Effect of tamsulosin on urethral tone in healthy male cats.

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.

Generalised neuromuscular blockade after intraurethral administration of atracurium besilate in a male cat with urethral obstruction.

A 4-year-old, entire, male, domestic long-haired cat was presented with an acute history of stranguria and dysuria and diagnosed with urolithiasis causing urethral obstruction. The patient was induced to general anaesthesia and several unsuccessful attempts to flush the uroliths retrogradely towards the bladder were made. An intraurethral administration of the neuromuscular blocking agent atracurium was performed as it has been reported to facilitate urethral catheterisation without any side effects. Respiratory arrest developed after 15 minutes from atracurium administration, which was promptly recognized and treated with mechanical ventilation. The absence of muscle contraction in response to a nerve stimulation confirmed a generalised muscle blockade. Approximately 35 minutes after, a muscle response to nerve stimulation appeared. Neostigmine combined with glycopyrrolate was administered resulting in complete recovery from neuromuscular blockade. In conclusion, the use of intraurethral atracurium can result in systemic absorption of the drug with subsequent generalised neuromuscular blockade.

Effect of prazosin on feline recurrent urethral obstruction.

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.

A prospective randomized study of efficacy of 2 treatment protocols in preventing recurrence of clinical signs in 51 male cats with obstructive idiopathic cystitis.

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.

Holter Monitoring (24-Hour ECG) Parameter Dynamics in Patients with Ischemic Heart Disease and Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.

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 (Qmax) 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.

The effect of prazosin on outcome in feline urethral obstruction.

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.

Effect of Doxazosin on Autonomic Nervous Control and Urodynamics of Rat Urinary Bladder during Modeled Infravesical Obstruction.

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 P0, markedly increased maximal (premicturitional) pressure Pmax, and increased amplitude of spontaneous oscillations of intravesical pressure ΔPdet in filled bladder. Doxazosin produced no significant effect on Pmax rise during IVO, but prevented elevation of P0 and increment of ΔPdet 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.

Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

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.

Evaluation of meloxicam for the treatment of obstructive feline idiopathic cystitis.

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.

Standards of care for feline urethral catheters in the UK.

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.

Efficacy of intravesical pentosan polysulfate sodium in cats with obstructive feline idiopathic cystitis.

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.

The effect of pentoxifylline on detrusor muscle contractility after partial urethral obstruction in a rat model.

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.

Leonurine ameliorates kidney fibrosis via suppressing TGF-ß and NF-κB signaling pathway in UUO mice.

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-ß, TNF-α, IL-6 and IL-1ß 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-ß/Smad3 and NF-κB pathway.

Reduction of obstruction related bladder overactivity by the guanylyl cyclase modulators BAY 41-2272 and BAY 60-2770 alone or in combination with a phosphodiesterase type 5 inhibitor.

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.

Stereological comparison of the effects of pentoxifylline, captopril, simvastatin, and tamoxifen on kidney and bladder structure after partial urethral obstruction in rats.

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.

Intravesical glycosaminoglycans for obstructive feline idiopathic cystitis: a pilot study.

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.

Stereological Comparison of the Effects of Pentoxifylline, Captopril, Simvastatin, and Tamoxifen on Kidney and Bladder Structure After Partial Urethral Obstruction in Rats

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.

[Effect of coicis semen oil on renal interstitial fibrosis in rats with unilateral urethral obstruction].

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.

Spinal cord FAAH in normal micturition control and bladder overactivity in awake rats.

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.

Effect of intraurethral administration of atracurium besylate in male cats with urethral plugs.

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.