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INTRODUCTION AND OBJECTIVES: We have previously demonstrated in animal models that priapism is associated with upregulated expression of the opiorphin gene in corporal smooth muscle (CSM) tissue. In this study we have examined if hypoxia is a determining factor for up-regulated opiorphin expression in CSM, and if the up-regulation of opiorphin regulates other pathways associated with development of priapism. The hypothesis that vascular occlusion and ischemia is a mechanism for the development of vascular diseases associated with sickle cell disease dates back to 1948, although most recent studies have considered priapism to be a result from an imbalance between the “relaxant” and “constrictor” pathways causing heightened relaxation of CSM. METHODS: We have used an in vitro model of hypoxia to determine the genes expression in rat CSM of the rat opiorphin homologue (sialorphin, encoded by the vcsa1 gene) and two other genes associated with the development of priapism (adenosine 2 binding receptor, a2br, and hypoxia induced factor 1a, hif1a). We have looked at the expression of these genes in the CSM from a pre-priapic and priapic sickle cell mouse model. RESULTS: We demonstrate that hypoxia causes up-regulated expression of vcsa1, a2br and hif1a in CSM cells. However, when these cells are pretreated with siRNA against vcsa1 then hypoxia-induced upregulation of a2br and hif1a expression is prevented, suggesting that vcsa1 is important in the regulation of these genes. In the CSM of sickle cell mice the mouse opiorphin homologue is up-regulated in a pre-priapic life stage. The early up-regulation of the mouse opiorphin suggests that this is a response to the hypoxic conditions resulting from sickle cell disease rather than a response to priapism. CONCLUSIONS: Overall our results suggest that sickle cell disease causes hypoxia/ischemia in CSM tissue, resulting in increased opiorphin expression. Opiorphin then acts as a master regulator of compensatory smooth muscle “relaxant” pathways. It is the excessive activation of these “relaxant” pathways that results in priapism. In many aspects this hypothesis connects the 60 year old hypothesis that ischemia associated with sickle cell disease is a mechanism for the development of vascular diseases to the more recent studies where activation of relaxant pathways in corporal tissue are considered a primary mechanism for the development of priapism.

Purpose: Atropine has been used to block cholinergic neurotransmission in basic research and has received recent interest clinically in the intracavernosal pharmacotherapy of erectile dysfunction. It has been suggested that at a low dose (10-8 M), atropine blocks muscarinic receptors, and that at a large dose (10-3 M), it induces the release of EDRF. However, no report has supported this idea experimentally. We tried to confirm the action of atropine in cavernosal tissue and define its mechanism.Materials and Methods: Strips of rabbit corpus cavernosum were mounted in organ chambers. On the precontracted muscle strips with phenylephrine (PHE; 5 x 10-6 M), atropine was treated with increasing concentration from 10-11 M. The relaxing activity of atropine was observed in deendothelialized tissue and preparation with treatment with methylene blue (10-4 M), pyrogallol (10-4 M), NW-nitro-L-arginine (L-NNA; 3 x 10-4 M) and indomethacin (10-4 M). To evaluate the relationship of atropine to Ca++, the muscl...

INTRODUCTION AND OBJECTIVES: Mirodenafil is a newly developed selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED).To evaluate the efficacy, safety and tolerability of mirodenafil in the treatment of erectile dysfunction(ED) in Korean men with diabetes. METHODS: A multicenter, randomized, double-blind, placebocontrolled, parallel-group, fixed-dose study was conducted with 112 subjects who were randomized to either placebo or mirodenafil 100 mg on demand for 12 weeks. Primary efficacy variable was the erectile function (EF) domain scores of the International Index of Erectile Dysfunction (IIEF) questionnaire. Secondary efficacy variables included change in the scores of IIEF question 3 and 4 (IIEF Q3 and Q4) from baseline, change in all domain scores in the IIEF from baseline, Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), the Global Assessment Question (GAQ) and the Life Satisfaction Checklist (LSC). RESULTS: After 12 weeks of treatment, mirodenafil group showed significantly greater change in the IIEF-EF domain score from baseline compared to placebo group (9.3 vs. 1.4, P 0.0001). The changes from baseline in the mirodenafil group in IIEF Q3 (1.7 vs. 0.4, P 0.0001) and Q4 (1.7 vs. 0.3, P 0.0001) were higher compared to the placebo group. Differences between the mirodenafil and placebo groups were significant in the SEP2 (82.0% vs. 55.2%, P 0.0003), SEP3 (68.9% vs. 22.3%, P 0.0001). Difference in GAQ i°YESi responses was also significant (76.9% vs. 19.1%, P 0.0001). Normal EF domain scores (iA26) at study end were achieved by 32.7% and 9.4% in the mirodeniafl and placebo groups, respectively (P 0.0031). As for LSC scores, the mirodenafil group showed significantly greater improvements in sexual life and partner relationship than the placebo group. Most treatment-associated AEs were mild that resolved spontaneously. CONCLUSIONS: Mirodenafil is an effective and well-tolerated agent for the treatment of diabetic patients with ED in Korea.

To clarify the correlation between erotic and nocturnal erections, and to evaluate the diagnostic efficacy of the audiovisual stimulation penogram as an initial screening test for impotent patients, a comparative study of 137 impotent patients was designed. The audiovisual stimulation penogram shows dynamic penile blood flow change during audiovisual stimulation using a radioisotope (99mtechnetium) and is classified as type 1--similar findings to normal volunteers, type 2A--impossible erection due to insufficient blood flow, type 2B--unstable erection due to severe fluctuation in blood flow and type 2C--delayed erection. The compatibility ratios of the audiovisual stimulation penogram types 1, 2A and 2C with some tests for nocturnal erection were relatively high (63 to 80%) and when compared to the final diagnosis all but 1 of the compatible cases with nocturnal erection studies were able to be diagnosed correctly. However, the compatibility ratio of the audiovisual stimulation penogram type 2B was markedly low (35%) and this group had complicated etiologies, including many more psychogenic than organic causes. Although the mechanisms of the erotic and nocturnal erections have not been fully elucidated to date, our results suggest that the audiovisual stimulation penogram seems to be an appropriate initial screening step if we refine the criteria for type 2B, and a comprehensive interpretation of the tests for erotic and nocturnal erections will result in a more accurate diagnosis.

Purpose: The change in arterial flow velocity with age in patients with a normal response to pharmacological injection was evaluated.Materials and Methods: We studied 64 patients with erectile dysfunction who responded well to intracavernous injection of 10 micro g. prostaglandin E1 with well sustained penile rigidity for longer than 1 hour and normal cavernous arterial flow velocities on color Doppler ultrasonography. The men were classified into 4 groups according to age younger than 30 years, and 30 to 39, 40 to 49 and 50 years old or older. Flow parameters were compared.Results: The statistically significant decreasing tendency of peak systolic velocity with age was revealed by a simple regression test (p = 0.003). The greatest decrease was observed between patients in the third and fourth decades. When comparing the peak systolic velocity according to timing of measurement, the greatest velocities occurred at later measurements after the fifth decade, while in younger patients these values we...

Purpose: We investigated penile sensory levels in patients with primary premature ejaculation to determine whether there is an etiological basis for this condition.Materials and Methods: Penile biothesiometry was performed in 120 patients with primary premature ejaculation without erectile dysfunction and neurological deficit, and in 66 normal potent male volunteers. Vibratory thresholds were recorded at the glans penis, penile shaft, scrotum and index finger using a biothesiometer.Results: On the glans penis and penile shaft the values in patients with premature ejaculation were significantly less than those in normal potent men (p less than 0.001). In normal potent men an age dependency of biothesiometric parameters was noted, with a significant increase in vibratory threshold at the glans penis and penile shaft in older patients. However, in patients with premature ejaculation there were consistently decreased values without age dependency at the glans penis and penile shaft (p greater than 0.0...