NERVE GROWTH FACTOR BLADDER TISSUE LEVELS IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA AND DETRUSOR OVER ACTIVITY TREATED WITH TAMSULOSIN

INTRODUCTION & OBJECTIVES: Following Bladder Outlet Obstruction (BOO) in experimental models, Nerve Growth Factor-dependent plasticity in the autonomic nervous system may be responsible for the genesis and maintaining of deta'usoroveractivity. Actually, there is no consistent information on how these mechanisms specifically interact in humans. We measured Nerve Growth Factor (NGF) concentrations in bladder tissues biopsies taken from patients affected by BOO and detrusor over activity due to Benign Prostatic Hyperplasia, before and during treatment with tamsulosin. We alsocompared NGF content with nrodynamic data. MATERIAL & METHODS: 18 patients underwent urodynamics with recording of uninhibited detrusor contractions (UDC) threshold and UDC maximum pressure (pmax), detmsor pressure at maximum flow rate (pDetQmax) and maximum flow rate (Qmax), before and at 1 and 3 months after the beginning of treatment with Tamsulosin (0.4 mg once daily). NGF levels were measured in tissues homogenatebyELISA(Promega,Madison-WI).Thesensitivity-was 15.6pg/mlofNGF.Datawere expressed as ng/mg protein (mean of duplicate samples). RESULTS: On urodynamics, we detected a significant increase in UDC threshold, a significant reduction in pDetQmax and a significant increase in Qmax at 1 and 3 months as compared to baseline. A significant reduction in bladder NGF content was observed at 1 and 3 months, as compared to baseline values (see Table below). 814 THE EVALUATION OF DETRUSOR REGENERATION BIOCO1MI'A- TIBILITY IN THE RAT MODEL USING PORCINE SMALL INTESTI NAL SUBMUCOSA Ayyildiz A?, Hurl E.1, Nuhoglu B.1, Gurdal M), Caydere M.a, Ustu~ tI.:, Germiyanoglu C. ~Ministry of Health Ankara Education and Research Hospital, Dept. of Urotogy, Ankara, Turkey, 2Ministry of Health Ankara Education and Research Hospita, Dept. of Pathology, Ankara, Turkey INTRODUCTION & OBJECTIVES: Recently, the using biomaterials for a l type reconstructive surgery are so common that we aimed to evaluate long-terla results of small intestinal submueosa, biodegradable material, used in bladder augmentation as a bioscaffold. MATERIAL & METHODS: 16 female Sprague-Dawley rats underwent partial cystectomy with immediate bladder augmentation with SIS. 2x5 cm SIS was anastomosed tightly to the dome. Bladder was harvested for histologic evaluation at 8. months to research of the long-term results. Sections were stained with Masson's hematoxylin-eozin, S-100, F8 and Masson's trictuome stains. RESULTS: All animals were alive at 8.month. Macroscopically, gross view of the materials (2x5) were not seen, all bladders were completely dilated without evidence of diverticular formation and extravasation in the region of the lgafi. The colour of grafts' area was white compared with surrounding native bladder. Perivesical adhesion was minima}ly determined. Stone fon~aation was not detected in all bladders. There were no evidence of postoperative glob vesicale, hydroureteronephrosis and UTI. Histologically, the excellent transitional epithelial layer covered the graft's surface as the continue of the host epithelium. There were no any inflamatory cells in atl layers of bladder wall. Collagen fibers and dissemine fibroblasts were observed without the muscle fiber regeneration. All parts of the grafts' area looked as a soft tissue without the material. Increased neovascularization without lymphatic proliferation were detected. There was no evidence of nerve regeneration. CONCLUSIONS: SIS may be widely used in reconstructive surgery because of well-biocompatibility at the long-term period. Finally, further investigations have to be performed as a clinical research. 816 EFFECT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITOR ON CONNEXIN EXPRESSION AFTER BLADDER OUTLET OBSTRUCTION IN RATS Kim J.C, Kim H.S., Sen S.h, Hong S.H., Hwang T.K. The Catholic University of Korea, Urology, Seonl, South Korea INTRODUCTION & OBJECTIVES: Detrusor overaetivity and storage symptoms are frequently associated with bladder outlet obstruction (BOO) and this may be related with increased electrical coupling. Connexins (Cx) constitute a family of transmembrane proteins that form gap junction channels allowing metabolic and electrical coupling of cellular networks. Angiotensin II is one of the factors that influence the expression of connexins. Therefore, the inhibition of angiotensin II may affect the expression of Cxs and bladder function. This study was performed to investigate the changes in Cx26 and C×43 expression after administration of angiotensin-convertingenzyme (ACE) inhibitor in rats with BOO and how these changes participate in functional changes of the rat bladder. MATERIAL & METHODS: A total of 50 Sprague-Dawleyrats were used for this study and divided into 10 sham-operated control and 40 experimental groups. Partial BOO was induced to experimental groups that were divided into two subgroups, consisting of one group with obstruction only (obstruction group) (n=20) and another group with administration of ACE inhibitor (ACE inhibitor treated group) (n=20). Cystometrograms (CMG) were performed 2 weeks after partial BOO, and contraction pressure, interval of contraction, and presence of uninhibited contraction were checked. The bladders of each group were dissected out, weighed. The immunohistochemical staining was performed for localization of Cx26 and Cx43. Total RNA was extracted from each bladder and reverse transcriptase polymerase chain reaction (RT-PCR) was performed for the analysis Cx26 and Cx43 mRNA. RESULTS: Compared with the control group, the bladder weight was significantlyincreased in ACE inhibitor treated and obstruction group (P<0.05). On CMG, there was no significant difference in contraction pressure among the three groups. The contraction interval was significantlydecreased in the obstruction group and recovered in the ACE inhibitor treated group (P<0.05). On immunohistochemicalstaining, the Cx26 was localizedin urotheliltmand Cx43 in urothelial and muscular layer. The staining intensity of Cx26 and Cx43 were increased in obstruction group compared to the control group, whereas the staining intensity of Cx26 and Cx43 in ACE inhibitor treated group was decreased compared to the obstruction group. The RT-PCR analysis demonstrated that the levels of both Cx26 and Cx43 mRNA were increased in obstruction group compared to the control group. However, the level of both Cx26 and Cx43 mRNA were decreased in ACE inhibitor treated group compared to the obstruction group. CONCLUSIONS: These data suggest that ACE inhibitor can reduce detrusor over activity through down-regulation of gap junctions in overactive bladder cansed by BOO. Therefore, the ACE inhibitor may be useful for the treatment of overactive bladder symptom associated with bladder outlet obstruction. UDC thres- hold (ml) UDC max. pressure (cmH20) pDetQmax (cmH20) Qmax (ml) NGF (ng/mg) Baseline (mean ±SD) I86.5 -1:85.2 49.6 ±19.7 65.8 ±12.6 8.5 ~3.7 56.3 ~28.7 1 month (mean £SD) 231.7 ±56 37.l ±14.8 60.5 ±7.7 12.9 ±2 38.6 ±12.9 3 months (mean ±SD) 241.4 ±54.1 43.7 ±20.2 56.7 ±8.6 12.4 ±3.2 41.8 ±6.9 p levels p<0.05 n.s. p<0.05 p<0.05 p<0.05 CONCLUSIONS: These results demonstrate in humans that the reduction of NGF bladder tissue content due to pharmacological reliefof obstruction induces a subsequent decrease of detrusor over activity. It is possible to consider NGF bladder tissue content as a marker of the severity of BOO and as predictor of the response to treatment.