Long-term therapeutic effect of cell therapy on improvement in erectile function in a rat model with pelvic neurovascular injury.

OBJECTIVE: To determine the long-term therapeutic effect amongst three human cell types on erectile function recovery in a rat model of dual neurovascular-injury erectile dysfunction (NVED). MATERIALS AND METHODS: A dual NVED model was established in athymic rats by crushing the bilateral cavernous nerves and ligating the bilateral internal pudendal neurovascular bundles. At the time of defect creation, three different types of human cell populations (2.5 × 106  cells/0.2 mL: umbilical vein endothelial cells, adipose-derived stem cells, and amniotic fluid-derived stem cells) were injected intracavernously into the penile tissue. Saline injection (0.2 mL) served as a control group. Erectile function and histomorphological analyses of penile tissues were assessed 12 weeks after defect creation and cell or saline injection. RESULTS: The ratio of intracavernous pressure to mean arterial pressure (functional indicator) was significantly higher in the cell therapy groups compared to the saline-injected control group (P < 0.05). Immunofluorescence staining showed more cells expressing biomarkers of endothelial, smooth muscle, and nerve cells within the penile tissue in the cell therapy groups when compared to the control group. CONCLUSIONS: Cell therapy enhanced erectile function and ameliorated the histological changes 12 weeks after pelvic neurovascular injury in vivo, indicating that cell therapy may improve the long-term outcomes in neurogenic, myogenic and vascular tissue regeneration in the treatment of NVED.

Bladder outlet obstruction causes up-regulation of nicotinic acetylcholine receptors in bladder-projecting pelvic ganglion neurons.

Pelvic ganglion (PG) neurons relay sympathetic and parasympathetic signals to the lower urinary tract, comprising the urinary bladder and bladder outlet, and are thus essential for both storage and voiding reflexes. Autonomic transmission is mediated by activation of the nicotinic acetylcholine receptor (nAChR) in PG neurons. Previously, bladder outlet obstruction (BOO), secondary to benign prostatic hyperplasia, was found to increase soma sizes of bladder-projecting PG neurons. To date, however, it remains unknown whether these morphological changes are accompanied by functional plasticity in PG neurons. In the present study, we investigated whether BOO alters acetylcholine receptor (nAChR) transcript expression and current density in bladder PG neurons. Partial ligation of the rat urethra for six weeks induced detrusor overactivity (DO), as observed during cystometrical measurement. In rats exhibiting DO, membrane capacitance of parasympathetic bladder PG neurons was selectively increased. Real-time PCR analysis revealed that BOO enhanced the expression of the transcripts encoding the nAChR α3 and ß4 subunits in PG neurons. Notably, BOO significantly increased ACh-evoked current density in parasympathetic bladder PG neurons, whereas no changes were observed in sympathetic bladder and parasympathetic penile PG neurons. In addition, other ligand-gated ionic currents were immune to BOO in bladder PG neurons. Taken together, these data suggest that BOO causes upregulation of nAChR in parasympathetic bladder PG neurons, which in turn may potentiate ganglionic transmission and contribute to the development of DO.

Effects of neutral pH and low-glucose degradation product-containing peritoneal dialysis fluid on systemic markers of inflammation and endothelial dysfunction: a randomized controlled 1-year follow-up study.

BACKGROUND: The local peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) have been extensively described. However, the systemic effects of prolonged prescription of these solutions are unknown. This study aimed to evaluate the effects of neutral pH and low-GDP PDF on systemic inflammation and endothelial dysfunction markers in peritoneal dialysis (PD) patients. METHODS: This is a multicenter, open labeled, randomized controlled trial including one hundred fifty-two patients initiating continuous ambulatory peritoneal dialysis for end-stage renal disease from seven centers in Korea. Participants were randomly allocated to conventional PDF (Stay safe®; Fresenius Medical Care, Bad Homburg, Germany) or low-GDP PDF (Balance®; Fresenius Medical Care) and were followed for 1 year. Primary outcome variable was the inflammation and endothelial dysfunction index (IEDI), a composite score derived from serum levels of soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cellular adhesion molecule (sVCAM)-1 and high-sensitivity C-reactive protein (hs-CRP). sICAM-1, sVCAM-1, residual renal function (RRF), peritoneal membrane transport characteristics, ultrafiltration volume and nutritional parameters were measured as secondary outcome variables. RESULTS: Of 152 patients randomized, 146 (low-GDP: conventional PDF, 79:67) patients entered the trial (46% male, 53% with diabetes mellitus). At 12-month follow-up, the low-GDP group had significantly lower levels of IEDI, sICAM-1 and sVCAM-1 compared to the conventional group; hs-CRP was not different between groups. Peritoneal transport characteristics, RRF, nutritional parameters, incidence of peritonitis and death-censored technique survival were not different between groups. CONCLUSION: Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.

Efficacy of bladder-preserving therapy for patients with t3b, t4a, and t4b transitional cell carcinoma of the bladder.

PURPOSE: Radical cystectomy has been the most widely used method in the treatment of bladder cancer, but it is limited by major problems. Therefore, we investigated the results of bladder-preserving treatment in patients with T3b, T4a, and T4b transitional carcinoma of the bladder who underwent transurethral resection of bladder cancer and subsequent administration of chemotherapy. MATERIALS AND METHODS: Of all patients who were diagnosed with bladder cancer and underwent bladder-preserving treatment between January 2001 and August 2008, 78 patients with at least 12 months of follow-up data were enrolled in this study. All patients received gemcitabine (1,000 mg/m(2)) and cisplatin (70 mg/m(2)) once per month postoperatively for a total of 6 months and completed a follow-up visit every 3 months. The patient survival rate and prognostic factors (age, tumor size, differentiation, number of lesions, stage, and presence of hydronephrosis) were assessed. The Kaplan-Meier method was used to analyze survival rate, and Cox multiple regression analysis was used for prognostic factors. RESULTS: The mean patient age was 68.32+/-8.6 years, the mean duration of follow-up was 54.70+/-32.8 months, and the median duration of follow-up was 49.0 months. The 5-year survival rate was 66.2%. Single lesions were found in 28 cases (35.9%), and multiple lesions were found in 50 cases (64.1%). Stage T3b lesions were identified in 56 cases (71.8%), stage T4a lesions were identified in 16 cases (20.5%), and stage T4b lesions were identified in 6 cases (7.7%). Tumor size was less than 4 cm in 4 cases (59.0%) and greater than 4 cm in 32 (41.0%). Hydronephrosis was present in 21 cases (26.9%). In the 5-year survival analysis, prognostic factors significantly influencing survival rate were T-stage of the tumor and absence of hydronephrosis and complete regression after treatment (p<0.05). Multivariate analysis revealed that tumor stage and the absence of hydronephrosis were statistically significant prognostic indicators. CONCLUSIONS: In patients with T3b, T4a, and T4b transitional carcinoma of the bladder, bladder preservation may prevent a decrease in quality of life. Also, our findings suggest that this approach could be considered a primary treatment option for patients with T3b stage tumors without evidence of hydronephrosis.