of distigmine with the bladder muscarinic receptors may partly contribute to the therapeutic and/or side effects seen in the treatment of detrusor underactivity.

The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.

PubMed

Persyn, Sara; De Wachter, Stefan; Wyndaele, Jean-Jacques; Eastham, Jane; Gillespie, James

2016-07-01

β3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the β3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by β1/β2-adrenoceptor mechanisms. No evidence was obtained for any β3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of β3-adrenergic agonists remains unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Sex steroid receptors in male human bladder: expression and biological function.

PubMed

Chavalmane, Aravinda K; Comeglio, Paolo; Morelli, Annamaria; Filippi, Sandra; Fibbi, Benedetta; Vignozzi, Linda; Sarchielli, Erica; Marchetta, Matilde; Failli, Paola; Sandner, Peter; Saad, Farid; Gacci, Mauro; Vannelli, Gabriella B; Maggi, Mario

2010-08-01

In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens. Within the bladder, LUTS are linked to RhoA/Rho-kinase (ROCK) pathway overactivity. To investigate the effects of changing sex steroids on bladder smooth muscle. ER α, ER β, GPR30/GPER1 and aromatase mRNA expression was analyzed in male genitourinary tract tissues, and cells isolated from bladder, prostate, and urethra. Estrogen and G1 effect on RhoA/ROCK signaling output like cell migration, gene expression, and cytoskeletal remodeling, and [Ca(2+) ](i) was also studied in hB cells. Contractile studies on bladder strips from castrated male rats supplemented with estradiol and testosterone was also performed. The effects of classical (ER α, ER β) and nonclassical (GPR30/GPER1) estrogen receptor ligands (17 β-estradiol and G1, respectively) and androgens on RhoA/ROCK-.mediated cell functions were studied in hB cells. Contractility studies were also performed in bladder strips from castrated male rats supplemented with testosterone or estradiol. Aromatase and sex steroid receptors, including GPR30, were expressed in human bladder and mediates several biological functions. Both 17 β-estradiol and G1 activated calcium transients and induced RhoA/ROCK signaling (cell migration, cytoskeleton remodeling and smooth muscle gene expression). RhoA/ROCK inhibitors blunted these effects. Estrogen-, but not androgen-supplementation to castrated rats increased sensitivity to the ROCK inhibitor, Y-27632 in isolated bladder strips. In hB cells, testosterone elicited effects similar to estrogen, which were abrogated by blocking its aromatization through letrozole. Our data indicate for the first time that estrogen-more than androgen-receptors up-regulate RhoA/ROCK signaling. Since an altered estrogen/androgen ratio characterizes conditions, such as aging, obesity and metabolic syndrome, often associated to LUTS, we speculate that a relative hyperestrogenism may induce bladder overactivity through the up-regulation of RhoA/ROCK pathway. © 2010 International Society for Sexual Medicine.

Modulation of smooth muscle tonus in the lower urinary tract: interplay of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP).

PubMed

Lin, Guiting; Fandel, Thomas M; Shindel, Alan W; Wang, Guifang; Banie, Lia; Ning, Hongxiu; Lue, Tom F; Lin, Ching-Shwun

2011-07-01

To assess and compare the expression and activity of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP) in rat bladder and urethra. Bladder and urethral smooth muscles were obtained from 2-month-old female Sprague-Dawley rats. They were analysed by real-time polymerase chain reaction for the mRNA expression of MLCK and myosin phosphatase-targeting subunit of protein phosphatase type 1 (MYPT1, a subunit of MLCP). Levels of MLCK and MYPT1 mRNA expression were determined as a ratio to the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The tissues were also analysed by Western blotting for MLCK and MYPT1 protein expression as a ratio to the expression of β-actin. A two-step enzymatic activity assay using phosphorylated and dephosphorylated smooth muscle myosin was used to assess MLCK and MLCP activity. MLCK mRNA expression was higher in the bladder than in the urethra [mean (sd) ratio to GAPDH: 0.26 (0.17) vs 0.14 (0.12); P = 0.09]. MYPT1 mRNA expression was significantly higher in the bladder than in the urethra [mean (sd) ratio to GAPDH: 2.31 (1.04) vs 0.56 (0.36); P = 0.001]. Expression of both MLCK and MYPT1 protein was significantly higher in the bladder compared with the urethra [mean (sd) ratio to β-actin: 1.63 (0.25) vs 0.91 (0.29) and 0.97 (0.10) vs 0.37 (0.29), respectively; both P < 0.001]. Enzymatic assay identified significantly greater MLCK activity in the bladder than in the urethra. While, MLCP activity was lower in the bladder than in the urethra. In healthy young female rats, MLCK activity is higher and MLCP activity is lower in the bladder relative to the urethra. These differences probably play a role in modulating the functional differences between bladder and urethral smooth muscle tone. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Co-cultures provide a new tool to probe communication between adult sensory neurons and urothelium.

PubMed

O'Mullane, Lauren M; Keast, Janet R; Osborne, Peregrine B

2013-08-01

Recent evidence suggests that the urothelium functions as a sensory transducer of chemical, mechanical or thermal stimuli and signals to nerve terminals and other cells in the bladder wall. The cellular and molecular basis of neuro-urothelial communication is not easily studied in the intact bladder. This led us to establish a method of co-culturing dorsal root ganglion sensory neurons and bladder urothelial cells. Sensory neurons and urothelial cells obtained from dorsal root ganglia and bladders dissected from adult female Sprague-Dawley® rats were isolated by enzyme treatment and mechanical dissociation. They were plated together or separately on collagen coated substrate and cultured in keratinocyte medium for 48 to 72 hours. Retrograde tracer labeling was performed to identify bladder afferents used for functional testing. Neurite growth and complexity in neurons co-cultured with urothelial cells was increased relative to that in neuronal monocultures. The growth promoting effect of urothelial cells was reduced by the tyrosine kinase inhibitor K252a but upstream inhibition of nerve growth factor signaling with TrkA-Fc had no effect. Fura-2 calcium imaging of urothelial cells showed responses to adenosine triphosphate (100 μM) and activation of TRPV4 (4α-PDD, 10 μM) but not TRPV1 (capsaicin, 1 μM), TRPV3 (farnesyl pyrophosphate, 1 μM) or TRPA1 (mustard oil, 100 μM). In contrast, co-cultured neurons were activated by all agonists except farnesyl pyrophosphate. Co-culturing provides a new methodology for investigating neuro-urothelial interactions in animal models of urological conditions. Results suggest that neuronal properties are maintained in the presence of urothelium and neurite growth is potentiated by a nerve growth factor independent mechanism. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

PubMed Central

Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.

2016-01-01

Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r2 = 0.87–0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2. Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1–0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10–50% of the change in pelvic urine/medullary Po2. Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

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

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.

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.

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.

Inflatable bladder provides accurate calibration of pressure switch

NASA Technical Reports Server (NTRS)

Smith, N. J.

1965-01-01

Calibration of a pressure switch is accurately checked by a thin-walled circular bladder. It is placed in the pressure switch and applies force to the switch diaphragm when expanded by an external pressure source. The disturbance to the normal operation of the switch is minimal.

[Impacts on urodynamic parameters and the protein expressions of M2 and M3 receptors of detrusor in the rats of detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8)].

PubMed

Liu, Yi; Wang, Xuerui; Li, Tianran; Lin, Liting; Shi, Guangxia; Fu, Yuanbo; Liu, Cunzhi

2017-04-12

To discuss the effects on detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8) and its mechanism. Thirty female adult SD rats were selected. The model of detrusor hyperreflexia was prepared with complete spinal transection at T 9 , of which, 20 rats were randomized into a model group (10 rats) and a moxibustion group (10 rats). A sham-operation group (10 rats) was set up for sham-spinal transection. In the moxibustion group, when urine incontinence occurred (about in 2 weeks of modeling), the ginger-salt-isolated moxibustion at "Shenque" (CV 8) was given, 3 moxa cones each time, once a day, continuously for 7 days. After treatment, in each group, the urodynamic parameters were determined, after which, the bladder detrusor was collected. Western blot was used to determine the protein expressions of M2 and M3 receptors. Compared with the sham-operation group, the micturition interval was shortened apparently ( P <0.01); the maximal bladder pressure was increased apparently ( P <0.01); the protein expression of M2 receptor in the detrusor was increased significantly ( P <0.05) and that of M3 receptor had no apparent change ( P >0.05) in the rats of the model group. Compared with the model group, the micturition interval was longer apparently ( P <0.01), the maximal bladder pressure was reduced apparently ( P <0.01), the protein expression of M2 receptor in the detrusor was reduced significantly ( P <0.05) and that of M3 receptor had no apparent change ( P >0.05) in the rats of the moxibustion group.Compared with the sham-operation group, the results of the above indicators were not different significantly in the moxibustion group (all P >0.05). The ginger-salt-isolated moxibustion at "Shenque" (CV 8) suppresses the overactive bladder in the rat with spinal transection and its effect mechanism is possibly relevant with reducing the protein expression of detrusor M2 and inhibiting the excessive contraction of the detrusor.

Ultrasound assessment of bladder wall thickness as a screening test for detrusor instability.

PubMed

Abou-Gamrah, Amgad; Fawzy, Mounir; Sammour, Hazem; Tadros, Sherif

2014-05-01

The aim of the current study was to evaluate the diagnostic accuracy of transvaginal ultrasound measurement of bladder wall thickness (BWT) in diagnosis of over active bladder (OAB). The current prospective study was conducted at Ain Shams University Maternity Hospital over 2 years. Patients presented to the urogynecology outpatient clinic with symptoms of urinary frequency, urgency, nocturia and/or urge incontinence were included in this study. The allocated patients were divided into two groups; Group 1(study group): fifty (50) patients with urodynamic diagnosis of detrusor instability (OAB) were included. Group 2 (control): fifty (50) patients with urodynamic diagnosis of stress incontinence were included. Using a transvaginal probe, BWT was measured in three sites at the thickest part of (a) the dome of the bladder (b) the trigone, and (c) the anterior wall of the bladder. An average of the three measurements was considered as the mean bladder thickness. A total of 100 patients with lower urinary symptoms were finally analyzed. There were no statistical significant differences between both groups regarding age, parity and body mass index, while there was statistically longer disease duration in group 2. Excluding urgency, there was statistical significant difference (P < 0.001) regarding lower urinary tract symptoms namely frequency, urgency incontinence, coital incontinence and nocturia. Patients in group 1 were more positive to symptoms of frequency, urgency incontinence, and nocturia, while patients in group 2 were more positive regarding coital incontinence. The thickness of trigon, dome, anterior wall and mean BWT was significantly higher in group 1 when compared to group 2. Receiver operator characteristics curve was constructed for estimating the association between mean BWT and prediction of OAB in patients with lower urinary tract symptoms. Mean BWT at 4.78 mm was considered as best cut-off value for prediction of OAB with sensitivity of 90 % and specificity of 78 %. Mean BWT was significantly associated with OAB > 4.78 mm as denoted by the significantly large area under the curve [AUC], AUC was 0.905. In women with lower urinary tract symptom, transvaginal ultrasounds measured mean BWT seems to be an effective non invasive diagnostic tool for prediction of OAB.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

PubMed

Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

2016-06-01

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

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

Vanderlaan, M.; Fong, S.; King, E.B.

To improve identification of preneoplastic bladder cancer cells, we have studied two enzyme histochemical changes in bladder tumors induced in male Fisher 344 rats by the carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine. In early areas of focal nodular hyperplasia there was a dramatic increase in staining for NADH:menadione oxidoreductase (diaphorase) activity. In nonfocal areas as well, there were many individual cells with intense staining, while the controls were of uniform moderate staining. Large papillomas and carcinomas often showed heterogeneous staining, ..gamma..-Glutamyltranspeptidase (GGT) was absent from normal urothelium and from all tumors except the most advanced carcinomas and large papillomas. In old, carcinogen-exposed animals, GGTmore » activity was seen in the luminal surface of tumors and in the interlesion urothelium. In newborn rats and in rats with regenerative hyperplasia following wounding of the urothelium, the diaphorase staining was less than that in the untreated adult. Our findings suggest that increased diaphorase activity may serve to identify early islands of carcinogen-induced, enzymatically altered bladder cells, while GGT will not.« less

New clinical trial open for patients with muscle-invasive bladder cancer | Center for Cancer Research

Cancer.gov

Muscle-invasive bladder cancer is an aggressive form of bladder cancer in which the tumor invades deep into the musculature of the bladder wall, making it more likely to spread to other parts of the body. Standard treatment involves cisplatin-based chemotherapy followed by radical cystectomy, which is surgery to remove the bladder and nearby organs. However, many patients don’t receive chemotherapy before surgery or may not respond to it. Other patients are ineligible for cisplatin treatment due to poor kidney function. CCR investigators are leading a phase III trial to determine whether an immunotherapy drug given shortly after cystectomy can help these patients. Read more…

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.

Pure Small Cell Carcinoma of the Bladder: A Case Report

PubMed Central

Trabelsi, Amel; Abdelkrim, Soumaya Ben; Tebra, Samah; Gharbi, Olfa; Jaidane, Lilia; Bouaouina, Noureddine; Abbassi, Dajla Bakir; Mokni, Moncef

2010-01-01

Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases. PMID:29147197

Pure Small Cell Carcinoma of the Bladder: A Case Report.

PubMed

Trabelsi, Amel; Abdelkrim, Soumaya Ben; Tebra, Samah; Gharbi, Olfa; Jaidane, Lilia; Bouaouina, Noureddine; Abbassi, Dajla Bakir; Mokni, Moncef

2010-06-01

Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases.

Effects of seven chemicals on DNA damage in the rat urinary bladder: a comet assay study.

PubMed

Wada, Kunio; Yoshida, Toshinori; Takahashi, Naofumi; Matsumoto, Kyomu

2014-07-15

The in vivo comet assay has been used for the evaluation of DNA damage and repair in various tissues of rodents. However, it can give false-positive results due to non-specific DNA damage associated with cell death. In this study, we examined whether the in vivo comet assay can distinguish between genotoxic and non-genotoxic DNA damage in urinary bladder cells, by using the following seven chemicals related to urinary bladder carcinogenesis in rodents: N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), glycidol, 2,2-bis(bromomethyl)-1,3-propanediol (BMP), 2-nitroanisole (2-NA), benzyl isothiocyanate (BITC), uracil, and melamine. BBN, glycidol, BMP, and 2-NA are known to be Ames test-positive and they are expected to produce DNA damage in the absence of cytotoxicity. BITC, uracil, and melamine are Ames test-negative with metabolic activation but have the potential to induce non-specific DNA damage due to cytotoxicity. The test chemicals were administered orally to male Sprague-Dawley rats (five per group) for each of two consecutive days. Urinary bladders were sampled 3h after the second administration and urothelial cells were analyzed by the comet assay and subjected to histopathological examination to evaluate cytotoxicity. In the urinary bladders of rats treated with BBN, glycidol, and BMP, DNA damage was detected. In contrast, 2-NA induced neither DNA damage nor cytotoxicity. The non-genotoxic chemicals (BITC, uracil, and melamine) did not induce DNA damage in the urinary bladders under conditions where some histopathological changes were observed. The results indicate that the comet assay could distinguish between genotoxic and non-genotoxic chemicals and that no false-positive responses were obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression of Hsp27 correlated with rat detrusor contraction after acute urinary retention.

PubMed

Xiong, Zhiyong; Wang, Yongquan; Gong, Wei; Zhou, Zhansong; Lu, Gensheng

2013-09-01

Heat shock protein 27 (Hsp27) can regulate actin cytoskeleton dynamics and contractile protein activation. This study investigates whether Hsp27 expression is related to bladder contractile dysfunction after acute urinary retention (AUR). Female rats were randomized either to AUR by urethral ligation or to normal control group. Bladder and smooth muscle strip contraction at time points from 0 h to 7 days after AUR were estimated by cystometric and organ bath studies. Hsp27 expression in bladder tissue at each time point was detected with immunofluorescence, Western blots, and real-time PCR. Expression of the three phosphorylated forms of Hsp27 was detected by Western blots. Smooth muscle ultrastructure was observed by transmission electron microscopy. Data suggest that maximum detrusor pressure and both carbachol-induced and spontaneous detrusor strip contraction amplitude decreased gradually for the duration from 0 to 6 h, and then increased gradually to near-normal values at 24 h. Treatment of muscle strips with the p38MAK inhibitor, SB203580, inhibited carbachol-induced contractions. Smooth muscle ultrastructure damage was the highest at 6 h after AUR, and then lessened gradually during next 7 days, and ultrastructure was close to normal. Expressions of Hsp27 mRNA and protein and the proteins of the three phosphorylated forms were higher at 0 h, decreased to lower levels up to 6 h, and then gradually increased. Therefore, we conclude that rat bladder contractile function after AUR worsens during 0-6 h, and then gradually recovers. The findings of the current study suggest that Hsp27 modulates bladder smooth muscle contraction after AUR, and that phosphorylation of Hsp27 may be an important pathway modulating actin cytoskeleton dynamics in bladder smooth muscle contraction and reconstruction after injury.

Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

PubMed

Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

2007-05-01

We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.

Age-Related Alterations in Regeneration of the Urinary Bladder after Subtotal Cystectomy

DTIC Science & Technology

2013-11-01

buffer. The bladders were cut into approximately equally sized strips along the longitudinal axis. The strips were denuded of the urothelium and sub... urothelium and then were attached to tissue holds at one end and to force transducers at the other end in an organ bath system (Danish Myo Technology...of the urothelium and the bladder wall to reseal immediately after STC in old animals. This suppo- sition is consistent with the decreased PCNA

Urachal Tumor: A Case Report of an Extremely Rare Carcinoma.

PubMed

Palla Garcia, José; Sampaio, Rita; Peixoto, Carlos

2017-01-01

The urachus is a tubular structure that connects the bladder to the allantois in the embryonic development, involuting after the third trimester. The urachus carcinoma is an extremely rare tumor that accounts for <1% of all bladder cancers. We report a case of a 46-year-old woman, with no past medical history, complaining of hematuria with 6-month duration and a physical exam and an abdominal computed topographic scan revealing an exophytic mass of 6.8 cm longer axis that grew depending on the anterior bladder wall, invading the anterior abdominal wall. Cystoscopy detected mucosal erosion. The biopsy showed structures of adenocarcinoma of enteric type. The surgical specimen showed urachus adenocarcinoma of enteric type with stage IVA in the Sheldon system and stage III in the Mayo system. This case has a 3-year follow-up without disease recurrence.

[Virtual CT-pneumocystoscopy: indications, advantages and limitations. Our experience].

PubMed

Regine, Giovanni; Atzori, Maurizio; Buffa, Vitaliano; Miele, Vittorio; Ialongo, Pasquale; Adami, Loredana

2003-09-01

The use of CT volume-rendering techniques allows the evaluation of visceral organs without the need for endoscopy. Conventional endoscopic evaluation of the bladder is limited by the invasiveness of the technique and the difficulty exploring the entire bladder. Virtual evaluation of the bladder by three-dimensional CT reconstruction offers potential advantages and can be used in place of endoscopy. This study investigates the sensitivity of virtual CT in assessing lesion of the bladder wall to compare it with that of conventional endoscopy, and outlines the indications, advantages and disadvantages of virtual CT-pneumocystography. Between September 2001 and May 2002, 21 patients with haematuria and positive cystoscopic findings were studied. After an initial assessment by ultrasound, the patients underwent pelvic CT as a single volumetric scan after preliminary air distension of the bladder by means of 12 F Foley catheter. The images were processed on an independent workstation (Advantage 3.0 GE) running dedicated software for endoluminal navigation. The lesions detected by endoscopy were classified as sessile or pedunculated, and according to size (more or less than 5 mm). Finally, the results obtained at virtual cystoscopy were evaluated by two radiologists blinded to the conventional cystoscopy results. Thirty lesions (24 pedunculated, 6 sessile) were detected at conventional cystoscopy in 16 patients (multiple polyposis in 3 cases). Virtual cystoscopy identified 23 lesions (19 pedunculated and 4 sessile). The undetected lesions were pedunculated <5 mm (5 cases) and sessile (2 cases). One correctly identified pedunculated lesion was associated with a bladder stone. Good quality virtual images were obtained in all of the patients. In only one patient with multiple polyposis the quality of the virtual endoscopic evaluation was limited by the patient's intolerance to bladder distension, although identification of the lesions was not compromised. The overall sensitivity was 77%; this was higher for pedunculated lesions (79%) than for sessile lesions (50%). The virtual technique is less invasive and tends to be associated with fewer complications than is conventional cystoscopy. It also demonstrated a good sensitivity for evaluating pedunculated lesions, allowing evaluation of the bladder base and anterior wall, sites that are commonly poorly accessible at conventional cystoscopy. Further advantages of the virtual technique include the possibility of accurately measuring the extent of the lesion and obtaining virtual images even in patients with severe urethral obstruction and active bleeding. The limitations include the inability to obtain tissue for histologic examination or to perform endoscopic resection of pedunculated lesions. The technique is less sensitive than conventional cystoscopy in the detection of sessile lesions or very small polyps (<5 mm). Furthermore, diffuse wall thickening reduces bladder distension thereby preventing optimal evaluation. The most valuable indication appears to be the follow-up of treated wall lesions. Virtual CT-pneumocystoscopy can replace conventional cystoscopy in cases with pedunculated lesions when there is no need for biopsy, when the lesions are located at the bladder base or when cystoscopic instrumentation cannot be introduced into the bladder due to stenosis. Virtual pneumocystoscopy can also be used in the follow-up of treated polypoid lesions in association with pelvic CT-angiography.

Loxoprofen inhibits facilitated micturition reflex induced by acetic acid urinary bladder infusion of the rats.

PubMed

Shinozaki, Sachiyo; Saito, Motoaki; Kawatani, Masahito

2005-02-01

Prostaglandins (PGs) are well known as one of the chemical mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), PG synthesis inhibitors, are used for anti-nociception and/or anti-inflammation. We examine the effect of loxoprofen, an NSAID, on micturiton in acetic acid-induced bladder inflammation of the rats. In cystometrogram study with saline infusion into the urinary bladder, loxoprofen did not alter the interval of bladder contraction (IC, 107% of the control). IC was shortened by acetic acid infusion (65% of the control) and loxoprofen prolonged the IC (162% of acetic acid infused period). This prolonged IC was approximately same as the control. Loxoprofen did not alter the threshold pressure and the maximal voiding pressure. These data suggest that PGE2 might not play a part of normal micturition and may play a part of the micturition reflex during acetic acid infusion. That is, loxoprofen might be useful for pathological hyperreflex of the micturition.

Xanthine crystals induced by topiroxostat, a xanthine oxidoreductase inhibitor, in rats, cause transitional cell tumors.

PubMed

Shimo, Takeo; Moto, Mitsuyoshi; Ashizawa, Naoki; Matsumoto, Koji; Iwanaga, Takashi; Saito, Kazuhiro

2014-04-01

The present study was performed to elucidate the underlying mechanism of transitional cell tumors found in the carcinogenicity testing of topiroxostat, a xanthine oxidoreductase inhibitor, in which topiroxostat was orally given to F344 rats at 0.3, 1, and 3 mg/kg for 2 years. In the urinary bladder, transitional cell papillomas and/or carcinomas were seen in males receiving 0.3, 1, and 3 mg/kg (1/49, 3/49, and 10/50, respectively). In the kidney, transitional cell papillomas and/or carcinomas in the pelvis were seen in 2/50 males and 1/50 females receiving 3 mg/kg. In the mechanistic study by 52-week oral treatment with topiroxostat at 3 mg/kg to F344 male rats, with and without citrate, simple and papillary transitional cell hyperplasias of the urinary bladder epithelium were observed in 5/17 in the topiroxostat-alone treatment group, along with xanthine-induced nephropathy, in contrast to neither xanthine crystals nor lesions in urinary organs by co-treatment group with citrate. As for sex differences of urinary bladder tumors, the BrdU labeling index for epithelial cells of the urinary bladder by 5-week oral treatment with topiroxostat at 10 mg/kg to F344 rats was increased in males only, showing consistency with histopathological findings. Therefore, the present study indicates that transitional cell tumors induced by topiroxostat in rats were due to physical stimulation to transitional cells of xanthine crystals/calculi and provides that other factors were not implicated in this tumorigenesis. Furthermore, the present study suggests that such tumors do not predict for humans since topiroxostat-induced xanthine deposition is a rodent-specific event.

Prevention of Chemically-Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy

PubMed Central

Lubet, Ronald A.; Scheiman, James M.; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M. Margaret; Boring, Daniel L.; Steele, Vernon E.; Grubbs, Clinton J.

2015-01-01

The COX inhibitors (NSAIDs/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2 specific inhibitors have progressed to clinical trials, and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular (CV) effects. Certain NSAIDs (e.g., naproxen (NPX)] have a good cardiac profile, but can cause gastric toxicity. The present studies examined protocols to reduce this toxicity of NPX. Female Fischer-344 rats were treated weekly with the urinary bladder specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/Kg BW/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/Kg BW/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), NPX alone or combined with omeprazole prevented cancers; yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN treated rats were administered NPX: (A) daily, (B) 1 week daily NPX/1wk vehicle, (C) 3 weeks daily NPX/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C and D resulted in palpable cancers in 27%, 22%, 19% and 96% of rats (P<0.01). Short-term NPX treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols which should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g. NPX) in clinical prevention trials. PMID:25762530

Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy.

PubMed

Lubet, Ronald A; Scheiman, James M; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M Margaret; Boring, Daniel L; Steele, Vernon E; Grubbs, Clinton J

2015-04-01

The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder-specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN -: treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P < 0.01). Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. ©2015 American Association for Cancer Research.

Comparison of the effects of several potassium-channel openers on rat bladder and rat portal vein in vitro.

PubMed Central

Edwards, G.; Henshaw, M.; Miller, M.; Weston, A. H.

1991-01-01

1. The ability of several K-channel openers to inhibit KCl-induced contractions of rat bladder detrusor and spontaneous mechanical activity in rat portal vein was examined. 2. Lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 dose-dependently relaxed rat detrusor, precontracted with 20 mM KCl. With the exception of pinacidil, concentrations of these agents below 30 microM did not inhibit 80 mM KCl-included contractions. Pinacidil (10 microM) produced a small, but significant (P < 0.05) relaxation of 80 mM KCl-induced mechanical activity. Minoxidil sulphate and BRL 38226 produced some relaxation of 20 mM but not 80 mM KCl-induced contractions. 3. Glibenclamide (0.3-3 microM) antagonized the relaxant effects of lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 in a competitive manner (pA2 values 6.3-6.6). The effects of minoxidil sulphate and BRL 38226 were fully antagonized by 3 microM glibenclamide. 4. Lemakalim, pinacidil, S 0121, BRL 38226 and minoxidil sulphate were each approximately 8 times more potent as inhibitors of the spontaneous contractions of rat portal vein than KCl-induced contractions of the rat detrusor. Minoxidil sulphate was approximately 30 times more potent in the rat portal vein than in the bladder. This may indicate that either minoxidil sulphate is acting at different recognition sites in these two tissues, or that this compound has an additional mechanism of action in the portal vein. 5. With the exception of minoxidil sulphate, all the compounds tested stimulated 86Rb efflux and 42K efflux from preloaded rat detrusor strips.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1364839

Suture material in bladder surgery: a comparison of polydioxanone, polyglactin, and chromic catgut.

PubMed

Stewart, D W; Buffington, P J; Wacksman, J

1990-06-01

A comparison of polydioxanone, polyglactin, and chromic catgut suture was performed in 120 rat bladders studying propensity for infection, degree of inflammation, calculogenic potential, changes in urine pH, and suture absorption. None of the sutures predisposed to infection and there was wide variability but no correlation in urine pH. Although initially the polydioxanone incited a greater inflammatory response, by six months all three sutures were similar. The absorption of polydioxanone was slower than chromic catgut suture, but similar to the absorption of polyglactin. There was no significant difference in calculogenic potential between the suture materials tested over a six-month period. Based on this study in rats, polydioxanone suture would appear to be equal to catgut and polyglactin suture in bladder surgery.

Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

PubMed

Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

1987-04-01

Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG to surfaces and suggest that it is the primary component mediating attachment within the bladder. Moreover, the data suggest that the BCG-fibronectin interaction may be a requisite first step for the initiation of the antitumor activity in intravesical BCG for bladder cancer.

Toward Self-Control Systems for Neurogenic Underactive Bladder: A Triboelectric Nanogenerator Sensor Integrated with a Bistable Micro-Actuator.

PubMed

Arab Hassani, Faezeh; Mogan, Roshini P; Gammad, Gil G L; Wang, Hao; Yen, Shih-Cheng; Thakor, Nitish V; Lee, Chengkuo

2018-04-24

Aging, neurologic diseases, and diabetes are a few risk factors that may lead to underactive bladder (UAB) syndrome. Despite all of the serious consequences of UAB, current solutions, the most common being ureteric catheterization, are all accompanied by serious shortcomings. The necessity of multiple catheterizations per day for a physically able patient not only reduces the quality of life with constant discomfort and pain but also can end up causing serious complications. Here, we present a bistable actuator to empty the bladder by incorporating shape memory alloy components integrated on flexible polyvinyl chloride sheets. The introduction of two compression and restoration phases for the actuator allows for repeated actuation for a more complete voiding of the bladder. The proposed actuator exhibits one of the highest reported voiding percentages of up to 78% of the bladder volume in an anesthetized rat after only 20 s of actuation. This amount of voiding is comparable to the common catheterization method, and its one time implantation onto the bladder rectifies the drawbacks of multiple catheterizations per day. Furthermore, the scaling of the device for animal models larger than rats can be easily achieved by adjusting the number of nitinol springs. For neurogenic UAB patients with degraded nerve function as well as degenerated detrusor muscle, we integrate a flexible triboelectric nanogenerator sensor with the actuator to detect the fullness of the bladder. The sensitivity of this sensor to the filling status of the bladder shows its capability for defining a self-control system in the future that would allow autonomous micturition.

Foam rigidized inflatable structural assemblies

NASA Technical Reports Server (NTRS)

Tinker, Michael L. (Inventor); Schnell, Andrew R. (Inventor)

2010-01-01

An inflatable and rigidizable structure for use as a habitat or a load bearing structure is disclosed. The structure consists of an outer wall and an inner wall defining a containment member and a bladder. The bladder is pressurized to erect the structure from an initially collapsed state. The containment member is subsequently injected with rigidizable fluid through an arrangement of injection ports. Exhaust gases from the curing rigidizable fluid are vented through an arrangement of exhaust ports. The rate of erection can be controlled by frictional engagement with a container or by using a tether. A method for fabricating a tubular structure is disclosed.

Computer-aided detection of bladder mass within non-contrast-enhanced region of CT Urography (CTU)

NASA Astrophysics Data System (ADS)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Zhou, Chuan

2016-03-01

We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). We have previously developed methods for detection of bladder masses within the contrast-enhanced region of the bladder. In this study, we investigated methods for detection of bladder masses within the non-contrast enhanced region. The bladder was first segmented using a newly developed deep-learning convolutional neural network in combination with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensityprojection- based method. The non-contrast region was smoothed and a gray level threshold was employed to segment the bladder wall and potential masses. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify lesion candidates as a prescreening step. The lesion candidates were segmented using our autoinitialized cascaded level set (AI-CALS) segmentation method, and 27 morphological features were extracted for each candidate. Stepwise feature selection with simplex optimization and leave-one-case-out resampling were used for training and validation of a false positive (FP) classifier. In each leave-one-case-out cycle, features were selected from the training cases and a linear discriminant analysis (LDA) classifier was designed to merge the selected features into a single score for classification of the left-out test case. A data set of 33 cases with 42 biopsy-proven lesions in the noncontrast enhanced region was collected. During prescreening, the system obtained 83.3% sensitivity at an average of 2.4 FPs/case. After feature extraction and FP reduction by LDA, the system achieved 81.0% sensitivity at 2.0 FPs/case, and 73.8% sensitivity at 1.5 FPs/case.

Differences in muscle activation patterns during pelvic floor muscle contraction and Valsalva maneuver.

PubMed

Thompson, Judith A; O'Sullivan, Peter B; Briffa, N Kathryn; Neumann, Patricia

2006-01-01

To investigate the different muscle activation patterns around the abdomino-pelvic cavity in continent women and their effect on pressure generation during a correct pelvic floor muscle (PFM) contraction and a Valsalva maneuver. Thirteen continent women were assessed. Abdominal, chest wall, and PFM activity and vaginal and intra-abdominal pressure (IAP), were recorded during two tasks: PFM contraction and Valsalva whilst bladder base position was monitored on trans-abdominal ultrasound. A correct PFM contraction was defined as one that resulted in bladder base elevation and a Valsalva resulted in bladder base depression. Comparison of the mean of the normalized EMG activity of all the individual muscle groups was significantly different between PFM contraction and Valsalva (P = 0.04). During a correct PFM contraction, the PFM were more active than during Valsalva (P = 0.001). During Valsalva, all the abdominal muscles (IO (P = 0.006), EO (P < 0.001), RA (P = 0.011)), and the chest wall (P < 0.001) were more active than during PFM contraction. The change in IAP was greater during Valsalva (P = 0.001) but there was no difference in the change in vaginal pressure between PFM contraction and Valsalva (P = 0.971). This study demonstrates a difference in muscle activation patterns between a correct PFM contraction and Valsalva maneuver. It is important to include assessment of the abdominal wall, chest wall, and respiration in the clinical evaluation of women performing PFM exercises as abdominal wall bracing combined with an increase in chest wall activity may cause rises in IAP and PFM descent. (c) 2005 Wiley-Liss, Inc.

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.

HPLC assisted Raman spectroscopic studies on bladder cancer

NASA Astrophysics Data System (ADS)

Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

2015-04-01

We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

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.

Ultrasonographic evaluation of the canine urinary bladder following cystotomy for treatment of urolithiasis.

PubMed

Mariano, Abigail D; Penninck, Dominique G; Sutherland-Smith, James; Kudej, Raymond K

2018-05-01

OBJECTIVE To describe the ultrasonographic appearance of the urinary bladder incision site in dogs that underwent cystotomy for treatment of urolithiasis. DESIGN Prospective, longitudinal study. ANIMALS 18 client-owned dogs. PROCEDURES Dogs underwent urinary bladder ultrasonography at baseline (≤ 1 day before surgery) and at 1 day and approximately 2, 6, and 12 weeks after cystotomy for urocystolith removal. A baseline ratio between ventral (cystotomy site) and corresponding dorsal midline wall thickness was calculated and used to account for measurement variations attributable to bladder distension at subsequent visits. Patient signalment, weight, medications administered, urocystolith composition, and culture results were recorded. Clinical signs, reoccurrence of hyperechoic foci, and suture visualization were recorded at follow-up examinations. Variables were evaluated for association with cystotomy site thickening and resolution of thickening. RESULTS Median wall thickness at the ventral aspect of the bladder was significantly greater than that of the corresponding dorsal aspect at baseline. Cystotomy site thickening peaked 1 day after surgery and decreased at subsequent visits in a linear manner. Twelve weeks after surgery, 5 of 10 clinically normal dogs evaluated had persistent cystotomy site thickening. Eleven of 18 dogs had reoccurrence of hyperechoic foci within the bladder at some time during the study (median time to first detection, 17 days after surgery). CONCLUSIONS AND CLINICAL RELEVANCE Persistent cystotomy site thickening can be present up to 3 months after cystotomy for urolithiasis in dogs without lower urinary tract signs. Reoccurrence of hyperechoic foci in the bladder, although subclinical, was detected earlier and at a higher rate than anticipated.

Expression of HSP 70 and its mRNAS during ischemia-reperfusion in the rat bladder.

PubMed

Saito, Motoaki; Tominaga, Lika; Nanba, Eiji; Kinoshita, Yukako; Housi, Daisuke; Miyagawa, Ikuo; Satoh, Keisuke

2004-08-27

HSP 70 is an important protein that repairs damaged tissue after injury. In the present study, we investigated the expression of HSP 70 and its mRNAs during ischemia-reperfusion in the rat bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the bladder dome. Male Wistar rats, 8 weeks old, were divided into six groups: controls, 30-min ischemia, 30-min ischemia and 30-, 60-minute, 1- and 7-day reperfusion, groups A, B, C, D, E, and F, respectively. In functional studies, contractile responses to carbachol were measured in these groups. The expression of HSP 70-1/2 mRNAs was quantified using a real-time PCR method, and that of HSP 70 proteins was measured using ELISA in the bladders. In the functional study, Emax values of carbachol to bladders in the A, B, C, D, E and F groups were 9.3 +/- 1.3, 7.9 +/- 1.7, 4.3 +/- 0.8, 4.2 +/- 0.7, 4.5 +/- 0.6, and 8.1 +/- 1.2 g/mm2, respectively. In the control group, the expression of HSP 70-1/2 mRNA was detected, and the expression of HSP 70-1 mRNAs was significantly higher than that of HSP 70-2 mRNAs in each group. The expression of HSP 70-1 mRNA increased in groups B and C, but decreased in groups D, E, and F. The expression of HSP 70-2 mRNA in group C was significantly higher than that of groups A, D, E, and F. The expression of HSP 70-1/2 mRNAs after 1 day or 1 week of reperfusion was similar to control levels. The expression of HSP 70 proteins was increased shortly after the expression of their mRNAs. The expression of HSP 70 after 1 day or 1 week of reperfusion was almost identical to control levels. Our data indicate that contractile responses of the bladder were decreased by ischemia reperfusion, and that expression of HSP 70 and its mRNAs appeared to increase after a short period of the insult.

Management of the complications of BPH/BOO.

PubMed

Speakman, Mark J; Cheng, Xi

2014-04-01

Most men will develop histological BPH if they live long enough. Approximately, half will develop benign prostatic enlargement (BPE) and about half of these will get BOO with high bladder pressures and low flow, this in turn leads to detrusor wall hypertrophy. Many of these men will only have lower urinary tract symptoms (LUTS) but a significant number will also suffer the other complications of BPH. These include urinary retention (acute and chronic), haematuria, urinary tract infection, bladder stones, bladder wall damage, renal dysfunction, incontinence and erectile dysfunction. Recognition of the complications of BPH/BOO early allows more effective management of these complications. This is particularly important for the more serious urinary infections and also for high-pressure chronic retention (HPCR). Complications of LUTS/BPH are very rare in clinical trials because of their strict inclusion and exclusion criteria but are more common in real life practice.

Bladder function after sacrospinous hysteropexy and vaginal wall repair in women with uterovaginal prolapse.

PubMed

Sayed Ahmed, Waleed A; Taha, Omima T; Hamdy, Mostafa A; Ibrahim, Zakia M; Elshahat, Amal M

2018-05-01

To evaluate the impact of repair of uterovaginal prolapse using sacrospinous hysteropexy and vaginal wall repair on the bladder function. The study was conducted at the urogynecology clinic of Suez Canal University Hospitals, Ismailia from January 2014 to March 2016. This study included women with a diagnosis of uterovaginal prolapse and wishing to preserve their uteri. Bladder function was evaluated through assessment of urological symptoms using a standardized questionnaire - the urogenital distress inventory (UDI-6) - in addition to urodynamic studies just before and six-months after the sacrospinous hysteropexy ± associated vaginal wall repair operation. Twenty-seven patients completed the study with a mean age of 36.5 ± 4 years. Only 3 women had sacrospinous hysteropexy with no additional procedures. Other procedures included anterior colporrhaphy (12), posterior colporrhaphy (9) and perineorrhaphy (15). Based on UDI-6, there was no significant difference between the pre- and post-operative symptoms of stress urinary incontinence (SUI) [8/27 (29.6%) vs. 9/27 (33.3%) respectively; p value = 0.7]. The pre- and post-operative symptoms of urge urinary incontinence were also insignificantly different [13/27 (48.1%) vs. 15/27 (55.5%); p value = 0.5]. The total score of UDI-6 increased from 24.5 ± (14.2) to 32.8 ± (29.4) which was not statistically significant (p value = 0.12). Urodynamically, voiding dysfunction was found less frequently after the operation, however the difference was statistically insignificant [9/27 (33.3%) vs. 8/27 (29.6%); p value = 0.7]. Sacrospinous hysteropexy and associated vaginal wall repair do not affect the bladder function either subjectively or objectively. Copyright © 2018. Published by Elsevier B.V.

Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women.

PubMed

Shoae-Hassani, Alireza; Sharif, Shiva; Seifalian, Alexander M; Mortazavi-Tabatabaei, Seyed Abdolreza; Rezaie, Sassan; Verdi, Javad

2013-10-01

To investigate manufacturing smooth muscle cells (SMCs) for regenerative bladder reconstruction from differentiation of endometrial stem cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri, opens up the possibility of using these cells for tissue engineering applications, such as building up natural tissue to repair prolapsed pelvic floors as well as building urinary bladder wall. Human EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium supplemented with myogenic growth factors. The myogenic factors included: transforming growth factor β, platelet-derived growth factor, hepatocyte growth factor and vascular endothelial growth factor. Differentiated SMCs on bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR), western blot (WB) and immunocytochemistry (ICC) analyses. Histology confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth factors decreased the proliferation rate of EnSCs, but they differentiated the human EnSCs into SMCs more efficiently on hydrogel matrices and expressed specific SMC markers including α-smooth muscle actin, desmin, vinculin and calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the hydrogel-coated matrices was significantly higher than uncoated cultures. Human EnSCs were successfully differentiated into SMCs, using hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration without any immunological complications in women. Currently work is in progress using bioabsorbable nanocomposite materials as EnSC scaffolds for developing urinary bladder wall tissue. © 2013 The Authors. BJU International © 2013 BJU International.

Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

PubMed

Nguyen, Huyen T; Shah, Zarine K; Mortazavi, Amir; Pohar, Kamal S; Wei, Lai; Jia, Guang; Zynger, Debra L; Knopp, Michael V

2017-05-01

To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.

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.

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.

Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis.

PubMed

Song, Phil Hyun; Chun, So Young; Chung, Jae-Wook; Kim, Yeon Yong; Lee, Hyo Jung; Lee, Jun Nyung; Ha, Yun-Sok; Yoo, Eun Sang; Kwon, Tae Gyun; Kim, Jeongshik; Kim, Dae Hwan; Kim, Bum Soo

2017-09-01

We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

Inhibitory effect of standardized cannabis sativa extract and its ingredient cannabidiol on rat and human bladder contractility.

PubMed

Capasso, Raffaele; Aviello, Gabriella; Borrelli, Francesca; Romano, Barbara; Ferro, Matteo; Castaldo, Luigi; Montanaro, Vittorino; Altieri, Vincenzo; Izzo, Angelo A

2011-04-01

To evaluate the effect of a Cannabis sativa extract enriched in cannabidiol (CBD) botanic drug substance (BDS) and pure CBD, on bladder contractility in vitro. Cannabis based-medicines, including CBD-enriched extracts, have been shown to reduce urinary urgency, incontinence episodes, frequency, and nocturia in patients with multiple sclerosis. Strips were cut from male Wistar rats and the human bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation, acetylcholine, KCl, and α,β-methylene adenosine triphosphate. CBD BDS significantly reduced the contractions induced by acetylcholine, but not those induced with electrical field stimulation, KCl, or α,β-methylene adenosine triphosphate in the isolated rat bladder. The inhibitory effect of CBD BDS was not significantly modified by the cannabinoid or opioid receptor antagonists or by modulators of calcium levels, but it was increased by ruthenium red and capsazepine, 2 transient receptor potential vanilloid type-1 blockers. In humans, CBD BDS and pure CBD significantly reduced acetylcholine-induced contractions, an effect that was not changed by the transient receptor potential vanilloid type-1 blockers. Our data have suggested that CBD BDS reduces cholinergic-mediated contractility and that this effect is modulated by transient receptor potential vanilloid type-1 in rats but not in humans. CBD is the chemical ingredient of CBD BDS responsible for such activity. If confirmed in vivo, such results could provide a pharmacologic basis to explain, at least in part, the efficacy of Cannabis medicines in reducing incontinence episodes in patients with multiple sclerosis. Copyright © 2011 Elsevier Inc. All rights reserved.

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

[A case of eosinophilic cystitis mimicking an invasive bladder cancer].

PubMed

Okazaki, Satoshi; Hori, Jun-Ichi; Kita, Masafumi; Yamaguchi, Satoshi; Kawakami, Norihiro; Kakizaki, Hidehiro

2014-12-01

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

Abdominal wall dysfunction in adult bladder exstrophy: a treatable but under-recognized problem.

PubMed

Manahan, M A; Campbell, K A; Tufaro, A P

2016-08-01

Bladder exstrophy is defined by urogenital and skeletal abnormalities with cosmetic and functional deformity of the lower anterior abdominal wall. The primary management objectives have historically been establishment of urinary continence with renal function preservation, reconstruction of functional and cosmetically acceptable external genitalia, and abdominal wall closure of some variety. The literature has focused on the challenges of neonatal approaches to abdominal wall closure; however, there has been a paucity of long-term followup to identify the presence and severity of abdominal wall defects in adulthood. Our goal was to characterize the adult disease and determine effective therapy. A retrospective review of a consecutive series of six patients was performed. We report and characterize the presence of severe abdominal wall dysfunction in these adult exstrophy patients treated as children. We tailored an abdominal wall and pelvic floor reconstruction with long-term success to highlight a need for awareness of the magnitude of the problem and its solvability. The natural history of abdominal wall laxity and the long-term consequences of cloacal exstrophy closure have gone unexplored and unreported. Evaluation of our series facilitates understanding in this complex area and may be valuable for patients who are living limited lives thinking that no solution is available.

Contractile activity of ATP and diadenosine tetraphosphate on urinary bladder in the rats: role of superoxide anion and urothelium.

PubMed

Khattab, M M; Al-Hrasen, M N

2006-04-01

Both ATP and diadenosine tetraphosphate (AP(4)A) produced a dose-dependent contraction of rat isolated urinary bladder rings. The AP(4)A dose-response curve was to the left of that of ATP, and the maximum response was greater than that produced by ATP. Mechanical removal of the urothelium increased the contractile response to ATP by between 53% and 71%, and that to AP(4)A by 42% (at highest AP(4)A concentration) to 68% at lower concentration. Inhibition of Cu/Zn superoxide dismutase with diethylthiocarbamate (DETCA, 5 mm) significantly reduced the ATP-evoked contraction by 31% (at high ATP concentration) to 40% at low ATP concentration. Similarly, the AP(4)A-induced contractions were significantly decreased by 27% at low AP(4)A level to 38% at higher concentrations. Induction of exogenous superoxide anion stress by the use of the superoxide anion generator, pyrogallol (0.5 mm), significantly decreased both ATP- and AP(4)A-induced contractions of the rat urinary bladder over the whole dose range. Contractile responses to ATP decreased by 36-40%, and those to AP(4)A by 44-49%. In conclusion, the urinary bladder urothelium exerts an inhibitory control over the purinergic contractility produced by adenine mononucleotides and dinucleotides. Superoxide anion stress, whether endogenous or exogenous, attenuates the ATP-induced as well as AP(4)A-induced contractility.

Protective effects of a by-product of the pecan nut industry (Carya illinoensis) on the toxicity induced by cyclophosphamide in rats Carya illinoensis protects against cyclophosphamide-induced toxicity.

PubMed

Benvegnú, D; Barcelos, R C S; Boufleur, N; Reckziegel, P; Pase, C S; Müller, L G; Martins, N M B; Vareli, C; Bürger, M E

2010-01-01

This study investigated the antioxidant effects of pecan nut (Carya illinoensis) shell aqueous extract (AE) on toxicity induced by cyclophosphamide (CP) in the heart, kidney, liver, bladder, plasma and erythrocytes of rats. Rats were treated with water or pecan shell AE (5%) ad libitum, replacing drinking water for 37 days up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the organs were removed. Rats treated with CP showed an increase in lipid peroxidation (LP) and decrease in reduced glutathione (GSH) levels in all structures. Catalase (CAT) activity was increased in the heart and decreased in liver and kidney. Besides, CP treatment decreased plasmatic vitamin C (VIT C) levels and induced bladder macroscopical and microscopical damages. In contrast, co-treatment with pecan shell AE prevented the LP development and the GSH depletion in all structures, except in the heart and plasma, respectively. CAT activity in the heart and liver as well as the plasmatic VIT C levels remained unchanged. Finally, AE prevented CP-induced bladder injury. These findings revealed the protective role of pecan shell AE in CP-induced multiple organ toxicity.

Imaging features of colovesical fistulae on MRI.

PubMed

Tang, Y Z; Booth, T C; Swallow, D; Shahabuddin, K; Thomas, M; Hanbury, D; Chang, S; King, C

2012-10-01

MRI is routinely used in the investigation of colovesical fistulae at our institute. Several papers have alluded to its usefulness in achieving the diagnosis; however, there is a paucity of literature on its imaging findings. Our objective was to quantify the MRI characteristics of these fistulae. We selected all cases over a 4-year period with a final clinical diagnosis of colovesical fistula which had been investigated with MRI. The MRI scans were reviewed in a consensus fashion by two consultant uroradiologists. Their MRI features were quantified. There were 40 cases of colovesical fistulae. On MRI, the fistula morphology consistently fell into three patterns. The most common pattern (71%) demonstrated an intervening abscess between the bowel wall and bladder wall. The second pattern (15%) had a visible track between the affected bowel and bladder. The third pattern (13%) was a complete loss of fat plane between the affected bladder and bowel wall. MRI correctly determined the underlying aetiology in 63% of cases. MRI is a useful imaging modality in the diagnosis of colovesical fistulae. The fistulae appear to have three characteristic morphological patterns that may aid future diagnoses of colovesical fistulae. To the authors' knowledge, this is the first publication of the MRI findings in colovesical fistulae.

Perforation of the urinary bladder caused by transurethral insertion of a pencil for the purpose of masturbation in a 29-year-old female.

PubMed

Bantis, Athanasios; Sountoulides, Petros; Kalaitzis, Christos; Giannakopoulos, Stelios; Agelonidou, Eleni; Foutzitzi, Soultana; Touloupidis, Stavros

2010-01-01

The urethra is a usual site of introduction of foreign bodies for autoerotic stimulation. We present an unusual case of bladder perforation caused by foreign body that was self-inserted in the urethra and consequently slipped inside the bladder in a 29-year-old female patient with psychiatric disease. The patient was referred to our department for macroscopic hematuria and abdominal pain. Imaging studies revealed the presence of a foreign body in the pelvic area which had perforated the left lateral wall of the bladder. The foreign body was removed via open cystotomy. In psychiatric patients hematuria and pelvic pain may result from insertion of a foreign body in the bladder usually during masturbation.

Perforation of the Urinary Bladder Caused by Transurethral Insertion of a Pencil for the Purpose of Masturbation in a 29-Year-Old Female

PubMed Central

Bantis, Athanasios; Sountoulides, Petros; Kalaitzis, Christos; Giannakopoulos, Stelios; Agelonidou, Eleni; Foutzitzi, Soultana; Touloupidis, Stavros

2010-01-01

The urethra is a usual site of introduction of foreign bodies for autoerotic stimulation. We present an unusual case of bladder perforation caused by foreign body that was self-inserted in the urethra and consequently slipped inside the bladder in a 29-year-old female patient with psychiatric disease. The patient was referred to our department for macroscopic hematuria and abdominal pain. Imaging studies revealed the presence of a foreign body in the pelvic area which had perforated the left lateral wall of the bladder. The foreign body was removed via open cystotomy. In psychiatric patients hematuria and pelvic pain may result from insertion of a foreign body in the bladder usually during masturbation. PMID:20862362

EVALUATION OF CONTRAST-ENHANCED ULTRASONOGRAPHY AS A METHOD FOR DETECTING GALLBLADDER NECROSIS OR RUPTURE IN DOGS.

PubMed

Bargellini, Paolo; Orlandi, Riccardo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Peterson, Mark E; Rishniw, Mark; Boiti, Cristiano

2016-11-01

Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical. © 2016 American College of Veterinary Radiology.

OK-432 Suppresses Proliferation and Metastasis by Tumor Associated Macrophages in Bladder Cancer.

PubMed

Tian, Yuan-Feng; Tang, Kun; Guan, Wei; Yang, Tao; Xu, Hua; Zhuang, Qian-Yuan; Ye, Zhang-Qun

2015-01-01

OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.

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.

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

Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects ofmore » MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

Quantification of effectiveness of bilateral and unilateral neuromodulation in the rat bladder rhythmic contraction model

PubMed Central

2013-01-01

Background Using the isovolumetric bladder rhythmic contraction (BRC) model in anesthetized rats, we have quantified the responsiveness to unilateral and bilateral stimulation of the L6 spinal nerve (SN) and characterized the relationship between stimulus intensity and inhibition of the bladder micturition reflex. Methods A wire electrode was placed under either one or both of the L6 SN roots. A cannula was placed into the bladder via the urethra and the urethra was ligated. Saline infusion induced BRC. Results At motor threshold (Tmot) intensity, SN stimulation of both roots (10 Hz) for 10 min reduced bladder contraction frequency from 0.63 ± 0.04 to 0.17 ± 0.09 contractions per min (26 ± 14% of baseline control; n = 10, p < 0.05). However, the same intensity of unilateral stimulation (n = 15) or sequential stimulation of both SNs (e.g. 5 min per side alternatively for a total of 10 min or 20 min) was less efficacious. The greater sensitivity to bilateral stimulation is not dependent upon precise bilateral timing of the stimulation pulses. Bilateral stimulation also produced both acute and prolonged- inhibition on bladder contractions in a stimulation intensity dependent fashion. Conclusions Using the bladder rhythmic contraction model, bilateral stimulation was more effective than unilateral stimulation of the SN. Clinical testing should be conducted to further compare efficacies of unilateral and bilateral stimulation. Bilateral stimulation may allow the use of lower stimulation intensities to achieve higher efficacy for neurostimulation therapies on urinary tract control. PMID:23866931

A huge bladder calculus causing acute renal failure.

PubMed

Komeya, Mitsuru; Sahoda, Tamami; Sugiura, Shinpei; Sawada, Takuto; Kitami, Kazuo

2013-02-01

A 81-year-old male was referred to our emergency outpatient unit due to acute renal failure. The level of serum creatinine was 276 μmol/l. A CT scan showed bilateral hydronephroureter, large bladder stone (7 cm × 6 cm × 6 cm) and bladder wall thickness. He was diagnosed as post renal failure due to bilateral hydronephroureter. Large bladder stone is thought to be the cause of bilateral hydronephroureter and renal failure. To improve renal failure, we performed open cystolithotomy and urethral catheterization. Three days after the surgery, the level of serum creatinine decreased to 224 μmol/l. He was discharged from our hospital with uneventful course. Bladder calculus is thought to be a rare cause of renal failure. We summarize the characteristics of bladder calculus causing renal failure. We should keep that long-term pyuria and urinary symptom, and repeated urinary tract infection can cause huge bladder calculus and renal failure in mind.

A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy.

PubMed

Showalter, Timothy N; Nawaz, A Omer; Xiao, Ying; Galvin, James M; Valicenti, Richard K

2008-02-01

There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.

Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.

PubMed

Doss, Mohan; Zhang, James J; Bélanger, Marie-José; Stubbs, James B; Hostetler, Eric D; Alpaugh, Katherine; Kolb, Hartmuth C; Yu, Jian Q

2010-12-01

F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans. Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software. The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data. Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Anticancer benefits of early versus late use of rapamycin in a rat model of urothelial carcinoma.

PubMed

Chang, C-H; Fu, Y-C; Li, J-R; Shu, K-H; Ho, H-C; Shiu, Y-N; Wu, M-J

2014-05-01

We previously reported both in vivo and in vitro effects of rapamycin on urothelial carcinoma. Clinically, the use of rapamycin could not completely prevent the recurrence of urothelial carcinoma. Therefore, we designed this study to compare the difference of efficacy between early and late use of rapamycin in a rat model of urothelial carcinoma. The rat model of urothelial carcinoma was induced by adding 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to the drinking water for up to 20 weeks in male Fisher-344 rats. Rapamycin was fed orally from the 1st day, 5th week, 9th week, 13th week, and 17th week. The antitumor effects of different periods of rapamycin treatment were assessed grossly and microscopically. Papillary tumors of urinary bladder were successfully induced in the BBN group. Simultaneous use of rapamycin and BBN from the 1st day of treatment significantly reduced the tumor growth in urinary bladder: 80% of the rats had no tumor and 20% had low-grade tumors. Adding rapamycin from the 5th week was associated with more tumor growth: 20% of the rats had no tumors, 20% had low-grade tumors, and 60% had high-grade tumors. Moreover, in the groups with rapamycin treatment from the 9th week, 13th week, and 17th week, all rats developed high-grade papillary tumors in urinary bladder, as did the control group that received no rapamycin. The study results suggest that the anticancer effect of rapamycin on urothelial carcinoma is stage dependent. Early use of rapamycin provides better anticancer effect, whereas late use of rapamycin fails to inhibit the cancer growth. Copyright © 2014 Elsevier Inc. All rights reserved.

In vitro and in vivo effects of CpG-Oligodeoxynucleotides (CpG-ODN) on murine transitional cell carcinoma and on the native murine urinary bladder wall.

PubMed

Olbert, Peter Jochen; Schrader, Andres Jan; Simon, Corinna; Dalpke, Alexander; Barth, Peter; Hofmann, Rainer; Hegele, Axel

2009-06-01

Intravesical BCG instillation is established and efficient in the prophylaxis of recurrent transitional cell carcinoma. A Th-1 biased immune response is postulated. Recent work has proven the efficacy of synthetic CpG-Oligodeoxynucleotides (ODN) as inducers and adjuvants for a strong Th1-response and there is evidence for a direct and/or adjuvant anti-neoplastic effect. The purpose of this study was to examine the local effects of CpG-ODN on the murine bladder wall after intravesical instillation and the effects on cytokine expression in an orthotopic murine bladder cancer model. Histopathology, immunohistochemistry and fluorescence microscopy were performed after different instillation schedules of stimulatory, non-stimulatory biotinylized and FITC-labelled CpG-ODN into the murine bladder. MB-49 murine bladder cancer cells were tested for TLR-9 expression to exclude a potential direct responsiveness to CpG-ODN. Furthermore induction of apoptosis was tested by annexin V staining and FACS analysis of CpG-ODN stimulated tumor cells. In an orthotopic C57/Bl6 murine bladder cancer model, the expressions of IL-12, IFNgamma, IL-10 and TGF-beta were evaluated after repeated CpG-ODN treatment. Single and repeated instillation of CpG-ODN induced subepithelial and urothelial lymphocytic infiltrations with consecutive apoptoses. PBS and non-stimulative ODN induced no visible reaction. Bladder submucosa stained positive for biotin. Controls showed no endogenic biotin staining. FITC-labelled ODN adhered to the bladder mucosa and penetration of the mucosal barrier was not detected. MB-49 TCC cells did not express TLR-9 and CpG-ODN did not induce apoptosis in these cells. Repeated intravesical instillations of CpG-ODN in orthotopic murine tumor bearing urinary bladders resulted in significant up-regulation of both Th-1 and Th-2 cytokines. CpG-ODNs have promising anti-neoplastic potential. They exert a pronounced immunological response both in the native murine urinary bladder and in murine TCC. The mechanisms of action appear to be mediated immunologically, There was no direct effect of CpG-ODN on the tumor cells in this model.

[Clinical study of bladder injury].

PubMed

Abe, Kazuhiro; Oishi, Yukihiko; Onodera, Syoichi; Ikemoto, Isao; Kiyota, Hiroshi; Asano, Koji; Ueda, Masataka; Wada, Tetsuro; Tashiro, Kazuya

2002-03-01

Since bladder injury has no specific clinical symptoms, accurate diagnosis at first consultation is relatively difficult. To elucidate the clinical characters type of injury, clinical symptoms, laboratory findings, methods of therapy and diagnosis, we reviewed 15 patients with bladder injury over a 9-year-period 1990-1998 (10 were traumatic injuries and 5 spontaneous injuries). We found no specific clinical symptom of bladder injury. Bladder injury may occur anywhere in the bladder wall, but most commonly occurred at the dome of the bladder (60.0%). Gross hematuria was not seen in 40.0% of the cases. The accuracy of diagnosis at first consultation was relatively low (46.7%) and the tendency to make a misdiagnosis as acute abdomen on digestive organs was found. Of the traumatic injuries 60% were afflicted in the drunken state, so alcohol intoxication was considered as an important enviromental factor of bladder injury. Surgical repair of injury sites was employed in 11 cases (73.3%: 7 were intraperitoneal injuries, 4 were extraperitoneal injuries), 4 cases were managed with indwelling urethral catheter. With appropriate treatment, the prognosis is excellent.

Retrograde and transganglionic transport of horseradish peroxidase-conjugated cholera toxin B subunit, wheatgerm agglutinin and isolectin B4 from Griffonia simplicifolia I in primary afferent neurons innervating the rat urinary bladder.

PubMed

Wang, H F; Shortland, P; Park, M J; Grant, G

1998-11-01

In the present study, we investigated and compared the ability of the cholera toxin B subunit, wheat germ agglutinin and isolectin B4 from Griffonia simplicifolia I conjugated to horseradish peroxidase, to retrogradely and transganglionically label visceral primary afferents after unilateral injections into the rat urinary bladder wall. Horseradish peroxidase histochemical or lectin-immunofluorescence histochemical labelling of bladder afferents was seen in the L6-S1 spinal cord segments and in the T13-L2 and L6-S1 dorsal root ganglia. In the lumbosacral spinal cord, the most intense and extensive labelling of bladder afferents was seen when cholera toxin B subunit-horseradish peroxidase was injected. Cholera toxin B subunit-horseradish peroxidase-labelled fibres were found in Lissauer's tract, its lateral and medial collateral projections, and laminae I and IV-VI of the spinal gray matter. Labelled fibres were numerous in the lateral collateral projection and extended into the spinal parasympathetic nucleus. Labelling from both the lateral and medial projections extended into the dorsal grey commissural region. Wheat germ agglutinin-horseradish peroxidase labelling produced a similar pattern but was not as dense and extensive as that of cholera toxin B subunit-horseradish peroxidase. The isolectin B4 from Griffonia simplicifolia I-horseradish peroxidase-labelled fibres, on the other hand, were fewer and only observed in the lateral collateral projection and occasionally in lamina I. Cell profile counts showed that a larger number of dorsal root ganglion cells were labelled with cholera toxin B subunit-horseradish peroxidase than with wheat germ agglutinin- or isolectin B4-horseradish peroxidase. In the L6-S1 dorsal root ganglia, the majority (81%) of the cholera toxin B subunit-, and almost all of the wheat germ agglutinin- and isolectin B4-immunoreactive cells were RT97-negative (an anti-neurofilament antibody that labels dorsal root ganglion neurons with myelinated fibres). Double labelling with other neuronal markers showed that 71%, 43% and 36% of the cholera toxin B subunit-immunoreactive cells were calcitonin gene-related peptide-, isolectin B4-binding- and substance P-positive, respectively. A few cholera toxin B subunit cells showed galanin-immunoreactivity, but none were somatostatin-, vasoactive intestinal polypeptide-, or neuropeptide Y-immunoreactive or contained fluoride-resistant acid phosphatase. The results show that cholera toxin B subunit-horseradish peroxidase is a more effective retrograde and transganglionic tracer for pelvic primary afferents from the urinary bladder than wheat germ agglutinin-horseradish peroxidase and isolectin B4-horseradish peroxidase, but in contrast to somatic nerves, it is transported mainly by unmyelinated fibres in the visceral afferents.

Human urinary bladder regeneration through tissue engineering - an analysis of 131 clinical cases.

PubMed

Pokrywczynska, Marta; Adamowicz, Jan; Sharma, Arun K; Drewa, Tomasz

2014-03-01

Replacement of urinary bladder tissue with functional equivalents remains one of the most challenging problems of reconstructive urology over the last several decades. The gold standard treatment for urinary diversion after radical cystectomy is the ileal conduit or neobladder; however, this technique is associated with numerous complications including electrolyte imbalances, mucus production, and the potential for malignant transformation. Tissue engineering techniques provide the impetus to construct functional bladder substitutes de novo. Within this review, we have thoroughly perused the literature utilizing PubMed in order to identify clinical studies involving bladder reconstruction utilizing tissue engineering methodologies. The idea of urinary bladder regeneration through tissue engineering dates back to the 1950s. Many natural and synthetic biomaterials such as plastic mold, gelatin sponge, Japanese paper, preserved dog bladder, lyophilized human dura, bovine pericardium, small intestinal submucosa, bladder acellular matrix, or composite of collagen and polyglycolic acid were used for urinary bladder regeneration with a wide range of outcomes. Recent progress in the tissue engineering field suggest that in vitro engineered bladder wall substitutes may have expanded clinical applicability in near future but preclinical investigations on large animal models with defective bladders are necessary to optimize the methods of bladder reconstruction by tissue engineering in humans.

Some aspects of the inhibition of the action of antidiuretic hormone by lithium ions in the rat kidney and bladder of the toad Bufo marinus

PubMed Central

Harris, Carol A.; Jenner, F. A.

1972-01-01

1. The effect of intravenous infusions of various ions on the antidiuretic action of antidiuretic hormone has been studied in rats. 2. Lithium (13 mmol/l.) reversibly inhibits the antidiuretic responses. Similar concentrations of potassium, rubidium, strontium, magnesium, choline and calcium do not. Lithium has a similar effect on the antidiuretic activity of oxytocin. 3. The inhibition is not simply related to blood nor whole body lithium concentrations. 4. Lithium (2 mmol/l.) in contact with the serosal surface also inhibits the transport of water facilitated by either 0·5 U/l. antidiuretic hormone or 1·1 mmol/l. cyclic adenosine monophosphate in the isolated toad bladder. 5. Choline (2 mmol/l.) on the serosal surface also inhibits the transport of water facilitated by vasopressin in the toad bladder. PMID:4358411

Glutamine supplementation prevents collagen expression damage in healthy urinary bladder caused by radiotherapy.

PubMed

Rocha, Beatriz Rodrigues; Gombar, Flavia Meirelles; Barcellos, Leilane Maria; Costa, Waldemar Silva; Barcellos Sampaio, Francisco Jose; Ramos, Cristiane Fonte

2011-01-01

Patients who have had pelvic radiotherapy as part of their cancer therapy may develop subsequent urinary bladder effects such as hyperactive bladder, incontinence, and dysuria. Therefore, the goal of this study was to evaluate whether glutamine supplementation could prevent collagen expression damage in healthy urinary bladder caused by radiotherapy. Fifteen adult Wistar rats were separated into a control group that received food and water ad libitum (C group), an irradiated group that received a single pelvic radiation dose of 1164 cGy (I group), and an irradiated group supplemented with l-glutamine every day during the entire experimental period (0.65 g/kg of body weight; I+G group). All animals were sacrificed 15 d after irradiation. The extracellular matrix and muscle were quantified by a morphometric method. Picro Sirius Red was used to visualize the different collagen types. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to determine collagen type I and III expressions. The extracellular matrix (C group 36.84±4.37, I group 31.64±5.00, I+G group 35.53±2.60, P=0.0001), muscle (C group 36.43±6.15, I group 29.39±7.08, I+G group 31.38±3.14, P=0.0001), and gene expressions of collagen type I (C group 1.067±0.31, I group 0.579±0.17, I+G group 1.816±0.66, P=0.0009) and type III (C group 0.99±0.28, I group 0.54±0.13, I+G group 1.07±0.28, P=0.0080) were decreased in the I group. Apart from muscle, glutamine supplementation prevented these alterations. Immunohistochemistry and Picro Sirius Red showed similar results. Supplementation with l-glutamine seems to prevent bladder wall damage in relation to extracellular matrix volumetric density and collagen expression. These results suggest that glutamine supplementation could be efficient in protecting healthy tissues from the adverse effects of radiotherapy. Copyright © 2011. Published by Elsevier Inc.

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host.

PubMed

Chaudhry, Rajeev; Madden-Fuentes, Ramiro J; Ortiz, Tara K; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S; Ross, Sherry S; Seed, Patrick C

2014-05-01

Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

CHEMOPREVENTIVE EFFICACY OF NAPROXEN AND NO-NAPROXEN IN RODENT MODELS OF COLON, URINARY BLADDER, AND MAMMARY CANCERS

PubMed Central

Steele, Vernon E.; Rao, Chinthalapally V.; Zhang, Yuting; Patlolla, Jagan; Boring, Daniel; Kopelovich, Levy; Juliana, M. Margaret; Grubbs, Clinton J.; Lubet, Ronald A.

2009-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically; and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal (GI) ulceration and may increase cardiovascular (CV) events. Naproxen appears to cause the lowest CV events of the common NSAIDs other than aspirin. NO-naproxen was tested based on the finding that adding a nitric oxide (NO) group to NSAIDs may help alleviate GI toxicity. In the azoxymethane (AOM)-induced rat colon aberrant crypt foci (ACF) model, naproxen administered at 200 and 400 ppm in the diet reduced mean ACFs in the colon by about 45–60%, respectively. NO-naproxen was likewise administered in the diet at roughly equimolar doses (300 and 600 ppm), and reduced total ACF by 20–40%, respectively. In the hydroxybutyl (butyl) nitrosamine (OH-BBN) rat urinary bladder cancer model, NO-naproxen was given at 183 ppm or 550 ppm in the diet, and naproxen at 128 ppm. The NO-naproxen groups had 77% and 73% decreases, respectively, in the development of large urinary bladder tumors, while the 128 ppm naproxen group also showed a strong decrease (69%). If treatments were started three months after OH-BBN, NO-naproxen (550 ppm) and naproxen (400 ppm) were also highly effective (86–94% decreases). In the methylnitrosourea (MNU)-induced mammary cancer model in rats, NO-naproxen and naproxen showed non-significant inhibitions (12 and 24%) at 550 and 400 ppm, respectively. These data show that both naproxen and NO-naproxen are effective agents against urinary bladder and colon, but not mammary, carcinogenesis. PMID:19892664

Neuroanatomic and behavioral correlates of urinary dysfunction induced by vaginal distension in rats.

PubMed

Palacios, J L; Juárez, M; Morán, C; Xelhuantzi, N; Damaser, M S; Cruz, Y

2016-05-01

The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by vaginal distension (VD) in female rats. In experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by VD or sham (SH) procedures. Electroneurograms of the dorsal nerve of the clitoris (DNC) were also recorded. In experiment 2, histological characteristics of the bladder and major pelvic ganglion of VD and SH rats were evaluated. In experiment 3, urinary parameters were determined in conscious animals during 6 h of dark and 6 h of light before and 3 days after VD or SH procedures. VD significantly increased distal vagina width (P < 0.001) and the length of the motor branch of the sacral plexus (P < 0.05), DNC (P < 0.05), and vesical nerves (P < 0.01) and decreased DNC frequency and amplitude of firing. VD occluded the pelvic urethra, inducing urinary retention, hematomas in the bladder, and thinness of the epithelial (P < 0.05) and detrusor (P < 0.01) layers of the bladder. Major pelvic ganglion parameters were not modified after VD. Rats dripped urine in unusual places to void, without the stereotyped behavior of micturition after VD. The neuroanatomic injuries after VD occur alongside behavioral signs of urinary incontinence as determined by a new behavioral tool for assessing micturition in conscious animals.

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.

Cone Beam CT Imaging Analysis of Interfractional Variations in Bladder Volume and Position During Radiotherapy for Bladder Cancer

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

Yee, Don, E-mail: dony@ualberta.c; Parliament, Matthew; Rathee, Satyapal

2010-03-15

Purpose: To quantify daily bladder size and position variations during bladder cancer radiotherapy. Methods and Materials: Ten bladder cancer patients underwent daily cone beam CT (CBCT) imaging of the bladder during radiotherapy. Bladder and planning target volumes (bladder/PTV) from CBCT and planning CT scans were compared with respect to bladder center-of-mass shifts in the x (lateral), y (anterior-posterior), and z (superior-inferior) coordinates, bladder/PTV size, bladder/PTV margin positions, overlapping areas, and mutually exclusive regions. Results: A total of 262 CBCT images were obtained from 10 bladder cancer patients. Bladder center of mass shifted most in the y coordinate (mean, -0.32 cm).more » The anterior bladder wall shifted the most (mean, -0.58 cm). Mean ratios of CBCT-derived bladder and PTV volumes to planning CT-derived counterparts were 0.83 and 0.88. The mean CBCT-derived bladder volume (+- standard deviation [SD]) outside the planning CT counterpart was 29.24 cm{sup 3} (SD, 29.71 cm{sup 3}). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm{sup 3} (SD, 21.64 cm{sup 3}). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm{sup 3} (SD, 36.51 cm{sup 3}). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm{sup 3} (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm{sup 3} (SD, 3.97 cm{sup 3}). CBCT bladder/ PTV volumes significantly differed from planning CT counterparts (p = 0.047). Conclusions: Significant variations in bladder and PTV volume and position occurred in patients in this trial.« less

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.

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

Pneumovesicoscopic treatment of congenital bladder diverticula in children: our experience.

PubMed

Marte, Antonio; Sabatino, Maria D; Borrelli, Micaela; Del Balzo, Biago; Nino, Fabiano; Prezioso, Maurizio; Parmeggiani, Pio

2010-02-01

In this article, we report our experience with diverticulectomies of symptomatic congenital bladder diverticula in children, which was performed by utilizing pneumovesicoscopy. Six boys, 4-8 years of age (mean, 5.6) underwent pneumovesicoscopic diverticulectomy at our institution from June 2007 to June 2008. There were 4 right-single diverticula and 2 double-left diverticula. Under cystoscopic control, after the cystopexy to the abdominal wall, a midline 5-mm trocar for a 0-degree telescope and two lateral 3-mm reusable trocars through the anterolateral wall of the bladder in the midclavicular line were introduced, insufflating the bladder with carbondioxide to 10-12 mm Hg pressure. The diverticulum/a were inverted into the bladder and the mucosa around the neck was circumcized by using scissors and a monopolar hook. The defect was sutured with interrupted sutures and the bladder was drained with a Foley catheter, which was introduced at the site of the 5-mm port, and a urethral catheter. Mean operative time was 110 minutes. No major peri- or postoperative complications were recorded, except that the displacement of one of the lateral trocars that resulted in gas leakage in 1 case. The trocar was replaced and the procedure was completed. An ultrasound and a voiding cystourethrogram, performed from 3 to 6 months after the operation, showed the disappearance of the diverticulum/a. In our experience, pneumovesicoscopic diverticulectomy is an easy, safe procedure and can be considered a valid alternative to the open or laparoscopic procedures. It also provides no postoperative discomfort and a good cosmetic result.

Mucinous adenocarcinoma of the bladder associated with long term suprapubic tube: a case report.

PubMed

Bauman, Tyler M; Potretzke, Theodora A; Potretzke, Aaron M; Siegel, Cary L; Brandes, Steven B

2015-12-03

Chronic indwelling catheters may induce histologic changes within the bladder, and these changes are sometimes pre-malignant. There are many documented cases of squamous cell carcinoma associated with indwelling catheters, but only three cases of catheter-associated adenocarcinoma have been reported. In this case report, we present radiographic findings of a case of mucinous adenocarcinoma of the bladder and suprapubic (SP) tract in a quadriplegic patient. A 71-year-old male with a history of spinal cord injury presented with hematuria and SP discharge after SP catheterization for 51 years. CT urography was performed and revealed an irregular, infiltrative, and heterogeneous mass arising from the anterior bladder at the level of the suprapubic catheter and extending along the SP tube tract. Cystoscopy and biopsy revealed an adenocarcinoma of the anterior bladder and stoma with extensive associated mucin production and a background of acute and chronic inflammation. Surgical therapy included cystoprostatectomy, abdominal wall resection, ileal conduit creation, and abdominal wall reconstruction. The final diagnosis was a high-grade, T2a/N0/M0 (Stage II) mucinous adenocarcinoma of the bladder. There has been no evidence of tumor recurrence over the previous 5 years. Few cases of adenocarcinoma associated with long term indwelling catheter have been reported in the literature, and due to the rarity of this disease process, the prognosis with surgical therapy is not well known. The patient described herein has been free of recurrence for the previous five years, suggesting that surgery is a viable management option for these patients.

Cystitis glandularis in a cat.

PubMed

Agut, Amalia; Carrillo, Juana D; Soler, Marta; García, Juan D; Belda, Eliseo; Gómez, Miguel A; Bernabe, Antonio

2014-04-01

An 8-year-old intact male Persian cat was presented for investigation of chronic haematuria. The cat had episodes of haematuria on several occasions that were non-responsive to antimicrobial therapy. Abdominal ultrasound examination revealed dilation of the renal pelvis and ureters of both kidneys. The urinary bladder wall was thickened, a mass of heterogeneous echogenicity filled the lumen of the bladder, and two parallel thin hyperechoic lines were identified within the lumen, which suggested a urethral catheter. Differential diagnoses for the urinary bladder mass included cystitis and neoplasia. The mass was surgically removed from the urinary bladder, and a urethral catheter was found embedded in the mass. Histopathological findings were consistent with cystitis glandularis of a typical type. Periodic bladder ultrasonographic studies were performed; at the time of writing, over 2 years later, recurrence had not been detected.

DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

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...

Towards nonionizing photoacoustic cystography

NASA Astrophysics Data System (ADS)

Kim, Chulhong; Jeon, Mansik; Wang, Lihong V.

2012-02-01

Normally, urine flows down from kidneys to bladders. Vesicoureteral reflux (VUR) is the abnormal flow of urine from bladders back to kidneys. VUR commonly follows urinary tract infection and leads to renal infection. Fluoroscopic voiding cystourethrography and direct radionuclide voiding cystography have been clinical gold standards for VUR imaging, but these methods are ionizing. Here, we demonstrate the feasibility of a novel and nonionizing process for VUR mapping in vivo, called photoacoustic cystography (PAC). Using a photoacoustic (PA) imaging system, we have successfully imaged a rat bladder filled with clinically being used methylene blue dye. An image contrast of ~8 was achieved. Further, spectroscopic PAC confirmed the accumulation of methylene blue in the bladder. Using a laser pulse energy of less than 1 mJ/cm2, bladder was clearly visible in the PA image. Our results suggest that this technology would be a useful clinical tool, allowing clinicians to identify bladder noninvasively in vivo.

Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells.

PubMed

Liu, Quanliang; Wang, Xinghuan

2013-11-01

Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro . Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro . TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma.

Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells

PubMed Central

LIU, QUANLIANG; WANG, XINGHUAN

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro. Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro. TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma. PMID:24223658

Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy.

PubMed

Wognum, S; Bondar, L; Zolnay, A G; Chai, X; Hulshof, M C C M; Hoogeman, M S; Bel, A

2013-02-01

Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumor and the lack of visible anatomical landmarks for validation. The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight parameters were determined for the weighted S-TPS-RPM. The weighted S-TPS-RPM registration algorithm with optimal parameters significantly improved the anatomical accuracy as compared to S-TPS-RPM registration of the bladder alone and reduced the range of the anatomical errors by half as compared with the simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. The weighted algorithm reduced the RDE range of lipiodol markers from 0.9-14 mm after rigid bone match to 0.9-4.0 mm, compared to a range of 1.1-9.1 mm with S-TPS-RPM of bladder alone and 0.9-9.4 mm for simultaneous nonweighted registration. All registration methods resulted in good geometric accuracy on the bladder; average error values were all below 1.2 mm. The weighted S-TPS-RPM registration algorithm with additional weight parameter allowed indirect control over structure-specific flexibility in multistructure registrations of bladder and bladder tumor, enabling anatomically coherent registrations. The availability of an anatomically validated deformable registration method opens up the horizon for improvements in IGART for bladder cancer.

[Placenta accreta--prenatal diagnosis, treatment].

PubMed

Tsankova, M; Marinov, B; Bozhilov, D; Pirnareva, E

2013-01-01

Placenta accreta is a potentially life threatening obstetric condition that requires a multidisciplinary management. Placenta praevia and previous Cesarean section are the two most important known risk factors for placenta accreta. This study presents two patients having both of the foremention risk factors diagnosed ultrasonographically with placenta accreta in the second trimester. Ultrasound findings considered suggestive of placenta accreta are: presence of placental lacunae (vascular spaces), loss of the hyperehoic uterine serosa-bladder wall interface, loss of the retroplacental hypoechoic clear space, hypervascularity of the interface between the uterine wall and the bladder wall/isthmico-cervical zone, presence of placenta praevia, either anterior or posterior, overlying the uterine scar. Both of the cases with suspected placenta accreta ended successfully by planned preterm Cesarean hysterectomy with the placenta left in situ. Placenta accreta is a significant cause of maternal morbidity and mortality and the most common reason for urgent postpartum hysterectomy.

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.

Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

PubMed

Davidson, Mayer B

2016-08-01

In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Empty-bladder (hysterographic) view on US for evaluation of intrauterine devices. Work in progress.

PubMed

Carroll, R; Gombergh, R

1987-06-01

Ultrasound scanning of the pelvis with an empty bladder permits a true frontal view of the uterus to be easily obtained. This view is comparable to the en face view seen at hysterography performed with contrast material. Good definition both of the endometrium and the uterine wall makes this the optimal method for the evaluation of an intrauterine contraceptive device.

Neuromodulation of the neural circuits controlling the lower urinary tract

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Gerasimenko, Yury P.; Taccola, Giuliano; Edgerton, V. Reggie

2017-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. PMID:27381425

Carbachol-Induced Signaling through Thr696-Phosphorylation of Myosin Phosphatase Targeting Subunit 1 (MYPT1) in rat Bladder Smooth Muscle Cells

PubMed Central

Alwaal, Amjad; Wang, Guifang; Banie, Lia; Lin, Ching-Shwun; Lin, Guiting; Lue, Tom F.

2016-01-01

Purpose Lines of evidence suggest that Rho-associated protein kinase (ROCK) mediated myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation play a central role in smooth muscle contraction. However, the physiological significance of MYPT1 phosphorylation at Thr696 catalyzed by ROCK in bladder smooth muscle remains controversial. We attempt to directly observe the quantitative protein expression of RhoA/ROCK and phosphorylation of MYPT1 at Thr696 after carbachol administration in rat bladder smooth muscle cells (RBMSCs). Materials and Methods Primary cultured smooth muscle cells were obtained from rat bladders. The effects of both concentration and time-course induced by the muscarinic agonist carbachol were investigated by assessing the expression of Rho A/ROCK and MYPT1 phosphorylation at Thr696 using Western blot. Results In the dose-course studies, carbachol showed significant increase of phosphorylation of MYPT1 at Thr696 (p-MYPT1) from concentrations of 15 μM to 100 μM based on Western blot results (p < 0.05, ANOVA test). In the time-course studies, treatment of cells with 15 μM of carbachol significantly enhanced the expression of p-MYPT1 from 3 to 15 hr (p < 0.05, ANOVA test) and induced the expression of Rho A from 10 to 120 min (p < 0.05, ANOVA test). Conclusions Carbachol can induce the expression of ROCK pathway, leading to MYPT1 phosphorylation at Thr696 and thereby sustained RBSMCs contraction. PMID:27118568

Carbachol-induced signaling through Thr696-phosphorylation of myosin phosphatase-targeting subunit 1 (MYPT1) in rat bladder smooth muscle cells.

PubMed

Liu, Benchun; Lee, Yung-Chin; Alwaal, Amjad; Wang, Guifang; Banie, Lia; Lin, Ching-Shwun; Lin, Guiting; Lue, Tom F

2016-08-01

Lines of evidence suggest that Rho-associated protein kinase (ROCK)-mediated myosin phosphatase-targeting subunit 1 (MYPT1) phosphorylation plays a central role in smooth muscle contraction. However, the physiological significance of MYPT1 phosphorylation at Thr696 catalyzed by ROCK in bladder smooth muscle remains controversial. We attempt to directly observe the quantitative protein expression of Rho A/ROCK and phosphorylation of MYPT1 at Thr696 after carbachol administration in rat bladder smooth muscle cells (RBMSCs). Primary cultured smooth muscle cells were obtained from rat bladders. The effects of both concentration and time-course induced by the muscarinic agonist carbachol were investigated by assessing the expression of Rho A/ROCK and MYPT1 phosphorylation at Thr696 using Western blot. In the dose-course studies, carbachol showed significant increase in phosphorylation of MYPT1 at Thr696 (p-MYPT1) from concentrations of 15-100 μM based on Western blot results (p < 0.05, ANOVA test). In the time-course studies, treatment of cells with 15 μM of carbachol significantly enhanced the expression of p-MYPT1 from 3 to 15 h (p < 0.05, ANOVA test) and induced the expression of Rho A from 10 to 120 min (p < 0.05, ANOVA test). Carbachol can induce the expression of ROCK pathway, leading to MYPT1 phosphorylation at Thr696 and thereby sustained RBSMCs contraction.

Endogenous Stem Cells Were Recruited by Defocused Low-Energy Shock Wave in Treating Diabetic Bladder Dysfunction.

PubMed

Jin, Yang; Xu, Lina; Zhao, Yong; Wang, Muwen; Jin, Xunbo; Zhang, Haiyang

2017-04-01

Defocused low-energy shock wave (DLSW) has been shown effects on activating mesenchymal stromal cells (MSCs) in vitro. In this study, recruitment of endogenous stem cells was firstly examined as an important pathway during the healing process of diabetic bladder dysfunction (DBD) treated by DLSW in vivo. Neonatal rats received intraperitoneal injection of 5-ethynyl-2-deoxyuridine (EdU) and then DBD rat model was created by injecting streptozotocin. Four weeks later, DLSW treatment was performed. Afterward, their tissues were examined by histology. Meanwhile, adipose tissue-derived stem cells (ADSCs) were treated by DLSW in vitro. Results showed DLSW ameliorated voiding function of diabetic rats by recruiting EdU + Stro-1 + CD34 - endogenous stem cells to release abundant nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Some EdU + cells overlapped with staining of smooth muscle actin. After DLSW treatment, ADSCs showed higher migration ability, higher expression level of stromal cell-derived factor-1 and secreted more NGF and VEGF. In conclusion, DLSW could ameliorate DBD by recruiting endogenous stem cells. Beneficial effects were mediated by secreting NGF and VEGF, resulting into improved innervation and vascularization in bladder.

Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine.

PubMed

Dornelas, Conceição Aparecida; Santos, Alessandra Marques Dos; Correia, Antonio Lucas Oliveira; Juanes, Camila de Carvalho; Coelho, João Paulo Ferreira; Cunha, Bianca Lopes; Maciel, André Vinicius Vieira; Jamacaru, Francisco Vagnaldo Fechine

2016-01-01

to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones. o objetivo deste trabalho é avaliar o efeito da L-lisina nos epitélios vesical e intestinal de ratas submetidas à vesicossigmoidostomia. quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido à vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas à vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Após oito semanas os animais foram sacrificados. na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de células transicionais, papiloma de células transicionais e metaplasia escamosa. Quanto à ocorrência de focos de criptas aberrantes nos colos dos animais operados, não foi evidenciado diferença estatística significante em nenhum dos fragmentos distal, proximal e médio, e todos juntos (P=1,0000). apesar de, estatisticamente, não ter havido promoção de carcinogênese nos epitélios dos ratos tratados com L-lisina, no tempo observado, é nítida a histogênese da carcinogênese de bexiga em sua fase inicial, no epitélio vesical, em todos os ratos operados, estando esta provavelmente associada à infecção crônica e aos diminutos cálculos vesicais.

Interstitial cystitis intravesical therapy

PubMed Central

2017-01-01

Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy. Treatment strategies focus on restoring lower urinary tract epithelial function, inhibiting neural activation, controlling allergies and relieving symptoms. In this review, current intravesical therapy will be discussed, as well as what lies on the horizon for intravesical therapy in IC. PMID:28791236

Unexpected complication after cystometry in the hypocompliant urinary bladder: formation of a knot in the double lumen urethral catheter--a case report.

PubMed

Ayyildiz, Ali; Huri, Emre; Nuhoğlu, Bariş; Germiyanoğlu, Cankon

2006-01-01

Urodynamic evaluation is frequently used in the follow-up of the treatment and diagnosis of incontinence, which develops in connection with a neurogenic or non-neurogenic reason. There is no identified serious complication during or after urodynamic evaluation, present in the literature up to date. Hematuria, due to the urethral catheter, the development of oedema in the urinary bladder wall and the development of urinary bladder spasm as a result of catheter irritation, are some of the complications, which may occur. In this paper, twist and knot formation in the double lumen urethral catheter after cystometry of a patient with a hypocompliant urinary bladder, has been presented.

Altered neurogenic and mechanical responses to acetylcholine, ATP and substance P in detrusor from rat with outlet obstruction.

PubMed

Pinna, C; Sanvito, P; Puglisi, L

2006-08-22

The well-known side effects of anticholinergic compounds used to treat urinary incontinence caused by detrusor overactivity have addressed the interest on other pharmacological intervention. The purpose of the present work was to investigate the possible changes in purinergic and cholinergic components of parasympathetic neurotransmission in obstructed rat bladders with detrusor overactivity, and to examine the effect of the association of suramin, atropine and indomethacin on nerve-mediated responses to electrical field stimulation (EFS). Mechanical responses to exogenous acetylcholine, ATP and substance P were also evaluated. Altered sensitivities to acetylcholine and to the sensory neurotransmitter substance P, but unchanged sensitivity to the stable ATP analogue alpha,beta-methyleneATP were observed in bladders from obstructed rats. Suramin and atropine inhibited purinergic and cholinergic components of the neurogenic responses evoked by EFS in detrusor strips from control and obstructed rats. Interestingly, suramin enhanced the antagonistic effect of atropine on neurogenic responses of detrusor strips at all frequencies of stimulation tested. Our results suggest that the association between an antimuscarinic drug and an antagonist of P2X purinoceptors such as suramin might be helpful to reduce the therapeutic dosage of the antimuscarinic drug, along with its side effects. This approach may be of interest in the therapy of patients with bladder incontinence caused by detrusor overactivity, which do not even respond to a maximal dosage of antimuscarinic drug.

Sex differences in neonatal and young adult rat lower urinary tract function caused by bladder reduction.

PubMed

Chien, China; Chang, Huiyi Harriet; Wu, Hsi-Yang

2015-08-01

Pediatric urinary incontinence has been proposed as a cause for adult urinary incontinence, yet animal models mimic the findings of overactive bladder more closely than dysfunctional voiding. We used the bladder reduction (BR) model to study the effects of early external urethral sphincter (EUS) dysfunction on the maturation of lower urinary tract function in neonatal and young adult rats of both sexes. To determine long-term alterations in bladder and EUS function in young adult rats caused by neonatal BR. 46 Sprague-Dawley rats underwent BR and 52 underwent sham surgery at 1 week of age. At 3, 6, and 9 weeks of life, cystometry was carried out, 8-OH-DPAT (serotonergic receptor agonist) and WAY 100,635 (serotonergic receptor antagonist) were administered intravenously. Pressure threshold (PT), volume threshold (VT), storage tonic AUC, contraction area under the curve (AUC), EUS burst amplitude and burst duration were measured at baseline and after administration of serotonergic agents. PT increased in 3-week BR females compared with shams (31.1 vs. 22.7 cm H2O, p < 0.01), in conjunction with less efficient EUS emptying, as burst amplitude was suppressed (BR 0.04 vs. sham 0.07 mV, p < 0.05). VT subsequently increased in 9-week BR females compared with shams (0.81 vs. 0.36 mL, p < 0.05). Although 3-week BR males also experienced suppressed burst amplitude (BR 0.17 vs. sham 0.28 mV, p < 0.05), they showed no difference in PT at 3 weeks or VT at 9 weeks compared with sham males. The burst amplitude returned to normal in 6- and 9-week BR animals of both sexes, confirming a spontaneous recovery of EUS function over time. The thresholds for voiding in male rats are not as sensitive to early changes in EUS function compared with female rats. The response to serotonergic agents was identical between BR and sham animals. In the female animals, 8-OH-DPAT increased storage tonic AUC and burst duration, whereas in male animals, 8-OH-DPAT increased contraction AUC, burst amplitude, and burst duration. WAY 100,635 reversed the enhancements of EUS function caused by 8-OH-DPAT. BR caused a temporary impairment of EUS emptying at 3 weeks of life, similar to dysfunctional voiding, while serotonergic agonists remained effective at enhancing EUS emptying in BR animals. Although EUS emptying spontaneously improved, the increase in VT in female young adult rats suggests that timely treatment of EUS dysfunction is required to decrease the risk of long-term bladder dysfunction. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Ultrasound bladder wall thickness measurement in diagnosis of recurrent urinary tract infections and cystitis cystica in prepubertal girls.

PubMed

Milošević, Danko; Trkulja, Vladimir; Turudić, Daniel; Batinić, Danica; Spajić, Borislav; Tešović, Goran

2013-12-01

To evaluate urinary bladder wall thickness (BWT) assessed by ultrasound as a diagnostic tool for cystitis cystica. This was a 9-year prospective study comprising 120 prepubertal girls. Sixty subjects of whom half underwent cystoscopy represented cases while the other 60 (those with a single urinary tract infection and healthy subjects) represented controls. Based on receiver operating characteristics (ROC) analysis, BWT discriminated very well between cases and controls with area under the ROC curve close to 1.0. At the optimum cut-off defined at 3.9 mm, negative predictive value (NPV) was 100% leaving no probability of cystic cystitis with BWT <3.9 mm. Positive predictive value (PPV) was also very high (95.2%), indicating only around 4.82% probability of no cystic cystitis in patients with BWT values ≥3.9 mm. BWT could also distinguish between healthy subjects and those with a cured single urinary tract infection, although discriminatory properties were moderate (area under ROC 86.7%, PPV 78.8%, NPV 85.2%). Ultrasound mucosal bladder wall measurement is a non-invasive, simple and quite reliable method in diagnosis of cystitis cystica in prepubertal girls with recurrent urinary tract infections. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Fibrosarcoma of the urinary bladder in a cat

PubMed Central

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela

2015-01-01

Case summary A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months’ duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. Relevance and novel information To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia. PMID:28491352

Fibrosarcoma of the urinary bladder in a cat.

PubMed

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela; Greci, Valentina

2015-01-01

A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia.

Effects of Phenobarbital and Carbazole on Carcinogenesis of the Lung, Thyroid, Kidney, and Bladder of Rats Pretreated with N‐Bis(2‐hydroxypropyl)nitrosamine

PubMed Central

Masuda, Atsuko; Imaida, Katsumi; Ogiso, Tadashi; Ito, Nobuyuki

1988-01-01

Studies were made on potential modifying effects of phenobarbital (PB) and carbazole on tumor development induced by N‐bis(2‐hydroxypropyl)nitrosamine (DHPN), a wide‐spectrum carcinogen in rats. Effects on the lung, thyroid, kidney, bladder and liver were investigated. Male F344 rats were given 0.2% DHPN in their drinking water for 1 week and then 0.05% PB or 0.6% carbazole in their diet for 50 weeks. Control animals were treated with either DHPN or PB or carbazole only. Neither PB nor carbazole affected the incidence or histology of lung tumors. However, PB promoted the development of thyroid tumors and preneoplastic lesions of the liver, while carbazole promoted the induction of renal pelvic tumors. PMID:3133336

INDUCTION OF TRANSTITIONAL CELL HYPERPLASIA IN THE URINARY BLADDER AND ABERRANT CRYPT FOCI IN THE COLON OF RATS TREATED WITH INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

ABSTRACT

Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of drinking water containing disinfection by-products (DBPs). The present study...

GENE EXPRESSION CAN DIFFERENTIATE CARCINOGENIC FROM NON-CARCINOGENIC DOSES OF DIMETHYLARSINIC ACID (DMAv) IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS

EPA Science Inventory

Arsenic is an environmental concern worldwide, and drinking arsenic contaminated water has been associated with increased incidences of skin, lung and bladder cancer. Dimethylarsinic acid (DMAv) is a major metabolite of inorganic arsenic in rodents and humans and is the predomina...

DNA BINDING AND ADDUCT FORMATION OF AFLATOXIN B1 IN CULTURED HUMAN AND ANIMAL TRACHEOBRONCHIAL AND BLADDER TISSUES

EPA Science Inventory

DNA binding and adduct formation of aflatoxin B1 (AFB1) was studied in cultured bladder and tracheobronchial explants from human, monkey, dog, hamster and rat. Explants were exposed to (3H)AFB1 (1 micrometer final concentration) in PFHR-4 medium (pH 7.4) without serum for 24 h, a...

INTERSPECIES COMPARISONS OF BENZO(A)PYRENE METABOLISM AND DNA-ADDUCT FORMATION IN CULTURED HUMAN AND ANIMAL BLADDER AND TRACHEOBRONCHIAL TISSUES

EPA Science Inventory

Cultured bladder and tracheobronchial explants from human, monkey, dog, hamster, and rat were used to study the metabolism, covalent binding to DNA, and DNA:adduct formation of (3H0benzo(a)pyrene (BP). Both organs from all species formed large amounts (40 to 70% of total 3H in th...

Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.

PubMed

Vallo, Stefan; Gilfrich, Christian; Burger, Maximilian; Volkmer, Björn; Boehm, Katharina; Rink, Michael; Chun, Felix K; Roghmann, Florian; Novotny, Vladimir; Mani, Jens; Brisuda, Antonin; Mayr, Roman; Stredele, Regina; Noldus, Joachim; Schnabel, Marco; May, Matthias; Fritsche, Hans-Martin; Pycha, Armin; Martini, Thomas; Wirth, Manfred; Roigas, Jan; Bastian, Patrick J; Nuhn, Philipp; Dahlem, Roland; Haferkamp, Axel; Fisch, Margit; Aziz, Atiqullah

2016-10-01

To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men. Copyright © 2016 Elsevier Inc. All rights reserved.

Sonographic diagnosis of vesicouterine fistula.

PubMed

Park, O-R; Kim, T-S; Kim, H-J

2003-07-01

Vesicouterine fistula is one of the least common types of urogenital fistula, accounting for only 1-4% of all cases. We report a case of vesicouterine fistula after vacuum delivery in a woman with a history of a previous Cesarean section. The 29-year-old woman was hospitalized due to continuous serosanguinous vaginal leakage and hematuria. Transvaginal sonography demonstrated the presence of a fistulous tract between the uterus and the bladder. Cystoscopy demonstrated a small opening in the posterior bladder wall and a cystogram revealed a fistulous tract between the posterior portion of the bladder and the uterine cavity. Since the patient could not tolerate her symptoms, we decided to close the fistulous tract surgically. The fistulous tract was excised and the bladder and uterus were closed primarily. The bladder was drained with a Foley catheter for 12 days and subsequent follow-up of the patient has demonstrated urinary continence. Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Case report of metastatic invasive breast lobular carcinoma to the urinary bladder.

PubMed

Al Ibraheemi, Ahmed A

2016-01-01

Breast cancer is the most common cancer in women except skin cancer. The common metastatic sites include lymph node, lung, liver and bone. However, metastasis to the bladder is extremely rare. To our knowledge, this is the first case of breast cancer metastasis to urinary bladder in Jordan which is reported. Nine years after the initial diagnosis of lobular breast carcinoma, the patient suffered from left side leg edema; Ultrasonography and Computed tomography scanning showed thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of the bladder confirmed metastatic lesion from the breast. In contrast to the primary tumor, bladder metastasis showed negative expression of estrogen (ER) and progesterone (PR) receptors. However, Her2neu test was negative in both. The reported case confirms that bladder metastasis from breast cancer tend to occur late after the diagnosis of the primary tumor. Furthermore, bladder metastasis can be asymptomatic and heterogeneous in ER and PR expression in comparison with the primary tumor. This report supports the need for careful follow-up and early intervention whenever such clinical situation is suspected. This report supports further evaluation of receptor status at time of metastasis.

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

EPA Science Inventory

Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human
lymphocytes.

Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

[Values of the micronucleus test on animal epithelial cells exposed to titanium dioxide].

PubMed

Iurchenko, V V; Krivtsova, E K; Iuretseva, N A; Tul'skaia, E A; Mamonov, R A; Zholdakova, Z I; Sinitsyna, O O; Mal'tseva, M M; Pankratova, G P; Sycheva, L P

2011-01-01

The genetic safety of titanium dioxide (TD)-containing foods and cosmetic products has been little investigated. The study evaluated the mutagenic activity of TD in the micronucleus test with animal visceral mucosal epithelial cells. Two simethicone-coated anatase samples (mean size 160 and 33.2 nm) were inserted into the mouse stomach in doses of 40-200-1000 mg/kg seven times and applied as an ingredient of 10 and 25% cream (doses 250 and 625 mg/kg, respectively) to the hair-sheared rat skin once for 4 hours. Analysis of cytogenetic disorders (micronuclei, protrusions, and the atypical form of the nucleus) revealed no mutagenic properties of TD on the mucosal epithelium of the mouse and rat intestine, mouse prostomach, and rat uterine bladder. Enhanced mitotic activity was observed in all the study tissues after exposure of both samples to TD given in some or in all (in the rat urinary bladder mucosal epithelium) doses.

Review of Surgical Techniques of Experimental Renal Transplantation in Rats.

PubMed

Shrestha, Badri; Haylor, John

2017-08-01

Microvascular surgical techniques of renal transplant in rats have evolved over the past 5 decades to achieve successful rat renal transplant; these modifications have included surgical techniques to address the anatomic variations in the renal blood vessels and those to reduce ischemic and operation durations. Here, we review the surgical techniques of renal transplant in rats and evaluate the advantages and disadvantages of individual techniques of vascular and ureteric anastomoses. For this review, we performed a systematic literature search using relevant medical subject heading terms and included appropriate publications in the review. Since the first description of a rat model of renal transplant by Bernard Fisher and his colleagues in 1965, which used end-to-side anastomosis between the renal vein and renal artery to the recipient inferior vena cava and aorta, several vascular and ureteric anastomosis techniques have been modified. Vascular anastomosis techniques now include end-to-end anastomosis, use of donor aortic and inferior vena cava conduits, sleeve and cuff anastomoses, and application of fibrin glue. Likewise, restoration of the urinary tract can now be achieved by direct anastomosis of the donor ureter to the recipient bladder, end-to-end anastomosis between the donor and recipient ureters, and donor bladder cuff to the recipient bladder. There are advantages and disadvantages attributable to individual techniques. The range of vascular and ureteric anastomosis techniques that has emerged reflects the need for mastering more than one technique to suit the vascular anatomy of individual animals and to reduce operating time for achieving successful outcomes after renal transplant.

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

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.

Ultrasonographic anatomy of the healthy southern tigrina ( Leopardus guttulus) abdomen: comparison with domestic cat references.

PubMed

Müller, Thiago R; Marcelino, Raquel S; de Souza, Livia P; Teixeira, Carlos R; Mamprim, Maria J

2017-02-01

Objectives The aim of the study was to describe the normal abdominal echoanatomy of the tigrina and to compare it with the abdominal echoanatomy of the domestic cat. Reference intervals for the normal abdominal ultrasonographic anatomy of individual species are important for accurate diagnoses and interpretation of routine health examinations. The hypothesis was that the echoanatomy of the tigrina was similar to that of the domestic cat. Methods Eighteen clinically healthy tigrina were selected for abdominal ultrasound examination, in order to obtain normal parameters of the bladder, spleen, adrenal gland, kidney, gastrointestinal tract, liver and gall bladder, and Doppler parameters of liver and kidney vessels. Results The splenic parenchyma was consistently hyperechoic to the kidneys and liver. The liver, kidneys and spleen had similar echotexture, shape and dimensions when compared with the domestic cat. The gall bladder was lobulated and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The adrenal glands had a bilobulated shape. The urinary bladder had a thin echogenic wall. The Doppler parameters of the portal vein and renal artery were similar to the domestic cat. Conclusions and relevance The results support the hypothesis that the ultrasonographic parameters of the abdominal viscera of the southern tigrina are similar to those of the domestic cat.

Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy

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

Wognum, S.; Chai, X.; Hulshof, M. C. C. M.

2013-02-15

Purpose: Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumormore » and the lack of visible anatomical landmarks for validation. Methods: The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight parameters were determined for the weighted S-TPS-RPM. Results: The weighted S-TPS-RPM registration algorithm with optimal parameters significantly improved the anatomical accuracy as compared to S-TPS-RPM registration of the bladder alone and reduced the range of the anatomical errors by half as compared with the simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. The weighted algorithm reduced the RDE range of lipiodol markers from 0.9-14 mm after rigid bone match to 0.9-4.0 mm, compared to a range of 1.1-9.1 mm with S-TPS-RPM of bladder alone and 0.9-9.4 mm for simultaneous nonweighted registration. All registration methods resulted in good geometric accuracy on the bladder; average error values were all below 1.2 mm. Conclusions: The weighted S-TPS-RPM registration algorithm with additional weight parameter allowed indirect control over structure-specific flexibility in multistructure registrations of bladder and bladder tumor, enabling anatomically coherent registrations. The availability of an anatomically validated deformable registration method opens up the horizon for improvements in IGART for bladder cancer.« less

Alkaline phosphatase, 5'-nucleotidase and magnesium-dependent adenosine triphosphatase activities in the transitional epithelium of the rat urinary bladder.

PubMed

Zhang, S X; Kobayashi, T; Okada, T; García del Saz, E; Seguchi, H

1991-07-01

The cerium-based method was used to demonstrate cytochemically the ultrastructural localization of alkaline phosphatase (ALPase), 5'-nucleotidase (5'-Nase) and magnesium-dependent adenosine triphosphatase (Mg-ATPase) on the transitional epithelium of the rat urinary bladder. The reaction product for ALPase was found on the plasma membrane of all epithelial cells, except the luminal surface of superficial cells. The activity of 5'-Nase appeared on the plasma membrane of all bladder transitional epithelial cells, including the free surface of superficial cells. The Mg-ATPase reaction product was seen on the plasma membrane of superficial, intermediate and basal cells, but never on the luminal surface of superficial cells and it was only occasionally seen on the basal surface. The possible functions of these phosphatases have been discussed, and it was emphasized that the 5'-Nase activity present on the luminal surface of superficial cells may play a special role in the membrane movement of these cells in the transitional epithelium.

Resistance to infection of five different materials in a rat body wall model.

PubMed

Medberry, Christopher J; Tottey, Stephen; Jiang, Hongbin; Johnson, Scott A; Badylak, Stephen F

2012-03-01

Infection occurs after approximately 1% of hernia repair procedures. The resistance to infection of the repair materials is therefore an important consideration. We evaluated the infection resistance of five different materials in a rat model of body wall repair, two of which, urinary bladder matrix (UBM-ECM) and Revive, were not previously evaluated in a controlled model of infection. An inoculum of 1 × 10(8) colony forming units of Staphylococcus aureus was delivered to the wound site following implantation of an autograft, UBM-ECM, Proceed, Prolene, or Revive. Infection was monitored by white blood cell counts, body temperature, bacterial culture, and histomorphologic analysis of the implant site. Infection was shown in all groups through increased white blood cell count and body temperature. Animals with UBM-ECM returned to pre-surgery body temperature before all other groups. Substantial bacterial clearance was found in the autograft, UBM-ECM, and Prolene. Histomorphologic analysis showed evidence for persistent bacterial infection in Prolene, Proceed, and Revive 28 d after implantation, whereas the autograft and UBM-ECM appeared free of infection. The autograft showed a pyogranulomatous inflammatory reaction at 28 d while UBM-ECM was similar to uninfected controls. Superior infection resistance was shown by UBM-ECM compared with the other materials, which were substantially equivalent. Histomorphologic analysis clearly showed an increased ability to resist persistent bacterial infection for UBM-ECM. Our results suggest UBM-ECM may be useful as a repair material in areas of high risk for infection. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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.

Systemic functional expression of N-acetyltransferase polymorphism in the F344 Nat2 congenic rat

PubMed Central

Hein, David W.; Bendaly, Jean; Neale, Jason R.; Doll, Mark A.

2008-01-01

Rat lines congenic for the rat N-acetyltransferase 2 [(RAT)Nat2] gene were constructed and characterized. F344 (homozygous Nat2 rapid) males were mated to WKY (homozygous Nat2 slow) females to produce heterozygous F1. F1 females were then backcrossed to F344 males. Heterozygous acetylator female progeny from this and each successive backcross were identified by rat Nat2 genotyping and mated with F344 rapid acetylator males. Following ten generations of backcross mating, heterozygous acetylator brother/sister progeny were mated to produce the homozgygous rapid and slow acetylator Nat2 congenic rat lines. p-Aminobenzoic acid (selective for rat NAT2) and 4-aminobiphenyl N-acetyltransferase activities were expressed in all tissues examined (liver, lung, esophagus, stomach, small intestine, colon, pancreas, kidney, skin, leukocytes, and urinary bladder in male and female rats and in breast of female and prostate of male rats). NAT2 expression in rat extrahepatic tissues was much higher than in liver. In each tissue, activities were Nat2-genotype dependent, with highest levels in homozygous rapid acetylators, intermediate levels in heterozygous acetylators, and lowest in homozygous slow acetylators. Sulfamethazine (selective for rat NAT1) N-acetyltransferase activities were observed in all tissues examined in both male and female rats except for breast (females), bladder and leukocytes. In each tissue, the activity was Nat2-genotype independent, with similar levels in homozygous rapid, heterozygous, and homozygous slow acetylators. These congenic rat lines are useful to investigate the role of NAT2 genetic polymorphism in susceptibility to cancers related to arylamine carcinogen exposures. PMID:18799801

Neuromodulation of the neural circuits controlling the lower urinary tract.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Gerasimenko, Yury P; Taccola, Giuliano; Edgerton, V Reggie

2016-11-01

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner. Copyright © 2016. Published by Elsevier Inc.

[Glandular squamous cell carcinoma of the urinary bladder].

PubMed

Kovylina, M V; Pushkar', D Iu; Zaĭrat'iants, O V; Rasner, P I

2006-01-01

The paper gives a clinical observation of a 52 year-old male with a rare histological urinary bladder tumor primary grandular-squamous-cell carcinoma (pT3N IM0). The tumor is represented by two components large acinic-cell adenocarcinoma and squamous-cell carcinoma with keratinization, which smoothly pass one into another; the tumor has grown through all layers of the urinary bladder wall but it has failed to grow into the peritoneum. A microscopic study has indicated that the urachus is intact. Metastases were found in 3 of 8 lymph nodes: one showed high-grade adenocarcinoma and two others displayed average-grade squamous-cell carcinoma.

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research.

PubMed

Kitta, Takeya; Kanno, Yukiko; Chiba, Hiroki; Higuchi, Madoka; Ouchi, Mifuka; Togo, Mio; Moriya, Kimihiko; Shinohara, Nobuo

2018-01-01

The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value. © 2017 The Japanese Urological Association.

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.

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

Variations in carbachol- and ATP-induced contractions of the rat detrusor: effects of gender, mucosa and contractile direction.

PubMed

Liang, Willmann; Leung, Ping Chung

2012-12-01

Contractile characteristics of the bladder may depend on variables such as gender, mucosa (MU) and direction of the contractions. However, definitive information is not yet available despite earlier studies on the effects of one variable or another. Here, we explored the differences in the rat detrusor attributable to gender, mucosa and contractile direction. K+, carbachol (CCh) and ATP were used as contractile stimuli on rat detrusor strips with and without MU. Contractility was monitored using a myograph system. Both tonic and phasic contractile activities were analyzed. MU-independent contractions induced by CCh were more potent in females, an effect specific to the longitudinal direction only. The maximal CCh response was larger also in females when MU was removed, suggesting a stronger MU-independent component in the contraction. The larger area under curves of the females under ATP stimulation showed dependence on MU and contractile direction as well. ATP-induced contractions in the males were affected more by MU in the transverse direction than in the females. Direction- and MU-dependent variability of ATP responses was also observed in the males but not in females. Findings here added new information to the understanding of bladder contractile physiology, providing insights into the quest for better drugs in managing bladder disorders.

Sonography of tumors and tumor-like lesions that mimic carcinoma of the urinary bladder

PubMed Central

Szopiński, Tomasz; Gołąbek, Tomasz; Ostasz, Oksana; Bojko, Stefania

2014-01-01

One of the basic abdominal organs that is assessed during transabdominal ultrasound examination for urological reasons is the urinary bladder. The bladder must be filled with urine. This is a prerequisite for a reliable assessment and, at the same time, an acoustic window in examining adjacent structures and organs, for instance the prostate gland. In some cases, doubts occur with respect to the nature of lesions detected. The paper presents anatomic lesions, defects and pathologies which might be erroneously interpreted as tumors of the urinary bladder, i.e. transitional cell carcinoma of the urinary bladder. The following lesions are discussed: 1) anatomic defects (including urachus remnants, ligaments that stabilize the bladder or cyst in the opening of the ureter into the bladder – ureterocele); 2) tumor- like lesions in the lumen of the urinary bladder (such as blood clots, fungus balls, stones or foreign bodies); 3) bladder wall pathologies (i.e. cystitis or endometriosis), focal decidual transformation of stromal cells or inflammatory pseudotumor; 4) lesions impressing on the bladder from the outside (the mesentery of the sigmoid colon, the bowel, pathological lesions in organs adjacent to the urinary bladder, inflammatory infiltration, vasogenic compression of the bladder, pelvic lipomatosis, pathological lesions of the pubic symphysis); 5) postoperative lesions. All these lesions may mimic carcinoma of the urinary bladder in sonography. Bearing this fact in mind is significant in establishing a diagnosis. Due to the malignant character of carcinoma of the urinary bladder and the need for aggressive surgical treatment, a correct diagnosis of this disease is essential for patients, particularly because the lack of adequate treatment and delayed treatment considerably affect prognosis. PMID:26672732

Effect of stimulation intensity and botulinum toxin isoform on rat bladder strip contractions.

PubMed

Smith, Christopher P; Boone, Timothy B; de Groat, William C; Chancellor, Michael B; Somogyi, George T

2003-07-15

The present experiments compared the inhibitory effects of botulinum toxin A (BoNT-A) and botulinum toxin D (BoNT-D) on neurally evoked contractions of rat bladder strips. We examined the effect of fatigue (trains of 100 shocks at 20Hz every 20s for 10min) followed by non-fatigue stimulation (trains of 100 shocks at 20Hz every 100s for 20min) on the onset of effect and potency of the two toxins. For non-fatigue experiments, strips were untreated (n=4); or incubated with 1.36nM BoNT-A (n=4). During fatigue experiments, strips were untreated (n=5); or treated with either 1.36nM BoNT-A (n=6) or 0.8nM BoNT-D (n=6). In non-fatigue experiments, BoNT-A produced significant decreases in contractile area after 1h of stimulation compared to untreated strips (P<0.05). After three series of fatigue stimulation, differences in recovery amplitude and area between untreated versus BoNT-A, and untreated versus BoNT-D bladder strips, were statistically significant (P<0.05). The onset of inhibitory effect was quicker in BoNT-D-treated strips, as a significant reduction (P<0.05) in recovery of contractile area was observed after 1h of stimulation compared to both untreated and BoNT-A-treated preparations. In addition, treated (BoNT-A and BoNT-D) and untreated bladder strips responded similarly to atropine, suggesting that the effects of BoNT result from inhibition of both acetylcholine and ATP release. Our results demonstrate that BoNT-D may be a more effective agent to inhibit transmitter release from autonomic nerves of the rat lower urinary tract. Moreover, in our hands, non-fatigue stimulation is as effective as fatigue stimulation in inhibiting bladder strip contractions.

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

Feeling Wall Tension in an Interactive Demonstration of Laplace's Law

ERIC Educational Resources Information Center

Letic, Milorad

2012-01-01

Laplace's Law plays a major role in explanations of the wall tension of structures like blood vessels, the bladder, the uterus in pregnancy, bronchioles, eyeballs, and the behavior of aneurisms or the enlarged heart. The general relation of Laplace's law, expressing that the product of the radius of curvature (r) and pressure (P) is equal to wall…

TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats

PubMed Central

Philyppov, Igor B.; Paduraru, Oksana N.; Gulak, Kseniya L.; Skryma, Roman; Prevarskaya, Natalia; Shuba, Yaroslav M.

2016-01-01

TRPA1 is a Ca2+-permeable cation channel that is activated by painful low temperatures (˂17 °C), irritating chemicals, reactive metabolites and mediators of inflammation. In the bladder TRPA1 is predominantly expressed in sensory afferent nerve endings, where it mediates sensory transduction. The contractile effect of its activation on detrusor smooth muscle (DSM) is explained by the release from sensory afferents of inflammatory factors – tachykinins and prostaglandins, which cause smooth muscle cell contraction. Diabetes is a systemic disease, with common complications being diabetic cystopathies and urinary incontinence. However, data on how diabetes affects bladder contractility associated with TRPA1 activation are not available. In this study, by using a rat model with streptozotocin-induced type I diabetes, contractility measurements of DSM strips in response to TRPA1-activating and modulating pharmacological agents and assessment of TRPA1 mRNA expression in bladder-innervating dorsal root ganglia, we have shown that diabetes enhances the TRPA1-dependent mechanism involved in bladder DSM contractility. This is not due to changes in TRPA1 expression, but mainly due to the general inflammatory reaction caused by diabetes. The latter leads to an increase in cyclooxygenase-2-dependent prostaglandin synthesis through the mechanisms associated with substance P activity. This results in the enhanced functional coupling between the tachykinin and prostanoid systems, and the concomitant increase of their impact on DSM contractility in response to TRPA1 activation. PMID:26935999

TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats.

PubMed

Philyppov, Igor B; Paduraru, Oksana N; Gulak, Kseniya L; Skryma, Roman; Prevarskaya, Natalia; Shuba, Yaroslav M

2016-01-01

TRPA1 is a Ca(2+)-permeable cation channel that is activated by painful low temperatures (<17°C), irritating chemicals, reactive metabolites and mediators of inflammation. In the bladder TRPA1 is predominantly expressed in sensory afferent nerve endings, where it mediates sensory transduction. The contractile effect of its activation on detrusor smooth muscle (DSM) is explained by the release from sensory afferents of inflammatory factors - tachykinins and prostaglandins, which cause smooth muscle cell contraction. Diabetes is a systemic disease, with common complications being diabetic cystopathies and urinary incontinence. However, data on how diabetes affects bladder contractility associated with TRPA1 activation are not available. In this study, by using a rat model with streptozotocin-induced type I diabetes, contractility measurements of DSM strips in response to TRPA1-activating and modulating pharmacological agents and assessment of TRPA1 mRNA expression in bladder-innervating dorsal root ganglia, we have shown that diabetes enhances the TRPA1-dependent mechanism involved in bladder DSM contractility. This is not due to changes in TRPA1 expression, but mainly due to the general inflammatory reaction caused by diabetes. The latter leads to an increase in cyclooxygenase-2-dependent prostaglandin synthesis through the mechanisms associated with substance P activity. This results in the enhanced functional coupling between the tachykinin and prostanoid systems, and the concomitant increase of their impact on DSM contractility in response to TRPA1 activation.

Application of high-intensity focused ultrasound for fetal therapy: experimental study using an animal model of lower urinary tract obstruction.

PubMed

Aoki, Hiroko; Ichizuka, Kiyotake; Ichihara, Mitsuyoshi; Matsuoka, Ryu; Hasegawa, Junichi; Okai, Takashi; Umemura, Shinichirou

2013-04-01

The purpose of this study is to investigate whether high-intensity focused ultrasound (HIFU) exposure is able to produce a fistula between the bladder and abdominal wall of a fetus with lower urinary tract obstruction (LUTO). We constructed a prototype HIFU transducer in combination with an imaging probe. HIFU was applied to the lower abdomen of a rabbit neonate that was complicated by LUTO as an experimental model to produce a fistula; HIFU was applied in a tank filled with degassed water. Exposed lesions were assessed by histological analysis at necropsy. When HIFU was applied at 5.5 kW/cm(2) of spatial-peak temporal average intensity (SPTA), a fistula was created between the lower abdominal wall and the urinary bladder; urine gushed out from the bladder through the fistula within 60 s after HIFU exposure. The findings suggest that fetal diseases such as LUTO can be non-invasively treated using HIFU exposure from even outside the maternal body, though this study was performed in a water tank.

Ultrasound findings in urinary shistosomaisis infection in school children in the Gezira State Central Sudan.

PubMed

Elmadani, Ahmed E; Hamdoun, Anas O; Monis, Ahmed; Karamino, Nhashal E; Gasmelseed, Nagla

2013-01-01

To evaluate the ultrasound findings of urinary schistosomiasis in Quran school (Khalwas) children in Gezira State Sudan, we studied all the students from two schools. A total of 103 boys were tested for urinary schistosomiasis using the urine filtration method. Schistosoma haematobium (S. haematobium) eggs were counted. Ultrasound was performed for all the positive subjects. Seventy-three (71%) subjects were positive for S. haematobium. The mean age was 11.3 ± 2.9 years. Sixty-six (90.4%) subjects showed urinary tract abnormalities. The findings revealed the following degrees of wall thickening: 53.0% mild, 18.2% moderate and 21.2% severe. Urinary bladder polyp(s) were noted in 43.3% (single) and 40.9% (multiple) of the subjects, and calcification of the bladder wall was observed in 7.6% subjects. Ureteric dilatation was noted in 38/73 (52.0%), while hydronephrosis was detected in 19/73 (26.3%). The vast majority of urinary tract schistomiasis lesions were in the urinary bladder. Ultrasound is a useful tool for identifying the morbidity of S. haematobium in endemic areas.

Eosinophilic cystitis with recurrent urinary retention: case report.

PubMed

Park, Hongzoo

2017-01-01

Eosinophilic cystitis is a rare inflammatory disease of the bladder whose origin, pathogenesis, and treatment are unknown. Frequency, dysuria, and hematuria are frequent symptoms. Here, we report a rare occurrence of recurrent urinary retention and repetitive catheterization. A 67-year-old male presented with acute urinary retention and intermittent gross hematuria of 2 weeks duration. Urethral catheterization followed by a trial without catheter, was successful. Complete blood count showed presence of eosinophils (eosinophilia) and computed tomography of kidneys, ureter and bladder with contrast showed thickened bladder wall and small prostate. Cystoscopy revealed an erythematous lesion over the anterior wall. The rest of the mucosa was normal. Transurethral biopsies of the lesion were performed and histologic examination showed features of eosinophilic cystitis. Despite multiple medication regimens containing corticosteroids and antihistamines, he presented with recurrent urinary retention, approximately once every month. After 6 months, he was started on bethanechol, which led to no catheterization for up to 2 years. To the best of our knowledge, this is the first report on the successful use of bethanechol as a treatment for eosinophilic cystitis with recurrent urinary retention.

Simultaneous uterine and urinary bladder rupture in an otherwise successful vaginal birth after cesarean delivery.

PubMed

Ho, Szu-Ying; Chang, Shuenn-Dhy; Liang, Ching-Chung

2010-12-01

Uterine rupture is the primary concern when a patient chooses a trial of labor after a cesarean section. Bladder rupture accompanied by uterine rupture should be taken into consideration if gross hematuria occurs. We report the case of a patient with uterine rupture during a trial of labor after cesarean delivery. She had a normal course of labor and no classic signs of uterine rupture. However, gross hematuria was noted after repair of the episiotomy. The patient began to complain of progressive abdominal pain, gross hematuria and oliguria. Cystoscopy revealed a direct communication between the bladder and the uterus. When opening the bladder peritoneum, rupture sites over the anterior uterus and posterior wall of the bladder were noted. Following primary repair of both wounds, a Foley catheter was left in place for 12 days. The patient had achieved a full recovery by the 2-year follow-up examination. Bladder injury and uterine rupture can occur at any time during labor. Gross hematuria immediately after delivery is the most common presentation. Cystoscopy is a good tool to identify the severity of bladder injury. Copyright © 2010 Elsevier. Published by Elsevier B.V. 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.

Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: potential applications to urological diseases.

PubMed

Hipp, Jason D; Davies, Kelvin P; Tar, Moses; Valcic, Mira; Knoll, Abraham; Melman, Arnold; Christ, George J

2007-02-01

To identify early diabetes-related alterations in gene expression in bladder and erectile tissue that would provide novel diagnostic and therapeutic treatment targets to prevent, delay or ameliorate the ensuing bladder and erectile dysfunction. The RG-U34A rat GeneChip (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing approximately 8799 genes) was used to evaluate gene expression in corporal and male bladder tissue excised from rats 1 week after confirmation of a diabetic state, but before demonstrable changes in organ function in vivo. A conservative analytical approach was used to detect alterations in gene expression, and gene ontology (GO) classifications were used to identify biological themes/pathways involved in the aetiology of the organ dysfunction. In all, 320 and 313 genes were differentially expressed in bladder and corporal tissue, respectively. GO analysis in bladder tissue showed prominent increases in biological pathways involved in cell proliferation, metabolism, actin cytoskeleton and myosin, as well as decreases in cell motility, and regulation of muscle contraction. GO analysis in corpora showed increases in pathways related to ion channel transport and ion channel activity, while there were decreases in collagen I and actin genes. The changes in gene expression in these initial experiments are consistent with the pathophysiological characteristics of the bladder and erectile dysfunction seen later in the diabetic disease process. Thus, the observed changes in gene expression might be harbingers or biomarkers of impending organ dysfunction, and could provide useful diagnostic and therapeutic targets for a variety of progressive urological diseases/conditions (i.e. lower urinary tract symptoms related to benign prostatic hyperplasia, erectile dysfunction, etc.).

Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide

PubMed Central

Ozguven, Ali A.; Yılmaz, Omer; Taneli, Fatma; Ulman, Cevval; Vatansever, Seda; Onag, Ali

2014-01-01

Objective: To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis. Materials and Methods: 35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues. Results: Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different. Conclusion: The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedulesin order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine. PMID:24741183

Naproxen induces cell cycle arrest and apoptosis in human urinary bladder cancer cell lines and chemically induced cancers by targeting PI3-K

PubMed Central

Kim, Mi-Sung; Kim, Jong-Eun; Lim, Do Young; Huang, Zunnan; Chen, Hanyong; Langfald, Alyssa; Lubet, Ronald A.; Grubbs, Clinton J.; Dong, Zigang; Bode, Ann M.

2014-01-01

Naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid) is a potent nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is widely used as an over-the-counter medication. Naproxen exhibits analgesic, anti-pyretic, and anti-inflammatory activities. Naproxen, as well as other NSAIDS, has been reported to be effective in the prevention of urinary bladder cancer in rodents. However, potential targets other than the COX isozymes have not been reported. We examined potential additional targets in urinary bladder cancer cells and in rat bladder cancers. Computer kinase profiling results suggested that phosphatidylinositol 3-kinase (PI3-K) is a potential target for naproxen. In vitro kinase assay data revealed that naproxen interacts with PI3-K and inhibits its kinase activity. Pull-down binding assay data confirmed that PI3-K directly binds with naproxen in vitro and ex vivo. Western blot data showed that naproxen decreased phosphorylation of Akt, and subsequently decreased Akt signaling in UM-UC-5 and UMUC-14 urinary bladder cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth and decreased cell viability by targeting PI3-K in both cell lines. Naproxen caused an accumulation of cells at the G1 phase mediated through CDK4, cyclin D1 and p21. Moreover, naproxen induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly (ADP-ribose) polymerase (PARP) in both cell types. Naproxen-induced cell death was mainly due to apoptosis in which a prominent down-regulation of Bcl-2 and up-regulation of Bax were involved. Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN). PMID:24327721

Dosimetry considerations in the enhanced sensitivity of male Wistar rats to chronic ethylene glycol-induced nephrotoxicity

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

Corley, R.A.; Wilson, D.M.; Hard, G.C.

2008-04-15

Male Wistar rats have been shown to be the most sensitive sex, strain and species to ethylene glycol-induced nephrotoxicity in subchronic studies. A chronic toxicity and dosimetry study was therefore conducted in male Wistar rats administered ethylene glycol via the diet at 0, 50, 150, 300, or 400 mg/kg/day for up to twelve months. Subgroups of animals were included for metabolite analysis and renal clearance studies to provide a quantitative basis for extrapolating dose-response relationships from this sensitive animal model in human health risk assessments. Mortality occurred in 5 of 20 rats at 300 mg/kg/day (days 111-221) and 4 ofmore » 20 rats at 400 mg/kg/day (days 43-193), with remaining rats at this dose euthanized early (day 203) due to excessive weight loss. Increased water consumption and urine volume with decreased specific gravity occurred at 300 mg/kg/day presumably due to osmotic diuresis. Calculi (calcium oxalate crystals) occurred in the bladder or renal pelvis at {>=} 300 mg/kg/day. Rats dying early at {>=} 300 mg/kg/day had transitional cell hyperplasia with inflammation and hemorrhage of the bladder wall. Crystal nephropathy (basophilic foci, tubule or pelvic dilatation, birefringent crystals in the pelvic fornix, or transitional cell hyperplasia) affected most rats at 300 mg/kg/day, all at 400 mg/kg/day, but none at {<=} 150 mg/kg/day. No significant differences in kidney oxalate levels, the metabolite responsible for renal toxicity, were observed among control, 50 and 150 mg/kg/day groups. At 300 and 400 mg/kg/day, oxalate levels increased proportionally with the nephrotoxicity score supporting the oxalate crystal-induced nephrotoxicity mode of action. No treatment-related effects on the renal clearance of intravenously infused {sup 3}H-inulin, a marker for glomerular filtration, and {sup 14}C-oxalic acid were observed in rats surviving 12 months of exposure to ethylene glycol up to 300 mg/kg/day. In studies with naive male Wistar and F344 rats (a less sensitive strain), a significant difference was observed in oxalate clearances between young rats (i.e. Wistar clearance < F344) but not in age-matched old rats. Regardless, the ratios of oxalate:inulin clearances in these two strains of rats, including those exposed to ethylene glycol, were all < 1, suggesting that a fraction of the filtered oxalate is reabsorbed. Other species, including humans, typically have clearance ratios > 1 and are more effective at clearing oxalic acid by both glomerular filtration and active secretion. Thus, the lower renal clearance and kidney accumulation of oxalates in male Wistar rats enhances their sensitivity, which will be a factor in human risk assessments. The benchmark dose values (BMD05, BMDL05) were 170 mg/kg/day and 150 mg/kg/day for nephropathy, and 170 mg/kg/day and 160 mg/kg/day for birefringent crystals, using incidence times severity data in each case. The NOAEL of 150 mg/kg/day is the same as that reported after 16-week exposure and appears to be a threshold dose below which no renal toxicity occurs, regardless of exposure duration.« less

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

Achanzar, William E.; Moyer, Carolyn F.; Marthaler, Laura T.

We previously reported prevention of urolithiasis and associated rat urinary bladder tumors by urine acidification (via diet acidification) in male rats treated with the dual peroxisome proliferator-activated receptor (PPAR){alpha}/{gamma} agonist muraglitazar. Because urine acidification could potentially alter PPAR signaling and/or cellular proliferation in urothelium, we evaluated urothelial cell PPAR{alpha}, PPAR{delta}, PPAR{gamma}, and epidermal growth factor receptor (EGFR) expression, PPAR signaling, and urothelial cell proliferation in rats fed either a normal or an acidified diet for 5, 18, or 33 days. A subset of rats in the 18-day study also received 63 mg/kg of the PPAR{gamma} agonist pioglitazone daily for themore » final 3 days to directly assess the effects of diet acidification on responsiveness to PPAR{gamma} agonism. Urothelial cell PPAR{alpha} and {gamma} expression and signaling were evaluated in the 18- and 33-day studies by immunohistochemical assessment of PPAR protein (33-day study only) and quantitative real-time polymerase chain reaction (qRT-PCR) measurement of PPAR-regulated gene expression. In the 5-day study, EGFR expression and phosphorylation status were evaluated by immunohistochemical staining and egfr and akt2 mRNA levels were assessed by qRT-PCR. Diet acidification did not alter PPAR{alpha}, {delta}, or {gamma} mRNA or protein expression, PPAR{alpha}- or {gamma}-regulated gene expression, total or phosphorylated EGFR protein, egfr or akt2 gene expression, or proliferation in urothelium. Moreover, diet acidification had no effect on pioglitazone-induced changes in urothelial PPAR{gamma}-regulated gene expression. These results support the contention that urine acidification does not prevent PPAR{gamma} agonist-induced bladder tumors by altering PPAR{alpha}, {gamma}, or EGFR expression or PPAR signaling in rat bladder urothelium.« less

Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Cohen, Samuel M

2009-06-30

Arsenite (As(III)), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of As(III) and dimethylarsinous acid (DMA(III)) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as l-ascorbate and N-acetylcysteine, did not inhibit As(III)-induced cytotoxicity but they were more effective at inhibiting DMA(III)-induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100ppm As(III). Immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by As(III) treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit As(III)-induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

Nonspecific esterase reaction in hyperplastic urinary bladder epithelium induced by administration of N-butyl-N-(4-hydroxybutyl)nitrosamine, freezing and formalin instillation in rats.

PubMed Central

Akagi, A.; Otsuka, H.

1988-01-01

Chronological changes in nonspecific esterase (NSE) activity in hyperplasia of the bladder mucosa in Wistar rats induced by the administration of 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for up to 20 weeks and in reversible regenerative hyperplasia by freeze ulceration and 20% formalin instillation in the bladder were compared. In regenerative hyperplasia foci with strong NSE activity could not be proved throughout the experimental period, while the foci were detected in hyperplastic epithelium induced by BBN treatment for more than 3 weeks. The focus of NSE high activity persisted for 56 weeks after withdrawal of the carcinogen and the focus or area with the same NSE reaction appeared in papilloma and transitional cell carcinoma seen in weeks 7 to 20 of BBN treatment. The appearance of focal strong activity of NSE seemed to be a promising marker for the precursor lesions of bladder tumors. Short uniform, pleomorphic microvilli were observed on the cell surface of preneoplastic and carcinomatous lesions by BBN as well as on that of regenerative hyperplasia after freeze ulceration and formalin instillation. Images Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:3390388

Endoscopic optical coherence tomography with a modified microelectromechanical systems mirror for detection of bladder cancers

NASA Astrophysics Data System (ADS)

Xie, Tuqiang; Xie, Huikai; Fedder, Gary K.; Pan, Yingtian

2003-11-01

Experimental results of a modified micromachined microelectromechanical systems (MEMS) mirror for substantial enhancement of the transverse laser scanning performance of endoscopic optical coherence tomography (EOCT) are presented. Image distortion due to buckling of MEMS mirror in our previous designs was analyzed and found to be attributed to excessive internal stress of the transverse bimorph meshes. The modified MEMS mirror completely eliminates bimorph stress and the resultant buckling effect, which increases the wobbling-free angular optical actuation to greater than 37°, exceeding the transverse laser scanning requirements for EOCT and confocal endoscopy. The new optical coherence tomography (OCT) endoscope allows for two-dimensional cross-sectional imaging that covers an area of 4.2 mm × 2.8 mm (limited by scope size) and at roughly 5 frames/s instead of the previous area size of 2.9 mm × 2.8 mm and is highly suitable for noninvasive and high-resolution imaging diagnosis of epithelial lesions in vivo. EOCT images of normal rat bladders and rat bladder cancers are compared with the same cross sections acquired with conventional bench-top OCT. The results clearly demonstrate the potential of EOCT for in vivo imaging diagnosis and precise guidance for excisional biopsy of early bladder cancers.

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.

Method of Remotely Constructing a Room

DOEpatents

Michie, J. D.; De Hart, R. C.

1971-10-05

The testing of nuclear devices of high explosive yield has required that cavities of relatively large size be provided at considerable distances below the surface of the earth for the pre-detonation emplacement of the device. The construction of an essentially watertight chamber or room in the cavity is generally required for the actual emplacement of the device. A method is described of constructing such a room deep within the earth by personnel at the surface. A dual wall bladder of a watertight, pliable fabric material is lowered down a shaft into a selected position. The bladder is filled with a concrete grout while a heavy fluid having essentially the same density as the grout is maintained on both sides of the bladder, to facilitate complete deployment of the bladder by the grout to form a room of desired configuration. (10 claims)

Method of remotely constructing a room

DOEpatents

Michie, J.D.; De Hart, R.C.

1971-10-05

The testing of nuclear devices of high explosive yield has required that cavities of relatively large size be provided at considerable distances below the surface of the earth for the pre-detonation emplacement of the device. The construction of an essentially watertight chamber or room in the cavity is generally required for the actual emplacement of the device. A method is described of constructing such a room deep within the earth by personnel at the surface. A dual wall bladder of a watertight, pliable fabric material is lowered down a shaft into a selected position. The bladder is filled with a concrete grout while a heavy fluid having essentially the same density as the grout is maintained on both sides of the bladder, to facilitate complete deployment of the bladder by the grout to form a room of desired configuration. (10 claims)

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

NASA Astrophysics Data System (ADS)

Pan, Y. T.; Xie, T. Q.; Du, C. W.; Bastacky, S.; Meyers, S.; Zeidel, M. L.

2003-12-01

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.

Rapidly quantifying the relative distention of a human bladder

NASA Technical Reports Server (NTRS)

Companion, John A. (Inventor); Heyman, Joseph S. (Inventor); Mineo, Beth A. (Inventor); Cavalier, Albert R. (Inventor); Blalock, Travis N. (Inventor)

1989-01-01

A device and method of rapidly quantifying the relative distention of the bladder in a human subject are disclosed. The ultrasonic transducer which is positioned on the subject in proximity to the bladder is excited by a pulser under the command of a microprocessor to launch an acoustic wave into the patient. This wave interacts with the bladder walls and is reflected back to the ultrasonic transducer, when it is received, amplified and processed by the receiver. The resulting signal is digitized by an analog-to-digital converter under the command of the microprocessor and is stored in the data memory. The software in the microprocessor determines the relative distention of the bladder as a function of the propagated ultrasonic energy; and based on programmed scientific measurements and individual, anatomical, and behavioral characterists of the specific subject as contained in the program memory, sends out a signal to turn on any or all of the audible alarm, the visible alarm, the tactile alarm, and the remote wireless alarm.

Rapidly quantifying the relative distention of a human bladder

NASA Technical Reports Server (NTRS)

Companion, John A. (Inventor); Heyman, Joseph S. (Inventor); Mineo, Beth A. (Inventor); Cavalier, Albert R. (Inventor); Blalock, Travis N. (Inventor)

1991-01-01

A device and method was developed to rapidly quantify the relative distention of the bladder of a human subject. An ultrasonic transducer is positioned on the human subject near the bladder. A microprocessor controlled pulser excites the transducer by sending an acoustic wave into the human subject. This wave interacts with the bladder walls and is reflected back to the ultrasonic transducer where it is received, amplified, and processed by the receiver. The resulting signal is digitized by an analog to digital converter, controlled by the microprocessor again, and is stored in data memory. The software in the microprocessor determines the relative distention of the bladder as a function of the propagated ultrasonic energy. Based on programmed scientific measurements and the human subject's past history as contained in program memory, the microprocessor sends out a signal to turn on any or all of the available alarms. The alarm system includes and audible alarm, the visible alarm, the tactile alarm, and the remote wireless alarm.

Synthetic Bursae for Robots

NASA Technical Reports Server (NTRS)

Lovchik, Christopher S.

2005-01-01

Synthetic bursae are under development for incorporation into robot joints that are actuated by motor-driven cables in a manner similar to that of arthropod joints actuated by muscle-driven tendons. Like natural bursae, the synthetic bursae would serve as cushions and friction reducers. A natural bursa is a thin bladder filled with synovial fluid, which serves to reduce friction and provide a cushion between a bone and a muscle or a tendon. A synthetic bursa would be similar in form and function: It would be, essentially, a compact, soft roller consisting of a bladder filled with a non-Newtonian fluid. The bladder would be constrained to approximately constant volume. The synthetic bursa would cushion an actuator cable against one of the members of a robot joint and would reduce the friction between the cable and the member. Under load, the pressure in the bladder would hold the opposite walls of the bladder apart, making it possible for them to move freely past each other without rubbing.

Use of prophylactic antibiotics for intra-vesicle Botox® injection.

PubMed

Khan, Mohammad Hassan; Baldo, Omer; Koenig, Philip; Shaikh, Naeem

2017-03-01

Botox injection in bladder wall is increasingly used in urology for over active bladder and neurogenic bladder. Aim of this audit is to assess the incidence of UTI after procedure and need for routine use of pre and post procedure antibiotics. It was case notes and lab results based retrospective study of all the patients attended for intra-vesicle Botox injection. Rate of UTI's were lower in the group who received antibiotics pre and post operatively as compared to those who did not. Routine antibiotics use lowers the risk of UTI's in patients receiving intra-vesicle botox. Neurourol. Urodynam. 36:828-828, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A numerical simulation of peristaltic motion in the ureter using fluid structure interactions.

PubMed

Vahidi, Bahman; Fatouraee, Nasser

2007-01-01

An axisymmetric model with fluid-structure interactions (FSI) is introduced and solved to perform ureter flow and stress analysis. The Navier-Stokes equations are solved for the fluid and a linear elastic model for ureter is used. The finite element equations for both the structure and the fluid were solved by the Newton-Raphson iterative method. Our results indicated that shear stresses were high around the throat of moving contracted wall. The pressure gradient magnitude along the ureter wall and the symmetry line had the maximum value around the throat of moving contracted wall which decreased as the peristalsis propagates toward the bladder. The flow rate at the ureter outlet at the end of the peristaltic motion was about 650 mm3/s. During propagation of the peristalsis toward the bladder, the inlet backward flow region was limited to the areas near symmetry line but the inner ureter backward flow regions extended to the whole ureter contraction part. The backward flow was vanished after 1.5 seconds of peristalsis propagation start up and after that time the urine flow was forward in the whole ureter length, so reflux is more probable to be present at the beginning of the wall peristaltic motion.

Characterization of muscarinic and P2X receptors in the urothelium and detrusor muscle of the rat bladder.

PubMed

Ogoda, Masaki; Ito, Yoshihiko; Fuchihata, Yusuke; Onoue, Satomi; Yamada, Shizuo

2016-05-01

Muscarinic and purinergic (P2X) receptors play critical roles in bladder urothelium under physiological and pathological conditions. Aim of present study was to characterize these receptors in rat bladder urothelium and detrusor muscle using selective radioligands of [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS) and αβ-methylene ATP [2,8-(3)H]tetrasodium salt ([(3)H]αβ-MeATP). Similar binding parameters for each radioligand were observed in urothelium and detrusor muscle. Pretreatment with N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard) mustard revealed co-existence of M2 and M3 receptors, with the number of M2 receptors being larger in the urothelium and detrusor muscle. Intravesical administration of imidafenacin and Dpr-P-4 (N → O) (active metabolite of propiverine) displayed significant binding of muscarinic receptors in the urothelium and detrusor muscle. The treatment with cyclophosphamide (CYP) or resiniferatoxin (RTX) resulted in a significant decrease in maximal number of binding sites (Bmax) for [(3)H]NMS and/or [(3)H]αβ-MeATP in the urothelium and detrusor muscle. These results demonstrated that 1) pharmacological characteristics of muscarinic and P2X receptors in rat bladder urothelium were similar to those in the detrusor muscle, 2) that densities of these receptors were significantly altered by pretreatments with CYP and RTX, and 3) that these receptors may be pharmacologically affected by imidafenacin and Dpr-P-4 (N → O) which are excreted in the urine. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Chen, Baowei; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

2012-09-28

Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100 ppm As(V). DMPS (2800 ppm) co-administered in the diet significantly reduced the As(V)-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA. Copyright © 2012. Published by Elsevier Ireland Ltd.

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.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

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

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

Schooneveldt, G.; Kok, H.P.; Bakker, A.

Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CTmore » scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.« less

Evaluation of Musa (Paradisiaca Linn. cultivar)--"Puttubale" stem juice for antilithiatic activity in albino rats.

PubMed

Prasad, K V; Bharathi, K; Srinivasan, K K

1993-10-01

The fresh juice of Musa stem (Puttubale) was tested for its antilithiatic activity. Zinc discs were implanted in the urinary bladder of albino rats to induce urolithiasis. The stones formed were mainly of magnesium ammonium phosphate with traces of calcium oxalate. Musa stem juice (3 mL/rat/day orally) was found to be effective in reducing the formation and also in dissolving the pre-formed stones.

Vesicoureteral reflux (image)

MedlinePlus

... in the bladder wall, which can cause vesicoureteral reflux. Vesicoureteral reflux is a condition that allows urine to go ... and kidneys causing repeated urinary tract infections. The reflux of urine exposes the ureters and kidney to ...

Novel multi-system functional gains via task specific training in spinal cord injured male rats.

PubMed

Ward, Patricia J; Herrity, April N; Smith, Rebecca R; Willhite, Andrea; Harrison, Benjamin J; Petruska, Jeffrey C; Harkema, Susan J; Hubscher, Charles H

2014-05-01

Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

Elevated urinary urea by high-protein diet could be one of the inducements of bladder disorders.

PubMed

Liu, Ming; Li, Min; Liu, Jiangfeng; Wang, Hongkai; Zhong, Dandan; Zhou, Hong; Yang, Baoxue

2016-02-16

Previous work found that urea accumulation in urothelial cells caused by urea transporter B knockout led to DNA damage and apoptosis that contributed to the carcinogenesis. The purpose of this study is to explore the potential connection between high urinary urea concentration and the bladder disorders. A high protein diet rat model was conducted by feeding with 40 % protein diet. In-silico modeling and algorithm, based on the results of microarray and proteomics from the bladder urothelium, were used for the reconstruction of accurate cellular networks and the identification of novel master regulators in the high-protein diet rat model. Pathway and biological process enrichment analysis were used to characterize predicted targets of candidate mRNAs/proteins. The expression pattern of the most significant master regulators was evaluated by qPCR and immunohistochemistry. Based on the analysis of different expressed mRNAs/proteins, 15 significant ones (CRP, MCPT2, MCPT9, EPXH2, SERPING1, SRGN, CDKN1C, CDK6, CCNB1, PCNA, BAX, MAGEB16, SERPINE1, HSPA2, FOS) were highly identified and verified by qPCR and immunohistochemistry. They were involved in immune and inflammatory response, cell cycle arrest, apoptosis and pathways in cancer. These abnormally activated processes caused the bladder interstitial congestion and inflammatory infiltrates under the thinner urothelium, cell desquamation, cytoplasm vacuolization, nucleus swelling and malformation in the high-protein diet group. We provided evidences that high urinary urea concentration caused by high-protein diet might be a potential carcinogenic factor in bladder.

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

Novel [corrected] medical management of primary bladder endometriosis with dienogest: a case report.

PubMed

Takagi, H; Matsunami, K; Ichigo, S; Imai, A

2011-01-01

Because of its low incidence, medical treatment of has not yet been well established although surgical excision is generally considered effective. We report the first case of primary bladder endometriosis successfully managed with a novel progestin dienogest. A 39-year-old woman, nulligravida, presented with lower urinary tract symptoms, especially during menstruation. Cystoscopy, with subsequent cold cup biopsy, revealed a solitary submucosal mass (2 x 2 cm) in the bladder on the posterior wall; histopathology revealed the diagnosis of extraperitoneal endometriosis. MRI and laparoscopy confirmed no peritoneal endometriosis implants or adenomyosis. She was treated with oral 2 mg/day dienogest for six months. The measurable lesion exhibited a remarkable reduction in its size, accompanied with immediate relief of the lesion-related symptoms. At one year after medication cessation, she is well and symptom-free. Dienogest may be a novel conservative alternative for bladder endometriosis, in particular for women who wish to avoid surgical intervention.

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

Xanthogranulomatous cystitis: a challenging imitator of bladder cancer.

PubMed

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-06-29

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature.

Scaffolds for whole organ tissue engineering: Construction and in vitro evaluation of a seamless, spherical and hollow collagen bladder construct with appendices.

PubMed

Hoogenkamp, Henk R; Pot, Michiel W; Hafmans, Theo G; Tiemessen, Dorien M; Sun, Yi; Oosterwijk, Egbert; Feitz, Wout F; Daamen, Willeke F; van Kuppevelt, Toin H

2016-10-01

The field of regenerative medicine has developed promising techniques to improve current neobladder strategies used for radical cystectomies or congenital anomalies. Scaffolds made from molecularly defined biomaterials are instrumental in the regeneration of tissues, but are generally confined to small flat patches and do not comprise the whole organ. We have developed a simple, one-step casting method to produce a seamless large hollow collagen-based scaffold, mimicking the shape of the whole bladder, and with integrated anastomotic sites for ureters and urethra. The hollow bladder scaffold is highly standardized, with uniform wall thickness and a unidirectional pore structure to facilitate cell infiltration in vivo. Human and porcine bladder urothelial and smooth muscle cells were able to attach to the scaffold and maintained their phenotype in vitro. The closed luminal side and the porous outside of the scaffold facilitated the formation of an urothelial lining and infiltration of smooth muscle cells, respectively. The cells aligned according to the provided scaffold template. The technology used is highly adjustable (shape, size, materials) and may be used as a starting point for research to an off-the-shelf medical device suitable for neobladders. In this study, we describe the development of a simple, one-step casting method to produce a seamless large hollow collagen-based scaffold mimicking the shape of the whole bladder with integrated anastomotic sites for ureters and urethra. The hollow bladder scaffold is highly standardized with uniform wall thickness and a unidirectional pore structure to facilitate cell infiltration in vivo. The closed luminal surface and the porous exterior of the scaffold facilitated the formation of a urothelial lining and infiltration of smooth muscle cells, respectively. The applied technology is highly adjustable (shape, size, materials) and can be the starting point for research to an off-the-shelf medical device suitable for neobladders. Copyright © 2016. Published by Elsevier Ltd.

Technique of Antireflux Procedure without Creating Submucosal Tunnel for Surgical Correction of Vesicoureteric Reflux during Bladder Closure in Exstrophy.

PubMed

Sunil, Kanoujia; Gupta, Archika; Chaubey, Digamber; Pandey, Anand; Kureel, Shiv Narain; Verma, Ajay Kumar

2018-01-01

To report the clinical application of the new surgical technique of antireflux procedure without creating submucosal tunnel for surgical correction of vesicoureteric reflux during bladder closure in exstrophy. Based on the report of published experimental technique, the procedure was clinically executed in seven patients of classic exstrophy bladder with small bladder plate with polyps, where the creation of submucosal tunnel was not possible, in last 18 months. Ureters were mobilized. A rectangular patch of bladder mucosa at trigone was removed exposing the detrusor. Mobilized urteres were advanced, crossed and anchored to exposed detrusor parallel to each other. Reconstruction included bladder and epispadias repair with abdominal wall closure. The outcome was measured with the assessment of complications, abolition of reflux on cystogram and upper tract status. At 3-month follow-up cystogram, reflux was absent in all. Follow-up ultrasound revealed mild dilatation of pelvis and ureter in one. The technique of extra-mucosal ureteric reimplantation without the creation of submucosal tunnel is simple to execute without risk and complications and effectively provides an antireflux mechanism for the preservation of upper tract in bladder exstrophy. With the use of this technique, reflux can be prevented since the very beginning of exstrophy reconstruction.

Effects of exposure to pile-driving sounds on the lake sturgeon, Nile tilapia and hogchoker

PubMed Central

Halvorsen, Michele B.; Casper, Brandon M.; Matthews, Frazer; Carlson, Thomas J.; Popper, Arthur N.

2012-01-01

Pile-driving and other impulsive sound sources have the potential to injure or kill fishes. One mechanism that produces injuries is the rapid motion of the walls of the swim bladder as it repeatedly contacts nearby tissues. To further understand the involvement of the swim bladder in tissue damage, a specially designed wave tube was used to expose three species to pile-driving sounds. Species included lake sturgeon (Acipenser fulvescens)—with an open (physostomous) swim bladder, Nile tilapia (Oreochromis niloticus)—with a closed (physoclistous) swim bladder and the hogchoker (Trinectes maculatus)—a flatfish without a swim bladder. There were no visible injuries in any of the exposed hogchokers, whereas a variety of injuries were observed in the lake sturgeon and Nile tilapia. At the loudest cumulative and single-strike sound exposure levels (SELcum and SELss respectively), the Nile tilapia had the highest total injuries and the most severe injuries per fish. As exposure levels decreased, the number and severity of injuries were more similar between the two species. These results suggest that the presence and type of swim bladder correlated with injury at higher sound levels, while the extent of injury at lower sound levels was similar for both kinds of swim bladders. PMID:23055066

Effects of exposure to pile-driving sounds on the lake sturgeon, Nile tilapia and hogchoker.

PubMed

Halvorsen, Michele B; Casper, Brandon M; Matthews, Frazer; Carlson, Thomas J; Popper, Arthur N

2012-12-07

Pile-driving and other impulsive sound sources have the potential to injure or kill fishes. One mechanism that produces injuries is the rapid motion of the walls of the swim bladder as it repeatedly contacts nearby tissues. To further understand the involvement of the swim bladder in tissue damage, a specially designed wave tube was used to expose three species to pile-driving sounds. Species included lake sturgeon (Acipenser fulvescens)--with an open (physostomous) swim bladder, Nile tilapia (Oreochromis niloticus)--with a closed (physoclistous) swim bladder and the hogchoker (Trinectes maculatus)--a flatfish without a swim bladder. There were no visible injuries in any of the exposed hogchokers, whereas a variety of injuries were observed in the lake sturgeon and Nile tilapia. At the loudest cumulative and single-strike sound exposure levels (SEL(cum) and SEL(ss) respectively), the Nile tilapia had the highest total injuries and the most severe injuries per fish. As exposure levels decreased, the number and severity of injuries were more similar between the two species. These results suggest that the presence and type of swim bladder correlated with injury at higher sound levels, while the extent of injury at lower sound levels was similar for both kinds of swim bladders.

Multimodal flexible cystoscopy for creating co-registered panoramas of the bladder urothelium

NASA Astrophysics Data System (ADS)

Seibel, Eric J.; Soper, Timothy D.; Burkhardt, Matthew R.; Porter, Michael P.; Yoon, W. Jong

2012-02-01

Bladder cancer is the most expensive cancer to treat due to the high rate of recurrence. Though white light cystoscopy is the gold standard for bladder cancer surveillance, the advent of fluorescence biomarkers provides an opportunity to improve sensitivity for early detection and reduced recurrence resulting from more accurate excision. Ideally, fluorescence information could be combined with standard reflectance images to provide multimodal views of the bladder wall. The scanning fiber endoscope (SFE) of 1.2mm in diameter is able to acquire wide-field multimodal video from a bladder phantom with fluorescence cancer "hot-spots". The SFE generates images by scanning red, green, and blue (RGB) laser light and detects the backscatter signal for reflectance video of 500-line resolution at 30 frames per second. We imaged a bladder phantom with painted vessels and mimicked fluorescent lesions by applying green fluorescent microspheres to the surface. By eliminating the green laser illumination, simultaneous reflectance and fluorescence images can be acquired at the same field of view, resolution, and frame rate. Moreover, the multimodal SFE is combined with a robotic steering mechanism and image stitching software as part of a fully automated bladder surveillance system. Using this system, the SFE can be reliably articulated over the entire 360° bladder surface. Acquired images can then be stitched into a multimodal 3D panorama of the bladder using software developed in our laboratory. In each panorama, the fluorescence images are exactly co-registered with RGB reflectance.

Expression of vesicular glutamate transporters in sensory and autonomic neurons innervating the mouse bladder.

PubMed

Brumovsky, Pablo R; Seal, Rebecca P; Lundgren, Kerstin H; Seroogy, Kim B; Watanabe, Masahiko; Gebhart, G F

2013-06-01

VGLUTs, which are essential for loading glutamate into synaptic vesicles, are present in various neuronal systems. However, to our knowledge the expression of VGLUTs in neurons innervating the bladder has not yet been analyzed. We studied VGLUT1, VGLUT2 and VGLUT3 in mouse bladder neurons. We analyzed the expression of VGLUT1, VGLUT2 and calcitonin gene-related peptide by immunohistochemistry in the retrograde labeled primary afferent and autonomic neurons of BALB/c mice after injecting fast blue in the bladder wall. To study VGLUT3 we traced the bladder of transgenic mice, in which VGLUT3 is identified by enhanced green fluorescent protein detection. Most bladder dorsal root ganglion neurons expressed VGLUT2. A smaller percentage of neurons also expressed VGLUT1 or VGLUT3. Co-expression with calcitonin gene-related peptide was only observed for VGLUT2. Occasional VGLUT2 immunoreactive neurons were seen in the major pelvic ganglia. Abundant VGLUT2 immunoreactive nerves were detected in the bladder dome and trigone, and the urethra. VGLUT1 immunoreactive nerves were discretely present. We present what are to our knowledge novel data on VGLUT expression in sensory and autonomic neurons innervating the mouse bladder. The frequent association of VGLUT2 and calcitonin gene-related peptide in sensory neurons suggests interactions between glutamatergic and peptidergic neurotransmissions, potentially influencing commonly perceived sensations in the bladder, such as discomfort and pain. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Human-urine diabetes assay and in vivo rat bladder assay using a fluorine-doped carbon nanotube catheter sensor.

PubMed

Ly, Suw Young; Lee, Jin Hui

2009-10-01

The creation of a novel biosensor consisting of a fluorine-doped carbon nanotube (FCN) was explored for use in cyclic voltammetric (CV) and square-wave stripping voltammetric (SW) glucose assay. In the experiment that was carried out in this study, analytical optimum conditions were attained at the low detection limit (S/N3) of 0.6 microg/L (3.3 x 10(-9) M). In the 0.1 mg/L spike, the relative standard deviation of 0.607 (n = 15) was obtained. This was used for the diagnosis of the urine of patients with diabetes. Moreover, the catheter-type electrode (CE) can be inserted into a rat bladder through the rat's organs. Thus, it can be connected with an electrochemical analyzer that can be fitted with an interface for the real-time in vivo analysis of metabolic glucose. The developed system can be used for organ treatment, biological analysis, and in vivo control.

The effect of hypoxia on neuroeffector transmission in the bovine retractor penis and rat anococcygeus muscles.

PubMed Central

Bowman, A.; McGrath, J. C.

1985-01-01

The effects of reducing the PO2 of the bathing fluid were studied on non-adrenergic non-cholinergic (NANC) transmission in isolated preparations of the bovine retractor penis muscle, the rat anococcygeus muscle, the guinea-pig taenia caeci and the guinea-pig urinary bladder. Hypoxia rapidly and reversibly impaired NANC transmission in the bovine retractor penis and rat anococcygeus muscles but did not affect transmission in the guinea-pig taenia caeci or bladder, suggesting that different NANC mechanisms are involved. Although neurally-evoked relaxation of the bovine retractor penis was impaired by hypoxia, relaxations produced by vasoactive intestinal peptide, prostaglandin E1, sodium nitroprusside or an inhibitory factor isolated from the bovine retractor penis were unaffected. Since the inhibitory factor is similar to, and may actually be the NANC transmitter, the results suggest that the site of action of hypoxia in impairing transmission is prejunctional at the inhibitory nerve endings. PMID:2994787

Evaluation and selection of anatomic sites for magnetic resonance imaging-guided mild hyperthermia therapy: a healthy volunteer study.

PubMed

V V N Kothapalli, Satya; Altman, Michael B; Zhu, Lifei; Partanen, Ari; Cheng, Galen; Gach, H Michael; Straube, William; Zoberi, Imran; Hallahan, Dennis E; Chen, Hong

2018-01-04

Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40-43 °C) for an extended duration (up to 1 h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times. A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1 °C were used as criteria for acceptable thermometry. Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41 ± 0.65, 1.86 ± 1.20, and 0.34 ± 0.44 °C, and precisions of 2.30 ± 1.21, 1.64 ± 0.56, and 0.48 ± 0.05 °C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56 ± 0.05 °C and 0.42 ± 0.50 °C, respectively, while the 60-min scans had accuracy and precision of 0.49 ± 0.03 °C and 0.56 ± 0.05 °C, respectively. Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.

The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle.

PubMed

Min, Chang Ho; Min, Young Sil; Lee, Sang Joon; Sohn, Uy Dong

2016-06-01

It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle.

The University of Chicago technique of complete intracorporeal pediatric robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy.

PubMed

Gundeti, Mohan S; Acharya, Sujeet S; Zagaja, Gregory P

2009-06-01

We present the University of Chicago technique for complete intracorporeal robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy. The operative steps of the open procedure were replicated laparoscopically using robotic assistance. Initially, five transperitoneal laparoscopic ports are placed prior to docking the da Vinci S robotic system. A 20 cm ileal segment is isolated, and the gastrointestinal anastomosis is performed in an end-to-end fashion using intracorporeal suturing. The appendix is anastomosed to the right posterior wall of the bladder over an 8F feeding tube in an extravesical fashion. Then, the bladder is incised in a coronal plane, and the simple detubularized ileal on-lay patch is anastomosed to the posterior and anterior walls of the bladder. A suprapubic catheter and pelvic drain are placed. Finally, the Mitrofanoff stoma is then fashioned. Cystography is done at 4 weeks postoperatively. This report suggests that robotic-assisted ileocystoplasty and appendicovesicostomy is feasible. A reasonable outcome with early recovery, resumption of normal activities, and excellent cosmesis can be achieved in select patients. A large case series, however, is necessary to determine whether a robotic-assisted approach provides any significant advantages over conventional open procedures.

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

PubMed

Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

2014-10-01

This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

Pneumovesical ureteric reimplantation using T-fastener: A modification for bladder wall anchorage.

PubMed

Lau, Chin Tung; Lan, Lawrence Chuen Leung; Wong, Kenneth Kak Yuen; Tam, Paul

2017-06-01

Bladder anchoring during pneumovesical ureteric reimplantation (PUR) can be difficult. Here we describe our new technique using a T-fastener (Kimberly Clark, Irving, TX, USA) to tackle this problem. A T-fastener has been applied to all patients who underwent PUR in our center since 2011. Seventeen consecutive cases were performed between 2011 and 2015. No bladder dislodgement or air leak was observed in any of the operations. No morbidity or mortality has been associated with the use of T-fasteners. In our experience, this technique is simple to learn and transferrable. It decreases intraoperative complications and helps to climb the learning curve. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Tachykinin antagonists and capsaicin-induced contraction of the rat isolated urinary bladder: evidence for tachykinin-mediated cotransmission.

PubMed

Maggi, C A; Patacchini, R; Santicioli, P; Giuliani, S

1991-06-01

1. The possible involvement of tachykinins (TKs) in the contraction produced by capsaicin in the rat isolated urinary bladder was addressed on the hypothesis that co-release of substance P (SP) and neurokinin A (NKA) occurs from sensory nerve terminals. 2. A low concentration of SP (30 nM) produced a rapid contraction which faded to baseline within 10 min. A low concentration of NKA (10 nM) produced a slowly developing contraction which was still evident at 10 min. Capsaicin (1 microM) produced a rapid phasic response and a tonic response (late response to capsaicin). Co-administration of SP and NKA mimicked the response to capsaicin more than each TK alone. 3. Fading of the response to SP was not caused by receptor desensitization and was partially prevented by peptidase inhibitors. 4. Spantide (3 microM) selectively antagonized the SP-induced contraction while L-659,877 (3-10 microM) or MEN 10,376 (10-30 microM) which are NK2 receptor selective antagonists selectively blocked the response to NKA. Co-administration of spantide and L-659,877 inhibited the response to both SP and NKA by an amount not greater than that produced by each antagonist alone. 5. Spantide selectively reduced the peak response to capsaicin, while leaving the late response unaffected. L-659,877 (3 microM) and MEN 10,376 (10 microM) selectively inhibited the late response to capsaicin while, at higher concentrations, also reduced the peak response to capsaicin. Co-administration of spantide and L-659,877 reduced the peak response to capsaicin more than that produced by each antagonist alone. 6. Bombesin (10 nM) produced a tonic contraction similar to that induced by NKA. The response to bombesin was not affected by spantide, L-659,877 or MEN 10,376. 7 P2. purinoceptor desensitization by repeated administration of alpha,betal-methylene ATP depressed the twitch response to electrical stimulation of postganglionic nerves but did not affect the peak or the late response to capsaicin. 8. We conclude that multiple TKs are coreleased by capsaicin in the rat bladder and mediate the capsaicin-induced contraction by activating both NKI and NK2 receptors. Endogenous TK with preferential affinity for the NK, receptor (putatively SP) are selectively involved in the peak response to capsaicin while endogenous TK with preferential affinity for the NK2 receptor (putatively NKA) are selectively involved in the late response to capsaicin and partly contribute to the peak response. These findings provide pharmacological evidence for tachykinin-mediated cotransmission in the rat urinary bladder. ATP is unlikely to be involved in the efferent function of capsaicin-sensitive sensory nerves in the rat bladder.

Quantification of Organ Motion During Chemoradiotherapy of Rectal Cancer Using Cone-Beam Computed Tomography

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

Chong, Irene; Hawkins, Maria; Hansen, Vibeke

2011-11-15

Purpose: There has been no previously published data related to the quantification of rectal motion using cone-beam computed tomography (CBCT) during standard conformal long-course chemoradiotherapy. The purpose of the present study was to quantify the interfractional changes in rectal movement and dimensions and rectal and bladder volume using CBCT and to quantify the bony anatomy displacements to calculate the margins required to account for systematic ({Sigma}) and random ({sigma}) setup errors. Methods and Materials: CBCT images were acquired from 16 patients on the first 3 days of treatment and weekly thereafter. The rectum and bladder were outlined on all CBCTmore » images. The interfraction movement was measured using fixed bony landmarks as references to define the rectal location (upper, mid, and low), The maximal rectal diameter at the three rectal locations was also measured. The bony anatomy displacements were quantified, allowing the calculation of systematic ({Sigma}) and random ({sigma}) setup errors. Results: A total of 123 CBCT data sets were analyzed. Analysis of variance for standard deviation from planning scans showed that rectal anterior and lateral wall movement differed significantly by rectal location. Anterior and lateral rectal wall movements were larger in the mid and upper rectum compared with the low rectum. The posterior rectal wall movement did not change significantly with the rectal location. The rectal diameter changed more in the mid and upper than in the low rectum. No consistent relationship was found between the rectal and bladder volume and time, nor was a significant relationship found between the rectal volume and bladder volume. Conclusions: In the present study, the anterior and lateral rectal movement and rectal diameter were found to change most in the upper rectum, followed by the mid rectum, with the smallest changes seen in the low rectum. Asymmetric margins are warranted to ensure phase 2 coverage.« less

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

Complications and salvage options after laser lithotripsy for a vesical calculus in a tetraplegic patient: a case report.

PubMed

Vaidyanathan, Subramanian; Singh, Gurpreet; Selmi, Fahed; Hughes, Peter L; Soni, Bakul M; Oo, Tun

2015-01-01

Laser lithotripsy of vesical calculi in tetraplegic subjects with long-term urinary catheters is fraught with complications because of bladder wall oedema, infection, fragile urothelium, bladder spasms, and autonomic dysreflexia. Severe haematuria should be anticipated; failure to institute measures to minimise bleeding and prevent clot retention can be catastrophic. We present an illustrative case. A tetraplegic patient underwent laser lithotripsy of vesical stone under general anaesthesia. During lithotripsy, severe bladder spasms and consequent rise in blood pressure occurred. Bleeding continued post-operatively resulting in clot retention. CT revealed clots within distended but intact bladder. Clots were sucked out and continuous bladder irrigation was commenced. Bleeding persisted; patient developed repeated clot retention. Cystoscopy was performed to remove clots. Patient developed abdominal distension. Bladder rupture was suspected; bed-side ultrasound scan revealed diffuse small bowel dilatation with mild peritoneal effusion; under-filled bladder containing small clot. Patient developed massive abdominal distension and ileus. Two days later, CT with oral positive contrast revealed intra-peritoneal haematoma at the dome of bladder with perforation at the site of haematoma. Free fluid was noted within the peritoneal cavity. This patient was managed by gastric drainage and intravenous fluids. Patient's condition improved gradually with urethral catheter drainage. Follow-up CT revealed resolution of bladder rupture, perivesical haematoma, and intra-peritoneal free fluid. If bleeding occurs, bladder irrigation should be commenced immediately after surgery to prevent clot retention. When bladder rupture is suspected, CT of abdomen should be done instead of ultrasound scan, which may not reveal bladder perforation. It is debatable whether laparotomy and repair of bladder rupture is preferable to nonoperative management in tetraplegics. Anti-muscarinic drugs should be prescribed prior to lithotripsy to control bladder spasms; aspirin and ibuprofen should be omitted. If significant bleeding occurs during lithotripsy, procedure should be stopped and rescheduled. Percutaneous cystolithotripsy using a wide channel could be quicker to clear stones, as larger fragments could be retrieved; lesser stimulant for triggering autonomic dysreflexia, as it avoids urethral manipulation. But in patients with small, contracted bladder, and protuberant abdomen, percutaneous access to urinary bladder may be difficult and can result in injury to bowels.

Diabetes attenuates urothelial modulation of detrusor contractility and spontaneous activity.

PubMed

Wang, Yi; Tar, Moses T; Fu, Shibo; Melman, Arnold; Davies, Kelvin P

2014-10-01

To investigate the effect of diabetes on urothelial modulation of bladder contractility. Bladder strips (urothelium intact or denuded) were prepared from 8-week-old streptozotocin-induced diabetic (n = 19) and non-diabetic control rats (n = 10). The effect of modulators of MaxiK (iberiotoxin and tetraethylammonium) and Kv7 (XE991 and retigabine) potassium channel activity were investigated for their effects on both carbachol-induced force generation and spontaneous contractile activity. In bladder strips from non-diabetic animals, the presence of the urothelium resulted in marked sensitivity to carbachol-induced force generation by modulators of MaxiK and Kv7 channel activity, whereas in the diabetic animal urothelial sensitivity to these agents was significantly diminished. Urothelial-intact bladder strips from non-diabetic animals were more sensitive to modulators of Kv7 activity in reducing the amplitude of spontaneous phasic contractions than urothelial-denuded bladder strips, whereas in diabetic animals the presence or absence of the urothelium did not alter the sensitivity to modulators of Kv7 activity. Spontaneous activity in the presence of tetraethylammonium was not affected by the urothelium in bladder strips from either diabetic or non-diabetic animals. The presence of the urothelium in bladders from non-diabetic animals modulates the activity of potassium blockers to affect bladder contractility, whereas in the diabetic bladder this effect is attenuated. These findings could help to explain the lack of success of pharmaceutical treatments targeting potassium channels to treat bladder pathology in patients with diseases imparing urothelial function. © 2014 The Japanese Urological Association.

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.

Commentary on "tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl) nitrosamine as the basis for urothelial cell carcinogenesis." He Z, Kosinska W, Zhao ZL, Wu XR, Guttenplan JB, Department of Basic Science, New York University Dental College, NY, USA.: Mutat Res 2012;742(1-2):92-5 [Epub 2011 Dec 4].

PubMed

Scherr, Douglas S

2014-02-01

Bladder cancer is one of the few cancers that have been linked to carcinogens in the environment and tobacco smoke. Of the carcinogens tested in mouse chemical carcinogenesis models, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is one that reproducibly causes high-grade, invasive cancers in the urinary bladder, but not in any other tissues. However, the basis for such a high-level tissue-specificity has not been explored. Using mutagenesis in lacI (Big Blue™) mice, we show here that BBN is a potent mutagen and it causes high-level of mutagenesis specifically in the epithelial cells (urothelial) of the urinary bladder. After a 2-6-week treatment of 0.05% BBN in the drinking water, mutagenesis in urothelial cells of male and female mice was about two orders of magnitude greater than the spontaneous mutation background. In contrast, mutagenesis in smooth muscle cells of the urinary bladder was about five times lower than in urothelial tissue. No appreciable increase in mutagenesis was observed in kidney, ureter, liver or forestomach. In lacI (Big Blue™) rats, BBN mutagenesis was also elevated in urothelial cells, albeit not nearly as profoundly as in mice. This provides a potential explanation as to why rats are less prone than mice to the formation of aggressive form of bladder cancer induced by BBN. Our results suggest that the propensity to BBN-triggered mutagenesis of urothelial cells underlies its heightened susceptibility to this carcinogen and that mutagenesis induced by BBN represents a novel model for initiation of bladder carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats.

PubMed

El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A

2015-12-01

Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells.

Biodistribution and photodynamic effect of protoporphyrin IX in rat urinary bladders after intravesical instillation of 5-aminolaevulinic acid

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Bown, Stephen G.

1995-03-01

Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Complications such as scarring of the detrusor muscle and prolonged cutaneous photosensitivity may be reduced by using the new photosensitizer precursor, 5- aminolaevulinic acid (ALA). After instillation of ALA, the concentration, pH, and time of bladder retention of ALA solution were found to be the key factors to a satisfactory PpIX buildup in the mucosa. The optimum PpIX fluorescence intensity ratio between mucosa and muscle layer is 10 to 1 with a pH 5.5, 1% ALA solution retained for 5 hours. Higher concentration resulted in more mucosal PpIX formation, but less selectivity. Unbuffered ALA was unsuitable for bladder instillation. Two days after laser treatment with 25 J/cm2 at 630 nm with optimal sensitization, typical histological findings were urothelial sloughing and lamina propria edema without obvious muscle damage. After 7 days, recovery of the urothelium was almost complete and fibroblast infiltration was minimal. ALA induced PpIX after bladder instillation may be an appropriate photosensitizer for future management of superficial bladder cancer.

[Using of cell biocomposite material in tissue engineering of the urinary bladder].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-06-01

In a systematic review, to present an overview of the current situation in the field of tissue engineering of urinary bladder related to the use of cell lines pre-cultured on matrices. The selection of eligible publications was conducted according to the method described in the article Glybochko P.V. et al. "Tissue engineering of urinary bladder using acellular matrix." At the final stage, studies investigating the application of matrices with human and animal cell lines were analyzed. Contemporary approaches to using cell-based tissue engineering of the bladder were analyzed, including the formation of 3D structures from several types of cells, cell layers and genetic modification of injected cells. The most commonly used cell lines are urothelial cells, mesenchymal stem cells and fibroblasts. The safety and efficacy of any types of composite cell structures used in the cell-based bladder tissue engineering has not been proven sufficiently to warrant clinical studies of their usefulness. The results of cystoplasty of rat bladder are almost impossible to extrapolate to humans; besides, it is difficult to predict possible side effects. For the transition to clinical trials, additional studies on relevant animal models are needed.

Detecting bladder fullness through the ensemble activity patterns of the spinal cord unit population in a somatovisceral convergence environment.

PubMed

Park, Jae Hong; Kim, Chang-Eop; Shin, Jaewoo; Im, Changkyun; Koh, Chin Su; Seo, In Seok; Kim, Sang Jeong; Shin, Hyung-Cheul

2013-10-01

Chronic monitoring of the state of the bladder can be used to notify patients with urinary dysfunction when the bladder should be voided. Given that many spinal neurons respond both to somatic and visceral inputs, it is necessary to extract bladder information selectively from the spinal cord. Here, we hypothesize that sensory information with distinct modalities should be represented by the distinct ensemble activity patterns within the neuronal population and, therefore, analyzing the activity patterns of the neuronal population could distinguish bladder fullness from somatic stimuli. We simultaneously recorded 26-27 single unit activities in response to bladder distension or tactile stimuli in the dorsal spinal cord of each Sprague-Dawley rat. In order to discriminate between bladder fullness and tactile stimulus inputs, we analyzed the ensemble activity patterns of the entire neuronal population. A support vector machine (SVM) was employed as a classifier, and discrimination performance was measured by k-fold cross-validation tests. Most of the units responding to bladder fullness also responded to the tactile stimuli (88.9-100%). The SVM classifier precisely distinguished the bladder fullness from the somatic input (100%), indicating that the ensemble activity patterns of the unit population in the spinal cord are distinct enough to identify the current input modality. Moreover, our ensemble activity pattern-based classifier showed high robustness against random losses of signals. This study is the first to demonstrate that the two main issues of electroneurographic monitoring of bladder fullness, low signals and selectiveness, can be solved by an ensemble activity pattern-based approach, improving the feasibility of chronic monitoring of bladder fullness by neural recording.

The role of metabotropic glutamate receptor mGlu5 in control of micturition and bladder nociception.

PubMed

Hu, Youmin; Dong, Li; Sun, Biying; Guillon, Marlene A; Burbach, Leah R; Nunn, Philip A; Liu, Xingrong; Vilenski, Olga; Ford, Anthony P D W; Zhong, Yu; Rong, Weifang

2009-01-23

In micturition control, the roles of ionotropic glutamate (iGlu) receptors NMDA and AMPA are well established, whereas little is known about the function of metabotropic glutamate (mGlu) receptors. Since antagonists for mGlu5 receptors are efficacious in animal models of inflammatory and neuropathic pain, we examined whether mGlu5 receptors play a role in the voiding reflex and bladder nociception and, if so, via centrally or peripherally localized receptors. The mGlu5 receptor antagonist MPEP dose-dependently increased the micturition threshold (MT) volume in the volume-induced micturition reflex (VIMR) model in anesthetized rats. Following doses of 5.2, 15.5 and 51.7micromol/kg of MPEP (intraduodenal), the MT was increased by 24.7+/-5.0%, 97.2+/-12.5% (P<0.01) and 128.0+/-28.3% (P<0.01) from the baseline, respectively (n=4-5; compared with 0.8+/-9.1% in the vehicle group). Infusing MPEP (0.3, 1mM) directly into the bladder also raised MT. However, the efficacious plasma concentrations of MPEP following intravesical dosing were similar to that after intraduodenal dosing (EC(50) of 0.11 and 0.27microM, respectively, P>0.05). MPEP also dose-dependently attenuated the visceromotor responses (VMR, total number of abdominal EMG spikes during phasic bladder distension) in anesthetized rats. The VMR was decreased to 1332.4+/-353.9 from control of 2886.5+/-692.2 spikes/distension (n=6, P<0.01) following MPEP (10micromol/kg, iv). Utilizing the isolated mouse bladder/pelvic nerve preparation, we found that neither MPEP (up to 3microM) nor MTEP (up to 10microM) affected afferent discharge in response to bladder distension (n=4-6). In contrast, MPEP attenuated the responses of the mesenteric nerves to distension of the mouse jejunum in vitro. These data suggest that mGlu5 receptors play facilitatory roles in the processing of afferent input from the urinary bladder, and that central rather than peripheral mGlu5 receptors appear to be responsible.

CT Urography: Segmentation of Urinary Bladder using CLASS with Local Contour Refinement

PubMed Central

Cha, Kenny; Hadjiiski, Lubomir; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Zhou, Chuan

2016-01-01

Purpose We are developing a computerized system for bladder segmentation on CT urography (CTU), as a critical component for computer-aided detection of bladder cancer. Methods The presence of regions filled with intravenous contrast and without contrast presents a challenge for bladder segmentation. Previously, we proposed a Conjoint Level set Analysis and Segmentation System (CLASS). In case the bladder is partially filled with contrast, CLASS segments the non-contrast (NC) region and the contrast-filled (C) region separately and automatically conjoins the NC and C region contours; however, inaccuracies in the NC and C region contours may cause the conjoint contour to exclude portions of the bladder. To alleviate this problem, we implemented a local contour refinement (LCR) method that exploits model-guided refinement (MGR) and energy-driven wavefront propagation (EDWP). MGR propagates the C region contours if the level set propagation in the C region stops prematurely due to substantial non-uniformity of the contrast. EDWP with regularized energies further propagates the conjoint contours to the correct bladder boundary. EDWP uses changes in energies, smoothness criteria of the contour, and previous slice contour to determine when to stop the propagation, following decision rules derived from training. A data set of 173 cases was collected for this study: 81 cases in the training set (42 lesions, 21 wall thickenings, 18 normal bladders) and 92 cases in the test set (43 lesions, 36 wall thickenings, 13 normal bladders). For all cases, 3D hand segmented contours were obtained as reference standard and used for the evaluation of the computerized segmentation accuracy. Results For CLASS with LCR, the average volume intersection ratio, average volume error, absolute average volume error, average minimum distance and Jaccard index were 84.2±11.4%, 8.2±17.4%, 13.0±14.1%, 3.5±1.9 mm, 78.8±11.6%, respectively, for the training set and 78.0±14.7%, 16.4±16.9%, 18.2±15.0%, 3.8±2.3 mm, 73.8±13.4% respectively, for the test set. With CLASS only, the corresponding values were 75.1±13.2%, 18.7±19.5%, 22.5±14.9%, 4.3±2.2 mm, 71.0±12.6%, respectively, for the training set and 67.3±14.3%, 29.3±15.9%, 29.4±15.6%, 4.9±2.6 mm, 65.0±13.3%, respectively, for the test set. The differences between the two methods for all five measures were statistically significant (p<0.001) for both the training and test sets. Conclusions The results demonstrate the potential of CLASS with LCR for segmentation of the bladder. PMID:24801066

Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach

NASA Astrophysics Data System (ADS)

Wang, Chuang; Udupa, Jayaram K.; Tong, Yubing; Chen, Jerry; Venigalla, Sriram; Odhner, Dewey; Guzzo, Thomas J.; Christodouleas, John; Torigian, Drew A.

2018-02-01

Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 - T stage < T2, with primary tumor locally confined to the bladder, and group 2 - T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

Intraperitoneal Urinary Bladder Perforation with Pneumoperitoneum in Association with Indwelling Foley Catheter Diagnosed in Emergency Department.

PubMed

Zhan, Chenyang; Maria, Pedro P; Dym, R Joshua

2017-11-01

Indwelling Foley catheter is a rare cause of urinary bladder perforation, a serious injury with high mortality that demands accurate and prompt diagnosis. While the gold standard for diagnosis of bladder injury is computed tomography (CT) cystography, few bladder ruptures associated with Foley catheter have been reported to be diagnosed in the emergency department (ED). An 83-year-old man with indwelling Foley catheter presented to the ED for hematuria and altered mental status. He was diagnosed to have intraperitoneal rupture of the urinary bladder in the ED using abdominal and pelvic CT without contrast, which demonstrated bladder wall discontinuity, intraperitoneal free fluid, and pneumoperitoneum. The patient was treated successfully with medical management and bladder drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first report of intraperitoneal urinary bladder perforation associated with Foley catheter diagnosed in the ED by CT without contrast. Pneumoperitoneum found in this case was a clue to the diagnosis and is a benign finding that does not necessitate urgent surgical intervention. The early and accurate diagnosis in this case allowed for effective management with good clinical outcome. The use of indwelling Foley catheter has a high prevalence, especially in long-term care facility residents, who are frequent visitors in the ED. Therefore, emergency physicians and radiologists should be familiar with the presentation and imaging findings of this potential injury associated with Foley catheters. Copyright © 2017 Elsevier Inc. All rights reserved.

Contractile activity of ATP and diadenosine tetraphosphate on urinary bladder in the rat: role of A1- and P2X-purinoceptors and nitric oxide.

PubMed

Khattab, M M; Al-Hrasen, M N; El-Hadiyah, T M

2007-01-01

1. Both adenosine-5'-triphosphate (ATP) and diadenosine tetraphosphate (AP4A) produced a dose-dependent contraction of the isolated rat urinary bladder rings. AP(4)A dose-response curve was to the left of that of ATP, and maximum response was greater than that produced by ATP. 2. 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the A1-purinergic receptor blocker (0.01 mm) significantly inhibited the ATP- and AP4A-induced contractions at the whole dose range. The inhibition was between 31-41%, and 15-25% for ATP and AP4A respectively. 3. Pyridoxal phosphate 6-azophenyl-2',4'-disulphonic acid (PPADS), the P2X-purinoceptor antagonist (0.01 mm) potently inhibited the bladder contractions in response to ATP and AP4A by around 75-80%. 4. The nitric oxide (NO) precursor L-arginine reduced the bladder contractile response to ATP by about 22-41% and that of AP4A to a lesser extent by around 20-32%. 5. The nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), did not produce any significant effect on ATP except for a weak inhibition of about 14% at the lowest dose of ATP. The contractions in response to AP4A were only slightly reduced by L-NAME by about 20%. 6. In conclusion, the contractile response of the bladder to ATP and to the dinucleotide AP4A is mediated mainly through P2X-purinoceptors and A1-purinergic receptors. In the detrusor muscle, NO donation possesses an inhibitory effect on ATP-mediated contractility more than that produced by the dinucleotide AP4A.

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.

Recurrent Urinary Tract Infections and Related Conditions (For Parents)

MedlinePlus

... UTIs. A promising vaccine that would protect against E. coli (the most common bacterium that causes UTIs) is ... extract are often suggested because they may prevent E. coli from attaching to the walls of the bladder. ...

Emphysematous cystitis occurred in the case treated with steroid for autoimmune hepatitis.

PubMed

Yoshino, Tateki; Ohara, Shinya; Moriyama, Hiroyuki

2013-01-01

Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients, which was characterized by air within the bladder wall and lumen. A 83-year-old woman was introduced to our department with fever elevation and abnormal findings of computed tomography (CT). She took orally prednisolone for autoimmune hepatitis. Pelvic CT revealed diffuse air throughout the bladder wall. Urinalysis showed combined hematuria and pyuria. Escherichia coli was detected in blood culture. Abnormal findings of complete blood count and laboratory examination included an elevated WBC count (12,200/μL), C-reactive protein (11.7 mg/dL), and creatinine (1.07 mg/dL). Cystoscopy confirmed diffuse submucosal emphysema throughout. On the basis of diagnosis with emphysematous cystitis, she was treated with antibiotics based on the results of blood culture and indwelling Foley catheter. After treatment, the improvement of inflammatory findings and submucosal emphysema on cystoscopy and CT were achieved.

Mixed metazoan and bacterial infection of the gas bladder of the lined seahorse-a case report.

PubMed

Anderson, Paul A; Petty, Barbara D

2013-03-01

Five wild-caught Lined Seahorses Hippocampus erectus from an aquarium system presented with altered buoyancy and distended upper trunks. Radiography of one specimen revealed a reduced air volume in the gas bladder. Pneumocystocentesis revealed a brown exudate of numerous leukocytes, parasite ova, and Gram- and acid-fast-positive bacilli under wet mounts and stains. Necropsies revealed enlarged, friable kidneys and distended gas bladders containing copious purulent exudate, necrotic tissue, and adult digeneans Dictysarca virens. Bacterial isolates from exudate cultures grown on Lowenstein-Jensen medium were identified as Gordonia sp. and Mycobacterium poriferae by high-performance liquid chromatography and 16S ribosomal DNA sequencing. Histopathology demonstrated a histiocytic response in kidney and gas bladder exudate, inflammation of the gas bladder wall, and infection of the gas bladder lumen with parasite ova and acid-fast-positive and Gomori's methenamine silver-positive bacilli. Praziquantel is prescribed for digenean infections but dissolves incompletely in seawater and is toxic to this host. Eradication of intermediate host vectors is a management option. Treatment of Gordonia infection has not been addressed in nonhuman animals, and there is no known effective treatment for Mycobacterium spp. infection in fishes. This is the first case report of digenean infection of the gas bladder in a syngnathid, Gordonia sp. infection in a nonhuman animal, and M. poriferae infection in a fish.

Enhanced Application of 18F-FDG PET/CT in Bladder Cancer by Adding Early Dynamic Acquisition to a Standard Delayed PET Protocol.

PubMed

Yoon, Hai-Jeon; Yoo, Jang; Kim, Yemi; Lee, Dong Hyeon; Kim, Bom Sahn

2017-10-01

We investigated the value of early dynamic (ED) PET for the detection and characterization of bladder cancer. Fifty-two bladder cancer patients were prospectively enrolled. The study protocol was composed of ED, whole-body (WB, 60 minutes after injection), and additional delayed (AD, 120 minutes after injection) PET acquisition. Early dynamic PET was acquired for 10 minutes and reconstructed as 5 frames at 2-minute intervals. A focal radiotracer accumulation confined to the bladder wall was considered as PET positive and referred for further quantitative measurement. SUVmax on ED (SUVmax, SUVmax, SUVmax, SUVmax, and SUVmax for 5 frames), WB (SUVmax), and AD PET (SUVmax) were measured. PET results were correlated with bladder cancer pathology variables. The sensitivities of ED, WB, and AD PET for bladder cancer were 84.6%, 57.7%, and 61.2%, respectively. The sensitivity of ED PET was significantly higher than that of WB (P = 0.002) and AD PET (P = 0.008). On ED PET, SUVmax was significantly correlated with muscle invasiveness, histological grade, and pathological tumor size (P = 0.018, P = 0.030, and P = 0.030). On WB and AD PET, only pathological tumor size showed significant positive correlation with SUVmax and SUVmax (P = 0.043 and P = 0.007). Early dynamic PET can help to detect and characterize bladder cancer.

Direct-Interface, Fusible Heat Sink

NASA Technical Reports Server (NTRS)

Lomax, Curtis; Webbon, Bruce

1992-01-01

Nonventing, regenerable, and self-contained heat sink absorbs heat in melting of ice by direct contact with forced flow of warm water. Elastic bladder contains water and ice. Connectors designed to prevent leaks easily connectable and disconnectable. Female portions embedded in wall of heat sink. After water frozen, male portions inserted and flow of warm water initiated. Water melts ice in and around female connectors, then flow passes between ice and bladder from inlet to outlet. Component of low-power portable refrigerator to operate for short time in picnic or camp setting.

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.

Subchronic toxicity studies of t-butyl alcohol in rats and mice.

PubMed

Lindamood, C; Farnell, D R; Giles, H D; Prejean, J D; Collins, J J; Takahashi, K; Maronpot, R R

1992-07-01

The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an important commodity chemical, an additive to unleaded gasoline, and a contaminant of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4% level of both sexes and species. Weight-gain depression was present in all dose levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female mice. Water consumption was increased at lower dose levels in male rats and decreased in the higher dose levels of both sexes of rats and female mice. Clinical signs in rats were ataxia in both sexes and hypoactivity in males. Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats, urine volumes were reduced, in association with crystalluria. Gross lesions at necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of transitional epithelia and inflammation of the urinary bladder. In male rats treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha-2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1% in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female rats and 4362.9 mg/kg/day for the female mice). The results indicate that in rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and males are more sensitive to t-butyl alcohol toxicity than females.

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.

In vivo magnetic resonance imaging of type I collagen scaffold in rat: improving visualization of bladder and subcutaneous implants.

PubMed

Sun, Yi; Geutjes, Paul; Oosterwijk, Egbert; Heerschap, Arend

2014-12-01

Noninvasive monitoring of implanted scaffolds is important to understand their behavior and role in tissue engineering, in particular to follow their degradation and interaction with host tissue. Magnetic resonance imaging (MRI) is well suited for this goal, but its application is often hampered by the low contrast of scaffolds that are prepared from biomaterials such as type I collagen. The aim of this study was to test iron oxide particles incorporation in improving their MRI contrasts, and to follow their degradation and tissue interactions. Scaffolds with and without iron oxide particles were implanted either subcutaneously or on the bladder of rats. At predetermined time points, in vivo MRI were obtained and tissues were then harvested for histology analysis and transmission electron microscopy. The result showed that the incorporation of iron oxide particles improved MRI contrast of the implants, providing information on their location, shapes, and degradation. Second, the host tissue reaction to the type I collagen implants could be observed in both MRI and histology. Finally, MRI also revealed that the degradation and host tissue reaction of iron particles-loaded scaffolds differed between subcutaneous and bladder implantation, which was substantiated by histology.

The role of the urothelium and ATP in mediating detrusor smooth muscle contractility.

PubMed

Santoso, Aneira Gracia Hidayat; Sonarno, Ika Ariyani Bte; Arsad, Noor Aishah Bte; Liang, Willmann

2010-11-01

To examine the contractility of urothelium-intact (+UE) and urothelium-denuded (-UE) rat detrusor strips under adenosine triphosphate (ATP) treatment. Purinergic signaling exists in the bladder but both the inhibitory effect of ATP on detrusor contractions and the function of urothelial ATP are not established. Detrusor strips were obtained from bladders of young adult rats. Isometric tension from both transverse and longitudinal contractions was measured using a myograph. The muscarinic agonist carbachol (CCh) was used to induce contractions, which were under the influences of different concentrations of ATP. In both +UE and -UE strips, 1 mM ATP suppressed CCh-induced contractions. In longitudinal contractions, ATP added to the inhibitory effect of urothelium on CCh responses. Removal of the urothelium, but with exogenous ATP added, recovered the CCh responses to the same level as in +UE strips with no added ATP. Transverse contractions were less susceptible to ATP in the presence of urothelium. We showed that the urothelium and ATP suppressed CCh-induced contractions to a similar extent. The findings suggest an inhibitory role of urothelial ATP in mediating detrusor smooth muscle contractility, which may be impaired in diseased bladders. Copyright © 2010 Elsevier Inc. All rights reserved.

[Surgical treatment of upper tract urothelial carcinomas by nephroureterectomy: state of the art review for the yearly scientific report of the French National Association of Urology].

PubMed

Neuzillet, Y; Colin, P; Phé, V; Shariat, S F; Rouprêt, M

2014-11-01

To review current knowledge about techniques of radical nephroureterectomy (RNU) for the treatment of the upper urinary tract cancer (UTUC). A systematic review of the literature search was performed from the database Medline (NLM, Pubmed), focused on the following key-words; nephroureterectomy; renal pelvis; ureter; bladder-cuff excision; urothelial carcinoma; surgery; lymph-node dissection; laparoscopy. The removal of a bladder-cuff during RNU is mandatory. After the surgical procedure, intravesical instillation of ametycine reduces significantly the risk of recurrence into the bladder. Ureteral stripping should not be practiced and continuity of the bladder wall must be restored to avoid compromising the post-operative instillation. Lymphadenectomy during RNU is of prognostic and therapeutic interests. However, the anatomic sites of lymphadenectomy and the number of nodes to be analyzed are not consensual. The oncological results of laparoscopic approach are similar to those of open surgery. The RNU must include a lymphadenectomy and an excision of a bladder-cuff and restore the sealing of the bladder to allow practicing of a EPOI. Laparoscopic or open surgery may be used equally, and must respect these rules to avoid compromising the oncological outcome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

21 CFR 876.5090 - Suprapubic urological catheter and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accessories is a flexible tubular device that is inserted through the abdominal wall into the urinary bladder with the aid of a trocar and cannula. The device is used to pass fluids to and from the urinary tract...

Inguinoscrotal hernia containing the urinary bladder successfully repaired using laparoscopic transabdominal preperitoneal repair technique: A case report.

PubMed

Tazaki, Tatsuya; Sasaki, Masaru; Kohyama, Mohei; Sugiyama, Yoichi; Uegami, Shinnosuke; Shintakuya, Ryuta; Imamura, Yuji; Nakamitsu, Atsushi

2018-05-23

We report herein a patient with an inguinoscrotal hernia containing the urinary bladder. The hernia was safely repaired using the laparoscopic transabdominal preperitoneal repair technique. A 76-year-old man was admitted to our hospital with abdominal pain, vomiting, and diarrhea. His scrotum was swollen to fist size. Abdominal CT showed herniation of the sigmoid colon and the bladder into the right inguinal region, and his abdominal pain was attributed to incarceration of the sigmoid colon; this was manually reduced. About 1 month later, we performed transabdominal preperitoneal repair. After the direct hernial orifice was identified, the bladder was noted to be sliding from the medial side of the hernia; this was reduced. Peeling on the medial side was carried out to the middle of the abdominal wall, and the myopectineal orifice was covered with mesh. The patient was discharged on postoperative day 1. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Xanthogranulomatous Cystitis: A Challenging Imitator of Bladder Cancer

PubMed Central

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-01-01

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature. PMID:20602075

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

Shirkhoda, A; Mauro, M.A.; Staab, E.V.

Fifty-four hemophiliac patients underwent a total of 94 studies using computed tomography (CT), ultrasound, or both. Not only common bleeding sites such as the iliopsoas muscles but also several unusual sites were encountered: these included th iliac bone, bowel wall, mesentery, rectus abdominis muscle, retroperitoneum, bladder wall, and scrotum. Both modalities gave comparable results, and each was helpful in (a) establishing the diagnosis, (b) evaluating the extent of bleeding and its effect on adjacent organs, and (c) demonstrating regression after treatment.

The effects of nicotine administration on the pathophysiology of rat aortic wall.

PubMed

Kugo, H; Zaima, N; Tanaka, H; Urano, T; Unno, N; Moriyama, T

2017-01-01

Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats.

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.

Wound repair in rat urinary bladder following electrocautery or holmium laser incision

NASA Astrophysics Data System (ADS)

Venzi, Giordano; Schmidlin, Franz R.; Gabbiani, Giulio; Delacretaz, Guy P.; Pittet, Brigitte; Leisinger, Hans-Juerg; Iselin, Christoph E.

1999-06-01

Woundhealing is a complex phenomenon which varies according the type of tissue but is also depending from the type of tissue injury. Electrocautery mainly induces coagulation necrosis while thermal damages induced by the Holmium laser primarily lead to tissue vaporization which may induce less tissue injury. The aim of this study was to evaluate the healing process of the Holmium laser induced lesions compared to electrocautery induced lesions in urothelial tissue by assessing the inflammatory response and myofibroblast behavior in sequential healing phases. A surgical wound was created in the urinary rat bladder of 32 rats either by electrocautery or by laser (N=16). The inflammatory response, the total lesion depth and the myofibroblast activity during woundhealing was then analyzed on a qualitative basis on days 0/2/4/8. The overall inflammatory response was comparable in both groups up to days two and four. However, at day eight less cellular inflammatory reaction and less myofibroblast activity was found in the specimen of lesions created by the Holmium laser. These results suggest that wound repair may be a less invasive process after Holmium laser than electrocautery.

[Study of cytogenetic and cytotoxic effect of non-contact electrochemically-activated waters in the five organs of rats].

PubMed

Sycheva, L P; Mikhaĭlova, R I; Beliaeva, N N; Zhurkov, V S; Iurchenko, V V; Savostikova, O N; Alekseeva, A V; Kribtsova, E K; Kovalenko, M A; Akhal'tseva, L V; Sheremet'eva, S M; Iurtseva, N A; Murav'eva, L V; Kamenetskaia, D B

2014-01-01

For the first time the multiorgan karyological analysis of five organs of rats was applied for the study of the cytogenetic and cytotoxic action of the four types of non-contact electrochemically activated water in the 30-days in vivo experiment. The effects of investigated waters were not detected in bone marrow polychromatic erythrocytes. "Anolyte" (ORP = -362 mV) did not have a negative effect on rats. "Catholyte-5" (ORP = +22 mV) and "Catholyte-25" (ORP = -60 mV) induced cytogenetic abnormalities in the bladder and fore stomach. The same catholytes and "Catholyte-40" (ORP = -10 mV) changed the proliferation indices: increased the mitotic index in the fore stomach epithelium and reduced the frequency of binucleated cells in the fore stomach, bladder and lungs. The increase in the rate of cells with cytogenetic abnormalities on the background of the promotion of mitotic activity can be considered as a manifestation of the negative effect, typical for catolytes, but the effect of each out of them has its own features.

Predicting the failure of retrograde ureteral stent insertion for managing malignant ureteral obstruction in outpatients

PubMed Central

WANG, JIN-YOU; ZHANG, HAI-LIANG; ZHU, YAO; QIN, XIAO-JIAN; DAI, BO; YE, DING-WEI

2016-01-01

Malignant ureteral obstruction (MUO) is an unpropitious sign that is commonly observed in patients with advanced incurable cancer. The present study aimed to evaluate predictive factors for the failure of retrograde ureteral stent insertion in the management of MUO in outpatients. A total of 164 patients with MUO were retrospectively assessed in this study. Clinical factors, including age, gender, type of malignancy, level of obstruction, cause of obstruction, pre-operative creatinine level, degree of hydronephrosis, condition of the contralateral ureter, prior radiotherapy, Eastern Cooperative Oncology Group performance status (ECOG PS), bladder wall invasion and technical failure, were recorded for each case. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for predicting the failure of retrograde ureteral stent insertion. In total, 38 out of 164 patients experienced bilateral obstruction, therefore, a total of 202 ureteral units were available for data analysis. The rate of insertion failure in MUO was 34.65%. Multivariate analyses identified ECOG PS, degree of hydronephrosis and bladder wall invasion as independent predictors for insertion failure. Overall, the present study found that rate of retrograde ureteral stent insertion failure is high in outpatients with MUO, and that ECOG PS, degree of hydronephrosis and bladder invasion are potential independent predictors of insertion failure. PMID:26870299

Pediatric robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy: complete intracorporeal--initial case report.

PubMed

Gundeti, Mohan S; Eng, Michael K; Reynolds, W Stuart; Zagaja, Gregory P

2008-11-01

To the best of our knowledge, we report the first case of complete intracorporeal robotic-assisted laparoscopic augmentation ileocystoplasty and Mitrofanoff appendicovesicostomy in a pediatric patient, outlining the surgical technique and short-term results. The operative steps of the open procedure were replicated laparoscopically using robotic-assistance. In brief, 5 transperitoneal laparoscopic ports were placed before docking the da Vinci S robotic system. A 20-cm ileal segment was isolated, and the gastrointestinal anastomosis was performed in an end-to-end fashion using intracorporeal suturing. The appendix was anastomosed to the right posterior wall of the bladder over an 8F feeding tube in an extravesical fashion. The bladder was incised in a coronal plane, and the simple ileal on-lay patch was anastomosed to the posterior and anterior walls of the bladder. A suprapubic catheter and pelvic drain were placed, and the Mitrofanoff stoma was then fashioned. Cystography was performed at 4 weeks postoperatively. This preliminary first successful report suggests that robotic-assisted ileocystoplasty and appendicovesicostomy is feasible. A reasonable outcome with early recovery, resumption of normal activities, and excellent cosmesis can be achieved in selected patients. However, whether a robotic-assisted approach provides any significant advantages over conventional open procedures is yet to be determined with a large case series.

Absorbed dose calculations in a brachytherapy pelvic phantom using the Monte Carlo method

PubMed Central

Rodríguez, Miguel L.; deAlmeida, Carlos E.

2002-01-01

Monte Carlo calculations of the absorbed dose at various points of a brachytherapy anthropomorphic phantom are presented. The phantom walls and internal structures are made of polymethylmethacrylate and its external shape was taken from a female Alderson phantom. A complete Fletcher‐Green type applicator with the uterine tandem was fixed at the bottom of the phantom reproducing a typical geometrical configuration as that attained in a gynecological brachytherapy treatment. The dose rate produced by an array of five 137Cs CDC‐J type sources placed in the applicator colpostats and the uterine tandem was evaluated by Monte Carlo simulations using the code penelope at three points: point A, the rectum, and the bladder. The influence of the applicator in the dose rate was evaluated by comparing Monte Carlo simulations of the sources alone and the sources inserted in the applicator. Differences up to 56% in the dose may be observed for the two cases in the planes including the rectum and bladder. The results show a reduction of the dose of 15.6%, 14.0%, and 5.6% in the rectum, bladder, and point A respectively, when the applicator wall and shieldings are considered. PACS number(s): 87.53Jw, 87.53.Wz, 87.53.Vb, 87.66.Xa PMID:12383048

Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

PubMed

Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

2000-04-01

Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity.

Bladder urothelial carcinoma extending to rectal mucosa and presenting with rectal bleeding

PubMed Central

Aneese, Andrew M; Manuballa, Vinayata; Amin, Mitual; Cappell, Mitchell S

2017-01-01

An 87-year-old-man with prostate-cancer-stage-T1c-Gleason-6 treated with radiotherapy in 1996, recurrent prostate cancer treated with leuprolide hormonal therapy in 2009, and bladder-urothelial-carcinoma in situ treated with Bacillus-Calmette-Guerin and adriamycin in 2010, presented in 2015 with painless, bright red blood per rectum coating stools daily for 5 mo. Rectal examination revealed bright red blood per rectum; and a hard, fixed, 2.5 cm × 2.5 cm mass at the normal prostate location. The hemoglobin was 7.6 g/dL (iron saturation = 8.4%, indicating iron-deficiency-anemia). Abdominopelvic-CT-angiography revealed focal wall thickening at the bladder neck; a mass containing an air cavity replacing the normal prostate; and adjacent rectal invasion. Colonoscopy demonstrated an ulcerated, oozing, multinodular, friable, 2.5 cm × 2.5 cm mass in anterior rectal wall, at the usual prostate location. Histologic and immunohistochemical analysis of colonoscopic biopsies of the mass revealed poorly-differentiated-carcinoma of urothelial origin. At visceral angiography, the right-superior-rectal-artery was embolized to achieve hemostasis. The patient subsequently developed multiple new metastases and expired 13 mo post-embolization. Comprehensive literature review revealed 16 previously reported cases of rectal involvement from bladder urothelial carcinoma, including 11 cases from direct extension and 5 cases from metastases. Patient age averaged 63.7 ± 9.6 years (all patients male). Rectal involvement was diagnosed on average 13.5 ± 11.8 mo after initial diagnosis of bladder urothelial carcinoma. Symptoms included constipation/gastrointestinal obstruction-6, weight loss-5, diarrhea-3, anorexia-3, pencil thin stools-3, tenesmus-2, anorectal pain-2, and other-5. Rectal examination in 9 patients revealed annular rectal constriction-6, and rectal mass-3. The current patient had the novel presentation of daily bright red blood per rectum coating the stools simulating hemorrhoidal bleeding; the novel mechanism of direct bladder urothelial carcinoma extension into rectal mucosa via the prostate; and the novel aforementioned colonoscopic findings underlying the clinical presentation. PMID:28690772

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

Liu, D; Chi, Z; Yang, H

Purpose: To investigate the performances of three commercial treatment planning systems (TPS) for intensity modulated radiotherapy (IMRT) optimization regarding cervical cancer. Methods: For twenty cervical cancer patients, three IMRT plans were retrospectively re-planned: one with Pinnacle TPS,one with Oncentra TPS and on with Eclipse TPS. The total prescribed dose was 50.4 Gy delivered for PTV and 58.8 Gy for PTVnd by simultaneous integrated boost technique. The treatments were delivered using the Varian 23EX accelerator. All optimization schemes generated clinically acceptable plans. They were evaluated based on target coverage, homogeneity (HI) and conformity (CI). The organs at risk (OARs) were analyzedmore » according to the percent volume under some doses and the maximum doses. The statistical method of the collected data of variance analysis was used to compare the difference among the quality of plans. Results: IMRT with Eclipse provided significant better HI, CI and all the parameters of PTV. However, the trend was not extension to the PTVnd, it was still significant better at mean dose, D50% and D98%, but plans with Oncentra showed significant better in the hight dosage volume, such as maximum dose and D2%. For the bladder wall, there were not notable difference among three groups, although Pinnacle and Oncentra systems provided a little lower dose sparing at V50Gy of bladder and rectal wall and V40Gy of bladder wall, respectively. V40Gy of rectal wall (p=0.037), small intestine (p=0.001 for V30Gy, p=0.010 for maximum dose) and V50Gy of right-femoral head (p=0.019) from Eclipse plans showed significant better than other groups. Conclusion: All SIB-IMRT plans were clinically acceptable which were generated by three commercial TPSs. The plans with Eclipse system showed advantages over the plans with Oncentra and Pinnacle system in the overwhelming majority of the dose coverage for targets and dose sparing of OARs in cervical cancer.« less

Neonatal cystitis-induced colonic hypersensitivity in adult rats: a model of viscero-visceral convergence.

PubMed

Miranda, A; Mickle, A; Schmidt, J; Zhang, Z; Shaker, R; Banerjee, B; Sengupta, J N

2011-07-01

The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms. Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days [(postnatal (PN) days 14-16)]. The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissues. CRD- or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-d-aspartic acid (NMDA)-NR1 subunit in the lumbo-sacral (L6-S1) spinal cord was examined using Western blot. The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan-treated rats was significantly higher than the saline-treated control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (P>0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared with saline-treated rats (P<0.05). Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does result in overexpression of spinal NR1 subunit in adult rats. © 2011 Blackwell Publishing Ltd.

Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

NASA Astrophysics Data System (ADS)

Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

2006-02-01

Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

A material sensitivity study on the accuracy of deformable organ registration using linear biomechanical models

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

Chi, Y.; Liang, J.; Yan, D.

2006-02-15

Model-based deformable organ registration techniques using the finite element method (FEM) have recently been investigated intensively and applied to image-guided adaptive radiotherapy (IGART). These techniques assume that human organs are linearly elastic material, and their mechanical properties are predetermined. Unfortunately, the accurate measurement of the tissue material properties is challenging and the properties usually vary between patients. A common issue is therefore the achievable accuracy of the calculation due to the limited access to tissue elastic material constants. In this study, we performed a systematic investigation on this subject based on tissue biomechanics and computer simulations to establish the relationshipsmore » between achievable registration accuracy and tissue mechanical and organ geometrical properties. Primarily we focused on image registration for three organs: rectal wall, bladder wall, and prostate. The tissue anisotropy due to orientation preference in tissue fiber alignment is captured by using an orthotropic or a transversely isotropic elastic model. First we developed biomechanical models for the rectal wall, bladder wall, and prostate using simplified geometries and investigated the effect of varying material parameters on the resulting organ deformation. Then computer models based on patient image data were constructed, and image registrations were performed. The sensitivity of registration errors was studied by perturbating the tissue material properties from their mean values while fixing the boundary conditions. The simulation results demonstrated that registration error for a subvolume increases as its distance from the boundary increases. Also, a variable associated with material stability was found to be a dominant factor in registration accuracy in the context of material uncertainty. For hollow thin organs such as rectal walls and bladder walls, the registration errors are limited. Given 30% in material uncertainty, the registration error is limited to within 1.3 mm. For a solid organ such as the prostate, the registration errors are much larger. Given 30% in material uncertainty, the registration error can reach 4.5 mm. However, the registration error distribution for prostates shows that most of the subvolumes have a much smaller registration error. A deformable organ registration technique that uses FEM is a good candidate in IGART if the mean material parameters are available.« less

Clinical Investigation Program (Tripler Army Medical Center)

DTIC Science & Technology

1991-10-01

temperatures - arterial and central venous blood pressure, relevant blood and urinary hormones, and urine flows will be measured via indwelling catheters...Analysis of central venous pressure recordings are not yet complete, but all experimentation is complete. 21 Detail Summary Sheet Prot No: llA91 Status... catheterized newborn rats are performed. Rats are instrumented with arterial, venous , and stomach catheters and a bladder cannula 3 to 7 days before

Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

PubMed

El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

2016-03-01

The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

Morphological modification of female bladder after prolonged use of soy-based diets.

PubMed

da Silva Faria, Tatiane; Soares, Lavínia Leal; Medeiros, Jorge L; Boaventura, Gilson T; Sampaio, Francisco J B; da Fonte Ramos, Cristiane

2009-01-20

The aim of this study was to compare the effects of a prolonged use of organic and transgenic soy upon the lipid profile and the collagen/muscle ratio of the detrusor muscle of the bladder. Wistar rats were fed three different diets from weaning until sacrifice (15 months old): control group (CG) casein-based diet; organic soy group (OSG) organic soy-based diet; genetically modified soy group (GMSG) transgenic soy-based diet. There was no difference in the food consumption or in the diet isoflavone components among the groups. Comparing to CG, both OSG and GMSG groups presented a significant (p<0.05) reduction in the body weight, triglycerides, cholesterol and the smooth muscle of the detrusor and a significant (p<0.05) increase of collagen fibers number of the detrusor muscle. These findings call into question that, the prolonged use of soy-based diets can be deleterious to the bladder by altering the collagen/muscle ratio what can cause bladder dysfunctions similar with that occurring during menopause.

Gynaecomastia: an unusual presenting symptom of bladder cancer.

PubMed

Ahmed, Mashrafi; Kanji, Aleem; Begum, Tahmina

2015-06-25

A 74-year-old man presented to the outpatient clinic with painful gynaecomastia. A detailed physical examination to sort out possible causes of the gynaecomastia, including intracranial tumour, liver cirrhosis, hyperthyroidism, and adrenal and testicular tumour, was negative. No offending agent was found in his medication list. A CT scan of the head and ultrasound of the scrotum did not show any mass lesion. His serum β-human chorionic gonadotropin (β-hCG) and oestradiol levels were elevated. A CT scan of the abdomen and pelvis revealed bladder wall thickening with soft tissue mass. A cystoscopic biopsy confirmed transitional cell carcinoma with muscle invasion. The patient was started on chemotherapy but responded poorly. This case report describes the β-hCG and oestradiol-secreting transitional cell carcinoma of the bladder presenting as gynaecomastia in an older man. 2015 BMJ Publishing Group Ltd.

Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats

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

Sato, Keiichiro, E-mail: Sato_Keiichiro@takeda.co.jp; Awasaki, Yasuyuki; Kandori, Hitoshi

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manualmore » counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats.« less

Suppressive effects of acid-forming diet against the tumorigenic potential of pioglitazone hydrochloride in the urinary bladder of male rats.

PubMed

Sato, Keiichiro; Awasaki, Yasuyuki; Kandori, Hitoshi; Tanakamaru, Zen-Yo; Nagai, Hirofumi; Baron, David; Yamamoto, Masaki

2011-03-15

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manual counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

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.

Pentosanpolysulfate coating of silicone reduces encrustation.

PubMed

Zupkas, P; Parsons, C L; Percival, C; Monga, M

2000-08-01

A significant problem associated with catheterization in the urinary tract is the encrustation of the catheter materials. One approach to reducing encrustation is to alter the surface properties of the catheters. We evaluated the effectiveness of coating with pentosanpolysulfate (PPS), a semisynthetic polysaccharide similar to heparin, in reducing encrustation and the foreign-body inflammatory response to silicone stents in the bladders of male New Zealand White rabbits. Sixteen rabbits were divided into three groups to receive placement in their bladders of uncoated (N = 7), PPS-coated (N = 7), or sham matrix-processed silicone rings (N = 2) via open cystotomy. After 50 days of maintenance on normal food and water, all rabbits were sacrificed, and the air-dried, unfixed silicone ring surfaces were examined by scanning electron microscopy. Bladders and remaining silicone rings were removed and preserved separately. Silicone rings, cleaned of all encrustation, were stained with toluidene blue to determine the presence or absence of PPS coating on the surface. Histologic examination revealed normal tissue in bladder sections exposed to coated silicone rings and an inflammatory response in sections from bladders having uncoated silicone rings. Coating with PPS was associated with an eightfold reduction in the amount of encrustation of silicone and a marked reduction in the inflammatory response of the bladder wall to the foreign body. A PPS coating may be useful in reducing the encrustation of long-term indwelling silicone stents or catheters in the human urinary tract.

Ultrasonographic evaluation of abdominal distension in 52 camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-08-01

The purpose of this study was to assess the diagnostic value of ultrasonography in the evaluation of abdominal distension in 52 camels (Camelus dromedarius). The conditions included trypanosomiasis (n=35), intestinal obstruction (n=12) and ruptured urinary bladder (n=5). Fifteen clinically normal camels were included as controls. Transabdominal and transrectal ultrasonography was carried out on all camels. In animals with trypanosomiasis, ultrasonographic findings included accumulation of massive amounts of hypoechoic abdominal fluids where liver, intestine, kidney, spleen and urinary bladder were imaged floating. Except in two cases of bile duct calcification and one of hepatic abscessation, no detectable abnormal sonographic lesions were detected while imaging the hepatic and renal parenchyma, and the heart and its valves and major blood vessels. In camels with intestinal obstruction, ultrasonographic findings included distended intestinal loops with markedly reduced or absent motility. In one camel, the intestinal lumen contained localised hyperechoic material that was consistent with a foreign body. Hypoechoic fluid with or without fibrin was seen between intestinal loops. In camels with ruptured urinary bladder, ultrasonographic findings included collapsed and perforated bladder, echogenic blood clots within the urinary bladder and peritoneal cavity, increased thickness of the bladder wall, floating intestines in hypoechogenic fluid and echogenic calculi within the urethra. Ultrasonography was considered a useful tool for the evaluation of dromedary camels with abdominal distension. Copyright © 2011 Elsevier Ltd. All rights reserved.

Extracorporeal shock wave markedly alleviates radiation-induced chronic cystitis in rat

PubMed Central

Chen, Yen-Ta; Chen, Kuan-Hung; Sung, Pei-Hsun; Yang, Chih-Chao; Cheng, Ben-Chung; Chen, Chih-Hung; Chang, Chia-Lo; Sheu, Jiunn-Jye; Lee, Fan-Yen; Shao, Pei-Lin; Sun, Cheuk-Kwan; Yip, Hon-Kan

2018-01-01

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can effectively inhibit radiation-induced chronic cystitis (CC). Adult male Sprague-Dawley (SD) rats (n = 24) were randomly divided into group 1 (normal control), group 2 (CC induced by radiation with 300 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.2 mJ/mm2/120 impulses/at days 1, 7, and 14 after radiation)]. Bladder specimens were harvested by day 28 after radiation. By day 28 after radiation, the degree of detrusor contraction impairment was significantly higher in group 2 than that in groups 1 and 3, and significantly higher in group 3 than that in group 1 (P<0.0001). The urine albumin concentration expressed an opposite pattern compared to that of detrusor function among the three groups (P<0.0001). The bladder protein expressions of inflammatory (TLR-2/TLR-4/IL-6/IL-12/MMP-9/TNF-α/NF-κB/RANTES/iNOS) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited a pattern identical to that of urine albumin in all groups (all P<0.0001). The cellular expressions of inflammatory (CD14+/CD68+/CD74+/COX-2/MIF+/substance P+) and cytokeratin (CK13+/HMW CK+/CK+17/CK+18/CK+19) biomarkers, and collagen-deposition/fibrotic areas as well as epithelial-damaged score displayed an identical pattern compared to that of urine albumin among the three groups (all P<0.0001). In conclusion, ECSW treatment effectively protected urinary bladder from radiation-induced CC. PMID:29636892

Activation of cholinergic receptors blocks non-adrenergic non-cholinergic contractions in the rat urinary bladder

PubMed Central

Henry Lai, H.; Smith, Christopher P.; Munoz, Alvaro; Boone, Timothy B.; Szigeti, Gyula P.; Somogyi, George T.

2008-01-01

In the present study, the plasticity of the non-adrenergic non-cholinergic (NANC) response was investigated. Isolated rat bladder strips were electrically stimulated and the evoked contractions were isometrically recorded. The NANC part of the contractions were unmasked by applying 500 nM 4-DAMP, a potent muscarinic antagonist. Treatment of the bladder strips with 10 μM carbachol (a cholinergic agonist) increased the muscle tone but did not alter the neurally evoked contractions. However, carbachol decreased: (1) the NANC response from 74.6% to 33.3% of control and (2) the purinergic contractile response to α,β methylene ATP (α,β mATP) (10 μM) from 97.0% to 43.4% (p<0.05). Treatment with the cholinesterase inhibitor eserine (10 μM) also significantly decreased the NANC response to 21.1% (p<0.0001). The purinergic receptor antagonist suramin (100μM) did not affect the neurally evoked contractions, however; subsequent addition of 4-DAMP decreased the contractions to 31%. Activation of the smooth muscle cholinergic receptors (with carbachol or eserine) and purinergic receptors (with α,β mATP) decreased the NANC contractions and the direct contractile response to α,β mATP. When the electrically evoked contractions were facilitated by the L-type Ca2+ channel activator, Bay-K 8644 the subsequent application of 4-DAMP did not unmask inhibited NANC contractions. We conclude that activation of muscarinic receptors by cholinergic agonist, carbachol or by endogenous acetylcholine (ACh) induce a cascade of events that leads to diminished purinergic response and consequently an inhibition of the bladder NANC response. PMID:18755252

A novel intracerebral hemorrhage-induced rat model of neurogenic voiding dysfunction: Analysis of lower urinary tract function

PubMed Central

CHO, YOUNG-SAM; KO, IL-GYU; KIM, CHANG-JU; KIM, KHAE-HAWN

2015-01-01

Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients with various neurological disorders, and may result in debilitating symptoms and serious complications, including chronic renal failure and recurrent urinary tract infections. Clinically, stroke is associated with voiding dysfunction. However, lower urinary tract function evaluation in an intracerebral hemorrhage (ICH) model has not, to the best of our knowledge, been reported. Therefore, in the present study, lower urinary tract function in ICH-induced rats was investigated and the results were compared with those obtained in normal rats. The effects of ICH on peripheral bladder function and central micturition centers [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats were divided into two groups: Control ICH-induced. Induction of ICH in the hippocampal CA1 region was performed using a stereotaxic frame and type IV collagenase. The effects of ICH on the central micturition centers were investigated by simultaneously determining the extent of neuronal activation (c-Fos) and nerve growth factor (NGF) expression, and assessing voiding function (urodynamically using cystometry). The results revealed that induction of ICH significantly enhanced bladder contraction pressure and time, while simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF expression levels in the neuronal voiding centers were significantly increased in the rats with induced ICH as compared with the control rats. Therefore, this ICH-induced NLUTD rat model may be a more appropriate method to analyze NLUTD in stroke patients than a cerebral infarction model, as the former more accurately reflects the nature of the hemorrhage in the two types of stroke. PMID:25954993

Emphysematous Cystitis Occurred in the Case Treated with Steroid for Autoimmune Hepatitis

PubMed Central

Yoshino, Tateki; Ohara, Shinya; Moriyama, Hiroyuki

2013-01-01

Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients, which was characterized by air within the bladder wall and lumen. A 83-year-old woman was introduced to our department with fever elevation and abnormal findings of computed tomography (CT). She took orally prednisolone for autoimmune hepatitis. Pelvic CT revealed diffuse air throughout the bladder wall. Urinalysis showed combined hematuria and pyuria. Escherichia coli was detected in blood culture. Abnormal findings of complete blood count and laboratory examination included an elevated WBC count (12,200/μL), C-reactive protein (11.7 mg/dL), and creatinine (1.07 mg/dL). Cystoscopy confirmed diffuse submucosal emphysema throughout. On the basis of diagnosis with emphysematous cystitis, she was treated with antibiotics based on the results of blood culture and indwelling Foley catheter. After treatment, the improvement of inflammatory findings and submucosal emphysema on cystoscopy and CT were achieved. PMID:23936723

Immunotherapy for bladder cancer

PubMed Central

Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

2015-01-01

It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

Bladder wall thickness in women with symptoms of overactive bladder and detrusor overactivity: Results from the randomised, placebo-controlled shrink study.

PubMed

Robinson, Dudley; Oelke, Matthias; Khullar, Vik; Wijkstra, Hessel; Tretter, Reiner; Stow, Bridget; Compion, Gerhard; Tubaro, Andrea

2016-09-01

Measurement of bladder wall thickness (BWT) by transvaginal ultrasound (TVUS) may be a less invasive method to diagnose overactive bladder (OAB) or detrusor overactivity (DO) and monitor response to therapy. This study assessed whether treatment with solifenacin affects BWT. This was a double-blind, randomised, placebo-controlled, phase 4 study. Adult women with OAB symptoms received solifenacin 5 or 10 mg or placebo once daily for 12 weeks. The co-primary endpoints were change from baseline to Week 12 in TVUS-measured BWT and urinary nerve growth factor. Only results for BWT are presented here. Overall, 547 patients were randomised, 501 patients had a baseline BWT measurement, and change from baseline could be calculated for 478 patients. Mean BWT at baseline was 5.08 mm (range 2.2-11.1, SD = 1.14) and was normally distributed. A significant reduction in BWT from baseline to 12 weeks versus placebo was observed with solifenacin 5 mg (-0.42 vs. -0.16 mm, P = 0.03), but not with the 10 mg dose or with pooled solifenacin, considered the primary comparison. Both solifenacin doses were associated with improvements in efficacy and patient satisfaction endpoints versus placebo. Solifenacin was well tolerated, with dry mouth being the most common adverse event. There was no consistent effect of solifenacin on BWT in women with OAB/DO, despite improvements in efficacy endpoints. This study suggests that routine clinical assessment of BWT with TVUS for monitoring the effects of OAB/DO treatment is not clinically useful. Neurourol. Urodynam. 35:819-825, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

A rare case of metastatic squamous urachal carcinoma.

PubMed

Andrei, S; Andrei, A; Rusu Muntean, G; Ungureanu, M; Herlea, V; Becheanu, G; Popescu, I

2013-01-01

Squamous cell carcinoma is a very rare type of urachal malignancy, only a few cases being reported in the medical literature. We present the case of a 49-year-old male patient diagnosed with infected squamous cell urachal carcinoma with multiple pulmonary metastases, after complaints of lower abdominal pain, abdominal mass and fever, without respiratory symptoms. The abdominal ultrasonography and the CT scan revealed a tumoral mass in the lower abdomen in contact with the abdominal wall and the urinary bladder dome, displacing the small bowel. Pulmonary nodular lesions were described in the left lobe pyramid. The intraoperative diagnosis was necrotic urachal tumor with urinary bladder dome invasion and suspected pulmonary metastases, and tumor ablation with bladder dome resection and suture of the bladder were performed. The histopathological result was poorly differentiated squamous cell carcinoma (G3), with negative resection margins. The patient recovered well after surgery, but the prognosis is very poor due to the metastatic stage in which the tumor was diagnosed, no standard chemotherapy regimen for the treatment of metastatic urachal carcinoma being known as effective until now. Celsius.

Role of potassium ion channels in detrusor smooth muscle function and dysfunction

PubMed Central

Petkov, Georgi V.

2013-01-01

Contraction and relaxation of the detrusor smooth muscle (DSM), which makes up the wall of the urinary bladder, facilitates the storage and voiding of urine. Several families of K+ channels, including voltage-gated K+ (KV) channels, Ca2+-activated K+ (KCa) channels, inward-rectifying ATP-sensitive K+ (Kir, KATP) channels, and two-pore-domain K+ (K2P) channels, are expressed and functional in DSM. They control DSM excitability and contractility by maintaining the resting membrane potential and shaping the action potentials that determine the phasic nature of contractility in this tissue. Defects in DSM K+ channel proteins or in the molecules involved in their regulatory pathways may underlie certain forms of bladder dysfunction, such as overactive bladder. K+ channels represent an opportunity for novel pharmacological manipulation and therapeutic intervention in human DSM. Modulation of DSM K+ channels directly or indirectly by targeting their regulatory mechanisms has the potential to control urinary bladder function. This Review summarizes our current state of knowledge of the functional role of K+ channels in DSM in health and disease, with special emphasis on current advancements in the field. PMID:22158596

Co-delivery of micronized urinary bladder matrix damps regenerative capacity of minced muscle grafts in the treatment of volumetric muscle loss injuries

PubMed Central

Corona, Benjamin T.

2017-01-01

Minced muscle grafts (MG) promote de novo muscle fiber regeneration and neuromuscular strength recovery in small and large animal models of volumetric muscle loss. The most noteworthy limitation of this approach is its reliance on a finite supply of donor tissue. To address this shortcoming, this study sought to evaluate micronized acellular urinary bladder matrix (UBM) as a scaffolding to promote in vivo expansion of this MG therapy in a rat model. Rats received volumetric muscle loss injuries to the tibialis anterior muscle of their left hind limb which were either left untreated or repaired with minced muscle graft at dosages of 50% and 100% of the defect mass, urinary bladder matrix in isolation, or a with an expansion product consisting of a combination of the two putative therapies in which the minced graft is delivered at a dosage of 50% of the defect mass. Rats survived to 2 and 8 weeks post injury before functional (in vivo neuromuscular strength), histological, morphological, and biochemical analyses were performed. Rats treated with the expansion product exhibited improved neuromuscular function relative to untreated VML after an 8 week time period following injury. This improvement in functional capacity, however, was accompanied with a concomitant reduction in graft mediated regeneration, as evidenced cell lineage tracing enable by a transgenic GFP expressing donor, and a mixed histological outcome indicating coincident fibrous matrix deposition with interspersed islands of nascent muscle fibers. Furthermore, quantitative immunofluorescence and transcriptional analysis following the 2 week time point suggests an exacerbated immune response to the UBM as a possible nidus for the observed suboptimal regenerative outcome. Moving forward, efforts related to the development of a MG expansion product should carefully consider the effects of the host immune response to candidate biomaterials in order to avoid undesirable dysregulation of pro-regenerative cross talk between the immune system and myogenic processes. PMID:29040321

Effect of [D-Phe6] bombesin (6-13) methylester, a bombesin receptor antagonist, towards bombesin-induced contractions in the guinea-pig and rat isolated urinary bladder.

PubMed

Maggi, C A; Coy, D H; Giuliani, S

1992-08-01

1. The effect of [D-Phe6] bombesin (6-13) methylester (OMe), a newly developed potent antagonist of bombesin receptors, has been investigated against bombesin-induced contractions of the guinea-pig and rat isolated urinary bladder. 2. Bombesin (0.1 nM-10 microM) produced a concentration-dependent contraction of the guinea-pig isolated bladder which approached the same maximum response as KCl (80 mM). The response to bombesin was antagonized in a competitive manner (rightward shift of the concentration-response curve without depression of the maximal response) by [D-Phe6] bombesin (6-13) OMe (0.3-10 microM). Degree of antagonism was concentration-dependent between 0.3 and 3 microM (dose ratios = 2.4, 9 and 39 in the presence of 0.3, 1, 3 microM of the antagonist). However, a larger concentration (10 microM) of the antagonist was not more effective (dose ratio = 36) than 3 microM. 3. Neither the action of bombesin nor the activity of the antagonist was influenced by peptidase inhibitors (bestatin, captopril and thiorphan 3 microM each) or by atropine, indomethacin, chlorpheniramine and desensitization of P2x purinoceptors by alpha, beta methylene ATP. 4. The bombesin antagonist was ineffective against contraction of the guinea-pig urinary bladder produced by the NK-1 tachykinin receptor-selective agonist, [Sar9] substance P sulphone. The action of the NK-1 receptor agonist was antagonized by L 668, 169 (3 microM), a cyclic peptide tachykinin antagonist. L 668, 169 had no effect toward bombesin-induced contraction. 5. The bombesin antagonist (1-10 microM) had no effect against the non-adrenergic non-cholinergic response of the guinea-pig isolated urinary bladder to electrical field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Spatial organization of musculature in the Himasthla elongata cercaria (Trematoda: Echinostomatidae)].

PubMed

Krupenko, D Iu

2011-01-01

Somatic muscles (body-wall and "parenchyma" musculature), muscles of suckers, alimentary tract and excretory bladder of Himasthla elongata cercaria were investigated using fluorescent phalloidin labelling and confocal microscopy. The arrangement of body-wall muscles differs between the certain parts of cercarial body and appears to be the most complicated in the collar district. Among the body-wall musculature, we described U-shaped muscles, which have never been found previously in trematodes. Muscles of oral and ventral suckers are grouped into 6-7 independent layers. In some of those layers, they are arranged bilaterally, which contradicts the tradition to consider the sucker as radially symmetric.

Cystic urogenital anomalies in ferrets (Mustela putorius furo).

PubMed

Li, X; Fox, J G; Erdman, S E; Lipman, N S; Murphy, J C

1996-03-01

Single or multiple semispherical to bilobulated fluid-filled cystic structures of variable size were observed on the dorsal aspects of the urinary bladder of four male and two female ferrets (Mustela putorius furo). All ferrets had been neutered. On physical examination, the cysts were palpated as caudal abdominal masses. Three of the six ferrets presented with dysuria, and two ferrets had signs compatible with endocrine dysfunction. Adrenal cortical hyperplasia or neoplasia were observed in all of the five ferrets examined. Sex hormones assayed in one of the six ferrets revealed elevated levels of serum estrodiol. The posterior aspect of the cysts was located on and/or attached to the trigone or neck of the bladder, with variable intraluminal communication with the bladder and/or the urethra. The anterior aspect of the cysts projected dorsally or dorsocranially into the caudal abdomen. The cysts were thin walled and contained urinelike fluid (n = 5) or viscous yellow fluid (n = 1). Histologically, the cyst walls were composed of three layers, epithelium, muscle, and serosa, with fibrovascular stroma between layers. The epithelium consisted of simple to stratified transitional, columnar, or squamous epithelial cells. The muscular layer consisted of intermittent bundles and/or single to double layers of continuous to discontinuous smooth muscle. The serosal layer consisted of loose fibrous stroma covered by flattened mesothelial cells. The cystic anomalies in these ferrets were most likely derived from the urogenital glands/ducts or other remnants.

Arena geometry and path shape: when rats travel in straight or in circuitous paths?

PubMed

Yaski, Osnat; Portugali, Juval; Eilam, David

2011-12-01

We show here that the global geometry of the environment affects the shape of the paths of travel in rats. To examine this, individual rats were introduced into an unfamiliar arena. One group of rats (n=8) was tested in a square arena (2 m × 2 m), and the other group (n=8) in a round arena (2 m diameter). Testing was in a total darkness, since in the absence of visual information the geometry is not perceived immediately and the extraction of environment shape is slower. We found that while the level of the rats' activity did not seem to differ between both arenas, path shape differed significantly. When traveling along the perimeter, path shape basically followed the arena walls, with perimeter paths curving along the walls of the round arena, while being straight along the walls of the square arena. A similar impact of arena geometry was observed for travel away from the arena walls. Indeed, when the rats abandoned the arena walls to crosscut through the center of the arena, their center paths were circuitous in the round arena and relatively straight in the square arena. We suggest that the shapes of these paths are exploited for the same spatial task: returning back to a familiar location in the unsighted environment. Copyright © 2011 Elsevier B.V. All rights reserved.

Is whole-body fluorine-18 fluorodeoxyglucose PET/CT plus additional pelvic images (oral hydration-voiding-refilling) useful for detecting recurrent bladder cancer?

PubMed

Yang, Zhongyi; Cheng, Jingyi; Pan, Lingling; Hu, Silong; Xu, Junyan; Zhang, Yongping; Wang, Mingwei; Zhang, Jianping; Ye, Dingwei; Zhang, Yingjian

2012-08-01

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers. From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months. Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively. PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

Surgical removal of a large vaginal calculus formed after a tension-free vaginal tape procedure.

PubMed

Zilberlicht, Ariel; Feiner, Benjamin; Haya, Nir; Auslender, Ron; Abramov, Yoram

2016-11-01

Vaginal calculus is a rare disorder which has been reported in association with urethral diverticulum, urogenital sinus anomaly, bladder exstrophy and the tension-free vaginal tape (TVT) procedure. We report a 42-year-old woman who presented with persistent, intractable urinary tract infection (UTI) following a TVT procedure. Cystoscopy demonstrated an eroded tape with the formation of a bladder calculus, and the patient underwent laser cystolithotripsy and cystoscopic resection of the tape. Following this procedure, her UTI completely resolved and she remained asymptomatic for several years. Seven years later she presented with a solid vaginal mass. Pelvic examination followed by transvaginal ultrasonography and magnetic resonance imaging demonstrated a large vaginal calculus located at the lower third of the anterior vaginal wall adjacent to the bladder neck. This video presents the transvaginal excision and removal of the vaginal calculus.

Diagnosis of cystocele--the correlation between clinical and radiological evaluation.

PubMed

Altman, Daniel; Mellgren, Anders; Kierkegaard, Jonas; Zetterström, Jan; Falconer, Christian; López, Annika

2004-01-01

In patients with genital prolapse involving several compartments simultaneously, radiologic investigation can be used to complement the clinical assessment. Contrast medium in the urinary bladder enables visualization of the bladder base at cystodefecoperitoneography (CDP). The aim of the present study was to evaluate the correlation between clinical examination using the Pelvic Organ Prolapse Quantification system (POP-Q) and CDP. Thirty-three women underwent clinical assessment and CDP. Statistical analysis using Pearson's correlation coefficient ( r) demonstrated a wide variability between the current definition of cystocele at CDP and POP-Q ( r=0.67). An attempt to provide an alternative definition of cystocele at CDP had a similar outcome ( r=0.63). The present study demonstrates a moderate correlation between clinical and radiologic findings in patients with anterior vaginal wall prolapse. It does not support the use of bladder contrast at radiologic investigation in the routine preoperative assessment of patients with genital prolapse.

BILATERAL HYDRONEPHROSIS IN A SUGAR GLIDER (PETAURUS BREVICEPS).

PubMed

Cusack, Lara; Schnellbacher, Rodney; Howerth, Elizabeth W; Jiménez, David A; Mayer, Joerg; Divers, Stephen

2016-09-01

An adult, intact male sugar glider ( Petaurus breviceps ) presented for acute caudal abdominal swelling. Treatment by the referring veterinarian included aspiration of urine from the swelling. On physical examination, mild depression, pale mucus membranes, and caudal abdominal swelling were noted. Focused ultrasonographic assessment revealed a fluid-filled caudal abdominal structure and subjective bladder wall thickening. The following day, the sugar glider was severely depressed. Hematology results included hypoglycemia, hyperkalemia, hyponatremia, and azotemia. Ultrasonography revealed bilateral hydronephrosis and hydroureter. Despite supportive care, the animal died. Postmortem examination confirmed bilateral ureteral dilation, renal petechial hemorrhage, and dilation of the right renal pelvis. Submucosal edema, hemorrhage, and lymphoplasmacytic infiltration of the urinary bladder, ureters, and renal pelvises were noted. Hyperplasia of the urinary bladder and ureteral epithelium, coupled with inflammation, may have caused functional obstruction leading to bilateral hydronephrosis and hydroureter. This is the first reported case of hydronephrosis in a marsupial.

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

PubMed Central

Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A.; Tang, Moon-shong

2014-01-01

Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS. PMID:24939871

Bladder cancer diagnosis during cystoscopy using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Grimbergen, M. C. M.; van Swol, C. F. P.; Draga, R. O. P.; van Diest, P.; Verdaasdonk, R. M.; Stone, N.; Bosch, J. H. L. R.

2009-02-01

Raman spectroscopy is an optical technique that can be used to obtain specific molecular information of biological tissues. It has been used successfully to differentiate normal and pre-malignant tissue in many organs. The goal of this study is to determine the possibility to distinguish normal tissue from bladder cancer using this system. The endoscopic Raman system consists of a 6 Fr endoscopic probe connected to a 785nm diode laser and a spectral recording system. A total of 107 tissue samples were obtained from 54 patients with known bladder cancer during transurethral tumor resection. Immediately after surgical removal the samples were placed under the Raman probe and spectra were collected and stored for further analysis. The collected spectra were analyzed using multivariate statistical methods. In total 2949 Raman spectra were recorded ex vivo from cold cup biopsy samples with 2 seconds integration time. A multivariate algorithm allowed differentiation of normal and malignant tissue with a sensitivity and specificity of 78,5% and 78,9% respectively. The results show the possibility of discerning normal from malignant bladder tissue by means of Raman spectroscopy using a small fiber based system. Despite the low number of samples the results indicate that it might be possible to use this technique to grade identified bladder wall lesions during endoscopy.

Quantitative Evaluation of CART-Containing Cells in Urinary Bladder of Rats with Renovascular Hypertension

PubMed Central

Janiuk, I.; Kasacka, I.

2015-01-01

Recent biological advances make it possible to discover new peptides associated with hypertension. The cocaine- and amphetamine-regulated transcript (CART) is a known factor in appetite and feeding behaviour. Various lines of evidence suggest that this peptide participates not only in control of feeding behaviour but also in the regulation of the cardiovascular and sympathetic systems and blood pressure. The role of CART in blood pressure regulation led us to undertake a study aimed at analysing quantitative changes in CART-containing cells in urinary bladders (UB) of rats with renovascular hypertension. We used the Goldblatt model of arterial hypertension (two-kidney, one clip) to evaluate quantitative changes. This model provides researchers with a commonly used tool to analyse the renin-angiotensin system of blood pressure control and, eventually, to develop drugs for the treatment of chronic hypertension. The study was performed on sections of urinary bladders of rats after 3-, 14-, 28-, 42 and 91 days from hypertension induction. Immunohistochemical identification of CART cells was performed on paraffin for the UBs of all the study animals. CART was detected in the endocrine cells, especially numerous in the submucosa and muscularis layers, with a few found in the transitional epithelium and only occasionally in serosa. Hypertension significantly increased the number of CART-positive cells in the rat UBs. After 3 and 42 days following the procedure, statistically significantly higher numbers of CART-positive cells were identified in comparison with the control animals. The differences between the hypertensive rats and the control animals concerned not only the number density of CART-immunoreactive cells but also their localization. After a 6-week period, each of the rats subjected to the renal artery clipping procedure developed stable hypertension. CART appeared in numerous transitional epithelium cells. As this study provides novel findings, the question appears about the type of connection between hypertension and the functioning and activity of CART in the urinary tract (UT). The study gives rise to the assumption that high blood pressure can be a factor that intensifies CART secretion. In conclusion, the endocrine system of the urinary tract is modified by renovascular hypertension. This may affect the production of hormones and biologically active substances and contribute to the development of possible hypertension complications. In order to fully comprehend the role of the CART peptide in blood pressure regulation, further analyses are necessary. PMID:26150151