Phosphodiesterases as therapeutic targets.
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Biomedical subjects
Publications and source records attributed to Zhong-Cheng Xin.
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PURPOSE: We identify whether tachyphylaxis and priapism effects of sildenafil are related to regulation of phosphodiesterase-5 (PDE-5) expression. MATERIALS AND METHODS: Cavernous smooth muscle cells (CSMCs) were isolated from young rats and treated with 0, 1, 10 and 25 microM sildenafil with or without 100 microM of sodium nitroprusside for 3 and 7 days. The cells were subjected to reverse transcriptase-polymerase chain reaction and Western blot analysis for PDE-5 expression. Plasmid constructs carrying PDE-5A1 and PDE-5A2 promoters were transfected into COS-7 cells, treated with 25 microM sildenafil and analyzed for promoter activities. To simulate priapism, CSMCs were cultured under anoxia or hypoxia and then analyzed for PDE-5 expression. Furthermore, rats underwent bilateral pudendal arterial ligation for 1 day to 14 weeks, and corpus cavernous tissues were subjected to reverse transcriptase-polymerase chain reaction analysis for PDE-5 expression. RESULTS: Up-regulation of PDE-5 was noted in CSMCs treated with 25 microM sildenafil for 7 days. PDE-5 messenger RNA and protein levels were significantly increased in the 7-day sildenafil treated cultures. Sodium nitroprusside appeared to down-regulate PDE-5 expression. Sildenafil significantly increased the activities of PDE-5A1 promoter. PDE-5 expression was significantly reduced under anoxia and hypoxia. The corpus cavernous tissue showed a gradual decrease in PDE-5 expression under ischemia. CONCLUSIONS: Repeated treatment with sildenafil at high concentrations was needed to simulate tachyphylaxis in our cell culture system. Adequate oxygenation was important for PDE-5 expression. Thus, sicklemic patients may express PDE-5 at abnormally low levels, predisposing them at risk of stuttering priapism.
OBJECTIVES: To investigate the correlation between corpus cavernosum disruption and high-flow priapism for the understanding of high-flow priapism and its treatment. METHODS: To report the clinical data of a case of spontaneous idiopathic high-flow priapism. RESULTS: The diagnosis was made as right cavernosal artery disruption after angiography. The result of cavernosal blood gas analysis was normal. The penis became detumescent after the gelatin embolization treatment was performed. CONCLUSIONS: Spontaneous high-flow priapism of old people(non-ischemic) is rare in clinic. Blood gas analysis and angiography are needed to find the hemorrhage site when conservative treatment fails. Gelatin embolization or cavernosal artery ligation are usually effective in the subsequent treatment.
OBJECTIVES: The physicians knowledge and attitude to erectile dysfunction (ED) is very important to the diagnosis and management of this disease. We investigated the physicians and practitioners knowledge of ED, attitude to ED, and if they actively find the underlying ED patients. METHODS: Three hundreds and one physicians and practitioners in Beijing completed a questionnaire. The subjects included urologists, cardiologists, endocrinologists, surgeons, orthopaedicians and community practitioners. RESULTS: The definition of ED was well known by most subjects (83.4%). Many agreed that ED was a common condition in the aging men (85.0%), and it was an important health problem (78.7%) and it was the local signs of certain systemic diseases (89.7%). The most common risk factors of ED enumerated by the physicians were diabetes (45.5%), hypertension (12.6%) and coronary artery diseases (12.0%). 45.5% physicians met the patients who initiated questions about ED. 32.6% physicians would discuss ED with the patients if the patients initiate questions about ED. 95.0% non-urological physicians would refer the ED patients to urologists or andrologists. 43.5% of all the physicians never asked their patients about erectile function, this proportions in the subgroups of urologists, non-urological physicians and community practitioners were 7.2%, 55.3% and 60.5% respectively (P < 0.01). The most common reasons for the physicians not to initiate the inquiries about ED was "the patients would not have ED if they didnt complain about it" (42.2%), "there was no ED patients in my specialty" (20.9%), "diagnosis and treatment of ED was not my business" (17.3%), "have no time" (15.6%), "feel embarrassed" (13.6%). CONCLUSIONS: Most physicians regarded ED as an important health problem and a common condition in aging men, but they didnt take an active attitude to ED in their clinical practice.
Molecular biologic research on erectile dysfunction (ED), especially the elucidation of NO-cGMP signaling pathway which plays an important role on modulating corpus cavernosum smooth muscle dilation, has been made the great advance in past ten years. The further research on the penile erection related genes including nitric oxide synthase (NOS), phosphodiesterases (PDEs), K+ channal, insulin-like growth factor (IGF), heme oxygenase (HO), vascular endothelial growth factor (VEGF), cyclic GMP-dependent kinase (cGK I), angiotensin converting enzyme (ACE) and growth factor (GF) etc, has given the theoretical evidence for the clinical treatment of ED in future.