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Objectives: Alpha-adrenergic antagonists are commonly used to prevent recurrent urethral obstruction in cats with mixed reports of efficacy. No published data on tamsulosin use in cats are available. The objective of this study was to measure changes in urodynamic parameters and blood pressure in five healthy male cats before and after administration of tamsulosin orally for 4 and 10 days., Methods: Five young healthy adult male cats from a research colony were administered tamsulosin at 0.1 mg/cat PO q24h for 10 days. Urethral pressure profile and blood pressure measurements were performed before treatment and approximately 6 h after treatment on days 4 and 10. Maximum urethral closure pressure (MUCP) for the prostatic and penile urethra, functional urethral length (FPL), functional area (FA) and systolic blood pressures were recorded and compared between the time points., Results: Significant changes in blood pressure on day 4 (121.1 mmHg ± 20.2 mmHg) and on day 10 (112.6 mmHg ± 14.9 mmHg) compared with day 0 (141.1 mmHg± 33.4 mmHg) were not detected ( P  = 0.18) in anesthetized cats. No significant difference in MUCP, FA or FPL measurements were detected among baseline, day 4 and day 10 of treatment. Hematuria and transient pollakiuria were induced in two cats with 3.5 Fr urethral catheters., Conclusions and Relevance: Tamsulosin at 0.1 mg/cat PO q24h did not induce hypotension in healthy cats. Urodynamic testing performed 6 h after the tamsulosin pill was administered did not detect consistent decreases in urodynamic functions induced by tamsulosin. Repeated catheterization of tom cats with 3.5 Fr catheters may induce significant urethral trauma., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The aim of this study was to determine if male cats treated with 7 days of prazosin following relief of urethral obstruction (UO) experienced decreased rates of recurrent urethral obstruction (rUO) within 30 days vs those treated with 7 days of placebo., Methods: All castrated male cats presenting for the first time with UO from May 2014 to August 2017 were eligible for enrollment. Exclusion criteria included the administration of medications or passage of a urinary catheter prior to referral, the presence of heart disease or hypertension requiring medication, prior treatment with glucocorticoids, non-steroidal anti-inflammatory medications, prazosin or phenoxybenzamine, or radiographic identification of cystoliths. Cats were treated with standardized anesthetic and analgesic protocols, standardized indwelling urinary catheter management, and were hospitalized for care. A random numbers table was generated prior to study initiation and cats were randomized to receive either prazosin (0.5 mg PO q12h for 7 days) or placebo in a blinded fashion. A 30-day follow-up with owners via telephone was performed to identify the rate of rUO. Cats that did not receive the full course of study medication were removed from the analysis. The study was unblinded at the end of data collection., Results: Eighty cats were enrolled and 65 cats completed the study; 12 were excluded because they did not receive the study medication. Sixteen of 65 cats experienced rUO (25%). Of the 16 cats experiencing rUO, five received placebo (n = 5/28 [18%]) and 11 received prazosin (n = 11/37 [30%]). Ten of the cats that experienced rUO reblocked while still hospitalized. There was no significant difference in frequency of rUO in cats treated with prazosin vs placebo ( P  = 0.27)., Conclusions and Relevance: Prazosin administered at 0.5 mg PO q12h did not decrease the rate of rUO in this population of obstructed male cats vs placebo. These results further support evidence suggesting that prazosin may not be beneficial in prevention of feline rUO.

Background: Urethral obstruction (UO) is a common complication of feline idiopathic cystitis (FIC). Robust treatment recommendations to prevent its recurrence are scarce., Objectives: To evaluate meloxicam treatment for prevention of clinical recrudescence in male cats with obstructive FIC., Animals: Fifty-one client-owned cats., Methods: Prospective, randomized clinical trial. Every male cat with FIC-associated UO was deemed eligible for the study and was recruited during hospitalization. After discharge, cats were treated with phenoxybenzamine and alprazolam for 2 weeks, with (24 cats) or without (27 cats) low-dose meloxicam (0.025 mg/kg/day PO) and monitored for 6 months., Results: Cumulative number (%) of cats with recurrent UO at 10 days, 1-, 2-, and 6-months after discharge was 1 (2%), 2 (4%), 4 (8%), and 8 (16%), respectively. Overall, 12 (24%) cats experienced signs of recurrent FIC within 6 months, with (8 cats) or without (4 cats) concurrent UO. No difference in the cumulative incidence of UO within 6 months was detected with addition of meloxicam (odds ratio [95% confidence interval], 0.63 [0.13-2.97]; P = .70). All cats were alive at 6 months., Conclusions and Clinical Importance: No clinical benefit was detected with the addition of low-dose meloxicam to phenoxybenzamine and alprazolam treatment for 2 weeks after discharge. Nevertheless, this study was underpowered to identify potential differences, and its findings must be corroborated in larger studies., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Introduction: This study examined the dynamics of 24-h electrocardiogram (ECG) monitoring parameters (Holter monitoring) in patients with ischemic heart disease (IHD) before and after conservative or surgical treatment of patients with voiding and storage lower urinary tract symptoms (LTS) due to benign prostatic hyperplasia (BPH)., Methods: A total of eighty-three 57 to 81-year-old (mean age 70.4 ± 5.75 years) patients with LUTS/BPH and accompanying IHD were examined and treated at the Institute of Urology and Human Reproductive Health and Clinic of Cardiology of Sechenov University. All patients received recommended cardiac therapy at least 6 months before inclusion in the study., Results: Our study demonstrated that there is correlation between voiding and storage LUTS/BPH and Holter-detected cardiac impairments in patients with IHD/BPH. These data make it possible to consider LUTS/BPH (voiding and storage) as a factor in the additional functional and psychological load on the activity of patients with ischemic heart disease. Improvement of voiding and storage LUTS due to BPH and objective parameters of urination (Q max ) in patients treated with alpha-1 adrenoceptor blocker tamsulosin correlated with improvement of 24-h ECG monitoring parameters (Holter monitoring) in 72% of patients. Improvement of 24-h ECG monitoring parameters (Holter monitoring) 1 month after transurethral resection of the prostate (TURP) in IHD/BPH patients and indications for surgical treatment was observed in 65.7%. Negative dynamics of the Holter-based ECG was not registered in patients who were operated on., Conclusion: Holter monitoring helps to identify groups of patients in whom urinary impairments caused by prostatic hyperplasia negatively affect the course of IHD. Restored urination (either conservatively or operatively) in patients with BPH in 72% of cases decreased the number of fits of angina, thus influencing favourably the course of IHD., Trial Registration: ClinicalTrials.gov Identifier: NCT03856242.

Objective: To determine whether prazosin administration following urethral obstruction (UO) reduces the risk for recurrent urethral obstruction (rUO) or lower urinary tract signs, and to document adverse effects associated with prazosin use in cats., Design: Double-blinded, prospective, interventional study., Setting: University teaching hospital., Animals: A population of 47 consecutive male cats with UO not associated with urinary tract calculi >2 mm in diameter., Interventions: Cats were randomized to receive either prazosin (0.25 mg/cat PO q 12 h, n = 27) or placebo (n = 20) for 1 month following UO., Measurements and Main Results: Cats were monitored for rUO, severity of lower urinary tract signs, and medication adverse effects during hospitalization and through weekly conversations with the owner during the 1- month study period and once more at 6 months following discharge. There was no difference in the rUO rate among cats that received prazosin or placebo prior to hospital discharge (2/26 (7%) versus 1/19 (5%), P = 1.00), during the 1- month medication period (4/26 (15%) versus 3/18 (17%), P = 0.776), or at 6 months following treatment for UO (7/19 (37%) versus 4/13 (31%), P = 0.811). There was no difference in the severity of lower urinary tract signs reported by the owners at the 1-, 2-, 3-, or 4-week follow-up periods among the cats in either group (P = 0.62, 0.68, 0.33, 1.00, respectively). Reported adverse effects from prazosin administration included lethargy, ptyalism, diarrhea, anorexia, and malodorous stool., Conclusions: Although our study results failed to find a difference in the incidence of rUO and severity of lower urinary tract signs among cats receiving prazosin and those receiving placebo, these study results should be interpreted cautiously as our study was underpowered to identify such differences. Larger placebo-controlled, prospective studies are needed to determine the clinical utility of prazosin in prevention of rUO., (© Veterinary Emergency and Critical Care Society 2017.)

Objectives The aim of the study was to investigate the effect of the non-steroidal anti-inflammatory drug meloxicam on the clinical course of obstructive idiopathic cystitis in cats in a placebo-controlled clinical study. Methods Thirty-seven cats with obstructive idiopathic cystitis were enrolled. Cats received supportive treatment and an indwelling transurethral catheter for 48 h. On days 0 and 1, all cats received buprenorphine 0.01 mg/kg subcutaneously every 8 h. On day 1, cats were randomly assigned to the meloxicam (n = 18) or placebo group (n = 19) and received meloxicam (0.1 mg/kg on day 1, 0.05 mg/kg on days 2-5) or placebo orally for five consecutive days. Cats were monitored by repeated physical examinations and urinalysis, and with a 5 day questionnaire filled in by the owners after discharge and a telephone interview 3 months after presentation. Parameters for evaluation of treatment success were the occurrence of recurrent urethral obstruction, results of physical examinations and questionnaires. Results Recurrent urethral obstruction occurred in 4/18 cats (22%) in the meloxicam group and 5/19 cats (26%) in the placebo group ( P = 1.000). General demeanour and pain on abdominal palpation during hospitalisation improved significantly in both groups ( P <0.001). After discharge, with regard to general demeanour, food intake and voiding behaviour, there were no significant differences within or between groups at different time points. Conclusions and relevance Orally administered meloxicam for 5 days did not influence the incidence of recurrent urethral obstruction and the recovery from clinical signs in cats with obstructive feline idiopathic cystitis. The persistence of clinical signs in most of the cats 1 week after initial presentation indicates that symptomatic treatment for a longer period of time is warranted.

The therapeutic effect of doxazosin (40 μg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P 0 , markedly increased maximal (premicturitional) pressure P max , and increased amplitude of spontaneous oscillations of intravesical pressure ΔP det in filled bladder. Doxazosin produced no significant effect on P max rise during IVO, but prevented elevation of P 0 and increment of ΔP det in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.

Objectives: Obstructive feline idiopathic cystitis is a common emergency in small animal practice. There is evidence for a defective glycosaminoglycan layer in the urinary bladder of affected cats. The aim of this study was to investigate the effect of intravesical pentosan polysulfate sodium (PPS) in cats with obstructive feline idiopathic cystitis in a randomised, placebo-controlled, blinded clinical study., Methods: Thirty-five cats with obstructive feline idiopathic cystitis were enrolled into the study. On day 0, cats were randomised to receive either 30 mg PPS in saline (18 cats) or saline alone as placebo (17 cats) at the time of indwelling urinary catheter placement and then after 24 and 48 h. The catheter was clamped for 30 mins after administration before connecting it to a sterile urine collection system. The procedure was repeated after 24 and 48 h, and then the indwelling catheter was removed. Treatment success was assessed via the incidence of recurrent urethral obstruction, results of a scoring system for physical examination and daily urinalysis from day 0 to 5., Results: Recurrent urethral obstruction occurred in 3/18 cats of the verum group and 3/17 of the placebo group (P = 1.000). The verum group showed a significantly lower degree of microscopic haematuria between day 5 and day 0 (P ⩽0.05). The placebo group showed a significantly lower degree of dipstick haematuria between day 5 and day 0 (P ⩽0.05). There was no difference in the clinical score between the groups in the investigated time period., Conclusions and Relevance: Intravesical instillation of PPS three times within 48 h in the chosen dose had no influence on the incidence of recurrent urethral obstruction and clinical signs in cats with obstructive feline idiopathic cystitis., (© ISFM and AAFP 2015.)

Objectives: We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction., Methods: The effect of CP-533,536 (0.03-0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (UPP) was investigated in anesthetized rats pre-treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α1 -adrenoceptor agonist. The effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on residual urine volume (RV) and voiding efficiency (VE) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.)., Results: CP-533,536 dose-dependently decreased UPP elevated by midodrine in anesthetized rats. In contrast, CP-533,536 did not affect maximum voiding pressure, intercontraction interval, or intravesical threshold pressure. In conscious rats, midodrine (1 mg/kg, i.v.) markedly increased RV and reduced VE. CP-533,536 dose-dependently ameliorated increases in RV and decreases in VE induced by midodrine., Conclusions: These results suggest that a selective EP2 receptor agonist could ameliorate the elevation of RV and improve the reduction of VE in rats with functional urethral obstruction caused by stimulation of α1 -adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction., (© 2014 Wiley Publishing Asia Pty Ltd.)

Objectives: This study aimed to determine the standards of care for urethral catheters (UCs) placed in male cats for treatment of urethral obstruction (UO). It also assessed whether these standards were influenced by year of graduation of the veterinary surgeon (VS)., Methods: One hundred veterinary practices were randomly selected, and a telephone survey was conducted with a VS in the practice. Regarding the last urethral catheterisation performed for a male cat with UO, the VS was asked about the use of antibiotics while the catheter was in situ, whether a closed urinary collection system was used, whether aseptic skin preparation of the patient was performed and whether aseptic hand preparation was performed. A χ(2) test was used to determine whether there were significant differences in these percentages when considering year of graduation., Results: Twenty-seven percent of VSs did not use antibiotics while the urethral catheter was in place, 44% used closed urinary collection systems, 41% performed aseptic skin preparation of the patient and 60% aseptically prepared their hands and wore sterile gloves. There was a statistically significant (P <0.01) difference in antibiotic usage, closed collection system usage and aseptic hand preparation across graduation year groups., Conclusions and Relevance: Non-sterile urethral catheter placement with open urinary drainage and antibiotic prophylaxis is still a widespread practice among VSs; however, more recent graduates are more likely to perform the procedure aseptically with a closed urinary collection system and withholding of antibiotics. There is a need for further education for postgraduate veterinarians in the prevention of catheter-associated urinary tract infections in cats and further research to provide evidence-based guidelines for feline urethral catheter care., (© ISFM and AAFP 2015.)

Aims: To assess the urodynamic effects of soluble guanylyl cyclase (sGC) stimulator, BAY 41-2272, and activator, BAY 60-2770, (which both are able to induce cGMP synthesis even in the absence of nitric oxide (NO)) alone or in combination with a phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, in a model of partial urethral obstruction (PUO) induced bladder overactivity (BO)., Methods: Fifty-six male Sprague-Dawley rats were used, 31 of them underwent PUO. Fourteen rats were used for Western blots to assess PDE5 and sGC expression. For drug evaluation cystometry without anesthesia was performed three days following bladder catheterization., Results: Obstructed rats showed higher micturition frequency and bladder pressures than non-obstructed animals (Intermicturition Interval, IMI, 2.28 ± 0.55 vs. 3.60 ± 0.60 min (± standard deviation, SD); maximum micturition pressure, MMP, 70.1 ± 8.0 vs. 48.8 ± 7.2 cmH2O; both P < 0.05). In obstructed rats vardenafil, BAY 41-2272, and BAY 60-2770 increased IMI (2.77 ± 1.12, 2.62 ± 0.52, and 3.22 ± 1.04 min; all P < 0.05) and decreased MMP (54.4 ± 2.8, 61.5 ± 11.3, and 51.2 ± 6.3 cmH2O; all P < 0.05). When vardenafil was given following BAY 41-2272 or BAY 60-2770 no further urodynamic effects were observed. PDE5 as well as sGC protein expression was reduced in obstructed bladder tissue., Conclusions: Targeting sGC via stimulators or activators, which increase the levels of cGMP independent of endogenous NO, is as effective as vardenafil to reduce urodynamic signs of BO. Targeting the NO/cGMP pathway via compounds acting on sGC might become a new approach to treat BO., (© 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate the effect of pentoxifylline (PTX), a nonspecific type 4 phosphodiesterase inhibitor, on contractility of obstructed detrusor muscles., Methods: Sixty male Sprague-Dawley rats were randomized into three groups each containing 20 animals. The control groups included rats with induced BOO which received the solvent of PTX (drinking water), the sham group included rats with intact bladder outlet which received no treatment, and the treatment group was treated with PTX after induction of BOO. Four weeks after the operation and/or treatment, animals were killed and detrusor muscle of them was evaluated for contractility parameters., Results: Carbachol-induced detrusor muscle tension increased proportionally with concentration of carbachol. The maximum carbachol-inducing muscle tension was significantly higher in the sham group in comparison to the rats with BOO (P < 0.001). In the latter group, PTX treatment caused no significant improvement in the maximum carbachol-induced muscle tension compared to the control group. However, no significant difference was observed among the study groups concerning the pEC50 of carbachol (5.77 ± 0.10, 5.96 ± 0.64, and 5.84 ± 0.17 in the sham, control, and treatment groups, respectively). BOO resulted in a great but statistically non-significant (P = 0.074) decrease in electrically induced bladder contraction in comparison with the sham group. Treatment with PTX reversed this effect significantly (P = 0.023), and the obtained values were almost the same as those of the sham group., Conclusion: PTX improved detrusor muscle contractions in responses to electric stimulation in obstructed bladder. In contrast, no improvement was detected in contractile responses to the carbachol stimulation.

Fibrosis is one of the characteristic features of chronic kidney disease (CKD). Inflammatory reactions and oxidative stress are implicated in the pathogenesis of fibrosis of CKD. Leonurine (LEO) is one of the active compounds from Herba leonuri. In this study, we further evaluated its renoprotective effect in a mouse unilateral urethral obstruction (UUO), featuring the renal tubulointerstitial fibrosis and inflammation. In this model, pretreat of LEO before ureteral obstruction abolished the expression of fibronectin, suppressed the expression of α-SMA and type I/III collagen and down-regulated vimentin. LEO also modified the cytokine expression of TGF-β, TNF-α, IL-6 and IL-1β and suppressed the phosphorylation of Smad3. Moreover, LEO blocked phosphorylation of NF-κB, and inactivated the signaling pathways associated with the progression of kidney inflammatory response. Our data support that LEO is a candidate renoprotective compound for renal fibrosis through targeting the TGF-β/Smad3 and NF-κB pathway., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Limited studies have shown antifibrotic effects of pentoxifylline, captopril, simvastatin, and tamoxifen. No comparisons are available of the effects of these drugs on prevention of renal and bladder changes in partial urethral obstruction (PUO)., Materials and Methods: The rats were divided into six groups (n=7). The sham-operated rats (group I) only underwent laparotomy and did not receive any treatments. The PUO groups (group II-VI) received normal saline (PUO+NS), pentoxifylline (100 mg/kg/d; PUO+PEN), captopril (35 mg/kg/d; PUO+CAP), simvastatin (15 mg/kg/d; PUO+SIM), or tamoxifen (10 mg/kg/d; PUO+TAM) by gavage for 28 days. Then, the volume and/or length of the kidney components (tubules, vessels, and fibrous tissue) and the bladder components (epithelial and muscular layers, fibrous tissue, fibroblast and fibrocyte number) were quantitatively evaluated on the microscopic sections by use of stereological techniques., Results: The volume of renal and bladder fibrosis was significantly ameliorated in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups. Also, the volume and length of the renal tubules and vessels and bladder layers were more significantly protected in the PUO+PEN group, followed by the PUO+CAP, PUO+SIM, and PUO+TAM groups., Conclusions: Treatment of PUO with PEN was more effective in the prevention of renal and bladder fibrosis and in the preservation of renal and bladder structures.

Feline idiopathic cystitis is a common condition, often resulting in repeated episodes of life-threatening urethral obstruction. Defective urinary bladder glycosaminoglycans have been implicated as a causal factor. In this report, a commercially available glycosaminoglycan product was infused into the urinary bladders of cats with urethral obstruction from idiopathic cystitis to study the effect on repeated obstruction. In this randomized, blind, placebo-controlled clinical trial, the therapeutic protocol was well tolerated with no adverse effects. Whereas no glycosaminoglycan-treated cats (n = 9) developed repeated urethral obstruction during the 7 day follow-up period, 3/7 placebo-treated cats developed repeated obstructions. Approaching statistical significance (P = 0.06), these data suggest that further investigation of this new treatment option is warranted., (© ISFM and AAFP 2013.)

Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord., Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot., Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats., Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To study the effect and mechanism of Coicis Semen oil (Kanglaite injection, KLT) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO)., Method: Fifty-four male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KLT group. Renal interstitial fibrosis model was established in rats by UUO. After administration of KLT (15 mL x kg(-1) x d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) were measured by immunohistochemistry staining sections. The protein expression of p-Smad2 and Smad7 were detected by Western blot respectively., Result: The degree of tubular damage in KLT group was much lower than that in UUO group (P < 0.05). The expression of alpha-SMA and TGF-beta1 was decreased in both UUO group and KLT group, while it was significantly lower in KLT group at every time point. The protein expression of p-Smad2 was obviously decreased while the protein expressions of Smad7 was obviously increased in KLT group, compared with the UUO group (P < 0.05)., Conclusion: Coicis Semen oil could attenuate the tubulo-interstitial fibrosis, probable by intervening the TGF-beta/Smads signal transduction pathway of UUO rats.

Objective: To evaluate the effect of intraurethral administration of atracurium besylate for urinary obstruction resulting from urethral plugs in male cats., Methods: Forty-five male cats were divided into the treatment group (n=25), in which 4 mL atracurium besylate solution (0·5 mg/mL) was injected into the urethral lumen, and the control group (n=20), treated with saline. All cats were then submitted to retrograde flushing until the removal of the occlusion was obtained., Results: The percentage of cats in which the plug was removed at the first attempt was significantly (P<0·05) higher in the treatment group (64%) than in the control group (15%). Moreover, the mean (±SD) time required for the removal of the urethral obstruction was significantly shorter in the treatment group than in the control group (21·1 ±16·2 seconds versus 235·2 ±132·4 seconds; P<0·001)., Clinical Significance: The results of this study indicate that in adult male cats with urethral plugs, urethral administration of atracurium besylate increases the proportion of animals in which the obstruction is removed at the first attempt and reduces the time required to remove the urethral plugs., (© 2012 British Small Animal Veterinary Association.)

Background: In human patients with interstitial cystitis, intravesical instillation of alkalinized lidocaine sometimes is associated with sustained amelioration of symptoms beyond the acute treatment phase. Interstitial cystitis shares many features in common with feline idiopathic cystitis., Objective: To evaluate whether intravesical instillation of alkalinized lidocaine decreases recurrence of urethral obstruction and severity of clinical signs in cats with obstructive idiopathic LUTD., Animals: Twenty-six cats with obstructive idiopathic LUTD. Twelve cats in case group (treatment with alkalinized lidocaine) and 14 control cats (treatment with placebo or standard treatment)., Methods: Cats were randomly assigned to treatment (2 or 4 mg/kg lidocaine and sodium bicarbonate) or placebo groups (0.2 mL/kg saline solution and sodium bicarbonate). The intravesical instillation was done once a day for 3 days. Some cats underwent standard treatment only (indwelling urinary catheter for 3 days without intravesical instillations). A 2-week, 1-month, and 2-month follow-up after treatment was made using a questionnaire. The recurrence rate and amelioration scores of clinical signs were assessed and compared., Results: Recurrence of urethral obstruction was 58% (7/12) in the case group and 57% (8/14) in the control group. Amelioration scores were similar between the 2 groups., Conclusion and Clinical Importance: Intravesical administration of lidocaine for up to 3 consecutive days had no apparent beneficial effect on decreasing recurrence rate and severity of clinical signs in cats with obstructive idiopathic LUTD., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Aims: We evaluated effects of BoNT-A injections on bladder function and histomorphology in a male-rat-overactive-bladder model, created by partial urethral obstruction., Methods: A total of 45 male Sprague-Dawley rats were separated into 5 groups. Partial urethral obstruction (PUO) was created in all rats except the control group. At the 6th week after PUO, intradetrusor injections of 50 µl of saline (2 sham groups) or 50 µl BoNT-A (2 treatment groups) was performed. Treatment and sham groups were studied 5 and 30 days after injection and neuropharmacological and histomorphological findings on bladder tissues were compared to the control group., Results: Bladder muscle hypertrophy and connective tissue increase were detected at 5th and more prominent at 30th day after saline injection. Intradetrusor BoNT-A injection significantly reduced PUO-induced histological changes in the bladder tissue both at 5th and 30th day after injection. At 5th day after saline injection, a significantly increased contractile response to electrical field stimulation (EFS) and carbachol were recorded in the saline group and this effect disappeared at 30th day. There was no statistically significant difference between BoNT-A and control groups in terms of contractile responses to EFS and carbachol, both at 5th and 30th days., Conclusion: Partial urethral obstruction induces increased bladder tissue contractile responses to neurogenic and pharmacological stimulation and intradetrusor BoNT-A injections decrease these responses at 5th days after injection. As the unique finding of this study, intradetrusor BoNT-A injections appear to decrease bladder fibrosis secondary to PUO in the male rat model., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims: Beta3-adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3-AR selective agonists exert their effects via a peripheral site of action. However, β3-ARs have been found in brain tissue. This study examined whether β3-ARs are present in rat sacral spinal cord, and whether there are differences in β3-AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3-ARs for micturition., Methods: Thirty-eight male Sprague-Dawley rats underwent either PUO or sham-operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3-AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non-anesthetized animals before and after drug administration., Results: Beta3-ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3-AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P < 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non-obstructed rats. In obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P < 0.05)., Conclusions: Beta3-ARs are present in rat sacral spinal cord, and are significantly up-regulated after PUO. Besides their well-established peripheral site of action in the treatment of voiding dysfunction, β3-AR selective agonists might exert relevant effects at a central nervous site of action., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: We studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle., Materials and Methods: A total of 24 female Sprague-Dawley® rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies., Results: Mean ± SEM bladder weight was 0.97 ± 0.15 gm in controls and 0.53 ± 0.08 gm in cannabinor treated rats (p <0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 ± 0.07 and 0.06 ± 0.02 ml, mean micturition compliance was 0.032 ± 0.006 and 0.069 ± 0.016 ml/cm H(2)O, and mean bladder wall force at the start of flow was 950 ± 280 and 1,647 ± 325 mN/gm, respectively (each p <0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma®) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips., Conclusions: In rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The combination of muscarinic receptor and alpha(1)-adrenoceptor antagonists is increasingly used for benign prostatic hyperplasia related lower urinary tract symptoms. In addition to the well established peripheral site of action, little is known about the central effects of muscarinic receptor antagonists and muscarinic receptor/alpha(1)-adrenoceptor antagonist combinations on bladder function, partly due to poor brain penetration after systemic administration. We assessed the effects of intrathecal 5-hydroxymethyl tolterodine, an active metabolite of fesoterodine, in obstructed and nonobstructed rats, and of combined intrathecal 5-hydroxymethyl tolterodine/doxazosin in a rat model of partial urethral obstruction., Materials and Methods: We used 80 male Sprague-Dawley rats to test various doses of intrathecal 5-hydroxymethyl tolterodine and/or intrathecal doxazosin on urodynamic parameters. Urodynamic evaluation without anesthesia was done 3 days after bladder and intrathecal catheterization. Two weeks before urodynamics 40 rats underwent partial urethral obstruction., Results: Intrathecal 5-hydroxymethyl tolterodine had no urodynamic effects in nonobstructed rats. Compared to controls obstructed rats had increased bladder pressure and weight, and voiding frequency. In obstructed rats 5-hydroxymethyl tolterodine restored urodynamic parameters to those seen in nonobstructed animals. Doxazosin had effects similar to those of intrathecal 5-hydroxymethyl tolterodine. When the 2 drugs were combined, at the doses used only small additional effects were observed., Conclusions: Urodynamic changes in obstructed rats can be normalized by intrathecal 5-hydroxymethyl tolterodine and by intrathecal doxazosin. The central pathways on which the 2 drugs act seem to be up-regulated with partial urethral obstruction and less relevant under normal conditions., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the renal and cardiorespiratory effects of IV treatment with lactated Ringer's solution (LRS) or physiologic saline (0.9% NaCl) solution (PSS) in severely decompensated cats with urethral obstruction (UO)., Animals: 14 cats (4 cats were used only to establish infusion rates)., Procedures: An occluded urethral catheter was used to induce UO in each cat. After development of severe metabolic acidosis, hyperkalemia, and postrenal azotemia, the obstruction was relieved (0 hours); LRS or PSS (5 cats/group) was administered IV (gradually decreasing rate) beginning 15 minutes before and continuing for 48 hours after UO relief. Ten minutes before urethral catheter placement (baseline), at start of fluid therapy (SFT), and at intervals during fluid administration, various physical and clinicopathologic evaluations were performed., Results: Metabolic acidosis was detected in the PSS-treated group at SFT and 2 hours after relief of UO and in the LRS-treated group only at SFT The PSS-treated group had significantly lower blood pH and bicarbonate concentrations at 8 through 48 hours and lower base excess values at 2 through 48 hours, compared with the LRS-treated group. Hypocalcemia and hypernatremia were detected in the PSS-treated group at 2 and 12 hours, respectively. Absolute serum potassium and chloride concentrations did not differ significantly between groups at any time point., Conclusions and Clinical Relevance: Treatment with LRS or PSS appeared to be safe and effective in cats with experimentally induced UO; however, LRS was more efficient in restoring the acid-base and electrolyte balance in severely decompensated cats with UO.

Objective: To evaluate the urodynamic effects of fesoterodine, a new antimuscarinic agent, alone and combined with doxazosin, in a rat model of partial urethral obstruction (PUO), as 35-83% of men with bladder outlet obstruction (BOO) secondary to benign prostatic hyperplasia (BPH) have overactive bladder (OAB) syndrome, and as the combination of alpha(1)-adrenoceptor- and muscarinic-receptor antagonists has been proposed to be beneficial for these patients., Materials and Methods: Thirty-seven male Sprague-Dawley rats (250 g) had surgically induced PUO; 2 weeks later they were evaluated by cystometry with no anaesthesia or any restraint. After a 1-h period either 5-hydroxymethyl tolterodine (5-HMT, the active metabolite of fesoterodine, previously known as SPM 7605), doxazosin or a combination of both, was given intravenously (0.1 mg/kg body weight), and cystometry was continued for another 45 min. Fifteen healthy, age-matched rats served as a control., Results: At 2 weeks after surgery the obstructed rats had an greater bladder weight, threshold pressure (TP) and micturition frequency (MF), and lower bladder capacity (BCap) and micturition volume (MV) than the controls. 5-HMT did not cause urinary retention in obstructed rats, but decreased TP, maximum pressure (MP), spontaneous bladder activity (SA) and, paradoxically, increased MF. Doxazosin alone decreased TP, MP, MF and increased BCap and MV. 5-HMT and doxazosin together did not depress the ability to empty the bladder, and showed decreased TP, MP and SA., Conclusions: 5-HMT, alone and in combination, did not impair the voiding ability in obstructed rats. Doxazosin counteracted some of the 'negative' effects of 5-HMT in this model (increase of MF) and did not attenuate the 'positive' effects (decrease of bladder SA). In this model, the combination of 5-HMT and doxazosin appeared to be urodynamically safe and well tolerated.

Objective: To study the effects of the phosphodiesterase-5 inhibitor, vardenafil, on contraction and cyclic nucleotide levels in isolated detrusor preparations with and without mucosa, from control rats and rats with partial urethral obstruction (PUO) and intact mucosa., Materials and Methods: Female Sprague-Dawley rats were divided into groups subjected to PUO for 14 days (six), and sham-operated control rats (12). Detrusor preparations were mounted in organ baths and effects of increasing concentrations of vardenafil (1 nm to 100 microm) assessed on carbachol-activated (1 microm) preparations, and on contractions induced by transmural activation of nerves (electrical field stimulation, EFS). Levels of cGMP and cAMP were determined using radioimmunoassays., Results: Vardenafil caused concentration-dependent relaxations of carbachol-contracted detrusor, the mean (sd) of which at 100 microm was 91 (4)% in control and 100% in PUO rats. The -log 50% inhibitory concentration (IC(50)) was 4.41 (0.08) and 4.73 (0.05) (P < 0.01), respectively. Removing the mucosa increased the relaxant effect of vardenafil at 1-10 microm (P < 0.05) although -log IC(50) values were unaffected compared to the control. The cGMP levels ( pmol/mg protein) in control preparations increased from 2.5 (0.6) to 5.0 (0.8), and from 1.4 (0.2) to 7.2 (1.3) in obstructed bladders. In mucosa-denuded preparations the cGMP content increased from 0.6 (0.1) to 1.6 (0.4) in response to vardenafil. In control rats, the levels of cAMP increased from 12.8 (2.5) to 18.9 (0.9) (P < 0.05) after vardenafil. In mucosa-denuded preparations the cAMP levels after vardenafil increased from 16.5 (2.11) to 37.8 (3.4) (P < 0.01). In PUO bladders, the tissue content of cAMP increased from 12.6 (2.4) to 20.6 (3.4) (P < 0.01). Vardenafil concentration-dependently inhibited nerve-induced contractions in all groups studied. At 100 microm 19 (3)% of the control contraction remained, vs 8 (1)% for preparations from obstructed rats, and 11 (4)% in mucosa-denuded preparations., Conclusion: In normal rats, vardenafil relaxed carbachol- and inhibited EFS-induced contractions of detrusor preparations with and without urothelium, and in PUO rats with urothelium. Relaxations were accompanied by increases in both cAMP and cGMP content. It is proposed that vardenafil-induced relaxation of rat detrusor, also in obstructed and mucosa-denuded preparations, is mediated via cAMP.

Objective: To determine results of ultrasound-guided cystocentesis and percutaneous infusion of Walpole's solution for treatment of male goats with urolithiasis., Design: Retrospective case series., Animals: 25 male goats with urolithiasis treated with Walpole's solution., Procedures: Information obtained from the medical records included signalment, degree of urethral obstruction (partial vs complete), pertinent examination findings, concurrent illnesses, diet, other treatments administered, duration of hospitalization, whether the obstruction resolved, and outcome (ie, discharged vs euthanized)., Results: 14 (58%) animals had complete urethral obstruction, and 10 (42%) had partial obstruction (degree of urethral patency was not recorded in 1 animal). Walpole's solution was infused once in 18 (72%) animals, twice in 6 (24%) animals, and 3 times in 1 (4%) animal. The amount of Walpole's solution required to achieve the target urine pH of 4 to 5 ranged from 50 to 250 mL. In 20 (80%) goats, the urethral obstruction resolved, and the goat was discharged. The remaining 5 (20%) goats were euthanized because of unresolved urethral obstruction. Six of the 20 (30%) goats that were discharged were reexamined because of recurrence of urethral obstruction., Conclusions and Clinical Relevance: Results suggested that ultrasound-guided cystocentesis in combination with percutaneous infusion of Walpole's solution may be a useful treatment in male goats with obstructive urolithiasis.

Objectives: To investigate the effects of terazosin and melatonin on isolated rabbit bladder strips after partial bladder outlet obstruction and determine responses to agonist-induced contractility and changes in oxidant-antioxidant system., Methods: We created partial bladder outlet obstruction in 5 groups of rabbits, each containing 8. Rabbits with sham operation (group 1) received no drug treatment. Similarly, animals in group 2 underwent partial bladder outlet obstruction and received no drug treatment. Rabbits in groups 3 were administered 5 mg/day oral terazosin, and rabbits in group 4 received 10 mg/kg/day melatonin intraperitoneally. Animals in group 5 received both terazosin and melatonin. We removed their bladders and performed histopathological and biochemical measurements. We assessed tissue malondialdehyde and antioxidant enzyme activity levels and recorded in vitro contractility response to KCl in isolated organ baths., Results: The thickness of muscularis propria was significantly increased in group 2 compared with all other groups. KCl-evoked contractions after partial outlet obstruction were significantly impaired in group 3 and 4 animals receiving terazosin and melatonin, respectively. However, combined use of melatonin and terazosin in group 5 showed contractility responses similar to sham-operated animals (P <0.05). Melatonin administration to groups 4 and 5 showed decreased levels of lipid peroxidation. Similarly, animals receiving melatonin and melatonin plus terazosin showed statistically significant increase in antioxidant enzyme activities., Conclusions: In the present study, we showed that oxidative stress induced by partial bladder outlet obstruction can be successfully antagonized by the potent antioxidant melatonin, and its combined use with an alpha-antagonist such as terazosin may restore in vitro contractility.

Corynebacterium urealyticum is an uncommon cause of urinary tract infections in cats. However, it is difficult to diagnose and if left untreated it may result in irreversible bladder lesions. C urealyticum is a multiantibiotic-resistant bacterium whose culture requires special care. Risk factors for the occurrence of this infection include urological procedures, foreign bodies, bladder mucosa abnormalities, immuno-suppressed states and antibiotic treatment. This report describes an unusual case of C urealyticum urinary infection in a young cat with pre-existing urethral obstruction. C urealyticum was isolated in pure cultures from two urine samples. Clinical and ultrasound features, results of the urinalysis and urine culture are described as well as therapeutic treatment and eventual favourable outcome to treatment with amoxycillin-clavulanic acid.

Alpha(1)-adrenoceptor antagonists, called alpha(1)-blockers, are the first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Nonselective alpha(1)-blockers like prazosin were mainly used in the past, but prostate-specific alpha(1)-blockers such as tamsulosin or naftopidil are now the mainstream agents for the management of BPH, based on the function of alpha(1)-adrenoceptor subtypes. Recent studies on voiding dysfunction have clarified the association between BPH and overactive bladder (OAB), underlining the use of OAB treatment in the management of BPH, inducing the simultaneous administration of antimuscarinic agents. Every aspect of diversified BPH symptom can be controlled individually in a short period.

Alpha(1)-adrenoceptors are widely distributed in the human body and play important physiologic roles. Three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) have been cloned and show different pharmacologic profiles. In addition, a putative alpha(1)-adrenoceptor (alpha(1L) subtype) has also been proposed. Recently, three drugs (tamsulosin, naftopidil, and silodosin) have been developed in Japan for the treatment of urinary obstruction in patients with benign prostatic hyperplasia. In this review, we describe recent alpha(1)-adrenoceptor subclassifications and the pharmacologic characteristics (subtype selectivity and clinical relevance) of alpha(1)-adrenoceptor antagonists.

Aims: Our main aim was to compare the prostatic selectivity of silodosin with that of other alpha(1)-adrenoceptor (AR) antagonists., Methods: We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil., Results: In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65)., Conclusions: Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients., ((c) 2006 Wiley-Liss, Inc.)

Botulinum toxin is a presynaptic neuromuscular blocking agent that induces a selective and reversible muscle weakness of up to several months when injected intramuscularly in minute quantities. Different medical disciplines have applied the toxin to treat mainly muscular hypercontraction. For neurourologically impaired patients, the reported successful treatment of neurogenic detrusor overactivity and detrusor sphincter dyssynergia with botulinum-A toxin is a promising alternative option to conservative medication or surgery. This review of the literature presents current indications, techniques for and results of the use of botulinum toxin in neurourologically impaired patients and aims to give an insight into this new therapeutic option., (c) 2004 Prous Science. All rights reserved)

Objective: To evaluate the effect of the nonselective purinergic antagonist suramin and the alpha1-adrenergic antagonists, terazosin and BMY 7378, given intravenously or infused directly into the bladder during cystometry in conscious rats with bladder outlet obstruction induced by urethral ligation., Materials and Methods: Cystometry was performed in conscious female rats recording bladder volume capacity (BVC), evaluated as the amount of saline infused between two voiding cycles, and micturition volume (MV). Changes in frequency and amplitude of spontaneous non-voiding bladder contractions (NVC) were also recorded. The effects of the intravenous administration of suramin (100 mg/kg), BMY 7378 (1 mg/kg), and terazosin (0.3 mg/kg) on NVC, BVC and MV were evaluated in obstructed rats with bladder infusion of saline. The effects of infravesical infusion of suramin (3-10 micromol/L), terazosin (1 micromol/L) and BMY 7378 (10 micromol/L) were also evaluated and compared with values observed in control rats during saline infusion into the bladder., Results: Intravenous injection with suramin had no effects on NVC, BVC and MV, but suramin infused into the bladder induced a consistent reduction in the amplitude of NVC (significantly different from matched control animals) with a tendency to reduce their frequency. BVC and MV were slightly but significantly decreased by infravesical infusion of suramin. In contrast, BMY 7378 and terazosin, given intravenously, were extremely potent at inhibiting the frequency and amplitude of the NVC, but were inactive on NVC when infused into bladder., Conclusions: These findings confirm a role for alpha1-adrenergic receptors in bladder instability caused by bladder outlet obstruction. In addition, a purinergic neurotransmitter, presumably ATP, is shown to be involved.

Objectives: To evaluate the efficacy of a new approach for treatment of prostatic obstruction involving transperineal injection of dehydrated ethanol into the prostate using transrectal ultrasound (TRUS)., Methods: Dehydrated ethanol was injected transperineally into 11 patients with prostatic obstruction due to hyperplasia or carcinoma. Injections were performed under TRUS surveillance at bilateral sites of the prostate for an overall amount of 2 to 8 mL of ethanol for each patient., Results: There were no intraoperative complications, but postoperative urinary retention occurred in 1 patient who received catheterization for 3 days. The mean symptom score decreased from 17.7 +/- 6.0 (median 23) to 8.5 +/- 1.1 (median 3.5) at 3 months postoperatively (P < 0.01); mean peak urine flow rate increased from 5.3 +/- 4.0 mL/s (median 7) to 13.5 +/- 3.6 mL/s (median 14) (P < 0.05); and mean residual urine volume decreased from 231.9 +/- 209.8 mL (median 108) to 28.7 +/- 13.7 mL (median 34) (P < 0.01). There were no significant differences at 6 months when the same parameters were assessed. Pathologic findings for 2 patients with prostatic obstruction due to carcinoma showed only granulation tissue, with no evidence of malignancy in the treated area., Conclusions: Our preliminary data suggest that this technique can be performed as an outpatient procedure. It is considered an alternative treatment for prostatic obstruction due to benign hyperplasia or carcinoma, especially when there is a high operative risk.

Prazosin is a readily available alpha-adrenergic antagonist that may be useful in the management of functional urethral obstruction in companion animals. This study used urethral pressure profilometry to evaluate the urethral effects of prazosin and phenoxybenzamine in healthy, non-sedated, male Beagle dogs. Heart rate, indirect systolic, diastolic and mean arterial blood pressures were measured, and saline perfusion urethral pressure profilometry was performed at 0, 10, 20, and 40 min following intravenous administration of prazosin (0.025 mg/kg), phenoxybenzamine (0.2 mg/kg), or placebo. Maximal urethral pressure, maximal urethral closure pressure, post peak nadir, and all blood pressure parameters decreased significantly at nearly all treatment intervals following administration of prazosin compared with placebo. Less consistently significant reductions were observed following phenoxybenzamine administration. Maximal decreases in urethral pressure parameters were observed 20 min following the injection of prazosin; maximal blood pressure decreases were evident by 10 min postinjection. In this non-sedated dog model, urethral pressure profilometry was a sensitive method of detecting urethral effects of alpha antagonists. Repeatable reductions in urethral pressure measurements were observed, with prazosin effecting more consistently significant changes than phenoxybenzamine. Significant decreases in systolic, diastolic, and mean arterial blood pressures were seen with prazosin, but not phenoxybenzamine or placebo. Further study of selective alpha-1 antagonists in dogs is needed to determine appropriate oral dosing protocols that will produce maximal urethral effects with minimal hemodynamic effects, and to demonstrate clinical efficacy in dogs with functional urethral obstruction.

This study examined the ex-vivo occupancy by KMD-3213 of alpha1-adrenoceptors in the prostate and other tissues of rats in terms of tissue selectivity and duration of occupancy in relation to plasma concentration. Oral administration of KMD-3213 (0.2-20.2 micromol kg(-1), 0.5 h) dose-dependently decreased [3H]prazosin binding sites (Bmax) in the prostate (42-74%) and submaxillary gland (54-88%) compared with the control value. In contrast, there was only a slight change in the Bmax values in the spleen and cerebral cortex of KMD-3213-treated rats. The alpha1-adrenoceptor occupancy in the prostate and submaxillary gland was increased, with plasma free concentration of KMD-3213 at 0.5 h after oral administration of KMD-3213 (0.6-20.2 micromol kg(-1)). The receptor occupancy in these tissues was much greater than that in the spleen, heart or cerebral cortex. After oral administration of KMD-3213 (6.1 micromol kg(-1)), the alpha1-adrenoceptor occupancy in the prostate and submaxillary gland occurred rapidly, in parallel with the rise in the plasma concentration of the drug, and it lasted for at least 24 h, despite a remarkable decrease in the plasma concentration. It is concluded that KMD-3213 may produce fairly selective and sustained occupancy of alpha1-adrenoceptors in the prostate, a target organ for treatment of bladder outlet obstruction in patients with benign prostatic hyperplasia.

Efficacy and safety of alfuzosin administered as 3-times-daily and 2-times-daily formulations have been previously demonstrated in placebo-controlled studies, and these formulations have been commercially available in many countries. A once-daily formulation of alfuzosin administered through a novel prolonged-release system has been recently developed to improve the convenience of dosing and to provide optimal pharmacokinetic coverage over 24 hours. The results of 2 double-blind, placebo-controlled phase 3 studies in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia suggests that 10 mg of alfuzosin administered once daily without dose titration is superior to placebo in terms of symptom and urinary flow rate improvement. Orthostatic hypotension and first-dose phenomenon related to the alpha-blocking property were rare. The incidences of asthenia and fatigue were comparable to those seen with placebo. Ejaculatory disorders were very rare. The most frequently reported adverse event potentially related to alpha blockade was dizziness, which occurred in 5.0% of patients treated with 10 mg alfuzosin compared with 2.1% of patients given placebo.

Randomised controlled trials (RCTs) provide the best available external evidence for the use of alpha1-blockers in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Placebo-controlled and actively-controlled RCTs evidenced the efficacy of alpha1-blockers in augmenting urine flow, relieving symptoms, reducing bother and improving quality of life in patients with LUTS. This improvement involves both filling (irritative) and voiding (obstructive) symptoms, occurs promptly and is well-maintained over time. Treatment benefit is independent of prostate size and baseline prostate specific antigen (PSA). There is no evidence of relevant differences between the different alpha1-blockers in this regard and all alpha1-blockers can be accepted as appropriately efficacious at the presently recommended doses. The best available external evidence for relevant differential properties of alpha1-blockers relates to their clinical selectivity in terms of the absence/presence of ancillary cardiovascular, i.e. anti-hypertensive effects. Anti-hypertensive alpha1-blockers (terazosin and doxazosin in particular) are more likely to cause dizziness and other cardiovascular untoward effects, eventually leading to premature treatment discontinuation. Alfuzosin (although primarily developed as an anti-hypertensive agent) and tamsulosin in contrast, are better tolerated; the former nevertheless carries a more distinct risk of symptomatic impairment of blood pressure control. Although indirect comparisons between different studies suggest a higher risk of retrograde ejaculation with tamsulosin, this hypothesis failed to be confirmed in direct comparative RCTs.

Objective: To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO)., Methods: Data from 830 patients randomized into three European multicenter studies with similar protocols were analyzed. In two studies, patients were randomized to receive either tamsulosin, 0.4 mg once daily, or placebo, and in the third, patients were randomized to receive either a fixed dose of tamsulosin, 0.4 mg once daily, or alfuzosin, titrated to 2.5 mg three times daily. The studies employed a 2-week placebo run-in period, followed by a 12-week study period. Sexual function was assessed by related adverse events and by a sexual function score determined from a life-style questionnaire., Results: Abnormal ejaculation occurred significantly more frequently in patients treated with tamsulosin than in those receiving placebo (p = 0.045); however, the incidence of abnormal ejaculation was similar in patients receiving tamsulosin or alfuzosin in the comparative study. Abnormal ejaculation was not perceived as a major problem by the patients since it resulted in few treatment discontinuations (n = 3). It was also reversible on drug withdrawal. There was no difference between tamsulosin and placebo or alfuzosin with regard to the occurrence of decreased libido or impotence. In addition, there was no significant difference in the change in sexual function score between patients treated with tamsulosin and those treated with alfuzosin. Compared with patients receiving placebo, there was, however, a significant improvement in total sexual function score in patients receiving tamsulosin (p = 0.042)., Conclusions: Tamsulosin, 0.4 mg once daily, is well tolerated and has no overall negative impact on sexual function compared with placebo or alfuzosin. Compared with placebo, tamsulosin may even improve sexual function.

Involvement of the male genitalia by langerhans cell histiocytosis ist very rare. It has been reported in only three cases yet. We present a patient with recurrent disease of the skin of the penis and by proliferation involvement of the distal urethra and the corpus cavernosum. An overview of the disease and its therapy is given.

Objective: To analyze the clinical and urodynamic efficacy of treatment with doxazosin during 6 months for voiding phase disorders in patients with BPH., Methods: A prospective clinical and urodynamic study (before and after treatment) was performed in 65 consecutive male patients with BPH, aged 54-79 years (mean 66.7), to evaluate the results of treatment with doxazosin 4 mg/day during 6 months. Clinical evaluation included patient history and the International Prostatic Symptom Score (IPSS) and urodynamic evaluation included uroflowmetry with post-void residual data and pressure-flow test. A static urethral pressure profile was associated with the urodynamic voiding study., Results: The IPSS score improved significantly from 19.8 +/- 4.8 before treatment to 11.9 +/- 4.6 after treatment (p < 0.001). Urinary symptoms improved significantly more markedly after treatment (coeff. -0.45939) in patients with a lower IPSS score. The symptomatic improvement demonstrated by the IPSS did not correlate with the DRE or the transabdominal US prostatic volume. Mean maximum flow rate before treatment was 9.13 ml/sec and increased to 16.23 ml/sec after treatment (p < 0.01). Postvoid residual dropped from 21.7% to 12.5% (p < 0.01). In the pressure-flow test, foot-point PURR dropped significantly from 69 cms H2O to 45.9 cms H2O (p < 0.001). The PURR curvature diminished from 0.27416 to 0.15964 cms H2O (ml/sec2) (p < 0.01). A statistically significant improvement of the compressive (p < 0.001) and constrictive (p < 0.05) elements of lower urinary tract obstruction was observed. The urethral functional length of the urethral profile showed a significant reduction (pre-treatment: 5.56 cms; post-treatment 4.31 cms) (p < 0.05). A statistical correlation was found between the urethral functional length and the foot-point PURR post-treatment., Conclusions: Adrenergic blockade with doxazosin reduces both the compressive and constrictive elements of lower urinary tract obstruction in the voiding phase in patients with BPH, although no statistical correlation with the IPSS could be demonstrated.

Objectives: To correlate clinical and urodynamic findings with MRI in patients with spinal cord injury and detrusor-sphincter dyssynergia who were consecutively treated with transperineal injections of botulinum-A toxin (BTX-A) under EMG control., Methods: Six patients with spinal cord injury and upper motor neuron bladder dysfunction associated with detrusor-sphincter dyssynergia were prospectively analysed. One hundred international units (IU) BTX-A (Botox in 1 ml normal saline without preservative) diluted 1 to 1 with 1 ml gadopentetate were injected transperineally under EMG control. MRI was started immediately after needle withdrawal., Results: In all six patients gadopentetate was located in the external urethral sphincter on MRI. In no patient did traces of gadopentetate appear in the perineal musculature located in the vicinity of the external urethral sphincter. No patient developed resistance to BTX-A. All patients showed an (ongoing) improvement of their voiding function after BTX-A injections., Conclusions: Transperineal injections of BTX-A under EMG control are efficient in the release or amelioration of lower urinary tract obstruction due to detrusor sphincter dyssynergia in patients with spinal cord injury. Despite well described methods, EMG of the external urethral sphincter is difficult and it is not possible to definitively exclude false recordings of the surrounding perineal musculature. By the use of MRI it was shown that both the EMG recordings and transperineal injection method are precise.

Purpose: We assess the long-term effects of finasteride on bladder outlet obstruction and symptoms in the treatment of patients with benign prostatic hyperplasia., Materials and Methods: Of the original 36 patients assigned to treatment with 5 mg. finasteride daily (group 1) or placebo (group 2) for 6 months 27 completed an open extension study of 5 mg. finasteride for 4 more years. The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline, 6 months and 4.5 years., Results: The treatment resulted in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period, whereas improvement in maximum flow rate did not achieve statistical significance. Concomitantly, there was a significant improvement in obstructive and irritative symptoms., Conclusions: Finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely. However, the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly. The beneficial effect is long-lasting.