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MP89-08 POST-FINASTERIDE SYNDROME: REAL OR IMAGINED?
THE JOURNAL OF UROLOGYâ
Vol. 195, No. 4S, Supplement, Tuesday, May 10, 2016
determined diabetic rats randomly got intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs or MTs. Another eight normal rats equally received IC injection of PBS. MTs were generated with a hanging drop method and the injected cells were tracked in ADSCs and MTs injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. RESULTS: MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and tumour necrosis factor-stimulated gene 6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment better improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle and endothelial contents in diabetic rats, ameliorated local inflammation in CC. CONCLUSIONS: IC injection of MTs improves the erectile function and histopathological changes in streptozotocin-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors. Source of Funding: This work is supported by the National Natural Science Fundation of China: No. 81270693.
MP89-07 THE MECHANISMS OF NANOPARTICLE IMPROVING ADIPOSE DERIVED STEM CELLS THERAPY FOR ERECTILE DYSFUNCTON Haocheng Lin*, beijing, China, People’s Republic of; Nadeem Dhanani, Hubert Tseng, Glauco Souza, Grace Wang, Yanna Cao, Tien Ko, HOUSTON, TX; Hui Jiang, beijing, China, People’s Republic of; Run Wang, HOUSTON, TX INTRODUCTION AND OBJECTIVES: We previously reported a novel nanotechnology improved stem cell therapy in an animal model by retaining stem cells in the corpus cavernosum (CC) after intracavernosal injection (ICI). The present study was designed to look at the underlying mechanisms. METHODS: Adipose-derived stem cells (ADSCs) were magnetized with magnetic nanoparticles (NanoShuttle) to create NanoADSCs. 1X106 cells/rat injection dosage was set. 40 SD rats were performed bilateral cavernous nerve crush (BCNC) and were randomly assigned into 4 groups: BCNC, BCNC + ADSCs ICI, BCNC + NanoADSCs ICI, and BCNC + Nano-ADSCs ICI + magnet. Intracavernous pressure (ICP) and mean arterial pressure (MAP) was tested on the 28 days post ICI. Then, the penile tissues were collected for immunohistochemistry and western blot. RESULTS: ICP/MAP was significantly increased in NanoADSCs ICI + magnet group compared with other three groups. The expressions of a smooth muscle actin (aSMA), vascular endothelial growth factor (VEGF), transforming growth factor-b1 (TGFb1) and platelet endothelial cell adhesion molecule (PECAM-1) in the NanoADSCs group were significantly higher than other groups in western blot. New cell hyperplasia can be found in CC with increased express TGFb1, PECAM-1 and aSMA in histology. The increased TGFß1 expression was located in the hyperplasia area. CONCLUSIONS: Retaining of ADSCs by nanoparticle in CC improved erectile function in BCNC rat model. The underlying mechanisms may relate to the tissue repair and paracrine effect of the stem cells. The stem cells excess in CC may responsible for fibrosis in new cell hyperplasia area. Optimizing stem cells injection dosage is needed to exert best therapy effect. Source of Funding: This research was supported by a research grant from the Sexual Medicine Society of North America.
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MP89-08 POST-FINASTERIDE SYNDROME: REAL OR IMAGINED? Michael Butcher, Wesley Baas*, Aye Lwin, Bradley Holland, Michelle Herberts, Joseph Clemons, Kristin Delfino, Springfield, IL; Stanley E Althof, West Palm Beach, FL; Tobias S Kohler, Kevin T McVary, Springfield, IL INTRODUCTION AND OBJECTIVES: Post-finasteride syndrome (PFS) has recently been recognized as a medical disorder comprising a cluster of sexual, physical, and psychological/neurologic symptoms associated with 5-alpha reductase inhibitor (5ARI) use with purported persistent symptoms despite cessation of drug usage. The aim of this study was to help quantify reports, create a demographic of patient reports, and assess the cluster of symptoms to correlate consistency of the PFS complaints. METHODS: We collected the entire dataset of 3,295 Food and Drug Administration Adverse Event Reporting System (FAERS) cases that were submitted from April 2011 to October 2014 on all 5ARIs. We then evaluated the single-dose 5ARI monotherapies and analyzed these cases for symptoms and side effects associated with different doses. RESULTS: 2,048 monotherapy cases using 5ARIs were identified with 1581 being finasteride 1mg, 240 5mg, and 226 of unreported doses. Overall there was an increase event reporting as time progressed with the majority of these involving the 1mg dose. Finasteride was associated with many sexual side effects: decreased libido, ejaculatory disorder, erectile dysfunction, testicular atrophy, orgasmic disorders, hypogonadism, and overall increased sexual complaints. Other common complaints were dermatologic in nature (dry skin or thinning of skin) as well as changes in metabolism (weight gain, elevated glucose, and elevated lipids). Psychological/neurologic conditions of self-harm (suicide), slow cognition, psychological pathologies, emotional anhedonia, insomnia and overall psychological symptoms were prevalent with finasteride use. One mg of finasteride demonstrated more adverse events than the 5mg in the following areas: sexual dysfunction, libido decrease, ejaculation disorders, erectile dysfunction, testicular atrophy, hypogonadism, skin abnormalities, metabolic abnormalities, self-harm, slow cognition, depression, anxiety, emotional anhedonia, and insomnia. Dutasteride was never reported to cause a PFS-like symptom. CONCLUSIONS: FAERS data suggests that finasteride is associated with a diverse collection of symptoms, particularly in the 1 mg dosage. Dutasteride was not implicated for PFS, resulting in only one AE report. Whether or not PFS is real or imagined is not discernable within this context and database. Source of Funding: None
MP89-09 STROMAL DERIVED FACTOR-1 TREATMENT AUGMENTS NERVE REGENERATION VIA CXCR4 ACTIVATION OF NEUROTROPHIC FACTORS IN THE MAJOR PELVIC GANGLION IN A DOSEDEPENDENT FASHION Nikolai Sopko*, Hotaka Matsui, Max Kates, Denver Lough, Xiaopu Liu, Baltimore, MD; Emmanuel Weyne, Maarten Albersen, Leuven, Belgium; Kenneth Pienta, Trinity Bivalacqua, Baltimore, MD INTRODUCTION AND OBJECTIVES: SDF1 is a potent chemoattractant with endogenous neurotrophic and angiogenic properties, which acts through binding of its receptors CXCR4 and CXCR7. Its role in peripheral nerve regeneration is unknown. We used the major pelvic ganglion (MPG) explant model to investigate its effects on axonal regeneration of autonomic neurons. METHODS: MPGs from male Sprague-Dawley rats (300-350g, n¼5/group) were cultured in Matrigel with serum-free media with and without SDF1 (125ng/mL or 500ng/mL) or with SDF1 (500ng/mL) and the CXCR4 antagonist AMD3100 (5uM). Media/drugs were changed daily. Neurite lengths were measured at 24, 48, and 72 hours. MPGs
Vol. 195, No. 4S, Supplement, Tuesday, May 10, 2016
determined diabetic rats randomly got intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs or MTs. Another eight normal rats equally received IC injection of PBS. MTs were generated with a hanging drop method and the injected cells were tracked in ADSCs and MTs injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. RESULTS: MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and tumour necrosis factor-stimulated gene 6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment better improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle and endothelial contents in diabetic rats, ameliorated local inflammation in CC. CONCLUSIONS: IC injection of MTs improves the erectile function and histopathological changes in streptozotocin-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors. Source of Funding: This work is supported by the National Natural Science Fundation of China: No. 81270693.
MP89-07 THE MECHANISMS OF NANOPARTICLE IMPROVING ADIPOSE DERIVED STEM CELLS THERAPY FOR ERECTILE DYSFUNCTON Haocheng Lin*, beijing, China, People’s Republic of; Nadeem Dhanani, Hubert Tseng, Glauco Souza, Grace Wang, Yanna Cao, Tien Ko, HOUSTON, TX; Hui Jiang, beijing, China, People’s Republic of; Run Wang, HOUSTON, TX INTRODUCTION AND OBJECTIVES: We previously reported a novel nanotechnology improved stem cell therapy in an animal model by retaining stem cells in the corpus cavernosum (CC) after intracavernosal injection (ICI). The present study was designed to look at the underlying mechanisms. METHODS: Adipose-derived stem cells (ADSCs) were magnetized with magnetic nanoparticles (NanoShuttle) to create NanoADSCs. 1X106 cells/rat injection dosage was set. 40 SD rats were performed bilateral cavernous nerve crush (BCNC) and were randomly assigned into 4 groups: BCNC, BCNC + ADSCs ICI, BCNC + NanoADSCs ICI, and BCNC + Nano-ADSCs ICI + magnet. Intracavernous pressure (ICP) and mean arterial pressure (MAP) was tested on the 28 days post ICI. Then, the penile tissues were collected for immunohistochemistry and western blot. RESULTS: ICP/MAP was significantly increased in NanoADSCs ICI + magnet group compared with other three groups. The expressions of a smooth muscle actin (aSMA), vascular endothelial growth factor (VEGF), transforming growth factor-b1 (TGFb1) and platelet endothelial cell adhesion molecule (PECAM-1) in the NanoADSCs group were significantly higher than other groups in western blot. New cell hyperplasia can be found in CC with increased express TGFb1, PECAM-1 and aSMA in histology. The increased TGFß1 expression was located in the hyperplasia area. CONCLUSIONS: Retaining of ADSCs by nanoparticle in CC improved erectile function in BCNC rat model. The underlying mechanisms may relate to the tissue repair and paracrine effect of the stem cells. The stem cells excess in CC may responsible for fibrosis in new cell hyperplasia area. Optimizing stem cells injection dosage is needed to exert best therapy effect. Source of Funding: This research was supported by a research grant from the Sexual Medicine Society of North America.
e1139
MP89-08 POST-FINASTERIDE SYNDROME: REAL OR IMAGINED? Michael Butcher, Wesley Baas*, Aye Lwin, Bradley Holland, Michelle Herberts, Joseph Clemons, Kristin Delfino, Springfield, IL; Stanley E Althof, West Palm Beach, FL; Tobias S Kohler, Kevin T McVary, Springfield, IL INTRODUCTION AND OBJECTIVES: Post-finasteride syndrome (PFS) has recently been recognized as a medical disorder comprising a cluster of sexual, physical, and psychological/neurologic symptoms associated with 5-alpha reductase inhibitor (5ARI) use with purported persistent symptoms despite cessation of drug usage. The aim of this study was to help quantify reports, create a demographic of patient reports, and assess the cluster of symptoms to correlate consistency of the PFS complaints. METHODS: We collected the entire dataset of 3,295 Food and Drug Administration Adverse Event Reporting System (FAERS) cases that were submitted from April 2011 to October 2014 on all 5ARIs. We then evaluated the single-dose 5ARI monotherapies and analyzed these cases for symptoms and side effects associated with different doses. RESULTS: 2,048 monotherapy cases using 5ARIs were identified with 1581 being finasteride 1mg, 240 5mg, and 226 of unreported doses. Overall there was an increase event reporting as time progressed with the majority of these involving the 1mg dose. Finasteride was associated with many sexual side effects: decreased libido, ejaculatory disorder, erectile dysfunction, testicular atrophy, orgasmic disorders, hypogonadism, and overall increased sexual complaints. Other common complaints were dermatologic in nature (dry skin or thinning of skin) as well as changes in metabolism (weight gain, elevated glucose, and elevated lipids). Psychological/neurologic conditions of self-harm (suicide), slow cognition, psychological pathologies, emotional anhedonia, insomnia and overall psychological symptoms were prevalent with finasteride use. One mg of finasteride demonstrated more adverse events than the 5mg in the following areas: sexual dysfunction, libido decrease, ejaculation disorders, erectile dysfunction, testicular atrophy, hypogonadism, skin abnormalities, metabolic abnormalities, self-harm, slow cognition, depression, anxiety, emotional anhedonia, and insomnia. Dutasteride was never reported to cause a PFS-like symptom. CONCLUSIONS: FAERS data suggests that finasteride is associated with a diverse collection of symptoms, particularly in the 1 mg dosage. Dutasteride was not implicated for PFS, resulting in only one AE report. Whether or not PFS is real or imagined is not discernable within this context and database. Source of Funding: None
MP89-09 STROMAL DERIVED FACTOR-1 TREATMENT AUGMENTS NERVE REGENERATION VIA CXCR4 ACTIVATION OF NEUROTROPHIC FACTORS IN THE MAJOR PELVIC GANGLION IN A DOSEDEPENDENT FASHION Nikolai Sopko*, Hotaka Matsui, Max Kates, Denver Lough, Xiaopu Liu, Baltimore, MD; Emmanuel Weyne, Maarten Albersen, Leuven, Belgium; Kenneth Pienta, Trinity Bivalacqua, Baltimore, MD INTRODUCTION AND OBJECTIVES: SDF1 is a potent chemoattractant with endogenous neurotrophic and angiogenic properties, which acts through binding of its receptors CXCR4 and CXCR7. Its role in peripheral nerve regeneration is unknown. We used the major pelvic ganglion (MPG) explant model to investigate its effects on axonal regeneration of autonomic neurons. METHODS: MPGs from male Sprague-Dawley rats (300-350g, n¼5/group) were cultured in Matrigel with serum-free media with and without SDF1 (125ng/mL or 500ng/mL) or with SDF1 (500ng/mL) and the CXCR4 antagonist AMD3100 (5uM). Media/drugs were changed daily. Neurite lengths were measured at 24, 48, and 72 hours. MPGs