Abstract:
OBJECTIVE:To examine the effects of mirabegron, a selective β3 -adrenoceptor agonist that has recently been approved for the treatment of overactive bladder (OAB), on erectile function. Stimulation of β3 -adrenoceptors localised in cavernosal smooth muscle cells may play a physiological role in mediating penile erection, and offer a beneficial pharmacological action for patients who have OAB and erectile dysfunction (ED). MATERIALS AND METHODS:Corpus cavernosal (CC) specimens were obtained from patients with ED and Peyronie's disease undergoing penile prosthesis implantation. Erectile responses were also evaluated in vivo after intracavernosal injection (ICI) of mirabegron in anaesthetised rats. Mirabegron-elicited relaxation responses (10(-8) -10(-3) m) on phenylephrine-induced contraction were seen in human CC (HCC) and rat CC strips in isolated organ-bath studies. The effects of inhibitors, namely L-NAME [N(G) -nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase (NOS), 100 μm], ODQ [1H-(1,2,4) oxadiazolo(4,3-α) quinoxalin-1-one, a soluble guanylyl cyclase (sGC) inhibitor, 30μm], methylene blue (a NOS and sGC inhibitor, 20μm), SR59230A (β3 -adrenoceptor blocker, 1 μm), and fasudil [Rho-associated protein kinase (ROCK) inhibitor, 0.1 μm], on mirabegron-induced relaxation responses were evaluated. Responses to mirabegron were compared with responses to isoprenaline and nebivolol. Immunohistochemistry was used to localise β3 -adrenoceptors and ROCK in CC smooth muscle cells. In vivo rat data were expressed as intracavernosal pressure (ICP)/mean arterial pressure, and total ICP. RESULTS:Mirabegron resulted in a relaxation of phenylephrine-evoked CC contractions in a concentration-dependent manner and SR59230A antagonised the mirabegron-induced relaxations in HCC and rat CC. Other inhibitors, L-NAME, ODQ, and methylene blue, did not affect the mirabegron-induced relaxation responses. Mirabegron relaxation responses at concentrations (0.1-10 μm) were enhanced by fasudil (ROCK inhibitor) in rat but not in HCC strips. KCl-induced contractions in HCC and rat CC were partially inhibited by mirabegron. In vivo, ICI of mirabegron (doses of 0.1-1 mg/kg) had a minor effect on ICP when compared with vehicle administration. Immunohistochemistry data showed β3 -adrenoceptors localised in the smooth muscle cells of the HCC and rat CC. CONCLUSIONS:Mirabegron markedly relaxed isolated CC strips by activating β3 -adrenoceptors independently of the NO-cGMP pathway. There is also evidence of the existence of a close functional link between β3 -adrenoceptors and the RhoA/ROCK pathway. These results may support further clinical studies using combinations of mirabegron with ROCK and phosphodiesterase type 5 inhibitors (PDE5i) for the treatment of ED, especially in patients who do not respond to PDE5i therapy.
journal_name
BJU Intjournal_title
BJU internationalauthors
Gur S,Peak T,Yafi FA,Kadowitz PJ,Sikka SC,Hellstrom WJdoi
10.1111/bju.13515subject
Has Abstractpub_date
2016-09-01 00:00:00pages
464-74issue
3eissn
1464-4096issn
1464-410Xjournal_volume
118pub_type
杂志文章abstract:OBJECTIVE:To assess the possible relationship between treatment with selective serotonin-reuptake inhibitors (SSRIs) and the occurrence of nocturia. SUBJECTS AND METHODS:An unselected group of adult men and women, living in the city of Ostersund, Sweden, were sent a postal questionnaire containing questions on somatic...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2005.05408.x
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVES:To evaluate the value of multiparametric magnetic resonance imaging (mpMRI) in the detection of significant prostate cancer (PCa) and to compare transperineal MRI/ultrasonography fusion biopsy (fusPbx) with conventional transrectal systematic biopsy (sysPbx) in biopsy-naïve patients. PATIENTS AND METHODS:Th...
journal_title:BJU international
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/bju.14017
更新日期:2018-01-01 00:00:00
abstract::The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. As erectile dysfunction (ED) generally develops in the second half of life, the ultimate objective generally is not procreation, but ...
journal_title:BJU international
pub_type: 杂志文章,评审
doi:10.1111/j.1464-410X.2008.08267.x
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVES:To determine the clinical utility of blood tests as a screening tool for metabolic abnormalities in patients with kidney stone disease. SUBJECTS AND METHODS:Clinical and biochemical data from 709 patients attending the Oxford University Hospitals NHS Foundation Trust for assessment and treatment of kidney s...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.15250
更新日期:2020-09-23 00:00:00
abstract:OBJECTIVES:To determine if baseline characteristics, treatment efficacy, psychosocial outcomes or tolerability were associated with patient preference for sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS:In a...
journal_title:BJU international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1464-410X.2007.06916.x
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVES:To describe the step-by-step learning curve of the holmium laser enucleation of the prostate (HoLEP) surgical technique. SUBJECTS/PATIENTS AND METHODS:A prospective, multicentre observational study was conducted, involving surgeons experienced in transurethral resection of the prostate and open prostatectom...
journal_title:BJU international
pub_type: 杂志文章,多中心研究
doi:10.1111/bju.13124
更新日期:2016-03-01 00:00:00
abstract:OBJECTIVES:To investigate the long-term functional outcomes and complications after continent cutaneous diversion with the Lundiana pouch. PATIENTS AND METHODS:Complications, re-operations, renal function, and continence were ascertained from patient charts. Outcome variables were validated by a second and independent...
journal_title:BJU international
pub_type: 杂志文章,多中心研究
doi:10.1111/bju.13863
更新日期:2017-10-01 00:00:00
abstract:OBJECTIVE:To compare the effect of allowing patients to watch their cystoscopy on closed-circuit television and with an explanation during the procedure, with an explanation alone, as involving patients in the process of minimally invasive procedures like colonoscopy or colposcopy has been reported to alleviate pain an...
journal_title:BJU international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1464-410x.2003.04477.x
更新日期:2003-11-01 00:00:00
abstract:UNLABELLED:What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present s...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2012.11152.x
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVES:To use the Fragility Index to evaluate the robustness of statistically significant findings from urological randomised controlled trials (RCTs). MATERIALS AND METHODS:The 'Fragility Index' is defined as the minimum number of patients in one arm of a trial whose status would have to change from 'event' to 'n...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.14210
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:To review our experience in the management of secondary pelvi-ureteric junction obstruction (PUJO) comparing endopyelotomy with pyeloplasty. PATIENTS AND METHODS:We retrospectively analysed our database of 58 patients having undergone operative management of PUJO after failed primary management, including 41...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.12454
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:To detect occult regional lymph node metastases in patients with T3pN0M0 prostate cancer not recognized by routine haematoxylin and eosin staining, and to evaluate the clinical relevance of this finding. PATIENTS AND METHODS:Formalin-fixed and paraffin-embedded pelvic lymph nodes (1118) from 92 patients were...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.2000.00406.x
更新日期:2000-02-01 00:00:00
abstract:OBJECTIVE:To determine whether the temperature of 2% lignocaine hydrochloride gel affects the initial discomfort during instillation into the male urethra. PATIENTS AND METHODS:Sixty consenting men were randomized to receive 11 mL of 2% lignocaine hydrochloride gel (Instillagel, Farco-Pharma GmbH, Cologne, Germany) at...
journal_title:BJU international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1464-410x.1999.00346.x
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:To evaluate possible predictive factors of involution on ultrasonography (US) or disappearance of a prenatally detected multicystic dysplastic kidney (MCDK). PATIENTS AND METHODS:Forty-five children with unilateral MCDK detected by prenatal ultrasonography between 1989 and 2002 were analysed. All patients ex...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2005.05418.x
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:To describe a modification of the posterior prone retroperitoneoscopic nephrectomy, which allows the entire operation to be performed through a single instrument port. PATIENTS AND METHODS:With the patient prone, a retroperitoneal working space is created using a custom-made balloon lateral to the sacrospina...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2008.08232.x
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVE:To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0-7), moderate (8-19) and severe (>20) categories, predicts brachytherapy-related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherap...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2006.05887.x
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. PATIENTS AND METHODS:This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2010.09435.x
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVE:To compare transurethral resection in saline (TURIS), Greenlight laser vapo-enucleation of the prostate (GL.PVEP), and holmium laser enucleation of the prostate (HoLEP), for controlling lower urinary tract symptoms secondary to large benign prostatic hyperplasia (BPH) and to assess non-inferiority of 3-year r...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.15161
更新日期:2020-12-01 00:00:00
abstract:OBJECTIVE:To evaluate the variability of subjective tutor performance improvement (Pi) assessment and to compare it with a novel measurement algorithm: the Pi score. MATERIALS AND METHODS:The Pi-score algorithm considers time measurement and number of errors from two different repetitions (first and fifth) of the same...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.14621
更新日期:2019-04-01 00:00:00
abstract:OBJECTIVE:To explain differences over time between operative approach and surgeon type for adrenal surgery in the USA. PATIENTS AND METHODS:A retrospective cohort analysis was performed on all patients undergoing adrenalectomy between 2002 and 2011 using the Nationwide Inpatient Sample. Patients undergoing concurrent ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.12747
更新日期:2015-02-01 00:00:00
abstract:OBJECTIVE:To compare the expression of the seven known P2X receptors in human bladder from male patients with detrusor instability caused by symptomatic bladder outlet obstruction with that from control bladders, using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. PATIENTS AND METHODS...
journal_title:BJU international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1464-410x.2001.02179.x
更新日期:2001-05-01 00:00:00
abstract:OBJECTIVE:To study scrotal microvascularization and apply the findings to the design of reliable skin flaps for reconstructive surgery of complex urethral or panurethral stenoses. MATERIALS AND METHODS:In 15 cryopreserved male cadavers, scrotal skin vascularization was explored using macro- and microdissections, and t...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2008.08167.x
更新日期:2009-03-01 00:00:00
abstract:OBJECTIVE:To assess the changing distribution of stage in seminoma and nonseminomatous germ cell tumours (NSGCTs), as recent reports contained no detailed information on pT stage and vascular invasion, important factors in the decision for further treatment. PATIENTS AND METHODS:Histopathological reports from 1976 to ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2006.06424.x
更新日期:2006-10-01 00:00:00
abstract:UNLABELLED:What's known on the subject? and what does the study add?: Variations in the type of urinary diversion exist for patients undergoing radical cystectomy. Although its use has been increasing from 2001 to 2008, patients who are older, female, and primary insured by Medicaid are less likely to receive continent...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2012.11508.x
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVES:To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population. SUBJECTS AND METHODS:A cross-sectional postal survey of 10 000 men aged ≥40 years in N...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.14182
更新日期:2018-11-01 00:00:00
abstract:OBJECTIVE:To measure the prevalence of nocturia in general practice and to determine which factors are associated with nocturia. SUBJECTS AND METHODS:Data were collected from 3048 elderly men, who completed a questionnaire that was sent to every man aged 55-75 years in 21 general practices in Maastricht (the Netherlan...
journal_title:BJU international
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1464-410X.2006.06029.x
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE:To evaluate the therapeutic potential of sympatholytic agents on premature ejaculation in an animal model, using monitoring of rat seminal vesicle pressure change in response to electrical stimulation of the lesser splanchnic nerve. MATERIALS AND METHODS:Male Wistar rats (aged 12-14 weeks) were injected intr...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1046/j.1464-410x.1999.00173.x
更新日期:1999-09-01 00:00:00
abstract:OBJECTIVE:To determine if the biochemical composition of a renal calculus can be measured from 'dust' obtained during laser fragmentation. PATIENTS AND METHODS:This pilot study was set in a tertiary referral hospital between 2011 and 2013. Stone dust was aspirated through the ureteroscope during lasering and a stone f...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/bju.13448
更新日期:2016-10-01 00:00:00
abstract:OBJECTIVES:To report an audit of preoperative staging variables, case selection, stage migration and prostate-specific antigen (PSA) recurrence at five large centres in the south of England. To establish PSA outcome values after radical prostatectomy for clinically localized prostate cancer in the UK, and enable approp...
journal_title:BJU international
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1464-410X.2003.04715.x
更新日期:2004-04-01 00:00:00
abstract::Laparoendoscopic single-site surgery (LESS) and natural orifice transluminal endoscopic surgery (NOTES™) are new approaches to minimally invasive surgery. A number of technical challenges need to be overcome and new developments of equipment are required before widespread acceptance of either modality occurs. In this ...
journal_title:BJU international
pub_type: 杂志文章
doi:10.1111/j.1464-410X.2010.09665.x
更新日期:2010-09-01 00:00:00