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1.
Urol Res Pract ; 49(4): 225-232, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37877823

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate current urologic practice regarding the management of priapism in Turkey and compare with international guidelines. METHODS: Urologists and urology residents were invited to an online survey consisting of 30 multiple-choice questions on priapism-related clinical practices that were consid- ered most important and relevant to practices by using Google Forms. RESULTS: Total number of responses was 340. Respondents reported that they recorded a detailed patient's medical history and physical examination findings (n = 340, 100%) and laboratory testing, which includes corporal blood gas analysis (n=323, 95%). Participants announced that they performed Doppler ultrasound for 1/4 cases (n = 106, 31%), but 22% of the participants (n=75) replied that they performed in >75% of cases. Participants (n=311, 91%) responded that the first-line treatment of ischemic priapism is decompression of the corpus cavernosum. Moreover, most respondents (n = 320, 94%) stated that sympathomimetic injection drugs should be applied as the second step. About three-quarters of respondents (n = 247, 73%) indicated adrenaline as their drug of choice. Phosphodiesterase type 5 inhibitors seems to be the most pre- ferred drug for stuttering priapism (n=141, 41%). Participants (n=284, 84%) replied that corpora-glanular shunts should be preferred as the first. A large number of par- ticipants (n = 239, 70%) declared that magnetic resonance imaging can be performed in cases with delayed (>24 hours) priapism to diagnose corporal necrosis. Most of the participants (84%) responded that penile prosthesis should be preferred to shunts in cases with delayed (>48 hours) priapism. CONCLUSION: It would be appropriate to improve the training offered by professional associations and to give more training time to the management of priapism during residency.

3.
Andrologia ; 52(11): e13785, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32816318

ABSTRACT

The aim of our study was to compare melatonin levels of patients with lifelong premature ejaculation (LPE) (n:60) with healthy controls (n:30) and to investigate the changes of melatonin levels in the treatment with dapoxetine and sertraline. Age, body mass index, duration of marriage, weekly intercourse number, International Index of Erectile Function scores, Intravaginal Ejaculation Latency Time (IELT) and melatonin levels were recorded. LPE patients were divided into two treatment groups. The first group was included 30 patients, who received 60 mg dapoxetine for six weeks, twice a week, an hour before intercourse. The second group received 50 mg of sertraline daily, for six weeks. IELT and melatonin measures were repeated after the treatment. IELT (dapoxetine group: 41.22 ± 21.3 s, sertraline group: 48 ± 23.11 s, control group: 195.54 ± 84.14 s; p < .001) and melatonin levels (dapoxetine group: 5.75 ± 2.04 pg/mL, sertraline group: 5.49 ± 2.88 pg/mL, control group: 13.4 ± 12.09 pg/mL; p < .001) of both LPE groups were significantly lower than control group. Following the six-week sertraline (before: 48 ± 23.11 s, after: 101.01 ± 59.55 s; p < .001) and dapoxetine (before: 41.22 ± 21.3 s, after: 97.39 ± 44.1 s; p < .001) treatments, IELT increased. The melatonin levels increased in the sertraline group (before: 5.49 ± 2.88 pg/mL, after: 10.6 ± 7.37 pg/mL; p < .001). Our results indicate that melatonin levels of LPE patients are lower than levels of healthy volunteers. Furthermore, we found a significant increase in melatonin levels following sertraline treatment.


Subject(s)
Melatonin , Premature Ejaculation , Ejaculation , Humans , Male , Premature Ejaculation/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sertraline/therapeutic use , Treatment Outcome
4.
Urol Int ; 104(5-6): 459-464, 2020.
Article in English | MEDLINE | ID: mdl-32155628

ABSTRACT

INTRODUCTION: A number of factors that can impact the outcomes of percutaneous nephrolithotomy (PCNL) procedures have previously been investigated. Complex stones that extend to the anterior calyx could affect the success and complication rates of PCNL. OBJECTIVE: We analyzed the effect of anterior calyx involvement on the outcomes of patients with complex stones treated with PCNL. METHODS: A total of 132 consecutive patients who underwent PCNL due to complex stones (multiple, partial staghorn, or staghorn stones) between 2015 and 2017 were enrolled in this study. They were stratified into two groups based on whether the stone extended to the anterior calyx (group 1, n = 45) or not (group 2, n = 87). The stratification was achieved through contrast-enhanced computerized tomography (CT). Demographics, laboratory tests, and peri- and postoperative findings (operation and fluoroscopy duration, hospital stay, utilization of flexible instruments, access numbers, total blood count change, stone-free rate [SFR], and complications) were compared between the groups. The SFR was evaluated by plain kidney-ureter-bladder radiography or CT. RESULTS: The demographics, operation and fluoroscopy duration, access number, and hospital stay were similar between the groups (p < 0.05). A higher drop in the hemoglobin level in group 1 was identified (group 1 [2.14 ± 1.49 g/dL] vs. group 2 [1.43 ± 1.31 g/dL]) (p = 0.006). The SFR among the patients with extension to the anterior calyx was 60%, compared to 77% among the patients with no extension to the anterior calyx (p = 0.041). Flexible instruments were utilized in 60% of the patients of group 1, which was a higher rate than for group 2 (36%) (p = 0.007). Complication rates were similar in the two groups according to the Clavien-Dindo classification (p > 0.05). CONCLUSIONS: Our study demonstrated that complicated stones with extension to the anterior calyx are more challenging than cases without extension to the anterior calyx. This was noted by a lower SFR, a more prominent drop in total blood count, and more frequent utilization of flexible scopes.


Subject(s)
Nephrolithotomy, Percutaneous , Staghorn Calculi/surgery , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
5.
Balkan Med J ; 35(5): 373-377, 2018 09 21.
Article in English | MEDLINE | ID: mdl-29866640

ABSTRACT

Background: The ideal prophylaxis duration for transrectal ultrasonography-guided prostate biopsy is incompletely defined. Aims: To compare the infectious complications of transrectal ultrasonography-guided prostate biopsy with and without extended antibiotic prophylaxis. The secondary aim was to evaluate the risk factors for infectious complications. Study Design: Prospective observational study. Methods: Four hundred patients who underwent transrectal ultrasonography-guided prostate biopsy were recruited. Patients orally received either 750 mg ciprofloxacin 60 min before the procedure or 500 mg ciprofloxacin twice a day for a duration of 7 days with the initial dose administered 24 h prior to the procedure. All patients were followed-up for 4 weeks after the transrectal ultrasonography-guided prostate biopsy procedure for infectious complications. Screening of urine was carried out in all patients on the 3rd and 7th day after the procedure. Medical histories of all patients were collected prior to biopsy. Information on medical history include the following: hospitalization, urethral catheterization, or urinary tract infections within the past 12 months; antibiotic use within the last 3 months, prior urinary tract interventions, and previous transrectal ultrasonography-guided prostate biopsy and Charlson comorbidity indexes. Ultrasound-guided biopsy was carried out using General Electric's 7 MHz transrectal ultrasound device in the left decubitus position. Patients received one of the two ciprofloxacin-based prophylaxis regimens. Subsequent transrectal ultrasonography-guided prostate biopsy to all patients were followed-up for 30 days. Further follow-up of patients was carried out on the second and fourth weeks after transrectal ultrasonography-guided prostate biopsy, and symptoms, such as dysuria, rectal bleeding, fever, hematospermia, hematuria, and pollakiuria, were recorded. Results: Both groups presented similar baseline characteristics and medical history. Infectious complication rates within the 4-week follow-up were similar in both groups (single dose: 3% vs prolonged: 3%) (p>0.05). In both groups, infectious complications significantly increased than that at previous antibiotic usage (single: p=0.028; prolonged: p=0.040). Non-infectious complication ratios showed no significant variation (p>0.05). Conclusion: Pre-operative single dose of 750 mg oral ciprofloxacin compared with 7 days prolonged treatment resulted in similar infectious complication outcomes in patients undergoing transrectal ultrasonography-guided prostate biopsy. The use of antibiotics within the last 3 months increases the risk for post-transrectal ultrasonography-guided prostate biopsy infectious complications.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Antibiotic Prophylaxis/methods , Fluoroquinolones/administration & dosage , Image-Guided Biopsy/adverse effects , Postoperative Complications/prevention & control , Ultrasonography, Interventional/adverse effects , Urinary Tract Infections/prevention & control , Aged , Humans , Image-Guided Biopsy/methods , Male , Middle Aged , Postoperative Complications/etiology , Prospective Studies , Prostate/pathology , Prostate/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Rectum/surgery , Risk Factors , Treatment Outcome , Ultrasonography, Interventional/methods , Urinary Tract Infections/etiology
7.
Int Braz J Urol ; 43(1): 142-149, 2017.
Article in English | MEDLINE | ID: mdl-28124537

ABSTRACT

PURPOSE: To determine whether there is a difference in sexual function after modified and classical TOT procedures. MATERIALS AND METHODS: Of the 80 sexually active women with SUI, 36 underwent na original outside-in TOT as described by Delorme, and 44 underwent modified TOT procedure, between 2011 and 2015. The severity of incontinence and sexual function were evaluated using International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Female Sexual Function Index (FSFI) questionnaires preoperatively and 3 months after surgery. RESULTS: The postoperative ICIQ-SF score was significantly lower than the preoperative ICIQ-SF score in both groups (p=0.004 for modified TOT and p=0.002 for classical TOT). There was no significant difference in the ICIQ-SF score reduction between the two groups (14.1±2.1 vs. 14.4±1.9; p=0.892). Complication rates according to the Clavien-Dindo classification were also similar in both groups. In both groups, difference between preoperative and postoperative FSFI scores revealed a statistically significant improvement in all domains. Comparison of postoperative 3-month FSFI scores of modified and classical TOT groups showed statistically significant differences in arousal, lubrication and orgasm domains. Desire, satisfaction, pain and total FSFI scores did not differ significantly between two groups. CONCLUSION: The modified TOT technique is a simple, reliable and minimal invasive procedure. The cure rate of incontinence and complication rates are the same as those of the classical TOT technique. However, due to the positive effects of minimal tissue damage on sexual arousal and orgasmic function, modified TOT has an advantage over the classical TOT.


Subject(s)
Sexual Dysfunction, Physiological/physiopathology , Sexuality/physiology , Suburethral Slings , Urinary Incontinence, Stress/physiopathology , Urinary Incontinence, Stress/surgery , Adult , Aged , Cystoscopy/methods , Educational Status , Equipment Design , Female , Humans , Middle Aged , Needles , Patient Satisfaction , Postoperative Period , Preoperative Period , Prospective Studies , Quality of Life , Severity of Illness Index , Sexual Dysfunction, Physiological/psychology , Sexuality/psychology , Statistics, Nonparametric , Surveys and Questionnaires , Treatment Outcome
8.
Arch Ital Urol Androl ; 88(1): 4-6, 2016 Mar 31.
Article in English | MEDLINE | ID: mdl-27072168

ABSTRACT

PURPOSE: To evaluate the effect of postoperatively administering a low daily dose of tadalafil on the erectile function of patients who underwent a nerve-sparing radical prostatectomy (NSRP) due to localized prostate cancer (PCa). MATERIALS AND METHODS: Of 138 patients, who underwent NSRP due to PCa between 2012 and 2014, 55 patients who had not had pre-operative erectile dysfunction (ED) were included in the study. The mean age of the patients was 64 (54-72). On the 15th day after surgery, after ultrasound evaluation, all 55 patients started on a daily dose of 5 mg tadalafil that was continued for 2.5 months. The erectile function of patients was evaluated pre-operatively, post-operatively, and at the 3rd and 6th month after surgery using the International Index of Erectile Function (IIEF-5) test. None of the patients was treated with hormonal therapy or radiotherapy before or after surgery. RESULTS: Three patients were excluded from the study due to the adverse effects of tadalafil and two patients elected to discontinue the treatment. Of the remaining 50 patients whose pre-operative erectile function had been found normal, at 3 months after surgery, 36 (72%) had normal erectile function; of the remaining patients in the study six (12%) presented with mild, two (4%) with moderate, and six (12%) with severe ED. Six months after surgery, 35 patients (70%) had normal erectile function while seven (14%) had mild, three (6%) moderate and five (10%) severe ED. There was no statistically significant difference between the results obtained at the 3rd and 6th month follow-up (p > 0.05). Three patients reported adverse effects with tadalafil including flushes in 2 (3.6%) and a headache in 1 (1.8%). CONCLUSIONS: The administration of a 5 mg post-operative dose of tadalafil to patients that had undergone a bilateral NSRP was found to have a positive effect on the recovery and maintenance of erectile function. However, there is still a need to investigate a larger series of cases.


Subject(s)
Erectile Dysfunction/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Prostatectomy/methods , Tadalafil/therapeutic use , Aged , Erectile Dysfunction/etiology , Humans , Male , Middle Aged , Penile Erection/drug effects , Phosphodiesterase 5 Inhibitors/adverse effects , Prostatic Neoplasms/surgery , Tadalafil/adverse effects , Treatment Outcome
9.
Urology ; 88: 161-5, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26680245

ABSTRACT

OBJECTIVE: To investigate the value of anatomic and blood-flow measurements of the prostate via ultrasound in identifying medical treatment response of patients with lower urinary tract symptoms due to benign prostatic enlargement. A secondary objective of the study was to compare transabdominal-transrectal measurements. MATERIALS AND METHODS: Male patients (age range 50-80) with lower urinary tract symptoms who applied to our outpatient clinic to be diagnosed with benign prostatic enlargement that were eligible for medical management were included in the prospective study. Patients (n = 49) were administered with tamsulosin for management. At baseline evaluation, all patients underwent International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), transabdominal and transrectal ultrasound [prostate volume (PV), post-void rezidu and intravesical prostatic protrusion (IPP)], and prostate subcapsular resistive index value measurement. Follow-ups were carried out 1 and 3 months after treatment. At these time-points, patients were assessed with IPSS and uroflowmetry. RESULTS: IPP were identified to be negatively correlated with baseline Qmax values (P = .001, R = -0.485) and positively correlated with PSA (P = .013, R = 0.353) and PV (P = .003, R = 0.420). PV was related with resistive index (P = .026, R = 0.318) and PSA (P = .001, R = 0.619). Subsequent to medical treatment on the follow-ups, an overall improvement in the IPSS and Qmax was identified (P = .001). However, a negative correlation was identified in the change that occurred between IPSS and IPP (P = .004, R = -0.410). Other parameters were not correlated (P > .05) with the change in IPSS and Qmax. Transabdominal and transrectal measures were similar (P = .001). CONCLUSION: This study has shown that increased IPP values are associated with lower response to alpha-receptor specific management. Transabdominal measurements are sufficient for the evaluation compared with transrectal measurement.


Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Prostatic Hyperplasia/drug therapy , Sulfonamides/therapeutic use , Abdomen , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Prospective Studies , Prostate/blood supply , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Hyperplasia/diagnostic imaging , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/physiopathology , Rectum , Regional Blood Flow , Remission Induction , Tamsulosin , Treatment Outcome , Ultrasonography/methods
10.
BJU Int ; 110(8 Pt B): E402-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22520450

ABSTRACT

OBJECTIVES: To examine the effect of partial urethral obstruction (PUO) on bladder smooth muscle outward potassium current and the contribution of the large-conductance calcium-activated potassium (Maxi-K, BKCa) channel to this activity in smooth muscle cells isolated from bladders of sham-operated and PUO male rats using whole-cell patch clamp recording techniques. To determine the effect of PUO on the expression of the Maxi-K channel α and ß1 subunits and in vitro detrusor contractility. MATERIALS AND METHODS: Twenty adult male Sprague-Dawley rats were divided equally into two groups and subjected to surgical ligation of the urethra (PUO) or sham surgery (SHAM). After 2 weeks, the detrusors from PUO and SHAM rats were used for molecular analyses (mRNA and protein quantification of Maxi-K subunits) or organ bath contractility studies, or myocytes were isolated for conventional whole-cell patch clamp analyses. RESULTS: PUO increased bladder mass 2.5-fold and detrusor strips exhibited a more tonic-type contraction and increased contractility compared with controls (SHAM). Iberiotoxin (300 nM) sensitive Maxi-K channel current comprised about 40% of the outward whole-cell current in SHAM bladders but only about 8% in PUO bladders. Expression of the α subunit of the Maxi-K channel was significantly decreased ~40% while the expression of the ß1 subunit was increased ~2-fold at the mRNA level. The increase in ß1 expression was confirmed by Western blotting. CONCLUSIONS: Our findings show that obstruction of the rat bladder is associated with decreased Maxi-K channel activity of bladder smooth muscle cells, determined via direct current measurement. Increased expression of the ß1 subunit points to a compensatory reaction to decreased Maxi-K channel activity. Maxi-K channel openers or gene therapy may therefore provide therapeutic benefit for the overactive bladder.


Subject(s)
Large-Conductance Calcium-Activated Potassium Channels/physiology , Myocytes, Smooth Muscle/physiology , Urethral Obstruction/physiopathology , Urinary Bladder/physiopathology , Animals , Cells, Cultured , Male , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley
11.
Urol Int ; 87(4): 400-4, 2011.
Article in English | MEDLINE | ID: mdl-22086154

ABSTRACT

OBJECTIVES: A prospective randomized study was conducted to evaluate the safety and effectiveness of bipolar plasma vaporization with a novel electrode that produces vaporization of the tissue (transurethral vaporization of the prostate, TUVP) immersed in isotonic saline compared to the standard transurethral resection of the prostate (TURP) in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From February 2009 to February 2010, 90 patients with BPH were randomized into two groups, and underwent conventional TURP (group 1) or TUVP (group 2) utilizing bipolar plasma vaporization with an innovative electrode (Olympus Winter & Ibe GmbH, Hamburg, Germany). International Prostate Symptom Scores (IPSS), transrectal ultrasonographic findings, maximal urine flow rates (Qmax), and postvoiding residual urine (PVRU) volumes of all cases were evaluated preoperatively and 1 month, 3 months, and 1 year postoperatively. Preoperative and postoperative serum hemoglobin, hematocrit and sodium concentrations of all patients were measured. All patients included in the study were monitored for 1 year. RESULTS: In patients in group 1 (n = 47; mean age: 64.7 ± 7.3 years) TURP was performed. The patients in group 2 (n = 43; mean age: 65.4 ± 8.9 years) underwent bipolar TUVP. Cases in the two study groups matched for demographic characteristics and clinical parameters were assessed. The evaluation of IPSS scores, PVRU, Qmax, and prostatic volumes of the patients 1 month, 3 months, and 1 year postoperatively did not reveal any significant differences between the two groups. In group 2 (TUVP), postoperative catheter indwelling times were significantly shorter, and Na serum concentrations were also markedly lower (p < 0.005). CONCLUSION: We detected similar effectiveness and morbidity rates in both groups. Bipolar TUVP has advantages such as shorter catheter indwelling times and hospital stays, and fewer bleeding episodes without any risk of transurethral resection syndrome. We believe that TUVP might be an alternative to TURP which is currently the 'gold standard' treatment in BPH.


Subject(s)
Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/methods , Aged , Chi-Square Distribution , Electrodes , Equipment Design , Humans , Length of Stay , Male , Middle Aged , Prospective Studies , Prostatic Hyperplasia/physiopathology , Time Factors , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/instrumentation , Treatment Outcome , Turkey , Urinary Catheterization , Urodynamics , Volatilization
12.
J Androl ; 32(5): 502-8, 2011.
Article in English | MEDLINE | ID: mdl-21233397

ABSTRACT

Only a few studies have investigated the association between the severity of Peyronie disease (PD) and clinical parameters such as age and associated comorbidities. The aim of this study was to report the relationship between the degree of curvature of the penis and the clinical parameters among patients with PD. A total of 1001 patients with PD were evaluated retrospectively in terms of penile deformity, erectile status, and risk factors for systemic vascular diseases. The degree of curvature was assessed with a protractor during maximum erection in response to a combined injection and stimulation test and/or vacuum device. A modified Kelami classification was used to categorize penile deformities as follows: patients with deformities without curvature (notching, hourglass, and swan neck deformity, group 1), with mild curvature (≤ 30 degrees, group 2), with moderate curvature (31-60 degrees, group 3), or with severe curvature (> 60 degrees, group 4). Chi-square tests, 1-way analysis of variance, and univariate and multiple ordinal regression analyses were used for statistical analysis. Penile deformity without curvature was detected in 12.3% of the patients, whereas the curvature was less than 30 degrees in 39.5%, 30 to 60 degrees in 34.5%, and more than 60 degrees in 13.5% of the patients. Multiple ordinal regression analysis identified age (P = .013), side of deformity (P = .007), erectile dysfunction (P < .0001), and diabetes mellitus (P = .001) as significant independent predictors of the severity of penile curvature. In conclusion, patients' age, side of deformity, erectile function, and diabetes were significantly associated with the degree of curvature.


Subject(s)
Penile Induration/complications , Penile Induration/pathology , Adult , Age Factors , Aged , Cardiovascular Diseases/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Humans , Hypertension/epidemiology , Male , Middle Aged , Penile Induration/epidemiology , Retrospective Studies , Risk Factors , Young Adult
13.
BJU Int ; 106(4): 562-71, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20128782

ABSTRACT

OBJECTIVES: To examine the effect of partial urethral obstruction (PUO) on the sphingosine-1-phosphate (S1P, a bioactive lipid shown to modulate smooth muscle, SM) pathway in the bladders of male rats, and to determine the effect of PUO on the RhoA/Rho-kinase (ROK) pathway, and whether there is a molecular cross-talk with the S1P pathways associated with bladder overactivity (S1P1-S1P3, where S1P1 is associated with nitric oxide-mediated SM relaxation, and S1P2 and S1P3 receptors are associated more with SM contraction via the ROK pathway). MATERIALS AND METHODS: In all, 20 male rats were divided into two groups and underwent PUO or a sham operation (control). After 2 weeks all rats were killed humanely and bladder specimens used for in vitro organ-bath physiological contractility studies, and for mRNA and protein analyses of major S1P/ROK pathway constituents via real-time polymerase chain reaction and Western blotting, respectively. In addition, early-passage SM cells were transfected with recombinant sphingosine kinase (SPHK, the enzyme that converts sphingosine to S1P). RESULTS: Bladders from PUO rats had greater mRNA expression of the S1P2 and S1P3 receptors, as well as SPHK1, than the sham controls (4.78, 2.04 and 2.72 times, respectively). PUO rats also had significantly greater expression of RhoA and ROKalpha (1.76 and 2.19 times, respectively). Western blotting and organ-bath contractility studies showed similar changes at the protein and in vitro functional level, with an increased contractility of bladder strips from PUO rats to exogenous S1P. Transfection of SPHK into isolated SM cells increased ROK expression. CONCLUSIONS: We show for the first time that the S1P signalling pathway is significantly upregulated in response to PUO in male rats at both the molecular and in vitro functional levels, correlating with an activation of the RhoA/ROK pathway. Further, we provide novel data that SPHK overexpression increases ROK expression in vitro, suggesting a novel hypothesis of S1P-induced bladder overactivity in the mechanism for PUO-induced bladder dysfunction and the S1P signalling pathway as a possible therapeutic target for bladder overactivity.


Subject(s)
Lysophospholipids/metabolism , Sphingosine/analogs & derivatives , Up-Regulation/physiology , Urinary Bladder Neck Obstruction/metabolism , rho-Associated Kinases/metabolism , Animals , Blotting, Western , Male , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Sphingosine/metabolism , Up-Regulation/genetics , Urinary Bladder Neck Obstruction/genetics
14.
J Sex Med ; 6(10): 2661-71, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19686429

ABSTRACT

INTRODUCTION: Blebbistatin (BLEB) is a small cell permeable molecule originally reported as a selective inhibitor of myosin II isoforms expressed by striated muscle and non-muscle cells (IC(50) = 0.5-5 microM) with poor inhibition of turkey gizzard smooth muscle (SM) myosin II (IC(50) approximately 80 microM). However, recently it was found that BLEB can potently inhibit mammalian arterial SM (IC(50) approximately 5 microM). AIM: To investigate the effect of BLEB on corpus cavernosum SM (CCSM) tone and erectile function (EF). METHODS: CC tissue obtained from penile implant patients along with CC, aorta and bladder from adult male rats were used for BLEB organ bath studies. Intracavernosal BLEB was administered to rats and EF was assessed via intracavernous pressure (ICP). MAIN OUTCOME MEASURES: Effects of BLEB on agonist-induced CCSM, aorta and bladder contraction in vitro and ICP in vivo. RESULTS: BLEB completely relaxed human CCSM pre-contracted with phenylephrine (PE) in a dose-dependent manner decreasing tension by 76.5% at 10 microM. BLEB pre-incubation attenuated PE-induced contraction of human CC by approximately 85%. Human CC strips pre-contracted with endothelin-1 or KCl were almost completely relaxed by BLEB. Rat CCSM pre-contracted with PE showed BLEB relaxation comparable to human CCSM. BLEB inhibition was similar for rat aorta but slower for bladder. Both maximal ICP and ICP/mean arterial pressure were dose-dependently increased by BLEB intracavernous injections with full erection at 1 micromole. CONCLUSION: Our novel data reveals that BLEB nearly completely relaxes rat and human CCSM pre-contracted with a variety of potent agonists and exhibits tissue selectivity. Coupled with our in vivo data in which nanomole doses of BLEB significantly increase ICP, our data substantiates an important role for the SM contractile apparatus in the molecular mechanism for EF and suggests the possibility of BLEB binding at myosin II as a therapeutic treatment for ED by targeting SM contractile pathways.


Subject(s)
Heterocyclic Compounds, 4 or More Rings/pharmacology , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Myosin Type II/antagonists & inhibitors , Penis/drug effects , Adult , Aged , Animals , Aorta/drug effects , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Male , Middle Aged , Muscle Contraction/drug effects , Phenylephrine/pharmacology , Rats , Rats, Sprague-Dawley , Urinary Bladder/drug effects
15.
Mol Cell Endocrinol ; 303(1-2): 67-73, 2009 May 06.
Article in English | MEDLINE | ID: mdl-19428993

ABSTRACT

Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4 ng/ml to <0.04 ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2 mg in 100ml sesame oil every 4 days for 2 weeks) restored average levels of testosterone to 2 ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls.


Subject(s)
Gene Expression Regulation/physiology , Penile Erection , Penis/cytology , Protein Precursors/genetics , Salivary Proteins and Peptides/genetics , Testosterone/physiology , Animals , Male , Muscle Contraction , Muscle, Smooth , Orchiectomy , Penis/metabolism , Penis/physiology , Rats , Testosterone/blood
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