LB-S&T-29 SEMINAL CITRATE: A NEW MARKER FOR THE DETECTION OF PROSTATE CANCER?

Abstract

model. We investigated whether intrathecal (i.t.) ALX-1393 can inhibit the autonomic response during bladder HD in the IC/BPS rat model. METHODS: Animals Twelve Sprague-Dawley female white rats (200-250g) were divided into 2 groups (control, n¼12 and ALX-1393, n¼12, respectively). All rats received protamine sulfate (PS) 10mg/ml in the urinary bladder for 30 minutes followed by 750ug/ml lipopolysaccharide (LPS) instillation for 45 minutes. One week after the instillation, cystometry (n¼6, in both groups, respepctively) and HD (n¼6, in both groups) was performed.Hydrodistention and Cystometry Based on previous experiments, HD was performed at a pressure of 150-170 mmHg for 30 seconds with a 3 minute interval. Autonomic response was quantified as the difference of mean arterial pressure between baseline period prior to distension and during HD. Anesthesia was performed with Intraperitoneal injection of Zoletil (Tiletamine+Zolazepam) 0.1cc/100g and Rompun (Xylazine) 0.025~0.04/100g. After placing a PE-50 tubing into the bladder, awake cystometry was performed by infusing physiological saline at a slow infusion rate (0.04ml/min).Intrathecal administration of ALX-1393 Through the subarachnoid space, a polyethylene catheter was advanced and placed at L6-S1 spinal cord level. Saline (for control) or ALX-1393 was injected after 1st HD, and 2 more sessions were performed 5 and 30 minutes after saline or ALX-1393 injection.RESULTS: A significant increase in BP was consistently observed for 3 consecutive sessions of HD in control group (19.49AE5.50, 13.63AE6.22 and 17.18AE7.67mmH2O). In ALX-1393 group, minimal change of BP was observed during HD which was performed 5 minutes after ALX-1393 i.t. injection (4.22AE9.69mmH2O). The exaggerated autonomic response was observed 30 minutes after ALX-1393 i.t. injection (15.62AE8.60mmH2O). On cystometry, intercontraction interval (ICI) in control group demonstrated little change after saline i.t injection (12.17AE20.58, p¼0.207), while significantly prolonged ICI was seen immediately after ALX-1393 i.t injection (57.83AE24.86, p¼0.005).CONCLUSIONS: ALX-1393 inhibits the exaggerated autonomic responses during bladder HD and ameliorates detrusor overactivity in the IC/BPS rat model. These findings suggest that GlyT2 may be a novel therapeutic target for the treatment of IC/BPS.