Diabetes-induced alterations in urothelium function:Enhanced ATP release and nerve-evoked contractions in the streptozotocin rat bladder

Up to 80% of patients with diabetes mellitus develop lower urinary tract complications, most commonly diabetic bladder dysfunction (DBD). The aim of this study was to investigate the impact of diabetes on the function of the inner bladder lining (urothelium). Bladder compliance and intraluminal release of urothelial mediators, adenosine triphosphate (ATP) and acetylcholine (ACh) in response to distension were investigated in whole bladders isolated from 2‐ and 12‐week streptozotocin (STZ)‐diabetic rats. Intact and urothelium‐denuded bladder strips were used to assess the influence of the urothelium on bladder contractility. Intraluminal ATP release was significantly enhanced at 2 weeks of diabetes, although not at 12 weeks. In contrast, intraluminal ACh release was unaltered by diabetes. Bladder compliance was also significantly enhanced at both 2 and 12 weeks of diabetes, with greatly reduced intravesical pressures in response to distension. Nerve‐evoked contractions of bladder strips were significantly greater at 2 weeks of diabetes. When the urothelium was absent, nerve‐evoked contractions were reduced, but contractions remained significantly elevated at lower frequencies of stimulation (<5 Hz) in diabetics. Interestingly, although relaxations of bladder strips to isoprenaline were unaltered by diabetes, removal of the urothelium unmasked significantly enhanced relaxations in strips from 2‐ and 12‐week diabetic animals. In conclusion, diabetes alters urothelial function. Enhanced urothelial ATP release may be involved in the hypercontractility observed at early time points of diabetes. These alterations are time‐dependent and may contribute to the mechanisms at play during the development of diabetic bladder dysfunction.Full Tex

Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat

Background: The functional and molecular alterations of nerve growth factor (NGF) and Prostaglandin E2 (PGE2) and its receptors were studied in bladder and urine in streptozotocin (STZ)-induced diabetic rats. Methodology/Principal Findings: Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p) in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI) and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP)1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12. Conclusions/Significance: DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder. © 2014 Nirmal et al

Weekly epirubicin in patients with hormone-resistant prostate cancer

The aim of this study was to investigate the benefit of weekly epirubicin in the treatment of metastatic hormone-resistant prostate cancer. One hundred and forty-eight patients with metastatic hormone-resistant prostate cancer received weekly 30-min intravenous infusions of epirubicin 30 mg m2 of body surface area. The primary end-point was palliative response, defined as a reduction in pain intensity and an improvement in performance status. The secondary end-points were the duration of the palliative response, quality of life and survival. Fifty-seven (44%) of the 131 evaluable patients met the primary criterion of palliative response after six treatment cycles and 73 (56%) after 12 cycles; the median duration of the response was 9 months (range 1–11). The median global quality of life improved in 52% of the patients after six cycles and in 68% after 12 cycles. The 12- and 18-month survival rates were respectively 56 and 31%, with a median survival of 13+ months (range 1–36). The treatment was well tolerated: grade 3 neutropenia was observed in 8% of the patients, grade 3 anaemia in 7%, and grade 3 thrombocytopenia in 3%. None of the patients developed grade 4 toxicity or congestive heart failure. Weekly epirubicin chemotherapy can lead to a rapid and lasting palliative result in patients with metastatic HRPC, and have a positive effect on the quality of life and survival

Advances in the role of sacral nerve neuromodulation in lower urinary tract symptoms

Sacral neuromodulation has been developed to treat chronic lower urinary tract symptoms, resistant to classical conservative therapy. The suspected mechanisms of action include afferent stimulation of the central nervous system and modulation of activity at the level of the brain. Typical neuromodulation is indicated both in overactivity and in underactivity of the lower urinary tract. In the majority of patients, a unilateral electrode in a sacral foramen and connected to a pulse generator is sufficient to achieve significant clinical results also on long term. In recent years, other urological indications have been explored

Coping and Health-Related Quality of Life in Men With Prostate Cancer Randomly Assigned to Hormonal Medication or Close Monitoring

Prostatic carcinoma and its treatment have been associated with adverse effects on health-related quality of life (HRQoL). Individual differences in appraisal and coping have been suggested to mediate these HRQoL outcomes. A randomized trial of 65 men with non-localized prostate cancer compared several treatments and tested associations between appraisal, coping, and HRQoL. These patients, and 16 community volunteers matched for age and general health, undertook psychosocial assessments before treatment and after 6 months of treatment. Compared with baseline assessments, men on hormonal treatments reported impaired sexual function. Groups did not differ on emotional distress, existential satisfaction, subjective cognitive function, physical symptoms, or social and role functioning. For individuals, hormonal treatments were more frequently associated with decreased sexual, social and role functioning, but were also associated with improved physical symptoms. In hierarchical regression analysis, HRQoL was lower for men who had more comorbid illnesses, a history of neurological dysfunction, higher threat appraisals, or higher use of coping strategies at baseline. These results showed that pharmacological hormonal ablation for prostate cancer can improve or decrease HRQoL in different domains. HRQoL in men with prostate cancer was associated more strongly with appraisal and coping than with medical variables