Periprostatic adipose tissue (PPAT) supernatant from obese mice releases anticontractile substances and increases human prostate epithelial cell proliferation: the role of nitric oxide and adenosine.

Background: The prostate gland is surrounded by periprostatic adipose tissue (PPAT) that can release mediators that interfere in prostate function. In this study, we examined the effect of periprostatic adipose tissue supernatant obtained from obese mice on prostate reactivity in vitro and on the viability of human prostatic epithelial cell lines. Methods: Male C57BL/6 mice were fed a standard or high-fat diet after which PPAT was isolated, incubated in Krebs-Henseleit solution for 30 min (without prostate) or 60 min (with prostate), and the supernatant was then collected and screened for biological activity. Total nitrate and nitrite (NOx-) and adenosine were quantified, and the supernatant was then collected and screened for biological activity. NOx- and adenosine were quantified. Concentration-response curves to phenylephrine (PE) were obtained in prostatic tissue from lean and obese mice incubated with or without periprostatic adipose tissue. In some experiments, periprostatic adipose tissue was co-incubated with inhibitors of the nitric oxide (NO)-cyclic guanosine monophosphate pathway (L-NAME, 1400W, ODQ), adenylate cyclase (SQ22536) or with adenosine A2A (ZM241385), and A2B (MRS1754) receptor antagonists. PNT1-A (normal) and BPH-1 (hyperplasic) human epithelial cells were cultured and incubated with supernatant from periprostatic adipose tissue for 24, 48, or 72 h in the absence or presence of these inhibitors/antagonists, after which cell viability and proliferation were assessed. Results: The levels of NOx- and adenosine were significantly higher in the periprostatic adipose tissue supernatant (30 min, without prostate) when compared to the vehicle. A trend toward an increase in the levels of NOX was observed after 60 min. PPAT supernatant from obese mice significantly reduced the PE-induced contractions only in prostate from obese mice. The co-incubation of periprostatic adipose tissue with L-NAME, 1400W, ODQ, or ZM241385 attenuated the anticontractile activity of the periprostatic adipose tissue supernatant. Incubation with the supernatant of periprostatic adipose tissue from obese mice significantly increased the viability of PNT1-A cells and attenuated expression of the apoptosis marker protein caspase-3 when compared to cells incubated with periprostatic adipose tissue from lean mice. Hyperplastic cells (BPH-1) incubated with periprostatic adipose tissue from obese mice showed greater proliferation after 24 h, 48 h, and 72 h compared to cells incubated with culture medium alone. BPH-1 cell proliferation in the presence of PPAT supernatant was attenuated by NO-signaling pathway inhibitors and by adenosine receptor antagonists after 72 h. Conclusion: NO and adenosine are involved in the anticontractile and pro-proliferative activities of periprostatic adipose tissue supernatant from obese mice. More studies are needed to determine whether the blockade of NO and/or adenosine derived from periprostatic adipose tissue can improve prostate function.

BAY 41-2272, a soluble guanylate cyclase stimulator, relaxes isolated human ureter in a standardized in vitro model.

OBJECTIVE: To characterize the relaxation induced by BAY 41-2272 in human ureteral segments. MATERIALS AND METHODS: Ureter specimens (n = 17) from multiple organ human deceased donors (mean age 40 ± 3.2 years, male/female ratio 2:1) were used to characterize the relaxing response of BAY 41-2272. Immunohistochemical analysis for endothelial and neuronal nitric oxide synthase, guanylate cyclase stimulator (sGC) and type 5 phosphodiesterase was also performed. The potency values were determined as the negative log of the molar to produce 50% of the maximal relaxation in potassium chloride-precontracted specimens. The unpaired Student t test was used for the comparisons. RESULTS: Immunohistochemistry revealed the presence of endothelial nitric oxide synthase in vessel endothelia and neuronal nitric oxide synthase in urothelium and nerve structures. sGC was expressed in the smooth muscle and urothelium layer, and type 5 phosphodiesterase was present in the smooth muscle only. BAY 41-2272 (0.001-100 µM) relaxed the isolated ureter in a concentration dependent manner, with a potency and maximal relaxation value of 5.82 ± 0.14 and 84% ± 5%, respectively. The addition of nitric oxide synthase and sGC inhibitors reduced the maximal relaxation values by 21% and 45%, respectively. However, the presence of sildenafil (100 nM) significantly potentiated (6.47 ± 0.10, P <.05) this response. Neither glibenclamide or tetraethylammonium nor ureteral urothelium removal influenced the relaxation response by BAY 41-2272. CONCLUSION: BAY 41-2272 relaxes the human isolated ureter in a concentration-dependent manner, mainly by activating the sGC enzyme in smooth muscle cells rather than in the urothelium, although a cyclic guanosine monophosphate-independent mechanism might have a role. The potassium channels do not seem to be involved.

Life experiences of Brazilian men with urinary incontinence and erectile dysfunction following radical prostatectomy.

PURPOSE: The objective of this study was to explore the psychosocial meaning and repercussions on lifestyle associated with erectile dysfunction and urinary incontinence (UI) in men following radical prostatectomy. SUBJECTS AND SETTING: Ten men from Southeastern Brazil who underwent radical prostatectomy for prostate cancer were interviewed. All participants underwent treatment at a urology clinic during the period of September 2007 to February 2009. METHODS: A clinical-qualitative study was conducted, using semi-structured interviews with open-ended questions. All interviews were recorded and transcribed verbatim. Each man was interviewed once. The average length of the interviews was 37 minutes (range: 16 to 81 minutes). Data from the interviews were subjected to content thematic analysis and development of categories based on psychodynamic references. RESULTS: Three themes were identified: (1) sexuality called into question; (2) a body without governance; and (3) experiencing loss. These men reported difficulties in dealing both with the physical and emotional impotence resulting from the treatment. Urinary incontinence and erectile dysfunction affected their body by accentuating conflicts related to masculinity, triggering subjective feelings of powerlessness, and psychological distress. CONCLUSION: Study respondents assigned multiple psychological meanings to issues related to feelings of powerlessness in general, leading to a narcissistic wound. The men experienced UI as a bodily deficiency, and erectile dysfunction was experienced as a feeling of being devitalized. These results suggest that UI from prostate cancer treatment affects sexuality and self-esteem.

Umbilical grafting in treatment of recurrent stomal stenosis.

OBJECTIVES: The continent catheterizable conduit was first described by Mitrofanoff and is a good option for treating patients with urinary incontinence of different etiologies and those unable to perform transurethral self-catheterization. Stomal stenosis is the most common minor complication involved in this procedure and often is not an easily dealt with problem. Stenosis has a tendency to recur, and the surgical approach becomes progressively more difficult because of local fibrosis and retraction. We present our initial experience with a new surgical technique involving umbilical grafting for the treatment of stomal and urethral meatal stenosis. METHODS: Four female patients who presented with either recurrent stomal or urethral meatal stenosis underwent a new surgical approach with umbilical grafting for treatment. We present the results of this new technique. RESULTS: The initial clinical results of this innovative technique, at a median of 4 months of follow-up, showed that all 4 patients remained continent and mostly satisfied with their voiding pattern. CONCLUSIONS: The results of our study have shown that umbilical grafting is a viable option for the treatment of recurrent stomal and urethral stenosis.