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1.
Curr Urol Rep ; 22(4): 19, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33554283

RESUMO

PURPOSE OF THE REVIEW: The goal of this paper was to evaluate the impact on erectile and ejaculatory function after anterior and posterior urethroplasty. RECENT FINDINGS: With a rise in the use of urethroplasty, its impact on sexual function has come into question. For anterior urethroplasties, some degree of erectile dysfunction is common, but this tends to be transient, with most patients having a resolution of any de novo dysfunction by 12 months. Patients with posterior urethral strictures have a very high rate of erectile dysfunction prior to surgery and may show improvement after urethroplasty. Ejaculatory function tends to improve in patients due to alleviation of obstruction while some patients notice degradation in force of ejaculation. While urethroplasty has a minimal permanent effect on sexual function for most patients, there are some patients who notice improvement and others worsening. Patients should be counseled on these risks prior to urethroplasty.


Assuntos
Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Psicogênicas/etiologia , Uretra/cirurgia , Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Ejaculação/fisiologia , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Disfunção Erétil/psicologia , Humanos , Masculino , Pênis/irrigação sanguínea , Pênis/inervação , Pênis/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Risco , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Psicogênicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia , Uretra/inervação , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
2.
Am J Physiol Regul Integr Comp Physiol ; 320(1): R80-R87, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33146553

RESUMO

The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve. After determination of the threshold intensity (T) for PNS to induce an anal twitch, PNS (5 Hz, 0.2 ms, 2 T or 4 T) was applied during cystometrograms (CMGs). PNS (4-6 T) of 30-min duration was then applied repeatedly until bladder underactivity was produced. Following stimulation, control CMGs were performed over 1.5-2 h to determine the duration of bladder underactivity. When applied during CMGs, PNS (2 T and 4 T) significantly (P < 0.05) increased bladder capacity while PNS at 4 T also significantly (P < 0.05) reduced bladder contraction amplitude, duration, and area under contraction curve. Repeated application of 30-min PNS for a cumulative period of 3-8 h produced bladder underactivity exhibiting a significantly (P < 0.05) increased bladder capacity (173 ± 14% of control) and a significantly (P < 0.05) reduced contraction amplitude (50 ± 7% of control). The bladder underactivity lasted more than 1.5-2 h after termination of the prolonged PNS. These results provide basic science evidence supporting the proposal that abnormal afferent activity from external urethral/anal sphincter could produce central inhibition that underlies nonobstructive urinary retention (NOUR) in Fowler's syndrome. This cat model of UAB may be useful to investigate the mechanism by which sacral neuromodulation reverses NOUR in Fowler's syndrome.


Assuntos
Estimulação Elétrica , Nervo Pudendo/fisiopatologia , Reflexo , Uretra/inervação , Bexiga Inativa/etiologia , Bexiga Urinária/inervação , Urodinâmica , Animais , Gatos , Modelos Animais de Doenças , Feminino , Masculino , Fatores de Tempo , Bexiga Inativa/fisiopatologia
3.
Am J Physiol Renal Physiol ; 318(6): F1430-F1440, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32363884

RESUMO

The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. Understanding how aging affects LUT reflexes may help in the development of new treatments by identifying mechanistic targets. In this work, we studied the relationship between age and systems-level function of the LUT and tested the hypothesis that aging is related to weakening of reflexes that control voiding. Three groups of anesthetized female rats, young (4-7 mo old), mature (11-14 mo old), and old (18-24 mo old), were used to quantify the effect of aging on LUT reflexes. A double-lumen catheter enabled us to control the bladder volume and urethral flow rate independently, under quasi-isovolumetric bladder conditions. We systematically investigated the reflex bladder contractions evoked by combinations of rates of urethral infusion and bladder fill volumes as a function of age. Urethral infusion with the same flow rate evoked bladder contractions (via the augmenting reflex) in old animals less often than in younger animals. Furthermore, old animals needed more fluid in their bladders (relative to their bladder capacity) before urethra flow-evoked bladder contractions could be triggered at all, suggesting a delay in the switch of the LUT to "voiding mode." Old rats also showed longer and weaker bladder contractions than young or mature rats. Taken together, this suggests there is an age-related functional weakening and loss of sensitivity in LUT reflexes, which may contribute to age-related UAB symptoms.


Assuntos
Sintomas do Trato Urinário Inferior/fisiopatologia , Músculo Liso/inervação , Reflexo Anormal , Uretra/inervação , Bexiga Inativa/fisiopatologia , Bexiga Urinária/inervação , Micção , Fatores Etários , Animais , Modelos Animais de Doenças , Feminino , Sintomas do Trato Urinário Inferior/etiologia , Mecanotransdução Celular , Contração Muscular , Pressão , Ratos Sprague-Dawley , Fatores de Risco , Bexiga Inativa/etiologia , Urodinâmica
4.
Neurourol Urodyn ; 39(3): 916-925, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32040866

RESUMO

AIMS: The urethral dysfunction produced by a rat model of peripheral neurogenic detrusor underactivity (DU) using pelvic nerve crush (PNC) injury was characterized and then tested with the administration of tadalafil, a phosphodiesterase type 5 (PDE 5) inhibitor. METHODS: Ten days after producing PNC rats, awake cystometrograms (CMGs) and isovolumetric cystometrograms with urethral perfusion pressure (IC-UPP) measurements were performed. Also, in control rats, IC-UPP was recorded before and after intravenous atropine administration to determine if the reduction of bladder contraction pressure affects urethral relaxation during voiding. Then, CMG and IC-UPP measurements in PNC rats were recorded after intravenous administration of tadalafil. Lastly, real-time polymerase chain reaction was used to measure transcript levels of neuronal nitric oxide synthases (nNOS), endothelial nitric oxide synthases, and PDE 5 in urethral specimens from PNC and control rats. RESULTS: PNC rats demonstrated the characteristics of DU in CMG. Also, PNC rats exhibited significant decreases in isovolumetric bladder contraction amplitudes and urethral relaxation. Atropine attenuated the amplitude of isovolumetric bladder contractions; however, atropine did not affect urethral relaxation in control rats. Tadalafil decreased postvoid residual and increased voiding efficiency without changing bladder contraction amplitude in PNC rats. Also, tadalafil improved the amplitude of urethral relaxation during bladder contraction in PNC rats. Urethral nNOS transcript levels were upregulated in PNC rats compared to control rats. CONCLUSIONS: PNC rats revealed both DU and impaired urethral relaxation. PDE 5 inhibition in PNC rats enhanced urethral relaxation during voiding, resulting in improved voiding efficiency. Thus, urethral dysfunction could be a potential target for the treatment of inefficient voiding associated with neurogenic DU.


Assuntos
Traumatismos dos Nervos Periféricos/fisiopatologia , Inibidores da Fosfodiesterase 5/farmacologia , Tadalafila/farmacologia , Uretra/efeitos dos fármacos , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Inativa/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Micção/efeitos dos fármacos , Animais , Lesões por Esmagamento/fisiopatologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Feminino , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pelve , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Uretra/metabolismo , Uretra/fisiopatologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Micção/fisiologia
5.
Urology ; 137: 183-189, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926195

RESUMO

OBJECTIVE: To characterize the bulbospongiosus muscle (BSM) in patients with bulbar urethral strictures. MATERIALS AND METHODS: We studied 21 patients divided into 2 groups: Stricture Group (n = 14; mean age = 62.00 years) with bulbar stricture submitted to open urethroplasty; and Control Group (n = 7; mean age = 60.14 years) with penile strictures (hypospadias cripples, penile cancer and/or penile infection) who were submitted to perineal urethrostomy. Samples of the BSM were dissected and histologic sections were stained by histochemical and immunohistochemical techniques. Histomorphometric analyzes were performed on photomicrographs. Means were statistically compared using the unpaired Student t test and the Mann-Whitney test (P <.05). RESULTS: The etiology of bulbar urethral stricture was idiopathic in 2 cases (14.29%), post-TURP in 6 (42.86%), post open radical prostatectomy in 5 (35.71%) and post open prostatectomy in 1 case (7.14%). The average length of the stricture was 2.08 cm. The only parameter analyzed with significant difference between the groups was the vessels (significant difference between the control group: 5.11 ± 1.98% and stricture group: 3.57 ± 1.32%, P = .0460). The quantitative analysis of collagen (Control Group: 10.63 ± 5.37% and Stricture Group: 10.83 ± 4.55%, P = .9296); diameter of BSM muscle fibers (Control Group: 41.71 ± 14.63 µm and Stricture Group: 40.11 ± 8.59 µm, P = .76 and elastic system fibers (Control Group; 3.83 ± 1.54% and Stricture Group: 5.43 ± 2.90%, P = .2601) showed no significant difference. CONCLUSIONS: Histologic analysis showed a significant decrease of the BSM vessels in urethral stricture, without changes in elastic fibers, collagen, nerves, and muscle fiber diameter. These findings show that the bulbar urethral stricture causes minimal alterations in the structure of the BSM.


Assuntos
Doenças do Pênis , Pênis , Complicações Pós-Operatórias , Uretra , Estreitamento Uretral , Procedimentos Cirúrgicos Urológicos , Pesos e Medidas Corporais/métodos , Brasil , Constrição Patológica , Correlação de Dados , Técnicas de Imagem por Elasticidade/métodos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Doenças do Pênis/diagnóstico , Doenças do Pênis/etiologia , Pênis/patologia , Pênis/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Uretra/irrigação sanguínea , Uretra/inervação , Uretra/patologia , Uretra/cirurgia , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/epidemiologia , Estreitamento Uretral/etiologia , Estreitamento Uretral/patologia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Procedimentos Cirúrgicos Urológicos/métodos
6.
Differentiation ; 111: 22-40, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31654825

RESUMO

Development of the human prepuce was studied over the course of 9-17 weeks of gestation in 30 specimens. Scanning electron microscopy revealed subtle surface features that were associated with preputial development, namely the appearance of epidermal aggregates that appeared to be associated with formation of the preputial fold. Transverse and sagittal sections revealed that the epidermis of the glans is considerably thicker than that of the penile shaft. We described a novel morphogenetic mechanism of formation of the preputial lamina, namely the splitting of the thick epidermis of the glans into the preputial lamina and the epidermis via the intrusion of mesenchyme containing red blood cells and CD31-positive blood vessels. This process begins at 10-11 weeks of gestation in the proximal aspect of the glans and extends distally. The process is likely to be androgen-dependent and mediated via androgen receptors strategically localized to the morphogenetic process, but signaling through estrogen receptor may play a role. Estrogen receptor alpha (ESR1) has a very limited expression in the developing human glans and prepuce, while estrogen receptor beta (ESR2) is expressed more broadly in the developing preputial lamina, epidermis and urethra. Examination of the ontogeny of innervation of the glans penis and prepuce reveals the presence of the dorsal nerve of the penis as early as 9 weeks of gestation. Nerve fibers enter the glans penis proximally and extend distally over several weeks to eventually reach the distal aspect of the glans and prepuce by 14-16 weeks of gestation.


Assuntos
Morfogênese , Pênis/crescimento & desenvolvimento , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Uretra/crescimento & desenvolvimento , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pênis/inervação , Pênis/metabolismo , Pênis/ultraestrutura , Uretra/inervação , Uretra/metabolismo , Uretra/ultraestrutura
7.
Neurourol Urodyn ; 39(1): 181-189, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31724210

RESUMO

AIMS: We sought to determine whether somatic lumbar nerve transfer to the pelvic nerve's anterior vesical branch after sacral decentralization for detrusor muscle reinnervation also leads to aberrant innervation of the bladder outlet. METHODS: Twenty-six female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots (ie, sacral decentralization). Immediately afterward, 12 received genitofemoral nerve transfer and 9 received femoral nerve branch transfer. Five were left sacrally decentralized. Controls included 3 sham-operated and 6 unoperated. Eight months postsurgery, the bladder and urethra were injected with retrograde tracing dyes cystoscopically. After 3 weeks, detrusor and urethral pressures were assayed electrophysiologically immediately before euthanasia and characterization of neural reinnervation. RESULTS: Electrical stimulation of spinal cords or roots did not lead to increased urethral sphincter pressure in nerve transfer animals, compared with decentralized animals, confirming a lack of functional reinnervation of the bladder outlet. In contrast, mean detrusor pressure increased after lumbar cord/root stimulation. In sham/unoperated animals, urethral and bladder dye injections resulted in labeled neurons in sacral level neural structures (dorsal root ganglia [DRG], sympathetic trunk ganglia [STG], and spinal cord ventral horns); labeling absent in decentralized animals. Urethral dye injections did not result in labeling in lumbar or sacral level neural structures in either nerve transfer group while bladder dye injections lead to increased labeled neurons in lumbar level DRG, STG, and ventral horns, compared to sacrally decentralized animals. CONCLUSION: Pelvic nerve transfer for bladder reinnervation does not impact urethral sphincter innervation.


Assuntos
Transferência de Nervo/métodos , Nervos Espinhais/transplante , Uretra/inervação , Bexiga Urinária/inervação , Animais , Cães , Estimulação Elétrica , Feminino , Neurônios/fisiologia
8.
Int Urogynecol J ; 31(1): 63-71, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529330

RESUMO

A damaged sphincteric unit or support system, unstable urethral deformability or damaged sensory innervation are all potential causes of a dysfunctional urethral sphincter. With the current improvement in pharmacological targets and urodynamic understanding, studies have begun quantifying individual structures and their importance in closure pressure and consequently urethral continence. However, when it comes to the function of the longitudinal urethral smooth muscle layer, there is currently no consensus. The intent of this structured review is to critically examine literature regarding the female urethral anatomy and closure mechanism. We hypothesized that the longitudinal smooth muscle is a prerequisite for sufficient urethral closure and not merely involved during micturition. Overall opinions on a dysfunctional closure mechanism are controversial. Nonetheless, basic mechanics may be applied to understand simple urodynamics. With the assumption of longitudinal muscles forming a plug when contracted, this could have a substantial effect on the continence mechanism.


Assuntos
Músculo Liso/anatomia & histologia , Uretra/inervação , Humanos , Músculo Liso/fisiologia , Uretra/fisiologia
9.
J Neurosurg Spine ; 32(2): 258-268, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703192

RESUMO

OBJECTIVE: Previous patient surveys have shown that patients with spinal cord or cauda equina injuries prioritize recovery of bladder function. The authors sought to determine if nerve transfer after long-term decentralization restores bladder and sphincter function in canines. METHODS: Twenty-four female canines were included in this study. Transection of sacral roots and hypogastric nerves (S Dec) was performed in 6 animals, and 7 animals underwent this procedure with additional transection of the L7 dorsal roots (L7d+S Dec). Twelve months later, 3 L7d+S Dec animals underwent obturator-to-pelvic nerve and sciatic-to-pudendal nerve transfers (L7d+S Dec+Reinn). Eleven animals served as controls. Squat-and-void behaviors were tracked before and after decentralization, after reinnervation, and following awake bladder-filling procedures. Bladders were cystoscopically injected with Fluoro-Gold 3 weeks before euthanasia. Immediately before euthanasia, transferred nerves were stimulated to evaluate motor function. Dorsal root ganglia were assessed for retrogradely labeled neurons. RESULTS: Transection of only sacral roots failed to reduce squat-and-void postures; L7 dorsal root transection was necessary for significant reduction. Three L7d+S Dec animals showing loss of squat-and-void postures post-decentralization were chosen for reinnervation and recovered these postures 4-6 months after reinnervation. Each showed obturator nerve stimulation-induced bladder contractions and sciatic nerve stimulation-induced anal sphincter contractions immediately prior to euthanasia. One showed sciatic nerve stimulation-induced external urethral sphincter contractions and voluntarily voided twice following nonanesthetized bladder filling. Reinnervation was confirmed by increased labeled cells in L2 and the L4-6 dorsal root ganglia (source of obturator nerve in canines) of L7d+S Dec+Reinn animals, compared with controls. CONCLUSIONS: New neuronal pathways created by nerve transfer can restore bladder sensation and motor function in lower motor neuron-lesioned canines even 12 months after decentralization.


Assuntos
Transferência de Nervo , Raízes Nervosas Espinhais/lesões , Bexiga Urinária/inervação , Bexiga Urinária/cirurgia , Animais , Cães , Feminino , Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Radiculopatia/fisiopatologia , Sacro/fisiopatologia , Traumatismos da Medula Espinal/cirurgia , Uretra/inervação , Uretra/fisiopatologia , Micção/fisiologia
10.
Sci Rep ; 9(1): 13993, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570751

RESUMO

Patients suffer bilateral sacral plexus injuries experience severe problems with incontinence. We performed a cadaveric study to explore the anatomical feasibility of transferring ipsilateral S2 nerve root combined with a sural nerve graft to pudendal nerve for restoration of external anal and urethral sphincter function. The sacral nerve roots and pudendal nerve roots on the right side were exposed in 10 cadavers. The length from S2 nerve root origin to pudendal nerve at inferior border of piriformis was measured. The sural nerve was used as nerve graft. The diameters and nerve cross-sectional areas of S2 nerve root, pudendal nerve and sural nerve were measured and calculated, so as the number of myelinated axons of three nerves on each cadaver specimen. The length from S2 nerve root to pudendal nerve was 10.69 ± 1.67 cm. The cross-sectional areas of the three nerves were 8.57 ± 3.03 mm2 for S2, 7.02 ± 2.04 mm2 for pudendal nerve and 6.33 ± 1.61 mm2 for sural nerve. The pudendal nerve contained approximately the same number of axons (5708 ± 1143) as the sural nerve (5607 ± 1305), which was a bit less than that of the S2 nerve root (6005 ± 1479). The S2 nerve root in combination with a sural nerve graft is surgically feasible to transfer to the pudendal nerve for return of external urethral and anal sphincter function, and may be suitable for clinical application in patients suffering from incontinence following sacral plexus injuries.


Assuntos
Canal Anal/inervação , Nervo Pudendo/cirurgia , Raízes Nervosas Espinhais/cirurgia , Nervo Sural/transplante , Uretra/inervação , Adulto , Canal Anal/cirurgia , Estudos de Viabilidade , Incontinência Fecal/cirurgia , Feminino , Humanos , Masculino , Nervo Pudendo/anatomia & histologia , Raízes Nervosas Espinhais/anatomia & histologia , Nervo Sural/anatomia & histologia , Uretra/cirurgia , Incontinência Urinária/cirurgia
11.
Am J Physiol Renal Physiol ; 317(4): F1047-F1057, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411077

RESUMO

Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 106 MSCs at 1 h, 7 days, and 14 days after injury. Urethral leak point pressure testing with simultaneous external urethral sphincter electromyography and pudendal nerve electroneurography were performed 21 days after injury, and the urethrovaginal complex and pudendal nerve were harvested for semiquantitative morphometry of the external urethral sphincter, urethral elastin, and pudendal nerve. Two and three doses of MSCs significantly improved peak pressure; however, a single dose of MSCs did not. Single, as well as repeated, MSC doses improved urethral integrity by restoring urethral connective tissue composition and neuromuscular structures. MSC treatment improved elastogenesis, prevented disruption of the external urethral sphincter, and enhanced pudendal nerve morphology. These results suggest that MSC therapy for postpartum incontinence and SUI can be enhanced with multiple doses.


Assuntos
Doenças Neuromusculares/terapia , Transplante de Células-Tronco/métodos , Uretra/fisiopatologia , Incontinência Urinária por Estresse/terapia , Animais , Transplante de Medula Óssea/métodos , Tecido Conjuntivo/patologia , Elastina/metabolismo , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Compressão Nervosa , Doenças Neuromusculares/complicações , Doenças Neuromusculares/fisiopatologia , Período Pós-Parto , Nervo Pudendo/fisiopatologia , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/fisiopatologia , Vagina/lesões
12.
J Pharmacol Sci ; 139(4): 333-339, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30871873

RESUMO

The pharmacological profile of ASP2205 fumarate (ASP2205), a novel 5-HT2C receptor agonist, was evaluated in vitro and in vivo. ASP2205 showed potent and selective agonistic activity for the human 5-HT2C receptor, with an EC50 of 0.85 nM in the intracellular Ca2+ mobilization assay. Rat 5-HT2C receptor was also activated by ASP2205 with an EC50 of 2.5 nM. Intraduodenal administration (i.d.) of ASP2205 (0.1-1 mg/kg) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner. This ASP2205 (0.3 mg/kg i.d.)-induced LPP elevation was inhibited by SB242084 (0.3 mg/kg i.v.), a selective 5-HT2C receptor antagonist. Urethral closure responses induced by intravesical pressure loading in rats were enhanced by ASP2205 (0.3 mg/kg i.v.), which was abolished by pretreatment with SB242084 (0.3 mg/kg i.v.) and bilateral transection of the pudendal nerve. In contrast, ASP2205 (0.3 mg/kg i.v.) did not change the resting urethral pressure in rats. These results indicate that ASP2205 can enhance the pudendal nerve-mediated urethral closure reflex via the 5-HT2C receptor, resulting in the prevention of involuntary urine loss.


Assuntos
Fumaratos/farmacologia , Pressão , Reflexo/efeitos dos fármacos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Uretra/fisiologia , Animais , Azepinas , Relação Dose-Resposta a Droga , Feminino , Fumaratos/uso terapêutico , Quinolinas , Ratos Sprague-Dawley , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Uretra/inervação , Uretra/fisiopatologia , Incontinência Urinária por Estresse/prevenção & controle
13.
Neurourol Urodyn ; 38(3): 893-901, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30779374

RESUMO

AIMS: To analyze, in female rats, the anatomical and histological features of the urethra and its relationship with the vagina and clitoris, and its innervation. METHODS: Seventeen adult female Wistar rats were used. Gross anatomy and acetylcholinesterase (AchE) histochemistry were performed to describe the urethral features, adjacent structures, and innervation. The histomorphometric characteristics of the urethra were determined in transversal, longitudinal, or coronal sections stained with Masson's Trichrome. RESULTS: The female rat urethra is not a homogeneous tubular organ. The pre-pelvic and pelvic regions are firmly attached to the vagina with belt-like striated fibers forming a urethra-vaginal complex. The bulbar regions have curved segments and a narrow lumen. The clitoral region is characterized by a urethra-clitoral complex surrounded by a vascular plexus. The lumen area and thickness of the urethral layers significantly varied between regions (P < 0.05). Innervation of the urethra arrives from the major pelvic ganglion, the dorsal nerve of the clitoris (DNC), and the motor branch of the sacral plexus (MBSP). CONCLUSIONS: Differential tissular composition of the urethra may underlie urinary continence and voiding dysfunction through different physiological mechanisms. The urethra-vagina complex seems to be the main site controlling urinary continence through active muscular mechanisms, while the bulbar urethra provides passive mechanisms and the urethra-clitoris complex seems to be crucial for distal urethral closure by means of a periurethral vascular network.


Assuntos
Uretra/metabolismo , Uretra/fisiologia , Incontinência Urinária , Micção/fisiologia , Acetilcolinesterase/metabolismo , Animais , Composição Corporal , Clitóris/anatomia & histologia , Clitóris/inervação , Clitóris/fisiologia , Feminino , Plexo Hipogástrico/fisiologia , Plexo Lombossacral/fisiologia , Nervo Pudendo/fisiologia , Ratos , Ratos Wistar , Uretra/inervação , Vagina/anatomia & histologia , Vagina/inervação , Vagina/fisiologia
14.
Eur Urol Focus ; 5(5): 823-830, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29759661

RESUMO

BACKGROUND: The applicability of the sphincter complex integral theory to robotic-assisted radical prostatectomy (RARP) is unclear, with little known about the long-term effect of sphincter complex integrity on continence. OBJECTIVE: To determine whether the preoperative anatomical and functional features of the sphincter complex and the degree of nerve-sparing affect long-term continence after RARP. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 529 patients who underwent RARP at a single tertiary center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Anatomical factors, including membranous urethral length (MUL) and pelvic diaphragm length (PDL), were assessed using sagittal views of preoperative magnetic resonance imaging. MUL was defined as the distance from the posterior prostate apex to the urethra level at the penile bulb, and PDL was defined as the length of the urethra that met the planes created by the pelvic floor muscles. Functional parameters including maximum urethral closure pressure (MUCP) and functional urethral length were evaluated using preoperative measurements of the urethral pressure profiles. The degree of nerve-sparing was stratified as bilateral, unilateral, or none. Continence (pad-free status) was assessed according to anatomical and functional factors and nerve-sparing. We used binary logistic regression to assess factors predicting continence return 12 mo after RARP. RESULTS AND LIMITATIONS: Continence return rates 1, 3, 6, and 12 mo after RARP were 39.7%, 66.0%, 80.2%, and 87.0%, respectively. Continence return rates at 12 mo differed significantly in patients with MUL ≥11.7mm (91.9%) and <11.7mm (79.9%), PDL ≥9.9mm (96.7%) and <9.9mm (74.5%), and MUCP ≥66 cmH2O (89.7%) and <66 cmH2O (79.4%). The continence return rate was significantly higher in patients with bilateral (93.0%) than in patients with unilateral (78.1%) or no (76.7%) nerve-sparing. Multivariate analysis showed that PDL (odds ratio [OR]=2.187 per mm), MUCP (OR=1.037 per cmH2O), and bilateral nerve-sparing (OR=3.671) were independently associated with continence return 12 mo after RALP. CONCLUSIONS: The anatomical length and static pressure of the sphincter complex affected continence after RARP. Bilateral nerve-sparing was independently associated with long-term continence. PATIENT SUMMARY: Predisposing length and static pressure of the urinary sphincter affect continence after robotic-assisted radical prostatectomy. Nerve bundle preservation during surgery enhances postoperative return of continence.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Uretra , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Uretra/anatomia & histologia , Uretra/inervação , Uretra/fisiologia , Incontinência Urinária/prevenção & controle
15.
Anat Rec (Hoboken) ; 302(2): 201-214, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30290399

RESUMO

The aim of this study was to characterize the number, type and distribution of immunochemically identified nerves in epithelium and lamina propria of the female rat urethra. Urethras from female Sprague-Dawley rats (n = 12) were fixed, frozen and sectioned (8 µm). Standard immunohistochemical techniques were used to identify putative nerves using the following antibodies: calcitonin gene related peptide (cgrp), neuronal nitric oxide synthase (nNos), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (vacht). The number, distribution and characteristics of all immunoreactive (IR) structures adjacent to the urethral epithelium and in the lamina propria was assessed. In the bladder, few cgrp-IR and vacht-IR fibers were associated with the urothelium or suburothelium of the lateral wall. In contrast, large numbers of vacht-IR, nNos-IR and cgrp-IR fibers were found close to the epithelium and subepithelium of the bladder neck and throughout the urethra. The number of cgrp-IR fibers was significantly higher in the urethra in comparison with the bladder neck. A population of undescribed cgrp-IR cells associated with the bladder neck and proximal urethra has been characterized. Each of these cells appears to be associated with a nerve fiber. In the distal urethra, the number of peptidergic fibers penetrating the epithelium was significantly higher than the rest of the urethra. Clearly, this study has revealed a highly complex and heterogeneous network of putative afferent nerves fibers along the length of the urethra. These structural specializations need to be taken into account when probing the different functions of the urethra. Anat Rec, 302:201-214, 2019. © 2018 Wiley Periodicals, Inc.


Assuntos
Biomarcadores/metabolismo , Epitélio/inervação , Membrana Mucosa/inervação , Uretra/inervação , Animais , Anticorpos Monoclonais/imunologia , Peptídeo Relacionado com Gene de Calcitonina/imunologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Epitélio/metabolismo , Feminino , Membrana Mucosa/metabolismo , Óxido Nítrico Sintase Tipo I/imunologia , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/imunologia , Tirosina 3-Mono-Oxigenase/metabolismo , Uretra/metabolismo , Proteínas Vesiculares de Transporte de Acetilcolina/imunologia , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo
16.
Low Urin Tract Symptoms ; 11(2): O186-O192, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29266769

RESUMO

OBJECTIVE: Stress urinary incontinence (SUI) is a common disease condition in elderly women, suggesting that its etiology may be linked to aging. To investigate the hypothesis that urethral dysfunction and histopathological changes are possible contributors to SUI in elderly women, several parameters of urethral function, as well as histological parameters, were compared between young and aged rats. METHODS: Virgin female rats were examined at 3 different ages, namely 3, 12, and 24 months, corresponding to young, middle-aged, and aged rats, respectively. Urethral function was assessed by measuring the leak point pressure (LPP), pudendal nerve stimulation (PNS)-induced elevation in urethral pressure, and phenylephrine-induced increase in urethral perfusion pressure (UPP). Histopathological assessments were performed following hematoxylin and eosin (HE), Masson's trichrome, and immunofluorescence staining of urethral tissue. RESULTS: LPP of aged rats was significantly reduced compared to that of both young and middle-aged rats. PNS-induced elevation in urethral pressure in aged rats was also significantly lower than that in young rats. In contrast, there were no significant differences in the phenylephrine-induced increase in UPP between young and aged rats. Connective tissue area in the external urethral sphincter (EUS) layer was increased in aged rats, whereas the smooth muscle layer was histologically similar to that in young rats. The number of EUS fibers was significantly reduced in aged rats, whereas the cross-sectional area of EUS fibers increased from differed compared with young rats. CONCLUSION: We have demonstrated age-related changes in EUS function and morphology in the rat urethra, which are considered to be etiological risk factors for SUI in humans.


Assuntos
Modelos Animais de Doenças , Uretra/fisiopatologia , Incontinência Urinária por Estresse/fisiopatologia , Envelhecimento , Animais , Feminino , Imunofluorescência , Ratos , Ratos Sprague-Dawley , Uretra/inervação , Uretra/patologia , Incontinência Urinária por Estresse/etiologia
17.
Low Urin Tract Symptoms ; 11(2): O21-O27, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29105998

RESUMO

OBJECTIVE: The aim of the present study was to investigate associations between urethral sensation and urge urinary incontinence (UUI) in patients with and without detrusor overactivity (DO). METHODS: The medical records of 80 consecutive patients who underwent filling cystometry and urethral current perception threshold (CPT) tests were examined retrospectively. Following the exclusion of 4 patients not eligible for analysis, patients were classified into neurogenic DO, idiopathic DO, or DO-negative groups based on neurological and cystometric findings (n = 30, 12, and 34, respectively). Eleven DO-negative patients were defined as normal controls on cystometrograms (CMG) using the following exclusion criteria: bladder compliance <12.5 mL/cmH2 O, volume >275 mL at first filling sensation, and comorbidities possibly affecting lower urinary tract function. Thus, 53 patients were finally included in the study. Proximal urethral CPT was evaluated with intraurethral square-wave stimulation at 3 Hz to activate C-fiber afferents. RESULTS: Median CPT was higher in neurogenic and idiopathic DO than in the normal CMG group (11.3 and 9.0 vs. 2.8 mA, respectively; P < .05), as well as in patients with UUI (n = 19) compared with non-UUI patients (n = 34; 12.5 vs. 5.4 mA, respectively; P < .05). The proportion of UUI patients was significantly greater in the DO-positive groups than in the normal CMG group (P < .05). CPTs were not associated with bladder capacity at the first filling sensation (r = 0.11). CONCLUSION: Hyposensitive C-fibers of the proximal urethra may contribute to the development of urodynamic DO as well as UUI in patients complaining of lower urinary tract symptoms.


Assuntos
Fibras Nervosas Amielínicas/fisiologia , Uretra/inervação , Bexiga Urinária Hiperativa/complicações , Incontinência Urinária de Urgência/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Uretra/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Incontinência Urinária de Urgência/fisiopatologia , Urodinâmica , Adulto Jovem
19.
Nat Neurosci ; 21(9): 1229-1238, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30104734

RESUMO

Voluntary urination ensures that waste is eliminated when safe and socially appropriate, even without a pressing urge. Uncontrolled urination, or incontinence, is a common problem with few treatment options. Normal urine release requires a small region in the brainstem known as Barrington's nucleus (Bar), but specific neurons that relax the urethral sphincter and enable urine flow are unknown. Here we identify a small subset of Bar neurons that control the urethral sphincter in mice. These excitatory neurons express estrogen receptor 1 (BarESR1), project to sphincter-relaxing interneurons in the spinal cord and are active during natural urination. Optogenetic stimulation of BarESR1 neurons rapidly initiates sphincter bursting and efficient voiding in anesthetized and behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals their necessity in motivated urination behavior. The identification of these cells provides an expanded model for the control of urination and its dysfunction.


Assuntos
Tronco Encefálico/fisiologia , Neurônios/fisiologia , Uretra/inervação , Uretra/fisiologia , Micção/fisiologia , Animais , Tronco Encefálico/citologia , Eletromiografia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/fisiologia , Masculino , Camundongos , Vias Neurais/fisiologia , Odorantes , Optogenética , Transtornos Urinários/genética , Transtornos Urinários/fisiopatologia
20.
Neurourol Urodyn ; 37(8): 2614-2624, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29717501

RESUMO

AIMS: To assess the afferent innervation of various locations in the male lower urinary tract (LUT) using sensory evoked cortical potentials (SEPs). METHODS: Twelve healthy men (mean age: 29.6 ± 7.2 years, mean height: 1.8 ± 0.1 m) underwent repetitive slow (0.5 Hz/1 ms) and fast (3 Hz/0.2 ms) electrical stimulations of bladder (dome/trigone) and urethral (proximal/membranous/distal) locations with simultaneous cortical SEP recording (Cz-Fz). Latencies (ms) and peak-to-peak amplitudes (µV) for SEP components P1, N1, and P2 were analyzed. Tibial SEPs were assessed as methodological control. The reproducibility was investigated from between visits and inter-rater assessments using Bland-Altman plots. Statistical tests comprised analysis of variance (ANOVA), linear regressions, and paired t-tests. Values are given as mean ± standard deviation. RESULTS: Typical LUTSEPs with P1, N1, and P2 components were successfully detected (100% responder rate) for slow but less successfully for fast stimulation. The slow stimulation provided reproducible LUTSEPs with position specific N1 latencies: dome 125.6 ± 21.3 ms, trigone 122.9 ± 20.5 ms, proximal- 116.1 ± 21.4 ms, membraneous- 118.8 ± 29.3 ms, and distal urethra 108.8 ± 17.8 ms. Despite good inter-rater agreement, latency variability between and within subjects was higher for LUTSEPs than for tibial SEPs. N1 latencies became shorter (P < 0.01) with increasing subject age for bladder dome and distal urethra stimulation. CONCLUSIONS: LUTSEPs can be successfully obtained for different LUT locations in men using slow electrical stimulation. Location specific differences in N1 latencies may indicate different local afferent innervation. Larger variability of LUTSEPs versus tibial SEPs may be related to the more challenging approach and afferent fibre access within the LUT. Further studies optimizing measurement and analysis approach are required.


Assuntos
Potenciais Somatossensoriais Evocados/fisiologia , Uretra/fisiologia , Bexiga Urinária/fisiologia , Adulto , Análise de Variância , Estimulação Elétrica , Voluntários Saudáveis , Humanos , Masculino , Reprodutibilidade dos Testes , Uretra/inervação , Bexiga Urinária/inervação , Adulto Jovem
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