Reduced corporal fibrosis to protect erectile function by inhibiting the Rho-kinase/LIM-kinase/cofilin pathway in the aged transgenic rat harboring human tissue kallikrein 1.

Our previous studies have demonstrated that erectile function was preserved in aged transgenic rats (TGR) harboring the human tissue kallikrein 1 (hKLK1), while the molecular level of hKLK1 on corporal fibrosis to inhibit age-related erectile dysfunction (ED) is poorly understood. Male wild-type Sprague-Dawley rats (WTR) and TGR harboring the hKLK1 gene were fed to 4- or 18-month-old and divided into three groups: young WTR (yWTR) as the control, aged WTR (aWTR), and aged TGR (aTGR). Erectile function of all rats was assessed by cavernous nerve electrostimulation method. Masson's trichrome staining was used to evaluate corporal fibrosis in the corpus cavernosum. We found that the erectile function of rats in the aWTR group was significantly lower than that of other two groups. Masson's trichrome staining revealed that compared with those of the yWTR and aTGR groups, the ratio of smooth muscle cell (SMC)/collagen (C) was significantly lower in the aWTR group. Immunohistochemistry and Western blotting analysis were performed, and results demonstrated that expression of α-SMA was lower, while expressions of transforming growth factor-ß 1 (TGF-ß1), RhoA, ROCK1, p-MYPT1, p-LIMK2, and p-cofilin were higher in the aWTR group compared with those in other two groups. However, LIMK2 and cofilin expressions did not differ among three groups. Taken together, these results indicated that the RhoA/ROCK1/LIMK/cofilin pathway may be involved in the corporal fibrosis caused by advanced age, and hKLK1 may reduce this corporal fibrosis by inhibiting the activation of this pathway to ameliorate age-related ED.

[Concentration of basic fibroblast growth factor in plasma and cavernous corpus of aged rat].

OBJECTIVE: To investigate the concentration of basic fibroblast growth factor (bFGF) in aged rat plasma and penile tissues. METHODS: Twelve 24-month-old rats and ten 12-week-old rats were selected. We assessed the erectile responses of rats to cavernous nerve electrostimulation. Then the concentrations of bFGF in the rats' plasma and penile tissues were detected by ELISA kit and smooth muscle contents in the rats' cavernous corpus were evaluated by masson trichrome staining. RESULTS: Compared with the young rats, we found that the erectile function of the aged rats were significantly attenuated (The Max ICP/MAP in the aged rats were 0.41±0.05, 0.44±0.04 and 0.51±0.06 at 2.5 volts, 5.0 volts and 7.5 volts respectively while the Max ICP/MAP in the normal controls were 0.70±0.06, 0.75±0.07 and 0.81±0.04 at 2.5 volts, 5 volts and 7.5 volts respectively, P<0.05). The concentrations of bFGF [The bFGF levels in plasma and penile tissues in the aged rat were (6.43±0.51) µg/L and (598.6±51.7) pg/mg protein respectively while the bFGF levels in the normal control were (10.53±0.42) µg/L and (985.8±76.8) pg/mg protein] were significantly reduced (P<0.05). Furthermore, the smooth muscle contents in the aged rats' penile tissues (0.038±0.005) were dramatically decreased compared with the normal control (0.075±0.006, P<0.05). CONCLUSION: The reduced levels of bFGF may be related to the decreased smooth muscle contents in the penile tissues of the aged rats.

[Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia].

OBJECTIVE: To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH). METHODS: Using IIEF-5, we conducted a questionnaire investigation among 210 BPH patients before and after treated by PVP (n = 80) and transurethral resection of the prostate (TURP, n = 130). We also reviewed the clinical data and compared the pre- and post-operative penile erectile function between the two groups of patients. RESULTS: Follow-up was completed in 76 cases of PVP and 123 of TURP. The baseline data showed no statistically significant differences between the two groups in age, prostate volume, IPSS, QOL, Qmax, post void urine residual volume and IIEF-5 scores (P>0.05). Compared with the IEFF-5 score at the baseline (21.88 +/- 2.46), those at 3, 6 and 12 months after PVP were 16.72 +/- 3.17, 19.34 +/- 2.46 and 19.29 +/- 2. 18, respectively, significantly decreased at 3 months (P = 0.042), but with no remarkable difference at 6 and 12 months (P >0.05). Nor were there significant differences in the IIEF-5 score between the PVP and TURP groups at any time points (P>0.05). At 6 months after surgery, the incidence rates of erectile dysfunction were 11.7% and 13.7% in the TURP and PVP groups, respectively (P>0.05). CONCLUSION: PVP may reduce erectile function in some cases in the early stage after surgery, but this adverse effect does not last long and is basically similar to that of TURP.

Effect of silencing VDR gene in kidney on renal epithelial calcium transporter proteins and urinary calcium excretion in genetic hypercalciuric stone-forming rats.

OBJECTIVE: To address the molecular mechanisms that the vitamin D receptor (VDR) in the kidney might contribute to decreased renal calcium reabsorption in idiopathic hypercalciuria using genetic hypercalciuric stone-forming (GHS) rats. METHODS: We silenced the VDR gene in the GHS and normal control (NC) rat kidney in vivo using adenovirus vector-delivered microRNA targeting VDR through renal venous transduction. On days 3-21 after injection with adenovirus, the expression levels of the VDR, calcium-sensing receptor, and epithelial calcium transporters in the kidney were detected. The urine calcium and serum calcium, phosphorus, 1,25(OH)(2)D(3), and parathyroid hormone levels were measured. RESULTS: The basal expression levels in the kidney tissues of VDR, calbindin-D(28k), and calcium-sensing receptor were significantly greater in the GHS rats than in the NC rats, and the basal expression levels of transient receptor potential vanilloid receptor subtype 5, transient receptor potential vanilloid receptor subtype 6, calbindin-D(9k), and plasma membrane calcium-adenosine triphosphatase were significantly lower in the GHS rats than in the NC rats. VDR knockdown in the kidney caused significant increase in renal transient receptor potential vanilloid receptor subtype 5, sodium/calcium exchanger, and calbindin-D(9k) expression levels in the GHS rats. The GHS rats excreted significantly more urine calcium after VDR knockdown. The serum calcium, phosphorus, parathyroid hormone, and 1,25(OH)(2)D(3) levels were not altered during the study period in the GHS and NC rats. CONCLUSION: Our findings suggest that VDR knockdown in the kidney can upregulate the expression of transient receptor potential vanilloid receptor subtype 5 in GHS rats. However, VDR depletion results in an increase in urine calcium excretion. The role of VDR in the hypercalciuric formation needs to be elucidated further.

[Chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia: diagnosis and treatment].

OBJECTIVE: To investigate the features of chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia (NNDSD) and the effects of pelvic floor biofeedback in the treatment of the disease. METHODS: We included in this study 113 male patients, aged 15 - 48 (mean 36) years and diagnosed as having chronic prostatitis for 1 -2 (mean 1.2) years based on such typical symptoms as frequent micturition, urgent micturition, voiding pain, difficult void, etc, that lasted over 3 months, and the score > or = 1 on the first and second parts of NIH-CPSI. Urethritis, interstitial cystitis, urethral stricture and neurogenic bladder were excluded. All the patients underwent urodynamic examinations for the uroflow curve, Q(max), Pdet. max and MUCP. Biofeedback was carried out for those with non-neurogenic detrusor sphincter dyssynergia, and the effects were evaluated at 10 weeks. RESULTS: Twenty-one (18.6%) of the 113 cases were found to be NNDSD. Biofeedback treatment achieved obvious decreases in Q(max) (8.2 +/- 4.1), Pdet. max (125.1 +/- 75.3), MUP (124.3 +/- 23.3) and MUCP (101.5 +/- 43.6), as compared with 15.1 +/- 7.3, 86.3 +/- 54.2, 65.4 +/- 23.0 and 43.5 +/- 16.7 before the treatment (P < 0.05). Statistically significant differences were observed between pre- and post-treatment scores on voiding pain (4.0 +/- 2.0 vs 2.2 +/- 1.7), urination (7.9 +/- 2.1 vs 2.2 +/- 1.9), life impact (9.6 +/- 2.7 vs 2.9 +/- 2.6) and total scores (21.7 +/- 4.8 vs 8.4 +/- 4.6) (P < 0.05). CONCLUSION: Chronic prostatitis patients with LUTS may have NNDSD, which is urodynamically characterized by low Q(max), high intra-bladder pressure and increased urethral pressure in some patients. Urodynamic examinations may contribute to definite diagnosis and appropriate choice of treatment. Pelvic floor biofeedback has satisfactory short-term effects in the treatment of these patients.

[Hypothalamus may be involved in psychogenic erectile dysfunction].

OBJECTIVE: To study the changes of hypothalamus metabolism in patients with psychogenic erectile dysfunction (ED) so as to get some clues to the possible pathogenic factors and pathophysiological mechanism of the problem. METHODS: Six cases of psychogenic ED and 4 normal volunteers were studied by positron emission tomography (PET) for the characteristics of hypothalamus glucose metabolism. Following audiovisual sexual stimulation, the concentration of fluorine-18-fluorodeoxyglucose (18 F-FDG) was determined and the ratio of the left (right) hypothalamus count to the cerebrum count was calculated. RESULTS: Audiovisual sexual stimulation significantly increased 18F-FDG in the volunteers (left: 1.026 +/- 0.115 vs 2.400 +/- 0.210; right: 1.003 +/- 0.187 vs 2.389 +0.196, P < 0.05) as compared with the psychogenic ED patients (left: 2.781 +/- 0.156 vs 2.769 +/- 0.223; right: 2.809 +/- 0.129 vs 2.793 +/- 0.217, P > 0.05). CONCLUSION: Psychogenic ED may not be simply a functional disease; the hypothalamus may be involved in the pathophysiology of the problem.

[Comparison of different drugs on the treatment of benign prostate hyperplasia].

OBJECTIVE: To compare the differences of the efficacy and different therapeutic drugs on the treatment of benign prostatic hyperplasia (BPH) in order to ensure the optimal indication for different BPH patients. METHODS: A randomized, parallel-controlled, multicenter clinical trial was conducted. From September 2002 to December 2003 906 BPH patients were enrolled into 7 therapeutic groups, including selective-adrenoceptor antagonist (terazosin, doxazosin tamsulosin and naftopidil), 5 alpha-reductase inhibitor (finasteride and epristeride) and natural product (cernilton). International Prostate Symptom Score (IPSS) and Quality of Life (QOL), uroflowmetry, total prostatic volume (TPV) and transitional zone volume and residual urine were used as efficacy criteria. RESULTS: According to the baseline, the IPSS and Qmax were significantly correlated to the prostatic volume and transitional zone volume (P < 0.01). At average follow-up of 6 months, significant improvements in IPSS, QOL, Qmax and residual urine volume were observed in each therapeutic group, and no difference in IPSS improvement was found among the groups. Prostatic volume and transitional zone volume were significant decreased in 5alpha-reductase inhibitor groups (P < 0.05). In patients with baseline TPV greater than 35.5 cm3, the improvement of Qmax was more significant than that in patients with TPV less than 35.5 cm3 in finasteride group (P < 0.01) (5.7 ml/s and 2.2 ml/s respectively), and more significant symptomatic improvements were also found in cernilton, doxazosin and naftopidil group. In each group, the improvement of symptom were more significant in patients with IPSS higher than 20 points (P < 0.01). CONCLUSIONS: Each drug observed in this study can improve the subjective and objective symptoms significantly for BPH patients, especially for patients with higher IPSS baseline. When using 5alpha-reductase inhibitor, prostatic volume can be decreased significantly and more obviously subjective and objective improvement can be found in the patients with TPV greater than 35.5 cm3.

[A clinical study of prostat combined with an antibiotic for chronic nonbacterial prostatitis].

OBJECTIVE: To evaluate the efficacy and safety of Prostate in combination with an antibiotic for the treatment of chronic nonbacterial prostatitis. METHODS: A double-blind, parallel contrasted, multi-central method was applied in the study. After the Stamey test and expressed prostate secretion (EPS) examination, 160 patients with prostatitis were recruited and randomized into a trial group (80 cases with 1 case missing) and a control group (80 cases). In the trial group, the patients used the levofloxacin and Prostate during the first 4 weeks and Prostate only during the following 4 weeks. In the control group, the patients used the levofloxacin and placebo during the first 4 weeks, and placebo only during the following 4 weeks. Before and 4 and 8 weeks after the treatment, the patients were visited and evaluated by the national institute health-chronic prostatitis symptom index (NIH-CPSI), EPS, and asked about the side. RESULTS: After 4-week and 8-week treatment, the pain index dropped by 3.34 +/- 2.45 and 4.06 +/- 3.03 in the trial group, and effects. 2.28 +/- 2.42 and 3.30 +/- 3.29 in the control; the voiding index dropped by 2.22 +/- 1.79 and 2.77 +/- 2.04 in the trial group, and 1.24 +/- 1.67 and 1.83 +/- 2.25 in the control respectively. There was significant difference between pre-treatment and post-treatment in both the two groups (P < 0.01), while the difference was not significant between 4-week and 8-week post-treatment (P > 0.05). And there was significant difference between the two groups in the pain index and voiding index (P < 0.01), but not in the white blood cell count and lipid in the EPS (P > 0.05). No serious side effects were recorded, and the tolerance to Prostate and placebo showed no significant difference. CONCLUSION: Prostate in combination with an antibiotic can effectively relieve the pain and voiding symptoms and improve the life quality of the patients with nonbacterial prostatitis and well deserves to be recommended in clinical practice.

[The relaxation effects of six extracts from Chinese herbs on the corpus cavernosum tissue of rabbit in vitro].

OBJECTIVE: To study the relaxants effects of six extractions from Chinese Herbs (neferine, tetrandrine, kakonein, scutellarin, ginsenoside Rgl and ginsenoside Rb1) on the corpus cavernosum tissue of rabbit in vitro. METHODS: Isolated stripes of rabbit corpus cavernosum tissue were precontracted with 10(-5) mol/L phenylephrine (PE). Relaxation in response to cumulative doses of six extracts at (10(-8) - 10(-3)) mol/L was determined. RESULTS: On rabbit cavernosal muscle stripes precontracted with PE, neferine, tetrandrine, kakonein and scutellarin showed dose dependent relaxation. IC50 values were 4.60 x 10(-6), 3.73 x 10(-5), 8.03 x 10(-4) and 3.33 x 10(-3) mol/L, respectively. However, in the meantime, it was found that the relaxant effects of ginsenoside Rgl and ginsenoside Rbl less significant to stripes precontracted with PE. When the final concentration was 10(-3) mol/L, the relaxations were only (16.32 +/- 5.45)% and (11.21 +/- 3.10)%. CONCLUSION: Among the six extracts which showed relaxant effects to rabbit cavernosal muscle stripes precontracted with PE, neferine had greater functions than the other five extracts.

[Efficacy of traditional Chinese medicine and Western medicine in the treatment of Ureaplasma urealyticun and Chlamydia trachomatis infectious chronic prostatitis (report of 48 cases)].

OBJECTIVES: To elucidate the treatment of Ureaplasma urealyticum (UU) and Chlamydia trachomatis (CT) infectious chronic prostatitis. METHODS: Forty-eight cases of chronic prostatitis patients with UU and CT infections were treated with minocycline, Chinese medicine "Qianlieshulekeli" and alpha 1A adrenoceptorblocker (tamsulosin) for 6 weeks. The change of symptoms, expressed prostatic secretion (EPS) routine, and UU and CT detection results were observed before and after the treatment. The efficacy of treatment were evaluated by CPSI score. RESULTS: Remarkably effective-41 cases (85.4%), effective-5 cases (10.4%), noneffective-2 cases (4.2%). CPSI score reduced from (22 +/- 8) before treatment to (7 +/- 3) after treatment (P < 0.01). UU in 20 of 24 cases (83%) and CT in 25 of 28 cases (89%) turned negative after treatment. CONCLUSIONS: The therapy combining Chinese medicine with western medicine for the treatment of UU and CT infectious chronic prostatitis is successful.

Biofeedback therapy for chronic pelvic pain syndrome.

AIM: To evaluate the efficacy of biofeedback therapy in patients with chronic pelvic pain syndrome (CPPS). METHODS: From November 2001 to April 2002, patients visiting the Urological Outpatient Clinic of this Hospital were evaluated by means of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and classified by the NIH classification standard. Sixty-two patients of CPPS category III were involved in this study. All patients had been treated by conventional approaches such as antibiotics and alpha-blockers for more than half a year without any improvement. The expressed prostatic secretion results were as follows: WBC 5 to 9/high power field, lipid + approximately +++ and bacterial culture negative. Their NIH-CPSI were 12 approximately 40. All the 62 cases complained of micturitional irritation (frequency, urgency, splitted stream and sense of residual urine), 32 cases, of pain or discomfort at the testicular, penile, scrotal, pelvic or rectal region and 13 cases, of white secretion-dripping. The patients were treated by the Urostym Biofeedback equipment (Laborie Co., Canada) 5 times a week for 2 weeks with a stimulus intensity of 15 mA approximatley 23 mA and duration of 20 minutes. RESULTS: Sixty patients were significantly improved or cured, while no significant improvement in the remaining 2. No apparent side effect was observed. The NIH-CPSI dropped to 6 to 14 with an average reduction of 21 (P<0.01). In the 60 improved cases, pain was relieved after 2 approximately 3 treatment courses and other symptoms disappeared after 4 approximately 5 courses. CONCLUSION: Biofeedback therapy is a safe and effective treatment for CPPS. Large randomized clinical trials are needed to confirm its efficacy and to explore the mechanism of action.