We investigated whether dissimilar biochemical fractions originating in anatomically discrete sections of the pomegranate (Punica granatum) fruit might act synergistically against proliferation, metastatic potential, and phosholipase A2 (PLA2) expression of human prostate cancer cells in vitro . Proliferation of DU 145 human prostate cancer cells was measured following treatment with a range of therapeutically active doses of fermented pomegranate juice polyphenols (W) and sub-therapeutic doses of either pomegranate pericarp (peel) polyphenols (P) or pomegranate seed oil (Oil). Invasion across Matrigel by PC-3 human prostate cancer cells was measured following treatment with combinations of W, P and Oil such that the total gross weight of pomegranate extract was held constant. Expression of PLA2, associated with invasive potential, was measured in the PC-3 cells after treatment with the same dosage combinations as per invasion. Supra-additive, complementary and synergistic effects were proven in all models by the Kruskal-Wallis non-parametric H test at p < 0.001 for the proliferation tests, p < 0.01 for invasion, and p < 0.05 for PLA2 expression. Proliferation effects were additionally evaluated with CompuSyn software median effect analysis and showed a concentration index CI < 1, confirming synergy. The results suggest vertical as well as the usual horizontal strategies for discovering pharmacological actives in plants.

What's known on the subject? and What does the study add?• It is known that intravesical botulinum toxin (BT) is an effective treatment for overactive bladder, especially in the patients with neurogenic detrusor overactivity. Several studies have shown that diagnostic and health-related quality of life parameters improve after intravesical BT treatment.• The present study has the merit of reporting a 'real-life' experience in a large teaching hospital in the UK National Health Service. As opposed to controlled trials, this retrospective study based largely on patient choice, shows that most patients fail to persist with intravesical BT treatment, mainly due to tolerability issues. Objectives• To assess the long-term compliance with repeated injections of intravesical botulinum toxin (BT) in a 'real-life' mixed population of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity.• To identify the reasons why patients discontinued BT therapy and to explore the outcomes of those patients who did discontinue treatment. Patients and Methods• Retrospective evaluation of the case notes of a series of patients who had received intravesical BT treatment at a large UK teaching hospital.• No antibiotic prophylaxis was given for the procedure. Results• Over a period of 7 years, 268 patients were initiated on intravesical BT treatment for overactive bladder (OAB) at our institution, with 137 followed up for Ն36 months, with 80 patients having Ն60 months follow-up after their first injection.• Almost two-thirds of patients (61.3%) had discontinued intravesical BT therapy at 36 months, with a 63.8% discontinuation rate at 60 months.• The main reasons for discontinuation were tolerability issues, mainly urinary tract infections and the need for clean intermittent self-catheterisation. Primary and secondary losses of efficacy were of secondary importance.• Most of the patients that discontinued have remained under urology care and now receive alternative methods of treatment. Conclusions• Intravesical BT therapy is an effective short-term treatment for OAB.• With time, two-thirds of patients discontinued treatment usually because of the tolerability issues associated with treatment.

Our data demonstrate that women with higher preoperative MUCP do not have a better surgical outcome following stress incontinence surgery.

Objective To assess, using epirubicin-sensitive and multidrug resistant (MDR) derivatives of human bladder cancer cell lines in vitro , the probable effect of intravesical pH changes, with and without the MDR antagonist verapamil, on the uptake, intracellular distribution and cytotoxicity of epirubicin during intravesical chemotherapy. Materials and methods Incubations for cytotoxicity testing were carried out in buffered medium containing epirubicin, at pH values of 6.0-8.5, with verapamil where appropriate. The cytotoxicity of epirubicin, with and without verapamil, was determined using the tetrazolium cytotoxicity assay. Intracellular epirubicin fluorescence was assessed using flow cytometry and confocal microscopy. Flow cytometric total intracellular epirubicin fluorescence was measured at pH 6.0, 6.4, 6.8, 7.2, and 7.6, and confocal microscopy was carried out at pH 6.0 and 8.0. The MDR-reversing agent verapamil was added at 100 m g/mL to some incubations. Results Epirubicin cytotoxicity in resistant cell lines appears considerably enhanced by adding verapamil and further improved, especially in MDR cells, by alkalinization of the drug solution to pH 8.0. Flow cytometry results showed striking and consistent differences in epirubicin handling with pH. Sensitive cells can be induced to absorb considerably more drug at alkaline pH, whilst resistant cells show no such behaviour. Nuclear drug fluorescence was greater in sensitive cells at alkaline pH, but cytoplasmic drug fluorescence in the resistant cells was little changed by pH. Adding verapamil to resistant cells restored the sensitive phenotype of drug handling. Conclusion Buffering epirubicin to an alkaline pH before intravesical application should increase its intrinsic cytotoxicity. The potential for synergy at certain drug combinations will be enhanced by applying these findings. MDR reversal and fatty acid augmentation of drug uptake are discussed as examples.

Objectives To determine whether recent sexual intercourse might be a cause of microscopic haematuria in patients referred to a urological unit following dipstick detection of urinary haemoglobin. Subjects and methods Forty-eight volunteers (24 men and 24 women) consented to have heterosexual intercourse with their regular partner, and to provide samples of urine for testing before and from the ®rst void on the morning after intercourse. After appropriate instruction, volunteers tested their own urine for the presence of blood using standard dipsticks. Any volunteer with haematuria either before or after intercourse was offered a standard haematuria assessment. The results were analysed using the chi-squared test.Results None of the volunteers tested positively for haematuria immediately before sexual intercourse; six of the 24 women (25%), but no men, became positive after intercourse (P<0.01). Only one of the six women accepted the offer of a haematuria evaluation and no pathology was identi®ed. Conclusion These results suggest that up to a quarter of women develop microscopic haematuria as a direct result of sexual intercourse. A history of recent sexual intercourse should therefore be considered when assessing the clinical signi®cance of microscopic haematuria in women.