Utility of cystatin C as a potential bladder tumour biomarker confirmed by surface plasmon resonance technique.

BACKGROUND & OBJECTIVES: The determination of cystatin C (cysC) may be helpful in diagnosis and monitoring of cancer because the pathogenesis of cancer is linked with an increased activity of cysteine peptidases (cathepsins) and a decrease of cysC concentration. This study was aimed to examine the utility of cysC as a marker of bladder cancer (BCa) to be used in the diagnosis. METHODS: This study was conducted with 90 patients with BCa and 27 healthy people. Patients with other cancers, inflammation process and impaired renal function were excluded from the study. The concentrations of cysC in the plasma and urine were measured by surface plasmon resonance imaging technique. RESULTS: The concentration of cysC in the serum taken from the patients with BCa [0.35±0.02 µg/ml (range: 0.20-0.78 µg/ml)] was significantly (P<0.001) lower than the serum cysC concentration of the healthy people [0.68±0.05 µg/ml (range: 0.52-0.89 µg/ml)]. The urinary cysC concentration of the BCa patients [0.19±0.01 µg/ml (range: 0.09-0.34 µg/ml)] was not significantly different from the urinary cysC concentration of the healthy people [0.24±0.02 µg/ml (range: 0.16-0.33 µg/ml)]. Receiver operating characteristic (ROC) curve showed that BCa patients with cysC concentration <0.54 µg/ml [sensitivity: 87%; specificity: 92%; area under the curve (AUC) of ROC: 0.927; P=0.02] could be optimally separated from healthy people. The ROC curve further showed that superficial low-grade patients with cysC concentration lower than 0.36 µg/ml (sensitivity: 0.63%; specificity: 0.58%; AUC of ROC: 0.635; P=0.08) could not be optimally separated from high-risk tumour patients. INTERPRETATION & CONCLUSIONS: BCa patients have lower serum cysC concentration than the control group. Serum cysC may be considered as a potential marker of BCa but not its aggressiveness.

Structural arrangement of vesicouterine fistula revisited: An immunohistochemical study documenting the presence of the endometrium.

Previous research has described a woman of reproductive age who presented with a vesicouterine fistula (VUF) of 20 months' duration. The VUF was lined with a metaplastic glandular epithelium containing both estrogen receptors (ER) and progesterone receptors (PR) in abundance. The aim of the present investigation was to evaluate the histology of the VUF canal when exposure to urine of the cellular elements within the fistula was of much shorter duration. A 41-year-old woman who developed a VUF during her third cesarean section was treated with transvesical fistula excision, electrocoagulation, and subsequent attempted hormonal treatment. Later, the patient underwent open surgery fistula repair. Postoperative specimens were subjected to anatomopathological examination together with immunohistochemical staining for ER and PR using monoclonal anti-human antibodies. Herein, we present for the first time detailed microscopic evidence that, at two separate timepoints, the fistulous tract was lined with the endometrium, which covered approximately 80% of the length of the VUF canal. In its intermediate segment, the urothelium formed an additional layer on the surface of the endometrium. At both timepoints, in the columnar epithelial and stromal endometrial cells lining the fistula, both ER and PR were present in abundance. In conclusion, VUF in subjects of reproductive age fulfill criteria for endometriosis. This study provides a rationale for the conservative treatment of VUF consistent with the hormonal treatment of endometriosis.

Evaluation of Game Performance in Elite Male Sitting Volleyball Players.

The aims of the current study were (a) to analyze the differences in game performances of sitting volleyball athletes representing the different types of disabilities and (b) to assess whether the seated position vertical reach is one of the crucial factors in the game performance level of sitting volleyball athletes. One hundred male athletes from various national teams participating in the European Championships in Sitting Volleyball (2009) took part in this study. The athletes were categorized according to type of disability and the results of the vertical reach in a seated position. Thirtysix games were analyzed using the Game Performance Sheet for Sitting Volleyball. Twenty-three game performance parameters were studied. In addition, the sum and effectiveness of attacks, blocks, block services, services, ball receiving, and defensive actions were calculated. The main results indicated significant differences between athletes with minimal disability and athletes with single amputations from above the knee in the level of defensive performances and the summation of defensive actions. There was also a significant difference between athletes in relation to their vertical reach during activity and attacking actions, blocks, and ball receiving. In addition, there were strong relationships between the players' vertical reach scores and their activity and effectiveness in sitting volleyball. In conclusion, the accuracy of the World Organization Volleyball for Disabled classification systems for sitting volleyball players was confirmed. There is a strong relationship between players' vertical reach and their effectiveness in sitting volleyball.

[Cathepsin D and B activity in the serum of patients with urothelial bladder cancer]. / Aktywnosc katepsyn D i B w osoczu chorych na raka przejsciowokomórkowego pecherza moczowego.

UNLABELLED: The key role of cathepsin D and B is intralysosomal digestion of used cellular proteins and other proteins that enter cells through endocytosis. Under pathological conditions like cancer formation and growth, cathepsins from lysosomes are released. The aim of the study was to determin of cathepsin D and B activities in serum of patients with urothelial bladder cancer depending on disease severity and determination of its' changes after transurethral resection of tumor. MATERIAL AND METHODS: Experiment involved 50 patients. Blood samples were obtained from 18 healthy volunteers and 32 urothelial bladder cancer patients. Samples from people with suspected urothelial bladder cancer were collected three times: before the surgery, 2 weeks and 6 weeks after the surgical treatment. RESULTS: Our research showed that cathepsin D activity, measured as the level increment of acid soluble tyrosine, is the highest before the surgery in muscle invasive bladder tumor (pT2) (57,9 nmol/ml). 2 weeks and 6 weeks after the surgical treatment, cathepsin D activity is decreased. In case of cathepsin B activity, measured as the level of released p-nitroaniline, decreased, 2 weeks and 6 weeks after the surgical treatment in both cases of disease severity. CONCLUSION: Cathepsin D and B activities in the serum of patients with urothelial bladder cancer are directly proportional to disease severity and significantly higher compared with control group. Transuretral resection of the tumor leads to diminution of their activities in second and 6th week after the procedure.

Post-Transplant Nephroptosis as a Cause of Recurrent Urinary Tract Infections: A Case Report.

BACKGROUND: The aim of this study was to present a rare cause of recurrent urinary tract infections (UTIs) in a patient after kidney transplantation. METHODS: The patient's consent was obtained, and full medical documentation was reviewed. After analyzing the literature, only 3 case reports of post-transplant nephroptosis were found. RESULTS: A 32-year-old woman with a history of type 1 diabetes, after kidney and pancreas transplantation a year earlier, was admitted to the hospital due to another incident of fever, dysuria, and pain in the lower abdomen. UTIs had been recurring for several months despite prophylaxis, initially with co-trimoxazole and then with fosfomycin. There were no anatomic abnormalities, and tacrolimus concentrations always remained at the lower range of normal. Kinking of the ureter was suspected because of a change in the position of the transplanted kidney. Ultrasonography performed in the standing and lying positions confirmed the diagnosis. A double J catheter was inserted into the ureter. In the following months, no UTI or urinary retention recurrence was observed. CONCLUSIONS: Nephroptosis of a transplanted kidney is extremely rare. The standard place for graft implantation-the iliac fossa-significantly limits the potential for migration. Kidneys implanted intraperitoneally also do not show clinically significant mobility due to postoperative adhesions. Floating kidneys potentially lead to serious complications. In addition to pain, a migrating graft may cause urine retention, predisposing to UTI and acute kidney injury.

[Bilateral metastases of renal cell carcinoma to the ovaries--a case report]. / Obustronne przerzuty raka jasnokomórkowego nerki do jajników--opis przypadku.

Renal cell carcinoma accounts for 75% of renal neoplasms. Clear cell carcinoma is diagnosed in about 80% of the cases. Renal cell carcinoma most frequently metastasizes to the lungs (50-60%), lymph nodes (36%), bones (30-40%), liver (30-40%), and brain (5%). In other organs the metastasis changes are observed very rarely. Ovarian metastases are found in 0.5% of renal cancers. So far, only 23 cases of renal cell carcinoma metastases to the ovary have been reported in the literature. In 18 cases they were metastases of renal cell carcinoma of the clear cell type. The authors present a case of a 50-year-old woman with double-sided metastatic changes to the ovary from renal cell carcinoma. The patient was admitted to the Gynecological ward with preliminary diagnosis of ovarian tumors. Gynecological examination revealed double-sided ovarian tumors, 6-7cm in diameter. Computed tomography also showed a 155 x 80 mm hetrogenous, multiform tumor localized above the uterus. In addition, CT showed a 75 x 55 mm tumor in the lower pole, and a smaller one, 15 mm in diameter in the upper pole of the right kidney. Laboratory tests were normal. The antigen Ca 125 was 25 j/ml. Mammography cytology gastroscopy colonoscopy were normal. The consulting urologist proposed a two-stage treatment. In the first stage, the removal of the double-sided ovarian tumors was proposed, while in the second stage the right nephrectomy was suggested. Double-sided ovarian tumors were found and removed (in the wall of the cyst- yellow, solid masses) during the first operation. Intraoperative histological examination showed changes with unknown grade of malignancy in both ovaries (number of studies QN 291). The patient underwent total hysterectomy. On day 5 postoperatively the woman was discharged from the hospital in good condition with the recommendation to pick up the histological test result in two weeks time. The final histological examination showed metastatic changes of renal cell carcinoma of the clear cell type (number of studies QN569-582, QN 585-608). The diagnosis of bilateral renal cell carcinoma metastases to the ovaries was confirmed by immunohistochemical studies using antibodies CD 10 and Vimentin (number of studies CT 1558-1559). The patient was directed to the Urological Ward. The surgery confirmed the presence of the tumor in the lower pole (about 8 cm in size), and a smaller one (about 1 cm in size) in the upper pole of the right kidney. The right nephrectomy was performed. Histological examination confirmed the primary clear cell renal cell carcinoma. The patient was directed to the next oncological treatment.

Plasma aromatase as a sensitive and selective potential biomarker of bladder cancer and its role in tumorigenesis.

Bladder cancer (BCa) is the ninth most common cancer in the world and its early detection is crucial for successful therapy. Unfortunately, there are no satisfactory tools to detect BCa at early stages and BCa's confirmation muscle-invasive. The search for a suitable biomarker is therefore necessary and aromatase is a potential candidate. The purpose of the current study was to determine if aromatase serves as a biomarker of BCa. A Surface Plasmon Resonance Imaging biosensor was applied for the quantification and determination of aromatase. A total of 3 µl blood plasma was used for a single measurement. The results revealed that the aromatase concentration in the plasma of patients with BCa (n=78) ranged from 17.41-57.44 ng/ml. The range determined in healthy donors (n=18) was 2.59-7.74 ng/ml. Additionally, it was revealed that muscle invasive BCa samples exhibited elevated, statistically significant (P=0.01) average aromatase concentrations in blood plasma (38.64 ng/ml) when compared with non-muscle invasive samples (29.83 ng/ml). The results demonstrated that plasma aromatase may serve as an excellent bimarker of BCa with 100% sensitivity, 100% selectivity and an area under the curve value of the reciever operating characteristic curve equal to 1.0. Furthermore, the marker differenciated between muscle-invasive and non muscle-invasive BCa with a sensitivity of 60% and a specificity of 81%. In conclusion, aromatase may serve a role in bladder tumorigenesis.

Value of direct radionuclide cystography in diagnosing vesico-peritoneal fistulae.

A 36-year-old female patient underwent a laparoscopic surgery to remove a uterine fibroid. The procedure failed to relieve the pelvic pain, although its nature changed. After a period of observation, the patient was re-admitted to hospital on suspicion of a vesico-uterine fistula to be differentiated with endometriosis. Diagnostic investigations - cystography, cystoscopy, computed tomography and magnetic resonance - did not reveal a fistula. Laparoscopy was performed, with a possible biopsy in order to eliminate endometriosis. The result was negative, but chronic progressive reactive/inflammatory lesions were noticed, possibly indicating the presence of a vesico-peritoneal fistula. Therefore, a direct radionuclide cystography was performed. The scintigraphic images single-photon emission computed tomography (SPECT/CT) showed a radioactive spot, indicative of a vesico-peritoneal fistula. The fistula was treated for three months by catheterisation of the urinary bladder. The follow-up SPECT-CT did not reveal any urine leakage from the bladder. The clinical symptoms disappeared as well.

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism.

BACKGROUND: Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels. METHODS: This is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [ß-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days). RESULTS: Twenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m2). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9-831.2) vs. 583.0 (411.7-752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8-103.3) vs. 77.1 (60.5-109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4-0.64) vs. 0.59 (0.46-0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8-31.4) vs. 17.9 (15.0-22.0) U/l, p < 0.0001 and 3.3 (3.0-3.7) vs. 2.8 (2.3-3.2) U/l, p < 0.001, respectively]. CONCLUSIONS: Nephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.

A Comparison of Two Approaches to Laparoscopic Adrenalectomy: Lateral Transperitoneal Versus Posterior Retroperitoneal Approach.

BACKGROUND: Laparoscopic adrenalectomy is the gold standard for the surgical treatment of benign adrenal masses. It is most commonly performed using the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). The choice of the method depends on contraindications for a particular approach in an individual case and surgical experience. The objective of the article is to compare two approaches, LTA and PRA, in view of our own experience and literature review. OBJECTIVES: The objective of the article is to compare two approaches, LTA and PRA, in view of our own experience and literature. MATERIAL AND METHODS: The assessment involved morphological characteristics of tumors, indications for PRA and LTA, operative time, perioperative blood loss and postoperative complications. RESULTS: Seventy-seven of the examined 104 laparoscopic adrenalectomies were performed retroperitoneally; 27 - transperitoneally. The mean size of tumors in PRA was 4.6 cm and in LTA 6.2 cm. The mean total operative time was 91.8 min in the case of PRA and 153.1 min in LTA. No differences in the amount of blood loss between the two approaches were recorded. The average hospitalization post PRA lasted 2.03 days and post LTA 2.67 days. CONCLUSIONS: Laparoscopic adrenalectomy proves to be an effective and safe surgical technique both in the case of LTA and PRA. The technique to be used should be suited to surgical team's experience, patient's general condition and tumor size and location. In our experience, the most advantageous approach in the case of tumors of less than 7 cm is PRA.

[Role of Chlamydia trachomatis infection in the pathology of male urogenital tract]. / Rola zakazenia Chlamydia trachomatis w patologii meskiego narzadu moczowo-plciowego.

Based on literature data, the authors have presented the informations on epidemiology, pathogenesis, clinical picture, diagnostics and treatment of Chlamydia trachomatis urogenital infections in men.

Cathepsin D serum and urine concentration in superficial and invasive transitional bladder cancer as determined by surface plasmon resonance imaging.

Determination of cathepsin D (Cat D) concentration in serum and urine may be useful in the diagnosis of bladder cancer. The present study included 54 healthy patients and 68 patients with bladder cancer, confirmed by transurethral resection or cystectomy. Cat D concentration was determined using a surface plasmon resonance imaging biosensor. Cat D concentration in the serum of bladder cancer patients was within the range of 1.3-5.59 ng/ml, while for healthy donors it was within the range of 0.28-0.52 ng/ml. In urine, the Cat D concentration of bladder cancer patients was within the range of 1.35-7.14 ng/ml, while for healthy donors it was within the range of 0.32-0.68 ng/ml. Cat D concentration may represent an efficient tumor marker, as its concentration in the serum and urine of transitional cell carcinoma patients is extremely high when compared with healthy subjects.

Videoscopic adrenalectomy - when does retroperitoneal seem better?

INTRODUCTION: Videoscopic adrenalectomy is the gold standard for the surgical treatment of benign adrenal tumours. The two most common approaches are the lateral transperitoneal approach (LTA) and the posterior retroperitoneal approach (PRA). So far it has not been established which is the preferable one. The choice depends primarily on the surgeon's preference and contraindications for a particular approach in individual cases. AIM: To compare the two most common approaches for videoscopic adrenalectomy, LTA and PRA, based on a literature review and our own experience. MATERIAL AND METHODS: We reviewed the literature (PubMed and Cochrane 1990 - current) and analysed retrospectively our own patients who underwent videoscopic adrenalectomy between 2009 and 2013. The analysis covered patient features, tumour characteristics, reasons for qualification for each approach, operative time and postoperative complications. RESULTS: Out of 71 videoscopic adrenalectomies, 50 were performed using PRA and 21 using LTA. Patients in the PRA group on average were older, but had smaller tumours. There was no significant difference in perioperative morbidity between PRA and LTA. Mean blood loss and total operative time were smaller/shorter for the PRA group in comparison to the LTA group. Time to first oral intake and the average postoperative hospital stay were shorter for PRA than LTA. CONCLUSIONS: Videoscopic adrenalectomy is a safe and efficient technique performed using both LTA and PRA approaches. The choice of technique should be guided, most of all, by surgeon experience, patient characteristics, tumour size and location. Our preferable approach is PRA, especially for small (< 6 cm) benign tumours. We find LTA advantageous for tumours of larger size, with suspected malignant character (either primary or secondary), in ectopic position, as well as in patients lacking an ipsilateral kidney or when a simultaneous abdominal operation is planned.

Subclinical prostatic inflammation attributable to Chlamydia trachomatis in a patient with prostate cancer.

Chronic inflammation has long been linked to cancers with an infectious etiology. Subclinical intraprostatic inflammation is a frequent finding in prostatic specimens obtained during surgical procedures. Recent studies using biomolecular (amplification) methods showed that the incidence of cryptic bacterial infections of prostate gland may be underestimated. We present the case of 66 years old man with no symptoms of prostatitis in whom chronic Chlamydia trachomatis infection was diagnosed based on the patient's medical history and detection of chlamydial DNA in prostate biopsy specimen by means of ligase chain reaction. Two years later the patient was diagnosed with prostate cancer on repeated prostate biopsy.

Regulation of blood flow and microcirculation resistance in rabbit bladder.

PURPOSE: Human and animal studies have shown that filling, contraction and emptying produce cyclical changes in bladder blood flow. The mechanism of these hemodynamic changes remains unclear. We studied the regulation of bladder blood flow in the rabbit model. MATERIALS AND METHODS: A total of 18 male New Zealand White rabbits were anesthetized. Arterial pressure, intravesical pressure, and dome and base blood flow were measured simultaneously in the empty bladder, at 25 and 50 ml. intravesical volume, and after draining. These measurements were recorded before and then after intravenous administration of atropine, phentolamine, propranolol, L-arginine or N-nitro-L-arginine. Changes in dome and base microcirculation resistance, and blood flow after treatment were compared with those recorded before treatment. RESULTS: In the empty bladder dome microcirculation resistance was greater than at the base and base blood flow was greater than at the dome. Filling increased dome microcirculation resistance, decreased dome blood flow and increased base blood flow without changing base microcirculation resistance. Emptying produced much greater reactive hyperemia at the dome than at the base. Atropine did not alter microcirculation resistance or blood flow. Phentolamine had no effect on dome or base microcirculation resistance, blood flow in the empty bladder or at 25 ml. intravesical volume but it decreased dome microcirculation resistance at 50 ml. intravesical volume. Propranolol caused dome contraction, increased dome microcirculation resistance and decreased dome blood flow in the empty bladder, and at 25 and 50 ml. intravesical volume. Propranolol increased base blood flow without changing base microcirculation resistance. N-nitro-L-arginine increased dome microcirculation resistance in the empty bladder and at 25 ml. intravesical volume but decreased dome blood flow in the empty bladder alone. N-nitro-L-arginine increased base microcirculation resistance and decreased base blood flow in the empty bladder and at 25 ml. intravesical volume but not at 50 ml. intravesical volume. L-arginine decreased dome and base microcirculation resistance, and increased blood flow in the empty bladder, and at 25 and 50 ml. intravesical volume. Reactive hyperemia decreased after N-nitro-L-arginine and increased after L-arginine. CONCLUSIONS: Our studies show large variations in bladder dome and base microcirculation resistance and blood flow. Bladder blood flow appears to be largely regulated locally by nitric oxide mediated changes in bladder microcirculation resistance. beta-adrenergic receptors may regulate bladder blood flow indirectly by modulating dome tension and shifting blood flow between the dome and base. Mechanical changes in bladder wall and vasculature shape may also contribute to changes in microcirculation resistance.

Chronic ischemia increases prostatic smooth muscle contraction in the rabbit.

PURPOSE: We studied the effect of chronic ischemia on prostatic smooth muscle contraction in the rabbit. MATERIALS AND METHODS: New Zealand male rabbits weighing 3 to 3.5 kg were assigned to 2 groups. Group 1 (10 rabbits) underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet for 4 weeks and then a regular diet for 8 weeks. Control group 2 (10 rabbits) received a regular diet. After 12 weeks the animals were anesthetized. Iliac artery and prostate blood flow was recorded. Prostate tissues were prepared for isometric tension measurement, enzyme immunoassay to determine cyclic guanosine monophosphate (cGMP) release and histological examination. RESULTS: In group 1 atherosclerosis as well as a significant decrease in iliac artery and prostate blood flow were observed. Ischemia significantly increased prostatic tissue contraction, decreased cGMP release and led to capsular and stromal thickening, and epithelial atrophy. The alpha1-adrenoceptor blocker doxazosin and the phosphodiesterase-5 inhibitor sildenafil citrate significantly decreased the contraction of control and ischemic tissues. Doxazosin was more effective in decreasing contractions when it was combined with sildenafil or the nitric oxide (NO) precursor L-arginine. In contrast, doxazosin was less effective when it was combined with the NO synthase inhibitor N omega-nitro-L-arginine or with the guanylate cyclase inhibitor methylene blue. Doxazosin significantly increased cGMP release in control tissues but not in ischemic tissues. Sildenafil significantly increased cGMP release in control and ischemic tissues. CONCLUSIONS: Ischemia increased prostatic smooth muscle contraction and led to marked structural damage. Stimulators of NO synthesis and cGMP production enhanced the efficacy of doxazosin in decreasing prostatic tissue contraction. Sildenafil decreased contractility and increased cGMP release. Increased smooth muscle tone and structural changes in the ischemic prostate may suggest a role for prostate ischemia in resistance to urinary flow independent of prostate size.

Increased leukotriene and prostaglandin release, and overactivity in the chronically ischemic bladder.

PURPOSE: Chronic ischemia has been shown to alter bladder contractility. We studied the roles of cyclooxygenase (COX) and lipoxygenase products in ischemia induced bladder overactivity in the rabbit. MATERIALS AND METHODS: A total of 28 male New Zealand White rabbits were divided into 2 groups. In group 1 atherosclerotic occlusion of the iliac arteries was induced by balloon endothelial injury, followed by a short period of a high cholesterol diet. Group 2 received a regular diet alone. After 12 weeks blood flow measurements and cystometry were performed. Bladder tissues were processed for enzyme immunoassay of leukotrienes and prostaglandins (PGs), Western blotting of COX and lipoxygenase, isometric tension measurement and histology. RESULTS: Atherosclerotic occlusion of the iliac arteries significantly decreased bladder blood flow. Moderate ischemia caused bladder overactivity, while severe ischemia inhibited bladder contractions. Ischemia increased leukotriene B4, E4 and C4 release by 141%, 132% and 254%, and increased PG F2alpha and thromboxane A2 release by 95% and 93%, respectively, although it did not alter PG E2 release. Western blotting showed increased 5-lipoxygenase, COX-1 and COX-2 protein levels in ischemic bladder tissues. Moderate ischemia increased bladder smooth muscle contraction in response to carbachol and electrical field stimulation. Tissue treatment with the COX inhibitor indomethacin significantly increased control tissue contraction but had no effect on ischemic tissues. Treatment with the 5-lipoxygenase inhibitor REV5901 abolished this effect of indomethacin in control tissues. Treatment with REV5901 significantly decreased the contraction of ischemic tissues but had no significant effect on control tissues. The effect of indomethacin plus REV5901 was similar to the effect of REV5901 alone. Histology showed urothelial thickening and mild fibrosis in the moderately ischemic bladder. CONCLUSIONS: Chronic ischemia increased bladder 5-lipoxygenase, and COX-1 and COX-2 protein expression, and altered leukotriene and PG production. Treatment with COX and lipoxygenase inhibitors produced completely different effects in the ischemic bladder compared with the control bladder. Functional changes in the ischemic bladder were concurrent with structural changes in the urothelium. PGs modulate smooth muscle contractility in the healthy bladder. However, under ischemic conditions leukotrienes dominate bladder tone and appear to have a leading role in increased smooth muscle contraction and bladder overactivity.