Endoscopic Treatment of Studer's Orthotopic Neobladder Lithiasis

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Diogo Gil-Sousa

2015-05-01

Full Text Available Studer's neobladder lithiasis is a rare but important long term complication of this orthotopic bladder substitute technique. We report a case of a 45 year-old male patient, submitted to a radical cystoprostatectomy with a Studer's orthotopic neobladder 4 years before, presenting bad compliance to recommended urinary habits, increased production of mucus and high post voiding residue. CT scan and urethrocystography showed a distended pouch with 2 major sacculations with narrow communication and a stone in each sacculation. A minimally invasive endoscopic technique was successfully used in the treatment of the 2 small calculus.

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

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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.

Hemodynamic and metabolic characterization of orthotopic rat prostate carcinomas using dynamic MRI and proton magnetic resonance spectroscopy

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Kiessling, F.; Lichy, M.; Kauczor, H.U.; Schlemmer, H.P.; Grobholz, R.; Heilmann, M.; Meding, J.; Huber, P.E.; Peschke, P.

2003-01-01

The aim of this study was the noninvasive characterization of prostate carcinoma orthotopically implanted in rats using Gd-DTPA-assisted dynamic MRI (dMRI) and proton magnetic resonance spectroscopy ( 1 H-MRS). After surgical exposure of the prostate, Dunning R3327 orthotopic prostate carcinoma was induced by injecting cells of the MAT-LyLu subline. Six rats were examined 5 and 14 days after tumor induction with dMRI and 1 H-MRS at 1.5 T. Six tumor-free rats served as controls. Using an open two-compartment model, the parameters A (amplitude) and k ep (exchange rate constants) were calculated from the signal time curves of the dMRI. The relative signal intensities (Cho/Cr) of the resonances of choline (Cho) and the creatine-phosphocreatine complex (Cr) were computed from the MR spectra. Already after 5 days, the tumors in the prostate could be clearly identified based on the decrease in signal intensity to T2w and increase of A and k ep . High Cho/Cr levels and resonances of two lipid fractions (Lip 1 at 0.8-1.5 ppm and Lip 2 at 2.0-2.2 ppm) were observed by MRS in the highly necrotic tumors. The orthotopic rat prostate carcinoma model resembles human prostate carcinoma in regard to MR morphology, dMRI, and 1 H-MRS. The noninvasive characterization of perfusion and metabolism makes a comparative examination of different treatment modalities possible. (orig.) [de

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

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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.

MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

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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...

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

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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

Study of morbidity in orthotopic small intestine transplantation with Wistar rats: experimental study

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LEE André Dong Won; GAMA-RODRIGUES Joaquim; GALVÃO Flávio H.; WAITZBERG Dan L.

2002-01-01

Background - Transplantation of the small intestine is a surgical procedure currently under investigation for its possible application in the treatment of patients with short bowel syndrome, aiming at the reintroduction of an oral diet. Aim - To define the morbidity and mortality of intestinal transplantation in small animals using microsurgery. Intra and postoperative morbidity and mortality were studied in Wistar rats submitted to orthotopic intestinal allotransplantation. Material and Meth...

Bladder function in 17β-estradiol-induced nonbacterial prostatitis model in Wistar rat.

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Matsumoto, Seiji; Kawai, Yuko; Oka, Michiko; Oyama, Tatsuya; Hashizume, Kazumi; Wada, Naoki; Hori, Jun-ichi; Tamaki, Gaku; Kita, Masafumi; Iwata, Tatsuya; Kakizaki, Hidehiro

2013-06-01

To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17β-estradiol injection. Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

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

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Chong Liu

2016-01-01

Full Text Available 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.

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

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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

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

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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.

Bladder overdistension with polyuria in a hypertensive rat model.

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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.

Overexpression of Aquaporin-1 and Caveolin-1 in the Rat Urinary Bladder Urothelium Following Bladder Outlet Obstruction

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Sun-Ouck Kim

2013-12-01

Full Text Available Purpose This study was designed to investigate the effect of detrusor overactivity induced by partial bladder outlet obstruction (BOO on the expression of aquaporin 1 (AQP1 and caveolin 1 (CAV1 in the rat urinary bladder, and to determine the role of these molecules in detrusor overactivity. Methods Female Sprague-Dawley rats were divided into control (n=30 and experimental (n=30 groups. The BOO group underwent partial BOO, and the control group underwent a sham operation. After 4 weeks, an urodynamic study was performed to measure the contraction interval and contraction pressure. The expression and cellular localization of AQP1 and CAV1 were determined by western blot and immunofluorescence experiments in the rat urinary bladder. Results In cystometrograms, the contraction interval was significantly lower in the BOO group (2.9±1.5 minutes than in the control group (6.7±1.0 minutes (P<0.05. Conversely, the average contraction pressure was significantly higher in the BOO group (21.2±3.3 mmHg than in the control group (13.0±2.5 mmHg (P<0.05. AQP1 and CAV1 were coexpressed in the capillaries, arterioles, and venules of the suburothelial layer. AQP1 and CAV1 protein expression was significantly increased in the BOO rats compared to the control rats (P<0.05. Conclusions Detrusor overactivity induced by BOO causes a significant increase in the expression of AQP1 and CAV1, which were coexpressed in the suburothelial microvasculature. This finding suggests that AQP1 and CAV1 might be closely related to bladder signal activity and may have a functional role in BOO-associated detrusor overactivity.

Adherence of urease-induced crystals to rat bladder epithelium.

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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.

Urothelial Carcinoma Recurrence at an Ileal Orthotopic Neobladder and Unilateral Lower Ureter After Surgery

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Bunya Kawamoto

2016-11-01

Full Text Available The recurrence of urothelial carcinoma in an orthotopic neobladder is rare. We report the case of a 61-year-old man with a muscle-invasive bladder tumor that was treated using radical cystectomy and the creation of a Studer's orthotopic neobladder. However, nine years after the cystectomy, we detected a mass at the left ureteroileal anastomosis. We successfully performed Studer's neobladder resection, urethrectomy, and left nephroureterectomy to remove the entire mass. Pathological examination revealed urothelial carcinoma with adenocarcinoma in the neobladder and adenocarcinomatous metastasis in the mesenteric lymph node.

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

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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.

INVERSION OF ORTHOTOPIC INTESTINAL URINARY RESERVOIR TO PREVENT TENSION IN URETHRA-RESERVOIR ANASTOMOSIS AFTER RADICAL CYSTECTOMY

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V. A. Perepechay

2013-01-01

Full Text Available From 1995 to 2012 radical cystectomy were performed to 326 patients. Orthotopic intestinocistoplastika performed by Studer 69 (18.7% patients, including short mesostenium was in 48 (69.6%, which are combined into two groups. Group I - 15 (31.3% patients with orthotopic intestinocistoplasticy by Studer, II group - 33 (68.7% patients who made modification techniques Studer - inverts orthotopic ileocistoplastics. Cases of leak of the tank or anastomosis were not observed. Medium capacity of neobladder after removal of urethral catheter – 110 ml., in 3 months – 350 ml, in 12 months – 490.0 ml. Maximum pressure in the tank does not exceed 40 cm water column (average 30 cm H2O. Day retention – 94,7%, night confinement at a forced night miction – 79.0%. The proposed method of inverting orthotopic ileal neobladder can be recommended when overlapping of orthotopic urinary reservoir is impossible or associated with leaks of the anastomosis due to the insuf-ficient length of the mesentery using known techniques of orthotopic ileal bladder reconstruction.

Sodium Tanshinone IIA Sulfonate Ameliorates Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction by Inhibiting the TGF-β/Smad Pathway Activation.

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Xiaoxiao Jiang

Full Text Available Transforming growth factor (TGF-β1 is known to play a pivotal role in a diverse range of biological systems including modulation of fibrosis in several organs. The precise role of TGF-β/Smad signaling in the progression of bladder fibrosis secondary to partial bladder outlet obstruction (PBOO is yet to be conclusively. Using a rat PBOO model, we investigated TGF-β1 expression and exaimined whether sodium tanshinone IIA sulfonate (STS could inhibit TGF-β/Smad signaling pathway activation and ameliorate bladder fibrosis. Forty-eight female Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 16, PBOO operation without STS treatment group (n = 16 and PBOO operation with STS treatment group (n = 16. Thirty-two rats underwent the operative procedure to create PBOO and subsequently received intraperitoneal injections of STS (10 mg/kg/d; n = 16 or vehicle (n = 16 two days after the surgery. Sham surgery was conducted on 16 rats, which received intraperitoneal vehicle injection two days later. In each of the three groups, an equal number of rats were sacrificed at weeks 4 and 8 after the PBOO or sham operation. The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR. One-way analysis of variance was conducted to draw statistical inferences. At 4 and 8 weeks, the expression of TGF-β1 and phosphorylated Smad2 and Smad3 in STS-treated PBOO rats was significantly lower than in the PBOO rats not treated with STS. Alpha smooth muscle actin (α-SMA, collagen I and collagen III expression at 4 and 8 weeks post PBOO was lower in STS-treated PBOO rats when compared to that in PBOO rats not treated with STS. Our findings indicate that STS ameliorates bladder fibrosis by inhibiting TGF-β/Smad signaling pathway activation, and may prove to be a potential therapeutic measure for preventing bladder fibrosis secondary to PBOO

Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat.

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Jayabalan Nirmal

Full Text Available The functional and molecular alterations of nerve growth factor (NGF and Prostaglandin E2 (PGE2 and its receptors were studied in bladder and urine in streptozotocin (STZ-induced diabetic rats.Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12.DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder.

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

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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.

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

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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.

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

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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.

Stimulation of the sensory pudendal nerve increases bladder capacity in the rat.

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Hokanson, James A; Langdale, Christopher L; Sridhar, Arun; Grill, Warren M

2018-04-01

Pudendal nerve stimulation is a promising treatment approach for lower urinary tract dysfunction, including symptoms of overactive bladder. Despite some promising clinical studies, there remain many unknowns as to how best to stimulate the pudendal nerve to maximize therapeutic efficacy. We quantified changes in bladder capacity and voiding efficiency during single-fill cystometry in response to electrical stimulation of the sensory branch of the pudendal nerve in urethane-anesthetized female Wistar rats. Increases in bladder capacity were dependent on both stimulation amplitude and rate. Stimulation that produced increases in bladder capacity also led to reductions in voiding efficiency. Also, there was a stimulation carryover effect, and increases in bladder capacity persisted during several nonstimulated trials following stimulated trials. Intravesically administered PGE 2 reduced bladder capacity, producing a model of overactive bladder (OAB), and sensory pudendal nerve stimulation again increased bladder capacity but also reduced voiding efficiency. This study serves as a basis for future studies that seek to maximize the therapeutic efficacy of sensory pudendal nerve stimulation for the symptoms of OAB.

Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells.

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Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

2018-02-01

The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at -80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway

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Weng, T.I.; Chen, W.J.; Liu, S.H.

2005-01-01

Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-α translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator β-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-α translocation was impaired in the bladder; LPS did not affect PKC-δ translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-α translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment

Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer.

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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

Allopurinol Protects against Ischemia/Reperfusion-Induced Injury in Rat Urinary Bladders

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Ju-Hyun Shin

2015-01-01

Full Text Available Bladder ischemia-reperfusion (I/R injury results in the generation of reactive oxygen species (ROS and markedly elevates the risk of lower urinary tract symptoms (LUTS. Allopurinol is an inhibitor of xanthine oxidase (XO and thus can serve as an antioxidant that reduces oxidative stress. Here, a rat model was used to assess the ability of allopurinol treatment to ameliorate the deleterious effects of urinary bladder I/R injury. I/R injury reduced the in vitro contractile responses of longitudinal bladder strips, elevated XO activity in the plasma and bladder tissue, increased the bladder levels of tumor necrosis factor-α (TNF-α, c-Jun N-terminal kinase (JNK, and p38 mitogen-activated protein kinase, reduced the bladder levels of extracellular regulated kinase (ERK, and decreased and increased the bladder levels of Bcl-2 and Bax, respectively. I/R injury also elevated lipid peroxidation in the bladder. Allopurinol treatment in the I/R injury was generated significantly ameliorating all I/R-induced changes. Moreover, an in situ fluorohistological approach also showed that allopurinol reduces the generation of intracellular superoxides enlarged by I/R injury. Together, the beneficial effects of allopurinol reducing ROS production may be mediated by normalizing the activity of the ERK, JNK, and Bax/Bcl-2 pathways and by controlling TNF-α expression.

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

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

2010-08-01

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

Complications of Radical Cystectomy and Orthotopic Reconstruction

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Wei Shen Tan

2015-01-01

Full Text Available Radical cystectomy and orthotopic reconstruction significant morbidity and mortality despite advances in minimal invasive and robotic technology. In this review, we will discuss early and late complications, as well as describe efforts to minimize morbidity and mortality, with a focus on ileal orthotopic bladder substitute (OBS. We summarise efforts to minimize morbidity and mortality including enhanced recovery as well as early and late complications seen after radical cystectomy and OBS. Centralisation of complex cancer services in the UK has led to a fall in mortality and high volume institutions have a significantly lower rate of 30-day mortality compared to low volume institutions. Enhanced recovery pathways have resulted in shorter length of hospital stay and potentially a reduction in morbidity. Early complications of radical cystectomy occur as a direct result of the surgery itself while late complications, which can occur even after 10 years after surgery, are due to urinary diversion. OBS represents the ideal urinary diversion for patients without contraindications. However, all patients with OBS should have regular long term follow-up for oncological surveillance and to identify complications should they arise.

Estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract of female rats upon colon-bladder cross-sensitization.

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Xiao-Qing Pan

Full Text Available Co-morbidity of bladder, bowel, and non-specific pelvic pain symptoms is highly prevalent in women. Little evidence is present on modulation of pelvic pain syndromes by sex hormones, therefore, the objective of this study was to clarify the effects of hormonal fluctuations within the estrous cycle on regulatory neuropeptides in female rats using a model of neurogenic bladder dysfunction. The estrous cycle in female rats (Sprague-Dawley, 230-250 g was assessed by vaginal smears and weight of uterine horns. Neurogenic bladder dysfunction was induced by a single inflammatory insult to the distal colon. Protein expression of calcitonin gene related peptide (CGRP, substance P (SP, nerve growth factor (NGF, and brain derived neurotrophic factor (BDNF in the pelvic organs, sensory ganglia and lumbosacral spinal cord was compared in rats in proestrus (high estrogen vs diestrus (low estrogen. Under normal physiological conditions, concentration of SP and CGRP was similar in the distal colon and urinary bladder during all phases of the estrous cycle, however, acute colitis induced a significant up-regulation of CGRP content in the colon (by 63% and urinary bladder (by 54%, p≤0.05 to control of rats in proestrus. These changes were accompanied by a significant diminution of CGRP content in L6-S2 DRG after colonic treatment, likely associated with its release in the periphery. In rats with high estrogen at the time of testing (proestrus, experimental colitis caused a significant up-regulation of BDNF colonic content from 26.1±8.5 pg/ml to 83.4±32.5 pg/ml (N = 7, p≤0.05 to control and also induced similar effects on BDNF in the urinary bladder which was also up-regulated by 5-fold in rats in proestrus (p≤0.05 to respective control. Our results demonstrate estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract upon colon-bladder cross-sensitization, which may contribute to pain fluctuations in female patients

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

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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

Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

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Ailan Zhang

Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

DMAV in Drinking Water Activated NF-κB Signal Pathway and Increased TGF-β and IL-1β Expressions in Bladder Epithelial Cells of Rats

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Siqi Cao

2015-01-01

Full Text Available Dimethylarsinic acid (DMAV is the main product of arsenic methylation metabolism in vivo and is rat bladder carcinogen and tumor promoting agent. In this study, we measured the expressions of mRNA and proteins of NF-κB pathway members, IKKα, IKKβ, p65, and p50 in rat bladder epithelium by qRT-PCR and immunohistochemical analysis after rats received drinking water containing 100 and 200 ppm DMAV for 10 weeks. Transforming growth factor-β (TGF-β immunoexpression in rat bladder epithelium and urine level of IL-1β also were determined. We found that DMAV dramatically increased the mRNA levels of NF-κB p50 and IKKα in the bladder epithelium of rats compared to the control group. Immunohistochemical examinations showed that DMAV increased immunoreactivities of IKKα, IKKβ, and phospho-NF-κB p50 in the cytoplasm and phospho-NF-κB p50 and p65 in nucleus of rat urothelial cells. In addition, DMAV treated rats exhibited significantly increased inflammatory factor TGF-β immunoreactivity in bladder epithelium and IL-1β secretion in urine. These data suggest that DMAV could activate NF-κB signal pathway and increase TGF-β and IL-1β expressions in bladder epithelial cells of rats.

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

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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.

Effects of pudendal neuromodulation on bladder function in chronic spinal cord-injured rats

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Yin-Tsong Lin

2016-09-01

Conclusion: This study demonstrates the feasibility of using pudendal neuromodulation in chronic SCI rats. These results could aid in developing an advanced neural prosthesis to restore bladder function in clinical settings.

Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

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Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

2016-09-01

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

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Huang FYJ

2015-01-01

Full Text Available Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc showed a high relationship between cell number and its bioluminescent intensity (R2=0.99 in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05. As a result, the

Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

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de Fraga, Rogerio; Palma, Paulo; Dambros, Miriam; Riccetto, Cassio L Z; Mandarim-de-Lacerda, Carlos; Miyaoka, Ricardo

2009-05-01

The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17β-estradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers. Long-term estrogen deprivation caused significant changes in bladder innervations, which can be characterized by a decreased number of nerve fibers by 65% (p < 0.001).

Omega-3 Fatty Acids Inhibit Tumor Growth in a Rat Model of Bladder Cancer

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Belmiro Parada

2013-01-01

Full Text Available Omega-3 (ω-3 fatty acids have been tested on prevention and treatment of several cancer types, but the efficacy on “in vivo” bladder cancer has not been analyzed yet. This study aimed at evaluating the chemopreventive efficacy of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA mixture in an animal model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups during a 20-week protocol: control; carcinogen—N-butyl-N-(4-hydroxybutyl nitrosamine (BBN; ω-3 (DHA + EPA; and ω-3 + BBN. BBN and ω-3 were given during the initial 8 weeks. At week 20 blood and bladder were collected and checked for the presence of urothelium lesions and tumors, markers of inflammation, proliferation, and redox status. Incidence of bladder carcinoma was, control (0%, ω-3 (0%, BBN (65%, and ω-3 + BBN (62.5%. The ω-3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume was significantly reduced compared to the BBN (0.9 ± 0.1 mm3 versus 112.5 ± 6.4 mm3. Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP, TGF-β1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit the development of premalignant and malignant lesions in a rat model of bladder cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties.

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

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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.

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Parag N Gad

Full Text Available 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.

Analgesic effect of ADX71441, a positive allosteric modulator (PAM) of GABAB receptor in a rat model of bladder pain.

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Kannampalli, Pradeep; Poli, Sonia-Maria; Boléa, Christelle; Sengupta, Jyoti N

2017-11-01

Therapeutic use of GABA B receptor agonists for conditions like chronic abdominal pain, overactive bladder (OAB) and gastroesophageal reflux disease (GERD) is severely affected by poor blood-brain barrier permeability and potential side effects. ADX71441 is a novel positive allosteric modulator (PAM) of the GABA B receptor that has shown encouraging results in pre-clinical models of anxiety, pain, OAB and alcohol addiction. The present study investigates the analgesic effect of ADX71441 to noxious stimulation of the urinary bladder and colon in rats. In female Sprague-Dawley rats, systemic (i.p), but not intrathecal (i.t), administration of ADX71441 produced a dose-dependent decrease in viscero-motor response (VMR) to graded urinary bladder distension (UBD) and colorectal distension (CRD). Additionally, intra-cerebroventricular (i.c.v.) administration of ADX71441 significantly decreased the VMRs to noxious UBD. In electrophysiology experiments, the drug did not attenuate the responses of UBD-sensitive pelvic nerve afferent (PNA) fibers to UBD. In contrast, ADX71441 significantly decreased the responses of UBD-responsive lumbosacral (LS) spinal neurons in spinal intact rats. However, ADX71441 did not attenuate these LS neurons in cervical (C1-C2) spinal transected rats. During cystometrogram (CMG) recordings, ADX71441 (i.p.) significantly decreased the VMR to slow infusion without affecting the number of voiding contraction. These results indicate that ADX71441 modulate bladder nociception via its effect at the supra-spinal sites without affecting the normal bladder motility and micturition reflex in naïve adult rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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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 (PD bladder strips, were statistically significant (PD-treated strips, as a significant reduction (PD) 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.

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

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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 low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model.

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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.

Activation of muscarinic M-1 cholinoceptors by curcumin to increase contractility in urinary bladder isolated from Wistar rats.

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Cheng, Tse-Chou; Lu, Chih-Cheng; Chung, Hsien-Hui; Hsu, Chih-Chieh; Kakizawa, Nozomi; Yamada, Shizuo; Cheng, Juei-Tang

2010-04-05

Curcumin is an active principle contained in rhizome of Curcuma longa, and it has been recently mentioned to show affinity to muscarinic M-1 cholinoceptors (M(1)-mAChR). In the present study, we found that curcumin caused a concentration-dependent increase of muscle tone in urinary bladder isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block M(1)-mAChR. In radioligand-binding assay, specific binding of [(3)H]-oxotremorine (OXO-M) in the rat bladder homogenates was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PKC pathway, either U73122 (phospholipase C inhibitor) or chelerythrine (protein kinase C inhibitor), curcumin-stimulated contraction in urinary bladder was markedly reduced. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals to increase of muscle tone in urinary bladder through PLC-PKC pathway.

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

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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

Cyclophosphamide-induced cystitis reduces ASIC channel but enhances TRPV1 receptor function in rat bladder sensory neurons.

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Dang, Khoa; Bielefeldt, Klaus; Gebhart, G F

2013-07-01

Using patch-clamp techniques, we studied the plasticity of acid-sensing ion channels (ASIC) and transient receptor potential V1 (TRPV1) channel function in dorsal root ganglia (DRG) neurons retrogradely labeled from the bladder. Saline (control) or cyclophosphamide (CYP) was given intraperitoneally on days 1, 3, and 5. On day 6, lumbosacral (LS, L6-S2) or thoracolumbar (TL, T13-L2) DRG were removed and dissociated. Bladders and bladder DRG neurons from CYP-treated rats showed signs of inflammation (greater myeloperoxidase activity; lower intramuscular wall pH) and increased size (whole cell capacitance), respectively, compared with controls. Most bladder neurons (>90%) responded to protons and capsaicin. Protons produced multiphasic currents with distinct kinetics, whereas capsaicin always triggered a sustained response. The TRPV1 receptor antagonist A-425619 abolished capsaicin-triggered currents and raised the threshold of heat-activated currents. Prolonged exposure to an acidic environment (pH range: 7.2 to 6.6) inhibited proton-evoked currents, potentiated the capsaicin-evoked current, and reduced the threshold of heat-activated currents in LS and TL bladder neurons. CYP treatment reduced density but not kinetics of all current components triggered by pH 5. In contrast, CYP-treatment was associated with an increased current density in response to capsaicin in LS and TL bladder neurons. Correspondingly, heat triggered current at a significantly lower temperature in bladder neurons from CYP-treated rats compared with controls. These results reveal that cystitis differentially affects TRPV1- and ASIC-mediated currents in both bladder sensory pathways. Acidification of the bladder wall during inflammation may contribute to changes in nociceptive transmission mediated through the TRPV1 receptor, suggesting a role for TRPV1 in hypersensitivity associated with cystitis.

The role of urinary pH in o-phenylphenol-induced cytotoxicity and chromosomal damage in the bladders of F344 rats.

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Balakrishnan, S; Hasegawa, L; Eastmond, D A

2016-04-01

o-Phenylphenol (OPP) is a widely used fungicide and antibacterial agent that at high doses has been shown to cause bladder cancer in male F344 rats. The mechanisms underlying OPP-induced bladder carcinogenicity remain unclear but it has been proposed that a non-enzymatic pH-dependent autoxidation of phenylhydroquinone (PHQ), a primary metabolite of OPP, may be a key step in OPP-induced rat bladder carcinogenesis. To investigate this mechanism and to provide insights into the potential human health relevance of OPP-induced cancer, a series of in vitro and in vivo experiments were conducted. In human lymphoblastoid TK-6 cells and rat bladder epithelial NBT-II cells, strong increases in cytotoxicity were seen at a constant concentration of PHQ by increasing the buffer pH as well as by increasing concentrations of PHQ at a constant pH. In in vivo studies, male rats were administered OPP (4,000 and 8,000 ppm) in a diet supplemented with either 1% ammonium chloride or 3% sodium bicarbonate to produce acidic and alkaline urinary pH, respectively. Significant increases in cell proliferation as detected by 5-bromo-2'-deoxyuridine incorporation and micronucleus formation were seen in the bladder cells of OPP-treated rats with neutral or alkaline urinary pH but not in animals with the acidified urine. The results from these in vitro and in vivo studies provide support for the autoxidation hypothesis of bioactivation, and provide additional evidence that urinary pH can significantly influence the genotoxicity and carcinogenicity of this important agent. © 2016 Wiley Periodicals, Inc.

Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

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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.

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

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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.

Effect of short-term outlet obstruction on rat bladder nerve density and contractility

NARCIS (Netherlands)

Barendrecht, M. M.; Chichester, P.; Michel, M. C.; Levin, R. M.

2007-01-01

1 The present study was designed to investigate the relationship between innervation density and contractile responses to field stimulation and exogenous agonists at early time points after induction of bladder outlet obstruction (BOO) in rats. 2 When compared with sham-operated animals, 1, 3 and 7

Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in bladder ischemia-reperfusion injury in rats.

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Yucel, Mehmet; Kucuk, Aysegul; Bayraktar, Aslihan Cavunt; Tosun, Murat; Yalcinkaya, Soner; Hatipoglu, Namik Kemal; Erkasap, Nilufer; Kavutcu, Mustafa

2013-10-01

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia-reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p effects on ischemia/reperfusion stress related bladder tissue destruction.

Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.

OpenAIRE

Shakirova, Yulia; Swärd, Karl; Uvelius, Bengt; Ekman, Mari

2010-01-01

Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6weeks cause...

Estimation of Tumor Volumes by 11C-MeAIB and 18F-FDG PET in an Orthotopic Glioblastoma Rat Model

DEFF Research Database (Denmark)

Halle, Bo; Thisgaard, Helge; Hvidsten, Svend

2015-01-01

starting immediately after the injection of 11C-methylaminoisobutyric acid (11C-MeAIB). One hour later, 18F-FDG was injected, followed by a 3-h dynamic PET scan. Images were reconstructed using 2-dimensional ordered-subsets expectation maximization and 3-dimensional maximum a posteriori probability (MAP3D......UNLABELLED: Brain tumor volume assessment is a major challenge. Molecular imaging using PET may be a promising option because it reflects the biologically active cells. We compared the agreement between PET- and histology-derived tumor volumes in an orthotopic glioblastoma rat model...... with a noninfiltrating (U87MG) and an infiltrating (T87) tumor phenotype using 2 different radiotracers, 2 different image reconstruction algorithms, parametric imaging, and 2 different image segmentation techniques. METHODS: Rats with U87MG- and T87-derived glioblastomas were continuously scanned with PET for 1 h...

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

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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.

Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

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Martin B. Oleksiewicz

2008-01-01

Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

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Cheng, Fangzhou; Birder, Lori A; Kullmann, F Aura; Hornsby, Jack; Watton, Paul N; Watkins, Simon; Thompson, Mark; Robertson, Anne M

2018-04-01

In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

Can Spinal Bupivacaine Analgesia Treatment Make a Difference on Urinary Bladder Healing According to the Intramuscular Pethidine Analgesia Treatment in Rats?

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Yeswim Senayli

2007-01-01

Full Text Available We designed a study to compare the healing levels found with intramuscular pethidine with those found with intrathecal local anesthetic treatments. The urinary bladder is suggested to be the most useful tissue in the evaluation of the effects of the drugs. Nineteen male, Sprague-Dawley rats weighing 200–300 g were used in this study. A sagittal section was made in the urinary bladder after suitable anesthesia and laparotomy. Bladders were closed with 5-0 plain catguts 5 min later. There were nine rats in the control group and pethidine (0.5 g/kg was administered intramuscularly in the gluteal muscle region to treat pain after the operations. There were 11 rats in the study group and each received a spinal injection of 0.25% bupivacaine after the operation. Rats were followed for 7 days to define pain. Specimens, particularly the incised region of the bladder, were evaluated for inflammation and fibrosis. Grading scales were used for this purpose. Statistical analyses of the data were performed using the Chi-square test. Statistical analyses were nonsignificant for inflammation (p ≤ 0.151 and nonsignificant for fibrosis (p ≤ 0.105. The treatments may have the same effects on organ healing mechanisms. Statistical difference is not shown in this study, but use of other combinations of pain treatments to evaluate the healing may demonstrate which of these possibilities is true.

Anti-oxidant activity and attenuation of bladder hyperactivity by the flavonoid compound kaempferol.

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Huang, Yaw-Bin; Lin, Ming-Wei; Chao, Yun; Huang, Chi-Te; Tsai, Yi-Hung; Wu, Pao-Chu

2014-01-01

To evaluate the anti-oxidant activity of the flavonoid compound, kaempferol, and to examine its role in the suppression of oxidative stress and attenuation of bladder hyperactivity in a rat model of bladder injury. The anti-oxidative activity of kaempferol was examined in lipopolysaccharide-treated RAW264.7 macrophages by using flow cytometry. For in vivo studies, rats were pretreated with kaempferol or vehicle for 24 h. The rat urothelium was injured by the administration of protamine sulfate for 1.5 h and irritated by the subsequent infusion of potassium chloride for 4 h. Oxidative stress in the bladder tissue was assessed using chemiluminescence assay, and the bladder pressure was determination by cystomertrogram. Kaempferol significantly suppressed lipopolysaccharide-induced reactive oxygen species production in RAW264.7 rat macrophages. Exposure of the rat bladder to sequential infusion of protamine sulfate and potassium chloride induced bladder hyperactivity. Pretreatment with kaempferol, prevented the formation of reactive oxygen species and prolonged the intercontraction interval. Kaempferol suppresses oxidative stress and attenuates bladder hyperactivity caused by potassium chloride after protamine sulfate-induced bladder injury. © 2013 The Japanese Urological Association.

Modification of N-Methyl-N-Nitrosourea initiated bladder carcinogenesis in Wistar rats by terephthalic acid

International Nuclear Information System (INIS)

Cui Lunbiao; Shi Yuan; Dai Guidong; Pan Hongxin; Chen Jianfeng; Song Ling; Wang Shouling; Chang, Hebron C.; Sheng Hongbing; Wang Xinru

2006-01-01

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis

Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

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José Sereno

2010-01-01

Full Text Available To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL, on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl nitrosamine (BBN, CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P, and curative CEL (BBN+CEL-C groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%, BBN 13/20(65%, CEL 0/8(0%, CEL+BBN-P 1/8(12.5%, and BBN+CEL-C 6/8(75%. The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.

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

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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.

Molecular fingerprint of high fat diet induced urinary bladder metabolic dysfunction in a rat model.

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Andreas Oberbach

Full Text Available AIMS/HYPOTHESIS: Diabetic voiding dysfunction has been reported in epidemiological dimension of individuals with diabetes mellitus. Animal models might provide new insights into the molecular mechanisms of this dysfunction to facilitate early diagnosis and to identify new drug targets for therapeutic interventions. METHODS: Thirty male Sprague-Dawley rats received either chow or high-fat diet for eleven weeks. Proteomic alterations were comparatively monitored in both groups to discover a molecular fingerprinting of the urinary bladder remodelling/dysfunction. Results were validated by ELISA, Western blotting and immunohistology. RESULTS: In the proteome analysis 383 proteins were identified and canonical pathway analysis revealed a significant up-regulation of acute phase reaction, hypoxia, glycolysis, β-oxidation, and proteins related to mitochondrial dysfunction in high-fat diet rats. In contrast, calcium signalling, cytoskeletal proteins, calpain, 14-3-3η and eNOS signalling were down-regulated in this group. Interestingly, we found increased ubiquitin proteasome activity in the high-fat diet group that might explain the significant down-regulation of eNOS, 14-3-3η and calpain. CONCLUSIONS/INTERPRETATION: Thus, high-fat diet is sufficient to induce significant remodelling of the urinary bladder and alterations of the molecular fingerprint. Our findings give new insights into obesity related bladder dysfunction and identified proteins that may indicate novel pathophysiological mechanisms and therefore constitute new drug targets.

Effects of Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] on the urinary bladder of male Wistar rats

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Nascimento, Merielen Garcia; Cotrim Sartor de Oliveira, Maria Luiza; Lima, Adriano Silva; Camargo, Joao Lauro Viana de

2006-01-01

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide widely used on agricultural crops such as soy, cotton and sugar cane. In a previous long-term study this herbicide exerted carcinogenic activity on the urinary bladder mucosa of male Wistar rats. In general, the genotoxic and mutagenic potentials of Diuron are considered to be negative. The present study aimed to evaluate the mode of action of Diuron on the urinary bladder mucosa of male Wistar rats. Six-week old male Wistar rats were fed pelleted Nuvilab diet mixed with Diuron at 125, 500 and 2500 ppm. As a positive control, 8.3% sodium saccharin (NaS) was fed in the diet. Preceding the sacrifice of the animals at the 20th week, urinary pH was measured and the genotoxic potential of Diuron was evaluated by the comet assay. Histological urothelial lesions in the urinary bladder and in the renal pelvis mucosa, cell proliferation/apoptosis evaluations, and scanning electron microscopy (SEM) of the urinary bladder mucosa were also performed. No DNA changes were found in urothelial or peripheral blood cells, and urinary pH was comparable to controls in all Diuron groups. In the urinary bladder urothelium, the incidence of simple hyperplasia (SH) by light microscopy was significantly increased (7/10; p < 0.005) in the 2500 ppm Diuron group but not at the lower doses. By SEM, three of five animals treated with 2500 ppm Diuron showed urothelial cell necrosis and hyperplasia. In the renal pelvis, the incidence of SH was significantly increased in the Diuron 500 and 2500 ppm and in the NaS 8.3% groups. Cell proliferation was significantly increased in the Diuron 2500 ppm (p < 0.05) and NaS 8.3% (p < 0.05) groups. The results indicate that a high dietary concentration of Diuron is associated with urothelial necrosis and continuous regenerative cell proliferation that leads to urothelial hyperplasia

Suppression of progranulin expression inhibits bladder cancer growth and sensitizes cancer cells to cisplatin.

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Buraschi, Simone; Xu, Shi-Qiong; Stefanello, Manuela; Moskalev, Igor; Morcavallo, Alaide; Genua, Marco; Tanimoto, Ryuta; Birbe, Ruth; Peiper, Stephen C; Gomella, Leonard G; Belfiore, Antonino; Black, Peter C; Iozzo, Renato V; Morrione, Andrea

2016-06-28

We have recently demonstrated a critical role for progranulin in bladder cancer. Progranulin contributes, as an autocrine growth factor, to the transformed phenotype by modulating Akt-and MAPK-driven motility, invasion and anchorage-independent growth. Progranulin also induces F-actin remodeling by interacting with the F-actin binding protein drebrin. In addition, progranulin is overexpressed in invasive bladder cancer compared to normal tissue controls, suggesting that progranulin might play a key role in driving the transition to the invasive phenotype of urothelial cancer. However, it is not established whether targeting progranulin could have therapeutic effects on bladder cancer. In this study, we stably depleted urothelial cancer cells of endogenous progranulin by shRNA approaches and determined that progranulin depletion severely inhibited the ability of tumorigenic urothelial cancer cells to migrate, invade and grow in anchorage-independency. We further demonstrate that progranulin expression is critical for tumor growth in vivo, in both xenograft and orthotopic tumor models. Notably, progranulin levels correlated with response to cisplatin treatment and were upregulated in bladder tumors. Our data indicate that progranulin may constitute a novel target for therapeutic intervention in bladder tumors. In addition, progranulin may serve as a novel biomarker for bladder cancer.

Blebbistain, a myosin II inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstruction.

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Xinhua Zhang

Full Text Available Partial bladder outlet obstruction (PBOO, a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB and is associated with detrusor overactivity (DO. PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM and reports suggest varied BLEB efficacy for different SM myosin (SMM isoforms and/or SMM vs nonmuscle myosin (NMM. We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC alternatively spliced isoform SM-A (associated with tonic-type SM increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20% only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable

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

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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

Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat.

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Saito, Motoaki; Shimizu, Shogo; Ohmasa, Fumiya; Oikawa, Ryo; Tsounapi, Panagiota; Dimitriadis, Fotios; Kinoshita, Yukako; Satoh, Keisuke

2013-04-01

As increasing evidence suggest that α(1)-blockers prevent benign prostatic hyperplasia related overactive bladder and nocturia in the human, we investigated the effects of silodosin and naftopidil on hypertension-related bladder dysfunction in the spontaneously hypertensive rat (SHR) model. Twelve-week-old male SHRs received no treatment or treatment with silodosin (100 µg/kg, p.o.) or naftopidil (10 or 30 mg/kg, p.o.) once daily for 6 weeks. Wistar rats were used as normotensive controls. After 6-week treatment, voiding functions were estimated by metabolic cages (dark- and light-cycle separately) and cystometric studies. Furthermore, the bladder blood flow (BBF) was measured employing the hydrogen clearance method. SHRs showed significant increases in micturition frequency, and decreases in BBF and single voided volume in both metabolic cages and cystometrograms compared to the Wistar group. Treatment with silodosin normalized the decreased BBF, and treatment with naftopidil increased the BBF in a dose-dependent manner in the SHR group. Although treatment with silodosin and the high dose of naftopidil significantly inhibited micturition frequency in one day, only treatment with the high dose of naftopidil significantly inhibited micturition frequency and urine production in the light-cycle compared to the non-treated SHRs. Although treatment with silodosin and the high dose of naftopidil significantly increased single voided volume, only treatment with silodosin significantly inhibited non-voiding contractions in the cystometrgrams. Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production. Copyright © 2012 Wiley Periodicals, Inc.

Effects of combined treatment of tadalafil and tamsulosin on bladder dysfunction via the inhibition of afferent nerve activities in a rat model of bladder outlet obstruction.

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Furuta, Akira; Suzuki, Yasuyuki; Igarashi, Taro; Koike, Yusuke; Egawa, Shin; Yoshimura, Naoki

2018-03-08

To investigate the effects of combined treatment of tadalafil (a phosphodiesterase-5 inhibitor) and tamsulosin (an α 1 -adrenoceptor antagonist) on bladder dysfunction in a rat model of bladder outlet obstruction (BOO). Cystometry was performed in conscious female BOO rats 6 weeks after partially ligation of the urethra. Either tadalafil (0.03, 0.1 and 0.3 mg/kg) or tamsulosin (0.001, 0.003 and 0.01 mg/kg) was cumulatively applied intravenously at 30-min intervals to examine changes in cystometric parameters and blood pressures. Changes in cystometric parameters and blood pressures were also checked when tadalafil (0.3 mg/kg), tamsulosin (0.003 mg/kg) or both were intravenously applied. In BOO rats, application of either tadalafil (0.3 mg/kg) or tamsulosin (0.003, 0.01 mg/kg) alone significantly increased threshold pressures and intercontraction intervals whereas there were no significant changes in other cystometric parameters. In addition, because a significant reduction in blood pressures was detected after the administration of tamsulosin (0.01 mg/kg), tamsulosin at a lower dose (0.003 mg/kg) was used for the combined treatment. The combination therapy of tadalafil and tamsulosin induced a significantly larger rate of increase in intercontraction intervals (1.7 times) compared with monotherapy of either drug (1.3 times each) although the combined therapy did not affect blood pressures. These results suggest that the combination therapy of tadalafil and tamsulosin can induce the additive inhibitory effects on urinary frequency compared with monotherapy, more likely via inhibition of the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressures and intercontraction intervals without affecting bladder contractile function.

Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

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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

Transcriptional profile of diuron-induced toxicity on the urinary bladder of male Wistar rats to inform mode of action.

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Ihlaseh, Shadia M; Bailey, Kathryn A; Hester, Susan D; Jones, Carlton; Ren, Hongzu; Cardoso, Ana Paula F; Oliveira, Maria Luiza C S; Wolf, Douglas C; de Camargo, João Lauro V

2011-08-01

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. The present study evaluated the dose-dependent effects of mucosal alterations and transcriptional changes in the urinary bladder of rats exposed to diuron. Six-week-old male Wistar rats were treated with 0, 60, 125, 1250, and 2500 ppm of diuron in the diet for 20 weeks. Histologic examination showed urothelial hyperplasia present in rats treated with either 1250 or 2500 ppm of diuron but not 60 or 125 ppm. Comprehensive gene expression analyses of urothelial cell RNA were conducted using Affymetrix microarrays. The numbers of differentially expressed transcripts between each treatment group and control increased with diuron dose. Based on similar histology and gene expression responses, the treatment groups were regrouped into a high-dose (1250 and 2500 ppm) and low-dose group (60 and 125 ppm). These data suggest that persistent exposure to high dietary concentrations of diuron induces oxidative stress, increases cellular metabolism, and enhances cell death that is associated with sustained urothelial hyperplasia.

Detection of bladder tumors using optical coherence tomography

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Pan, Yingtian; Xie, Tuqiang; Wang, Zhenguo

2004-07-01

This paper summarizes the engineering development of our lab for endoscopic optical coherence tomography toward the ultimate goal to image bladder micro architecture and to diagnose bladder cancers. To test the utility and potential limitations of OCT setups for bladder tumor diagnosis, we used a rat bladder cancer model to track the morphological changes following tumor growth. Image results are presented, suggesting that OCT is able to differentiate cancerous lesions from inflammatory lesions based on OCT characterizations of epithelial thickness and backscattering changes of bladder tissue.

Effect of diabetes on the ion pumps of the bladder.

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Mustafa, Seham

2013-01-01

To establish whether the activities of Na+/K+-adenosine triphosphatase (ATPase) and Ca2+-ATPases ion pumps in bladder smooth muscle are altered as a consequence of diabetes and, if so, how this might contribute to bladder cystopathy. Urinary bladder dysfunction is a common occurrence in patients with diabetes. Pressure generation requires calcium and cytosolic ATP. Activities of these pumps are responsible for calcium homeostasis. Rat urinary detrusor muscle strips were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to the Na+/K+-ATPase pump inhibitor, ouabain, the plasma membrane Ca2+ ATPase inhibitor, vanadate, and the sarcoplasmic reticulum Ca2+ ATPase inhibitor, cyclopiazonic acid (CPA), were examined from normal and streptozocin-induced diabetic rats for 2, 4, and 12 weeks. Ouabain, vanadate, and CPA caused concentration-dependent contractions of bladder strips from diabetic and normal rats. The degree of contraction of diabetic bladder muscle was lower than that of controls. This reduction was a function of duration of diabetes. For ouabain, the reduction peaked at 2 weeks, with partial restoration to normal after diabetes induction. For vanadate and CPA, the reduction increased with the duration of diabetes. The ion pumps are important modulators of bladder smooth muscle tone, and in a rat model of streptozotocin-induced diabetes, the activity of these pumps is impaired. Although this is only a single model of diabetes, these findings suggest that a defect in these pumps may be an important component of the development of diabetic bladder cystopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

An animal model for the neuromodulation of neurogenic bladder dysfunction.

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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.

AB286. SPR-13 Sex differences and participation of Toll-like receptor 4 to rat bladder contractile function

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Szasz, Theodora; Burgess, Beth; Webb, R. Clinton

2016-01-01

Objective Innate immune mechanisms have been implicated in the pathophysiology of chronic sterile conditions such as hypertension and diabetes. We have recently demonstrated that Toll-like receptor 4 (TLR4) activation by endogenous molecules such as high mobility group box-1 (HMGB1) contributes to hypertrophy and hypercontractility in diabetic bladder dysfunction. It has been reported that women have a higher frequency of overactive bladder symptoms, while men have higher detrusor overactivity. We hypothesized that sex differences in the contribution of TLR4 to bladder contraction may underlie the sex differences observed clinically. Methods Female and male rat bladder contractile responses to carbacholine (CCh) and electrical field stimulation (EFS) were measured in the presence and absence of TLR4 inhibitor CLI-095 and in the presence and absence of urothelium. Results We observed that contractile responses to both CCh and EFS were higher in the male than the female bladder segments in both the presence and absence of urothelium [CCh Emax (mN): male + urothelium =84.3±1.2, male – urothelium =83.7±1.2, female + urothelium =49.8±0.8, female – urothelium =59.2±1.1; EFS 32 Hz (mN): male + urothelium= 84.9±7.1, male – urothelium =66.8±5.2, female + urothelium =57.8±5.9, female – urothelium =54.5±3.5]. Incubation of bladder segments with the TLR4 inhibitor CLI-095 significantly decreased contractile responses to both CCh and EFS in both sexes, irrespective of the presence of urothelium [CCh Emax (mN): male + urothelium =91.1±0.8, male – urothelium =75.4±1.8, female + urothelium =42.9±1.1, female – urothelium =52.5±1.1; EFS 32 Hz (mN): male + urothelium =80.8±7.9, male – urothelium =59.6±10.6, female + urothelium =43.3±2.6, female – urothelium =46.4±1.9]. Conclusions Our data suggest that although there are sex differences in the contractile function of the rat bladder in basal conditions, the participation of TLR4 to bladder contraction

Role of Nicotinic Acetylcholine Receptor α3 and α7 Subunits in Detrusor Overactivity Induced by Partial Bladder Outlet Obstruction in Rats

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Hyo Sin Kim

2015-03-01

Full Text Available Purpose: To investigate the role of α3 and α7 nicotinic acetylcholine receptor subunits (nAChRs in the bladder, using a rat model with detrusor overactivity induced by partial bladder outlet obstruction (BOO. Methods: Forty Sprague-Dawley rats were used: 10 were sham-operated (control group and 30 were observed for 3 weeks after partial BOO. BOO-induced rats were further divided into 3 groups: Two groups of 10 rats each received intravesicular infusions with hexamethonium (HM group; n=10 or methyllycaconitine (MLC group; n=10, which are antagonists for α3 and α7 nAChRs, respectively. The remaining BOO-induced rats received only saline infusion (BOO group; n=10. Based on the contraction interval measurements using cystometrogram, the contraction pressure and nonvoiding bladder contractions were compared between the control and the three BOO-induced groups. Immunofluorescent staining and Western blotting were used to analyze α3 and α7 nAChRs levels. Results: The contraction interval of the MLC group was higher than that of the BOO group (P<0.05. Nonvoiding bladder contraction almost disappeared in the HM and MLC groups. Contraction pressure increased in the BOO group (P<0.05 compared with the control group and decreased in the HM and MLC groups compared with the BOO group (P<0.05. Immunofluorescence staining showed that the α3 nAChR signals increased in the urothelium, and the α7 nAChR signals increased in the urothelium and detrusor muscle of the BOO group compared with the control group. Western blot analysis showed that both α3 and α7 nAChR levels increased in the BOO group (P<0.05. Conclusions: Alpha3 and α7 nAChRs are associated with detrusor overactivity induced by BOO. Furthermore, nAChR antagonists could help in clinically improving detrusor overactivity.

Fluoride absorption from the rat urinary bladder: a pH-dependent event

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Whitford, G.M.; Pashley, D.H.; Reynolds, K.E.

1977-01-01

Urinary bladder absorption of stable and radiofluoride was studied as a function of pH in anesthetized rats to further evaluate the influence of pH gradients on fluoride transport. Buffered pH values and stable fluoride concentrations ranged from 1.85 to 7.90 and from 0.012 to 8.81 mM, respectively. [ 14 C]inulin served as a marker for solute concentration changes due to water migration or dilution. The results indicate that bladder fluoride absorption is inversely related to pH over the 1.85 to 5.50 range. Mean, 15-min radiofluoride absorption values of 70 percent at pH 1.85, 37 percent at pH 3.95, and 5 percent at pH 5.50 were observed. These fractional absorption values were not significantly influenced by carrier fluoride concentration, the buffers used, or the presence of urine. Above pH 5.50, pH-independent absorption occurs to a slight extent. The results are consistent with a first-order absorptive process which occurs by the nonionic diffusion of hydrogen fluoride

Primary Signet-Ring Cell Carcinoma of the Urinary Bladder Successfully Managed with Radical Cystectomy in a Young Patient

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Farzad Allameh

2017-01-01

Full Text Available Primary signet-ring cell adenocarcinoma of bladder is a rare neoplasm, usually seen in middle age adults. We report the case of an 18-year-old man who presented with intermittent gross hematuria. Computed tomography imaging showed multifilling defects in the bladder. The patient underwent a transurethral resection of the bladder tumor. Histological findings were consistent with poorly differentiated mixed mucinous and signet-ring cell adenocarcinoma. We ruled out other possible origins of tumor by gastrointestinal endoscopy and colonoscopy. The patient was treated with radical cystectomy with prostate and seminal vesicle sparing technique and orthotopic diversion using “W” ileum pouch with pelvic lymphadenectomy to the bifurcation of the aorta was done. Six-month follow-up of patient showed normal conditions without metastatic spread or any recurrence.

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

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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 the chronic bacterial infection in urinary bladder carcinogenesis

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Higgy, N.A.

1985-01-01

The purpose of this thesis was to determine whether or not bacterial infection of the urinary bladder had a role in urinary bladder carcinogenesis. To investigate this proposition, four separate studies were conducted. The first study developed an experimental animal model where bacterial infection of the urinary bladder could be introduced and maintained for a period in excess of one year. The method of infection, inoculation of bacteria (Escherichia coli type 04) subserosally into the vesical wall, successfully caused persistent infection in the majority of animals. In the second study the temporal effects of bacterial infection on the induction of urothelial ornithine decarboxylase (ODC) and 3 H-thymidine uptake and DNA synthesis were examined. Bacterial infection of the urinary bladder induced urothelial ODC with a peak in enzyme activity 6 hr after infection. 3 H-Thymidine uptake and DNA synthesis peaked 48 hr after infection and coincided with the urothelial hyperplasia that occurred in response to the infection. In the third study the specific bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to rats concurrent with the urinary bacterial infection. In the fourth study rats were administered sodium nitrate and either dibutylamine or piperazine in the drinking water. The infected group developed bladder tumors while none were detected in the non-infected rats. From these studies it may be concluded that bacterial infection may have a significant role in the process of urinary bladder carcinogenesis

Urethral orifice hyaluronic acid injections: a novel animal model of bladder outlet obstruction.

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

2015-02-21

We produced a novel model of bladder outlet obstruction (BOO) by periurethral injection of hyaluronic acid and compared the cystometric features, postoperative complications, and histopathological changes of that model with that of traditional open surgery. Forty female Sprague-Dawley rats were divided into three groups. Fifteen rats were subcutaneously injected with 0.2 ml hyaluronic acid at 5, 7, and 12 o'clock around the urethral orifice. Another fifteen rats underwent traditional open partial proximal urethral obstruction surgery, and 10 normal rats used as controls. After 4 weeks, filling cystometry, postoperative complications, and histopathological features were evaluated in each group. Three rats were also observed for 12 weeks after hyaluronic acid injection to evaluate the long-term effect. Hyaluronic acid periurethral injection caused increased maximum cystometric capacity, maximum bladder pressure, micturition interval, and post-void residual urine volume compared with control (p injection group had significantly shorter operative time, less incidence of incision infection and bladder stone formation compared with the surgery group (p injection and surgery bladders; these were not observed in the control group. Bladder weight and thickness of smooth muscle in the injection and surgery groups were significantly greater than those in the control group (p injection or control groups. Rats periurethrally injected hyaluronic acid were stable the compound was not fully absorbed in any rat after 12 weeks. Hyaluronic acid periurethral injection generates a simple, effective, and persistent animal model of BOO with lower complications, compared with traditional surgery.

A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

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Chantal Scheepbouwer

Full Text Available Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.

Impact of complications and bladder cancer stage on quality of life in patients with different types of urinary diversions.

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Prcic, Alden; Aganovic, Damir; Hadziosmanovic, Osman

2013-12-01

Determine correlation between complications and stage of the disease and their impact on quality of life in patients with different types of ileal urinary derivation after radical cystectomy, and upon estimation of acquired results, to suggest the most acceptable type of urinary diversion. In five year period a prospective clinical study was performed on 106 patients, to whom a radical cystectomy was performed due to bladder cancer. Patients were divided into two groups, 66 patients with ileal conduit derivation and 40 patients with orthotopic derivation, whereby in each group a comparison between reflux and anti-reflux technique of orthotopic bladder was made. All patients from both groups filled the Sickness Impact Profile score six months after the operation. All patients had CT urography or Intravenous urography performed, as well as standard laboratory, vitamin B12 blood values, in order to evaluate early (ileus or subileus, wound dehiscence, bladder fistula, rupture of orthotopic bladder, urine extravazation) and late complications (VUR, urethral stricture, ureter stenosis, metabolic acidosis, mineral dis-balance, hypovitaminosis of vitamin B12, increased resorption of bone calcium, urinary infection, kidney damage, relapse of primary disease), so as disease stage and it's impact on quality of life. From gained results we observe that each category of SIP score correlates with different rate of correlation with the type of operation, group, T, N, and R grade, except work category. Average value of SIP score rises depending on the type of operation and T stage. It is notable that there is no difference in T1 stage, no matter the type of operation. So the average value of SIP score in T1 stage for conduit was 20.3, for Abol-Enein and Ghoneim 17.25 and Hautmann 18.75 respectively. Average value of SIP score in T2 stage for conduit was 31, for Abol-Enein and Ghoneim 19.1 and Hautmann 17.8. Average value of SIP score in T3 stage for conduit was 38.03, for Abol

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

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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.

Continuous Flushing of the Bladder in Rodents Reduces Artifacts and Improves Quantification in Molecular Imaging

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Steven Deleye

2014-07-01

Full Text Available In this study, we evaluated the partial volume effect (PVE of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG tracer accumulation in the bladder on the positron emission tomographic (PET image quantification in mice and rats suffering from inflammatory bowel disease. To improve the accuracy, we implemented continuous bladder flushing procedures. Female mice and rats were scanned using microPET/computed tomography (CT at baseline and after induction of acute colitis by injecting 2,4,6-trinitrobenzene sulfonic acid (TNBS intrarectally. During the scans, the bladder was continuously flushed in one group, whereas in the other group, no bladder flushing was performed. As a means of in vivo and ex vivo validation of the inflammation, animals also underwent colonoscopy and were sacrificed for gamma counting (subpopulation and to score the colonic damage both micro- and macroscopically as well as biochemically. At baseline, the microPET signal in the colon of both mice and rats was significantly higher in the nonflushed group compared to the flushed group, caused by the PVE of tracer activity in the bladder. Hence, the colonoscopy and postmortem analyses showed no significant differences at baseline between the flushed and nonflushed animals. TNBS induced significant colonic inflammation, as revealed by colonoscopic and postmortem scores, which was not detected by microPET in the mice without bladder flushing, again because of spillover of bladder activity in the colonic area. MicroPET in bladder-flushed animals did reveal a significant increase in 18F-FDG uptake. Correlations between microPET and colonoscopy, macroscopy, microscopy, and myeloperoxidase yielded higher Spearman rho values in mice with continuously flushed bladders during imaging. Comparable, although somewhat less pronounced, results were shown in the rat. Continuous bladder flushing reduced image artifacts and is mandatory for accurate image quantification in the pelvic region for both mice

Roles of Polyuria and Hyperglycemia on Bladder Dysfunction in Diabetes

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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

The dynamics of the cellular composition of urine sediment in conditions of an artificial bladder

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R. V. Savchuk

2017-10-01

Full Text Available Aim. The evaluation of the urine cytological profile in the dynamics of adaptation of the orthotopic bladder to the functional properties of the urinary reservoir and determination of the connection between the cellular composition of the urine with the functional role of the formed from the intestinal fragment neocyst in experimental conditions and in humans. Materials and methods. The material in experimental study were the results of a cytological study of the urine sediment obtained from 21 female pigs (mini-pigs. The portion of urine had received in experimental animals one month after orthotopic ileocystoplasty, 6 months and 1 year later and prepared as smear from the resulting precipitate. The level of lymphocytes, neutrophils, erythrocytes, as well as the superficial, intermediate and basal epitheliocytes evaluated during study. An analysis of the cell composition of centrifugal smears from the neocyst were performed in 21 patients with bladder cancer undergoing cystectomy and the formation of an orthotopic bladder, at various periods after surgery, from 3 months to 5 years. The preparation of a centrifugal sediment and the subsequent production of smears carried out as well as experimental animals. Results and conclusions. The results of study showed that the formation of an artificial bladder in experimental animals with a fragment of the ileum changes the composition of the cells of the urinary sediment mucosa. These changes consist of an increase in the content of red blood cells, a decrease in the number of lymphocytes and neutrophils and change in the number of epithelial cells. The cellular composition of the sediment changes with the increasing duration of the postoperative period and manifests by reduction and even disappearance of erythrocytes in smears. The level of lymphocytes and neutrophils is close to those observed in intact animals. The content and ratio of epithelial cells also approached to experimental animals. The

Preperitoneal placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction after radical cystoprostatectomy with orthotopic neobladder

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Jung Kwon Kim

2016-09-01

Full Text Available Purpose: To describe a case of safe placement of an inflatable penile prosthesis reservoir for postoperative erectile dysfunction (ED with a history of radical cystoprostatectomy with an orthotopic Studer neobladder. Materials and Methods: A 55-year-old bladder cancer patient, who underwent radical cystoprostatectomy with orthotopic Studer neobladder 2 years prior, suffered from postoperative ED. A 3-piece inflatable penile prosthesis was implanted via a penoscrotal incision. The alternative reservoir placement began with a longitudinal 4-cm incision, which was 2 finger-breaths to the left and lateral to the umbilicus. Thereafter, the anterior and posterior rectus sheaths were dissected and incised. Then, the transversalis fascia entering into the preperitoneal space was incised, followed by circumferential sweeping using the forefinger, and, finally, placement of a 100 mL ‘flat’ reservoir. The reservoir was filled with 65 mL saline and then evaluated for back pressure. The reservoir tubing exited through the defect of the rectus sheaths and tunneled through the abdominal fat into the penoscrotal wound. Results: Total operative time was 105 minutes, and the estimated blood loss was minimal. The patient was discharged at postoperative day 1 and experienced no perioperative complications. At the 6-month follow-up, there was no abdominal bulging from the preperitoneal reservoir, and the reservoir was not palpable. Conclusions: The preperitoneal placement of the flat reservoir at the level of the umbilicus is a safe and acceptable surgical technique for postoperative ED after radical cystoprostatectomy with orthotopic neobladder.

The Effect of Bladder Outlet Obstruction on alpha(1)- and beta-Adrenoceptor Expression and Function

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Barendrecht, Maurits M.; Frazier, Elfaridah P.; Vrydag, Wim; Alewijnse, Astrid E.; Peters, Stephan L. M.; Michel, Martin C.

2009-01-01

Aims: To explore possible changes in expression and/or function of alpha(1)- and beta-adrenoceptor subtypes as a cause for bladder dysfunction in a rat model of bladder outlet obstruction (BOO). Methods: BOO was induced in rats by partial urethral ligature. Contraction and relaxation experiments

Quantitative evaluation of CART-containing cells in urinary bladder of rats with renovascular hypertension

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I. Janiuk

2015-04-01

Full Text Available 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

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

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Masaki Ogoda

2016-05-01

Full Text Available 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-3H]scopolamine methyl chloride ([3H]NMS and αβ-methylene ATP [2,8-3H]tetrasodium salt ([3H]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 [3H]NMS and/or [3H]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.

Orthotopic neobladder reconstrution: postoperative CT appearance, complications and potential pitfalls

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Lee, Su Lim; Jung, Seung Eun; Im, Yeon Soo; Lee, Jae Mun; Lee, Ji Youl; Yoon, Moon Soo; Hahn, Seong Tai [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2003-08-01

To evaluate the postoperative CT appearance, complications and potential pitfalls of radical cystectomy with orthotopic neobladder reconstruction. We examined 46 patients [43 men and 3 women aged 34-72 (mean, 56.7) years] who had undergone neobladder reconstruction (ileocolic neobladder in 25 patients and ileal-W neobladder in 21). The CT scans were assessed in terms of their depiction of normal anatomy, namely the shape, location and internal architecture of the neobladder, the location of bladder bases, and the ureteral course. Early and late complications were also assessed. The characteristics of ileocolic neobadder were a right-side location, a lobulated outer margin, interal projections due to haustra or plication, a base in the retropubis, and right-side insertion of both ureters. In contrast, the characteristics of an ileal-W neobladder were a central location, an ovoid shape, nodular thickening at the ureteral insertion site, internal projections due to plication, and a retropubic bladder base. Early complications included hematoma with abscess formation (n=2), and postoperative peritonitis (n=1), while late complications were hydronephrosis due to stricture ar the ureteral anastomotic site (n=16), tumor recurrence at this site (n=1), distal ureteral stone (n=1), mucus urinary retention (n=1), incisional hernia (n=2), tumor recurrence in the pelvic side wall (n=1), carcinomatosis peritonei (n=1), and liver metastasis (n=2). A knowledge of normal anatomic changes is essential for the accurate interpretation of CT scans. CT is a useful modality of the evaluation of postoperative change and the complications occurring in patients who have undergone radial cystectomy with othotopic neobladder reconstruction.

Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.

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Shakirova, Yulia; Swärd, Karl; Uvelius, Bengt; Ekman, Mari

2010-12-15

Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6 weeks caused a 2.56-fold increase in the number of smooth muscle caveolae per μm membrane. No changes in the expression of caveolin-1 or cavin-1, normalized to β-actin were seen, but membrane area per unit muscle volume dropped to 0.346. Hypertrophy was associated with altered contraction in response to carbachol. The effect on contraction of cholesterol desorption, which disrupts lipid rafts and caveolae, was however not changed. Contraction in response to bradykinin resisted mβcd in control destrusor, but was inhibited by it after 6 weeks of obstruction. It is concluded that rat detrusor hypertrophy leads to an increased number of caveolae per unit membrane area. This change is due to a reduction of membrane area per volume muscle and it does not play a role for cholinergic activation, but promotes contraction in response to bradykinin after long-term obstruction. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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

2009-01-01

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 100 ppm 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.

Real-time bladder volume monitoring by the application of a new implantable bladder volume sensor for a small animal model

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Dong Sup Lee

2011-04-01

Full Text Available Although real-time monitoring of bladder volume together with intravesical pressure can provide more information for understanding the functional changes of the urinary bladder, it still entails difficulties in the accurate prediction of real-time bladder volume in urodynamic studies with small animal models. We studied a new implantable bladder volume monitoring device with eight rats. During cystometry, microelectrodes prepared by the microelectromechanical systems process were placed symmetrically on both lateral walls of the bladder, and the expanded bladder volume was calculated. Immunohistological study was done after 1 week and after 4 weeks to evaluate the biocompatibility of the microelectrode. From the point that infused saline volume into the bladder was higher than 0.6 mL, estimated bladder volume was statistically correlated with the volume of saline injected (p<0.01. Additionally, the microelectromechanical system microelectrodes used in this study showed reliable biocompatibility. Therefore, the device can be used to evaluate changes in bladder volume in studies with small animals, and it may help to provide more information about functional changes in the bladder in laboratory studies. Furthermore, owing to its biocompatibility, the device could be chronically implanted in conscious ambulating animals, thus allowing a novel longitudinal study to be performed for a specific purpose.

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators.

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Hassani, Faezeh Arab; Peh, Wendy Yen Xian; Gammad, Gil Gerald Lasam; Mogan, Roshini Priya; Ng, Tze Kiat; Kuo, Tricia Li Chuen; Ng, Lay Guat; Luu, Percy; Yen, Shih-Cheng; Lee, Chengkuo

2017-11-01

Underactive bladder or detrusor underactivity (DU) is defined as a reduction of contraction strength or duration of the bladder wall. Despite the serious healthcare implications of DU, there are limited solutions for affected individuals. A flexible 3D printed implantable device driven by shape memory alloys (SMA) actuators is presented here for the first time to physically contract the bladder to restore voluntary control of the bladder for individuals suffering from DU. This approach is used initially in benchtop experiments with a rubber balloon acting as a model for the rat bladder to verify its potential for voiding, and that the operating temperatures are safe for the eventual implantation of the device in a rat. The device is then implanted and tested on an anesthetized rat, and a voiding volume of more than 8% is successfully achieved for the SMA-based device without any surgical intervention or drug injection to relax the external sphincter.

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

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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.

A “Proteoglycan Targeting Strategy” for the Scintigraphic Imaging and Monitoring of the Swarm Rat Chondrosarcoma Orthotopic Model

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Caroline Peyrode

2011-01-01

Full Text Available Our lab developed 99mTc-NTP 15-5 radiotracer as targeting proteoglycans (PGs for the scintigraphic imaging of joint. This paper reports preclinical results of 99mTc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC. 99mTc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant 99mTc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14, whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study. 99mTc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology.

Wound repair in rat urinary bladder following electrocautery or holmium laser incision

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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.

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

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de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

The effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rats.

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Gao, Wansheng; He, Xiangfei; Li, Yunlong; Wen, Jianguo

2017-11-07

Immunophilin ligands are neuroregenerative agents binding to FK506 binding proteins, by which stimulate recovery of neurons in a variety of injury nerves. FK1706 is a novel immunophilin ligand which has neuroprotective and neuroregenerative effects but without immunosuppressive activity. At present, most reports about FK1706 in ameliorating nerve injury and functional recovery are limited to cavernous nerve injury and erectile function recovery. This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models. The numbers of regenerated myelinated axons of the pelvic parasympathetic nerve (PPN) in the three groups' rats (FK1706 + ETS, ETS and control groups) were evaluated. Their intravesical pressure (IVP), S100β and growth associated protein 43 (GAP43) expressions were also compared. In FK1706 + ETS group, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value. The average maximum of IVP in FK1706 + ETS group reached 76.3% of the value in control group. Their average number of myelinated axons of regenerated PPN reached 80% of the amount in control group. The nerve regeneration-associated markers data indicated that the expression level of S100β and GAP43 in FK1706 + ETS group was approximately 2-fold higher than that of ETS group (P side neurorrhaphy, FK1706 effectively enhanced the nerve regeneration and bladder function recovery.

Functional and Clinical Outcome of Ileal (Studer) Neo-bladder Reconstruction: Single Centre Experience from Pakistan

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Nazim, S. M.; Ather, M. H.; Abbas, F.

2014-01-01

Objective: To determine the medium and long-term outcome of orthotopic continent urinary diversion with ileal (Studer) neo-bladder following radical cystectomy. Study Design: Case series. Place and Duration of Study: Department of Surgery, The Aga Khan University Hospital, Karachi, from January 1998 to September 2010. Methodology: Thirty eight patients underwent radical cystectomy for invasive bladder tumor with ileal neo-bladder (Studer type) reconstruction. Peri-operative and late complications, functional outcome of neo-bladder, urinary continence, metabolic and upper urinary tract status and overall survival were evaluated in all patients. Results: A total of 29 patients (23 males and 6 females) with mean age of 59 +- 12 years were included for the final analysis. The mean duration of surgery (both radical cystectomy and urinary diversion) was 520 +- 70 minutes. Perioperative complication rate was 24% (n=7) with surgical site infection in 4 patients, sepsis in 1 patient and 2 had ureteroileal leak. At 6 months follow-up, 22 patients were fully continent while 7 patients had minimal stress / nocturnal incontinence. The continence rate was 93% (n=27) at one year follow-up. The mean capacity of neo-bladder at 6 months was 384 +- 66 mLs. The late complication rate was 17% (n=5). Three patients developed anastomotic stricture requiring transurethral incision of neo bladder neck, one formed stone in neo-bladder and one developed incision hernia. All patients had preserved renal functions on follow-up. The survival rate was 80% (n=23) at a median follow-up of 66.4 +- 36 months. Two patients developed local recurrence and four developed distant metastasis. Conclusion: Studer ileal neo-bladder is a safe and effective option for urinary diversion in select patients with good oncological and functional outcomes comparable to contemporary literature, even in a low volume center. (author)

Study of morbidity in orthotopic small intestine transplantation with Wistar rats: experimental study

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LEE André Dong Won

2002-01-01

Full Text Available Background - Transplantation of the small intestine is a surgical procedure currently under investigation for its possible application in the treatment of patients with short bowel syndrome, aiming at the reintroduction of an oral diet. Aim - To define the morbidity and mortality of intestinal transplantation in small animals using microsurgery. Intra and postoperative morbidity and mortality were studied in Wistar rats submitted to orthotopic intestinal allotransplantation. Material and Method - The animals were divided into three groups: group A (37 donor animals, group B (37 recipient animals, and group C (10 control animals. Group B was divided into three subgroups according to survival time. Subgroup TI consisted of animals that died during surgery or due to causes directly related to surgical intervention, subgroup T2 consisted of animals that died between the 4th and 29th postoperative day, and subgroup T3 consisted of animals that survived after 30 days. Transplanted animals were evaluated in terms of surgical technique used (vascular and intestinal anastomosis, graft quality, surgical time, and clinical parameters. The animals that died by the 29th postoperative day were submitted to autopsy and the remaining ones were sacrificed after 30 days. Result - There was a high rate of complication of a surgical nature. Early mortality rate, i.e., mortality up to the third postoperative day, was 54% with vascular anastomosis being the major cause of death. Surgical time was evaluated in a restricted and homogeneous group and showed a strong prognostic value in terms of successful transplantation. Clinical parameters such as weight loss, reduction of ingestion, reduction of motor activity and diarrhea were directly correlated with acute rejection. Conclusion - The experimented intestinal transplant is a procedure companied by considerable morbidity and mortality due to surgical complications in postoperative period, vascular anastomosis and

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

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Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

2018-01-01

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Do diosgenin ameliorate urinary bladder toxic effect of ...

African Journals Online (AJOL)

SWEET

2012-01-26

Jan 26, 2012 ... experimental animal models? ... BSO doses using a Swiss albino mouse model. Toxicity modulation ... bladder inflammation induced by CP in rats and mice .... 0.1 ml NADPH (nicotinamide adenine dinucleotide phosphate.

Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer

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Kim Wun-Jae

2011-04-01

Full Text Available Abstract Background Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis. Results The orthotopic urinary bladder cancer (OUBC model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC. Conclusion VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

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Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

2016-07-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

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

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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...

Evaluation of magnetic fluid hyperthermia (MFH) combined with external radiation in an orthotopic rat model of prostate cancer

International Nuclear Information System (INIS)

Johannsen, M.; Thiesen, B.; Taymoorian, K.; Gneveckow, U.; Waldoefner, N.; Koch, M.; Scholz, R.; Lein, M.; Jung, K.; Loening, S.A.; Jordan, A.

2005-01-01

Full text: Magnetic fluid hyperthermia (MFH) is a new concept of cancer treatment based on AC magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. Preliminary studies of MFH using nanoscaled aminosilan-coated magnetites have demonstrated the feasibility of minimally invasive MFH in the Dunning tumor model. Here we evaluated the effect of two sequential MFH treatments, combined with external radiation, in an orthotopic Dunning R3327-MatLyLu prostate cancer model. MFH led to a significant growth inhibition in this orthotopic model of the aggressive MatLyLu tumor variant. Furthermore, combined MFH and radiation with 20 Gy equally effective in inhibiting tumor growth as radiation with 60 Gy, suggesting a significant synergistic effect. Intratumoral deposition of magnetic fluids was found to be stable, allowing for serial MFH treatments without repeated injection. The optimal treatment schedules of this combination regarding temperatures, sequencing and fractionation need to be defined in further experimental studies. (author)

MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors.

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Tsuicheng D Chiu

Full Text Available Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT imaging alone. In this study, we characterized a research magnetic resonance (MR scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This

MR-CBCT image-guided system for radiotherapy of orthotopic rat prostate tumors.

Science.gov (United States)

Chiu, Tsuicheng D; Arai, Tatsuya J; Campbell Iii, James; Jiang, Steve B; Mason, Ralph P; Stojadinovic, Strahinja

2018-01-01

Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT) imaging alone. In this study, we characterized a research magnetic resonance (MR) scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV) was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This novel protocol

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

DEFF Research Database (Denmark)

Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer

2009-01-01

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....

Synthesis of 125 I - Salicyl Hydroxamic Acid for Urinary Bladder Imaging

International Nuclear Information System (INIS)

Ibrahim, I.T.; Abou EL Zahab, M.; Hamed, M.

2015-01-01

Salicylhydroxamic acid is a salicylate derivative. Radiolabeling of Salicyl hydroxamic acid ( SHA ) with iodine-125 may have considerable interest for imaging of urinary bladder. This study is aimed to optimize the radiolabeling yield of Salicyl hydroxamic with radio iodine (125-123) using chloramine - T (CAT) as an oxidizing agent with respect to factors that affect the reaction conditions such as SHA amount, CAT amount, reaction time and ph of the reaction mixture. In - vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 24 h. 125 I-SHA was injected via intravenous administration routes into normal male Sprague – Dawley rats. Bio - distribution studies have revealed that 125 I-SHA was excreted in urine with extent that it could give a clear image for urinary bladder especially if the bladder it tightly closed. The amount of 125 I - Salicyl hydroxamic excreted was increased in case of giving potassium bicarbonate to rat before injection of 125 I-SHA. The result of biodistribution study of 125 I - SHA in experimental animal suggest ed the possibility of using 123 I-SHA to image the urinary bladder

Enhancement of rat bladder contraction by artificial sweeteners via increased extracellular Ca2+ influx

International Nuclear Information System (INIS)

Dasgupta, Jaydip; Elliott, Ruth A.; Doshani, Angie; Tincello, Douglas G.

2006-01-01

Introduction: Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfame K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips. Methods: Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with α,β methylene ATP, potassium, calcium and carbachol. Results: Sweeteners 10 -7 M to 10 -2 M enhanced the contractile response to 10 Hz EFS compared to control (p -6 M, aspartame 10 -7 M and sodium saccharin 10 -7 M. Acesulfame K 10 -6 M increased the maximum contractile response to α,β methylene ATP by 35% (± 9.6%) (p -6 M increased the log EC 5 from -2.79 (± 0.037) to -3.03 (± 0.048, p -7 M from -2.74 (± 0.03) to 2.86 (± 0.031, p +2 channels

Experimental modified orthotopic piggy-back liver autotransplantation

International Nuclear Information System (INIS)

Roveda, L.; Zonta, A.; Staffieri, F.; Timurian, D.; DiVenere, B.; Bakeine, G.J.; Crovace, A.; Prati, U.

2009-01-01

The classical orthotopic liver autotransplantation is a very challenging and time wasting technique; it includes the division of major hepatic vessels and choledocus, and subsequent reconnection by end to end anastomoses. The caval end to end anastomoses are the most difficult to be performed and the interposition of a prosthesis can be required. We adopted the classical orthotopic liver autotransplantation technique in 2 patients affected with diffused liver metastases from colorectal cancer, for extracorporeal neutron capture therapy (BNCT). The procedure required very long operating times and the extracorporeal circulation (ECC) set up; furthermore the vena cava reconstruction was performed by the interposition of a goretex-prosthesis. We propose a 'modified orthotopic piggy-back technique' to simplify liver reconnection and shorten the operating time. Materials and methods: The technique was developed in the swine (25 kg body weight), under general anaesthesia. We performed the resection of the retro-hepatic vena cava with preservation of the caval flow during the anhepatic phase, by interposing a goretex-prosthesis. The reconstruction of the vena cava was then performed by a side-to-side cava-prosthesis anastomosis with lateral clamping of the prosthesis. The procedure was then completed according to the classical technique of liver transplantation. Results: The mean time for VC reconstruction was 56 (±10) min. and the mean time for side-to-side VC-prosthesis anastomosis was 13 (±4) min. Conclusions: The 'modified orthotopic piggy-back technique' can simplify the reimplant of the liver during autotransplantation and shorten the operating time. Furthermore also the time of total extracorporeal circulation is reduced, as during the anhepatic phase and during the side-to-side cava-prosthesis anastomosis the flow in the inferior vena cava is uninterrupted.

Experimental modified orthotopic piggy-back liver autotransplantation

Energy Technology Data Exchange (ETDEWEB)

Roveda, L. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)], E-mail: roveda.l@libero.it; Zonta, A. [Department of Surgery, University of Pavia, PV 27100 (Italy); Staffieri, F. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Timurian, D.; DiVenere, B. [Surgery ' Madonna delle Grazie' Hospital, Contrada Cattedra Ambulante, Matera, MT 75100 (Italy); Bakeine, G.J. [Laboratorio Nazionale di Tecnologie Avanzate e Nanoscienza (TASC), Basovizza, TR (Italy); Crovace, A. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Prati, U. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)

2009-07-15

The classical orthotopic liver autotransplantation is a very challenging and time wasting technique; it includes the division of major hepatic vessels and choledocus, and subsequent reconnection by end to end anastomoses. The caval end to end anastomoses are the most difficult to be performed and the interposition of a prosthesis can be required. We adopted the classical orthotopic liver autotransplantation technique in 2 patients affected with diffused liver metastases from colorectal cancer, for extracorporeal neutron capture therapy (BNCT). The procedure required very long operating times and the extracorporeal circulation (ECC) set up; furthermore the vena cava reconstruction was performed by the interposition of a goretex-prosthesis. We propose a 'modified orthotopic piggy-back technique' to simplify liver reconnection and shorten the operating time. Materials and methods: The technique was developed in the swine (25 kg body weight), under general anaesthesia. We performed the resection of the retro-hepatic vena cava with preservation of the caval flow during the anhepatic phase, by interposing a goretex-prosthesis. The reconstruction of the vena cava was then performed by a side-to-side cava-prosthesis anastomosis with lateral clamping of the prosthesis. The procedure was then completed according to the classical technique of liver transplantation. Results: The mean time for VC reconstruction was 56 ({+-}10) min. and the mean time for side-to-side VC-prosthesis anastomosis was 13 ({+-}4) min. Conclusions: The 'modified orthotopic piggy-back technique' can simplify the reimplant of the liver during autotransplantation and shorten the operating time. Furthermore also the time of total extracorporeal circulation is reduced, as during the anhepatic phase and during the side-to-side cava-prosthesis anastomosis the flow in the inferior vena cava is uninterrupted.

Fifteen years of experience radical cystectomy and intestinal urinary diversion

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M. I. Vasil’chenko

2017-01-01

Full Text Available Objective. Examination of the results of surgical treatment and analysis of the surgical technique and perioperative parameters in a series of radical cystectomy on the basis of its own 15 years of experience in the formation of orthotopic and heterotopic urinary reservoir of the ileum segment by developed and patented techniques in different versions: open radical cystectomy, laparoscopic radical cystectomy and robotassisted radical cystectomy.Materials and methods. A retrospective analysis of 310 radical cystectomy performed from 2000 to 2015, on the occasion of various pathologies of the bladder and prostate, as well as cancers of other organs (uterus, colon with involvement in the process of bladder tumor. Plastics of the bladder was performed from the segment of the terminal ileum. Formation of orthotopic bladder was performed by the method of M.I. Vasilchenko (RF patent for invention № 2337630 “Method of orthotopic bladder plastics” by M.I. Vasilchenko. The ureters are implanted by antireflux procedure. If unable to perform orthotopic bladder plastics recovery and self-urination, patients underwent the formation of heterotopic enteral reservoir with a holding valve.Results. It assesses the functionality and viability of organic shaped orthotopic and heterotopic urinary neocystis in the early and late postoperative periods in different versions. The proposed techniques have a beneficial effect on the improvement of the functional state and stabilization of the upper urinary tract. Analysis of morbidity and mortality was determined according to the classification of surgical complications on the Clavien–Dindo. This approach allowed to identify most of the complications and prevent an underestimation of the main negative results. Estimated oncologic efficacy of minimally invasive interventions laparoscopic radical cystectomy and robot-assisted radical cystectomy not inferior open radical cystectomy.Conclusions. Formation of

Silencing Intersectin 1 Slows Orthotopic Neuroblastoma Growth in Mice.

Science.gov (United States)

Harris, Jamie; Herrero-Garcia, Erika; Russo, Angela; Kajdacsy-Balla, Andre; O'Bryan, John P; Chiu, Bill

2017-11-01

Neuroblastoma accounts for 15% of all pediatric cancer deaths. Intersectin 1 (ITSN1), a scaffold protein involved in phosphoinositide 3-kinase (PI3K) signaling, regulates neuroblastoma cells independent of MYCN status. We hypothesize that by silencing ITSN1 in neuroblastoma cells, tumor growth will be decreased in an orthotopic mouse tumor model. SK-N-AS neuroblastoma cells transfected with empty vector (pSR), vectors expressing scrambled shRNA (pSCR), or shRNAs targeting ITSN1 (sh#1 and sh#2) were used to create orthotopic neuroblastoma tumors in mice. Volume was monitored weekly with ultrasound. End-point was tumor volume >1000 mm. Tumor cell lysates were analyzed with anti-ITSN1 antibody by Western blot. Orthotopic tumors were created in all cell lines. Twenty-five days post injection, pSR tumor size was 917.6±247.7 mm, pSCR was 1180±159.9 mm, sh#1 was 526.3±212.8 mm, and sh#2 was 589.2±74.91 mm. sh#1-tumors and sh#2-tumors were smaller than pSCR (P=0.02), no difference between sh#1 and sh#2. Survival was superior in sh#2-tumors (P=0.02), trended towards improved survival in sh#1-tumors (P=0.09), compared with pSCR-tumors, no difference in pSR tumors. Western blot showed decreased ITSN1 expression in sh#1 and sh#2 compared with pSR and pSCR. Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis.

Uric Acid or 1-Methyl Uric Acid in the Urinary Bladder Increases Serum Glucose, Insulin, True Triglyceride, and Total Cholesterol Levels in Wistar Rats

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T. Balasubramanian

2003-01-01

Full Text Available In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs, can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels.

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

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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.

High salt loading induces urinary storage dysfunction via upregulation of epithelial sodium channel alpha in the bladder epithelium in Dahl salt-sensitive rats

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Seiji Yamamoto

2017-11-01

Full Text Available We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC by using Dahl salt-resistant (DR and salt-sensitive (DS rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period. Cystometrogram showed the intercontraction intervals (ICI were significantly shorter in DS + HS group than in DR + HS group during infusion of saline. Subsequent infusion of amiloride significantly prolonged ICI in DS + HS group, while no intra-group difference in ICI was observed in DR + HS group. No intra- or inter-group differences in maximum intravesical pressure were observed. Protein expression levels of ENaCα in the bladder were significantly higher in DS + HS group than in DR + HS group. ENaCα protein was localized at bladder epithelium in both groups. In conclusion, high salt intake is considered to cause urinary storage dysfunction via upregulation of ENaC in the bladder epithelium with salt-sensitive hypertension, suggesting that ENaC might be a candidate for therapeutic target for urinary storage dysfunction.

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

Science.gov (United States)

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.

Bladder sensation measures and overactive bladder.

Science.gov (United States)

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

2009-09-01

We performed a prospective multicomponent study to determine whether subjective and objective bladder sensation instruments may provide data on sensory dysfunction in patients with overactive bladder. We evaluated 70 prospectively enrolled patients with urodynamics and questionnaires on validated urgency (Urgency Perception Score), general overactive bladder (Urogenital Distress Inventory) and quality of life (Incontinence Impact Questionnaire). We first sought a correlation between sensory specific (Urgency Perception Score) and quality of life questionnaire scores. We then assessed a correlation between sensory questionnaire scores and urodynamic variables, exploring the hypothesis that certain urodynamic parameters may be bladder sensation measures. We evaluated 2 urodynamic derivatives (first sensation ratio and bladder urgency velocity) to increase sensory finding discrimination. We noted a moderate correlation between the Urgency Perception Score (0.56) and the Urogenital Distress Inventory (0.74) vs the Incontinence Impact Questionnaire (each p Perception Score and bladder capacity (-0.25, p sensation ratio and bladder urgency velocity statistically significantly correlated with the Urgency Perception Score despite the lesser or absent correlation associated with the individual components of these derivatives. Bladder sensation questionnaires may be valuable to identify patients with sensory dysfunction and provide additional data not obtained in generalized symptom questionnaires. Urodynamic variables correlated with bladder sensation questionnaire scores and may be an objective method to assess sensory dysfunction.

Resultados de la ileocistoplastia ortotópica en pacientes con tumor vesical Orthotopic ileocystoplasty results in patient presenting vesical tumor

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Adolfo García García

2010-03-01

Full Text Available INTRODUCCIÓN. El cáncer de la vejiga es considerado un problema de salud tanto en Cuba como en el mundo. La cistectomía radical y sus variantes terapéuticas tienen la finalidad de curar o controlar la enfermedad, y conllevan la creación de un reservorio lo más semejante posible a la vejiga, por lo que se trabaja en la creación y perfeccionamiento de neovejigas a partir de un segmentointestinal. El objetivo de esta investigación fue evaluar los resultados de la ileocistoplastia ortotópica como procedimiento derivativo de la orina, después de la cistectomía total. MÉTODOS. Se realizó un estudio descriptivo, retrospectivo y prospectivo de 40 pacientes tratados en el Hospital «Hermanos Ameijeiras», en La Habana, entre los años 2000 y 2008. La fuente de información fueron los expedientes clínicos de los pacientes, y los datos se procesaron por medios automatizados. RESULTADOS. La mayor incidencia se encontró en los pacientes con 65 años de edad. La enuresis fue la forma de incontinencia urinaria que predominó y la mayoría de los pacientes tenían micciones voluntarias. Siete pacientes presentaron hidronefrosis y las fístulas del reservorio se relacionaron con la radioterapia. La mortalidad fue del 7,5 %. CONCLUSIONES. La ileocistoplastia ortotópica es un sustituto vesical aceptable en los pacientes con tumores vesicales.INTRODUCTION: The bladder cancer is considered a health problem in Cuba and worldwide. The aim of radical cystectomy and its therapeutical variants is to cure or control the disease and it is necessary the creation of a reservoir very similar to bladder and nowadays it is working in creation and improvement of the neo-bladders from an intestinal segment. The aim of present research was to assess the orthotopic ileocystoplasty results as urine derivative procedure after total cystectomy. METHODS: A prospective, retrospective and descriptive study was conducted in 40 patients seen in "Hermanos Ameijeiras

Characterization of dynamic physiology of the bladder by optical coherence tomography

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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.

Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

International Nuclear Information System (INIS)

Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

2013-01-01

Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

Orthotopic neobladder reconstruction after radical cystectomy in patients with a solitary functioning kidney: Clinical outcome and evaluation

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Aly, A.H.; Ezzat, A.; Hamed, A.

2011-01-01

To evaluate, in a prospective study, the clinical outcome of orthotopic neobladder reconstruction after radical cystectomy in patients with a solitary functioning kidney at the time of surgery. Patients and methods: This study included a total of 28 patients (25 males and three females) with muscle invasive bladder cancer and a solitary functioning kidney at the time of surgery who underwent radical cystectomy (anterior pelvic excentration for females) and urinary reconstruction using orthotopic neobladder at The National Cancer Institute, Cairo University between February 2004 and April 2009. The surgical procedures included ileocaecal neobladder in 19 patients, ileal neobladder (Studer) in five and sigmoid neobladder in four. All perioperative and long-term complications were recorded. The renal functions were evaluated using mainly serum creatinine level, abdominal ultrasonography and intravenous urography (IVU). Results: The mean age of patients was 51.4 years (range of 38-62 years) while the mean follow-up period was 41.4 months (range 18-62 months). Early complications included wound infections in five patients, urine leakage in six, abdominal dehiscence with deep venous thrombosis in two, intestinal obstruction and prolonged ileus in three. During the follow-up period, 21 renal units (75%) remained stable with normal serum creatinine level and normal radiological configuration of the kidney. The remaining seven patients (25%) developed varying degrees of renal deterioration either due to uretero-intestinal stricture in three patients (10.7%), who were all treated by open surgical revision of the anastomotic sites or due to stricture at the vesico-urethral anastomosis in four patients (14.3%) that had been successfully managed by endoscopic dilatation and internal ure-throtomy with stabilization of renal function. Severe metabolic acidosis occurred in one patient while mild forms occurred in three. These four patients required sodium bicarbonate therapy and

Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks

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Shen Jun; Wanibuchi, Hideki; Salim, Elsayed I.; Wei Min; Doi, Kenichiro; Yoshida, Kaoru; Endo, Ginji; Morimura,; Fukushima, Shoji

2003-01-01

The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of inorganic arsenics in human and experimental animals, was investigated in male Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided into three groups and received drinking water containing MMA(V) at doses of 0 (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences were found between the control and the MMA(V)-treated groups regarding clinical signs, mortality, hematological, and serum biochemistry findings. Quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci in liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)-treated group. In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium. A variety of tumors developed in rats of all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats and there were no significant differences among the groups. Thus, it could be concluded that, under the present experimental conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not cause tumor development in male F344 rats even after 2 years exposure

Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.

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Da Rocha, Mitscheli Sanches; Arnold, Lora L; De Oliveira, Maria Luiza Cotrim Sartor; Catalano, Shadia M Ihlaseh; Cardoso, Ana Paula Ferragut; Pontes, Merielen G N; Ferrucio, Bianca; Dodmane, Puttappa R; Cohen, Samuel M; De Camargo, João Lauro V

2014-05-01

Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

Leiomyoma of urinary bladder with bladder stone

International Nuclear Information System (INIS)

Farouk, K.; Gondal, M.; Khan, A.

2008-01-01

Leiomyoma of the urinary bladder is a rare benign mesenchymal tumour. We describe here a case of leiomyoma of the urinary bladder in a 65-year-old gentleman who presented with haematuria, passage of clots and combined obstructive and irritative urinary symptoms. The investigations revealed a vesical calculus and a mass on the left lateral wall of the urinary bladder. Cystolitholapaxy and transurethral resection of the tumour was performed. Histopathological report of the resected tumour revealed a leiomyoma of the urinary bladder. So far, a leiomyoma of the urinary bladder and a concomitant vesical calculus have not been described in literature. (author)

In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

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Chen, Gang; He, Yunfeng; Wu, Xiaohou; Zhang, Yao [Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China); Luo, Chunli [Department of Laboratory Medicine, Chongqing Medical University, Chongqing (China); Jing, Peng [Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China)

2012-07-13

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer. Key words: Single-walled carbon nanotubes; Bladder cancer; Drug vehicle; THP; Intravesical chemotherapy.

INVERTING ORTHOTOPIC ILEOCYSTOPLASTY FOR SHORT MESENTERY

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V. A. Perepechay

2010-01-01

Full Text Available During orthotopic ileocystoplasty, the short mesentery causes an increase in the risk of incompetence of anastomosis of the reservoir with the urethra. Inverting orthotopic ileocystoplasty ensures a free reservoir pull-through into the small pelvis and eliminates tissue tension in the anastomosis. The proposed procedure differs from the Studer operation in that the reservoir is sutured lengthwise, after which it is inverted between the mesenteric leaves. The posterior reservoir wall is anteverted and freely brought out into the small pelvis. This reduces the distance to the urethral stump by 3-4 cm. This procedure was used in 19 patients to be operated on. There were no cases of reservoir or reservoir-urethral anastomotic incompetence. The mean neocystic capacity was 110, 350, and 490 ml 0, 3, and 12 months, respectively, after urethral catheter removal. The maximum reservoir pressure does not exceed 40 (mean 30 cm H2O. Daytime urinary retention was 94.7%; nocturnal urinary retention during forced nocturnal miction was 79%. The obtained functional results compare well with those achieved during the similar procedures.

INVERTING ORTHOTOPIC ILEOCYSTOPLASTY FOR SHORT MESENTERY

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V. A. Perepechay

2014-07-01

Full Text Available During orthotopic ileocystoplasty, the short mesentery causes an increase in the risk of incompetence of anastomosis of the reservoir with the urethra. Inverting orthotopic ileocystoplasty ensures a free reservoir pull-through into the small pelvis and eliminates tissue tension in the anastomosis. The proposed procedure differs from the Studer operation in that the reservoir is sutured lengthwise, after which it is inverted between the mesenteric leaves. The posterior reservoir wall is anteverted and freely brought out into the small pelvis. This reduces the distance to the urethral stump by 3-4 cm. This procedure was used in 19 patients to be operated on. There were no cases of reservoir or reservoir-urethral anastomotic incompetence. The mean neocystic capacity was 110, 350, and 490 ml 0, 3, and 12 months, respectively, after urethral catheter removal. The maximum reservoir pressure does not exceed 40 (mean 30 cm H2O. Daytime urinary retention was 94.7%; nocturnal urinary retention during forced nocturnal miction was 79%. The obtained functional results compare well with those achieved during the similar procedures.

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

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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.

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

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Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A cli...

Evidence for inhibitory nicotinic and facilitatory muscarinic receptors in cholinergic nerve terminals of the rat urinary bladder.

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Somogyi, G T; de Groat, W C

1992-02-01

Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly increased 3H-ACh overflow in strips preloaded with 3H-choline. Oxotremorine (1 microM), an M2 receptor agonist and DMPP (10 microM) a nicotinic (N) receptor agonist decreased the release of ACh (50% and 55% respectively); whereas McN-A 343 (50 microM) an M1 receptor agonist increased the release (33%), indicating the presence of three types of modulatory receptors. The anticholinesterase agent, physostigmine in concentrations of 1, 5 and 25 microM and neostigmine (5 microM) increased ACh release (44-710%). However a low concentration of physostigmine (0.05 microM) decreased release. Pirenzepine, an M1 muscarinic antagonist or atropine blocked the increased ACh release in physostigmine-treated strips, but in normal strips pirenzepine did not change release and atropine increased release. McN-A 343 or prolonged application (15 min) of DMPP increased ACh release (376% and 391% respectively) in physostigmine-treated strips. The response to McN-A 343 was blocked by pirenzepine. d-Tubocurarine (DTC), a nicotinic receptor blocker, enhanced ACh release in the presence of physostigmine but proved to be ineffective in normal preparations. These findings suggest that all three cholinergic receptors (M1 facilitatory, N inhibitory and M2 inhibitory) are activated by endogenous ACh in physostigmine treated preparations whereas only M2-inhibitory receptors are activated in normal preparations. It will be important in future studies to determine whether M1 and M2 mechanisms can also be activated under more physiological conditions in the bladder and whether they are present at other cholinergic synapses.

Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy

International Nuclear Information System (INIS)

Fava, Rafaela Marono; Ferragut Cardoso, Ana Paula; Sanches da Rocha, Mitscheli; Nascimento e Pontes, Merielen Garcia; Viana de Camargo, João Lauro; Cotrim Sartor de Oliveira, Maria Luiza

2015-01-01

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity. However, these changes were not observed in a previous SEM study conducted in this laboratory. This study evaluated whether these early alterations are actually due to diuron cytotoxicity or artifacts related to different processing methods used for SEM analysis. Male Wistar rats were fed ad libitum with basal diet, 7.1% sodium saccharin (NaS) or 2.500 ppm diuron for seven days or 15 weeks. The urinary bladders were processed for histological and labeling indices examinations and for SEM using two different processing methods. The incidence of simple hyperplasia after 15 weeks of exposure to diuron or to NaS was significantly increased. By SEM, the incidences and severity of lesions were significantly increased in the diuron group independently of exposure time. The different SEM processing methods used allowed for visualization of swollen superficial cells after seven days of diuron exposure. Probably the absence these cells in a previous study was due to the use very few animals. Our results support the hypothesis that the swollen cell is an early key event due to diuron-induced cytotoxicity and is the result of a degenerative process involved in the non-genotoxic carcinogenic mode of action of high doses of diuron

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

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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.

Post-voiding residual urine and capacity increase in orthotopic urinary diversion: Standard vs modified technique

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Bančević Vladimir

2010-01-01

Full Text Available Background/Aim. Ever since the time when the first orthotopic urinary diversion (pouch was performed there has been a constant improvement and modification of surgical techniques. The aim has been to create a urinary reservoir similar to normal bladder, to decrease incidence of postoperative complications and provide an improved life quality. The aim of this study was to compare postvoiding residual urine (PVR and capacity of the pouch constructed by standard or modified technique. Methods. In this prospective and partially retrospective clinical study we included 79 patients. In the group of 41 patients (group ST pouch was constructed using 50-70 cm of the ileum (standard technique. In the group of 38 patients (group MT pouch was constructed using 25-35 cm of the ileum (modified technique. Postoperatively, PVR and pouch capacity were measured using ultrasound in a 3-, 6- and 12-month period. Results. Postoperatively, an increase in PVR and pouch capacity was noticed in both groups. Twelve months postoperatively, PVR was significantly smaller in the group MT than in the group ST [23 (0-90 mL vs 109 (0-570 mL, p < 0,001]. In the same period the pouch capacity was significantly smaller in the MT group than in the ST group [460 (290-710 mL vs 892 (480-2 050 mL, p < 0.001]. Conclusion. Postoperatively, an increase in PVR and pouch capacity was noticed during a 12-month period. A year following the operation the pouch created from a shorter ileal segment reached capacity of the 'normal' bladder with small PVR. The pouch created by standard technique developed an unnecessary large PVR and capacity.

Systemic Immunotherapy of Non–Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti–PD-L1 Immune Checkpoint Inhibitor

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Vandeveer, Amanda J.; Fallon, Jonathan K.; Tighe, Robert; Sabzevari, Helen; Schlom, Jeffrey; Greiner, John W.

2016-01-01

Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non–muscle invasive, nonmetastatic human urothelial carcinoma. While the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy. In this study, an aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49luc), was used to study the antitumor effects of avelumab, an antibody to PD-L1. MB49luc murine tumor cells form multifocal tumors on the mucosal wall of the bladder reminiscent of non–muscle invasive, nonmetastatic urothelial carcinomas. MB49luc bladder tumors are highly positive for the expression of PD-L1 and avelumab administration induced significant (P<0.05) antitumor effects. These antitumor effects were more dependent on the presence of CD4 than CD8 T cells, as determined by in vivo immune cell depletions. The findings suggest that in this bladder tumor model, interruption of the immune suppressive PD-1/PD-L1 complex releases a local adaptive immune response that, in turn, reduces tumor growth. This bladder tumor model can be used to further identify host antitumor immune mechanisms and evaluate combinations of immune-based therapies for carcinoma in situ and non–muscle invasive, nonmetastatic urothelial carcinoma, to provide the rationale for subsequent clinical studies. PMID:26921031

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.

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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...

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

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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

Lung transplantation in the rat. III. Functional studies in iso- and allografts

International Nuclear Information System (INIS)

Marck, K.W.; Prop, J.; Wildevuur, C.R.

1983-01-01

Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research

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

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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.

Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation : PROTON-trial

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Arshad, Freeha; Ickx, Brigitte; van Beem, Rachel T.; Polak, Wojciech; Grune, Frank; Nevens, Frederik; Ilmakunnas, Minna; Koivusalo, Anna-Maria; Isoniemi, Helena; Strengers, Paul F. W.; Groen, Henk; Hendriks, Herman G. D.; Lisman, Ton; Pirenne, Jacques; Porte, Robert J.

2013-01-01

Background: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during orthotopic liver

Surgical revascularization induces angiogenesis in orthotopic bone allograft

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Willems, Wouter F.; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T.

2012-01-01

Remodeling of structural bone allografts relies on adequate revascularization, which can theoretically be induced by surgical revascularization. We developed a new orthotopic animal model to determine the technical feasibility of axial arteriovenous bundle implantation and resultant angiogenesis. We

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

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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.

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

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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.

Spontaneous Bladder Perforation in an Infant Neurogenic Bladder: Laparoscopic Management

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Daniel Cabezalí Barbancho

2013-01-01

Full Text Available Spontaneous bladder perforation is an uncommon event in childhood. It is usually associated with bladder augmentation. We are presenting a case of bladder rupture in an infant with neurogenic bladder without prior bladder surgery. Three days after lipomyelomeningocele excision the patient showed signs and symptoms of acute abdomen. The ultrasound exploration revealed significant amount of intraperitoneal free fluid and therefore a laparoscopic exploration was performed. A posterior bladder rupture was diagnosed and repaired laparoscopically. Currently, being 3 years old, she keeps successfully dry with clean intermittent catheterization. Neurogenic bladder voiding function can change at any time of its evolution and lead to complications. Early diagnosis of spontaneous bladder rupture is of paramount importance, so it is essential to think about it in the differential diagnosis of acute abdomen.

Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model 
and Analysis of Biological Properties

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Yongchun ZHOU

2012-08-01

Full Text Available Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05. A significant difference was indicated by the survival rate within and between the groups (P<0.001. Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.

Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats

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Shevtsov, M. A.; Parr, M. A.; Ryzhov, V. A.; Zemtsova, E. G.; Arbenin, A. Yu; Ponomareva, A. N.; Smirnov, V. M.; Multhoff, G.

2016-01-01

Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues. PMID:27386761

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

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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

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

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Majewski, Wojciech; Wesolowska, Iwona; Urbanczyk, Hubert; Hawrylewicz, Leszek; Schwierczok, Barbara; Miszczyk, Leszek

2009-01-01

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 scanning 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 70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm 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 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

Tobacco experimental model to induce urinary bladder neoplasms

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José Alexandre Colli Neto

2014-01-01

Full Text Available OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin and the concentration of carbon dioxide (CO2 confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

Evaluation of early changes induced by diuron in the rat urinary bladder using different processing methods for scanning electron microscopy.

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Fava, Rafaela Marono; Ferragut Cardoso, Ana Paula; da Rocha, Mitscheli Sanches; Nascimento E Pontes, Merielen Garcia; de Camargo, João Lauro Viana; de Oliveira, Maria Luiza Cotrim Sartor

2015-07-03

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide carcinogenic to the rat urinary bladder at high dietary levels. The suggested non-genotoxic mode of action (MOA) of diuron encompasses cytotoxicity and necrosis followed by regenerative hyperplasia. Prenecrotic swollen cells as observed under scanning electron microscopy (SEM) have been reported as early morphological alterations, putatively related to diuron cytotoxicity. However, these changes were not observed in a previous SEM study conducted in this laboratory. This study evaluated whether these early alterations are actually due to diuron cytotoxicity or artifacts related to different processing methods used for SEM analysis. Male Wistar rats were fed ad libitum with basal diet, 7.1% sodium saccharin (NaS) or 2.500ppm diuron for seven days or 15 weeks. The urinary bladders were processed for histological and labeling indices examinations and for SEM using two different processing methods. The incidence of simple hyperplasia after 15 weeks of exposure to diuron or to NaS was significantly increased. By SEM, the incidences and severity of lesions were significantly increased in the diuron group independently of exposure time. The different SEM processing methods used allowed for visualization of swollen superficial cells after seven days of diuron exposure. Probably the absence these cells in a previous study was due to the use very few animals. Our results support the hypothesis that the swollen cell is an early key event due to diuron-induced cytotoxicity and is the result of a degenerative process involved in the non-genotoxic carcinogenic mode of action of high doses of diuron. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

NBI - plasma vaporization hybrid approach in bladder cancer endoscopic management.

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Stănescu, F; Geavlete, B; Georgescu, D; Jecu, M; Moldoveanu, C; Adou, L; Bulai, C; Ene, C; Geavlete, P

2014-06-15

A prospective study was performed aiming to evaluate the surgical efficacy, perioperative safety profile, diagnostic accuracy and medium term results of a multi-modal approach consisting in narrow band imaging (NBI) cystoscopy and bipolar plasma vaporization (BPV) when compared to the standard protocol represented by white light cystoscopy (WLC) and transurethral resection of bladder tumors (TURBT). A total of 260 patients with apparently at least one bladder tumor over 3 cm were included in the trial. In the first group, 130 patients underwent conventional and NBI cystoscopy followed by BPV, while in a similar number of cases of the second arm, classical WLC and TURBT were applied. In all non-muscle invasive bladder tumors' (NMIBT) pathologically confirmed cases, standard monopolar Re-TUR was performed at 4-6 weeks after the initial intervention, followed by one year' BCG immunotherapy. The follow-up protocol included abdominal ultrasound, urinary cytology and WLC, performed every 3 months for a period of 2 years. The obturator nerve stimulation, bladder wall perforation, mean hemoglobin level drop, postoperative bleeding, catheterization period and hospital stay were significantly reduced for the plasma vaporization technique by comparison to conventional resection. Concerning tumoral detection, the present data confirmed the NBI superiority when compared to standard WLC regardless of tumor stage (95.3% vs. 65.1% for CIS, 93.3% vs. 82.2% for pTa, 97.4% vs. 94% for pT1, 95% vs. 84.2% overall). During standard Re-TUR the overall (6.3% versus 17.4%) and primary site (3.6% versus 12.8%) residual tumors' rates were significantly lower for the NBI-BPV group. The 1 (7.2% versus 18.3%) and 2 (11.5% versus 25.8%) years' recurrence rates were substantially lower for the combined approach. NBI cystoscopy significantly improved diagnostic accuracy, while bipolar technology showed a higher surgical efficiency, lower morbidity and faster postoperative recovery. The combined

Cholinergic activation of neurons in the medulla oblongata changes urinary bladder activity by plasma vasopressin release in female rats.

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Cafarchio, Eduardo M; da Silva, Luiz A; Auresco, Luciana C; Ogihara, Cristiana A; Almeida, Roberto L; Giannocco, Gisele; Luz, Maria C B; Fonseca, Fernando L A; Sato, Monica A

2016-04-05

The central control of the micturition is dependent on cortical areas and other ascending and descending pathways in the brain stem. The descendent pathways from the pons to the urinary bladder (UB) can be direct or indirect through medullary neurons (MN). Chemical stimulation with l-glutamate of MN known for their involvement in cardiovascular regulation evokes changes in pelvic nerves activities, which innervate the urinary bladder. Different neurotransmitters have been found in medullary areas; nevertheless, their involvement in UB control is few understood. We focused to investigate if cholinergic activation of neurons in the medulla oblongata changes the urinary bladder activity. Carbachol (cholinergic agonist) or atropine (cholinergic antagonist) was injected into the 4thV in anesthetized female Wistar rats and the intravesical pressure (IP), mean arterial pressure (MAP), heart rate (HR) and renal conductance (RC) were recorded for 30 min. Carbachol injection into the 4thV increased IP with peak response at 30 min after carbachol and yielded no changes in MAP, HR and RC. Atropine injection into the 4thV decreased IP and elicited no changes in MAP, HR and RC. Plasma vasopressin levels evaluated by ELISA kit assay increased after carbachol into the 4th V. Intravenous blockade of V1 receptors prior to carbachol into the 4thV abolished the increase in IP evoked by carbachol. Therefore, our findings suggest that cholinergic activation of neurons in the medulla oblongata by carbachol injections into the 4thV increases IP due to plasma vasopressin release, which acts in V1 receptors in the UB. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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Somogyi, G.T.; de Groat, W.C. (Univ. of Pittsburgh, PA (USA))

1990-10-01

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. Activation 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.

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

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ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

2015-01-01

Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor.

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Vandeveer, Amanda J; Fallon, Jonathan K; Tighe, Robert; Sabzevari, Helen; Schlom, Jeffrey; Greiner, John W

2016-05-01

Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non-muscle invasive, nonmetastatic human urothelial carcinoma. Although the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy. In this study, an aggressive, bioluminescent orthotopic bladder cancer model, MB49 tumor cells transfected with luciferase (MB49(luc)), was used to study the antitumor effects of avelumab, an antibody to PD-L1. MB49(luc) murine tumor cells form multifocal tumors on the mucosal wall of the bladder reminiscent of non-muscle invasive, nonmetastatic urothelial carcinomas. MB49(luc) bladder tumors are highly positive for the expression of PD-L1, and avelumab administration induced significant (P < 0.05) antitumor effects. These antitumor effects were more dependent on the presence of CD4 than CD8 T cells, as determined by in vivo immune cell depletions. The findings suggest that in this bladder tumor model, interruption of the immune-suppressive PD-1/PD-L1 complex releases a local adaptive immune response that, in turn, reduces tumor growth. This bladder tumor model can be used to further identify host antitumor immune mechanisms and evaluate combinations of immune-based therapies for carcinoma in situ and non-muscle invasive, nonmetastatic urothelial carcinoma, to provide the rationale for subsequent clinical studies. Cancer Immunol Res; 4(5); 452-62. ©2016 AACR. ©2016 American Association for Cancer Research.

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

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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.

Orthotopic transplantation of cryopreserved mouse ovaries and gonadotrophin releasing hormone analogues in the restoration of function following chemotherapy-induced ovarian damage.

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Qing Li

Full Text Available Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I; cyclophosphamide only (group II; cyclophosphamide plus GnRHa (group III; cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV. Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide.

Bladder Management

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... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

Bladder Cancer

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... organ in your lower abdomen that stores urine. Bladder cancer occurs in the lining of the bladder. It ... urinate Low back pain Risk factors for developing bladder cancer include smoking and exposure to certain chemicals in ...

Bacillus Calmette–Guérin and anti-PD-L1 combination therapy boosts immune response against bladder cancer

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Wang Y

2018-05-01

Full Text Available Yonghua Wang,1 Jing Liu,2 Xuecheng Yang,1 Yanan Liu,1 Yong Liu,1 Yanjiang Li,1 Lijiang Sun,1 Xiaokun Yang,1 Haitao Niu1 1Department of Urology, 2Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China Background: Programmed death-ligand 1 (PD-L1 is a critical immune checkpoint molecule which promotes immunosuppression by binding to PD-1 on T-cells in tumor immunity. We have previously identified that activation of toll like receptor 4 (TLR-4, which serves an important role in the induction of antitumor immune response during Bacillus Calmette–Guérin (BCG immunotherapy, could upregulate PD-L1 expression in bladder cancer (BCa cells through the classical mitogen-activated protein kinase (MAPK pathway and subsequently weaken the cytotoxicity of cytotoxic T lymphocyte (CTL. It is, therefore, necessary to investigate the possible potential relationship between PD-L1 expression and BCG immunotherapy. Materials and methods: In this study we investigated the effects of BCG treatment on PD-L1 expression in BCa cells and also evaluated the efficacy of BCG and anti-PD-L1 combination therapy in immunocompetent orthotopic rat BCa models. Results: We found that PD-L1 expression was obviously upregulated in BCa cells in response to BCG treatment both in vitro and in vivo. Moreover, BCG and anti-PD-L1 combination treatment activated a potent antitumor immune response with the increase in the number and activity of tumor-infiltrating CD8+ T cells, as well as the reduction in myeloid-derived suppressor cells (MDSCs, and eventually elicits prominent tumor growth inhibition and prolonged survival, and was found to be much more effective than either agent alone. Conclusion: These findings highlight the adaptive dynamic regulation of PD-L1 in response to BCG immunotherapy and suggest that combination of BCG immunotherapy with PD-L1 blockade may be an effective antitumor strategy for improving treatment

Bladder stones after bladder augmentation are not what they seem.

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Szymanski, Konrad M; Misseri, Rosalia; Whittam, Benjamin; Lingeman, James E; Amstutz, Sable; Ring, Joshua D; Kaefer, Martin; Rink, Richard C; Cain, Mark P

2016-04-01

Bladder and renal calculi after bladder augmentation are thought to be primarily infectious, yet few studies have reported stone composition. The primary aim was to assess bladder stone composition after augmentation, and renal stone composition in those with subsequent nephrolithiasis. The exploratory secondary aim was to screen for possible risk factors for developing infectious stones. Patients treated for bladder stones after bladder augmentation at the present institution between 1981 and 2012 were retrospectively reviewed. Data were collected on demographics, surgeries and stone composition. Patients without stone analysis were excluded. Stones containing struvite, carbonate apatite or ammonium acid ureate were classified as infectious. The following variables were analyzed for a possible association with infectious bladder stone composition: gender, history of cloacal exstrophy, ambulatory status, nephrolithiasis, recurrent urea-splitting urinary tract infections, first vs recurrent stones, timing of presentation with a calculus, history of bladder neck procedures, catheterizable channel and vesicoureteral reflux. Fisher's exact test was used for analysis. Of the 107 patients with bladder stones after bladder augmentation, 85 met inclusion criteria. Median age at augmentation was 8.0 years (follow-up 10.8 years). Forty-four patients (51.8%) recurred (14 multiple recurrences, 143 bladder stones). Renal calculi developed in 19 (22.4%) patients with a bladder stone, and 10 (52.6%) recurred (30 renal stones). Overall, 30.8% of bladder stones were non-infectious (Table). Among patients recurring after an infectious bladder stone, 30.4% recurred with a non-infectious one. Among patients recurring after a non-infectious stone, 84.6% recurred with a non-infectious one (P = 0.005). Compared with bladder stones, renal stones were more likely to be non-infectious (60.0%, P = 0.003). Of patients with recurrent renal calculi after an infectious stone, 40.0% recurred with

Novel Neurostimulation of Autonomic Pelvic Nerves Overcomes Bladder-Sphincter Dyssynergia

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

2018-01-01

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

Neurogenic Bladder

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Peter T. Dorsher

2012-01-01

Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

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Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

Is abdominal wall contraction important for normal voiding in the female rat?

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Boone Timothy B

2007-03-01

Full Text Available Abstract Background Normal voiding behavior in urethane-anesthetized rats includes contraction of the abdominal wall striated muscle, similar to the visceromotor response (VMR to noxious bladder distension. Normal rat voiding requires pulsatile release of urine from a pressurized bladder. The abdominal wall contraction accompanying urine flow may provide a necessary pressure increment for normal efficient pulsatile voiding. This study aimed to evaluate the occurrence and necessity of the voiding-associated abdominal wall activity in urethane-anesthetized female rats Methods A free-voiding model was designed to allow assessment of abdominal wall activity during voiding resulting from physiologic bladder filling, in the absence of bladder or urethral instrumentation. Physiologic diuresis was promoted by rapid intravascular hydration. Intercontraction interval (ICI, voided volumes and EMG activity of the rectus abdominis were quantified. The contribution of abdominal wall contraction to voiding was eliminated in a second group of rats by injecting botulinum-A (BTX, 5 U into each rectus abdominis to induce local paralysis. Uroflow parameters were compared between intact free-voiding and BTX-prepared animals. Results Abdominal wall response is present in free voiding. BTX preparation eliminated the voiding-associated EMG activity. Average per-void volume decreased from 1.8 ml to 1.1 ml (p Conclusion The voiding-associated abdominal wall response is a necessary component of normal voiding in urethane anesthetized female rats. As the proximal urethra may be the origin of the afferent signaling which results in the abdominal wall response, the importance of the bladder pressure increment due to this response may be in maintaining a normal duration intermittent pulsatile high frequency oscillatory (IPHFO/flow phase and thus efficient voiding. We propose the term Voiding-associated Abdominal Response (VAR for the physiologic voiding-associated EMG

Radiation-induced hydronephrosis in the rat: a new experimental model

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Knowles, J.F.

1985-01-01

An experimental model for investigating the effects of localized X-irradiation on a single ureter or the bladder trigone in rats is described. Obstruction of the urinary tract in the irradiated region gives rise to hydroureter and hydronephrosis and the development of these, as detected urographically, gives a clear-cut end point. After irradiation of the ureter with a single dose of 37.4 gy many rats died of gut lesions but after 23.4 Gy only one such death occurred while 14 of 16 rats developed hydronephrosis. Irradiation of the bladder trigone was not associated with intercurrent deaths, even after 40 Gy, and after 25 Gy 9 of 11 rats developed hydronephrosis. (author)

Bladder necrosis: 'A man without a bladder'.

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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.

Effects of acute urinary bladder overdistension on bladder response during sacral neurostimulation.

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Bross, S; Schumacher, S; Scheepe, J R; Zendler, S; Braun, P M; Alken, P; Jünemann, K

1999-10-01

Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.

Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

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Charles C Peyton

Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

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

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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

Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

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Xiangfei, Chai; Hulshof, Maarten; Bel, Arjan [Department of Radiotherapy, Academic medical Center, University of Amsterdam, 1105 AZ, Amsterdam (Netherlands); Van Herk, Marcel; Betgen, Anja [Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam (Netherlands)

2012-06-21

In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

International Nuclear Information System (INIS)

Chai Xiangfei; Hulshof, Maarten; Bel, Arjan; Van Herk, Marcel; Betgen, Anja

2012-01-01

In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

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Onozawa, Mizuki; Miyanaga, Naoto; Hinotsu, Shiro

2012-01-01

The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

Bladder filling variation during radiation treatment of prostate cancer: Can the use of a bladder ultrasound scanner and biofeedback optimize bladder filling?

International Nuclear Information System (INIS)

Stam, Marcel R.; Lin, Emile N.J. Th. van; Vight, Lisette P. van der; Kaanders, Johannes; Visser, Andries G.

2006-01-01

Purpose: To investigate the use of a bladder ultrasound scanner in achieving a better reproducible bladder filling during irradiation of pelvic tumors, specifically prostate cancer. Methods and Materials: First, the accuracy of the bladder ultrasound scanner relative to computed tomography was validated in a group of 26 patients. Next, daily bladder volume variation was evaluated in a group of 18 patients. Another 16 patients participated in a biofeedback protocol, aiming at a more constant bladder volume. The last objective was to study correlations between prostate motion and bladder filling, by using electronic portal imaging device data on implanted gold markers. Results: A strong correlation between bladder scanner volume and computed tomography volume (r = 0.95) was found. Daily bladder volume variation was very high (1 Sd = 47.2%). Bladder filling and daily variation did not significantly differ between the control and the feedback group (47.2% and 40.1%, respectively). Furthermore, no linear correlations between bladder volume variation and prostate motion were found. Conclusions: This study shows large variations in daily bladder volume. The use of a biofeedback protocol yields little reduction in bladder volume variation. Even so, the bladder scanner is an easy to use and accurate tool to register these variations

Bladder Leiomyoma.

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Caliskan, Selahattin; Sungur, Mustafa

2017-03-01

Leiomyoma of the bladder is a very rare disorder that accounts for 0.43% of all bladder neoplasms. Although the pathophysiology of the bladder leiomyoma is unknown, there are some theories in it. The patients can be asymptomatic; and clinical symptoms, when present, are associated with the tumor size and location. Imaging techniques such as ultrasonography, intravenous urography, computed tomography, and magnetic resonance imaging are helpful but definitive diagnosis is made by histopathological examination. Surgical resection of tumor with transurethral, open, laparoscopic and robotic approaches is the main treatment. We present a case of leiomyoma of the bladder in an adult male patient.

Characterization of a Murine Model of Bioequivalent Bladder Wound Healing and Repair Following Subtotal Cystectomy

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Mona Zarifpour

2017-05-01

Full Text Available Previous work demonstrated restoration of a bioequivalent bladder within 8 weeks of removing the majority of the bladder (subtotal cystectomy or STC in rats. The goal of the present study was to extend our investigations of bladder repair to the murine model, to harness the power of mouse genetics to delineate the cellular and molecular mechanisms responsible for the observed robust bladder regrowth. Female C57 black mice underwent STC, and at 4, 8, and 12 weeks post-STC, bladder repair and function were assessed via cystometry, ex vivo pharmacologic organ bath studies, and T2-weighted magnetic resonance imaging (MRI. Histology was also performed to measure bladder wall thickness. We observed a time-dependent increase in bladder capacity (BC following STC, such that 8 and 12 weeks post-STC, BC and micturition volumes were indistinguishable from those of age-matched non-STC controls and significantly higher than observed at 4 weeks. MRI studies confirmed that bladder volume was indistinguishable within 3 months (11 weeks post-STC. Additionally, bladders emptied completely at all time points studied (i.e., no increases in residual volume, consistent with functional bladder repair. At 8 and 12 weeks post-STC, there were no significant differences in bladder wall thickness or in the different components (urothelium, lamina propria, or smooth muscle layers of the bladder wall compared with age-matched control animals. The maximal contractile response to pharmacological activation and electrical field stimulation increased over time in isolated tissue strips from repaired bladders but remained lower at all time points compared with controls. We have established and validated a murine model for the study of de novo organ repair that will allow for further mechanistic studies of this phenomenon after, for example, genetic manipulation.

Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

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Bharathi Raja Rajaganapathy

Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

Increased bladder wall thickness is associated with severe symptoms and reduced bladder capacity in patients with bladder pain syndrome

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Shu-Yu Wu

2016-12-01

Conclusion: There are obvious differences in bladder CT scans of patients with symptoms of bladder pain due to different etiology. Increased BWT was associated with increased pain scores and decreased bladder capacity in patients with KC and IC. BWT on a CT scan might be considered a marker for the severity of bladder inflammation.

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

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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

Necrotizing Encephalitis Caused by Disseminated Aspergillus Infection after Orthotopic Liver Transplantation

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Luis E. Barrera-Herrera

2015-01-01

Full Text Available Liver transplantation is the only available treatment for some patients with end-stage liver disease. Despite reduction in mortality rates due to advances related to surgical techniques, intensive medical management and immunosuppressive therapy, invasive fungal infections remain a serious complication in orthotopic liver transplantation. We report the case of an 18-year-old male diagnosed with autoimmune cirrhosis in 2009 who was assessed and listed for liver transplantation for massive variceal hemorrhage. One year after listing a successful orthotopic liver transplantation was performed. Uneventful early recovery was achieved; however, he developed pulmonary and neurological Aspergillus infection 23 and 40 days after surgery, respectively. Antibiotic therapy with voriconazole and amphotericin was started early, with no major response. Neuroimaging revealed multiple right frontal and right parietal lesions with perilesional edema; surgical management of the brain abscesses was performed. A biopsy with periodic acid-Schiff and Gomori stains revealed areas with mycotic microorganisms morphologically consistent with Aspergillus, later confirmed by culture. The patient developed necrotizing encephalitis secondary to aspergillosis and died. Necrotizing encephalitis as a clinical presentation of Aspergillus infection in an orthotopic liver transplant is not common, and even with adequate management, early diagnosis and prompt antifungal treatment, mortality rates remain high.

Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

International Nuclear Information System (INIS)

Hillman, Gilda G; Wang, Yu; Che, Mingxin; Raffoul, Julian J; Yudelev, Mark; Kucuk, Omer; Sarkar, Fazlul H

2007-01-01

We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more

Complex bladder-exstrophy-epispadias management: Causes of failure of initial bladder closure

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Kouame Dibi Bertin

2014-01-01

Full Text Available The success of the initial closure of the complex bladder-exstrophy remains a challenge in pediatric surgery. This study describes a personal experience of the causes of failure of the initial closure and operative morbidity during the surgical treatment of bladder-exstrophy complex. From April 2000 to March 2014, four patients aged 16 days to 7 years and 5 months underwent complex exstrophy-epispadias repair with pelvic osteotomies. There were three males and one female. Three of them had posterior pelvic osteotomy, one had anterior innominate osteotomy. Bladder Closure: Bladder closure was performed in three layers. Our first patient had initial bladder closure with polyglactin 4/0 (Vicryl ® 4/0, concerning the last three patients, initial bladder closure was performed with polydioxanone 4/0 (PDS ® 4/0. The bladder was repaired leaving the urethral stent and ureteral stents for full urinary drainage for three patients. In one case, only urethral stent was left, ureteral drainage was not possible, because stents sizes were more important than the ureteral diameter. Out of a total of four patients, initial bladder closure was completely achieved for three patients. At the immediate postoperative follow-up, two patients presented a complete disunion of the abdominal wall and bladder despite an appropriate postoperative care. The absorbable braided silk (polyglactin used for the bladder closure was considered as the main factor in the failure of the bladder closure. The second cause of failure of the initial bladder closure was the incomplete urine drainage, ureteral catheterisation was not possible because the catheters sizes were too large compared with the diameters of the ureters. The failure of the initial bladder-exstrophy closure may be reduced by a closure with an absorbable monofilament silk and efficient urine drainage via ureteral catheterisation.

Bladder Cancer Advocacy Network

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... Grants Bladder Cancer Think Tank Bladder Cancer Research Network Bladder Cancer Genomics Consortium Get Involved Ways to ... us? Who we are The Bladder Cancer Advocacy Network (BCAN) is a community of patients, caregivers, survivors, ...

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

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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 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.

Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

NARCIS (Netherlands)

Chai, Xiangfei; van Herk, Marcel; Betgen, Anja; Hulshof, Maarten; Bel, Arjan

2012-01-01

In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is

The relationship between the duration of acute cauda equina compression and functional outcomes in a rat model.

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Glennie, R Andrew; Urquhart, Jennifer C; Staudt, Michael D; Lawendy, Abdel-Rahman; Gurr, Kevin R; Bailey, Christopher S

2014-09-01

Immunohistochemical and behavioral study using a rat model of acute cauda equina syndrome (CES). To determine the effect of duration of extradural cauda equina compression (CEC) on bladder, sensory, and motor functions. Cauda equina syndrome is a devastating injury treated with surgical decompression. Controversy exists regarding the optimal timing of surgery. Animal models of CES have focused on motor recovery but have not evaluated pain behavior or bladder function. A 4-mm balloon-tipped Fogarty catheter was inserted between the fifth and sixth lumbar lamina into the dorsal epidural space and inflated to compress the nerve roots at the L5 level. Maximal inflation was maintained at a constant balloon pressure of 304 Kpa for 1 or 4 hours. The catheter was inserted but not inflated in sham animals. During a 4-week period, pain behavior, bladder function, and locomotor function were assessed. Postmortem bladders and the lesion site were collected for analysis. Mechanical allodynia was 2-fold greater in 1-hour CEC rats than 4-hour CEC (P=0.002) and sham-operated (P=0.001) rats at 4 weeks after injury. Hind limb locomotor function was not different between groups at 4 weeks after injury. Both the 1-hour and 4-hour CEC group rats retained greater volumes of urine than the sham-operated rats throughout the 4-week period (P<0.05). At 4 weeks, bladder weight and volume were 2-fold greater in the 4-hour CEC group than in the 1-hour CEC group (P=0.006 and P=0.01, respectively). Histology of the bladder wall revealed an overall thinning after 4-hour CEC. Histology of the lesion site revealed a greater overall severity of injury after 4-hour CEC than after 1-hour CEC (P=0.04) and sham operation (P=0.002). Our data suggest that recovery of motor function is less affected by the timing of decompression compared with bladder function and pain behavior. Early decompression preserved bladder function but was associated with allodynia. N/A.

Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

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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.

Bladder Cancer—Patient Version

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The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Smoking is a major risk factor for bladder cancer. Bladder cancer is often diagnosed at an early stage. Start here to find information on bladder cancer treatment, screening, research, and statistics.

Increased Bladder Wall Thickness in Diabetic and Nondiabetic Women With Overactive Bladder

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Hakkı Uzun

2013-06-01

Full Text Available Purpose: Bladder wall thickness has been reported to be associated with overactive bladder (OAB in women. Diabetic women have an increased risk for OAB syndrome and may have an increased risk for bladder wall thickness. Methods: A total of 235 female patients aged 40 to 75 years were categorized into four groups. The first group consisted of women free of urgency or urge urinary incontinence. The second group included nondiabetic women with idiopathic OAB. The third group consisted of women with diabetes and clinical OAB, and women with diabetes but without OAB constituted the fourth group. Bladder wall thickness at the anterior wall was measured by ultrasound by the suprapubic approach with bladder filling over 250 mL. Results: The diabetic (third group and nondiabetic (second group women with OAB had significantly greater bladder wall thickness at the anterior bladder wall than did the controls. However, the difference was not significant between the diabetic (third group and the nondiabetic (second group women with OAB. Women with diabetes but without OAB (fourth group had greater bladder wall thickness than did the controls but this difference was not significant. Additionally, the difference in bladder wall thickness between diabetic women with (third group and without (fourth group OAB was not significant. Conclusions: This is the first study to show that bladder wall thickness is increased in diabetic women with and without OAB. Additionally, nondiabetic women with OAB had increased bladder wall thickness. Further studies may provide additional information for diabetic and nondiabetic women with OAB, in whom the etiopathogenesis of the disease may be similar.

SMOOTH MYOCYTES AND COLLAGENOUS FIBERS OF THE URINARY BLADDER OF RATS IN DIABETES MELLITUS

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Nadiya Tokaruk

2015-12-01

Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine   Key words: diabetes mellitus; smooth myocytes; collagenous fibers.   Introduction. Diabetes mellitus (DM causes diabetic cystopathy, which is associated with detrusor dysfunction and the content of collagenous fibers. The results of the performed studies are ambiguous and often contradictory, requiring objective data which could be obtained on the basis of the simultaneous determination of relative areas of smooth myocytes and collagenous fibers and their ultrastructural study. Objective: To determine the peculiarities of the structural and metric organization of smooth myocytes and collagenous fibers of the urinary bladder (UB of rats during different stages of DM. Materials and methods. DM was modeled by streptozotocin in Wistar rats. Relative areas of the studied structures were defined on digital images of histological sections of UB stained by Mason using the original automatic way. Smooth myocytes were studied ultrastructurally. Results. During the 14th-28th day of DM development the percent of collagenous fibers area decreases and the percentage of smooth myocytes area of UB wall increases. The expanding of intercellular spaces and the development of vacuolar degeneration of myocytes are observed. During the 42nd-56th days the percentage of collagenous fibers area increases and the percentage of the area of smooth myocytes decreases. Ultrastructurally subsiding of vacuolar dystrophy, short-term baloon dystrophy, the appearance of dark myocytes, moderate karyorrhexis were observed. During the 70th day of the experiment the percentage of collagenous fibers and smooth myocytes areas does not change significantly, most dark myocytes are involutive, there are local fibrosis and myocyte sequestration areas. Conclusions. Ultrastructural changes are characterized by a pronounced polymorphism and have a chronological relationship. Author’s worked out original method of determination of the

Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)

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Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

2017-01-01

Purpose To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). Participants The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Findings to date Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. Future plans The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding

Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe).

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Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

2017-09-27

To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author. © Article author(s) (or their employer

Rat strains differ in susceptibility to Ureaplasma parvum-induced urinary tract infection and struvite stone formation.

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Reyes, Leticia; Reinhard, Mary; O'donell, L J; Stevens, Janet; Brown, Mary B

2006-12-01

Individuals with struvite uroliths are susceptible to recurrent urinary tract infections (UTI), sepsis, and renal disease. Unfortunately, little is known about the host-specific factors that predispose to this disease. In order to develop a rodent model that can address this problem, we inoculated female Fischer 344 (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host-adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats remained infected. Severe bladder lesions and struvite calculi were seen in 64% of F344 rats; in other rat strains, bladder lesions were mild or absent. F344 rats with struvite uroliths had the highest urinary levels of proinflammatory cytokines, such as GRO/KC, interleukin-1alpha (IL-1alpha), and IL-1beta. F344 rats without struvite stones at necropsy had milder bladder lesions and significantly lower urinary levels of proinflammatory cytokines but a more prominent inflammatory response than did other rat strains. Based on our results, struvite stone formation is linked to a robust inflammatory response that does not resolve UTI but instead promotes damage to surrounding tissues.

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

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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.

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

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

2014-10-01

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

Effects of water avoidance stress on peripheral and central responses during bladder filling in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP research network study.

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Zhuo Wang

Full Text Available Stress plays a role in the exacerbation and possibly the development of functional lower urinary tract disorders. Chronic water avoidance stress (WAS in rodents is a model with high construct and face validity to bladder hypersensitive syndromes, such as interstitial cystitis/bladder pain syndrome (IC/BPS, characterized by urinary frequency and bladder hyperalgesia and heightened stress responsiveness. Given the overlap of the brain circuits involved in stress, anxiety, and micturition, we evaluated the effects chronic stress has on bladder function, as well as its effects on regional brain activation during bladder filling. Female Wistar-Kyoto rats were exposed to WAS (10 days or sham paradigms. One day thereafter, cystometrograms were obtained during titrated bladder dilation, with visceromotor responses (VMR recorded simultaneously. Cerebral perfusion was assessed during passive bladder distension (20-cmH2O following intravenous administration of [14C]-iodoantipyrine. Regional cerebral blood flow was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. WAS animals compared to controls demonstrated a decreased pressure threshold and visceromotor threshold triggering the voiding phase. At 20-cmH2O, VMR was significantly greater in WAS animals compared to controls. WAS animals showed greater activation in cortical regions of the central micturition circuit, including the posterior cingulate, anterior retrosplenial, somatosensory, posterior insula, orbital, and anterior secondary ("supplementary" motor cortices, as well as in the thalamus, anterior hypothalamus, parabrachial and Barrington nuclei, and striatum. Seed analysis showed increased functional connectivity of WAS compared to control animals of the posterior cingulate cortex to the pontine parabrachial nucleus; of the Barrington nucleus to the anterior dorsal midline and ventrobasilar thalamus and somatosensory and

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

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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.

Alexithymia and anesthetic bladder capacity in interstitial cystitis/bladder pain syndrome.

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Chiu, Chui-De; Lee, Ming-Huei; Chen, Wei-Chih; Ho, Hoi Lam; Wu, Huei-Ching

2017-09-01

In contrast to the inconsistent results of organic causes, it has been found that psychological risk factors are reliably related to functional somatic syndromes (FSSs), including interstitial cystitis/bladder pain syndrome (IC/BPS). Compared to patients with acute cystitis, a subgroup of IC/BPS patients with a history of childhood relational trauma reported intensified unregulated affective states (i.e., anxiety and depression) and trauma-related psychopathology (i.e., dissociation). Nevertheless, it remains unknown whether psychosocial risk factors can be separated from bladder-centric factors. This study aimed to verify whether psychosocial factors such as alexithymia, which is a key psychological factor of FSSs, are less likely to be linked to a low bladder capacity in patients with IC/BPS. Ninety-four female IC/BPS patients were recruited from the outpatient departments of urology, obstetrics, and gynecology. Anxiety, depression, dissociation, childhood relational trauma, and alexithymia were assessed using standardized scales, and anesthetic bladder capacity was examined by cystoscopic hydrodistention. Positive correlations were found between anesthetic bladder capacity and the psychosocial variables, including alexithymia. An increased bladder capacity was associated with anxiety, dissociation, and childhood relational trauma, and a combination of high cognitive and low affective alexithymia mediated the correlations between bladder capacity and the psychosocial variables. Psychosocial variables that are associated with an aversive childhood relational environment and affect dysregulation may constitute a pathogenic trajectory that differs from bladder-centric defects such as a lower bladder capacity. The findings of this study support the notion that IC/BPS in some patients may be due to an FSS. Copyright © 2017 Elsevier Inc. All rights reserved.

Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

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Abe, Toyofumi; Yoshioka, Toshiaki; Sato, Mototaka; Mori, Naoki; Sekii, Ken-Ichiro; Itatani, Hiroaki

2011-01-01

We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

Sequential and simultaneous revascularization in adult orthotopic piggyback liver transplantation

NARCIS (Netherlands)

Polak, WG; Miyamoto, S; Nemes, BA; Peeters, PMJG; de Jong, KP; Porte, RJ; Slooff, MJH

The aim of the study was to assess whether there is a difference in outcome after sequential or simultaneous revascularization during orthotopic liver transplantation (OLT) in terms of patient and graft survival, mortality, morbidity, and liver function. The study population consisted of 102 adult

Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

International Nuclear Information System (INIS)

Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

2008-01-01

High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically

[Bladder-conserving treatment for bladder cancer: potential of and developments in radiotherapy].

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Hulshof, Maarten C C M; Pieters, Bradley R; Koning, Caro C E

2013-01-01

The standard treatment for muscle-invasive bladder cancer is surgical removal of the bladder and construction of a neobladder. Recently, important improvements have been made in the potential for bladder-conserving treatment using radiotherapy. External beam radiotherapy has undergone technological improvements, as a result of which it is possible to radiate the tumour more precisely while decreasing radiation to healthy tissue. Radiochemotherapy improves local recurrence-free and overall survival compared with radiotherapy alone. The results of this combined treatment are comparable with those of surgery. Additionally, Dutch radiotherapy departments have collected data in a national database of 1040 selected patients with confined bladder cancer. These patients were treated with external beam radiation, limited surgery and brachytherapy. The 5-year local recurrence-free survival was 75%. Bladder conserving treatment options for muscle-invasive bladder cancer should be discussed during the multidisciplinary meeting.

The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats

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Sang Wook Lee

2018-01-01

Full Text Available Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC-derived multipotent mesenchymal stem cells (M-MSCs on ketamine-induced cystitis (KC in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells of M-MSCs (KC+M-MSC group or PBS vehicle (KC group were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells to that of an identical dose of adult bone marrow (BM-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105 of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic

TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

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Rodrigo NITSCHE

2014-03-01

Full Text Available Context Hypogonadism is a common clinical situation in male patients with liver cirrhosis. Objectives The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD score. Methods In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Results Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10 and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD ≤18 - group (A (P<0.05. Conclusions Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD ≤18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation.

Bladder extension variability during pelvic external beam radiotherapy with a full or empty bladder

International Nuclear Information System (INIS)

Pinkawa, Michael; Asadpour, Branka; Siluschek, Jaroslav; Gagel, Bernd; Piroth, Marc D.; Demirel, Cengiz; Eble, Michael J.

2007-01-01

Background and purpose: Varying bladder fillings during radiotherapy lead to a changing dose-volume load to the bladder and adjacent structures. The aim of the study was to compare the extent of bladder wall movements during parallel series with full bladder (FB) and empty bladder (EB). Materials and methods: Three hundred and forty serial computed tomography (CT) scans were performed in 50 patients scheduled for primary and postoperative radiotherapy for prostate cancer. Each patient underwent two CT scans (with FB and EB) before and 2-3 times during radiotherapy. Displacements of the bladder wall were compared and correlated with changing bladder fillings. Results: The variability of FB was larger compared to EB volume (standard deviation of 124cc and 56cc; p < 0.01), but significant bladder wall displacement variabilities were only found at the anterior and superior borders. Within a bladder volume range between -100 and +200 ml relative to the FB planning scan, the mean bladder wall displacement remained <5 mm at the inferior, lateral, and posterior borders - as opposed to 15 and 21 mm at the anterior and superior borders. Conclusions: Treating the pelvis with EB compared to FB, bladder wall displacement can be only reduced at the superior and anterior borders. FB wall displacements are comparable with EB displacements at all other borders

A new problem in inflammatory bladder diseases: Use of mobile phones!

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Orhan Koca

2014-08-01

Full Text Available Purpose Technological developments provide a lot of conveniences to our lives. This issue is one of the risks that arise along with these conveniences. In our study we tried to understand the impact of electromagnetic waves from mobile phones on bladder tissue. Materials and Methods Twenty-one adult male albino rats were divided into three equal groups. Group 1 was exposed to electromagnetic wave for 8 hours per day for 20 days and then their bladders were taken off immediately. Group 2 was firstly exposed to electromagnetic wave for 8 hours per day for 20 days then secondly another for 20 days without exposition to electromagnetic wave and then their bladders were taken off. Group 3 was the control group and they were not exposed to electromagnetic wave. Results Under microscopic examination of bladder tissue, in the first group severe inflammatory cell infiltration was seen in lamina propria and muscle layer in contrast to intact urothelium. In the second group mild inflammatory cell infiltration was seen in lamina propria and muscle layer. The mean scores for the three groups were 5.5 ± 2.5, 0.8 ± 1.3 and 1.2 ± 1.5 respectively. Mean score of group 1 was statistically higher than others (p = 0.001. Conclusion Intensive use of mobile phones has negative impact on bladder tissue as well as the other organs. Keeping a minimum level of mobile phone use makes it easy to be kept under control of diseases in which inflammation is an etiologic factor.

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

Science.gov (United States)

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.

The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration.

Science.gov (United States)

Snow-Lisy, Devon C; Diaz, Edward C; Bury, Matthew I; Fuller, Natalie J; Hannick, Jessica H; Ahmad, Nida; Sharma, Arun K

2015-01-01

Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an

Rat Strains Differ in Susceptibility to Ureaplasma parvum-Induced Urinary Tract Infection and Struvite Stone Formation▿

Science.gov (United States)

Reyes, Leticia; Reinhard, Mary; O'Donell, L. J.; Stevens, Janet; Brown, Mary B.

2006-01-01

Individuals with struvite uroliths are susceptible to recurrent urinary tract infections (UTI), sepsis, and renal disease. Unfortunately, little is known about the host-specific factors that predispose to this disease. In order to develop a rodent model that can address this problem, we inoculated female Fischer 344 (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host-adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats remained infected. Severe bladder lesions and struvite calculi were seen in 64% of F344 rats; in other rat strains, bladder lesions were mild or absent. F344 rats with struvite uroliths had the highest urinary levels of proinflammatory cytokines, such as GRO/KC, interleukin-1α (IL-1α), and IL-1β. F344 rats without struvite stones at necropsy had milder bladder lesions and significantly lower urinary levels of proinflammatory cytokines but a more prominent inflammatory response than did other rat strains. Based on our results, struvite stone formation is linked to a robust inflammatory response that does not resolve UTI but instead promotes damage to surrounding tissues. PMID:16982825

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

Science.gov (United States)

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 pain syndrome

DEFF Research Database (Denmark)

Hanno, Philip; Nordling, Jørgen; Fall, Magnus

2011-01-01

Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has ex...... can be challenging, and misdiagnosis as a psychological problem, overactive bladder, or chronic urinary infection has plagued patients with the problem....

A Non-Invasive Bladder Sensory Test Supports a Role for Dysmenorrhea Increasing Bladder Noxious Mechanosensitivity

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TU, Frank F.; EPSTEIN, Aliza E.; POZOLO, Kristen E.; SEXTON, Debra L.; MELNYK, Alexandra I.; HELLMAN, Kevin M.

2012-01-01

Objective Catheterization to measure bladder sensitivity is aversive and hinders human participation in visceral sensory research. Therefore, we sought to characterize the reliability of sonographically-estimated female bladder sensory thresholds. To demonstrate this technique’s usefulness, we examined the effects of self-reported dysmenorrhea on bladder pain thresholds. Methods Bladder sensory threshold volumes were determined during provoked natural diuresis in 49 healthy women (mean age 24 ± 8) using three-dimensional ultrasound. Cystometric thresholds (Vfs – first sensation, Vfu – first urge, Vmt – maximum tolerance) were quantified and related to bladder urgency and pain. We estimated reliability (one-week retest and interrater). Self-reported menstrual pain was examined in relationship to bladder pain, urgency and volume thresholds. Results Average bladder sensory thresholds (mLs) were Vfs (160±100), Vfu (310±130), and Vmt (500±180). Interrater reliability ranged from 0.97–0.99. One-week retest reliability was Vmt = 0.76 (95% CI 0.64–0.88), Vfs = 0.62 (95% CI 0.44–0.80), and Vfu = 0.63, (95% CI 0.47–0.80). Bladder filling rate correlated with all thresholds (r = 0.53–0.64, p dysmenorrhea pain had increased bladder pain and urgency at Vfs and increased pain at Vfu (p’s dysmenorrhea pain was unrelated to bladder capacity. Discussion Sonographic estimates of bladder sensory thresholds were reproducible and reliable. In these healthy volunteers, dysmenorrhea was associated with increased bladder pain and urgency during filling but unrelated to capacity. Plausibly, dysmenorrhea sufferers may exhibit enhanced visceral mechanosensitivity, increasing their risk to develop chronic bladder pain syndromes. PMID:23370073

Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors.

Science.gov (United States)

Gacci, Mauro; Saleh, Omar; Cai, Tommaso; Gore, John L; D'Elia, Carolina; Minervini, Andrea; Masieri, Lorenzo; Giannessi, Claudia; Lanciotti, Michele; Varca, Virginia; Simonato, Alchiede; Serni, Sergio; Carmignani, Giorgio; Carini, Marco

2013-03-12

Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due

Allogeneic unresponsiveness to orthotopic cardiac transplants in DL-A-identical radiation chimeras

International Nuclear Information System (INIS)

Boyd, A.D.; Spencer, F.C.; Hirose, H.; Engelman, R.M.; Cannon, F.D.; Ferrebee, J.W.; Rapaport, F.T.

1975-01-01

Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor

[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].

Science.gov (United States)

Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N

2016-12-01

Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.

Immunosuppressive and postoperative effects of orthotopic liver transplantation on bone metabolism

NARCIS (Netherlands)

Guichelaar, MMJ; Malinchoc, M; Sibonga, J; Clarke, BL; Hay, JE

Bone loss occurs early after orthotopic liver transplantation (OLT) in all liver transplant recipients and leads to postoperative fractures, especially in cholestatic patients with the lowest bone mass. Little is known about the underlying changes in bone metabolism after OLT or about the etiology

Selective bladder preservation with curative intent for muscle-invasive bladder cancer. A contemporary review

International Nuclear Information System (INIS)

Koga, Fumitaka; Kihara, Kazunori

2012-01-01

Radical cystectomy plus urinary diversion, the reference standard treatment for muscle-invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long-term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder-sparing approaches for muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder-sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (Σ55-65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50-70% at 5 years), while preserving the native bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include muscle-invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle-invasive bladder cancer site; potential lack of curative intervention for regional lymph nodes; and increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high-dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (exempli gratia (e.g.) 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle-invasive bladder cancer patients with favorable

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

International Nuclear Information System (INIS)

Yee, Don; Parliament, Matthew; Rathee, Satyapal; Ghosh, Sunita; Ko, Lawrence; Murray, Brad

2010-01-01

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). 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 3 (SD, 29.71 cm 3 ). The mean planning CT-derived bladder volume outside the CBCT counterpart was 47.74 cm 3 (SD, 21.64 cm 3 ). The mean CBCT PTV outside the planning CT-derived PTV was 47.35 cm 3 (SD, 36.51 cm 3 ). The mean planning CT-derived PTV outside the CBCT-derived PTV was 93.16 cm 3 (SD, 50.21). The mean CBCT-derived bladder volume outside the planning PTV was 2.41 cm 3 (SD, 3.97 cm 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.

Chemoradiotherapy as a bladder-preservation approach for muscle-invasive bladder cancer. Current status and perspectives

International Nuclear Information System (INIS)

Sumiyoshi, Yoshiteru

2004-01-01

Radical cystectomy has been considered the (gold standard for the treatment of muscle-invasive bladder r cancer. However, because of disappointing results with radical surgery in terms of survival and decreased quality of life (QOL), bladder-preservation treatment has been introduced as an alternative to radical cystectomy. The primary purpose of the bladder-preservation approach has been to maximize overall cure rates, with the secondary purpose being to preserve the patient's bladder. The modalities used to ensure successful bladder preservation include radical transurethral resection (TUR), concurrent cisplatin (CDDP)-based chemotherapy, and radiotherapy. In patients who achieve a complete response (CR) after trimodality therapy, 5-year survival rates of more than 50%, the same as those of radical cystectomy, can be achieved and 70% of this group will retain an intact functional bladder. In this article, bladder-preservation studies using chemoradiotherapy are reviewed. (author)

Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study.

Science.gov (United States)

Rocha, Jeová Nina

2016-01-01

To determine adenosine 5'-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5'-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5'-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5'-triphosphate levels and no further increase in adenosine 5'-triphosphate was observed during bladder distension. Adenosine 5'-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5'-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5'-triphosphate itself. Determinar as concentra

Work Capacity of the Bladder During Voiding: A Novel Method to Evaluate Bladder Contractile Function and Bladder Outlet Obstruction

Directory of Open Access Journals (Sweden)

Ning Liu

2015-01-01

Full Text Available Background: Work in voiding (WIV of the bladder may be used to evaluate bladder status throughout urination rather than at a single time point. Few studies, however, have assessed WIV owing to the complexity of its calculations. We have developed a method of calculating work capacity of the bladder while voiding and analyzed the associations of bladder work parameters with bladder contractile function and bladder outlet obstruction (BOO. Methods: The study retrospectively evaluated 160 men and 23 women, aged >40 years and with a detrusor pressure at maximal flow rate (P det Q max of ≥40 cmH 2 O in men, who underwent urodynamic testing. The bladder power integration method was used to calculate WIV; WIV per second (WIV/t and WIV per liter of urine voided (WIV/v were also calculated. In men, the relationships between these work capacity parameters and P det Q max and Abrams-Griffiths (AG number were determined using linear-by-linear association tests, and relationships between work capacity parameters and BOO grade were investigated using Spearman′s association test. Results: The mean WIV was 1.15 ± 0.78 J and 1.30 ± 0.88 J, mean WIV/t was 22.95 ± 14.45 mW and 23.78 ± 17.02 mW, and mean WIV/v was 5.59 ± 2.32 J/L and 2.83 ± 1.87 J/L in men and women, respectively. In men, WIV/v showed significant positive associations with P det Q max (r = 0.845, P = 0.000, AG number (r = 0.814, P = 0.000, and Schafer class (r = 0.726, P = 0.000. Conversely, WIV and WIV/t showed no associations with P det Q max or AG number. In patients with BOO (Schafer class > II, WIV/v correlated positively with increasing BOO grade. Conclusions: WIV can be calculated from simple urodynamic parameters using the bladder power integration method. WIV/v may be a marker of BOO grade, and the bladder contractile function can be evaluated by WIV and WIV/t.

A case-control study on the association between bladder cancer and prior bladder calculus.

Science.gov (United States)

Chung, Shiu-Dong; Tsai, Ming-Chieh; Lin, Ching-Chun; Lin, Herng-Ching

2013-03-15

Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. This case-control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with bladder calculus for cases was 3.45 (95% CI = 2.39-4.99) that of controls. Among females, the OR was 3.05 (95% CI = 1.53-6.08) that of controls. These results add to the evidence surrounding the conflicting reports regarding the association between BC and prior bladder calculus and highlight a potential target population for bladder cancer screening.

Targeting experimental orthotopic glioblastoma with chitosan-based superparamagnetic iron oxide nanoparticles (CS-DX-SPIONs).

Science.gov (United States)

Shevtsov, Maxim; Nikolaev, Boris; Marchenko, Yaroslav; Yakovleva, Ludmila; Skvortsov, Nikita; Mazur, Anton; Tolstoy, Peter; Ryzhov, Vyacheslav; Multhoff, Gabriele

2018-01-01

Glioblastoma is the most devastating primary brain tumor of the central nervous system in adults. Magnetic nanocarriers may help not only for a targeted delivery of chemotherapeutic agents into the tumor site but also provide contrast enhancing properties for diagnostics using magnetic resonance imaging (MRI). Synthesized hybrid chitosan-dextran superparamagnetic nanoparticles (CS-DX-SPIONs) were characterized using transmission electron microscopy (TEM) and relaxometry studies. Nonlinear magnetic response measurements were employed for confirming the superparamagnetic state of particles. Following in vitro analysis of nanoparticles cellular uptake tumor targeting was assessed in the model of the orthotopic glioma in rodents. CS-DX-SPIONs nanoparticles showed a uniform diameter of 55 nm under TEM and superparamagentic characteristics as determined by T 1 (spin-lattice relaxation time) and T 2 (spin-spin relaxation time) proton relaxation times. Application of the chitosan increased the charge from +8.9 to +19.3 mV of the dextran-based SPIONs. The nonlinear magnetic response at second harmonic of CS-DX-SPIONs following the slow change of stationary magnetic fields with very low hysteresis evidenced superparamagnetic state of particles at ambient temperatures. Confocal microscopy and flow cytometry studies showed an enhanced internalization of the chitosan-based nanoparticles in U87, C6 glioma and HeLa cells as compared to dextran-coated particles. Cytotoxicity assay demonstrated acceptable toxicity profile of the synthesized nanoparticles up to a concentration of 10 μg/ml. Intravenously administered CS-DX-SPIONs in orthotopic C6 gliomas in rats accumulated in the tumor site as shown by high-resolution MRI (11.0 T). Retention of nanoparticles resulted in a significant contrast enhancement of the tumor image that was accompanied with a dramatic drop in T 2 values ( P chitosan-dextran magnetic particles demonstrated high MR contrast enhancing properties for the

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

Science.gov (United States)

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

The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration.

Directory of Open Access Journals (Sweden)

Devon C Snow-Lisy

Full Text Available Recent studies have demonstrated that mesenchymal stem cells (MSCs combined with CD34+ hematopoietic/stem progenitor cells (HSPCs can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2 and bladder smooth muscle content (~42% vs ~36% in Cyr61OX (over-expressing vs Cyr61KD (knock-down groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically

A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer. A prospective study

International Nuclear Information System (INIS)

Miyanaga, Naoto; Akaza, Hideyuki; Okumura, Toshiyuki

2000-01-01

A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. lntra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function. (author)

Detecting bladder fullness through the ensemble activity patterns of the spinal cord unit population in a somatovisceral convergence environment

Science.gov (United States)

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

Objective. 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. Approach. 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. Main results. 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. Significance. 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.

Establishment of a reversible model of prehepatic portal hypertension in rats.

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Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-08-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

Extract Against Toxic Sodium The Protective Role of Grape Seed Proanthocyanidins Nitrites and Gamma Irradiation Induced Histological Changes in Intestine and Urinary Bladder of Male Albino Rats

International Nuclear Information System (INIS)

Abd El- Azeem, M.G.; El-Nashar, D.E.M.

2010-01-01

Proanthocyanidins (a grape seed extract) possess a broad spectrum of biological activities. The present study was performed to investigate the effect of gamma radiation exposure and toxic sodium nitrites induced oxidative stress on the intestine and urinary bladder histologically and also to evaluate the possible protective role of proanthocyanidins. Seventy adult male albino rats, each weighing 95-105 g were used and divided into 7 groups as follows: The first group represents the control group. The second experimental group were exposed to 7 Gy gamma-rays as a single dose and sacrificed on the 7th day. The third experimental group received by a stomach tube daily 50 mg/kg b.wt of sodium nitrite for 4 weeks. The fourth experimental group received proanthocyanidins, Grape seed extracts (antioxidant) (100 mg/kg) body wt.) daily for seven days before irradiation and the continued for 14 days post irradiation. The fifth group of animals received grape seed extract after being exposed to gamma radiation for two weeks, while the sixth experimental group received the same antioxidant for seven days before and after received sodium nitrite (50 mg/kg) daily for 4 weeks. Finally, the seventh experimental groups was treated with the same antioxidant in same dose and time after received sodium nitrite for 4 weeks. The animals were then sacrificed on the end of each experimental duration. The results revealed that both gamma-radiation and sodium nitrite induced different histological changes in the intestine and urinary bladder of irradiated and sodium nitrite received animals. The effect of gamma radiation exposure showed marked degeneration of intestinal villi, vaculation in the lining epithelium cells and karyolytic nuclei. In addition, using sodium nitrite lead to necrosis of intestinal glandular cells. The effect of gamma radiation on urinary bladder was presented by, hyperplasia and vaculation of mucosal epithelium, congestion of blood capillaries. Rats from nitrite

Bladder cancer: overview and disease management. Part 1: non-muscle-invasive bladder cancer.

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Anderson, Beverley

2018-05-10

Part 1 of this two-part article provides an overview of bladder cancer and discusses its management. Since publication of a previous article entitled 'Understanding the role of smoking in the aetiology of bladder cancer' ( Anderson, 2009 ), the author has received many requests for an update. This article provides an overview of bladder cancer and its current management practices, underlining the continued role of smoking as the predominant risk factor in the disease's development. The management of bladder cancer is governed by specific guidelines. Management of non-muscle-invasive cancers, including surgical intervention with transurethral resection, and intravesical therapy using chemotherapy and immunotherapy agents, is discussed. Cystectomy (removal of the bladder), is sometimes necessary. Treatments are effective in reducing tumour recurrence, but the effects of the risks and side-effects on the individual's quality of life can be significant. The prevalence of bladder cancer, and the nature of its management make this cancer one of the most expensive for the NHS to treat. The effectiveness of health promotional strategies in increasing peoples' awareness of their risk of developing the disease, and in enabling them to change long-term health behaviours is discussed. The role of the multidisciplinary team is explored, along with that of the uro-oncology cancer nurse specialist. Part 2 will consider the management of muscle-invasive and metastatic bladder cancer.

OVERACTIVE BLADDER SYNDROME IN CHILDREN

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E.L. Vishnevskiy

2007-01-01

Full Text Available Overactive bladder is a specific syndrome characterized by bladder dysfunction that is clinically manifested by imperative urination (pollakiuria, urgency, urgent incontinence and nocturia. This state is very widely spread among children: every fifth child aged 4 to 7 shows typical bladder dysfunction. Quite often if urinary distresses are not studied well enough such children are falsely diagnosed with monosymptom enuresis, which, according to our information, actually happens in only 3,9% of cases. When examining children with urinary disorders it is reasonable to be geared to the protocol of European urologist association. According to this protocol, treatment should be started with antimuscarinimedications. The only antimuscarinic medication for treating children with hyperactive bladder that is legal in Russia is oxybutinin (Driptane, that is presently considered to be the «golden standard» of pharmaceutical treatment of overactive bladder for patients of any age. This statement is based on the modern idea of overactive bladder pathogenesis, that presupposes detrusorhypersensibility to acetylcholine. However, in some cases it might be reasonable to use some other medications, physiotherapy, sometimes as part of complex therapy. If individual dosage is observed, which will enable preventing or significantly lowering possible side effects, oxybutinin will be still considered «the golden standard» for treating overactive bladder for years to come in cases when detrusor hypersensibility to acetylcholine is the key component of bladder dysfunction pathogenesis.Key words: overactive bladder, oxybutinin, urination disorder, children.

Bladder Cancer—Health Professional Version

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Transitional cell carcinoma of the bladder can be low-grade or high-grade. Bladder cancer is also divided into muscle-invasive and nonmuscle-invasive disease. Find evidence-based information on bladder cancer including treatment, screening, research, and statistics.

Absence of orthotopic renal vein with aberrant suprarenal venous drainage; A case report

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Kim, Eu gene; Jeon, Yong Sun; Cho, Soon Gu; Hong, Kee Chun; Park, Keun Myung; Lee, Tack

2015-01-01

A CT scan of a 49-year-old female incidentally revealed a tortuous vascular structure in the right suprarenal space. According to angiographic evaluation of the right renal vessels, the right renal artery was single with normal diameter, and there was no venous drainage through the main right renal vein (orthotopic renal vein). The venous drainage of the right kidney flowed through the tortuous suprarenal vascular structure into the inferior vena cava. The color Doppler ultrasound revealed the monophasic waveform in that vascular structure without flow disturbance. The renal function and the result of urinalysis of the patient were normal, and any other congenital malformation was not found. Absence of the orthotopic renal vein and aberrant suprarenal venous drainage is a very rare congenital anomaly, and it should be discriminated from the other pathologic conditions

Absence of orthotopic renal vein with aberrant suprarenal venous drainage; A case report

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Kim, Eu gene; Jeon, Yong Sun; Cho, Soon Gu; Hong, Kee Chun; Park, Keun Myung; Lee, Tack [Inha University Hospital, Incheon (Korea, Republic of)

2015-06-15

A CT scan of a 49-year-old female incidentally revealed a tortuous vascular structure in the right suprarenal space. According to angiographic evaluation of the right renal vessels, the right renal artery was single with normal diameter, and there was no venous drainage through the main right renal vein (orthotopic renal vein). The venous drainage of the right kidney flowed through the tortuous suprarenal vascular structure into the inferior vena cava. The color Doppler ultrasound revealed the monophasic waveform in that vascular structure without flow disturbance. The renal function and the result of urinalysis of the patient were normal, and any other congenital malformation was not found. Absence of the orthotopic renal vein and aberrant suprarenal venous drainage is a very rare congenital anomaly, and it should be discriminated from the other pathologic conditions.

Detour technique, Dipping technique, or IIeal bladder flap technique for surgical correction of uretero-ileal anastomotic stricture in orthotopic ileal neobladder

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Mohamed Wishahi

2015-08-01

Full Text Available ABSTRACTBackground:Uretero-ileal anastomotic stricture (UIAS is a urological complication after ileal neobladder, the initial management being endourological intervention. If this fails or stricture recurs, surgical intervention will be indicated.Design and Participants:From 1994 to 2013, 129 patients were treated for UIAS after unsuccessful endourological intervention. Unilateral UIAS was present in 101 patients, and bilateral in 28 patients; total procedures were 157. The previous ileal neobladder techniques were Hautmann neobladder, detubularized U shape, or spherical shape neobladder.Surgical procedures:Dipping technique was performed in 74 UIAS. Detour technique was done in 60 renal units. Ileal Bladder flap was indicated in 23 renal units. Each procedure ended with insertion of double J, abdominal drain, and indwelling catheter.Results:Follow-up was done for 12 to 36 months. Patency of the anastomosis was found in 91.7 % of cases. Thirteen patients (8.3% underwent antegrade dilatation and insertion of double J.Conclusion:After endourological treatment for uretero-ileal anastomotic failure, basically three techniques may be indicated: dipping technique, detour technique, and ileal bladder flap. The indications are dependent on the length of the stenotic/dilated ureteral segment. Better results for long length of stenotic ureter are obtained with detour technique; for short length stenotic ureter dipping technique; when the stenotic segment is 5 cm or more with a short ureter, the ileal tube flap is indicated. The use of double J stent is mandatory in the majority of cases. Early intervention is the rule for protecting renal units from progressive loss of function.

Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature

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Morey Blinder

2013-05-01

Full Text Available Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications.

SU-F-J-05: The Effect of Air Pockets in the Urinary Bladder During Bladder Hyperthermia Treatment

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Schooneveldt, G.; Kok, H.P.; Bakker, A.; Geijsen, E.D.; Reijke, T.M. de; Crezee, J. [Academisch Medisch Centrum / Universiteit van Amsterdam, Amsterdam (Netherlands)

2016-06-15

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 CT 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.

Neuronal Activation in the Periaqueductal Gray Matter Upon Electrical Stimulation of the Bladder

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Céline Meriaux

2018-05-01

Full Text Available Reflexes, that involve the spinobulbospinal pathway control both storage and voiding of urine. The periaqueductal gray matter (PAG, a pontine structure is part of the micturition pathway. Alteration in this pathway could lead to micturition disorders and urinary incontinence, such as the overactive bladder symptom complex (OABS. Although different therapeutic options exist for the management of OABS, these are either not effective in all patients. Part of the pathology of OABS is faulty sensory signaling about the filling status of the urinary bladder, which results in aberrant efferent signaling leading to overt detrusor contractions and the sensation of urgency and frequent voiding. In order to identify novel targets for therapy (i.e., structures in the central nervous system and explore novel treatment modalities such as neuromodulation, we aimed at investigating which areas in the central nervous system are functionally activated upon sensory afferent stimulation of the bladder. Hence, we designed a robust protocol with multiple readout parameters including immunohistological and behavioral parameters during electrical stimulation of the rat urinary bladder. Bladder stimulation induced by electrical stimulation, below the voiding threshold, influences neural activity in: (1 the caudal ventrolateral PAG, close to the aqueduct; (2 the pontine micturition center and locus coeruleus; and (3 the superficial layers of the dorsal horn, sacral parasympathetic nucleus and central canal region of the spinal cord. In stimulated animals, a higher voiding frequency was observed but was not accompanied by increase in anxiety level and locomotor deficits. Taken together, this work establishes a critical role for the vlPAG in the processing of sensory information from the urinary bladder and urges future studies to investigate the potential of neuromodulatory approaches for urological diseases.

Mitochondrial stress and activation of PI3K and Akt survival pathway in bladder ischemia

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Yang JH

2017-06-01

Full Text Available Jing-Hua Yang,1 Mike B Siroky,1 Subbarao V Yalla,2 Kazem M Azadzoi3,4 1Department of Urology, VA Boston Healthcare System, Boston University School of Medicine, 2Department of Urology, VA Boston Healthcare System, Harvard Medical School, 3Department of Urology, 4Department of Pathology, VA Boston Healthcare System, Boston University School of Medicine, Boston, MA, USA Purpose: Detrusor overactivity contributes to bothersome constellation of lower urinary tract symptoms (LUTS in men and women as they age. However, the underlying mechanisms of non-obstructive detrusor overactivity and LUTS remain largely unknown. Growing evidence suggests that ischemia may be an independent factor in the development of non-obstructive bladder dysfunction. Our goal was to determine the effects of ischemia on detrusor function and voiding behavior and define redox-mediated cellular stress and cell survival signaling in the ischemic bladder. Materials and methods: Male Sprague Dawley rats were randomly divided into treatment (n=8 and control (n=8 groups. In the treatment group, iliac artery atherosclerosis and chronic bladder ischemia were induced. At 8 weeks after bladder ischemia, voiding patterns were examined in metabolic cages, cystometrograms were recorded in conscious animals, and then bladder blood flow was measured under general anesthesia. Bladder tissues were processed for assessment of transcription factors, markers of cellular and mitochondrial stress, mitochondrial respiration, and cell survival signaling pathway.Results: Atherosclerotic occlusive disease spread from the common iliac arteries to the internal iliac and vesical arteries and produced sustained bladder ischemia. Studies in metabolic cages showed increased micturition frequency and decreased voided volume in bladder ischemia. Conscious cystometrograms produced consistent data showing significant increase in micturition frequency and decreased voided volume and bladder capacity. Voiding

Effects of urinary bladder distention on location of the urinary bladder and urethra of healthy dogs and cats

International Nuclear Information System (INIS)

Johnston, G.R.; Osborne, C.A.; Jessen, C.R.; Feeney, D.A.

1986-01-01

Evaluation of the anatomic location of the distended and empty urinary bladders and urethras of healthy adult male and female dogs and cats by retrograde urethrocystography revealed substantial variations. In 15 dogs in lateral recumbency with empty bladder lumens, the caudal portion of the urinary bladder was within the pelvic canal in 5 of 7 male and 5 of 8 female dogs. In female dogs examined in ventrodorsal recumbency, only 4 of 8 had the empty urinary bladders in part within the pelvic canal. After luminal distention, 3 of 7 male and 3 of 8 female dogs, while in lateral recumbency, had the urinary bladders in part intrapelvically. However, when female dogs were placed in ventrodorsal recumbency, only 1 of 7 urinary bladders was in part within the pelvis. The urinary bladders of 14 cats were consistently within the abdominal cavity, irrespective of whether the bladder lumen was distended or empty. Urethral flexures occurred in dogs with intrapelvic bladders that were distended or empty. Urethral flexures were not found in cats. The urethras of dogs and cats in lateral recumbency were generally closer to the floor of the pelvis after urinary bladder distention than when the bladder was empty. The urethra of the dogs and cats in ventrodorsal recumbency was to the left or right of or on the midsagittal plane, whether the urinary bladder was empty or distended. A greater degree of lateral displacement was encountered in ventrodorsal recumbency after urinary bladder distention

Hypoxia and metastasis in an orthotopic cervix cancer xenograft model

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Chaudary, Naz; Mujcic, Hilda; Wouters, Bradly G.; Hill, Richard P.

2013-01-01

Background: Hypoxia can promote tumor metastasis by mechanisms that are believed to result from changes in gene expression. The current study examined the role of putative metastatic genes regulated by cyclic hypoxia in relation to metastasis formation in orthotopic models of cervix cancer. Methods: Orthotopic tumors derived from ME180 human cervix cancer cells or from early generation human cervix cancer xenografts were exposed to cyclic hypoxic conditions during growth in vivo and tumor growth and lymphnode metastases were monitored. Expression of the chemokine receptor CXCR4 and various genes in the Hedgehog (Hh) pathway were inhibited using genetic (inducible shRNA vs CXCR4) small molecule (AMD3100) or antibody (5E1) treatment (CXCR4 and Hh genes, respectively) during tumor growth. Results: As reported previously, exposure of tumor bearing mice to cyclic hypoxia caused a reduction of tumor growth but a large increase in metastasis. Inhibition of CXCR4 or Hh gene activity during tumor growth further reduced primary tumor size and reduced lymphatic metastasis to levels below those seen in control mice exposed to normoxic conditions. Conclusion: Blocking CXCR4 or Hh gene expression are potential therapeutic pathways for improving cervix cancer treatment

Leiomyoma of the bladder and MRI

International Nuclear Information System (INIS)

Kabbaj, N.; Dafiri, R.; Imani, F.; Benslimane, L.; Benchekroun, A.

1998-01-01

Unlike epithelial tumors, connective tissue tumors are uncommon, representing only 3 % of all bladder tumors. Leiomyoma of the bladder is the most frequent non-epithelial benign tumor of the bladder. Magnetic resonance imaging (MIR) is highly useful for diagnostic purposes and to determine the degree of extension. Only few reports of sonographic findings have been reported for leiomyoma of the bladder. The tumor usually develops within the bladder. Extra-vesicular formations have also been reported as well as a few intramural localizations. The characteristic feature is the absence of mucosal involvement. We analyzed the MRI findings in a case of leiomyoma of the bladder with intra and extra-vesicular development inflammatory reaction of the bladder wall and uterine adherences in a woman with a past history of chronic cystitis. The role of diagnostic MRI is discussed. (author)

Bladder pain syndrome

DEFF Research Database (Denmark)

Hanno, Philip; Nordling, Jørgen; Fall, Magnus

2011-01-01

Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has...

Calcifications of the bladder in schistosomiasis

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Wechmar, M. von; Vogel, H.

1989-01-01

In schistosomiasis calcification of the urinary bladder are characteristic signs that allow a corresponding diagnosis in endemic regions. Problems concerning differential diagnosis occur only in very rare cases. The calcifications of the bladder can be easily detected by native diagnostics. A late complication in an affected bladder is often a bladder carcinoma. (orig.) [de

Transurethral resection for botryoid bladder rhabdomyosarcoma

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Mitsuyuki Nakata

2018-01-01

Full Text Available The outcome of multimodal therapy for localized bladder rhabdomyosarcoma is quite good in terms of morbidity, and conservative surgery is generally recommended. However, in cases originating in the bladder neck, tumorectomy or partial cystectomy has adverse effects on bladder function. A 2-year-old girl underwent transurethral resection of a bladder tumor (TUR-BT, chemotherapy consisting of vincristine, actinomycin-D, and cyclophosphamide, and radiotherapy. She was in remission for 3 years when frequent urination became evident. Her bladder capacity and compliance were low; however, her urinary symptom was controlled using anticholinergic medication. Accordingly, TUR-BT could be an optional approach for bladder rhabdomyosarcoma. Keywords: Rhabdomyosarcoma, Transurethral resection, Conservative surgery

Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer.

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Okumura, Masaki; Ichihara, Hideaki; Matsumoto, Yoko

2018-11-01

Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

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.

Science.gov (United States)

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.

Image-guided radiotherapy of bladder cancer: bladder volume variation and its relation to margins

DEFF Research Database (Denmark)

Muren, Ludvig; Redpath, Anthony Thomas; Lord, Hannah

2007-01-01

: The correlation between the relative bladder volume (RBV, defined as repeat scan volume/planning scan volume) and the margins required to account for internal motion was first studied using a series of 20 bladder cancer patients with weekly repeat CT scanning during treatment. Both conformal RT (CRT) and IGRT......BACKGROUND AND PURPOSE: To control and account for bladder motion is a major challenge in radiotherapy (RT) of bladder cancer. This study investigates the relation between bladder volume variation and margins in conformal and image-guided RT (IGRT) for this disease. MATERIALS AND METHODS...... these patients were given fluid intake restrictions on alternating weeks during treatment. RESULTS: IGRT gave the strongest correlation between the RBV and margin size (R(2)=0.75; p10mm were required in only 1% of the situations when the RBV1, whereas isotropic margins >10...

Synthesis of 99mTc-oxybutynin for M3-receptor-mediated imaging of urinary bladder

International Nuclear Information System (INIS)

Moustapha, M.E.; Benha University, Benha; Motaleb, M.A.; Ibrahim, I.T.

2011-01-01

Radiolabeling of oxybutynin, a muscarinic acetylcholine (mACh) receptor antagonist agent with 99m Tc is of considerable interest for imaging of urinary bladder. This study is aimed to optimize radiolabeling yield of oxybutynin with 99m Tc using SnCl 2 x 2H 2 O as a reducing agent with respect to factors that affect the reaction conditions such as oxybutynin amount, stannous chloride amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 8 h. 99m Tc-oxybutynin was injected via subcutaneous and intravenous administration routes into normal Sprague-Dawley rats. Biodistribution studies have revealed that 99m Tc-oxybutynin exhibits high affinity and specificity for the muscarinic M 3 subtype located on the smooth muscle of urinary bladder relative to the M 1 and M 2 subtypes of the G protein coupled receptor (GPCR) superfamily. In vivo uptake of subcutaneous 99m Tc-oxybutynin in urinary bladder was 19.6 ± 0.42% ID at 0.5 h, whereas in intravenous administration route the accumulation in the urinary bladder was found to be 9.4 ± 0.31% ID at 0.5 h post injection. Administration of cold oxybutynin effectively blocked urinary bladder uptake and further confirms the high specificity of this complex for the M 3 receptor. (author)

HAMLET treatment delays bladder cancer development.

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Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

2010-04-01

HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Review of underactive bladder

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Yi-Huei Chang

2018-03-01

Full Text Available In clinical practice, many patients cannot empty their bladders within an acceptable duration. Common complaints include weak urinary stream and incomplete emptying, which may affect quality of life. Bladder emptying requires sufficient detrusor contractile power, velocity, and durability. The urodynamic term for inadequate detrusor contraction is detrusor underactivity (DU. Although this definition was provided by the ICS, it may not be clinically practical. Analogous to the relationship between overactive bladder (OAB and detrusor overactivity (DO, the symptom complex caused by DU is termed underactive bladder (UAB. Many conditions lead to UAB, such as advanced age, neurogenic bladder and BOO, but the definite pathophysiology directly leading to UAB is still being widely studied without a widely-accepted consensus. The preferred mainstream treatment for increased residual urine volume caused by UAB is intermittent catheterization, while pharmacotherapy is still disappointing after decades of development. There are no studies on surgical treatment for UAB with an acceptable level of evidence. We reviewed the recent literature on UAB and DU to provide a comprehensive discussion of the related presentation, etiology, diagnosis and management.

Biliary complications following orthotopic liver transplantation: May contrast-enhanced MR Cholangiography provide additional information?

Directory of Open Access Journals (Sweden)

Piero Boraschi

2016-01-01

Conclusions: Contrast-enhanced T1-weighted MR Cholangiography may improve the level of diagnostic confidence provided by conventional T2-weighted MR Cholangiography in the evaluation of biliary complications after orthotopic liver transplantation.

Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

International Nuclear Information System (INIS)

Pos, Floris J.; Koedooder, Kees; Hulshof, Maarten C.C.M.; Tienhoven, Geertjan van; Gonzalez Gonzalez, Dionisio

2003-01-01

Purpose: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. Methods and Materials: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. Results: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. Conclusion: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy

Influence of bladder and rectal volume on spatial variability of a bladder tumor during radical radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Pos, Floris J; Koedooder, Kees; Hulshof, Maarten C.C.M.; Tienhoven, Geertjan van; Gonzalez Gonzalez, Dionisio

2003-03-01

Purpose: To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. Methods and Materials: Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. Results: In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. Conclusion: In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy.

SOX4 expression in bladder carcinoma

DEFF Research Database (Denmark)

Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten

2006-01-01

The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease....... the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P bladder cell line HU609, SOX4...

Duplex gall bladder: bystander or culprit.

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Kumar, Jogender; Yadav, Arushi

2017-08-30

Gall bladder (GB) duplication is a rare anatomical malformation, which can be detected by preoperative imaging study. We present a case of duplex gall bladder in a 14-year-old boy who presented with abdominal pain. On ultrasound, he had right nephrolithiasis and duplex gall bladder. Duplex gall bladder was confirmed on MR cholangiopancreatography. There was a dilemma for surgical management of duplex gall bladder; however, he became asymptomatic after conservative treatment. Prophylactic surgery is not recommended for asymptomatic incidentally detected duplex gall bladder. Radiologists and paediatric surgeons should be sensitised about the exact anatomy of this entity. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bladder cancer and schistosomiasis

International Nuclear Information System (INIS)

Zaghloul, M.S.

2012-01-01

Schistosoma-associated bladder cancer was believed, for several decades, to be a completely unique entity of disease, different from urothelial cancer. This was probably due to its distinct clinico pathologic and demographic features that varied from those of urothelial entity. The carcinogenesis is an extremely complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation regulation process. In bladder cancer, many of these carcinogenic cascades were not fully documented or somewhat conflicting. In spite of the efforts performed, much is still needed to explore the presence or absence of the carcinogenic difference with a different etiology. The control of schistosomiasis in certain countries and the subsequent decrease in the intensity of infestation showed changing of features approaching that of urothelial tumors. However the schistosoma-associated bladder cancer presented in more advanced stages than schistosoma-non associated urothelial cancer. More recently, data are gathered that, upon applying the same treatment protocol and management care, stage by stage comparison of the treatment end-results were found to be similar in bladder cancer patients with a different etiology. All treatment options; including radical cystectomy with or without adjuvant or neoadjuvant chemo- or radiotherapy or tri modality bladder preserving treatment seem to lead to similar end-results regardless of etiologic factor(s) implicated in bladder cancer development.

Reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells.

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Nitta, Masahiro; Tamaki, Tetsuro; Tono, Kayoko; Okada, Yoshinori; Masuda, Maki; Akatsuka, Akira; Hoshi, Akio; Usui, Yukio; Terachi, Toshiro

2010-05-15

BACKGROUND.: Postoperative neurogenic bladder dysfunction is a major complication of radical hysterectomy for cervical cancer and is mainly caused by unavoidable damage to the bladder branch of the pelvic plexus (BBPP) associated with colateral blood vessels. Thus, we attempted to reconstitute disrupted BBPP and blood vessels using skeletal muscle-derived multipotent stem cells that show synchronized reconstitution capacity of vascular, muscular, and peripheral nervous systems. METHODS.: Under pentobarbital anesthesia, intravesical pressure by electrical stimulation of BBPP was measured as bladder function. The distal portion of BBPP with blood vessels was then cut unilaterally (experimental neurogenic bladder model). Measurements were performed before, immediately after, and at 4 weeks after transplantation as functional recovery. Stem cells were obtained from the right soleus and gastrocnemius muscles after enzymatic digestion and cell sorting as CD34/45 (Sk-34) and CD34/45 (Sk-DN). Suspended cells were autografted around the damaged region, whereas medium alone and CD45 cells were transplanted as control groups. To determine the morphological contribution of the transplanted cells, stem cells obtained from green fluorescent protein transgenic mouse muscles were transplanted into a nude rat model and were examined by immunohistochemistry and immunoelectron microscopy. RESULTS.: At 4 weeks after surgery, the transplantation group showed significantly higher functional recovery ( approximately 80%) than the two controls ( approximately 28% and 24%). The transplanted cells showed an incorporation into the damaged peripheral nerves and blood vessels after differentiation into Schwann cells, perineurial cells, vascular smooth muscle cells, pericytes, and fibroblasts around the bladder. CONCLUSION.: Transplantation of multipotent Sk-34 and Sk-DN cells is potentially useful for the reconstitution of damaged BBPP.

Pathobiology and Chemoprevention of Bladder Cancer

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Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

2011-01-01

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

Disulfide high mobility group box-1 causes bladder pain through bladder Toll-like receptor 4.

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Ma, Fei; Kouzoukas, Dimitrios E; Meyer-Siegler, Katherine L; Westlund, Karin N; Hunt, David E; Vera, Pedro L

2017-05-25

Bladder pain is a prominent symptom in several urological conditions (e.g. infection, painful bladder syndrome/interstitial cystitis, cancer). Understanding the mechanism of bladder pain is important, particularly when the pain is not accompanied by bladder pathology. Stimulation of protease activated receptor 4 (PAR4) in the urothelium results in bladder pain through release of urothelial high mobility group box-1 (HMGB1). HGMB1 has two functionally active redox states (disulfide and all-thiol) and it is not known which form elicits bladder pain. Therefore, we investigated whether intravesical administration of specific HMGB1 redox forms caused abdominal mechanical hypersensitivity, micturition changes, and bladder inflammation in female C57BL/6 mice 24 hours post-administration. Moreover, we determined which of the specific HMGB1 receptors, Toll-like receptor 4 (TLR4) or receptor for advanced glycation end products (RAGE), mediate HMGB1-induced changes. Disulfide HMGB1 elicited abdominal mechanical hypersensitivity 24 hours after intravesical (5, 10, 20 μg/150 μl) instillation. In contrast, all-thiol HMGB1 did not produce abdominal mechanical hypersensitivity in any of the doses tested (1, 2, 5, 10, 20 μg/150 μl). Both HMGB1 redox forms caused micturition changes only at the highest dose tested (20 μg/150 μl) while eliciting mild bladder edema and reactive changes at all doses. We subsequently tested whether the effects of intravesical disulfide HMGB1 (10 μg/150 μl; a dose that did not produce inflammation) were prevented by systemic (i.p.) or local (intravesical) administration of either a TLR4 antagonist (TAK-242) or a RAGE antagonist (FPS-ZM1). Systemic administration of either TAK-242 (3 mg/kg) or FPS-ZM1 (10 mg/kg) prevented HMGB1 induced abdominal mechanical hypersensitivity while only intravesical TLR4 antagonist pretreatment (1.5 mg/ml; not RAGE) had this effect. The disulfide form of HMGB1 mediates bladder pain directly (not

Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

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Liu, Xiang; Liu, Jun; Guan, Yubao; Li, Huiling; Huang, Liyan; Tang, Hailing; He, Jianxing

2012-04-01

To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT. A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice. The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner. The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.

Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

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Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

2014-09-15

The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

Molecular biology of bladder cancer.

Science.gov (United States)

Martin-Doyle, William; Kwiatkowski, David J

2015-04-01

Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

The paediatric neuropathic bladder

African Journals Online (AJOL)

pathophysiological terms, a neurogenic bladder is caused by a spinal reflex arc that occurs when ... and potential progressive renal damage because of high bladder ... creatinine level, can also be used to assess kidney function. Urodynamic ...

Discordance Between Preoperative and Postoperative Bladder Cancer Location: Implications for Partial-Bladder Radiation

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Goldsmith, Benjamin; Tucker, Kai; Conway, Robert Greg; He, Jiwei [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Malkowicz, S. Bruce [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John, E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-03-01

Purpose: There is strong interest in partial-bladder radiation whether as a boost or definitive therapy to limit long-term toxicity. It is unclear that a standard preoperative examination can accurately identify all sites of disease within the bladder. The purpose of this study was to determine the correlation between preoperative localization of bladder tumors with postoperative findings to facilitate partial-bladder radiation techniques when appropriate. Methods and Materials: We examined patients with clinically staged T1-T4 invasive transitional cell carcinoma (TCC) or TCC with variant histology with no history of radiation or partial cystectomy undergoing radical cystectomy. Patients were scored as “under-detected” if a bladder site was involved with invasive disease (≥T1) at the time of cystectomy, but not identified preoperatively. Patients were additionally scored as “widely under-detected” if they had postoperative lesions that were not identified preoperatively in a given site, nor in any adjacent site. Rates of under-detected and widely under-detected lesions, as well as univariate and multivariate association between clinical variables and under-detection, were evaluated using logistic regression. Results: Among 222 patients, 96% (213/222) had at least 1 area of discordance. Fifty-eight percent of patients were under-detected in at least 1 location, whereas 12% were widely under-detected. Among 24 patients with a single site of disease on preoperative evaluation, 21/24 (88%) had at least 1 under-detected lesion and 14/24 (58%) were widely under-detected. On multivariate analysis, only solitary site of preoperative disease was associated with increased levels of under-detection of invasive disease (OR = 4.161, 95% CI, 1.368-12.657). Conclusion: Our study shows a stark discordance between preoperative and postoperative localization of bladder tumors. From a clinical perspective, incomplete localization of all sites of disease within the bladder

Review of Surgical Techniques of Experimental Renal Transplantation in Rats.

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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.

Bladder wall biomechanics: A comprehensive study on fresh porcine urinary bladder

DEFF Research Database (Denmark)

Sami Jokandan, Maryam; Ajalloueian, Fatemeh; Edinger, Magnus

2018-01-01

Regenerative medicine for reconstructive urogenital surgery has been widely studied during the last two decades. One of the key factors affecting the quality of bladder regeneration is the mechanical properties of the bladder scaffold. Insight into the biomechanics of this organ is expected to as...... applied here reveals distinct information, outcomes from the combination of the three can be considered as a helpful data-base to refer to for researchers aiming to regenerate the bladder......., the anisotropic behavior of bladder was evident at strain loads higher than 200%. According to DMA, storage modulus was found to be consistently higher than loss modulus in both directions, revealing the elasticity of the BW. The stress-strain curves of both uniaxial and BB tests showed similar trends. However......, the ultimate stress measured from BB was found to be around 5 times of the relevant stress from uniaxial loading. The ultimate strain in BB (389.9 ± 59.8) was interestingly an approximate average of longitudinal (358 ± 21) and circumferential (435 ± 69) rupture strains. Considering that each testing mode...

Bladder wash cytology, quantitative cytology, and the qualitative BTA test in patients with superficial bladder cancer

NARCIS (Netherlands)

van der Poel, H. G.; van Balken, M. R.; Schamhart, D. H.; Peelen, P.; de Reijke, T.; Debruyne, F. M.; Schalken, J. A.; Witjes, J. A.

1998-01-01

Two new methods for the detection of transitional tumor cells in bladder wash (karyometry: QUANTICYT) and voided urine material (BARD BTA test) were compared with bladder wash cytology for the prediction of histology and tumor recurrence. Bladder wash material and voided urine were sampled from 138

The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

Science.gov (United States)

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.

Matrix metalloproteinase 2 genotype is associated with nonanastomotic biliary strictures after orthotopic liver transplantation

NARCIS (Netherlands)

Ten Hove, W. Rogier; Korkmaz, Kerem S.; den Dries, Sanna Op; de Rooij, Bert-Jan F.; van Hoek, Bart; Porte, Robert J.; van der Reijden, Johan J.; Coenraad, Minneke J.; Dubbeld, Jeroen; Hommes, Daniel W.; Verspaget, Hein W.

Background: Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are involved in connective tissue remodelling in chronic liver disease and complications after OLT. Aim: To evaluate the relationship between

Presumptive migrating gall bladder mucocoele in two dogs with gall bladder rupture.

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Burchell, R K; Thornton, L; Lim, C K; Murakami, M; Nakamura, Y; Gal, A

2017-12-13

A 10-year-old neutered female soft-coated wheaten terrier and a 10-year-old, entire female Pomeranian were presented for vomiting and anorexia. Using ultrasound, an oval structure with a stellate, kiwifruit-like appearance typical of a gall bladder mucocoele was observed in the caudal abdomen of the soft-coated wheaten terrier and adjacent to the liver in the Pomeranian. There was also a moderate volume of abdominal effusion in both dogs. Cytology of the peritoneal fluid indicated a sterile exudative process but varied between the two dogs, with an absence of bile pigment in the soft-coated wheaten terrier and marked bile peritonitis in the Pomeranian. An entire free-floating ectopic mucocoele was confirmed via exploratory laparotomy with concomitant gall bladder rupture and common bile duct obstruction. Both dogs recovered completely after surgery. This is the first report of cases of gall bladder rupture with entire free-floating gall bladder mucocoeles in dogs. © 2017 British Small Animal Veterinary Association.

Portable bladder ultrasound: an evidence-based analysis.

Science.gov (United States)

2006-01-01

The aim of this review was to assess the clinical utility of portable bladder ultrasound. TARGET POPULATION AND CONDITION Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary

Current management of overactive bladder.

Science.gov (United States)

Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

2008-10-01

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

Researchers studying alternative to bladder removal for bladder cancer patients | Center for Cancer Research

Science.gov (United States)

A new phase I clinical trial conducted by researchers at the Center for Cancer Research (CCR) is evaluating the safety and tolerability, or the degree to which any side effects can be tolerated by patients, of a two-drug combination as a potential alternative to bladder removal for bladder cancer patients. The trial targets patients with non-muscle invasive bladder cancer (NMIBC) whose cancers have stopped responding to traditional therapies. Read more...

Estimation of bladder wall location in ultrasound images.

Science.gov (United States)

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.

Cystoscopic enucleation of bladder leiomyoma

Directory of Open Access Journals (Sweden)

Ghassan A Barayan

2012-01-01

Full Text Available We are presenting a rare case of bladder leiomyoma. A 61-year-old female patient was found to have a bladder mass during a work up of lower urinary tract symptoms. After full investigation, she underwent transurethral excision of the mass. The histopathology revealed typical feature of bladder leiomyoma. No recurrence was seen after a follow-up period of 12 months.

Finite element based bladder modeling for image-guided radiotherapy of bladder cancer

NARCIS (Netherlands)

Chai, Xiangfei; van Herk, Marcel; van de Kamer, Jeroen B.; Hulshof, Maarten C. C. M.; Remeijer, Peter; Lotz, Heidi T.; Bel, Arjan

2011-01-01

Purpose: A biomechanical model was constructed to give insight into pelvic organ motion as a result of bladder filling changes. Methods: The authors used finite element (FE) modeling to simulate bladder wall deformation caused by urine inflow. For ten volunteers, a series of MRI scans of the pelvic

The role of imaging in pediatric bladder augmentation

Energy Technology Data Exchange (ETDEWEB)

Breen, Micheal; Chow, Jeanne S. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Phelps, Andrew [UCSF Benioff Children' s Hospital San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Estrada, Carlos [Boston Children' s Hospital, Department of Urology, Boston, MA (United States)

2015-09-15

Bladder augmentation (also called augmentation cystoplasty) refers to a number of surgical methods that increase the capacity and compliance of the urinary bladder. Imaging has an important role in the postoperative evaluation of bladder augmentation. The most common augmentation procedures utilize enteric segments to augment the bladder. The various types of bladder augmentation have characteristic appearances on different imaging modalities. Spontaneous bladder perforation is a complication that is seen in both early and late post-operative periods and it is one of the most important complications for radiologists to be aware of as it is life-threatening. We review the indications for bladder augmentation in children, the surgical techniques employed, the normal postoperative appearances on imaging studies and the role of imaging complications of bladder augmentation including delayed spontaneous bladder rupture, which is life-threatening. (orig.)

Orthotopic liver transplantation as a rescue operation for recurrent hepatocellular carcinoma after partial hepatectomy

OpenAIRE

Shao, Zhuo; Lopez, Rocio; Shen, Bo; Yang, Guang-Shun

2008-01-01

AIM: To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess the risk factors associated with post-OLT mortality.

Medical management of overactive bladder

Directory of Open Access Journals (Sweden)

Sarvpreet S Ubee

2010-01-01

Full Text Available Overactive bladder (OAB, as defined by the International Continence Society, is characterized by a symptom complex including urinary urgency with or without urge incontinence, usually associated with frequency and nocturia. OAB syndrome has an incidence reported from six European countries ranging between 12-17%, while in the United States; a study conducted by the National Overactive Bladder Evaluation program found the incidence at 17%. In Asia, the prevalence of OAB is reported at 53.1%. In about 75%, OAB symptoms are due to idiopathic detrusor activity; neurological disease, bladder outflow obstruction (BOO intrinsic bladder pathology and other chronic pelvic floor disorders are implicated in the others. OAB can be diagnosed easily and managed effectively with both non-pharmacological and pharmacological therapies. The first-line treatments are lifestyle interventions, bladder training, pelvic floor muscle exercises and anticholinergic drugs. Antimuscarinics are the drug class of choice for OAB symptoms; with proven efficacy, and adverse event profiles that differ somewhat.

Bladder preservation for locally advanced bladder cancer by transurethral resection, systemic chemotherapy and radiation

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Honda, Masahito; Satoh, Mototaka; Tujimoto, Yuichi; Takada, Tuyoshi; Matsumiya, Kiyomi; Fujioka, Hideki

2006-01-01

Twenty-three out of 31 patients with clinical T2-4a N0 M0 bladder cancer and given a trial of trimodality therapy including transurethral resection (TUR), systemic chemotherapy and radiation between 1991 and 2002 completed this therapy. The other 8 dropped out because of insufficient clinical effect. Local bladder recurrence was seen in 3 patients and the bladder preservation rate was 64.5%. Nineteen of the 23 patients showed a complete histological response on a subsequent TUR specimen, the other 4 were not examined for histological response. Thirteen of the 19 patients showed a complete histological response after maximal TUR and systemic chemotherapy, while 6 did after TUR, chemotherapy and radiotherapy. Bladder cancer was T2 in, 15, T3 in 1, and T4a in 3 patients. The CR rate for T2 cancer was significantly higher than that for T3-4a cancer. The 5-year disease-specific survival of the 23 patients treated with preservation therapy was 67.1%. Some of the patients with locally advanced bladder cancer may benefit from this preservation therapy. (author)

Full-thickness endometriosis of the bladder

DEFF Research Database (Denmark)

Kjer, Jens Jørgen; Kristensen, Jens; Hartwell, Dorthe

2014-01-01

referral centres in Denmark for surgical treatment of stage III and IV endometriosis. POPULATION: Thirty-one women with deep infiltrating bladder endometriosis. METHODS: All women presenting in the Department of Obstetrics and Gynaecology with deep infiltrating bladder endometriosis between March 2002...... and March 2011. We included only patients with symptomatic full-thickness bladder detrusor endometriosis and mucosal involvement. All patients had had bladder symptoms for two to seven years. MAIN OUTCOME MEASURES: Symptoms after surgery and recurrence rate. RESULTS: The main preoperative symptom...

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats.

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Hasumura, Mai; Imai, Toshio; Cho, Young-Man; Ueda, Makoto; Hirose, Masao; Nishikawa, Akiyoshi; Ogawa, Kumiko

2011-01-01

Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex

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Jeová Nina Rocha

Full Text Available ABSTRACT Objective: To evaluate the effect of neuronal nitric oxide synthase on the striated urethral sphincter and the urinary bladder. Materials and Methods: A coaxial catheter was implanted in the proximal urethra and another one in the bladder of female rats, which were anesthetized with subcutaneous injection of urethane. The urethral pressure with saline continuous infusion and bladder isovolumetric pressure were simultaneously recorded. Two groups of rats were formed. In group I, an intrathecal catheter was implanted on the day of the experiment at the L6-S1 level of the spinal cord; in group II, an intracerebroventricular cannula was placed 5-6 days before the experiment. Results: It was verified that the group treated with S-methyl-L-thio-citrulline, via intrathecal pathway, showed complete or partial inhibition of the urethral sphincter relaxation and total inhibition of the micturition reflexes. The urethral sphincter and the detrusor functions were recovered after L-Arginine administration. When S-methyl-L-thio-citrulline was administered via intracerebroventricular injection, there was a significant increase of urethral sphincter tonus while preserving the sphincter relaxation and the detrusor contractions, at similar levels as before the use of the drugs. Nevertheless there was normalization of the urethral tonus when L-Arginine was applied. Conclusions: The results indicate that, in female rats anaesthetized with urethane, the nNOS inhibitor administrated through the intrathecal route inhibits urethral sphincter relaxation, while intracerebroventricular injection increases the sphincter tonus, without changing bladder function. These changes were reverted by L-Arginine administration. These findings suggest that the urethral sphincter and detrusor muscle function is modulated by nitric oxide.

Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

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Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2013-06-01

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

Tumour cell expansion in bladder epithelium

NARCIS (Netherlands)

J.M.J. Rebel (Annemarie)

1995-01-01

textabstractBladder cancer is common in western society. The major problem of patients with superficial bladder cancer is the high recurrence rate and multifocality of these tumours. In 70 % of the patients superficial bladder cancer recurs after local resection of the tumour within 15 years. The

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

OpenAIRE

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. B...

Long-term survival of bladder preservation therapy with radiation and chemotherapy for locally invasive bladder cancer

International Nuclear Information System (INIS)

Noguchi, Sumio; Takase, Kazunori; Kubota, Yoshinobu; Masuda, Mitsunobu; Yao, Masahiro; Hosaka, Masahiko

1998-01-01

The prognoses and prognostic factors of the 54 patients with locally invasive bladder cancer who underwent bladder preservation therapy at Yokohama City University Hospital between 1977 and 1995 were analyzed statistically. The therapeutic modalities of bladder preservation were mainly radiation or chemotherapy. The prognosis for the patients who underwent bladder preservation therapy was worse than that for the patients who underwent total cystectomy. The prognostic factors of these patients were size and grade of tumor, presence of hydronephrosis and performance status (PS) of the patients by univariate analysis. Tumor grade was the most predictable prognostic factor using multivariate analysis. Only 17 patients survived more than 5 years after treatment; 78% of the survivors had good PS (0 or 1). Five of them died of cancer and two patients were alive with cancer. All of them had G3 tumors. These results suggest that patients with locally invasive G2 tumor could be candiates for bladder preservation therapy and patients who underwent bladder preservation therapy should be evaluated at 10 years post-therapy. (author)

Application of Bladder Acellular Matrix in Urinary Bladder Regeneration: The State of the Art and Future Directions

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Marta Pokrywczynska

2015-01-01

Full Text Available Construction of the urinary bladder de novo using tissue engineering technologies is the “holy grail” of reconstructive urology. The search for the ideal biomaterial for urinary bladder reconstruction has been ongoing for decades. One of the most promising biomaterials for this purpose seems to be bladder acellular matrix (BAM. In this review we determine the most important factors, which may affect biological and physical properties of BAM and its regeneration potential in tissue engineered urinary bladder. We also point out the directions in modification of BAM, which include incorporation of exogenous growth factors into the BAM structure. Finally, we discuss the results of the urinary bladder regeneration with cell seeded BAM.

Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimensional ultrasound bladder scanner

International Nuclear Information System (INIS)

Ahmad, Rozilawati; Hoogeman, Mischa S.; Quint, Sandra; Mens, Jan Willem; Pree, Ilse de; Heijmen, Ben J.M.

2008-01-01

Background and Purpose: For cervical cancer patients, bladder filling variations may result in inadequate EBRT target coverage, unless large safety margins are used. For a group of patients who received full bladder instructions, inter-fraction variations and time trends in bladder volume were quantified, and a 3D ultrasound (US) scanner was tested for on-line bladder volume measurements. Methods and materials: For 24 patients, the bladder volume was measured with US at the time of the planning CT scan, and twice weekly during the course of RT. Comparisons of US with planning CT were used to assess the bladder scanner accuracy. Patients were treated in prone on a belly board, EPID images were acquired to correlate set-up errors with bladder filling variations. Results: Measured US and CT bladder volumes were strongly correlated (R = 0.97, slope 1.1 ± 0.1). The population mean bladder volume at planning of 378 ± 209 ml (1 SD) reduced to 109 ± 88 ml (1 SD) in week 6, a reduction by 71% (average reduction 46 ml/week), revealing a large inter-fraction time trend. Intra-patient variation in bladder volume during RT was 168 ml (1 SD) (range 70-266 ml). Rotation around the LR axis was significantly correlated with bladder volume changes. Conclusions: Despite a full bladder instruction, bladder volumes reduced dramatically during treatment, implying large time trends in target position of these patients. The portable US scanner provides a quick and reliable measurement of the bladder volume, which might assist future online treatment adaptation

Near-infrared spectroscopy for evaluation of cerebral autoregulation during orthotopic liver transplantation

DEFF Research Database (Denmark)

Nissen, P.; Pacino, H.; Frederiksen, H.J.

2009-01-01

in 33 patients, 19 females, who underwent orthotopic liver transplantation (OLT). We evaluated whether S(c)O(2) would remain stable over a wide range of MAP and whether an eventual drop in S(c)O(2) could be related to a low MAP. RESULTS: Among the 31 of 33 patients for whom a NIRS signal could...

Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors

International Nuclear Information System (INIS)

Tuomela, Johanna; Valta, Maija; Seppänen, Jani; Tarkkonen, Kati; Väänänen, H Kalervo; Härkönen, Pirkko

2009-01-01

Prostate cancer metastasizes to regional lymph nodes and distant sites but the roles of lymphatic and hematogenous pathways in metastasis are not fully understood. We studied the roles of VEGF-C and VEGFR3 in prostate cancer metastasis by blocking VEGFR3 using intravenous adenovirus-delivered VEGFR3-Ig fusion protein (VEGFR3-Ig) and by ectopic expression of VEGF-C in PC-3 prostate tumors in nude mice. VEGFR3-Ig decreased the density of lymphatic capillaries in orthotopic PC-3 tumors (p < 0.05) and inhibited metastasis to iliac and sacral lymph nodes. In addition, tumor volumes were smaller in the VEGFR3-Ig-treated group compared with the control group (p < 0.05). Transfection of PC-3 cells with the VEGF-C gene led to a high level of 29/31 kD VEGF-C expression in PC-3 cells. The size of orthotopic and subcutaneous PC-3/VEGF-C tumors was significantly greater than that of PC-3/mock tumors (both p < 0.001). Interestingly, while most orthotopic PC-3 and PC-3/mock tumors grown for 4 weeks metastasized to prostate-draining lymph nodes, orthotopic PC-3/VEGF-C tumors primarily metastasized to the lungs. PC-3/VEGF-C tumors showed highly angiogenic morphology with an increased density of blood capillaries compared with PC-3/mock tumors (p < 0.001). The data suggest that even though VEGF-C/VEGFR3 pathway is primarily required for lymphangiogenesis and lymphatic metastasis, an increased level of VEGF-C can also stimulate angiogenesis, which is associated with growth of orthotopic prostate tumors and a switch from a primary pattern of lymph node metastasis to an increased proportion of metastases at distant sites

Should the bladder be full or empty during gynecologic brachytherapy applications? A bladder dose volume histogram analysis and implications for treatment

International Nuclear Information System (INIS)

Dusenbery, Kathryn E.; Lewandowski, Loretta A.; Higgins, Patrick D.

1996-01-01

Purpose: Chronic radiation cystitis is an uncommon but debilitating late complication of definitive external beam (EB) and brachytherapy (BT) for cervix cancer. During BT an indwelling catheter is usually placed in the bladder, collapsing it closer to the BT sources. We have devised a method to deliver BT with a full bladder. The difference in bladder dose in the full and empty state were analyzed during definitive EBT and BT for cervix cancer. Methods: The technique of Lyman and Wolbarst (1) were used to evaluate the bladder complication probability for a representative cervix cancer patient undergoing EBT and BT. DVHs were generated from CT scans obtained with a full and empty bladder. Three possible dose prescriptions were analyzed. Results: The DVH for the full and empty situations are shown. With the bladder full, the volume of bladder predicted to receive ≥ 80 Gy was approximately 10% for all dose schemes evaluated, whereas with the bladder empty, up to 50% of the bladder volume received ≥ 80 Gy. Conclusions: A distended bladder improves the DVH. A technique for performing full bladder LDR brachytherapy will be discussed

Genetics Home Reference: bladder cancer

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... Testing Registry: Malignant tumor of urinary bladder Other Diagnosis and Management Resources (1 link) MedlinePlus Encyclopedia: Bladder Cancer General Information from MedlinePlus (5 links) Diagnostic Tests ...

Contemporary Management of Bladder Cancer

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Bell, David; Fradet, Yves

1991-01-01

Bladder cancer is currently the fifth most common cancer in Western society, and its incidence appears to be increasing. Important advances have recently occurred in both diagnostic and therapeutic approaches to bladder neoplasms. Presentation is not unique, and physician awareness is important to identify patients who are at risk for bladder neoplasia and consequently require further investigation. A diagnostic approach and contemporary management are discussed. ImagesFigure 1Figure 4 PMID:21229043

Tissue pO2 of Orthotopic 9L and C6 Gliomas and Tumor-Specific Response to Radiotherapy and Hyperoxygenation

International Nuclear Information System (INIS)

Khan, Nadeem; Li Hongbin; Hou, Huagang; Lariviere, Jean P.; Gladstone, David J.; Demidenko, Eugene; Swartz, Harold M.

2009-01-01

Purpose: Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO 2 ) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO 2 in rats using a new and potentially widely useful method, multisite in vivo electron paramagnetic resonance oximetry. Methods and Materials: Intracerebral 9L and C6 tumors were established in the left hemisphere of syngeneic rats, and electron paramagnetic resonance oximetry was successfully used for repeated tissue pO 2 measurements after 9.3 Gy of radiation and during carbogen breathing for 5 consecutive days. Results: Intracerebral 9L gliomas had a pO 2 of 30-32 mm Hg and C6 gliomas were relatively hypoxic, with a pO 2 of 12-14 mm Hg (p 2 of the contralateral brain was 40-45 mm Hg in rats with either 9L or C6 gliomas. Irradiation resulted in a significant increase in pO 2 of the 9L gliomas only. A significant increase in the pO 2 of the 9L and C6 gliomas was observed in rats breathing carbogen, but this effect decreased during 5 days of repeated experiments in the 9L gliomas. Conclusion: These results highlight the tumor-specific effect of radiation (9.3.Gy) on tissue pO 2 and the different responses to carbogen inhalation. The ability of electron paramagnetic resonance oximetry to provide direct repeated measurements of tissue pO 2 could have a vital role in understanding the dynamics of hypoxia during therapy that could then be optimized by scheduling doses at times of improved tumor oxygenation

Developments in bladder cancer

International Nuclear Information System (INIS)

Denis, L.; Niijima, T.; Prout, G.; Schroder, F.H.

1986-01-01

This book contains 20 selections. Some of the titles are: Guidelines for Radiation Therapy in Clinical Research on Bladder Cancer; Transitional Cell Carcinoma in Situ; Policy on Monitoring and Reporting Results; Standardization of Protocol Formnd The Role of Cytology in the Diagnosis, Detection and Follow-up of Bladder Cancer

Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder

DEFF Research Database (Denmark)

Ajalloueian, Fatemeh; Lemon, Greg; Hilborn, Jöns

2018-01-01

and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration...... in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research...

Bladder wall thickness and ultrasound estimated bladder weight in healthy adults with portative ultrasound device

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Selcen Kanyilmaz

2013-01-01

Full Text Available Background: The aim of this study was to investigate bladder wall thickness (BWT and ultrasound estimated bladder weight (UEBW values in healthy population with a portative ultrasound device and their relationship with demographic parameters. Materials and Methods: The study was carried out in Neurorehabilitation Clinic of Ege University Hospital. Ninety-five subjects (48 women and 47 men aged between 18 and 56 were included in the study. BWT and UEBW were determined non-invasively with a portative ultrasound device; Bladder Scan BVM 6500 (Verathon Inc., WA, USA at a frequency of 3.7 MHz at functional bladder capacity. These values were compared by gender, and their relation was assessed with age, body mass index (BMI and parity. Results: Mean BWT was 2.0 ± 0.4 mm and UEBW was 44.6 ± 8.3 g at a mean volume of 338.0 ± 82.1 ml. Although higher results were obtained in men at higher bladder volumes, the results did not differ significantly by gender. Correlation analyses revealed statistically significant correlation between UEBW and age (r = 0.32. BWT was negatively correlated with volume (r = -0.50 and bladder surface area (r = -0.57. Also, statistically significant correlations were observed between UEBW and volume (r = 0.36, bladder surface area (r = 0.48 and BWT (r = 0.25. Conclusion: Determined values of BWT and UEBW in healthy population are estimated with portative ultrasound devices, which are future promising, for their convenient, easy, non-invasive, time-efficient hand-held use for screening.

Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

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Mingliang Li

Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

Ultrasound: Bladder (For Parents)

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... If You Have Questions Print en español Ultrasonido: vejiga What It Is A bladder ultrasound is a safe and painless test that ... Exam: Voiding Cystourethrogram (VCUG) Ultrasound: Renal (Kidneys, Ureters, Bladder) Urinary ... only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

Preoperative balloon occluded arterial infusion chemotherapy for locally invasive bladder cancer. Accurate staging for bladder preservation

International Nuclear Information System (INIS)

Hayashi, Norio; Arima, Kiminobu; Kawamura, Juichi; Tochigi, Hiromi

1999-01-01

The possibility of bladder preservation by preoperative balloon occluded arterial infusion (BOAI) chemotherapy was studied in 111 patients with locally invasive bladder cancer. BOAI was performed by blocking the blood flow of the internal iliac artery and by performing intra-arterial infusion of adriamycin (50 mg/body) and cisplatin (100 mg/body). Before BOAI the clinical diagnosis was T2 in 36, T3a in 29, T3b in 27, T4 in 11 and after BOAI it was T0 in 1, T1 in 27, T2 in 25, T3a in 20, T3b in 20, and T4 in 10. Down staging was observed on diagnostic images in 46.6%. Thirty patients (27.0%) received transurethral resection of bladder tumor (TUR-Bt) and their bladder could be preserved. The 5-year cancer-specific survival rate was 100% in pT0 (n=9), 97.5% in pT1 (n=47), 79.9% in pT2 (n=21), 80.0% in pT3a (n=6), 39.9% in pT3b (n=18) and 51.9% in pT4 cases (n=9). For the bladder preservation, accurate staging diagnosis is required. Since 1992, endorectal magnetic resonance imaging (MRI) has been used in addition to imaging diagnosis for improving the accuracy of staging diagnosis. The accuracies of staging diagnosis with and without endorectal MRI were 62.5% and 44.0%, respectively. BOAI as a neoadjuvant chemotherapy has the possibility of bladder-preserving therapy in locally invasive bladder cancer. Also, the endorectal MRI can improve the accuracy of staging diagnosis, which is important for the bladder preservation. (author)

Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

Science.gov (United States)

Schumacher, S; Bross, S; Scheepe, J R; Alken, P; Jünemann, K P

1999-01-01

Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

Bladder filling variation during conformal radiotherapy for rectal cancer

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Sithamparam, S.; Ahmad, R.; Sabarudin, A.; Othman, Z.; Ismail, M.

2017-05-01

Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients.

Bladder filling variation during conformal radiotherapy for rectal cancer

International Nuclear Information System (INIS)

Sithamparam, S; Ahmad, R; Sabarudin, A; Othman, Z; Ismail, M

2017-01-01

Conformal radiotherapy for rectal cancer is associated with small bowel toxicity mainly diarrhea. Treating patients with a full bladder is one of the practical solutions to reduce small bowel toxicity. Previous studies on prostate and cervix cancer patients revealed that maintaining consistent bladder volume throughout radiotherapy treatment is challenging. The aim of this study was to measure bladder volume variation throughout radiotherapy treatment. This study also measured the association between bladder volume changes and diarrhea. Twenty two rectal cancer patients were recruited prospectively. Patients were planned for treatment with full bladder following departmental bladder filling protocol and the planning bladder volume was measured during CT-simulation. During radiotherapy, the bladder volume was measured weekly using cone-beam computed tomography (CBCT) and compared to planning bladder volume. Incidence and severity of diarrhea were recorded during the weekly patient review. There was a negative time trend for bladder volume throughout five weeks treatment. The mean bladder volume decreased 18 % from 123 mL (SD 54 mL) during CT-simulation to 101 mL (SD 71 mL) on the 5th week of radiotherapy, but the decrease is not statistically significant. However, there was a large variation of bladder volume within each patient during treatment. This study showed an association between changes of bladder volume and diarrhea (P = 0.045). In conclusion bladder volume reduced throughout radiotherapy treatment for conformal radiotherapy for rectal cancer and there was a large variation of bladder volume within patients. (paper)

Adaptive radiotherapy for bladder cancer using deformable image registration of empty and full bladder

DEFF Research Database (Denmark)

Juneja, Prabhjot; Caine, H.; Hunt, P.

2015-01-01

to conv-PTV. In conclusion, the results of this pilot study indicate that the use of a-PTVs could result in substantial decrease in the course averaged planning target volume. This reduction in the PTV is likely to decrease the radiation related toxicity and benefit bladder cancer patients. Currently...... mm) for bladder planning target volume (PTV). The goal of this retrospective study is to define, evaluate and optimize new patient-specific anisotropic PTVs (a-PTVs) using deformable image registration (DIR) between empty and full bladder computed tomography (CT) scans. This will provide an ART...

Interstitial cystitis: painful bladder syndrome

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R F Sholan

2018-02-01

Full Text Available Interstitial cystitis, or painful bladder syndrome, is a chronic inflammatory disease of a bladder of unknown etiology. It negatively affects the quality of life, causes depressive disorders, anxiety, and sexual dysfunction. Despite numerous studies, the etiology of interstitial cystitis is still unclear and it’s considered as painful bladder syndrome with multifactorial origin. According to the US National Health and Nutrition Examination Survey, 470/100 000 people (60/100 000 men, 850/100 000 women are diagnosed with interstitial cystitis. Diagnosis of the disease is difficult and is substantially based on clinical symptoms. Pelvic pain, urinary urgency, frequency and nocturia are the basic complaints in this pathology. The diagnosis requires exclusion of diseases with similar manifestations. So interstitial cystitis is frequently misdiagnosed as urinary tract infection, overactive bladder, urethral obstruction or diverticulosis, chronic prostatitis, bladder cancer, vulvodynia, endometriosis, and chronic pelvic pain. Etiopathogenesis of the disease is uncertain, which makes etiologic treatment impossible. Currently scientific discussions on the causes of disease continue as well as different treatment regimens are offered, but are often ineffective, palliative and temporary. The treatment for intersticial cystitis should focus on restoring normal bladder function, prevention of relapse of symptoms and improvement of patients’ quality of life. The literature review presents current view on the terminology, epidemiology, diagnosis and treatment of interstitial cystitis.

Bladder Dysfunction and Vesicoureteral Reflux

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Ulla Sillén

2008-01-01

Full Text Available In this overview the influence of functional bladder disturbances and of its treatment on the resolution of vesicoureteral reflux (VUR in children is discussed. Historically both bladder dysfunction entities, the overactive bladder (OAB and the dysfunctional voiding (DV, have been described in conjunction with VUR. Treatment of the dysfunction was also considered to influence spontaneous resolution in a positive way. During the last decades, however, papers have been published which could not support these results. Regarding the OAB, a prospective study with treatment of the bladder overactivity with anticholinergics, did not influence spontaneous resolution rate in children with a dysfunction including also the voiding phase, DV and DES (dysfunctional elimination syndrome, most studies indicate a negative influence on the resolution rate of VUR in children, both before and after the age for bladder control, both with and without treatment. However, a couple of uncontrolled studies indicate that there is a high short-term resolution rate after treatment with flow biofeedback. It should be emphasized that the voiding phase dysfunctions (DV and DES are more severe than the genuine filling phase dysfunction (OAB, with an increased frequency of UTI and renal damage in the former groups. To be able to answer the question if treatment of bladder dysfunction influence the resolution rate of VUR in children, randomized controlled studies must be performed.

Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

International Nuclear Information System (INIS)

Ihlaseh-Catalano, Shadia M.; Bailey, Kathryn A.; Cardoso, Ana Paula F.; Ren, Hongzu; Fry, Rebecca C.; Camargo, João Lauro V.de; Wolf, Douglas C.

2014-01-01

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

Effect of Hyperoxygenation on Tissue pO2 and Its Effect on Radiotherapeutic Efficacy of Orthotopic F98 Gliomas

International Nuclear Information System (INIS)

Khan, Nadeem; Mupparaju, Sriram M.S.; Hekmatyar, Shahryar K.; Hou Huagang; Lariviere, Jean P.; Demidenko, Eugene; Gladstone, David J.; Kauppinen, Risto A.; Swartz, Harold M.

2010-01-01

Purpose: Lack of methods for repeated assessment of tumor pO 2 limits the ability to test and optimize hypoxia-modifying procedures being developed for clinical applications. We report repeated measurements of orthotopic F98 tumor pO 2 and relate this to the effect of carbogen inhalation on tumor growth when combined with hypofractionated radiotherapy. Methods and Materials: Electron paramagnetic resonance (EPR) oximetry was used for repeated measurements of tumor and contralateral brain pO 2 in rats during 30% O 2 and carbogen inhalation for 5 consecutive days. The T 1 -enhanced volumes and diffusion coefficients of the tumors were assessed by magnetic resonance imaging (MRI). The tumors were irradiated with 9.3 Gy x 4 fractions in rats breathing 30% O 2 or carbogen to determine the effect on tumor growth. Results: The pretreatment F98 tumor pO 2 varied between 8 and 16 mmHg, while the contralateral brain had 41 to 45 mmHg pO 2 during repeated measurements. Carbogen breathing led to a significant increase in tumor and contralateral brain pO 2 ; however, this effect declined over days. Irradiation of the tumors in rats breathing carbogen resulted in a significant decrease in tumor growth and an increase in the diffusion coefficient measured by MRI. Conclusions: The results provide quantitative measurements of the effect of carbogen inhalation on intracerebral tumor pO 2 and its effect on therapeutic outcome. Such direct repeated pO 2 measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcome by scheduling doses at times of improved tumor oxygenation. EPR oximetry is currently being tested for clinical applications.

Urinary diversion after cystectomy: An Indian perspective

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Deepak Jain

2008-01-01

Full Text Available Radical cystectomy remains the standard treatment for muscle-invasive carcinoma bladder. Various methods have been described for the urinary diversion. In the last 150 years urinary diversion has evolved from cutaneous ureterostomy to the orthotopic neobladder. Especially during the last 20 years, much advancement has been made. We hereby have reviewed the current approaches being used at different centers in India. We have also analyzed the evolution of diversion from conduit to the orthotopic substitution at our center.

Action of naftopidil on spinal serotonergic neurotransmission for inhibition of the micturition reflex in rats.

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Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki; Hattori, Tsuyoshi

2017-03-01

We examined the mechanism of action of naftopidil, an α1D/A blocker, on spinal descending serotonergic neurotransmission for the micturition reflex. We examined (1) urinary 5-hydroxyindole acetic acid (5-HIAA) after intraperitoneal administration of saline, para-chlorophenylalanine (PCPA; a serotonin synthetic enzyme inhibitor), and/or 5-hydroxytryptophan (5-HTP; a serotonin precursor); (2) isovolumetric cystometry after intraperitoneal administration of saline, PCPA, and/or 5-HTP and intravenous injection of naftopidil; and (3) isovolumetric cystometry before and after intrathecal administration of serotonin (5-HT) receptor antagonists and intravenous injection of naftopidil. PCPA decreased and 5-HTP increased urinary 5-HIAA/creatinine. Intraperitoneal injection of PCPA did not influence cystometric parameters. Intraperitoneal injection of 5-HTP significantly shortened the interval between bladder contractions. Intravenous injection of naftopidil transiently abolished bladder contractions. However, the duration of abolishment of bladder contractions after injection of naftopidil in rats given PCPA was significantly shorter than that in rats given vehicle, but significantly longer than that in rats given PCPA and 5-HTP. Intrathecal injection of 5-HT1B, 5-HT3, or 5-HT7 receptor antagonists significantly prolonged the interval between bladder contractions. Intrathecal injection of 5-HT1D or 5-HT2B receptor antagonists significantly shortened the interval between bladder contractions. Combined administration of the maximum non-effective dose of 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, or 5-HT3 receptor antagonists and intravenous injection of naftopidil significantly shortened the duration of abolishment of bladder contraction compared to intravenous injection of naftopidil alone. Naftopidil may inhibit the micturition reflex via 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT3 receptors in the spinal cord. Neurourol. Urodynam. 36:604-609, 2017. © 2016 Wiley Periodicals, Inc. �

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

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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.

Listeria monocytogenes following orthotopic liver transplantation: Central nervous system involvement and review of the literature

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Listeria monocytogene is a well-recognized cause of bacteremia in immunocompromised individuals, including solid organ transplant recipients, but has been rarely reported following orthotopic liver transplantation. We describe a case of listeria meningitis that occurred within a week after liver transplantation. The patient developed a severe headache that mimicked tacrolimus encephalopathy, and was subsequently diagnosed with listeria meningitis by cerebrospinal fluid culture. The infection was successfully treated with three-week course of intravenous ampicillin. Recurrent hepatitis C followed and was successfully treated with interferon alfa and ribavirin. Fourteen cases of listeriosis after orthotopic liver transplantation have been reported in the English literature. Most reported cases were successfully treated with intravenous ampicillin. There were four cases of listeria meningitis, and the mortality of them was 50%.Early detection and treatment of listeria meningitis are the key to obtaining a better prognosis.

Outcome of urinary bladder recurrence after partial cystectomy for en bloc urinary bladder adherent colorectal cancer resection.

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Luo, Hao Lun; Tsai, Kai Lung; Lin, Shung Eing; Chiang, Po Hui

2013-05-01

Around 10 % of colorectal cancers are locally advanced at diagnosis. There are higher incidences for sigmoid and rectal cancer adhered to urinary bladder (UB) rather than other segments of colon cancer. Surgeons often performed partial cystectomy as possible for preservation of patient's life quality. This study investigates prognostic factors in patients who underwent bladder preservation en bloc resection for UB adherent colorectal cancer. From 2000 to 2011, 123 patients with clinically UB involvement colorectal cancer underwent primary colorectal cancer with urinary bladder resection. Seventeen patients were excluded because of the concurrent distant metastasis at diagnosis and another 22 patients were excluded because of total cystectomy with uretero-ileal urinary diversion. Finally, 84 patients with clinical stage IIIC (T4bN0M0, according to AJCC 7th edition) that underwent en bloc colorectal cancer resection with partial cystectomy were enrolled into this study for further analysis. Preoperative colovesical fistula and positive CT result were significantly more in the urinary bladder invasion group (p = 0.043 and 0.010, respectively). Pathological UB invasion is an independent predictor of intravesical recurrence (p = 0.04; HR, 10.71; 95 % CI = 1.12∼102.94) and distant metastasis (p = 0.016; HR, 4.85; 95 % CI = 1.34 ∼ 17.53) in multivariate analysis. For bladder preservation en bloc resection of urinary bladder adherent colorectal cancer, the pathological urinary bladder invasion is significantly associated with more urinary bladder recurrence and distant metastasis. This result helps surgeons make decisions at surgical planning and establish follow-up protocol.

Urinary bladder cancer: role of MR imaging.

Science.gov (United States)

Verma, Sadhna; Rajesh, Arumugam; Prasad, Srinivasa R; Gaitonde, Krishnanath; Lall, Chandana G; Mouraviev, Vladimir; Aeron, Gunjan; Bracken, Robert B; Sandrasegaran, Kumaresan

2012-01-01

Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle. © RSNA, 2012.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

Science.gov (United States)

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Bladder rupture caused by postpartum urinary retention.

Science.gov (United States)

Dueñas-García, Omar Felipe; Rico, Hugo; Gorbea-Sanchez, Viridiana; Herrerias-Canedo, Tomas

2008-08-01

Postpartum bladder rupture is an uncommon surgical emergency and a diagnostic challenge. A primigravida delivered a healthy newborn without complications at 39.4 weeks of gestation. The patient was admitted 80 hours postpartum with abdominal pain, oliguria, hematuria, and pain that worsened during the previous 4 hours. An inserted Foley catheter drained only a small amount of urine, and serum creatinine was elevated (3.5 mg/dL). A laparotomy was performed and revealed a 10-cm hole in the urinary bladder. The bladder was repaired and the patient was discharged 15 days after surgery. The follow-up cystoscopy revealed adequate healing of the bladder. Urinary retention can lead to serious complications, including bladder rupture. Postpartum bladder rupture due to urinary retention should be ruled out if there is a history of abdominal pain, oliguria, and elevated of serum creatinine.

Applications of Nanotechnology in Bladder Cancer Therapy

Directory of Open Access Journals (Sweden)

Jong-Wei Hsu

2012-01-01

Full Text Available Effective therapies can prevent superficial bladder cancer from developing into muscle-invasive stage or more severe stages which require radical cystectomy and negatively affect life quality. In terms of therapeutic approaches against superficial bladder cancer, intravesical (regional therapy has several advantages over oral (systemic therapy. Though urologists can directly deliver drugs to bladder lesions by intravesical instillation after transurethral resection, the efficacy of conventional drug delivery is usually low due to the bladder permeability barrier and bladder periodical discharge. Nanoparticles have been well developed as pharmaceutical carriers. By their versatile properties, nanoparticles can greatly improve the interactions between urothelium and drugs and also enhance the penetration of drugs into urothelium with lesions, which dramatically improves therapeutic efficacy. In this review, we discuss the advances of nanotechnology in bladder cancer therapy by different types of nanoparticles with different encapsulating materials.

Surgical Management of Anatomic Bladder Outlet Obstruction in Males with Neurogenic Bladder Dysfunction: A Systematic Review.

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Noordhoff, Toscane C; Groen, Jan; Scheepe, Jeroen R; Blok, Bertil F M

2018-03-15

Surgical treatment of anatomic bladder outlet obstruction (BOO) may be indicated in males with neurogenic bladder dysfunction. A bothersome complication after surgery is urinary incontinence. To identify the optimal practice in the surgical treatment of anatomic BOO in males with neurogenic bladder dysfunction, due to multiple sclerosis, Parkinson disease, spinal cord injury (SCI), spina bifida, or cerebrovascular accident (CVA). A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Medline, Embase, Cochrane controlled trial databases, Web of Science, and Google Scholar were searched for publications until January 2017. A total of 930 abstracts were screened. Eight studies were included. The types of anatomic BOO discussed were benign prostate obstruction, urethral stricture, and bladder neck sclerosis. The identified surgical treatments were transurethral resection of the prostate (TURP) in patients with Parkinson, CVA or SCI, endoscopic treatment of urethral stricture by laser ablation or urethrotomy (mainly in SCI patients), and bladder neck resection (BNR) in SCI patients. The outcome of TURP may be highly variable, and includes persistent or de novo urinary incontinence, regained normal micturition control, and urinary continence. Good results were seen in BNR and endoscopic urethrotomy studies. Laser ablation and cold knife urethrotomy resulted in restarting intermittent catheterization or adequate voiding. Overall, a high risk of bias was found. This systematic review provides an overview of the current literature on the outcome of several surgical approaches of different types of anatomic BOO in males with neurogenic bladder dysfunction. Identifying the optimal practice was impossible due to limited availability of high-quality studies. The outcome of several surgical approaches in males with neurogenic bladder dysfunction with benign prostate obstruction, urethral stricture

Salinomycin nanoparticles interfere with tumor cell growth and the tumor microenvironment in an orthotopic model of pancreatic cancer.

Science.gov (United States)

Daman, Zahra; Faghihi, Homa; Montazeri, Hamed

2018-05-02

Recently, salinomycin (SAL) has been reported to inhibit proliferation and induce apoptosis in various tumors. The aim of this study was to deliver SAL to orthotopic model of pancreatic cancer by the aid of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The NPs were physico-chemically characterized and evaluated for cytotoxicity on luciferase-transduced AsPC-1 cells in vitro as well as implanted orthotopically into the pancreas of nude mice. SAL (3.5 mg/kg every other day) blocked tumor growth by 52% compared to the control group after 3 weeks of therapy. Western blotting of tumor protein extracts indicated that SAL treatment leads to up-regulation of E-cadherin, β-catenin, and transforming growth factor beta receptor (TGFβR) expressions in AsPC-1 orthotopic tumor. Noteworthy, immunofluorescence staining of adjacent tumor sections showed that treatment with SAL NPs cause significant apoptosis in the tumor cells rather than the stroma. Further investigations also revealed that TGFβR2 over-expression was induced in stroma cells after treatment with SAL NPs. These results highlight SAL-loaded PLGA NPs as a promising system for pancreatic cancer treatment, while the mechanistic questions need to be subsequently tested.

Permeability and ultrastructure of human bladder epithelium

DEFF Research Database (Denmark)

Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L

1983-01-01

Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed...

Radio-chemo-therapy with 5FU and cisplatin for bladder cancer after TUR-bladder

International Nuclear Information System (INIS)

Schuchardt, U.; Birkenhake, S.; Leykam, S.; Martus, P.; Sauer, R.

1996-01-01

Purpose/Objective: To determine toxicity and efficacy of radio-chemo-therapy (RCT) with 5FU and cisplatin in patients with bladder cancer. Endpoints are initial response, cystectomy-rates and overall-survival. Materials and Methods: From 11/93 to 1/95 13 patients suffering from bladder cancer were first treated with TUR-bladder (TURB). Patient characteristics were as follows: Within 6 weeks after operation the pelvis was irradiated with 54.0 Gy (median) in conventional fractionation (10 MV photons 4-field-box). The bladder was boosted up to 59.4 Gy (median) in isocentric rotation technique. 7 patients were treated with 45 Gy paraaortal. During the first and 5th treatment week chemotherapy (CT) was simultaneously given: 800 mg/m 2* d CISPLATIN as bolus-infusion 30 min prior to RT. 2 months later a further TURB was performed for restaging. Cystectomy was recommended, if invasive cancer was found at this time. Acute hematological and gastrointestinal toxicity was recorded according to the WHO-criteria. Results: At least 81% (e.g. 75% of 2nd course) of CT was applied in 10/13 patients. Median doses were 3500 mg/m 2 5FU and 200 mg/m 2 CISPLATIN. Acute toxicity to bladder and bowel reached grade 2 WHO only. Hematotoxicity (median values) and results ar shown in the following table. Conclusion: Concomitant RCT with 5FU and CISPLATIN seems to be a promising modality for organ-preserving therapy of bladder cancer. Preliminary results show sufficient effect and acceptable toxicity. Since patient number is still low, further investigation is recommended

Selective bladder preservation by combined modality therapy for invasive bladder cancer

Energy Technology Data Exchange (ETDEWEB)

Kachnic, L A; Kaufman, D S; Zietman, A L; Dallow, K C; Griffin, P P; Heney, N M; Althausen, A F; Shipley, W U

1995-07-01

Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

Selective bladder preservation by combined modality therapy for invasive bladder cancer

International Nuclear Information System (INIS)

Kachnic, L. A.; Kaufman, D. S.; Zietman, A. L.; Dallow, K. C.; Griffin, P. P.; Heney, N. M.; Althausen, A. F.; Shipley, W. U.

1995-01-01

Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

Generic method for automatic bladder segmentation on cone beam CT using a patient-specific bladder shape model

International Nuclear Information System (INIS)

Schoot, A. J. A. J. van de; Schooneveldt, G.; Wognum, S.; Stalpers, L. J. A.; Rasch, C. R. N.; Bel, A.; Hoogeman, M. S.; Chai, X.

2014-01-01

Purpose: The aim of this study is to develop and validate a generic method for automatic bladder segmentation on cone beam computed tomography (CBCT), independent of gender and treatment position (prone or supine), using only pretreatment imaging data. Methods: Data of 20 patients, treated for tumors in the pelvic region with the entire bladder visible on CT and CBCT, were divided into four equally sized groups based on gender and treatment position. The full and empty bladder contour, that can be acquired with pretreatment CT imaging, were used to generate a patient-specific bladder shape model. This model was used to guide the segmentation process on CBCT. To obtain the bladder segmentation, the reference bladder contour was deformed iteratively by maximizing the cross-correlation between directional grey value gradients over the reference and CBCT bladder edge. To overcome incorrect segmentations caused by CBCT image artifacts, automatic adaptations were implemented. Moreover, locally incorrect segmentations could be adapted manually. After each adapted segmentation, the bladder shape model was expanded and new shape patterns were calculated for following segmentations. All available CBCTs were used to validate the segmentation algorithm. The bladder segmentations were validated by comparison with the manual delineations and the segmentation performance was quantified using the Dice similarity coefficient (DSC), surface distance error (SDE) and SD of contour-to-contour distances. Also, bladder volumes obtained by manual delineations and segmentations were compared using a Bland-Altman error analysis. Results: The mean DSC, mean SDE, and mean SD of contour-to-contour distances between segmentations and manual delineations were 0.87, 0.27 cm and 0.22 cm (female, prone), 0.85, 0.28 cm and 0.22 cm (female, supine), 0.89, 0.21 cm and 0.17 cm (male, supine) and 0.88, 0.23 cm and 0.17 cm (male, prone), respectively. Manual local adaptations improved the segmentation

[To the issue of postreperfusion syndrome predictors in orthotopic liver transplantation (OLT)].

Science.gov (United States)

Kiseleva, E A; Ushakova, I A; Kim, E F; Matveev, G P; Biriulina, N Iu; Vabishchevich, A V

2012-01-01

The aim of the study is revelation of postperfusion syndrome (pPS) predictors in orthotopic liver transplantation (OLT). Was conducted a retrospective analysis of anesthesia maintainance protocols during orthotopic liver transplantation in 261 patients aged from 6 months to 60 years. Investigated the effect of various factors on the development of PPS by the application of methods of non-parametric statistics. Significantly more frequent development of the PPS is noted in the age group from 3 to 18 years (up to 30% of patients). In recipients older than 18 years the frequency of the development of the PPS does not depend on age, with an average of 14%. The development of the PPS does not depend on the recipient sex, the nature of the pathology which served as an indication to the OTP, the initial severity of the state, type of OTP (living related donor or cadaveric transplantation, primary or re-transplantation), the transplant warm ischemia duration, use, or the lack of venous-venous bypass, metabolic status of the patient. The obtained results do not contradict to the data of foreign publications. Among parameters available for screening, predictor of PPS was not detected.

Imaging of urinary bladder tumors

International Nuclear Information System (INIS)

Hadjidekov, G.

2015-01-01

Full text: Primary bladder neoplasms account for 2%-6% of all tumors, with urinary bladder cancer ranked as the fourth most common cancer in males. Transitional cell carcinoma (TCC) is the most common subtype of urothelial tumour accounting for approximately 90% of all urothelial cancers. It is typically observed in men aged 50-70 years with history of smoking or occupational exposure to carcinogens. Most urothelial neoplasms are low-grade papillary tumors, with high incidence of recurrence, requires rigorous follow-up but have a relatively good prognosis. Other bladder neoplasm include squamous cell carcinoma accounts for 2%-15% mainly according to geographic location; adenocarcinoma - less than 2% /both occurring in the context of chronic bladder infection and irritation/; mesenchymal tumors in 5%, with the most common examples being rhabdomyosarcoma in children and leiomyosarcoma in adults. More rare mesenchymal tumors include paraganglioma, lymphoma, leiomyoma and solitary fibrous tumor which have no specific typical imaging findings to be differentiated. Multidetector computed tomography urography is an efficient tool for diagnosis and follow-up in patients with transitional cell carcinoma and it can be considered the primary radiologic method for detection, staging and assessment of the entire urothelium regarding the multicentric nature of TCC. MRI is rapidly expanding modality of choice especially in locally staging the tumor and in controversies. Accurate TNM staging is primordial in choosing treatment and prognosis for patients with bladder carcinoma. Correct interpretation and classification of the tumour is helpful for the urologists to determine further management in these cases. The learning objectives of the presentation are: to illustrate the spectrum of CT and MRI findings and to assess their clinical value in patients with transitional cell carcinoma and some other bladder neoplasm; to discuss the TNM staging based on the imaging findings; to be

Bladder filling variations during concurrent chemotherapy and pelvic radiotherapy in rectal cancer patients: early experience of bladder volume assessment using ultrasound scanner

International Nuclear Information System (INIS)

Chang, Jee Suk; Yoon, Hong In; Cha, Hye Jung; Chang, Yoon Sun; Cho, Yeo Na; Keum, Ki Chang; Koom, Woong Sub

2013-01-01

To describe the early experience of analyzing variations and time trends in bladder volume of the rectal cancer patients who received bladder ultrasound scan. We identified 20 consecutive rectal cancer patients who received whole pelvic radiotherapy (RT) and bladder ultrasound scan between February and April 2012. Before simulation and during the entire course of treatment, patients were scanned with portable automated ultrasonic bladder scanner, 5 times consecutively, and the median value was reported. Then a radiation oncologist contoured the bladder inner wall shown on simulation computed tomography (CT) and calculated its volume. Before simulation, the median bladder volume measured using simulation CT and bladder ultrasound scan was 427 mL (range, 74 to 1,172 mL) and 417 mL (range, 147 to 1,245 mL), respectively. There was strong linear correlation (R = 0.93, p < 0.001) between the two results. During the course of treatment, there were wide variations in the bladder volume and every time, measurements were below the baseline with statistical significance (12/16). At 6 weeks after RT, the median volume was reduced by 59.3% to 175 mL. Compared to the baseline, bladder volume was reduced by 38% or 161 mL on average every week for 6 weeks. To our knowledge, this study is the first to prove that there are bladder volume variations and a reduction in bladder volume in rectal cancer patients. Moreover, our results will serve as the basis for implementation of bladder training to patients receiving RT with full bladder.

Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

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Rajan Rajabalaya

2016-08-01

Full Text Available The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT for the treatment of overactive bladder (OAB. Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE, vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%–91.68% and vesicle size was 253–845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB.

Laparoscopic hernia repair and bladder injury.

Science.gov (United States)

Dalessandri, K M; Bhoyrul, S; Mulvihill, S J

2001-01-01

Bladder injury is a complication of laparoscopic surgery with a reported incidence in the general surgery literature of 0.5% and in the gynecology literature of 2%. We describe how to recognize and treat the injury and how to avoid the problem. We report two cases of bladder injury repaired with a General Surgical Interventions (GSI) trocar and a balloon device used for laparoscopic extraperitoneal inguinal hernia repair. One patient had a prior appendectomy; the other had a prior midline incision from a suprapubic prostatectomy. We repaired the bladder injury, and the patients made a good recovery. When using the obturator and balloon device, it is important to stay anterior to the preperitoneal space and bladder. Prior lower abdominal surgery can be considered a relative contraindication to extraperitoneal laparoscopic hernia repair. Signs of gas in the Foley bag or hematuria should alert the surgeon to a bladder injury. A one- or two-layer repair of the bladder injury can be performed either laparoscopically or openly and is recommended for a visible injury. Mesh repair of the hernia can be completed provided no evidence exists of urinary tract infection. A Foley catheter is placed until healing occurs.

Prothrombin complex concentrate in the reduction of blood loss during orthotopic liver transplantation: PROTON-trial

NARCIS (Netherlands)

F. Arshad (Freeha); B. Ickx (Brigitte); R.T. van Beem (Rachel); W.G. Polak (Wojciech); F. Grüne (Frank); F. Nevens (Frederik); M. Ilmakunnas (Minna); A.M. Koivusalo (Anna-Maria); H. Isoniemi (Helena); P.F.W. Strengers; H.J.M. Groen (Henk); H.G.D. Hendriks (Herman); T. Lisman (Ton); J. Pirenne (Jacques); R.J. Porte (Robert)

2013-01-01

textabstractBackground: In patients with cirrhosis, the synthesis of coagulation factors can fall short, reflected by a prolonged prothrombin time. Although anticoagulants factors are decreased as well, blood loss during orthotopic liver transplantation can still be excessive. Blood loss during

Comparison of Bladder Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome

Science.gov (United States)

2017-09-01

PROJECT NUMBER Kenneth M. Peters 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...AWARD NUMBER: W81XWH-16-1-0307 TITLE: Comparison of Bladder-Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain...Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Bladder injuries frequently missed in polytrauma patients

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Tanweer Karim

2010-05-01

Full Text Available Tanweer Karim, Margaret Topno, Vinod Sharma, Raymond Picardo, Ankur HastirSurgery, MGM Medical College, Kamothe, Navi Mumbai, IndiaAbstract: Bladder injuries are very common in patients who have had road traffic accidents. The method of diagnosis and management of such injuries is well established and accepted. However, trauma to the bladder can be associated with other life-threatening injuries which are frequently missed, and often diagnosed during laparotomy for other reasons. The aim of this study was to diagnose bladder injury in polytrauma patients as early as possible, taking into consideration the fact that these patients are hemodynamically unstable and require rapid evaluation and management. In order to achieve our objective, we used bedside sonography with retrograde instillation of normal saline to diagnose bladder injury in addition to use of the conventional retrograde cystogram.Keywords: bladder injury, bladder rupture, retrograde cystogram

Polymeric film of 6-arm-poly(ethylene glycol) amine graphene oxide with poly (ε-caprolactone): Adherence and growth of adipose derived mesenchymal stromal cells culture on rat bladder

Science.gov (United States)

Durán, Marcela; Durán, Nelson; Luzo, Angela C. M.; Duarte, Adriana S. S.; Volpe, Bruno B.; Ceragioli, Helder J.; Andrade, Patricia F.; De Souza, Joel G.; Fávaro, Wagner J.

2017-06-01

Nanotechnology has been more present in different fields related to health. The need to find a durable material, of easy use, and which does not interfere significantly in the growth and differentiation of stem cells for the construction of a scaffold for use in urologic surgery, with the purpose of reducing infections, regeneration times and even graft rejection during reconstitution in patients with urethral stricture was conducted a broad survey of information about this and came to the consensus of this project: using graphene oxide, a widely studied nanomaterials which has been presenting numerous beneficial results when in contact with the adipose-derived stem cells. Advanced techniques for the growth, differentiation and proliferation of adipose-derived stem cells were used, as well as the characterization of graphene oxide sheets. For this study, it was prepared the graphene oxide/6 ARM-Poly (ethylene glycol) amine films with poly (ε-caprolactone). The graphene suspension in organic solvent was prepared by using an ultrasonicator bath and subsequently, the film was formed by solvent evaporation. Total characterization of graphene oxide/6 ARM-PEG-amine/ poly (ε-caprolactone) film was carried out. It was tested growth and adhesion of adipose-derived stem cells on the film, as well as, were verified the histopathological effects of this scaffold when implanted in the urinary bladder to repair the lesion. Our results demonstrated that this scaffold with adipose-derived stem cells enhanced the repair in rat urinary bladder defect model, resulting in a regular bladder. Improved organized muscle bundles and urothelial layer were observed in animals treated with this scaffold with adipose-derived stem cells compared with those treated only suture thread or scaffold. Thus, our biomaterial could be suitable for tissue engineered urinary tract reconstruction.

Polymeric film of 6-arm-poly(ethylene glycol) amine graphene oxide with poly (ε-caprolactone): Adherence and growth of adipose derived mesenchymal stromal cells culture on rat bladder

International Nuclear Information System (INIS)

Durán, Marcela; Durán, Nelson; Fávaro, Wagner J.; Luzo, Angela C.M.; Duarte, Adriana S. S.; Volpe, Bruno B.; Ceragioli, Helder J.; Andrade, Patricia F.; De Souza, Joel G.

2017-01-01

Nanotechnology has been more present in different fields related to health. The need to find a durable material, of easy use, and which does not interfere significantly in the growth and differentiation of stem cells for the construction of a scaffold for use in urologic surgery, with the purpose of reducing infections, regeneration times and even graft rejection during reconstitution in patients with urethral stricture was conducted a broad survey of information about this and came to the consensus of this project: using graphene oxide, a widely studied nanomaterials which has been presenting numerous beneficial results when in contact with the adipose-derived stem cells. Advanced techniques for the growth, differentiation and proliferation of adipose-derived stem cells were used, as well as the characterization of graphene oxide sheets. For this study, it was prepared the graphene oxide/6 ARM-Poly (ethylene glycol) amine films with poly (ε-caprolactone). The graphene suspension in organic solvent was prepared by using an ultrasonicator bath and subsequently, the film was formed by solvent evaporation. Total characterization of graphene oxide/6 ARM-PEG-amine/ poly (ε-caprolactone) film was carried out. It was tested growth and adhesion of adipose-derived stem cells on the film, as well as, were verified the histopathological effects of this scaffold when implanted in the urinary bladder to repair the lesion. Our results demonstrated that this scaffold with adipose-derived stem cells enhanced the repair in rat urinary bladder defect model, resulting in a regular bladder. Improved organized muscle bundles and urothelial layer were observed in animals treated with this scaffold with adipose-derived stem cells compared with those treated only suture thread or scaffold. Thus, our biomaterial could be suitable for tissue engineered urinary tract reconstruction. (paper)

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells.

Science.gov (United States)

Lee, Hyun-Wook; Wang, Hsiang-Tsui; 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

2014-06-15

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.

Can we improve transurethral resection of the bladder tumour for nonmuscle invasive bladder cancer?

NARCIS (Netherlands)

Liem, Esmee Iml; de Reijke, Theo M.

2017-01-01

Purpose of review The recurrence rate in patients with nonmuscle invasive bladder cancer is high, and the quality of transurethral resection of the bladder (TURB) tumour influences recurrence risk. We review new methods that aim to improve the effectiveness of TURB, and highlight studies of the past

Overactive bladder – 18 years – Part II

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Jose Carlos Truzzi

2016-04-01

Full Text Available ABSTRACT Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics – pillars of the overactive bladder pharmacotherapy – started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning – as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder – 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.

Non-muscle-invasive bladder cancer

DEFF Research Database (Denmark)

Malmström, Per-Uno; Agrawal, Sachin; Bläckberg, Mats

2017-01-01

The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden...

Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics.

Science.gov (United States)

Kuo, Hann-Chorng

2011-09-01

The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxinA injections at bladder base/trigone and compare with injections at bladder body or bladder body/trigone for the treatment of idiopathic detrusor overactivity (IDO) refractory to antimuscarinics. A single blind, randomized, paralleled, actively controlled trial was performed in patients with urodynamically proven IDO who failed antimuscarinic therapy. Patients were randomly assigned to receive intravesical injections of 100 U of onabotulinumtoxinA into three different bladder sites. All treatments were evaluated by voiding diary variables, urgency severity score, urodynamic studies, and patient perception of bladder condition. Long-term success rates over 12 months were also determined. Among the patients, 37 were randomized to injections in the bladder body, 35 into the bladder body/trigone, and 33 into the bladder base/trigone. Successful results were reported in 76 (72%) patients at 3 months: 26 (70%) in the bladder body group, 26 (74%) in the bladder body/trigone group, and 24 (73%) in the bladder base/trigone group. There were no significant differences in success rates, changes in urgency and urgency incontinence episodes, urodynamic variables, or long-term success rates among the three subgroups. The incidence of adverse events was similar among three groups. No vesicoureteral reflux was noted in all patients with or without involving trigone injection. Intravesical onabotulinumtoxinA injection is an effective treatment for IDO regardless of the bladder injection site. Bladder base/trigone injection is as safe and effective as bladder body injections with or without trigone involvement. Copyright © 2011 Wiley-Liss, Inc.

Neurogenic bladder in spinal cord injury patients

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Al Taweel W

2015-06-01

Full Text Available Waleed Al Taweel, Raouf SeyamDepartment of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaAbstract: Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury.Keywords: neurogenic bladder, spinal cord injury, urodynamics, intestine, intermittent catheterization

Gall bladder function test with Ceruletid

International Nuclear Information System (INIS)

Schindler, G.

1981-01-01

Compared with the stimulating food given orally in the gall bladder function test the administration of the decapeptide Ceruletid which is related with Cholecystokinin has the advantage of avoiding resorption disturbances in the upper gastrointestinal tract. To 100 patients with positive peroral cholecystography, Ceruletid was injected i.m. in a dose of 0.4 μg/kg body weight. The contrasting of the main bile duct was thus increased from 10% to 86%. The oral stimulating food brings an increase to appr. 20%. A special importance is assigned to the frequent diagnosis of adenomyomatoses which, with 6%, lies significantly above the 0.8% achieved by means of the oral stimulating food. More contractile segments of the gall bladder wall can cause pain symptoms which are typical for the biliary tract. Adenomyomatoses in the region of the infundibulum of the gall bladder cause colicky pains and are, as generally accepted, an absolute indication for a surgical intervention. The finding of small gall bladder conrements is often connected with a strong diminution of the gall bladder in order to prevent the small concrements from being overlapped by the non-contrasting bladder bile. Therefore, the application of Ceruletid should be considered also within the frame of the intravenous cholegraphy, thinking of the large number of normal gall bladder findings which were obtained with the oral stimulating food as the only diagnostical help. (orig./MG) [de

Arsenic and urinary bladder cell proliferation

International Nuclear Information System (INIS)

Luster, Michael I.; Simeonova, Petia P.

2004-01-01

Epidemiologic studies have demonstrated that a close association exists between the elevated levels of arsenic in drinking water and the incidence of certain cancers, including transitional cell carcinomas of the urinary bladder. We have employed in vitro and in vivo models to examine the effects of sodium arsenite on the urinary bladder epithelium. Mice exposed to 0.01% sodium arsenite in drinking water demonstrated hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. This occurred in the absence of amorphous precipitates and was accompanied by the accumulation of trivalent arsenite (iAs 3+ ), and to a lesser extent dimethylarsenic (DMA), arsenate (iAs 5+ ), and monomethylarsenic (MMA) in bladder tissue. In contrast to the bladder, urinary secretion was primarily in the form of DMA and MMA. Arsenic-induced cell proliferation in the bladder epithelium was correlated with activation of the MAP kinase pathway, leading to extracellular signal-regulated kinase (ERK) kinase activity, AP-1 activation, and expression of AP-1-associated genes involved in cell proliferation. Activation of the MAP kinase pathway involved both epidermal growth factor (EGF) receptor-dependent and -independent events, the latter involving Src activation. Studies summarized in this review suggest that arsenic accumulates in urinary bladder epithelium causing activation of specific signaling pathways that lead to chronic increased cell proliferation. This may play a non-epigenetic role in carcinogenesis by increasing the proliferation of initiated cells or increasing the mutational rate

A Boy with a Large Bladder Stone

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Kuo-Shen Chow

2008-08-01

Full Text Available Despite the frequent association of urinary tract infection with vesicoureteral reflux and urinary calculi, since vesicouretal reflux is induced by bladder stones, the coexistence of vesicoureteral reflux and bladder stones is rare. Because of its occurrence in children belonging to poor socioeconomic groups, it is believed to be a deficiency disorder. Most cases of bladder stones occur between the ages of 2 and 5 years. Common clinical presentations of bladder stones include urinary dribbling and enuresis, frequency of micturition, pain during micturition, pelvic pain and hematuria. We report the occurrence of a large bladder stone in a boy, who experienced intermittent lower abdominal pain and urinary incontinence, both during the day and at night. He had been diagnosed with enuresis and treated in pediatric clinics for 1 year. Delayed diagnosis resulted in bladder stone formation. The stone was larger than 2.5 cm and open vesicolithotomy was therefore selected as the best and safest treatment choice. His symptoms disappeared after surgery. Thorough metabolic and environmental evaluations of such cases are required on an individual basis. Bladder stones should be considered as a possible diagnosis in children presenting with urinary incontinence.

Cases of a Borderline Pathology That Can Mimic Bladder Cancer: Primary Amyloidosis of Urinary Bladder

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Cemal Selçuk İşoğlu

2015-06-01

Full Text Available Amyloidosis is a disease characterised by accumulation of a fibrillar protein called amyloid in the extracellular space. The kidneys, ureters and the bladder can be affected in the urinary tract. However, primary amyloidosis of bladder is a rare entity. Macroscopic hematuria could be the first and only symptom of primary amyloidosis of the bladder; therefore, it has similar findings with urinary tract malignancies. Histopathological evaluation is mandatory for the diagnosis. Follow-up should always include cystoscopic evaluation as recurrence is expected in the natural course.

Long term evaluation of functional and morphological bladder alterations on alloxan-induced diabetes and aging: experimental study in rats Avaliação funcional e morfológica tardia de alterações na bexiga secundárias ao diabetes induzido por aloxano e no envelhecimento: estudo experimental em ratos

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Antonio Antunes Rodrigues Jr

2008-01-01

Full Text Available PURPOSE: to evaluate structural and functional effects of Alloxan- induced diabetes and aging on bladder of rats. METHODS: evaluations were performed in three groups: A - 8 weeks of age, B - 44 weeks of age, C - 44 weeks of age with alloxan-induced diabetes. Muscle layer thickness, extracellular matrix fibrosis and collagen were quantified on digital images of bladder samples. Cystometric evaluations before surgical vesical denervation (SVD, included maximum cystometric capacity (MCC, maximum bladder pressure (MBP, bladder contraction frequency (VCF, duration of bladder contraction (DC, threshold pressure (TP and bladder compliance (BC. After SVD, maximum cystometric capacity (MCC, BC and maximum urethral closing pressure (MUCP were also measured. RESULTS: Reduced extracellular matrix fibrosis concentration and contraction strength were found in the bladders of group C. Before SVD, bladder compliance was not different between groups. Alterations were observed in MCC after SVD. CONCLUSIONS: We did not notice smooth muscle hypertrophy in Alloxan-induced diabetic rats after 44 weeks. There was alteration in the total and relative amount of fibrosis and collagen. The cystometric studies support the idea that this morphological alterations are important to determine the different bladder functional patterns found in the aging and the Alloxan-induced diabetic animals.OBJETIVOS: avaliar alterações estruturais e funcionais da bexiga de ratos machos, associadas ao diabetes induzido por aloxano e ao envelhecimento. MÉTODOS: três grupos de animais: A - 8 semanas de idade; B- 44 semanas de idade; C - 44 semanas de idade com diabetes induzido por aloxano, foram avaliados. Realizadas medidas de espessura da camada muscular, fibrose de matriz extracelular e quantidade de colágeno, através de análise de imagem digital dos tecidos. Realizados também testes cistométricos, antes da desnervação vesical cirúrgica (DVC, para avaliar capacidade vesical (CV

Contemporary management of low-risk bladder cancer

NARCIS (Netherlands)

Falke, J.; Witjes, J.A.

2011-01-01

Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the

Changes in cholangiocyte bile salt transporter expression and bile duct injury after orthotopic liver transplantation

NARCIS (Netherlands)

Hoekstra, H.; Op Den Dries, S.; Buis, C.I.; Khan, A.A.; Gouw, A.S.H.; Groothuis, G.M.M.; Lisman, T.; Porte, R.J.

2010-01-01

Background: Bile salts have been shown to contribute to bile duct injury after orthotopic liver transplantation (OLT). Cholangiocytes modify bile composition by reabsorption of bile salts (cholehepatic shunt) and contribute to bile flow by active secretion of sodium and water via cystic fibrosis

The concept of peripheral modulation of bladder sensation.

Science.gov (United States)

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 β 3 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

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

Science.gov (United States)

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

2016-07-01

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

Molecular Diagnosis in Bladder Cancer

NARCIS (Netherlands)

T.C.M. Zuiverloon (Tahlita)

2013-01-01

textabstractEpidemiologyBladder cancer (BC) is the most prevalent type of urothelial cancer and is associated with thehighest costs of all cancer types due to intensive patient surveillance. Because bladder tumorsfrequently recur, patients need to be monitored extensively [1-4]. Incidence increases

Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron.

Science.gov (United States)

Ihlaseh-Catalano, Shadia M; Bailey, Kathryn A; Cardoso, Ana Paula F; Ren, Hongzu; Fry, Rebecca C; de Camargo, João Lauro V; Wolf, Douglas C

2014-11-05

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bladder exstrophy: An overview of the surgical management

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Veereshwar Bhatnagar

2011-01-01

Full Text Available Background: The surgical management of urinary bladder exstrophy is challenging. This paper describes the personal experience in a tertiary care hospital over a period exceeding a quarter of a century. Methods: During the period 1984-2010, 248 patients of the epispadias-exstrophy complex have been treated. The cases of classical bladder exstrophy (n = 210 form the basis of this paper. The stages/procedures used in the surgical reconstruction of bladder exstrophy included bladder closure with anterior abdominal wall reconstruction, bladder neck repair, ureteric reimplantation, epispadias repair and augmentation colocystoplasty in various combinations. Some of these patients had their initial operations done prior to 1984 or in other hospitals. Evaluation methods included, amongst others, clinical evaluation and urodynamic assessment. Eight patients opted out of treatment; 15 patients underwent permanent urinary diversion by either ureterosigmoidostomy or colon conduit. The remaining 187 patients were treated with bladder reconstruction, and of these, 132 patients have had at least one attempt at bladder neck reconstruction with 56 of these patients having undergone an augmentation colocystoplasty. Results: A total of 105 patients had socially acceptable continence: 57 from the bladder neck reconstruction group and 48 from the bladder augmentation group. Further attempts at continence surgery have been offered to the inadequately continent patients. Conclusions: Surgical management of bladder exstrophy demands patience and perseverance. It is possible to provide all patients with socially acceptable continence with bladder neck division and catheterizable continent stoma as the last resort. Urodynamic assessment has emerged as an essential tool in the follow-up evaluation of these patients. Anticholinergic medication with imipramine or oxybutinin is a useful adjunct in the overall management.

Radiotherapy of bladder cancer

International Nuclear Information System (INIS)

Ikeda, Yoshiyuki

1978-01-01

Methods of treating bladder cancer include surgery, radiotherapy and chemotherapy, as well as various combinations of these. The author investigated clinically and histopathologically the therapeutic results of preoperative irradiation in cases of bladder cancer. 1. The survival rates (crude survival rates) in forty cases of bladder cancer were 90% after one year, 62.5% after three years and 46% after five years from the treatment. 2. As the result of irradiation, urogram improved in 25%, which was comparatively remarkable in high stage cases. There were no cases of deterioration of urogram findings caused by irradiation. Cystoscopy revealed disappearance or remarkable shrinkage of the tumors in 35% of the total cases and effects of the irradiation was observed not correlated to the stage and grade. 3. With respect to the histopathological changes, the changes became greater as the dosage increased and the higher the stage and grade were the more remarkable tendency was observed. 4. From our clinical observations such as urogram, cystoscopy and histopathologically, we estimated the optimum dosage of preoperative irradiation for bladder cancer is 3000 - 4000 rad. Thus, we concluded that the radiotherapy is effective in reducing both surgical invasion and postoperative recurrence. (author)

Modeling bladder cancer in mice: opportunities and challenges

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Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory

2015-01-01

The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency.

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Regadas, Rommel Prata; Reges, Ricardo; Cerqueira, João Batista Gadelha; Sucupira, Daniel Gabrielle; Jamacaru, Francisco Vagnaldo F; Moraes, Manoel Odorico de; Gonzaga-Silva, Lúcio Flávio

2014-01-01

The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique

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Jie Ni

2016-02-01

Full Text Available Prostate cancer (CaP is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D ultrasound system equipped with photoacoustic (PA imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8. Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r2 = 0.948, 0.955, and 0.953, respectively and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001. The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research.

Invasive bladder cancer: treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation

International Nuclear Information System (INIS)

Shipley, William U.; Zietman, Anthony L.; Kaufman, Donald S.; Althausen, Alex F.; Heney, Niall M.

1997-01-01

Purpose: Combined modality therapy has become the standard oncologic approach to achieve organ preservation in many malignancies. Methods and Materials: Although radical cystectomy has been considered as standard treatment for invasive bladder carcinoma in the United States, good results have been recently reported from several centers using multimodality treatment, particularly in patients with clinical T2 and T3a disease who do not have a ureter obstructed by tumor. Results: The components of the combined treatment are usually transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation therapy. Following an induction course of therapy a histologic response is evaluated by cystoscopy and rebiopsy. Clinical 'complete responders' (tumor site rebiopsy negative and urine cytology with no tumor cells present) continue with a consolidation course of concurrent chemotherapy and radiation. Those patients not achieving a clinical complete response are recommended to have an immediate cystectomy. Individually the local monotherapies of radiation, TURBT, or multidrug chemotherapy each achieve a local control rate of the primary tumor of from 20 to 40%. When these are combined, clinical complete response rates of from 65 to 80% can be achieved. Seventy-five to 85% of the clinical complete responders will remain with bladders free of recurrence of an invasive tumor. Conclusions: Bladder conservation trials using combined modality treatment approaches with selection for organ conservation by response of the tumor to initial treatment report overall 5-year survival rates of approximately 50%, and a 40-45% 5-year survival rate with the bladder intact. These modern multimodality bladder conservation approaches offer survival rates similar to radical cystectomy for patients of similar clinical stage and age. Bladder-conserving therapy should be offered to patients with invasive bladder carcinoma as a realistic alternative to radical

Giant Leiomyosarcoma of the Urinary Bladder.

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Ribeiro, José G A; Klojda, Carlos A B; Araújo, Claudio P De; Pires, Lucas A S; Babinski, Marcio A

2016-05-01

The bladder leiomyosarcoma is a rare and agressive mesenchymal tumour, and adult women of reproductive age have a higher incidence of developing the bladder leiomyosarcoma. The pathophysiology of the disease is not certain, and its main symptoms are hematuria, dysuria and abdominal pain. There are not a considerable amount of cases described in the literature. We report a case of a giant leiomyosarcoma of the urinary bladder in a 31-year-old woman.

Effect of experimental diabetes on cholinergic, purinergic and peptidergic motor responses of the isolated rat bladder to electrical field stimulation or capsaicin.

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Benkó, Rita; Lázár, Zsófia; Pórszász, Róbert; Somogyi, George T; Barthó, Loránd

2003-09-30

An attempt has been made to pharmacologically isolate cholinergic, P(2) purinoceptor-mediated and peptidergic (capsaicin-sensitive, tachykinin-mediated) contraction of the guanethidine-treated rat bladder detrusor preparation, in vitro. The effect of experimental diabetes was assessed on these types of contraction. Responses were evoked by electrical field stimulation (single shocks or 1 Hz for 30 s or 10 Hz for 40 s). Single shocks and 1-Hz stimulation were applied in the presence of (a). atropine (1 microM) or (b). P(2) purinoceptor antagonists (50 microM pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) [PPADS] plus 100 microM suramin. Long-term electrical field stimulation (10 Hz for 40 s) (c). was applied with both atropine and the P(2) purinoceptor antagonists present in the organ bath. The effects of capsaicin (d). and ATP (e). were also studied. Three groups of experimental animals were used: streptozotocin-treated (50 mg.kg(-1) i.p., 8 weeks before the experiment), parallel solvent-treated and untreated rats. (a). Responses to electrical field stimulation in the presence of atropine were reduced by half by PPADS plus suramin, but were resistant to capsaicin tachyphylaxis. They were enhanced in preparations taken from diabetic rats. (b). Contractions to electrical field stimulation in the presence of PPADS plus suramin were reduced by 2/3 by atropine, but were left unchanged by capsaicin or diabetes. (c). Contractions to long-term stimulation had a quick and a sustained phase. Especially the latter was inhibited by capsaicin tachypyhlaxis; it was also strongly reduced in preparations taken from diabetic rats. (d). Contractions to capsaicin (30 nM and 1 microM) were resistant to tetrodotoxin, strongly reduced by a combination of tachykinin NK(1) and NK(2) receptor antagonists, and slightly reduced in preparations from diabetic animals. Capsaicin (1 microM) had no acute inhibitory action on cholinergic or purinergic responses, nor did it cause relaxation

Dimethylarsinic acid: Results of chronic toxicity/oncogenicity studies in F344 rats and in B6C3F1 mice

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Arnold, Lora L.; Eldan, Michal; Nyska, Abraham; Gemert, Marcia van; Cohen, Samuel M.

2006-01-01

Dimethylarsinic acid (DMA V , cacodylic acid), a foliar herbicide, was administered in the diet to B6C3F1 mice (at dose levels of 0, 8, 40, 200, and 500 ppm) and to F344 rats (at dose levels of 0, 2, 10, 40, and 100 ppm) for 2 years, according to US EPA guidelines. In mice, there were no treatment-related tumors observed at any site. Treatment-related progressive glomerulonephropathy and nephrocalcinosis were observed in the kidneys in both sexes. The incidence of vacuolation of the epithelium in the urinary bladder was increased in both sexes, but was not associated with cytotoxicity, necrosis or hyperplasia. Based on non-neoplastic lesions found in the urinary bladder, the NOEL for mice was assessed to be 40 ppm in males and 8 ppm in females. In rats, treatment-related mortality occurred early in the study in five males in the 100 ppm group and in one male in the 40 ppm group. Papillomas and carcinomas with degeneration of the urothelium, necrosis and urothelial cell hyperplasia, were found in the urinary bladders of both sexes. In male rats, one papilloma was found in each of the 10 and 40 ppm groups; one urothelial cell carcinoma was found in the 2 ppm group and two in the 100 ppm group. Four papillomas and six urothelial cell carcinomas were found in the female 100 ppm group. Non-neoplastic treatment-related kidney lesions were confined to the 40 and 100 ppm levels and included necrosis, pyelonephritis, medullary nephrocalcinosis and tubular cystic dilation, hyperplasia of the epithelial lining of the papilla, and pelvic urothelial cell hyperplasia. All of these kidney changes appear to be related to an increase in the aging nephropathy of the rat. Dose-related increases in the height of the thyroid follicular epithelium were also noted in males and females, however, such changes reflect an adaptive response of the thyroid to decreased levels of circulating thyroid hormone, rather than an adverse effect. Based on the kidney and bladder lesions, the NOEL for

[A case of pulmonary tuberculosis complicated with an orthotopic liver transplantation].

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Kamiya, Hiroyuki; Toyota, Emiko; Kobayashi, Nobuyuki; Kudo, Koichiro

2006-04-01

The infectious disease is one of the most important complications related to the organ transplantation. Patients using immunosuppressive agents often present atypical tuberculosis and the treatment of such case is far more difficult in some cases due to the liver damage and/or the drug interaction. We report a case of pulmonary tuberculosis in a patient of 60-year-old man using tacrolimus after an orthotopic liver transplantation. He had liver transplanted orthotopically for the long-term history of chronic hepatitis B and subsequent liver failure on January 28, 2004. An abnormal shadow was first detected on his chest X-ray film on October, 2004. He was admitted to our hospital after the smear of the gastric juice showed some acid-fast bacilli and tubercle bacilli were confirmed by polymerase chain reaction (PCR). Tuberculin skin test was positive (erythema 10 x 10) and the computed tomography (CT) scan of his chest revealed a nodular opacity with some smaller nodules scattered around in the right upper lobe. We started four anti-tuberculous drugs other than pyrazinamide (PZA) and rifampicin (RFP), which included isoniazid (INH), ethambutol (EB), streptomycin (SM), levofloxacin (LVFX). The liver enzyme was transiently elevated (AST 123 IU/I, ALT 103 IU/I) but improved after desensitization against INH. The blood concentration of tacrolimus preserved between 5 and 7 ng/ml and there was no need to change the dosage.

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

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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.

Short-term effect of acute and repeated urinary bladder inflammation on thigmotactic behaviour in the laboratory rat [v1; ref status: indexed, http://f1000r.es/56e

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Rosemary H Morland

2015-05-01

Full Text Available Understanding the non-sensory components of the pain experience is crucial to developing effective treatments for pain conditions. Chronic pain is associated with increased incidence of anxio-depressive disorders, and patients often report feelings of vulnerability which can decrease quality of life. In animal models of pain, observation of behaviours such as thigmotaxis can be used to detect such affective disturbances by exploiting the influence of nociceptive stimuli on the innate behavioural conflict between exploration of a novel space and predator avoidance behaviour. This study investigates whether acute and repeated bladder inflammation in adult female Wistar rats increases thigmotactic behaviour in the open field paradigm, and aims to determine whether this correlates with activation in the central amygdala, as measured by c-Fos immunoreactivity. Additionally, up-regulation of inflammatory mediators in the urinary bladder was measured using RT-qPCR array featuring 92 transcripts to examine how local mediators change under experimental conditions. We found acute but not repeated turpentine inflammation of the bladder increased thigmotactic behaviour (decreased frequency of entry to the inner zone in the open field paradigm, a result that was also observed in the catheter-only instrumentation group. Decreases in locomotor activity were also observed in both models in turpentine and instrumentation groups. No differences were observed in c-Fos activation, although a general increased in activation along the rostro-caudal axis was seen. Inflammatory mediator up-regulation was greatest following acute inflammation, with CCL12, CCL7, and IL-1β significantly up-regulated in both conditions when compared to naïve tissue. These results suggest that acute catheterisation, with or without turpentine inflammation, induces affective alterations detectable in the open field paradigm accompanied by up-regulation of multiple inflammatory mediators.

Conformal radiotherapy of urinary bladder cancer

International Nuclear Information System (INIS)

Muren, Ludvig Paul; Smaaland, Rune; Dahl, Olav

2004-01-01

Recent advances in radiotherapy (RT) are founded on the enhanced tumour visualisation capabilities of new imaging modalities and the precise deposition of individualised radiation dose distributions made possible with the new systems for RT planning and delivery. These techniques have a large potential to also improve the results of RT of urinary bladder cancer. Major challenges to take full advantage of these advances in the management of bladder cancer are to control, and, as far as possible, reduce bladder motion, and to reliably account for the related intestine and rectum motion. If these obstacles are overcome, it should be possible in the near future to offer selected patients with muscle invading bladder cancer an organ-sparing, yet effective combined-modality treatment as an alternative to radical surgery

A study of image-guided radiotherapy of bladder cancer based on lipiodol injection in the bladder wall

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Soendergaard, Jimmi; Muren, Ludvig Paul; Elstroem, Ulrik Vindelev; Grau, Cai; Hoeyer, Morten; Oerding Olsen, Kasper

2010-01-01

Purpose. We have tested a procedure of focal injection of the contrast medium Lipiodol as a fiducial marker for image-guided boost of the tumor in bladder cancer radiotherapy (RT). In this study, we have evaluated the feasibility and the safety of the method as well as the inter- and intra-fraction shift of the bladder tumor. Materials and methods. Five patients with muscle invasive urinary bladder cancer were included in the study. Lipiodol was injected during flexible cystoscopy into the submucosa of the bladder wall at the periphery of the tumor or the post resection tumor-bed. Cone-beam CT (CBCT) scans were acquired daily throughout the course of RT. Results. Lipiodol demarcation of the bladder tumor was feasible and safe with only a minimum of side effects related to the procedure. The Lipiodol spots were visible on CT and CBCT scans for the duration of the RT course. More than half of all the treatment fractions required a geometric shift of 5 mm or more to match on the Lipiodol spots. The mean intra-fraction shift (3D) of the tumor was 3 mm, largest in the anterior-posterior and cranial-caudal directions. Conclusion. This study demonstrates that Lipiodol can be injected into the bladder mucosa and subsequently visualized on CT and CBCT as a fiducial marker. The relatively large inter-fraction shifts in the positions of Lipiodol spots compared to the intra-fraction movement indicates that image-guided RT based on radio-opaque markers is important for RT of the bladder cancer tumor.

Experimental model of bladder instability in rabbits

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Balasteghin K.T.

2003-01-01

Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study

NARCIS (Netherlands)

Vermeulen, S.; Hanum, N.; Grotenhuis, A.J.; Castano-Vinyals, G.; Heijden, A.G. van der; Aben, K.K.H.; Mysorekar, I.U.; Kiemeney, L.A.L.M.

2015-01-01

BACKGROUND: Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case-control studies worldwide. METHODS: Information on (i) history and age at onset of

MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

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Jeong Youp Park

Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

Building tools for image-guided adaptive radiotherapy of bladder cancer

NARCIS (Netherlands)

Chai, X.

2012-01-01

From this thesis, we can conclude that the injection of lipiodol markers into the bladder wall is a feasible method to track bladder tumors for IGRT of partial bladder. We succeeded in developing a biomechanical bladder model and bladder segmentation methods for online CBCT, which are useful tools

X-ray volume imaging in bladder radiotherapy verification

International Nuclear Information System (INIS)

Henry, Ann M.; Stratford, Julia; McCarthy, Claire; Davies, Julie; Sykes, Jonathan R.; Amer, Ali; Marchant, Tom; Cowan, Richard; Wylie, James; Logue, John; Livsey, Jacqueline; Khoo, Vincent S.; Moore, Chris; Price, Pat

2006-01-01

Purpose: To assess the clinical utility of X-ray volume imaging (XVI) for verification of bladder radiotherapy and to quantify geometric error in bladder radiotherapy delivery. Methods and Materials: Twenty subjects undergoing conformal bladder radiotherapy were recruited. X-ray volume images and electronic portal images (EPIs) were acquired for the first 5 fractions and then once weekly. X-ray volume images were co-registered with the planning computed tomography scan and clinical target volume coverage assessed in three dimensions (3D). Interfraction bladder volume change was described by quantifying changes in bladder volume with time. Bony setup errors were compared from both XVI and EPI. Results: The bladder boundary was clearly visible on coronal XVI views in nearly all images, allowing accurate 3D treatment verification. In 93.5% of imaged fractions, the clinical target volume was within the planning target volume. Most subjects displayed consistent bladder volumes, but 25% displayed changes that could be predicted from the first three XVIs. Bony setup errors were similar whether calculated from XVI or EPI. Conclusions: Coronal XVI can be used to verify 3D bladder radiotherapy delivery. Image-guided interventions to reduce geographic miss and normal tissue toxicity are feasible with this technology

Antibacterial activity of probiotics in bladder tumor patients

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Molchanov R.N.

2014-09-01

Full Text Available The chronic urinary tract infection (UTI is a risk factor that worsens a natural course of bladder tumors. Using of probiotics, possessing antagonistic influence on pathogenic microflora and immunocorrection effect, for preventive maintenance and treat¬ment of a chronic UTI in bladder tumor patients is an actual and perspective direction. The goal of the research was studying antimicrobial and anti-inflammatory effect of a single bladder instillation of either lactobacilli or aerococci in bladder tumor patients. In the preoperative period a single bladder instillation with either lactobacterin or a-bacterin preparation to 35 bladder tumor patients was done. Bacteriuria, leucocyturia, lactobacilli and aerococci count in urine were measured before and in 1, 3, 6 and 24 hours after instillation. Decrease in bacteriuria level in both groups of patients was revealed. Lactobacilli and aerococci count in urine gradually decreased up to complete elimination in 24 hours (in 1 patient who received lactobacterin (12,5 % and in 9 patients who received a-bacterin. (40,9 %. Leucocyturia study did not show statistically confidence dynamics throughout the observation period in both groups. Thus, bladder instillation with lactobacterin or a-bacterin leads to suppression of uropathogenic microflora in bladder tumor patients; in the majority of patients spontaneous elimination of lactobacilli and aerococci occurs within 24 hours.

Long-term follow-up of advanced bladder adenocarcinoma

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Karen Korkes

2009-12-01

Full Text Available Objective: to evaluate patients treated with primary bladder adenocarcinoma at our institution. Methods: A review of 30 patients diagnosed with bladder adenocarcinoma at a single institution from 1994 of 2005 was undertaken. Cases of primary bladder adenocarcinoma were retrospectively evaluated. Rresults: Out of 490 patients with bladder carcinoma, 30 had bladder adenocarcinoma: 22 metastatic tumors, eight (1.6% primary adenocarcinoma. Of these, three (0.6% were primary non-urachal and five (1.0% were urachal adenocarcinoma. All patients were men with mean age of 55.8 years (range 37-83. Dysuria and hematuria were the main symptoms reported. Of the total, four patients had cancer-related mortality. Cconclusion: Primary bladder adenocarcinoma is a rare neoplasm, observed in 1.6% patients with bladder malignancies. Late diagnosis limits therapeutic possibilities. Partial cystectomy seems to have unsatisfactory results and radical cystectomy, although remains as the gold standard, have no proven efficacy. New methods of adjuvant treatment must be studied to improve treatment outcomes, as high mortality is observed despite treatment.

HPLC assisted Raman spectroscopic studies on bladder cancer

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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.

Comparison of the efficacy and feasibility of laser enucleation of bladder tumor versus transurethral resection of bladder tumor: a meta-analysis.

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Yang, Huan; Wang, Ning; Han, Shanfu; Male, Musa; Zhao, Chenming; Yao, Daqiang; Chen, Zhiqiang

2017-12-01

The transurethral resection of bladder tumor (TURBT) remains the most widely used method in the surgical treatment of the non-muscle invasive bladder tumor (NMIBT). Despite its popularity, the laser technique has been widely used in urology as an alternative, via the application of transurethral laser enucleation of bladder tumor. The aim of the present study was to compare the efficacy and feasibility between transurethral laser enucleation and transurethral resection of bladder tumor. A systematic search of the following databases was conducted: PubMed, Wed of Science, Cochrane Library, EMBASE, Google scholar, and Medline. The search included studies up to the 1st of January 2017. The outcomes of interest that were used in order to assess the two techniques included operation time, catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, 24-month-recurrence rate, and the postoperative adjuvant intravesical chemotherapy. A total of 13 trials with 2012 participants were included, of which 975 and 1037 underwent transurethral laser enucleation and transurethral resection of bladder tumor, respectively. No significant difference was noted in the operation time between the two groups, although significant differences were reported for the variables catheterization time, hospitalization time, obturator nerve reflex, bladder perforation, bladder irritation, and 24-month-recurrence rate. In the mitomycin and epirubicin subgroups, no significant differences were observed in the laser enucleation and TURBT methods with regard to the 24-month-recurrence rate. The laser enucleation was superior to TURBT with regard to the parameters obturator nerve reflex, bladder perforation, catheterization time, hospitalization time, and 24-month-recurrence rate. Moreover, laser enucleation can offer a more accurate result of the tumor's pathological stage and grade.

Tumorigenicity of sodium ascorbate in male rats.

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Cohen, S M; Anderson, T A; de Oliveira, L M; Arnold, L L

1998-06-15

Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat

Resistance to DNA Damaging Agents Produced Invasive Phenotype of Rat Glioma Cells—Characterization of a New in Vivo Model

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Sonja Stojković

2016-06-01

Full Text Available Chemoresistance and invasion properties are severe limitations to efficient glioma therapy. Therefore, development of glioma in vivo models that more accurately resemble the situation observed in patients emerges. Previously, we established RC6 rat glioma cell line resistant to DNA damaging agents including antiglioma approved therapies such as 3-bis(2-chloroethyl-1-nitrosourea (BCNU and temozolomide (TMZ. Herein, we evaluated the invasiveness of RC6 cells in vitro and in a new orthotopic animal model. For comparison, we used C6 cells from which RC6 cells originated. Differences in cell growth properties were assessed by real-time cell analyzer. Cells’ invasive potential in vitro was studied in fluorescently labeled gelatin and by formation of multicellular spheroids in hydrogel. For animal studies, fluorescently labeled cells were inoculated into adult male Wistar rat brains. Consecutive coronal and sagittal brain sections were analyzed 10 and 25 days post-inoculation, while rats’ behavior was recorded during three days in the open field test starting from 25th day post-inoculation. We demonstrated that development of chemoresistance induced invasive phenotype of RC6 cells with significant behavioral impediments implying usefulness of orthotopic RC6 glioma allograft in preclinical studies for the examination of new approaches to counteract both chemoresistance and invasion of glioma cells.

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

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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 ...

Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

International Nuclear Information System (INIS)

Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

1988-01-01

Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed

Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation

NARCIS (Netherlands)

de Rooij, Bert-Jan F.; van der Beek, Martha T.; van Hoek, Bart; Vossen, Ann C. T. M.; ten Hove, W. Rogier; Roos, Anja; Schaapherder, Alexander F.; Porte, Robert J.; van der Reijden, Johan J.; Coenraad, Minneke J.; Hommes, Daniel W.; Verspaget, Hein W.

2011-01-01

Background & Aims: The lectin pathway of complement activation is a crucial effector cascade of the innate immune response to pathogens. Cytomegalovirus (CMV) infection occurs frequently in immunocompromised patients after orthotopic liver transplantation (OLT). Single-nucleotide polymorphisms

Metabolic activation of the bladder carcinogen 4-nitrobiphenyl (NBP)

International Nuclear Information System (INIS)

Swaminathan, S.

1986-01-01

The metabolism of NBP, a dog bladder carcinogen, was examined in vitro using rat liver tissues. NBP was metabolized by enzymes localized both in the microsomes and cytosol. The microsomal enzyme activity was inducible by Aroclor 1254 and phenobarbital. High pressure liquid chromatography analysis of the ethyl acetate extract of the reaction mixture, following incubation of [ 3 H]NBP with NADPH and microsomes, revealed four radioactive and UV absorbing peaks with retention times of 5, 8, 14 and 28 min. The peaks at 8, 14 and 28 min corresponded with 4-aminobiphenyl (ABP), NBP and azoxy biphenyl, respectively. The early eluting component with a retention time of 5 min has been tentatively identified as a ring hydroxylated derivative. In contrast to microsomal metabolism, cytosol-mediated metabolism yielded only one major metabolite identified as ABP. Cytosol-mediate reduction was inhibited by the xanthine oxidase inhibitor allopurinol. In vitro incubation of NBP with NADH and commercial preparations of xanthine oxidase also yielded ABP and the formation of the latter was blocked by allopurinol. Xanthine oxidase catalyzed also the binding of [ 3 H]NBP to DNA and proteins; the binding was inhibited by allopurinol. These data support the hypothesis that the nitro reduction step is involved in the activation of the bladder carcinogen NBP, and that the nitroreductases occur in both the microsomes and cytosol. The cytosolic activity is primarily due to xanthine oxidase

Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

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Paulo Roberto Wille

2001-01-01

Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

Subchronic toxicity studies of t-butyl alcohol in rats and mice.

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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.

In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

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Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

2017-03-01

Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

Immunodominant PstS1 antigen of mycobacterium tuberculosis is a potent biological response modifier for the treatment of bladder cancer

International Nuclear Information System (INIS)

Sänger, Christian; Busche, Andreas; Bentien, Gabriele; Spallek, Ralf; Jonas, Fatima; Böhle, Andreas; Singh, Mahavir; Brandau, Sven

2004-01-01

Bacillus Calmette Guérin (BCG)-immunotherapy has a well-documented and successful clinical history in the treatment of bladder cancer. However, regularly observed side effects, a certain degree of nonresponders and restriction to superficial cancers remain a major obstacle. Therefore, alternative treatment strategies are intensively being explored. We report a novel approach of using a well defined immunostimulatory component of Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate transport protein PstS1 which represents the phosphate binding component of a mycobacterial phosphate uptake system is known to be a potent immunostimulatory antigen of M. tuberculosis. This preclinical study was designed to test the potential of recombinant PstS1 to serve as a non-viable and defined immunotherapeutic agent for intravesical bladder cancer therapy. Mononuclear cells (PBMCs) were isolated from human peripheral blood and stimulated with PstS1 for seven days. The activation of PBMCs was determined by chromium release assay, IFN-γ ELISA and measurement of lymphocyte proliferation. The potential of PstS1 to activate monocyte-derived human dendritic cells (DC) was determined by flow cytometric analysis of the marker molecules CD83 and CD86 as well as the release of the cytokines TNF-α and IL-12. Survival of presensitized and intravesically treated, tumor-bearing mice was analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA, splenocyte proliferation assay and immunohistochemistry. Our in vitro experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-γ release and proliferation of PBMCs. Further investigations showed the potential of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies in an orthotopic murine bladder cancer model demonstrated the therapeutic potential of intravesically applied PstS1

Suburothelial Bladder Contraction Detection with Implanted Pressure Sensor.

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Steve J A Majerus

Full Text Available Managing bladder pressure in patients with neurogenic bladders is needed to improve rehabilitation options, avoid upper tract damage, incontinence, and their associated co-morbidities and mortality. Current methods of determining bladder contractions are not amenable to chronic or ambulatory settings. In this study we evaluated detection of bladder contractions using a novel piezoelectric catheter-free pressure sensor placed in a suburothelial bladder location in animals.Wired prototypes of the pressure monitor were implanted into 2 nonsurvival (feline and canine and one 13-day survival (canine animal. Vesical pressures were obtained from the device in both suburothelial and intraluminal locations and simultaneously from a pressure sensing catheter in the bladder. Intravesical pressure was monitored in the survival animal over 10 days from the suburothelial location and necropsy was performed to assess migration and erosion.In the nonsurvival animals, the average correlation between device and reference catheter data was high during both electrically stimulated bladder contractions and manual compressions (r = 0.93±0.03, r = 0.89±0.03. Measured pressures correlated strongly (r = 0.98±0.02 when the device was placed in the bladder lumen. The survival animal initially recorded physiologic data, but later this deteriorated. However, endstage intraluminal device recordings correlated (r = 0.85±0.13 with the pressure catheter. Significant erosion of the implant through the detrusor was found.This study confirms correlation between suburothelial pressure readings and intravesical bladder pressures. Due to device erosion during ambulatory studies, a wireless implant is recommended for clinical rehabilitation applications.

Novel research approaches for interstitial cystitis/bladder pain syndrome: thinking beyond the bladder

OpenAIRE

Mullins, Chris; Bavendam, Tamara; Kirkali, Ziya; Kusek, John W.

2015-01-01

Despite years of basic and clinical research focused on interstitial cystitis/bladder pain syndrome (IC/BPS), including clinical trials of candidate therapies, there remains an insufficient understanding of underlying cause(s), important clinical features and a lack of effective treatments for this syndrome. Progress has been limited and is likely due to many factors, including a primary focus on the bladder and lower urinary tract as origin of symptoms without adequately considering the pote...

Bladder cancer

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... Dye workers, rubber workers, aluminum workers, leather workers, truck drivers, and pesticide applicators are at the highest ... examining the inside of the bladder with a camera), with biopsy Intravenous pyelogram - IVP Pelvic CT scan ...

Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

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Rommel Prata Regadas

2014-08-01

Full Text Available Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME; 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days, all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC (1.04 ± 0.22, volume threshold (VT (1.86 ± 0.35, and micturition cycle (MC (1.34 ± 0.11 compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30, respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42 and VT (0.76 ± 0.24 compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53 and MC (0.76 ± 0.22 compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18, VT (0.97 ± 0.52 and MC (0.68 ± 0.30 compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

Postmortem MRI of bladder agenesis

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Barber, Brendan R. [St George' s Hospital, Radiology Department, London (United Kingdom); Weber, Martin A. [Great Ormond Street Hospital for Children, Department of Histopathology, London (United Kingdom); Bockenhauer, Detlef [Great Ormond Street Hospital for Children, Department of Nephrology, London (United Kingdom); Hiorns, Melanie P.; McHugh, Kieran [Great Ormond Street Hospital for Children, Radiology Department, London (United Kingdom)

2011-01-15

We report a 35-week preterm neonate with bladder agenesis and bilateral dysplastic kidneys. A suprapubic catheter was inadvertently inserted into one of the larger inferior cysts of the left dysplastic kidney. A postmortem MRI scan was performed with the findings being confirmed on autopsy. We are unaware of another postmortem MRI study demonstrating bladder agenesis. (orig.)