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Otitis media (OM) accounts for more than 20 million clinic visits in the United States every year. Resistance to antibiotics has hampered current management of the disease. Identification of genetic factors underlying susceptibility to OM is greatly needed in order to develop alternative treatment strategies. Genetically defined inbred mouse strains offer a powerful tool for dissecting genetic and environmental factors that may lead to OM in mice. Here, we report a study of middle ear function of 61 genetically diverse inbred strains of mice using tympanometry. Of the 61 inbred strains tested, the 129P1/ReJ, 129P3/J, 129S1/SvImJ, 129X1/SvJ, A/HeJ, BALB/cJ, BUB/BnJ, C57L/J, EL/SuzSeyFrkJ, FVB/NJ, I/LnJ, LP/J, NZB/BlNJ, PL/J and YBR/Ei strains exhibited tympanograms that were statistically different from other healthy strains according to parameters including middle ear pressure, volume and compliance. These differences are most likely the result of genetic factors that, when understood, will facilitate prevention and treatment of otitis media in humans. In addition, a negative correlation between age and compliance of the tympanic membrane was discovered. This is the first report to successfully use tympanometry to measure mouse middle ear function, which has been a challenge for the hearing research field because of the mouse's tiny ear size.

Diabetes induced alterations of M3-muscarinic receptors (M3-mAChR) in the urothelium and muscle layer of the urinary bladder were studied using streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into two groups; group I: normal control rats; group II: STZ-induced diabetic rats, 2 weeks after induction. The bladder was divided into urothelium and muscle layer by microdissection. Tissue M3-mAChR protein levels were measured by Western blotting. Expression of the mRNA that encoded M3-mAChR was estimated using the method of reverse transcription combined with polymerase chain reaction (RT-PCR). M3-mAChR protein and mRNA expressions were found in both the urothelium and muscle layer of the rat urinary bladder. In control rats, the M3-mAChR protein expression ratio in the urothelium and muscle layer was 1:1.87; that for mRNA was 1:0.74. Two weeks after induction of diabetes, the M3-mAChR mRNA expression in the urothelium and muscle layer were significantly increased by 45.7% (P<0.01, n=8) and 80.8% (P<0.001, n=8), respectively. Correspondingly, the bladder M3-mAChR protein levels were significantly increased by 50.0% (P<0.01, n=8) in the urothelium and 147.1% (P<0.001, n=8) in the muscle layer of the diabetic rats. In conclusion, M3-mAChR mRNA and protein are expressed in both the urothelium and muscle layer of the rat urinary bladder. STZ-induced diabetes increases mRNA and protein expression of the M3-mAChR in the urothelium as well as the muscle layer.

Aims: The urodynamic findings and voiding habits in patients with concomitant clinical benign prostatic hyperplasia (BPH) and detrusor overactivity (DO) presenting with or without the symptom of urgency were compared., Materials and Methods: 84 BPH patients with an urodynamic diagnosis of DO by conventional cystometry were included in the study. The patients were grouped according to the presence or absence of the symptom of urgency. The urodynamic findings, urinary diary and clinical information were analyzed., Results: Among the 84 BPH-DO patients, 52 reported the symptom of urgency while 32 did not. There were no significant differences in mean age, International Prostate Symptom Score and flow rate between the two groups. Patients without urgency had a higher incidence of terminal DO and abnormal bladder sensation. The occurrence of unfelt phasic DO was also significantly higher in this group. Sphincter electromyography showed conscious and subconscious sphincter contractions associated with DO. The urinary diary showed lower 24-hour urinary output, smaller bladder functional capacity and average voided volume in the BPH-DO patients without urgency., Conclusions: BPH patients with DO may neglect the symptom of urgency due to abnormal bladder sensation, or negate the symptom by subconscious sphincter contraction to abort the overactivity. Some may avoid the symptom by drinking less fluid and emptying the bladder at a smaller volume., (Copyright 2007 S. Karger AG, Basel.)

Purpose: To minimize the operative time of hand assisted retroperitoneoscopic nephroureterectomy by avoiding position change we report an especially designed surgical position., Materials and Methods: A total of 41 patients with upper tract transitional cell carcinoma who underwent hand assisted retroperitoneoscopic nephroureterectomy and bladder cuff resection were enrolled. Patients lay supine, and the flank and hip on the lesion side were elevated 30 degrees. The legs were extended and abducted in the Johnnie Walker position, allowing the operator to stand between them. Operation was completed via a 7 to 8 cm Gibson incision and 2 additional laparoscopic ports., Results: All procedures were successful except 1 open conversion due to bleeding, in which there was no need to reposition the patient. Average patient age was 65.2 years (range 34 to 85), mean operative time was 207.6 minutes (range 130 to 345) and mean estimated blood loss was 166 ml (range 50 to 900). Simultaneous transurethral endoscopic procedures were performed in 11 patients in the same position. Time to oral intake and ambulation was 2.1 and 2.0 days, respectively. Two patients had postoperative complications, including pneumonia and wound hematoma in 1 each. No complication was related to the position., Conclusions: The Johnnie Walker position minimizes operative time by eliminating the delay caused by patient positioning and draping changes, allowing better coordination for the surgeon and assistant, and permitting more efficient use of the nondominant hand. The retroperitoneal approach prevents bowel interference in the visual field, making laparoscopic surgery in this modified supine position possible. Nephroureterectomy, bladder cuff resection and endoscopic procedures can be done with ease with the patient in this position.

Diabetes associated alterations of M2-muscarinic receptors (M2-mAChR) in the urothelium and muscle layer of the urinary bladder were studied using streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into two groups; group I: normal control rats; group II: STZ-induced diabetic rats, 2 weeks after induction. The bladder was divided into urothelium and muscle layer by microdissection. Tissue M2-mAChR protein levels were measured by Western blotting. Expression of the mRNA that encoded M2-mAChR was estimated using the method of reverse transcription combined with polymerase chain reaction (RT-PCR). M2-mAChR protein and mRNA expressions were found in both the urothelium and muscle layer of the rat urinary bladder. In control rats, the M2-mAChR protein expression ratio in the urothelium and muscle layer was 1:1.66; that for mRNA was 1:0.97. Two weeks after induction of diabetes, the M2-mAChR mRNA expression in the urothelium and muscle layer were significantly increased by 44.4% (P<0.01, n=8) and 28.6% (P<0.01, n=8), respectively. Correspondently, the bladder M2-mAChR protein levels were significantly increased by 33.3% (P<0.001, n=8) in the urothelium and 25.3% (P<0.01, n=8) in the muscle layer of the diabetic rats. In conclusion, M2-mAChR mRNA and protein are expressed in both the urothelium and muscle layer of the rat urinary bladder. STZ-induced diabetes increases mRNA and protein expression of the M2-mAChR in the urothelium as well as the muscle layer.

The present study examined the effect of chronic fluoxetine administration on the feeding behavior of fructose-fed rats. Male fructose-fed rats were divided into two groups: (1) control fructose-fed rats (CFR), and (2) fructose-fed rats treated with oral fluoxetine 5 mg/kg/day for 30 days (FFR). The feeding behaviors and plasma glucose levels in response to either serotonin (5-HT, 5 mg/kg) or saline injection were studied. The results showed 5-HT increased CFR plasma glucose in a dose-dependent fashion while FFR demonstrated significantly lower responses to 5-HT stimulation. 5-HT significantly increased the feeding latency and decreased the amount of food intake in the CFR. Fluoxetine treatment did not affect the 5-HT effect on food intake amount but significantly reduced the 5-HT effect on feeding latency. Putting the animals in a new environment increased the 5-HT effect on feeding latency further; the effect was ameliorated in the FFR. In conclusion, 5-HT induced hyperglycemia, increased feeding latency and decreased food intake amount in fructose-fed rats. Chronic administration of fluoxetine counteracted the 5-HT effects on blood glucose level and feeding latency, but not on the amount of food intake.

Background: Many assays have investigated GPx activity but there are few reports of immunoreactive methods of GPx plasma determinations and their relationship with plasma selenium., Methods: A cross-sectional analysis of selenium and GPx was carried out on 170 adults randomly selected from the electoral role. Blood samples were collected and analysed for plasma GPx using a commercial enzyme-linked immunosorbent assay (ELISA) kit and plasma selenium using magnetic sector ICP-MS. Further investigations of GPx level were carried out using one-dimensional (1D) and two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE)., Results: Plasma GPx was associated with plasma Se level (r(2)=0.24, P<0.0001). Mean (range) Se was 108.9 (67.4-268.0) microg/l. Mean (range) plasma GPx was 18.5 (3.8-43.8) microg/ml, significantly higher than the theoretical mean GPx of around 6.5-6.9 microg/ml based on ICP-MS results and the proportion of Se in intact GPx. GPx was higher in males than females and lower in current than non-smokers and ex-smokers. PAGE analysis of glycine dissociated ELISA wells revealed GPx as well as a number of unknown proteins with significant variability between high and low GPx samples., Conclusions: Plasma GPx is correlated with Se status, however, there is considerable GPx variability between patients and ELISA methods appear to significantly overestimate true plasma GPx.

The present study examined the effect of 5-hydroxytraptamine (5-HT) on the feeding behavior of transgenic mice with neuropeptide Y (NPY) overexpression. Solution of 5-HT (1, 2.5 or 5 mg/kg) was administered intraperitoneally into (1) NPY-overexpressing mice, and (2) wild-type mice with 2-deoxy-d-glucose (2-DG) induced hyperphagia. The NPY-overexpressing mice were further divided into five groups: (1) control mice, (2) mice treated with 5-HT (5 mg/kg), (3) mice treated with 5-HT (5 mg/kg) and ketanserin (0.5 or 1 mg/kg), a 5-HT2A receptor antagonist, (4) mice treated with insulin (1 IU/kg), and (5) mice treated with insulin (1 IU/kg) and 5-HT (5 mg/kg). Food intake and plasma glucose levels were measured. The results showed that 5-HT reduced hyperphagia in both NPY-overexpressing mice and 2-DG-treated mice in dose-dependent manner. Hyperglycemia was induced by 5-HT administration. Ketanserin antagonized the 5-HT induced hypophagia and hyperglycemia. Insulin, on the other hand, prevented 5-HT induced hyperglycemia but not the hypophagic effect. In conclusion, 5-HT reduces hyperphagia in the NPY-overexpressing rat through action on 5-HT2A receptors and this hypophagic effect of 5-HT does not depend on the hyperglycemia.

Aims: To study the effect of psychological motivation on the voided volume during uroflowmetry in aged-male volunteers., Methods: An open contest of free-flow rate was held for the elderly community. People over 60 years old with no prior history of lower urinary tract symptoms were invited to compete. Participants were given the suggestion to void only when strong desire was experienced because greater the volume, faster the flow. One month later, 20 of the male participants were asked to come back for an office uroflowmetry, given the instruction to hold until strong desire was experienced. The results of the maximum flow rate, mean flow rate, and voided volume were compared between these two tests., Results: In the first uroflowmetry, the average voided volume for the 20 participants was 532+/- 109 ml; maximum flow rate and average flow rate were 27.1+/- 9.4, and 17.2+/- 6.4 ml/sec, respectively. The voided volume decreased significantly in the second uroflowmetry (338+/- 82 ml, P<0.01); the maximum and average flow rates did not changed significantly (24.2+/- 9.5 and 14.9+/- 6.9 ml/sec, respectively). No participant had a shift of more than one standard deviation between the two tests on the Siroky's flow-rate nomogram., Conclusions: With psychological motivation to win the contest, the participants showed greater tolerance to bladder filling. This suggests that the state of mind can affect the perception on bladder sensation. On the other, the performance on emptying function is not significantly improved by motivation., (Neurourol. Urdynam. (c) 2005 Wiley-Liss, Inc.)

Introduction: This study was undertaken to investigate the effects of pumpkin seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T-P) prostate growth in rats., Materials and Methods: Forty adult Wistar rats were divided into five groups, including: one control group, rats treated with vehicle only, one group treated with T-P, and two groups of T-P-treated rats, one receiving orally pumpkin seed oil alone and one group receiving orally pumpkin seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to-body weight ratio was determined after sacrifice. The total protein concentration was measured by using a protein assay. Some ventral prostatic tissues were histologically examined after hematoxylin-eosin staining., Results: Histological sections of the ventral prostate showed that the architecture of the prostate glands became hyperplastic in the T-P rats, but not in the control or vehicle-treated animals. As compared with the control or vehicle group, T-P rats had a significantly higher prostatic weight-to-body weight ratio for the ventral prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001, respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or pumpkin seed oil combined with Phytosterol-F had a significantly lower weight ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and significantly lower protein levels within both lobes (p=0.03 and p=0.003, respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had some additive effect on the total protein synthesis within the ventral prostate (p=0.02)., Conclusion: Pumpkin seed oil alone or combined with Phytosterol-F can block the T-P-induced increases in prostatic weight-to-body weight ratio and protein synthesis., (Copyright (c) 2006 S. Karger AG, Basel.)

Objective: To assess changes associated with diabetes in urinary bladder nerve-growth factor (NGF) and NGF receptor p75NTR expression using a streptozotocin (STZ)-induced diabetic rat model., Materials and Methods: Male Wistar rats (32) were divided into four equal groups: group I, vehicle-treated normal rats; group II, vehicle-treated 9-week STZ-diabetic rats; group III, insulin-treated 9-week STZ-diabetic rats; group IV, phlorizin-treated 9-week STZ-diabetic rats. Bladder NGF levels were measured by enzyme-linked immunosorbent assay. Expressions of the mRNAs that encoded NGF and NGF receptor p75NTR in the rat bladder were evaluated using reverse transcription-polymerase chain reaction., Results: The mean (SEM) NGF level in the STZ-diabetic rat bladder was significantly lower than in the control group, at 56.56 (8.28) and 84.33 (11.05) pg/microg protein, respectively (P < 0.01). The mRNA expressions of bladder NGF and p75NTR in the diabetic rats were significantly lower than in the control group (P < 0.05 and <0.001, respectively). Treatment with either insulin or phlorizin restored the normal blood sugar level; moreover, the bladder NGF levels and the expressions of both NGF and p75NTR mRNAs were normal., Conclusion: The decrease in the genetic expression of NGF and p75NTR might be responsible for the pathogenesis of diabetic cystopathy while hyperglycaemia is part of the cause of these changes.

This study investigated the role of the sorbitol pathway on the genetic up-regulation of the cardiac M(2) muscarinic receptor (M(2)-mAChR) in streptozotocin (STZ)-induced diabetic rats. Three-month-old male Wistar rats were divided into five groups: (1) normal controls; (2) rats rendered diabetic by streptozotocin; (3) rats fed with glucose; (4) rats injected with sorbitol; and (5) diabetic rats treated with ONO-2235, an aldose reductase inhibitor. The M(2) muscarinic receptor (M(2)-mAChR) protein and mRNA densities of the heart tissue were measured by Western immunoblotting and Northern blotting, respectively. The densities of M(2)-mAChR protein and mRNA in the heart were significantly increased in diabetic rats, and rats given either glucose or sorbitol. When diabetic rats were treated with ONO-2235, the increases in heart M(2)-mAChR protein and mRNA were significantly reduced. The findings suggest that hyperglycemia and the sorbitol pathway are involved in the pathogenesis of diabetic heart disease in STZ-induced diabetic rats. Aldose reductase inhibitors may be useful in the treatment and prevention of cardiac complication in diabetes.

Objectives: To describe and compare primary urethral carcinomas in South Taiwan with those in the USA and to explore the influence of chronic arsenic exposure., Methods: From 1988 to 2001, there were 21 pathologically proven primary urethral carcinomas diagnosed and treated at our hospital (14 males, 7 females). Seven of 14 male patients were chronically exposed to arsenic in drinking water for an average of 23 years. We compared our cases to three studies in the USA (80 males, 179 females), and analyzed the influence of chronic arsenic exposure by onset age, histology, staging, and outcome., Results: Male patients with localized tumors had better survival compared to those with advanced tumors (p = 0.0045 in males, p = 0.07 in females). In comparison to the three studies in the USA, there was an unusual higher frequency of bulbomembranous adenocarcinoma at our center (43 vs. 18%, 2 and 0%, respectively, p < 0.0001), particularly among those with chronic arsenic exposure (73 vs. 14%, p = 0.031)., Conclusions: In South Taiwan, there was a high frequency of bulbomembranous urethral adenocarcinoma, which might be associated with chronic arsenic exposure. Although the implications of such an observation are minimal owing to its rarity, it is worth exploring., (Copyright 2005 S. Karger AG, Basel.)

The inhibitory effect of buflomedil on alpha1A-adrenoceptor (AR) in the prostate of Wistar rat was investigated in this study. Normotensive and spontaneous hypertensive rats were orally fed with buflomedil (150 mg/kg). The drug effects on blood pressure and heart rate were monitored by photoelectric volume oscillometric method. Prostate tissue strips from normotensive rats were contracted in vitro in organ bath by phenylephrine (10(-8) to 10(-2)M). The inhibitory effects of buflomedil (10(-9) to 10(-7)M) on the phenylephrine-induced contractions were measured. Radioligand binding displacement study by buflomedil was performed on rat prostate alpha1A-adrenoceptor (AR) and spleen alpha1B-AR. Furthermore the effects of buflomedil and WB-4101 on phenylephrine (10 microM) activated uptake of 2-[14C]-deoxy-d-glucose (2-DG) into C2C12 cells were evaluated. The results showed that buflomedil feeding did not alter the systolic blood pressure of either spontaneous hypertensive rats or normal rats. Dose-inhibition curves of phenylephrine-induced prostate contraction demonstrated a higher potency of buflomedil than tamsulosin. Buflomedil displaced [3H]prazosin binding in a concentration-dependent manner both in rat prostate alpha1A-AR and spleen alpha1B-AR. The ratio of affinity to alpha1A-AR and alpha1B-AR for buflomedil was 4.06/6.84, indicating selectivity on alpha1A-AR over alpha1B-AR. Activation of C2C12 cell alpha1A-AR by phenylephrine increased the glucose uptake to 116%. Both buflomedil and WB-4101 inhibited the uptake in a concentration-dependent manner. In conclusion, the findings showed that buflomedil has preferential alpha1A-AR antagonistic effect to inhibit prostate contraction without significantly affecting the blood pressure.

The main aim of this study was to investigate the feasibility of using nonionic polymeric micelles of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) as a carrier for oral DNA delivery in vivo. The size and appearance of DNA/PEO-PPO-PEO polymeric micelles were examined, respectively, by dynamic light scattering and atomic force microscopy, and their zeta potential was measured. Expression of the delivered lacZ gene in various tissues of nude mice was assessed qualitatively by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of sections and quantitatively by measuring enzyme activity in tissue extracts, using the substrate of beta-galactosidase, chlorophenol red-beta-D-galactopyranoside. In addition, the types of cells expressing the lacZ gene in the duodenum were identified by histological analysis. DNA/PEO-PPO-PEO polymeric micelles are a single population of rounded micelles with a mean diameter of 170 nm and a zeta potential of -4.3 mV. Duodenal penetration of DNA/PEO-PPO-PEO polymeric micelles was evaluated in vitro by calculating the apparent permeability coefficient. The results showed a dose-independent penetration rate of (5.75 +/- 0.37) x 10(-5) cm/sec at low DNA concentrations (0.026-0.26 microg/microl), but a decrease to (2.89 +/- 0.37) x 10(-5) cm/sec at a concentration of 1.3 microg/microl. Furthermore, when 10 mM RGD peptide or 10 mM EDTA was administered before and concurrent with the administration of DNA/PEO-PPO-PEO polymeric micelles, transport was inhibited ([0.95 +/- 0.57] x 10(-5) cm/sec) by blocking endocytosis or enhanced ([29.8 +/- 5.7] x 10(-5) cm/sec) by opening tight junctions, respectively. After oral administration of six doses at 8-hr intervals, the highest expression of transferred gene lacZ was seen 48 hr after administration of the first dose, with gene expression detected in the villi, crypts, and goblet cells of the duodenum and in the crypt cells of the stomach. Reporter gene activity was seen in the duodenum, stomach, and liver. Activity was also seen in the brain and testis when mice were administered 10 mM EDTA before and concurrent with DNA/PEO-PPO-PEO polymeric micelle administration. lacZ mRNA was detected in these five organs and in the blood by reverse transcription-polymerase chain reaction. Taken together, these results show efficient, stable gene transfer can be achieved in mice by oral delivery of PEO-PPO-PEO polymeric micelles.

Diabetes-associated alterations in prostate alpha(1A)-adrenoceptor (alpha(1A)-AR) gene expression were studied using a streptozotocin (STZ) induced diabetic rat model. Male Wistar rats were divided into four groups: group I animals were vehicle-treated normal rats; group II consisted of vehicle-treated, STZ-diabetic rats; group III represented insulin-treated, STZ-diabetic rats (0.5 IU/kg three times daily for 4 days), and group IV animals were phlorizin-treated, STZ-diabetic rats (1 mg/kg three times daily for 4 days). The expression of mRNA that encoded protein of alpha(1A)-AR in the rat prostate was studied using reverse transcription combined with polymerase chain reaction. The alpha(1A)-AR protein expression in the prostate was studied by Western blotting analysis with a polyclonal antiserum. A 2.51 +/- 0.21-fold increase in the mRNA level of alpha(1A)-AR was observed in the prostate of diabetic rats (n = 8, p < 0.05). Similarly, there was a 2.23 +/- 0.10-fold increase in the alpha(1A)-AR protein level (n = 8, p < 0.05). Both insulin and phlorizin treatments restored the normal levels of mRNA and protein expression. In conclusion, the gene expression of alpha(1A)-AR is increased in the prostate of diabetic rats. Hyperglycemia plays a major role in this alteration., (Copyright 2003 S. Karger AG, Basel)

Objectives: To explore the clinical significance of p53 and HER-2/neu coexpression by immunohistochemistry in patients with invasive bladder cancer in Taiwan., Methods: Paraffin-embedded tumor blocks were obtained from 67 patients with invasive bladder cancer subjected to radical cystectomy, bilateral lymph node dissection, and urinary diversion with or without systemic chemotherapy. Two observers (N.H.C. and T.S.T.), blinded to clinical outcome, reviewed the immunohistochemical staining for p53 (PAb1801) and HER-2/neu (Ab-17). The results were analyzed for progression-free survival and patient survival., Results: Positive staining for p53 and HER-2/neu was found in 30 (44.8%) and 39 (58.2%) patients. In contrast to HER-2/neu, p53 expression was significantly associated with tumor grade and pathologic stage (p = 0.040 and 0.004, respectively), and tended to be related to the nodal status (p = 0.080). Most importantly, coexpression of p53 and HER-2/neu significantly correlated with nodal metastases (p = 0.020). Univariate and multivariate analysis revealed p53 and nodal status as two independent prognostic factors. Additionally, patients with p53 and HER-2/neu coexpression had the shortest time to relapse and overall survival, irrespective of whether adjuvant chemotherapy was given or not (p = 0.005 and 0.030)., Conclusions: In invasive bladder cancer, p53 was an important prognostic factor since its expression correlated with tumor grade and stage, even nodal status, whereas HER-2/neu did not show prognostic significance. Tumors with p53 and HER-2/neu coexpression were associated with nodal metastases, probably resulting in decreased progression-free survival. Although some basic studies provide some important supports, studies including larger patient cohorts would still be required to prove the hypothesis that p53 and HER-2/neu-coexpressing tumors have a worse prognosis and are more resistant to a cisplatin-based multidrug regimen., (Copyright 2003 S. Karger AG, Basel)

Emphysematous pyelonephritis (EPN) is a rapidly progressive and potentially life-threatening necrotizing infection of the renal parenchyma characterized by the presence of gas. Bilateral EPN is a rare disease process with a high mortality rate. Bleeding associated with EPN is an extremely rare complication. Necrotizing fasciitis is a rare but serous condition with a poor prognosis. Herein we present a rare case of bilateral EPN combined with subcapsular hematomas which progressed to the development of disseminated necrotizing fasciitis., (Copyright 2003 S. Karger AG, Basel)

Aim: To present an alternative technique of implanting the tension-free vaginal tape (TVT) to minimize the risk of bladder perforation or major pelvic injuries., Patients and Methods: Sixteen female patients with stress urinary incontinence were operated on. The procedure was performed under epidural/spinal anesthesia. A vaginal inverted U incision was made. Dissection was performed alongside the urethra bilaterally and the index finger bluntly dissected into the Retzius space after perforation of the endopelvic fascia. The TVT needle was passed through the lower abdominal wall guided by finger. The rest of the procedure was then finished up as originally described., Results: All patients underwent the operation smoothly without any bladder perforation or major pelvic injury. The mean operative time was 49 (range 32-87) min, and no patient had blood loss >100 ml. All patients could void satisfactorily within 2 weeks. Postoperatively, 94% of the patients (15/16) reported complete dryness, and 6% (1/16) significantly improved. At follow-up after 6 months, the dry rate was 87% (14/16) and the improvement rate 13% (2/16). The 24-hour pad test was significantly improved: preoperatively 112 +/- 43 g; postoperatively 8.5 +/- 4 g (p < 0.001). The maximum flow rate was not significantly reduced: preoperatively 27.1 +/- 8.9 ml/s, postoperatively 24.6 +/- 6.4 ml/s (p > 0.05). No patient had residual urine >50 ml., Conclusions: The reported technique offers an alternative way for TVT implantation. The intent is to minimize the risk of major pelvic injury and bladder perforation without compromising the surgical outcomes. Such benefit may outweigh the additional trouble of periurethral dissection., (Copyright 2003 S. Karger AG, Basel)

The study investigated the effect of a traditional Chinese herbal preparation 'Ba-Wei-Die-Huang-Wan' on the cholinergic function of the urinary bladder in diabetic rats, as well as its influence on the protein expression of muscarinic M(2) receptors. Wistar rats were divided into three groups: (1) control rats; (2) 2-week streptozotocin-induced diabetic rats; and (3) diabetic rats treated with Ba-Wei-Die-Huang-Wan 26 mg/kg thrice daily for 3 days. A dose-response study was performed for bladder muscle strip contractile response to a muscarinic agonist, arecaidine propargyl ester (APE). The amount of M(2) receptor protein in the bladder was measured by Western immunoblotting using monoclonal antibodies. The bladder contractile response to APE was significantly increased in the diabetic rats compared to the control. The M(2) receptor protein density was also significantly higher by 106% (P < 0.01, n = 8) in diabetes. Ba-Wei-Die-Huang-Wan treatment significantly lowered the plasma glucose level of the diabetic rats. The increases in contractile response to APE as well as the M(2) receptor protein density were partially reversed by the treatment. In conclusion, there was an over-expression of M(2) receptor resulting in hyper-contractility in the bladder of diabetic rats. Ba-Wei-Die-Huang-Wan significantly alleviated the alterations.

Spontaneous pyeloduodenal fistula is extremely rare. Most of the etiologies belong to chronic renal inflammatory disease, especially in patients with renal calculi. In published studies, only 2 cases have been reported in association with renal malignancy. We report a case of spontaneous pyeloduodenal fistula associated with transitional cell carcinoma, which has not been previously described in published reports.

Purpose: We have previously developed and reported an ultrasound based real-time tracking system for renal stones. In the current study we continued to verify the reliability of this tracking system by a simulated animal test., Materials and Methods: We used 13 prerecorded ultrasound stone trajectories to test the system. The real-time tracking system was implemented on the Litemed 9200 electrohydraulic lithotriptor (LiteMed Co., Taipei, Taiwan). An artificial stone and tap water were sealed in a balloon. The balloon was inserted into the pelvis of a pig kidney. While the kidney was affixed to and moved by a simulator, it was immersed in a specifically designed simulated animal model tank containing tap water. The stone was localized by ultrasound. The kidney was moved by the simulator according to a prerecorded stone trajectory. A total of 3,000 shock waves were delivered to the stone. For each recorded stone trajectory experiments were done under nontracking and tracking conditions. We performed tests of the fragment-to-weight ratio, which denotes the performance of a shock wave lithotriptor when fragmenting a stone., Results: The mean fragment-to-weight ratio was 55.3% +/- 25.9% in the nontracking and 100% +/- 0% in the tracking group. The difference in these 2 groups was statistically significant (paired t test p <0.01)., Conclusions: The ultrasound based real-time tracking system proved to improve the performance of a shock wave lithotriptor significantly when fragmenting stones in a simulated animal test. We believe that the tracking system would greatly reduce the number of shocks and time needed for treating renal stones.

A 47-year-old man complained of a constellation of prostatitis-like symptoms for 4 years. Physical examination revealed a firm nodule within the scrotum. Surgical excision was performed under local anesthesia and microscopic examination confirmed scrotal calcinosis. The patient remained symptom free for at least 12 months after excision. Although the real mechanism of prostatitis-like symptoms is unknown, this rare disease may be considered in the differential diagnosis or etiologies of chronic prostatitis, and meticulous physical examination of the scrotum is necessary for patients presenting with chronic prostatitis syndrome.

This study investigated the role of sorbitol, a metabolic product of glucose, in the pathogenesis of rat diabetic cystopathy. Three-month-old male Wistar rats were divided into four groups: 1) normal controls; 2) rats rendered diabetic by streptozotocin; 3) rats fed with glucose; and 4) rats injected with sorbitol. The M(2) muscarinic receptor (M(2)-mAChR) protein and mRNA densities of the bladder tissue were measured by Western immunoblot and Northern blot, respectively. The streptozotocin-induced diabetic rats were then treated with ONO-2235, an aldose reductase inhibitor. The bladder M(2)-mAChR protein and mRNA were compared between the treated and untreated diabetic rats. The densities of M(2)-mAChR protein and mRNA in the bladder tissue were significantly increased in diabetic rats, and rats given either glucose or sorbitol (increases in receptor protein: 27.3 +/- 3.3, 19.8 +/- 2.3, and 18.0 +/- 2.1%; increases in mRNA: 39.6 +/- 3.7, 33.1 +/- 2.9, and 20.2 +/- 2.2%, respectively). When diabetic rats were treated with ONO-2235, the increases in bladder M(2)-mAChR protein and mRNA were significantly alleviated. The findings suggest that sorbitol plays a role in the pathogenesis of diabetic cystopathy in rats rendered diabetic by streptozotocin. Aldose reductase inhibitors may be useful in the treatment and prevention of diabetic cystopathy., (Copyright 2002 Wiley-Liss, Inc.)

The M(3) receptor (M(3)-mAChR) is the major muscarinic subtype in the animal bladder responsible for detrusor contraction. The alterations in its protein quantity and biosynthesis during diabetic cystopathy were investigated. 3-month-old male Wistar rats were divided into two groups: (1) 2-week diabetic rats and (2) normoglycemic control rats. Diabetes was induced by a single intravenous injection of 60 mg/kg streptozotocin. The amount of M(3) receptor protein in the rat bladder body tissue was measured by Western immunoblotting using monoclonal antibodies. For determination of M(3) muscarinic receptor mRNA in the bladder tissue, the method of Northern blotting was employed. The results of the Western immunoblotting showed that the amount of M(3)-mAChR protein in the diabetic bladder was significantly increased by about 70.2 +/- 8.5% when compared to the control bladder (p < 0.05, n = 8). Northern blotting demonstrated a 54.7 +/- 6.0% increase of M(3)-mAChR mRNA in the diabetic bladder (p < 0.05, n = 8). The findings of the present study demonstrated an upregulation of M(3)-mAChR biosynthesis in the diabetic urinary bladder. This phenomenon offers an explanation of the increased contractility after muscarinic stimulation of the detrusor muscle of diabetic animals., (Copyright 2002 S. Karger AG, Basel)

Objective: To evaluate the long-term durability of transurethral microwave thermotherapy (TUMT) with Prostcare for symptomatic benign prostatic hyperplasia (BPH)., Patients and Methods: From August 1993 to July 1994, a total of 65 patients with symptomatic BPH who underwent TUMT using the Prostcare apparatus (Bruker Spectospin, Wissembourg, France) with low-energy protocol (maximal power 52 W) were enrolled into a short-term evaluation. Subsequent follow-up information was collected in July 1999. If patients had had any further therapy for BPH, the date of retreatment was considered as an endpoint of TUMT efficacy. If no further therapy for BPH had been needed, they were re-assessed for overall satisfaction., Results: The median follow-up period was 49 months. Twenty patients were excluded for various reasons, including 17 with loss of follow-up and 3 with new diseases that could affect the voiding status. Thirty-eight (84.4%) of 45 valuable patients had received further therapy for BPH, including medication (n = 21, 46.7%), and endoscopic surgery (n = 17, 37.7%). The times to pharmacologic or endoscopic retreatment after TUMT were 8.9+/-11.1 and 23.0+/-14.4 months, respectively (p = 0.0003, log rank test). Only 7 (15.5%) patients had no further treatment, with 3 having satisfactory improvements, but 4 feel dissatisfied yet not needing any further therapy. In addition, 2 patients complained of erectile dysfunction after TUMT and 1 was diagnosed with prostate cancer 50 months after TUMT. In addition, there was no significant difference for all baseline values among three groups with no retreatment or retreatment with medication or endoscopic surgery., Conclusion: At the 5-year follow-up, the long-term durability of low-energy TUMT with Prostcare is only exhibited in a few patients and the overall retreatment rate was 84.4%. Thus, patient should be informed of the high probability of supplementary treatment after TUMT.

Transitional cell carcinoma of the upper urinary tract is an uncommon neoplasm. Relatively little information is available regarding the clinical relevance of molecular markers. This study was performed to examine the importance of nm23-H1 gene expression (NM23-H1) in this type of tumors. Immunohistochemical expression of NM23-H1 was analyzed in 90 cases of upper urinary tract cancer, and was compared for its prognostic significance with conventional biological indicators. High expression of NM23-H1 was found in 7 cases (8%), intermediate expression in 32 cases (36%), and low expression in 51 cases (57%). Reduced NM23-H1 (defined as intermediate or low level of expression) was associated with a higher histological grading (p=0.002), invasive tumor growth (p=0. 002), or an increased proliferating cell nuclear antigen labeling index (p=0.004). NM23-H1 tended to inversely relate to later recurrence or long-term survival (p=0.06), but, only tumor staging was found to be significant in predicting clinical outcome (p=0.002). nm23-H1 appears to function as a tumor suppressor for upper urinary tract cancer, however, evaluation of NM23-H1 provides limited prognostic information.

The clinical value of p21WAF1/CIP1 in superficial bladder cancer remains controversial. To address the question, we examined the expression patterns of p21 and p53 gene products and compared for their significance in a total of 89 cases of superficial (pTa/pT1) bladder cancer. Over-expression of p21 was detected in 32 of 89 (36%) tumors. But, the expression status did not correlate with biological indicators or clinical outcome (p > 0.1, respectively). Factors predicting clinical outcome were multiplicity for tumor recurrence (p = 0.0002) or patient survival (p = 0.03), and the histological grading for disease progression (p = 0.02) or patient survival (p = 0.05). Taking into account the p53 status, a trend approaching better prognosis for p53+p21+ tumors was observed compared with that of p53+p21- bladder cancer (p = 0.08). Our data indicate that evaluation of p21 status does not provide better prognostic information compared with conventional biological indicators of superficial bladder cancer. Maintenance of p21 appears to abrogate the deleterious effects of p53 alterations in the tumorigenesis of human bladder.

Purpose: To assess our short-term experience with transurethral microwave thermotherapy (TUMT) for symptomatic benign prostatic hyperplasia (BPH)., Patients and Methods: From August 1993 through July 1994, in total 65 patients with symptomatic BPH were enrolled into this study. The patients' ages ranged from 56 to 95 years with a mean of 70 years. Under local anesthesia with intraurethral instillation of Xylocaine jelly only, all patients received one session of TUMT for up to 60 min with Prostcare equipment. Uroflowmetry was performed and international prostatic symptom score (IPSS) determined before 3 and 6 months after TUMT for assessment of efficacy. All adverse events were recorded and evaluated for clinical relevance., Results: At 3 and 6 months following TUMT, the mean IPSS decreased from 19.7 +/- 6.8 (baseline) to 12.8 +/- 8.2 (-46%) and to 15.5 +/- 9.0 (-21%), respectively; the maximal urine flow rate at 3 and 6 months increased from 9.1 +/- 4.8 ml/s (baseline) to 11.0 +/- 4.9 ml/s (+21%) and to 10.9 +/- 5.6 ml/s (+19%), respectively. During TUMT, burning sensation was the most frequent complaint (38.5%), followed by urethral discomfort (29.2%) and urgency (9.2%). Two patients (3.1%) interrupted TUMT, because of intolerable pain. Following TUMT micturition pain (73.8%) and gross hematuria (45.9%) were the most adverse events. Most of these adverse events disappeared within 2 weeks. One patient suffered from skin erosion over the penoscrotal junction 1 week later. None had retrograde ejaculation; 1 patient complained of erectile dysfunction., Conclusion: Although the efficacy of TUMT with Prostcare became less prominent 6 months after TUMT, TUMT was still a tolerable, safe alternative treatment of BPH, especially in patients who were not suitable for transurethral resection of the prostate or anesthesia., (Copyright 2000 S. Karger AG, Basel)

The effect of N-(biphenylyl-methyl)imidazole, losartan potassium, a newly developed antihypertensive type 1 angiotensin II receptor antagonist on the rat erectile function, was studied. Sexually active 9-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were given losartan 60 mg/kg intraperitoneal injections. Mean blood pressure (MBP) dropped significantly in both SHR and WKY rats (for SHR: from 140 +/- 8 to 114 +/- 5 mm Hg, p < 0.05, n = 8; for WKY: from 113 +/- 7 to 79 +/- 9 mm Hg, p < 0.05, n = 8). On the contrary, the intracavernous pressure (ICP) of SHR and WKY rats did not differ significantly from that of the corresponding controls receiving saline injections (p > 0.05, n = 8 for each group). For the chronic study, the rats were fed with losartan 30 mg/kg/day for 30 days. MBP decreased significantly in SHR but not in WKY rats (for SHR: from 137 +/- 7 to 113 +/- 5 mm Hg, p < 0.05, n = 8; for WKY: from 110 +/- 6 to 107 +/- 5 mm Hg, p > 0.05, n = 8). The ICP of the losartan-treated rats was not significantly different from that of control rats (p > 0.05, n = 8 for each group). In contrast, WKY rats receiving guanethidine 1 mg/kg/day for 30 days showed significantly decreased ICP. Angiotensin II (10(-9)-10(-5) M) and losartan (10(-9)- 10(-5) M) did not induce significant contractile responses of the cavernosal strip when tested in vitro. On the other hand, methoxamine 10(-4) M induced good contractile responses. In conclusion, the present study demonstrated that angiotensin II did not cause significant change in the contractile status of rat corpus cavernosum. Correspondingly, the type 1 angiotensin II inhibitor effectively lowered blood pressure but did not affect cavernosal contractile function, thus is useful clinically in the treatment of hypertensive disorders without significant detrimental effects on male sexual function., (Copyright 2000 S. Karger AG, Basel)

Objective: The aim of our study was to determine whether there is an increased incidence of urothelial cancer, especially transitional cell carcinoma (TCC), in uremic patients on dialysis., Methods: Retrospective chart analyses were completed for 1,910 uremic patients undergoing maintenance dialysis between January 1987 and December 1997. The incidence of urinary tract cancer was assessed. Only the patients with cancers diagnosed after start of dialysis were enrolled in the study., Results: Of the 1,910 patients, 70 had concomitant urinary tract cancers. Nineteen patients (0.99%), including 17 patients with TCC and 2 patients with renal cell carcinoma, were diagnosed after the initiation of dialysis. The average duration from dialysis to TCC diagnosis was 38.3 (range 2-144) months. Painless gross hematuria was the cardinal symptom in 16 of the 17 patients with TCC. In the 17 patients with TCC, no distant metastases were found at the time of diagnosis. Fourteen patients (82.3%) were stage 0 or A, and 1 patient was stage B1., Conclusions: The 0.89% incidence of TCC in our dialysis patients was high as compared with that of the general population. The risks of developing urinary TCC in dialysis patients were examined, and we suggest that immunosuppressive stage, dialysis procedure, and chronic bladder irritation (decreased urinary wash effect) may play a part in the development of urinary TCC in dialysis patients. Early detection of hematuria due to regular visits and decreased exposure of urinary tract epithelium to carcinogens from urine may explain why early-stage TCC was seen in most of our patients.

The M2 receptor (M2-mAChR) is quantitatively the dominant muscarinic subtype in animal bladders. The alterations in its protein quantity and biosynthesis during diabetic cystopathy were investigated. Three-month-old male Wistar rats were divided into two groups: (1) 2-week-old diabetics; and (2) normoglycemic control rats. Diabetes was induced by single intravenous injection of 60 mg/kg streptozotocin. The amount of M2 receptor protein in the rat bladder body tissue was measured by Western immunoblotting using monoclonal antibodies. For determination of M2 muscarinic receptor mRNA in the bladder tissue, the method of Northern blotting was employed. The results of the Western immunoblotting showed that the amount of M2-mAChR protein in the diabetic bladder was significantly increased by 40.0 +/- 6.2% when compared with the control bladder (P < 0.05, n = 8). The Northern blotting demonstrated a 69.3 +/- 8.5% increase of the M2-mAChR mRNA in the diabetic bladder (P < 0.05, n = 8). The findings of the present study demonstrated an up-regulation of M2-mAChR biosynthesis in the diabetic urinary bladder. This phenomenon could lead to increased reactivity to acetylcholine and thus results in detrusor instability.

Rationale and Objectives: Ureteric jet index (UJI), a newly developed technique derived from color Doppler ultrasonography, may hold promise in evaluating renal function because of its ability to evaluate individual renal function and the use of nonionizing radiation. To assess the usefulness of UJI, the authors in this study analyzed the relation between UJI and the glomerular filtration rate (GFR)., Methods: Fifteen adult patients with a wide range of renal function were included in this study. Subjects were well hydrated before color Doppler ultrasonography examinations. The UJI formula was: Vmean (average jet velocity) x D (jet duration) x F (jet frequency). GFR was calculated by the radionuclide method. Correlations between UJI, serum creatinine, and GFR were analyzed., Results: Ureteric jet index had only a fair correlation with GFR. The coefficient of correlation value was 0.61, and the standard error of estimate of GFR was 17.9 mL/min., Conclusions: With the measurement of UJI, color Doppler ultrasound can provide both structural images and individual renal function information. It could substitute for a renal scan in determining individual renal function when a radionuclide examination is unavailable. Even if a renal scan were available, UJI can play a valuable role in the ultrasound examination of patients with suspected impaired renal function, providing further assessment of individual renal function.

Many commonly used antihypertensive drugs such as diuretics and beta-blockers can interfere with sexual function in both sexes, causing loss of libido, impairment of erectile function and ejaculation in men, and delay or prevent orgasm in women. Newly developed antihypertensive drugs should ideally not interfere with the patients' quality of life including sexual function. This study examined the effects of losartan, a nonpeptide, specific antagonist for type I angiotensin II receptors, on the male sexual behavior of rats. Spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were treated with losartan 30 mg/ kg/day or saline control for 7, 30 and 90 days. Dark-cycle video recording was used to analyze the male sexual activities of the rats. No significant alteration in male sexual performance was observed after 7 and 30 days of treatment with losartan. In contrast, SHRs treated with propranolol 5 mg/kg/day showed increases in intromission latency, ejaculation latency and postejaculatory period indicating decreased libido and erectile and ejaculatory function. Upon completion of 90 days of losartan administration, the mount latency of the SHR was significantly increased, suggesting a decrease in libido although other parameters were unchanged and there was no effect in WKY rats. It is therefore concluded that losartan may have an advantage in preservation of sexual function when used clinically for the treatment of hypertensive disorders.

Background: We evaluated whether p53 and bcl-2 expression has any predictive value on the outcome of postoperative adjuvant intravesical chemotherapy for superficial bladder transitional cell carcinoma (TCC)., Materials and Methods: Immunostaining for p53 and bcl-2 was performed on paraffin-embedded tumor tissues obtained from 100 patients with superficial bladder TCC. 56 had solitary and 44 had multiple tumors; 36 were grade I, 53 grade II and 11 grade III; 50 were stage pTa and 50 stage pT1. They all received transurethral resection (TUR) and weekly intravesical instillation chemotherapy with either Thiotepa (70 patients) or Epirubicin (30 patients) for consecutive 8 doses postoperatively., Results: Overall, 7 (7%) tumors were p53+ and 12 (12%) tumors were bcl-2+. Of these, only one tumor was combined p53+ and bcl-2+. The status of tumor p53 and bcl-2 positivity was found to be not significantly correlated with either tumor grade or stage. After adjuvant intravesical chemotherapy, tumor recurrence is significantly correlated with tumor multifocality (p = 0.0002) but not with tumor grade and stage. Compared with p53- or bcl-2- tumors, patients with p53+ or bcl-2+ tumors do not show a higher tumor recurrence rate. The number of recurrence-free patients was also not significantly different in p53+ versus p53- tumors, bcl-2+ versus bcl-2- tumors. Six (6%) patients eventually developed disease progression, and none stained positively for either p53 or bcl-2., Conclusions: We conclude that in superficial bladder TCC the status of tumor p53 and bcl-2 expression is not correlated with stage and grade. Their expression, either alone or combined, has no predictive role on the outcome of post-TUR intravesical chemotherapy on tumor recurrence.

Purpose: We provided direct evidence for the existence of purinergic innervation in the rat urinary bladder., Materials and Methods: The non-adrenergic non-cholinergic (NANC) innervation was studied in 4-month-old Wistar rats. Electric-field stimulation (EFS) of the detrusor muscle strips in the presence of four autonomic blockers (atropine 10(-6) M, guanethidine 10(-6) M, phentolamine 10(-6) M and propranolol 10(-6) M) showed NANC contractions accounted for about 50% of the maximum contractile response. The adenyl purines released from nerves by EFS were detected by HPLC after conversion to ethenopurines. The amount of total purine released was frequency-dependent and could be totally suppressed by tetradotoxin (10(-6) M). The amount of ATP released was significantly greater than those for ADP, AMP and adenosine (p < 0.05, n = 4). Desensitization induced by alpha, beta-MeATP (10(-6) to 10(-4) M), a P2x receptor agonist, reduced the NANC contraction. In addition, the NANC contraction was also abolished by P2 receptor blocker suramin (10(-4) to 10(-3) M) and P2x receptor blocker PPADS (10(-5) to 10(-4) M.)., Conclusion: The results of the present study give evidence to support purinergic nerve-mediated bladder smooth muscle contractions in the rat. Among the purine nucleotides, ATP is the dominant purinergic neurotransmitter released and P2x receptor activation is responsible for the NANC contractile response.

Glucose homeostasis was studied in the spontaneously hypertensive rat (SHR). The fasting plasma glucose levels were similar in the SHR and normotensive Wistar-Kyoto (WKY) rat (102.7+/-2.4 vs. 107.4+/-4.2 mg/dl, P > 0.01). One hour after glucose challenge, the plasma glucose level was slightly but insignificantly increased in both SHR and WKY rat (117+/-2.5 vs. 114.3+/-3.2 mg/dl, P > 0.01). After N(G)nitro-L-arginine methyl ester (L-NAME) 20 mg/kg per day was administered intraperitoneally (i.p.) for 4 days, the plasma glucose level was significantly increased in the rats (SHR 167.3+/-4.9; WKY rat 136.0+/-4.8 mg/dl); the increase was significantly more pronounced in the SHR. The fasting insulin levels were similar in the SHR and WKY rats (2.3+/-0.4 vs. 2.0+/-0.3 ng/ml, P > 0.01). One hour after glucose challenge, the insulin level was significantly increased in the WKY rat (4.8+/-0.7 ng/ml) but not in the SHR (2.2+/-0.4 ng/ml). With L-NAME treatment, plasma insulin increase was noted in the WKY rat but not SHR (4.6+/-0.6 vs. 2.6+/-0.4 ng/ml, n = 8, P < 0.01). One hour after insulin 1 IU/kg was injected intramuscularly (i.m.), the plasma glucose level was significantly decreased in both the SHR (from 115.0+/-6.5 to 48.6+/-3.6 mg/dl, n = 8) and WKY rat (from 108.3+/-3.8 to 52.6+/-4.2 mg/dl, n = 8). No significant difference was noted between the decrease of the two groups (P > 0.01). The present findings suggested that NO plays a role in the glucose homeostasis of rats. NO-synthase blockade resulted in an increase of plasma glucose level. The SHR maintains normal glucose level and tolerance in spite of a defective insulin release response. This is probably due the compensatory effect of a more prominent NO-dependent glucose homeostatic function.

Background: Haphazard cell proliferation is a fundamental biologic defect in cancer. Thus, assessment of the growth fraction provides a valuable index of biological property for human neoplasm. Proliferating cell nuclear antigen (PCNA) expression has been used to estimate the growth fraction of human cancer, and its prognostic value. Information in transitional cell carcinoma (TCC) of the upper urinary tract, however, is very few., Materials and Methods: A total of 73 patients with TCC of the upper urinary tract was collected between July 1988 and December 1995 for this study. The labeling index of PCNA immunostaining was correlated with clinicopathologic factors and compared for its prognostic value with a median follow-up of 54 months., Results: The PCNA index was positively associated with histological grading, tumor stage and patient prognosis (P = 0.00, respectively). Multivariate analysis demonstrated that significant factors in relation to patient survival were tumor stage (P = 0.01), followed by PCNA index (P = 0.04) and gender of patients (P = 0.04). Multiple comparison revealed that PCNA index set at 0.30 had prognostic value in terms of patient survival (P = 0.00), and the risk of metachronous bladder recurrence (P = 0.02)., Conclusion: Our data suggested that assessment of PCNA index may be used as an adjuvant prognostic factor for patients with TCC of the upper urinary tract.

The subtyping of alpha1-adrenoceptors responsible for mediating contraction in isolated corpus cavernosum of mature male Wistar rats was studied pharmacologically. Concentration-response studies of the cavernosal smooth muscle to three agonists: methoxamine, norepinephrine and octopamine showed that methoxamine exhibited the highest potency in inducing contractile response; the respective pD2 values were: 6.22, 5.83 and 5.38. In the presence of 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB4101), a specific antagonist for alpha1A-adrenoceptors, a parallel rightward shift of the concentration-response curve to methoxamine was observed. On the other hand, chloroethylclonidine (CEC) caused a rightward shift of the concentration-response curve to methoxamine with significant suppression of the maximum response. The pA2 value for WB4101 obtained from Schild plot was 9.03 +/- 0.06 with slope (95% CL) equal to 0.955 (1.088-0.832). In the absence of extracellular calcium ions, the methoxamine-induced contraction was reduced by 92%. Ca2(+)-Channel blockers, nifedipine 10(-6) M and diltazem 10(-6) M decreased the contractile response by 18 and 23%, respectively. The present findings suggest that alpha1A-adrenoceptors are responsible for the methoxamine-induced contraction of the rat cavernosal smooth muscle.

The functional role of non-adrenergic non-cholinergic (NANC) nerves in the autonomic control of the male mini-pig bladder neck was investigated in the present study. Electrical stimulation of muscle strips from male mini-pig bladder neck showed biphasic response with initial phasic contraction followed by post-contractile relaxation. Electrical stimulation in the presence of four autonomic blockers (atropine 10(-6) M, propanolol 10(-6) M, phentolamine 10(-6) M) showed suppression of 68 +/- 15% of the contractile response (P < 0.05, n = 8) but no significant change in the relaxation response. Alpha-chymotrypsin 2 U/ml, L-NG-monomethyl-L-arginine acetate (a nitric oxide synthetase inhibitor) 10(-4) M, 8-phenylthlophylline (a P1-purinoceptor antagonist) 10(-6) M, and pyridoxal-phosphate-6-azophenyl-2', 4'-disulphoric acid tetrasodium salt (a P2Y-purinoceptor antagonist) 3 x 10(-5) M did not alter the NANC response significantly. On the other hand, reactive blue-2 (a P2Y-purinoceptor antagonist) 3 x 10(-5) significantly reduced the relaxation by 79 +/- 9%. The result suggested that the P2Y-purinoceptor is involved in the electrically induced NANC post-contractile relaxation of the mini-pig bladder neck smooth muscle.

1. Contractile responses of smooth muscle from the Wistar rat urinary bladder were studied with the use of muscarinic agonists and antagonists. 2. McN-A-343 induced only weak contractile responses of the bladder muscle. In contrast, oxotremorine showed higher potency than either acetylcholine or bethanechol in inducing a contractile response (the respective pD2 values were 6.38 +/- 0.25, 4.82 +/- 0.24 and 4.42 +/- 0.14). 3. The M2 antagonists, methoctramine (10(-9) M to 10(-5) M) and gallamine (10(-9) M to 10(-5) M), did not reduce acetylcholine-induced (10(-5) M) contractions of the bladder muscle strip. On the other hand, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP, 10(-10) M to 10(-7) M), an M3 receptor blocker, effectively antagonized the acetylcholine-induced contractions in a concentration-dependent manner. 4-DAMP had a similar pA2 value to those of the non-selective antagonists, atropine and scopolamine (pA2 values were 8.26 +/- 0.05, 8.36 +/- 0.05 and 8.41 +/- 0.11, respectively). Pirenzepine, and M1 blocker, antagonized the contractions at higher concentrations (10(-8) M to 10(-5) M, pA2 = 6.23 +/- 0.04). 4. It is concluded that (1) the dominant muscarinic receptor subtype responsible for smooth muscle contraction in the rat urinary bladder is M3; and (2) the muscarinic agonist oxotremorine was more potent than acetylcholine and bethanechol in inducing a contractile response.

Synaptosomes are nerve-end particles (NEP) isolated by using the technique of differential centrifugation. The synaptosome offers a good model for biochemical and pharmacological studies of the nerve endings. No report has been made on synaptosome isolation from the urinary bladder. The purpose of our work was to develop the use of synaptosome in the research of neurophysiology and neuropharmacology of the urinary bladder. Synaptosome-rich fraction was prepared from tissue homogenate of male Wistar rat urinary bladder by differential centrifugation (1000, 17,000 and 100,000 g) with discontinuous sucrose gradient. Electron microscopy showed synaptosomes as thin-walled bags containing a large number of synaptic vesicles. Two types of synaptosomes were easily discerned: those containing small agranular vesicles, and those containing dense-cored vesicles. The acetylcholine, norepinephrine, epinephrine and dopamine contents in the preparation were measured by the method of high-performance liquid chromatography. The respective concentrations were 300.4 +/- 30.1, 962.8 +/- 58.5, 617.3 +/- 59.8 and 1354.8 +/- 144.2 pmol/mg synaptosomal protein. In conclusion, it has been demonstrated that synaptosome-rich fractions can be prepared from the rat urinary bladder. Thus it is possible to apply this methodology for the investigation of the neurobiology of urinary bladders.

Three-month-old male Wistar rats were rendered diabetic with a single intravenous injection of streptozotocin (60 mg/kg body weight). Two weeks after induction of diabetes, synaptosome-rich fractions were prepared from urinary bladder tissue homogenate of the diabetic rats and control rats by differential centrifugation (1000 x g, 17,000 x g and 100,000 x g) with discontinuous sucrose gradient. Synaptosomal acetylcholine, norepinephrine, epinephrine and dopamine were measured by the method of high-performance liquid chromatography. The respective neurotransmitter concentrations for the diabetic rats were 1537.8 +/- 65.3, 4757.7 +/- 361.9, 3720.7 +/- 276.1, and 2447.8 +/- 196.8 pmol/mg synaptosomal protein, respectively; those for the control rats were 338.1 +/- 25.0, 1009.0 +/- 54.6, 645.3 +/- 52.2, and 1426.1 +/- 123.9 pmol/mg protein, respectively. Thus, the synaptosomal concentrations for all the measured neurotransmitters were significantly higher in the diabetic rats (P < 0.05 for each comparison). In conclusion, it has been demonstrated that the vesicle-bound acetylcholine and catecholamines in the synaptosome-rich fraction of the urinary bladder were significantly increased in 2-week diabetic rats. This finding would suggest impaired neurotransmitter release from both the bladder sympathetic and parasympathetic efferent nerve endings in early streptozotocin-induced diabetes.

Synaptosome-rich fractions were prepared from tissue homogenate of the urinary bladder of the spontaneously hypertensive rat and normotensive Wistar-Kyoto rat by differential centrifugation (1000 x g, 17 000 x g and 100 000 x g) with discontinuous sucrose gradient. Synaptosomal acetylcholine, norepinephrine, epinephrine and dopamine were measured by the method of high-performance liquid chromatography. The respective neurotransmitter concentrations for the normotensive rats were 300.4 +/- 30.1, 962.8 +/- 58.5, 617.3 +/- 59.8, and 1354.8 +/- 144.2 pmol/mg synaptosomal protein. For the hypertensive rats, the acetylcholine concentration (203.8 +/- 23.0 pmol/mg protein) was significantly lower (P < 0.05), while the norepinephrine, epinephrine and dopamine concentrations (1459.0 +/- 180.3, 971.3 +/- 62.2, and 2161.0 +/- 243.4 pmol/mg protein, respectively) were significantly higher (P < 0.05 for all) than those of the normotensive rats. In conclusion, it has been demonstrated that the vesicle-bound catecholamines in the synaptosome-rich fraction of the urinary bladder were significantly increased in hypertensive rats. On the contrary, the synaptosomal acetylcholine concentration was significantly decreased. These findings are suggestive of increased sympathetic innervation and decreased parasympathetic innervation in the urinary bladder of the spontaneously hypertensive rat.

Tissue concentration of norepinephrine and neuropeptide-Y immunoreactivity (NPY-IR) were measured in the urinary bladder, urethra, prostate and corpus cavernosum of the spontaneously hypertensive rat, as well as the normotensive Wistar-Kyoto rat. The results showed significantly increased tissue norepinephrine concentrations in the urinary bladder, urethra and prostate of the spontaneously hypertensive rat when compared to those of the normotensive rat (hypertensive, n = 18: 18.3 +/- 2.1, 14.9 +/- 1.7, 22.6 +/- 2.3 vs. normotensive, n = 18: 11.2 +/- 1.9, 10.4 +/- 1.3, 16.7 +/- 2.4 nmol/g tissue, respectively, P < 0.05 in each case). No difference was noted in the cavernosal tissue (hypertensive, n = 18: 11.3 +/- 1.6 vs. normotensive, n = 18: 10.1 +/- 1.8 nmol/g tissue, P > 0.01). Correspondingly, tissue NPY-IR was significantly increased in the bladder, urethra and prostate tissue of the spontaneously hypertensive rat (hypertensive, n = 18: 39.7 +/- 5.6, 25.3 +/- 3.4, 31.5 +/- 2.8 vs. normotensive, n = 18: 27.4 +/- 3.1, 18.6 +/- 2.7, 24.2 +/- 3.2 pmol/g tissue, respectively, P < 0.05 in each case). Again, no significant difference was observed in the cavernosal tissue (hypertensive, n = 18: 15.9 +/- 2.2 vs. normotensive, n = 18: 14.8 +/- 2.6 pmol/g tissue, P > 0.01). It is therefore concluded that increased tissue concentration of norepinephrine and NPY-IR were present in the urinary bladder, urethra and prostate of the spontaneously hypertensive rat. The significance of such biochemical findings needs further investigation but may suggest increased sympathetic innervation or activity. On the contrary, no corresponding changes were observed in the corpus cavernosum of the hypertensive rat.

Objectives: We presented and analyzed our results in order to determine the relationship between patient survival and tumor grade and/or stage. In addition, a retrospective tumor DNA ploidy study was done to evaluate its possible role in predicting future tumor recurrence in the bladder., Methods: A total of 112 patients with upper urinary tract transitional cell carcinomas (TCCs) were recorded at our hospital. Of these, 68 patients without concurrent bladder tumors (ages ranged from 36 to 80, mean 62.4 years; male:female = 1:1.2) were treated by nephroureterectomy and bladder cuff resection. They were followed up for 14-79 months (average 38.2 months). Eight (36.4%) of the 22 patients who had stage C or D tumors had received adjuvant systemic methotrexate, vinblastine, epirubicin, cisplatin chemotherapy after surgery. DNA flow cytometry using paraffin-blocked tumor specimens was performed on the tumors of 52 patients., Results: Their pathologic stages and grades were 11 at stage 0, 15 at stage A, 20 at stage B, 14 at stage C, 8 at stage D; 9 of grade I, 41 of grade II, and 18 of grade III. Postoperatively, 13 patients (19.1%) subsequently developed bladder tumors with a latent period ranging from 2 to 37 months (average 14.9 months). The difference of the tumor DNA ploidy distribution pattern among tumors of high versus low stages and/or grades is not statistically significant (p > 0.05). Overall, the 5-year survival rates for patients with low- and high-stage tumors were 100 and 66.7%, respectively; for patients with grade I-II and III tumors they were 93.6 and 28.3%, respectively., Conclusions: Patient survival was mainly related to both tumor stages (p = 0.0037) and grades (p = 0.0001), rather than to tumor DNA ploidy. For patients with grade II upper urinary tract tumors, tumor DNA ploidy seems to provide no additional predictive value on subsequent tumor recurrence in the bladder.