New Kid on the Block: The Efficacy of Phytomedicine Extracts Urox® in Reducing Overactive Bladder Symptoms in Rats.

The aim of the current study was to determine if phytomedicine (Urox®) would reverse retinyl acetate (RA)-induced changes characteristic of bladder overactivity. There were 60 rats divided into the following 4 groups: I-control, II-received RA to induce detrusor overactivity (DO), III-received Urox (840 mg daily for 14 days), and IV-received combination of RA and Urox®. The cystometry was performed 2 days after the last dose of Urox®. Next, urothelium thickness and biochemical parameter measurements were performed. In group IV, a decrease in basal pressure and detrusor overactivity index was noted when compared to group II. Furthermore, in group IV the following parameters were increased: threshold pressure, voided volume, intercontraction interval, and bladder compliance in comparison with group II. There were significant elevations in c-Fos expression in the neuronal voiding centers in group II, while the expression of c-Fos in group IV was normalized. No significant changes in the values of the analyzed biomarkers in group III were found, while in group II, an elevation in BDNF, NGF, CGRP, ATP, Rho kinase, malondialdehyde, 3-nitrotyrosine, TRPV1, OCT-3, and VAChT and then a decrease in E-cadherin and Z01 were found. A successful restoration of all the abovementioned biomarkers' levels was observed in group IV. Phytomedicine extracts (Urox®) were found to be potent in reversing RA-induced changes in several cystometric and biochemical parameters that are determinants of overactive bladder (OAB). The actions of Urox® were proved to be dependent on several factors, such as growth factors and several OAB biomarkers but not pro-inflammatory cytokines.

A systematic review of preventive and therapeutic options for symptoms of cystitis in patients with bladder cancer receiving intravesical bacillus Calmette-Guérin immunotherapy.

Local adverse effects are the most common clinical issues in patients with bladder cancer receiving intravesical BCG immunotherapy. The aim of this systematic review was to present available options for prevention and treatment of cystitis symptoms related to bacillus Calmette-Guérin (BCG) intravesical instillations. A literature search within the Medline database was conducted in June 2018 with the following search terms: adverse events, Bacillus Calmette-Guerin, BCG, bladder cancer, cystitis, dose, dwell time, dysuria, frequency, intravesical instillations, haematuria, pain, side effects, toxicity and urgency. Eighteen relevant original articles were identified, including 15 randomized controlled trials. Potentially effective options to prevent symptoms of cystitis are BCG dose reduction, intravesical hyaluronic acid instillations and oral prulifloxacin or ofloxacin administration. For the treatment of BCG-related cystitis, available options include oral pentosan polysulphate or a combination of intravesical hyaluronic acid and chondroitin sulphate. The included studies were characterized by high heterogeneity in terms of BCG strains, schedules and endpoints. Studies on treatment of BCG-related cystitis included only small number of patients. Studies on directed medical interventions did not consider the influence on the BCG efficacy. Among few proposed preventive or therapeutic options for symptoms of cystitis related to BCG, none was proven to be both definitively effective and oncologically safe.

Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern.

BACKGROUND: Men with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this population if empirical treatment is needed. The goal of this study was to evaluate variations in prevalence, composition and antimicrobial susceptibility of bacterial flora in men with indwelling catheters subjected to surgery for BPH in chosen time periods since 1994. Necessary changes in empirical therapy were also assessed. METHODS: All patients with indwelling catheters admitted to a single urological center for BPH surgery in the years 1994-1996, 2004-2006, and 2011-2015 were considered. Catheterization times and results of urine cultures from samples collected at admission were evaluated. Susceptibility for selected antimicrobials was compared separately for Gram negative and Gram positive species. For each agent and for their combinations effectiveness of empirical therapy was calculated dividing the number of patients with bacteriuria susceptible to the agents by the total number of patients with bacteriuria. RESULTS: Bacteriuria was present in 70% of 169, 72% of 132, and 69% of 156 men in the respective time periods. The incidence of Gram-positive strains increased from 10 to 37% (P < 0.001). Their susceptibility to amoxicillin/clavulanate was fluctuating (81, 61, 77%; P=NS). No vancomycin-resistant strain was present. Gram-negative flora composition was stable. Their susceptibility decreased to ciprofloxacin (70 to 53%; P = 0.01) and amoxicillin/clavulanate (56 to 37%; P < 0.01) while it increased to gentamycin (64 to 88%; P < 0.001) and co-trimoxazole (14 to 62%; P < 0.001); susceptibility to amikacin remained high (> 85%). Only two cases of resistance to carbapenems in 2004-2006 were found. In vitro effectiveness of amikacin + amoxicillin/clavulanate in empirical therapy was slowly decreasing (87 to 77%; P=NS). Imipenem was found the most effective single agent (90-95%) and its efficacy was even improved by adding vancomycin (97-98%). CONCLUSIONS: Substantial rise in the incidence of Gram-positive species and fluctuations in antimicrobial susceptibility patterns were found. Empirical therapy of genitourinary infection in catheterized men with BPH should now involve antimicrobial agents effective both to Enterococci and Enterobacteriaceae. Periodic monitoring and publishing data on antimicrobial susceptibility for this population is necessary.

Perioperative chemotherapy in muscle-invasive bladder cancer: overview and the unmet clinical need for alternative adjuvant therapy as studied in the MAGNOLIA trial.

The European Association of Urology Research Foundation has proposed that alternatives to perioperative chemotherapy should be evaluated. The MAGNOLIA study represents a unique opportunity to investigate the concept of immunotherapy in muscle-invasive bladder cancer.

Ciprofloxacin and furagin in acute cystitis: comparison of early immune and microbiological results.

Furagin (a nitrofurantoin analogue) has the same efficacy in treating acute cystitis as ciprofloxacin, however the duration of therapy is longer. We established a hypothesis that therapy with ciprofloxacin results in faster resolution of mucosal inflammation in comparison with furagin. Rates of urinary secretion of immunoglobulins class A, M and G and interleukin-8 (IL-8) were evaluated before and after initiation of therapy in adult women presenting with acute cystitis confirmed by urine culture. Women were randomised into two groups receiving either ciprofloxacin 250mg twice a day for 3 days (n=13) or furagin 100mg three times a day for 7 days (n=14). Median lengths of follow-up were 4 days and 5 days in the ciprofloxacin and furagin groups, respectively. Treatment with ciprofloxacin resulted in faster eradication of pathogens. No bacteria or nitrates were detected in the ciprofloxacin group, whilst leukocyte esterase was positive in only one case. In the furagin group there were four positive cultures, seven cases with positive nitrates and five cases with positive esterase. Secretion rates of all four substances dropped significantly, but the changes over time were similar in both groups.

Patient-adjusted intermittent electrostimulation for treating stress and urge urinary incontinence.

OBJECTIVE: To assess the safety and efficacy of pelvic floor muscle electrostimulation (ES) in women with stress urinary incontinence (SUI) or mixed UI (MUI, urge and interstitial cystitis), using a new portable electrostimulator (Miniaturo, Biocontrol Medical Inc., Yehud, Israel) which delivers different forms of stimulation for treating these two conditions. PATIENTS AND METHODS: For SUI the stimulator is activated on demand only by a sudden increase in intra-abdominal pressure; for frequency and urgency a milder, continuous ES is used. The intensity of ES can be adjusted according to the patient's sensation. Women were enrolled into the study after satisfying inclusion criteria and pad testing; 23 participated in two study groups, i.e. 16 with SUI and seven with MUI (severe frequency, urgency and urge, and mild SUI). The pelvic floor muscles were stimulated through an electrode inserted paraurethrally, positioned similarly in all patients. In patients with SUI and MUI a pressure sensor was also inserted into the rectum, to record intra-abdominal pressure. Stimulation was applied for 1-4 h in patients with SUI and for 6 h in those with MUI. The evaluation was based on urinary symptoms (frequency, urgency, leaking episodes), quality-of-life questionnaires and pad tests at baseline and during stimulation. RESULTS: All patients in both groups improved significantly; of the 16 patients with SUI, nine were completely dry during ES, and the remaining seven had a reduced mean pad weight, from 23 to 6 g (74%). There was no significant reduction in pad weight after sham ES (17 g before vs 24.2 g after). In four patients with SUI who continued ES for 4 h the mean cumulative stimulation time (calculated from the stimulator memory) was 3 min (1.3% of 4 h). In the MUI group there were no leakage episodes during ES and significant reductions in voiding variables (Student's t-test) in all. The mean (Sd) voiding frequency, urinary urgency and leaking episodes decreased from 8.1 (4.2) to 1.9 (1.5), 6.4 (2.3) to 0.7 (1.3) and 2.1 (0.7) to 0.7 (0.5) (all P < 0.001), respectively. CONCLUSIONS: The concept of this ES system for treating UI is promising; this study supports the efficacy of this form of ES but no conclusions about clinical efficacy are possible at this stage, and thus a trial to evaluate the safety and efficacy of this implantable device is ongoing.