- Email: [email protected]
MP68-05 COMPARISON OF THE EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NERVE GROWTH FACTOR (NGF) INHIBITION ON BLADDER FUNCTION OF MICE WITH SPINAL CORD INJURY (SCI)
THE JOURNAL OF UROLOGYâ
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Vol. 195, No. 4S, Supplement, Monday, May 9, 2016
positively associated with MMP-2 (p¼0.0074) and MMP-9/NGAL (p<0.0001). In male UCPPS patients, none of the proteins studied were significantly correlated with either pain or urinary severity after adjustment for multiple comparisons. CONCLUSIONS: VEGF, VEGF-R1, and MMP-9 may serve as clinically useful diagnostic markers for UCPPS in males. In females, MMP-9/NGAL, MMP-2, and VEGF may inform prognosis within patients with UCPPS. Source of Funding: NIH NIDDK U01 DK103227, DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316
MP68-04 CLOCK GENES REGULATE CIRCADIAN RHYTHM OF VNUT EXPRESSION, CONNEXIN26 EXPRESSION AND STRETCHEVOKED ATP RELEASE IN THE CULTURED UROTHELIAL CELLS Tatsuya Ihara*, yamanashi, Japan; Satoru Kira, Tatsuya Miyamoto, Norifumi Sawada, Hiroshi Nakagomi, Takahiko Mitsui, Hideki Kobayashi, Mitsuharu Yoshiyama, Masayuki Takeda, Yuki Nakamura, Atsuhito Nakao, Eiji Shigetomi, Yohichi Shinozaki, Shuichi Koizumi, Chuo, Japan INTRODUCTION AND OBJECTIVES: Clock genes exist in almost all the cells and organs, and the products of Per, Cry, Bmal and Clock have the most important role to regulate circadian rhythm as representative clock genes. It has been known that lower urinary tract function is also regulated by clock genes. We previously reported that the Clock mutant mouse (ClockD19/D19) showed phenotype of nocturia (NOC) and nocturnal polyuria (NP). We hypothesis that clock genes regulate circadian rhythm of perception of the bladder fullness through the circadian expression of the ATP transmitters such as VNUT and Connexin26 in urothelium, which release ATP after mechanical stretch stimulation and send signals of urine perception to the CNS. In this study, we investigated the circadian rhythm of urine perception in mouse primary urothelial cell cultures (MPUCC), measuring the gene and protein expression of VNUT, Connexin26, and the ATP release after stretch stimulation. METHODS: MPUCC isolated from C57BL/6 mice (WT) and C57BL/6 ClockD19/D19 were used. To reset and synchronize the gene expression rhythms in each cells, 50% horse serum shock (HSS) were added for 2hrs. Samples were collected every 4hrs from 12hrs later after HSS. That time was defined as 0. The expression of major clock genes, VNUT, and Connexin26 in MPUCC was investigated by RTPCR and Western blot. Released ATP after stretch stimulation was quantified using luciferin-luciferase bioluminescence assay. Statistical analyses were done by one-way ANOVA. RESULTS: In addition to major clock genes (e.g. Per2 and Bmal1), the expressions of mRNA and proteins of VNUT and Connexin26, showed circadian rhythm in WT. Meanwhile, these circadian rhythm were disrupted in ClockD19/D19 mice. ATP release after stretch stimulation showed circadian rhythm in WT, but ClockD19/D19 lost this circadian rhythm. These oscillation changes were almost same as circadian rhythm of VNUT- and Connexin26-mRNA (Fig.1), which indicated that CLOCK could regulate the perception of bladderfullness. CONCLUSIONS: Clock genes regulate circadian rhythm of perception of the bladder fullness, and disruption of clock genes could induce NOC and NP. Redressing of abnormalities of clock genes can lead to novel treatment of NOC/NP.
Source of Funding: Astellas pharma Inc
MP68-05 COMPARISON OF THE EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NERVE GROWTH FACTOR (NGF) INHIBITION ON BLADDER FUNCTION OF MICE WITH SPINAL CORD INJURY (SCI) Naoki Wada*, Takahiro Shimizu, Shun Takai, Nobutaka Shimizu, Pradeep Tyagi, William de Groat, Anthony Kanai, Pittsburgh, PA; Hidehiro Kakizaki, Asahikawa, Japan; Naoki Yoshimura, Pittsburgh, PA INTRODUCTION AND OBJECTIVES: BDNF and NGF are reportedly involved in changes in neural pathways to induce lower urinary tract (LUT) dysfunction such as detrusor overactivity (DO) and inefficient voiding following SCI. However, it has not been well clarified how these two growth factors differentially affect storage and voiding functions after SCI. Therefore, we investigated the effects of anti-NGF or anti-BDNF antibody treatment on cystometric parameters in SCI mice. METHODS: SCI was produced by complete transection of the Th8/9 spinal cord in female C57BL/6N mice. Three weeks later, an osmotic pump was placed subcutaneously to administer vehicle (group A), 10mg/kg/hr of anti-BDNF antibody (group B) or 10mg/kg/hr of antiNGF antibody (group C) for 1 week. Four weeks after transection, SCI mice were evaluated using continuous or single-filling cystometry under an awake condition. RESULTS: In continuous cystometry, voiding efficiency was significantly increased in the groups B (21%) and C (26%) compared to the group A (14%), and postvoid residual volume (PVR) was lower in the group C (0.14ml) vs. the group A (0.25ml). There was also a tendency of the reduction in non-voiding contractions (NVC) in the group C without statistical significance. Micturition pressure (MP) or intercontraction intervals were not different among the groups. In single cystometry, voided volume (0.085 vs. 0.038 ml) and voiding efficiency (42% vs. 18%) in the group B were significantly increased compared to the group A, and PVR of the group C was lower than that of the group A (0.11 vs. 0.15 ml). MP, maximum cystometric capacity or NVC was not different among groups. CONCLUSIONS: Both anti-BDNF and anti-NGF antibody treatments improved voiding dysfunction as shown by increased voiding efficiency due to increased voided volume or decreased PVR in SCI mice. In addition, the anti-NGF, but not anti-BDNF, treatment marginally improved NVCs. These results suggest that BDNF and NGF are involved in SCI-induced voiding dysfunction resulting in inefficient voiding, but have minor roles in storage dysfunction to induce DO in mice, in contrast to the previous findings in SCI rats showing the greater contribution of bladder NGF or BDNF overexpression to DO.
THE JOURNAL OF UROLOGYâ
Vol. 195, No. 4S, Supplement, Monday, May 9, 2016
e891
MP68-07 A NOVEL MECHATRONIC INFUSION-DRAINAGE DEVICE TO ASSESS LUT FUNCTION IN NEURO-IMAGING €rich and Basel, Switzerland; Matthias Walter, Lorenz Leitner*, Zu € rg Diefenbacher, Ma €rstetten, € rich, Switzerland; Jo Johann Wanek, Zu € rich, Switzerland; Martina D. Liechti, Switzerland; Lars Michels, Zu €rich, London, United Kingdom; Thomas M. Kessler, Ulrich Mehnert, Zu Switzerland
Source of Funding: NIH P01 DK093424
MP68-06 FORMATION OF DOUBLE-STRANDED RNA ACTIVATES STRESS KINASES AND INITIATES CYTOSKELETON ORGANIZATION AND CELL DEGENERATION IN BLADDER ISCHEMIA Jing-Hua Yang, Zuohui Zhao, Han-Pil Choi, Kazem Azadzoi*, Boston, MA INTRODUCTION AND OBJECTIVES: Double-stranded RNA (ds-RNA) is RNA with two complementary strands, which is not readily detected in normal tissues but is produced as a replicative intermediate in cellular stress conditions. By binding to and activating stress kinases and inducing mRNA degradation, ds-RNA can serve as a potent stimulus to cellular and subcellular structural modifications. We examined the formation and structural consequences of ds-RNA in chronic bladder ischemia. METHODS: A rat bladder ischemia model was developed by creating aorto-iliac arteries atherosclerosis. After 8 weeks, the animals underwent metabolic cage studies then hemodynamic measurements and cystometrograms (CMG) were obtained. Bladder tissues were processed for RT-PCR of ds-RNA precursor Alu-RNA, dot blot analysis of ds-RNA formation, western blotting of ds-RNA-dependent protein kinase (PKR), mass spectrometry, ELISA of stress markers, and transmission electron microscopy (TEM). RESULTS: Chronic bladder ischemia increased micturition frequency, decreased voided volume and led to detrusor instability. Ischemia upregulated Alu-RNA expression and led to the formation of ds-RNA and activation of the stress kinase PKR in the bladder. These changes were associated with cellular lipid and protein stress markers. Accumulation of ds-RNA and phosphorylation of PKR resulted in DNA damage, loss of proteins, and activation of degenerative pathways. Mass spectrometry and Gen Ontology analysis suggested cytoskeleton organization and degenerative activities mediated by ubiquitination and increased proteolysis, peptidase and hydrolase activities. EM confirmed cytoskeleton organization and cell degeneration characterized by swollen mitochondria with disrupted membrane and decreased granules, swollen elongated ER, collagen invasion of smooth muscle cells and nerve fibers, sporadic loss of epithelial mucosal membrane, twisted smooth muscle cells, diffused vacuolization, and loss of neural structural integrity. CONCLUSIONS: We report the formation of ds-RNA and subsequent phosphorylation of PKR in bladder ischemia. Activation of dsRNA/PKR pathway in the bladder resulted in widespread structural modifications via mechanisms involving DNA damage, mRNA degradation and loss of proteins. Our data suggest a close link between dsRNA/PKR pathway, proteolysis, cytoskeleton organization and loss of cellular structural integrity. Formation of ds-RNA and activation of PKR may precede cellular ultrastructural deterioration and play a central role in loss of smooth muscle cells and neurodegeneration in the ischemic overactive bladder. Source of Funding: Supported by Grant BLR&D MERIT 1I01BX001428 from the U.S. Department of Veterans Affairs.
INTRODUCTION AND OBJECTIVES: Recent functional MRI (fMRI) studies revealed supraspinal networks involved in perception and processing of bladder distension in response to bladder filling. However, significance of supraspinal network activity and network localisations varied between studies. This might be related to the different bladder stimulation protocols used and their different level of stimulation task precision. We therefore developed a new automated, multi-configurable infusion-drainage device (IDD) to improve precision of bladder filling tasks during fMRI and to provide a base for standardization of filling protocols. METHODS: The IDD is based on electrohydrostatic actuation. The design includes a master and slave pneumatic cylinder linked over an extension hose and a motorised slider to provide force and motion. To evaluate performance quality volume delivery accuracy, i.e. estimated volume (flowrate * infusion time) vs measured volume, was tested preforming repetitive infusion-drainage cycles at different flowrates (80 to 400mL/min) and infusion times (3 to 60sec). MR-compatibility was evaluated using a proton sphere phantom. Pilot feasibility tests in healthy subjects and patients with lower urinary tract (LUT) symptoms undergoing fMRI during bladder stimulation were performed. In all subjects the bladder was prefilled through a transurethral catheter upon a persistent desire to void. The scan paradigm comprised automated, repetitive bladder filling and withdrawal of 100mL saline. RESULTS: Technical aspects: Mean volume delivery accuracy for different flowrates and filling volumes was between 99.11.2% and 99.90.2%. MR-compatibility was demonstrated with a small decrease in signal-to-noise ratio (SNR), i.e. 1.13% for anatomical and 0.54% for functional scans and a decrease of 1.76% for time-variant SNR. Device testing in volunteers: Automated, repetitive bladder filling and drainage was well tolerated by healthy subjects and patients. The paradigm elicited robust (p¼0.05, FWE-corrected) brain activity in areas known to be involved in supraspinal LUT control. A strong temporal correlation between LUT stimulation and blood oxygenation level dependent (BOLD) signal changes in such areas was detected. CONCLUSIONS: This study introduces a new MR-compatible and synchronised IDD, designed to stimulate the LUT during fMRI. High system accuracy was achieved. BOLD signal changes were in line with results from existing literature. Using this automated IDD and according standardized study protocols helps to improve precision, repeatability and comparability between studies. Source of Funding: Swiss National Science Foundation (SNSF), Wings for Life, Emily Dorothy Lagemann Stiftung
MP68-08 INHIBITION OF NEUROGENIC, CHOLINERGIC, AND ADRENERGIC CONTRACTION OF HUMAN BLADDER SMOOTH MUSCLE BY THE THROMBOXANE RECEPTOR ANTAGONIST, PICOTAMIDE Martin Hennenberg*, Yiming Wang, Frank Strittmatter, Anna Ciotkowska, Beata Rutz, Christian Stief, Christian Gratzke, Munich, Germany INTRODUCTION AND OBJECTIVES: Male lower urinary tract symptoms include storage symptoms, which are mostly caused by an overactive bladder (OAB) due to spontaneous detrusor contractions. Anticholinergic treatment represents the goldstandard of medical therapy, but discontinuation rates are high, due to disappointing efficacy and side effects. In addition to muscarinic receptors, detrusor
e890
Vol. 195, No. 4S, Supplement, Monday, May 9, 2016
positively associated with MMP-2 (p¼0.0074) and MMP-9/NGAL (p<0.0001). In male UCPPS patients, none of the proteins studied were significantly correlated with either pain or urinary severity after adjustment for multiple comparisons. CONCLUSIONS: VEGF, VEGF-R1, and MMP-9 may serve as clinically useful diagnostic markers for UCPPS in males. In females, MMP-9/NGAL, MMP-2, and VEGF may inform prognosis within patients with UCPPS. Source of Funding: NIH NIDDK U01 DK103227, DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316
MP68-04 CLOCK GENES REGULATE CIRCADIAN RHYTHM OF VNUT EXPRESSION, CONNEXIN26 EXPRESSION AND STRETCHEVOKED ATP RELEASE IN THE CULTURED UROTHELIAL CELLS Tatsuya Ihara*, yamanashi, Japan; Satoru Kira, Tatsuya Miyamoto, Norifumi Sawada, Hiroshi Nakagomi, Takahiko Mitsui, Hideki Kobayashi, Mitsuharu Yoshiyama, Masayuki Takeda, Yuki Nakamura, Atsuhito Nakao, Eiji Shigetomi, Yohichi Shinozaki, Shuichi Koizumi, Chuo, Japan INTRODUCTION AND OBJECTIVES: Clock genes exist in almost all the cells and organs, and the products of Per, Cry, Bmal and Clock have the most important role to regulate circadian rhythm as representative clock genes. It has been known that lower urinary tract function is also regulated by clock genes. We previously reported that the Clock mutant mouse (ClockD19/D19) showed phenotype of nocturia (NOC) and nocturnal polyuria (NP). We hypothesis that clock genes regulate circadian rhythm of perception of the bladder fullness through the circadian expression of the ATP transmitters such as VNUT and Connexin26 in urothelium, which release ATP after mechanical stretch stimulation and send signals of urine perception to the CNS. In this study, we investigated the circadian rhythm of urine perception in mouse primary urothelial cell cultures (MPUCC), measuring the gene and protein expression of VNUT, Connexin26, and the ATP release after stretch stimulation. METHODS: MPUCC isolated from C57BL/6 mice (WT) and C57BL/6 ClockD19/D19 were used. To reset and synchronize the gene expression rhythms in each cells, 50% horse serum shock (HSS) were added for 2hrs. Samples were collected every 4hrs from 12hrs later after HSS. That time was defined as 0. The expression of major clock genes, VNUT, and Connexin26 in MPUCC was investigated by RTPCR and Western blot. Released ATP after stretch stimulation was quantified using luciferin-luciferase bioluminescence assay. Statistical analyses were done by one-way ANOVA. RESULTS: In addition to major clock genes (e.g. Per2 and Bmal1), the expressions of mRNA and proteins of VNUT and Connexin26, showed circadian rhythm in WT. Meanwhile, these circadian rhythm were disrupted in ClockD19/D19 mice. ATP release after stretch stimulation showed circadian rhythm in WT, but ClockD19/D19 lost this circadian rhythm. These oscillation changes were almost same as circadian rhythm of VNUT- and Connexin26-mRNA (Fig.1), which indicated that CLOCK could regulate the perception of bladderfullness. CONCLUSIONS: Clock genes regulate circadian rhythm of perception of the bladder fullness, and disruption of clock genes could induce NOC and NP. Redressing of abnormalities of clock genes can lead to novel treatment of NOC/NP.
Source of Funding: Astellas pharma Inc
MP68-05 COMPARISON OF THE EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NERVE GROWTH FACTOR (NGF) INHIBITION ON BLADDER FUNCTION OF MICE WITH SPINAL CORD INJURY (SCI) Naoki Wada*, Takahiro Shimizu, Shun Takai, Nobutaka Shimizu, Pradeep Tyagi, William de Groat, Anthony Kanai, Pittsburgh, PA; Hidehiro Kakizaki, Asahikawa, Japan; Naoki Yoshimura, Pittsburgh, PA INTRODUCTION AND OBJECTIVES: BDNF and NGF are reportedly involved in changes in neural pathways to induce lower urinary tract (LUT) dysfunction such as detrusor overactivity (DO) and inefficient voiding following SCI. However, it has not been well clarified how these two growth factors differentially affect storage and voiding functions after SCI. Therefore, we investigated the effects of anti-NGF or anti-BDNF antibody treatment on cystometric parameters in SCI mice. METHODS: SCI was produced by complete transection of the Th8/9 spinal cord in female C57BL/6N mice. Three weeks later, an osmotic pump was placed subcutaneously to administer vehicle (group A), 10mg/kg/hr of anti-BDNF antibody (group B) or 10mg/kg/hr of antiNGF antibody (group C) for 1 week. Four weeks after transection, SCI mice were evaluated using continuous or single-filling cystometry under an awake condition. RESULTS: In continuous cystometry, voiding efficiency was significantly increased in the groups B (21%) and C (26%) compared to the group A (14%), and postvoid residual volume (PVR) was lower in the group C (0.14ml) vs. the group A (0.25ml). There was also a tendency of the reduction in non-voiding contractions (NVC) in the group C without statistical significance. Micturition pressure (MP) or intercontraction intervals were not different among the groups. In single cystometry, voided volume (0.085 vs. 0.038 ml) and voiding efficiency (42% vs. 18%) in the group B were significantly increased compared to the group A, and PVR of the group C was lower than that of the group A (0.11 vs. 0.15 ml). MP, maximum cystometric capacity or NVC was not different among groups. CONCLUSIONS: Both anti-BDNF and anti-NGF antibody treatments improved voiding dysfunction as shown by increased voiding efficiency due to increased voided volume or decreased PVR in SCI mice. In addition, the anti-NGF, but not anti-BDNF, treatment marginally improved NVCs. These results suggest that BDNF and NGF are involved in SCI-induced voiding dysfunction resulting in inefficient voiding, but have minor roles in storage dysfunction to induce DO in mice, in contrast to the previous findings in SCI rats showing the greater contribution of bladder NGF or BDNF overexpression to DO.
THE JOURNAL OF UROLOGYâ
Vol. 195, No. 4S, Supplement, Monday, May 9, 2016
e891
MP68-07 A NOVEL MECHATRONIC INFUSION-DRAINAGE DEVICE TO ASSESS LUT FUNCTION IN NEURO-IMAGING €rich and Basel, Switzerland; Matthias Walter, Lorenz Leitner*, Zu € rg Diefenbacher, Ma €rstetten, € rich, Switzerland; Jo Johann Wanek, Zu € rich, Switzerland; Martina D. Liechti, Switzerland; Lars Michels, Zu €rich, London, United Kingdom; Thomas M. Kessler, Ulrich Mehnert, Zu Switzerland
Source of Funding: NIH P01 DK093424
MP68-06 FORMATION OF DOUBLE-STRANDED RNA ACTIVATES STRESS KINASES AND INITIATES CYTOSKELETON ORGANIZATION AND CELL DEGENERATION IN BLADDER ISCHEMIA Jing-Hua Yang, Zuohui Zhao, Han-Pil Choi, Kazem Azadzoi*, Boston, MA INTRODUCTION AND OBJECTIVES: Double-stranded RNA (ds-RNA) is RNA with two complementary strands, which is not readily detected in normal tissues but is produced as a replicative intermediate in cellular stress conditions. By binding to and activating stress kinases and inducing mRNA degradation, ds-RNA can serve as a potent stimulus to cellular and subcellular structural modifications. We examined the formation and structural consequences of ds-RNA in chronic bladder ischemia. METHODS: A rat bladder ischemia model was developed by creating aorto-iliac arteries atherosclerosis. After 8 weeks, the animals underwent metabolic cage studies then hemodynamic measurements and cystometrograms (CMG) were obtained. Bladder tissues were processed for RT-PCR of ds-RNA precursor Alu-RNA, dot blot analysis of ds-RNA formation, western blotting of ds-RNA-dependent protein kinase (PKR), mass spectrometry, ELISA of stress markers, and transmission electron microscopy (TEM). RESULTS: Chronic bladder ischemia increased micturition frequency, decreased voided volume and led to detrusor instability. Ischemia upregulated Alu-RNA expression and led to the formation of ds-RNA and activation of the stress kinase PKR in the bladder. These changes were associated with cellular lipid and protein stress markers. Accumulation of ds-RNA and phosphorylation of PKR resulted in DNA damage, loss of proteins, and activation of degenerative pathways. Mass spectrometry and Gen Ontology analysis suggested cytoskeleton organization and degenerative activities mediated by ubiquitination and increased proteolysis, peptidase and hydrolase activities. EM confirmed cytoskeleton organization and cell degeneration characterized by swollen mitochondria with disrupted membrane and decreased granules, swollen elongated ER, collagen invasion of smooth muscle cells and nerve fibers, sporadic loss of epithelial mucosal membrane, twisted smooth muscle cells, diffused vacuolization, and loss of neural structural integrity. CONCLUSIONS: We report the formation of ds-RNA and subsequent phosphorylation of PKR in bladder ischemia. Activation of dsRNA/PKR pathway in the bladder resulted in widespread structural modifications via mechanisms involving DNA damage, mRNA degradation and loss of proteins. Our data suggest a close link between dsRNA/PKR pathway, proteolysis, cytoskeleton organization and loss of cellular structural integrity. Formation of ds-RNA and activation of PKR may precede cellular ultrastructural deterioration and play a central role in loss of smooth muscle cells and neurodegeneration in the ischemic overactive bladder. Source of Funding: Supported by Grant BLR&D MERIT 1I01BX001428 from the U.S. Department of Veterans Affairs.
INTRODUCTION AND OBJECTIVES: Recent functional MRI (fMRI) studies revealed supraspinal networks involved in perception and processing of bladder distension in response to bladder filling. However, significance of supraspinal network activity and network localisations varied between studies. This might be related to the different bladder stimulation protocols used and their different level of stimulation task precision. We therefore developed a new automated, multi-configurable infusion-drainage device (IDD) to improve precision of bladder filling tasks during fMRI and to provide a base for standardization of filling protocols. METHODS: The IDD is based on electrohydrostatic actuation. The design includes a master and slave pneumatic cylinder linked over an extension hose and a motorised slider to provide force and motion. To evaluate performance quality volume delivery accuracy, i.e. estimated volume (flowrate * infusion time) vs measured volume, was tested preforming repetitive infusion-drainage cycles at different flowrates (80 to 400mL/min) and infusion times (3 to 60sec). MR-compatibility was evaluated using a proton sphere phantom. Pilot feasibility tests in healthy subjects and patients with lower urinary tract (LUT) symptoms undergoing fMRI during bladder stimulation were performed. In all subjects the bladder was prefilled through a transurethral catheter upon a persistent desire to void. The scan paradigm comprised automated, repetitive bladder filling and withdrawal of 100mL saline. RESULTS: Technical aspects: Mean volume delivery accuracy for different flowrates and filling volumes was between 99.11.2% and 99.90.2%. MR-compatibility was demonstrated with a small decrease in signal-to-noise ratio (SNR), i.e. 1.13% for anatomical and 0.54% for functional scans and a decrease of 1.76% for time-variant SNR. Device testing in volunteers: Automated, repetitive bladder filling and drainage was well tolerated by healthy subjects and patients. The paradigm elicited robust (p¼0.05, FWE-corrected) brain activity in areas known to be involved in supraspinal LUT control. A strong temporal correlation between LUT stimulation and blood oxygenation level dependent (BOLD) signal changes in such areas was detected. CONCLUSIONS: This study introduces a new MR-compatible and synchronised IDD, designed to stimulate the LUT during fMRI. High system accuracy was achieved. BOLD signal changes were in line with results from existing literature. Using this automated IDD and according standardized study protocols helps to improve precision, repeatability and comparability between studies. Source of Funding: Swiss National Science Foundation (SNSF), Wings for Life, Emily Dorothy Lagemann Stiftung
MP68-08 INHIBITION OF NEUROGENIC, CHOLINERGIC, AND ADRENERGIC CONTRACTION OF HUMAN BLADDER SMOOTH MUSCLE BY THE THROMBOXANE RECEPTOR ANTAGONIST, PICOTAMIDE Martin Hennenberg*, Yiming Wang, Frank Strittmatter, Anna Ciotkowska, Beata Rutz, Christian Stief, Christian Gratzke, Munich, Germany INTRODUCTION AND OBJECTIVES: Male lower urinary tract symptoms include storage symptoms, which are mostly caused by an overactive bladder (OAB) due to spontaneous detrusor contractions. Anticholinergic treatment represents the goldstandard of medical therapy, but discontinuation rates are high, due to disappointing efficacy and side effects. In addition to muscarinic receptors, detrusor