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MP19-16 PROTEASE ACTIVATED RECEPTOR-3 EXPRESSION IS DECREASED IN HUMAN BENIGN PROSTATIC HYPERPLASIA
THE JOURNAL OF UROLOGYâ
e194
BPH+SEs groups received daily oral doses of SE (228 and 457 mg/kg) for 5 weeks. After 5 weeks, all rats were sacrificed and the prostates and blood were collected, used for evaluation of oxidative stress, apoptosis, and the activity of 5-alpha reductase. RESULTS: BPH group showed a markedly increased prostate weight than in the control group, whereas rats in BPH+SEs groups showed a decreased prostate weight. The oxidative stress markers, activity of superoxide dismutase in serum and the level of 8-hydroxy2-deoxyguanosine, and the activity of 5-alpha reductase in serum and prostate were significantly higher in BPH group compared to the control group and it was reduced in the SE treated groups. Also, the concentration of caspase-3 was significantly increased in BPH group compared to the control group and it was decreased in BPH+SEs groups. CONCLUSIONS: These results showed that SE is effective in decreasing the volume and suppressing the proliferation of the prostate. We suggest that SE may have a potency to replace or assist the medicine now in use for the treatment of BPH. Source of Funding: none
MP19-14 POST TURP STRICTURE! UROLOGIST’S DILEMMA - CAN WE PREVENT THEM? e A RESEARCH PERSEPECTIVE. Suresh Patankar, Suresh Patankar*, Pune, India INTRODUCTION AND OBJECTIVES: Incidence of urethral stricture (US) is common problem after TURP surgery. The formation of US is due to fibrosis of connective tissue rich in collagen type I, due to up regulation of CTFF expression and is closed to scar formation. Usually causes of urethral stricture following TURP are from urological procedures and manipulation of the urethra like surgical instrumentation, catheter trauma, prolonged endoscopic surgeries, etc. Presently various preclinical studies are being carried out using animal models to understand the mechanism and prevention of US. Halofuginone (HF) derived from Chinese herb inhibits periurethral type I collagen deposition and helps in prevention of US in animal model. In this presentation results of phase II clinical study carried out on the novel herbal formulation for prevention of US post TURP are presented. METHODS: The formulation Anuradha oil (AO) was prepared from Curcuma longa Rhizomes, Glycyrrhiza glabra Rhizomes, Hamiltonia suaveoleans Stem bark, Typha angustifolia flowers, Azadirchta indica leaves, using Sesamum indicum Seed oil as base and or pig fat in certain proportion. The preclinical safety and efficacy on various wound size was carried out using OECD guidelines in rodents. A prospective, phase II, randomized, double arm Controlled clinical studies in 128 patients (n¼64) following TURP was conducted after the approval of Institutional Ethics Committee. The treatment group received 2.5 ml of AO while control received vehicle for 3 to 12 weeks. The gland size, resection time, procedure and catheter duration was kept more or less same. Assessment for Dysuria was done by VAS, rate of stricture formation by Endoscopic examination and IPSS score at 3, 6 and 12 Weeks. The results were analyzed by Chi-Square Test using 2013 Graph Pad Software, Inc. RESULTS: The preclinical studies revealed no untoward reaction after application of AO for 28 days using OECD guidelines in rodents. Clinically there was no statistically significant difference in gland size, resection time, procedure & catheterization duration and IPSS score in control and AO treated group. However, the incidence of dysuria and stricture rate was found to be significantly less at Day 1 (p<0.002), 3 weeks (p<0.03, p< 0.02), 6 and 12 weeks (p<0.04 & p< 0.05, and p< 0.04 & p<0.03) in AO treatment group as compared to control group respectively. CONCLUSIONS: AO showed encouraging results to prevent US in Post TURP patients; however, phase III study in large sample size is needed before final conclusion. Source of Funding: none
Vol. 191, No. 4S, Supplement, Saturday, May 17, 2014
MP19-15 PROSTATIC INFLAMMATION TRIGGERS VOIDING DYSFUNCTION BY NEURAL CROSS-TALK. Sanghee Lee*, Guang Yang, Jerry Gipp, Wade Bushman, Madison, WI INTRODUCTION AND OBJECTIVES: A high incidence of prostatic inflammation in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) has been previously reported. We postulate that prostatic inflammation sensitizes afferent fibers from the bladder resulting in changes in bladder function. We show here that afferent innervation of the bladder and prostate originate from overlapping groups of dorsal root ganglia and that prostatic inflammation induces increased urinary frequency. METHODS: A retro-grade neuro-tracer Fast Blue was applied to each of the prostate lobes, anterior, dorsal-lateral and ventral as well as the seminal vesicle and bladder in adult C57BL/6 mice. Tissues including pelvic organs and DRGs were harvested at post-application day 7. Prostatic inflammation was induced by trans-urethral instillation of uropathogenic E.coli 1677. Cystitis was prevented by continuous administration of nitrofurantoin (NTF). We performed metabolic cage tests to determine voiding behavior, while using H&E staining and bacterial culture to validate our animal model. RESULTS: Our study clearly demonstrates that prostate and bladder share afferent innervation via convergent DRGs in spinal segment T13, L1, L2, L6 and S1. Mice inoculated with E.coli + NTF exhibited bacterial infection and intense inflammation in the prostate while the bladder exhibited neither bacterial infection nor evidence of inflammation. Mice in E.coli + NTF group showed significantly increased voiding frequency and decreased volume per void as compared to a control group. CONCLUSIONS: These observations support the hypothesis that prostatic inflammation can induce abnormal voiding behavior by pelvic cross-sensitization. Source of Funding: R01DK075700
MP19-16 PROTEASE ACTIVATED RECEPTOR-3 EXPRESSION IS DECREASED IN HUMAN BENIGN PROSTATIC HYPERPLASIA Tristan Nicholson*, Tyler Bauman, Priyanka Sehgal, Madison, WI; Tihomir Miralem, Rochester, NY; Wei Huang, William Ricke, Madison, WI INTRODUCTION AND OBJECTIVES: While the cause of abnormal prostate growth in benign prostatic hyperplasia (BPH) remains incompletely understood, it is likely that growth factors secreted by the stroma promote epithelial growth. Protease activated receptors (PARs) are G-protein coupled receptors with diverse biologic functions, that have been shown to enhance prostate cell proliferation, and induce production of fibroblast growth factors. While PAR-1 and PAR-2 have been studied in BPH, PAR-3 expression has not been previously evaluated in the prostate. Therefore, we investigated expression of PAR-3 in human BPH. METHODS: We performed multiplexed immunohistochemistry to detect PAR-3 in normal prostate tissue (96 cores from 52 patients) and BPH (n ¼ 48 cores from 24 patients) on a tissue microarray. We used a multispectral imaging platform for automated scanning, tissue, cell and compartment segmentation and marker quantification. RESULTS: In the epithelium of BPH cores, we observed a decrease in nuclear PAR-3 expression (-40%, P < 0.0001) and cytoplasmic expression (-41%, P < 0.0001). In the stroma, we found that PAR-3 expression was also decreased in BPH in the nucleus (-35%, P < 0.0001) and cytoplasm (-15%, P ¼ 0.01), relative to normal prostate tissue. CONCLUSIONS: In contrast to other reports about PAR-1 and PAR-2 expression in BPH, we found nuclear and cytoplasmic PAR-3 expression is decreased in the stroma and epithelium of BPH. To our knowledge, this is the first characterization of PAR-3 expression in BPH. Source of Funding: F30DK093173
R01DK093690,
T32GM07356,
e194
BPH+SEs groups received daily oral doses of SE (228 and 457 mg/kg) for 5 weeks. After 5 weeks, all rats were sacrificed and the prostates and blood were collected, used for evaluation of oxidative stress, apoptosis, and the activity of 5-alpha reductase. RESULTS: BPH group showed a markedly increased prostate weight than in the control group, whereas rats in BPH+SEs groups showed a decreased prostate weight. The oxidative stress markers, activity of superoxide dismutase in serum and the level of 8-hydroxy2-deoxyguanosine, and the activity of 5-alpha reductase in serum and prostate were significantly higher in BPH group compared to the control group and it was reduced in the SE treated groups. Also, the concentration of caspase-3 was significantly increased in BPH group compared to the control group and it was decreased in BPH+SEs groups. CONCLUSIONS: These results showed that SE is effective in decreasing the volume and suppressing the proliferation of the prostate. We suggest that SE may have a potency to replace or assist the medicine now in use for the treatment of BPH. Source of Funding: none
MP19-14 POST TURP STRICTURE! UROLOGIST’S DILEMMA - CAN WE PREVENT THEM? e A RESEARCH PERSEPECTIVE. Suresh Patankar, Suresh Patankar*, Pune, India INTRODUCTION AND OBJECTIVES: Incidence of urethral stricture (US) is common problem after TURP surgery. The formation of US is due to fibrosis of connective tissue rich in collagen type I, due to up regulation of CTFF expression and is closed to scar formation. Usually causes of urethral stricture following TURP are from urological procedures and manipulation of the urethra like surgical instrumentation, catheter trauma, prolonged endoscopic surgeries, etc. Presently various preclinical studies are being carried out using animal models to understand the mechanism and prevention of US. Halofuginone (HF) derived from Chinese herb inhibits periurethral type I collagen deposition and helps in prevention of US in animal model. In this presentation results of phase II clinical study carried out on the novel herbal formulation for prevention of US post TURP are presented. METHODS: The formulation Anuradha oil (AO) was prepared from Curcuma longa Rhizomes, Glycyrrhiza glabra Rhizomes, Hamiltonia suaveoleans Stem bark, Typha angustifolia flowers, Azadirchta indica leaves, using Sesamum indicum Seed oil as base and or pig fat in certain proportion. The preclinical safety and efficacy on various wound size was carried out using OECD guidelines in rodents. A prospective, phase II, randomized, double arm Controlled clinical studies in 128 patients (n¼64) following TURP was conducted after the approval of Institutional Ethics Committee. The treatment group received 2.5 ml of AO while control received vehicle for 3 to 12 weeks. The gland size, resection time, procedure and catheter duration was kept more or less same. Assessment for Dysuria was done by VAS, rate of stricture formation by Endoscopic examination and IPSS score at 3, 6 and 12 Weeks. The results were analyzed by Chi-Square Test using 2013 Graph Pad Software, Inc. RESULTS: The preclinical studies revealed no untoward reaction after application of AO for 28 days using OECD guidelines in rodents. Clinically there was no statistically significant difference in gland size, resection time, procedure & catheterization duration and IPSS score in control and AO treated group. However, the incidence of dysuria and stricture rate was found to be significantly less at Day 1 (p<0.002), 3 weeks (p<0.03, p< 0.02), 6 and 12 weeks (p<0.04 & p< 0.05, and p< 0.04 & p<0.03) in AO treatment group as compared to control group respectively. CONCLUSIONS: AO showed encouraging results to prevent US in Post TURP patients; however, phase III study in large sample size is needed before final conclusion. Source of Funding: none
Vol. 191, No. 4S, Supplement, Saturday, May 17, 2014
MP19-15 PROSTATIC INFLAMMATION TRIGGERS VOIDING DYSFUNCTION BY NEURAL CROSS-TALK. Sanghee Lee*, Guang Yang, Jerry Gipp, Wade Bushman, Madison, WI INTRODUCTION AND OBJECTIVES: A high incidence of prostatic inflammation in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) has been previously reported. We postulate that prostatic inflammation sensitizes afferent fibers from the bladder resulting in changes in bladder function. We show here that afferent innervation of the bladder and prostate originate from overlapping groups of dorsal root ganglia and that prostatic inflammation induces increased urinary frequency. METHODS: A retro-grade neuro-tracer Fast Blue was applied to each of the prostate lobes, anterior, dorsal-lateral and ventral as well as the seminal vesicle and bladder in adult C57BL/6 mice. Tissues including pelvic organs and DRGs were harvested at post-application day 7. Prostatic inflammation was induced by trans-urethral instillation of uropathogenic E.coli 1677. Cystitis was prevented by continuous administration of nitrofurantoin (NTF). We performed metabolic cage tests to determine voiding behavior, while using H&E staining and bacterial culture to validate our animal model. RESULTS: Our study clearly demonstrates that prostate and bladder share afferent innervation via convergent DRGs in spinal segment T13, L1, L2, L6 and S1. Mice inoculated with E.coli + NTF exhibited bacterial infection and intense inflammation in the prostate while the bladder exhibited neither bacterial infection nor evidence of inflammation. Mice in E.coli + NTF group showed significantly increased voiding frequency and decreased volume per void as compared to a control group. CONCLUSIONS: These observations support the hypothesis that prostatic inflammation can induce abnormal voiding behavior by pelvic cross-sensitization. Source of Funding: R01DK075700
MP19-16 PROTEASE ACTIVATED RECEPTOR-3 EXPRESSION IS DECREASED IN HUMAN BENIGN PROSTATIC HYPERPLASIA Tristan Nicholson*, Tyler Bauman, Priyanka Sehgal, Madison, WI; Tihomir Miralem, Rochester, NY; Wei Huang, William Ricke, Madison, WI INTRODUCTION AND OBJECTIVES: While the cause of abnormal prostate growth in benign prostatic hyperplasia (BPH) remains incompletely understood, it is likely that growth factors secreted by the stroma promote epithelial growth. Protease activated receptors (PARs) are G-protein coupled receptors with diverse biologic functions, that have been shown to enhance prostate cell proliferation, and induce production of fibroblast growth factors. While PAR-1 and PAR-2 have been studied in BPH, PAR-3 expression has not been previously evaluated in the prostate. Therefore, we investigated expression of PAR-3 in human BPH. METHODS: We performed multiplexed immunohistochemistry to detect PAR-3 in normal prostate tissue (96 cores from 52 patients) and BPH (n ¼ 48 cores from 24 patients) on a tissue microarray. We used a multispectral imaging platform for automated scanning, tissue, cell and compartment segmentation and marker quantification. RESULTS: In the epithelium of BPH cores, we observed a decrease in nuclear PAR-3 expression (-40%, P < 0.0001) and cytoplasmic expression (-41%, P < 0.0001). In the stroma, we found that PAR-3 expression was also decreased in BPH in the nucleus (-35%, P < 0.0001) and cytoplasm (-15%, P ¼ 0.01), relative to normal prostate tissue. CONCLUSIONS: In contrast to other reports about PAR-1 and PAR-2 expression in BPH, we found nuclear and cytoplasmic PAR-3 expression is decreased in the stroma and epithelium of BPH. To our knowledge, this is the first characterization of PAR-3 expression in BPH. Source of Funding: F30DK093173
R01DK093690,
T32GM07356,