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1.
Niger J Clin Pract ; 22(12): 1737-1741, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793482

RESUMO

Background: Neonates feel pain. There is a concern among practitioners that pain of injecting analgesics to neonates prior to circumcision could as well be the same as the pain of the procedure. This has made many reluctant to offer effective analgesia for circumcision. If eutectic mixture of local anesthetics (EMLA) provides analgesia comparable to dorsal penile nerve block (DPNB), it will obviate needle prick and encourage analgesia use in neonatal circumcision. Aim: To determine how the analgesic efficacy of EMLA compares with that of DPNB in neonatal plastibell circumcision. Methods: A prospective study of 110 male neonates for plastibell circumcision randomized into two groups: A and B, of 55 each, received EMLA or DPNB as analgesia prior to circumcision, respectively. The pulse rates and SpO2 were recorded with pulse oximeter pre-procedural and at four stages of the procedure (adhesiolysis, dorsal slit, tying, and excision) for each neonate. Also the modification of neonatal infant pain scale (NIPS) was recorded during the procedure. Results: There were differential changes in SpO2 (lower absolute mean values) and pulse rate (higher absolute mean values) for neonates who received EMLA when compared with DPNB before the procedure. These differences were significant with SpO2 at adhesiolysis (91.0% and 95.0%), dorsal slitting (90.9% and 94.7%), and excision stages (93.4% and 95.3), respectively (P < 0.05). They were also significant with the pulse rates at adhesiolysis (167.9 and 158.6), dorsal slitting (174.3 and 161.7), and tying stages (182.2 and 169.0), respectively (P values = 0.013, 0.015, and 0.044, respectively). This shows DPNB is better than EMLA. However, the difference was not significant at the tying stage with SpO2 and at excision stage with PR (P > 0.05). Conclusion: EMLA produces analgesic effect. However, it does not provide effective analgesia for plastibell circumcision in neonates. DPNB provides a better analgesia than EMLA for neonatal plastibell circumcision.


Assuntos
Anestésicos Locais/uso terapêutico , Circuncisão Masculina , Lidocaína/uso terapêutico , Bloqueio Nervoso , Dor/prevenção & controle , Pênis/inervação , Prilocaína/uso terapêutico , Anestesia Local , Humanos , Lactente , Recém-Nascido , Combinação Lidocaína e Prilocaína , Masculino , Dor/etiologia , Manejo da Dor/métodos , Medição da Dor , Estudos Prospectivos , Resultado do Tratamento
2.
Acta Cir Bras ; 34(9): e201900901, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800678

RESUMO

PURPOSE: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. METHODS: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. RESULTS: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). CONCLUSIONS: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.


Assuntos
Pênis/irrigação sanguínea , Pênis/inervação , Traumatismos dos Nervos Periféricos/prevenção & controle , Inibidores da Fosfodiesterase 5/farmacologia , Substâncias Protetoras/farmacologia , Tadalafila/farmacologia , Animais , Colágeno/análise , Colágeno/efeitos dos fármacos , Tecido Elástico/anatomia & histologia , Tecido Elástico/efeitos dos fármacos , Disfunção Erétil/prevenção & controle , Imuno-Histoquímica , Masculino , Pênis/efeitos dos fármacos , Pênis/patologia , Prostatectomia/efeitos adversos , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes
3.
Urology ; 134: 228-231, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31560912

RESUMO

Pudendal nerve decompression surgery has not been studied or reported for the treatment of penile numbness in the absence of pain. Herein, we report a case of a male patient with chronic numbness of the penis and erectile dysfunction in the absence of pelvic pain who was found to have pudendal nerve entrapment. This patient was treated with surgical decompression of the pudendal nerves that resulted in the return of genital sensation and erections. Thus, we propose that pudendal nerve entrapment may be considered as a cause of penile numbness and that pudendal nerve decompression surgery in these patients may be effective.


Assuntos
Disfunção Erétil/etiologia , Hipestesia/etiologia , Pênis/inervação , Neuralgia do Pudendo/diagnóstico , Adulto , Constipação Intestinal/etiologia , Descompressão Cirúrgica , Incontinência Fecal/etiologia , Humanos , Masculino , Exame Neurológico , Neuralgia do Pudendo/complicações , Neuralgia do Pudendo/cirurgia , Incontinência Urinária/etiologia
4.
Urology ; 131: 136-143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202856

RESUMO

OBJECTIVE: To determine if combined administration of LIMK2 and JNK inhibitors in a rat model of erectile dysfunction induced by cavernosal nerve (CN) injury could restore erectile function by suppressing both cavernosal apoptosis and fibrosis via rectification of molecular pathways related to the structural alterations. METHODS: Sixty 12-week-old male Sprague-Dawley rats were categorized into 4 groups: (1) Sham-surgery (Sham) group, (2) CN-crush-injury (CNCI), (3) CNCI group (CNCI+L+1.0J) treated with a combination of 10.0 mg/kg LIMK2-inhibitors and low-dose (1.0 mg/kg) JNK-inhibitors, and (4) CNCI group (CNCI+L+10.0J) treated with a combination of 10.0 mg/kg LIMK2-inhibitors and a high dose (10.0 mg/kg) of JNK-inhibitors. Ten days after surgery, erectile response, histological-studies, and Western-blot was investigated. RESULTS: The CNCI group showed a reduced maximal ICP/MAP or AUC/MAP, decreased immunohistochemical-staining of α-SMA, decreased SM/collagen ratio, increased phospho-cJun-positive apoptotic cells, increased phospho-LIMK2-positive fibroblasts, increased cJun-phosphorylation, increased LIMK2/Cofilin-phosphorylation, decreased Bcl-2/Bax ratio, and increased protein-expression of fibronectin, compared to the Sham group. Both the CNCI+L+1.0J and CNCI+L+10.0J groups showed improvements in erectile-responses, content of cavernosal α-SMA, number of phospho-cJun-positive apoptotic cells, Bcl-2/Bax ratio and cJun phosphorylation. Their improvements in the CNCI+L+10.0J group showed a tendency to be greater than those in the CNCI+L+1.0J group. Also, in the 2 treatment groups, rectification of SM/collagen ratio, number of phospho-LIMK2-positive fibroblasts, LIMK2/Cofilin-phosphorylation, and protein-expression of fibronectin was observed. CONCLUSION: This study suggests that combined inhibition of JNK and LIMK2 may improve erectile function by suppressing cavernosal apoptosis and fibrosis via restoration of cJun/Bcl-2/Bax and LIMK2/Cofilin pathways at 10 days after CN injury.


Assuntos
Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Quinases Lim/antagonistas & inibidores , Pênis/lesões , Pênis/inervação , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Animais , Modelos Animais de Doenças , Combinação de Medicamentos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
5.
Biomed Res Int ; 2019: 6875756, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032356

RESUMO

Background: General anesthesia combining with a caudal block (CB) has been commonly performed in pediatric patients undergoing circumcision surgeries. However, some severe complications have been suspected of a caudal block in the combined use. To avoid these issues of a caudal block, this study introduces a novel dorsal penile nerve block (DPNB) via perineum guided by ultrasound as an alternative to a caudal block in pediatric circumcision surgeries. Methods: A total of 104 pediatric patients scheduled for circumcision surgeries were involved and randomly divided into 2 groups: the CB group (n=52) and the DPNB group (n=52). A laryngeal mask was inserted followed by induction and maintenance anesthesia of inhaled sevoflurane. In the DPNB group, a dorsal penile nerve block (DPNB) guided by a real-time ultrasonography was performed by a single injection via perineum of 0.25% ropivacaine plus 0.8% lidocaine with total injection volume of 3-5ml. In the CB group, a dose of 0.5 ml/kg was given via the caudal canal following the same general anesthesia with that of Group DPNB. The time to the first analgesic demand after surgery is the key data collected for comparing between the two study groups. Heart rates and respiratory rates changes before and during the surgical procedure, pain score when leaving the PACU, and the time taken for the first micturition after a surgery were also recorded to analyze the differences in analgesic effects between the CB and DPNB groups. Results: No significant difference in heart rates and respiratory rates was found between the two groups before and during the surgery. Pain scores were similar before pediatric patients leave the PACU. However, the time taken for the first micturition after a surgery in Group DPNB is shorter than Group CB. The patients in Group DPNB asked for analgesics later than those in Group CB. Additionally, no significant differences in adverse effects were noted between two groups except the numbness of the lower limbs occurring less in Group DPNB. Conclusions: The ultrasound-guided dorsal penile nerve block via perineal approach can basically act as a safe and effective alternative to the caudal block in pediatric patients undergoing circumcision surgeries. Clinical Trials identifier is ChiCTR-IPR-15006670. Protocol is available at http://www.chictr.org.cn/showproj.aspx?proj=11319.


Assuntos
Anestesia Geral/métodos , Circuncisão Masculina/métodos , Pênis/cirurgia , Nervo Pudendo/efeitos dos fármacos , Criança , Pré-Escolar , Humanos , Lidocaína/administração & dosagem , Masculino , Bloqueio Nervoso/métodos , Medição da Dor/métodos , Pênis/inervação , Ropivacaina/administração & dosagem
6.
Int J Radiat Oncol Biol Phys ; 103(5): 1212-1220, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30529374

RESUMO

PURPOSE: Radiation therapy (RT) offers an important and curative approach to treating prostate cancer, but it is associated with a high incidence of erectile dysfunction (ED). It is not clear whether the etiology of radiation-induced ED (RI-ED) is driven by RT-mediated injury to the vasculature, the nerves, or both. This pilot study sought to distinguish the effects of vascular and nerve injury in RI-ED by applying a vascular radioprotectant in a rat model of prostate RT. METHODS: A single dose of the thrombopoietin mimetic (TPOm; RWJ-800088), previously shown to mitigate radiation-induced vascular injury, was administered 10 minutes after single-fraction conformal prostate RT. Nine weeks after RT, rats were assessed for erectile and arterial function. Nerve markers were quantified with reverse transcriptase polymerase chain reaction. Immunofluorescent microscopy further characterized vascular effects of RT and TPOm. RESULTS: Sham animals and animals that received RT and TPOm showed significant arterial vasodilation in response to systemic hydralazine (24.1% ± 7.3% increase; P = .03 in paired t test). However, animals that received RT and vehicle were unable to mount a vasodilatory response (-7.4% ± 9.9% increase; P = .44 in paired t test). TPOm prevented RT-induced change in the penile artery cross-sectional area (P = .036), but it did not ameliorate cavernous nerve injury as evaluated by gene expression of neuronal injury markers. Despite significant structural and functional vascular protective effects and some trends for differences in nerve injury/recovery markers, TPOm did not prevent RI-ED at 9 weeks, as assessed by intracavernous pressure monitoring after cavernous nerve stimulation. CONCLUSIONS: These data suggest that vascular protection alone is not sufficient to prevent RI-ED and that cavernous nerve injury plays a key role in RI-ED. Further research is required to delineate the multifactorial nature of RI-ED and to determine if TPOm with modified dosing regimens can mitigate against nerve injury either through direct or vascular protective effects.


Assuntos
Disfunção Erétil/prevenção & controle , Pênis/efeitos da radiação , Peptídeos/administração & dosagem , Próstata/efeitos da radiação , Protetores contra Radiação/administração & dosagem , Vasodilatação/efeitos da radiação , Animais , Artérias/diagnóstico por imagem , Artérias/efeitos dos fármacos , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Hidralazina/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Manometria/métodos , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Ereção Peniana/efeitos da radiação , Pênis/irrigação sanguínea , Pênis/efeitos dos fármacos , Pênis/inervação , Projetos Piloto , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Ultrassonografia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
7.
BJU Int ; 123(3): 465-473, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30303604

RESUMO

OBJECTIVES: To evaluate the 1-year efficacy of chitosan membrane (ChiMe) application on the neurovascular bundles (NVBs) after nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) in potency recovery rate. To compare the results with those of a contemporary cohort of patients who did not benefit from chitosan use. PATIENTS AND METHODS: Patients in the ChiMe group were enrolled at our institution from July 2015 to September 2016 in a preliminary phase II study. All of them underwent NS-RARP with ChiMe applied on the NVBs and were followed over time to complete a 1-year follow-up. The control group was composed of patients who underwent NS-RARP at our institution without the application of ChiMe from January 2015. The patients were further classified into two groups based on the amount of nerves spared: Group A, comprised patients who underwent a monolateral or bilateral full NS; Group B, comprised patients in which a full NS was not performed. The demographics, peri- and postoperative data, and complications were recorded and compared. Potency recovery was recorded for Group A vs Group B in both the ChiMe and the control groups. RESULTS: In all, 136 patients were enrolled in the ChiMe group and 334 patients in the control group. There were no differences between groups in terms of baseline variables. Based on the amount of nerves preserved, 183 patients were included in Group A and 287 in Group B. Odds ratios at different time points showed that the only two factors influencing potency recovery were the amount of nerves preserved (Group A vs Group B) and the application or not of ChiMe on the NVBs spared. Comparing the ChiMe vs control groups at different time points, we found a statistically significant improvement in the potency recovery rate in the ChiMe group at 1 month (36.76% vs 25.88%; P = 0.02) and 2 months (52.2% vs 39.22%; P = 0.01) after surgery, showing a favourable trend at every time point of the entire follow-up period, even if not significant after the second postoperative month. In Group A, the log-rank test showed a statistically significant difference between the ChiMe vs control groups (P = 0.02), in particular at 1 and 2 months after surgery (P = 0.02 and P = 0.01, respectively). CONCLUSION: The application of ChiMe on the NVBs resulted in a higher potency recovery rate at 1 and 2 months after a bilateral or monolateral full NS-RARP. A trend of a higher and shorter potency recovery rate showed it to be favourable to use ChiMe, even in the cohort of patients who did not undergo a full NS procedure.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Quitosana/uso terapêutico , Ereção Peniana/efeitos dos fármacos , Prostatectomia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Materiais Biocompatíveis/farmacologia , Quitosana/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Ereção Peniana/fisiologia , Pênis/inervação , Pênis/fisiologia , Estudos Prospectivos , Prostatectomia/efeitos adversos , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
8.
J Clin Monit Comput ; 33(1): 155-163, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29520678

RESUMO

Bulbocavernosus reflex (BCR) monitoring is used to assess the integrity of urinary and bowel function. In this study, we evaluated the feasibility of BCR monitoring during untethering surgery in infants and children to predict postoperative urinary and bowel dysfunction. The records of 22 patients ranging from 4 days to 10 years old (mean 2.7 ± 3.3 years) were reviewed. Anesthesia was maintained by propofol or sevoflurane/opioid without neuromuscular blockade. BCR waveforms induced by electrical stimulation (20-40 mA, train-of-four pulses with 500 Hz) to the penis or clitoris were recorded from bilateral external anal sphincters. To assess the sensitivity and specificity of BCR monitoring, we investigated the association between a significant continuous decrease in BCR amplitude at the end of surgery and postoperative urinary and bowel dysfunction after surgery. Reproducible baseline BCR waveforms were successfully recorded in 20 of 22 patients (90.9%). A significant continuous decrease in BCR amplitude was observed in 8 patients. The results of intraoperative BCR monitoring included three true-positives, twelve true-negatives, five false-positives, and zero false-negatives. Therefore, the sensitivity and specificity of BCR monitoring used to predict postoperative urinary and bowel dysfunction were 100 and 70.6%, respectively. BCR monitoring during untethering surgery in infants and children under general anesthesia was found to be a feasible method to prevent postoperative urinary and bowel dysfunction.


Assuntos
Anestesia/métodos , Clitóris/inervação , Estimulação Elétrica/instrumentação , Monitorização Intraoperatória/instrumentação , Pênis/inervação , Canal Anal , Anestésicos/uso terapêutico , Criança , Pré-Escolar , Estimulação Elétrica/métodos , Reações Falso-Positivas , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Monitorização Intraoperatória/métodos , Reflexo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
Med Hypotheses ; 122: 19-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30593410

RESUMO

Erectile dysfunction after nerve injury is a common disease after radical prostatectomy. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which plays an important role in the survival of existing neurons, the differentiation of new neurons, and synaptic plasticity. It has been demonstrated that low-intensity pulsed ultrasound (LIPUS) accelerates bone healing and axonal regeneration after injury. LIPUS may also be able to stimulate neuronal activity and enhance the levels of neurotrophic factors. Evidence suggests that elevated levels of BDNF in the brain have protective effects against neurodegenerative diseases. Previous studies have shown that the treatment on cavernous nerve injury repair, and protective effect plus neuro-regeneration effect by low-intensity pulsed ultrasound. They shared the similar mechanism including several trophic factors stimulation, Pl3K/akt pathway activation, and anti-fibrosis mechanism. We hypothesized that due to its combined neuroregenerative and protective effects, the non-invasive and easy-to-use method of LIPUS stimulation could have a therapeutic effect on erectile dysfunction stemming from cavernous nerve injury.


Assuntos
Disfunção Erétil/terapia , Inflamação , Prostatectomia/efeitos adversos , Ondas Ultrassônicas , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Masculino , Modelos Teóricos , Regeneração Nervosa , Doenças Neurodegenerativas/metabolismo , Pênis/lesões , Pênis/inervação , Ratos , Ratos Sprague-Dawley
10.
Minerva Chir ; 74(1): 28-36, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30037182

RESUMO

INTRODUCTION: From 25% to 95% of those who have undergone radical prostatectomy (RP) report erectile dysfunction 12 months after surgery. We attempt a review of the available evidence regarding the anatomy of the cavernous nerves and the surgical refinements to enhance sexual function recovery after surgery. EVIDENCE ACQUISITION: The PubMed/Medline database was searched. Duplicates were removed. Studies were selected by the authors according to the aim of the present review. EVIDENCE SYNTHESIS: The cavernous nerves are deemed responsible for erections, but their exact function is still a matter of debate. They do not necessarily have the same distribution in all individuals: in most the cases, these nerves are located posterolaterally, however, it is not uncommon to find some fibers on the anterolateral aspects of the prostate, especially towards the apex. Several technical strategies were proposed in order to intraoperatively identify and spare the neurovascular bundles: despite all efforts, clinical results are still only partially satisfying. CONCLUSIONS: The recovery of potency is one of the most unpredictable outcomes after RP. The advent of the robotic surgical system seems to have brought a trend towards a faster recovery of erectile function.


Assuntos
Ereção Peniana , Prostatectomia , Neoplasias da Próstata/cirurgia , Recuperação de Função Fisiológica , Humanos , Masculino , Pênis/inervação , Prostatectomia/métodos
11.
J Reconstr Microsurg ; 35(2): 129-137, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30078177

RESUMO

INTRODUCTION: Phalloplasty attempts to achieve a functional and aesthetic phallus. Sensation is a key component for sexual pleasure. Sensation is also important for protection in the setting of penile implant insertion. Little data are available on genital sensibility outcomes after phalloplasty, and there are no standardized approaches for assessment of either sensibility or erogenous perception. METHODS: A literature search of PubMed, Google Scholar, and MEDLINE databases was conducted with terms related to genital sensibility after phalloplasty. Data on patient demographics, nerves used for coaptation, and measurements of genital sensibility were collected. Pooled event rates were determined for recovered glans sensibility and recovered erogenous sensation using a Freeman-Tukey arcsine transformation. RESULTS: A total of 341 articles were identified of which 26 met the inclusion criteria for final analysis. The dorsal cutaneous branch of the pudendal nerve and ilioinguinal were the most common donor nerves. The lateral and medial antebrachial cutaneous and lateral femoral cutaneous were the most common recipient nerves. Pooled event rates suggest that some recovered glans sensibility occurs in more than 70% of cismale patients and in more than 90% of transmale patients. Recovered "erogenous" sensation occurs in more than 75% of cismale patients and more than 95% of transmale patients. In cismale patients, outcomes of recovered glans sensibility and erogenous sensation may be better for upper extremity recipient nerves than lower extremity recipient nerves. CONCLUSIONS: Based on the limited data in current literature on genital sensibility after phalloplasty, it is difficult to draw evidence-based conclusions. Yet data support improved outcomes with innervation. A validated outcome measure of "erogenous sensation" and a standardized approach to measuring cutaneous sensibility are required.


Assuntos
Pênis/cirurgia , Nervo Pudendo/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Recuperação de Função Fisiológica/fisiologia , Sensação/fisiologia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Coito , Estética , Humanos , Masculino , Satisfação do Paciente , Pênis/inervação , Resultado do Tratamento
12.
Acta cir. bras ; 34(9): e201900901, 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1054695

RESUMO

Abstract Purpose: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. Methods: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. Results: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). Conclusions: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.


Assuntos
Animais , Masculino , Pênis/inervação , Pênis/irrigação sanguínea , Substâncias Protetoras/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Traumatismos dos Nervos Periféricos/prevenção & controle , Tadalafila/farmacologia , Pênis/efeitos dos fármacos , Pênis/patologia , Prostatectomia/efeitos adversos , Imuno-Histoquímica , Distribuição Aleatória , Reprodutibilidade dos Testes , Colágeno/análise , Colágeno/efeitos dos fármacos , Ratos Wistar , Tecido Elástico/anatomia & histologia , Tecido Elástico/efeitos dos fármacos , Disfunção Erétil/prevenção & controle
13.
J Sex Med ; 15(11): 1558-1569, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30415811

RESUMO

INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement. AIM: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively. METHODS: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system. MAIN OUTCOME MEASURE: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array. RESULTS: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01). CLINICAL IMPLICATIONS: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury. STRENGTH & LIMITATIONS: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice. CONCLUSION: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569.


Assuntos
Disfunção Erétil/terapia , Pênis/inervação , Idoso , Terapia por Estimulação Elétrica , Eletrodos Implantados , Desenho de Equipamento , Disfunção Erétil/etiologia , Disfunção Erétil/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Prostatectomia/efeitos adversos , Traumatismos do Sistema Nervoso/complicações
14.
Biosci Rep ; 38(5)2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30279203

RESUMO

The significance of perineural invasion (PNI) present in penile cancer (PC) is controversial. In order to clarify the predictive role of PNI in the inguinal lymph node (ILN) metastases (ILNM) and oncologic outcome of patients, we performed this meta-analysis and systematic review. The search of PubMed, Embase, and Web of Science was conducted for appropriate studies, up to 20 January 2018. The pooled odds ratio (OR) and hazard ratio (HR) with their 95% confidence interval (CI) were applied to evaluate the difference in ILNM and oncologic outcome between patients present with PNI and those who were absent. A total of 298 in 1001 patients present with PNI were identified in current meta-analysis and systematic review. Significant difference was observed in ILNM between PNI present and absent from patients with PC (OR = 2.98, 95% CI = 2.00-4.45). Patients present with PNI had a worse cancer-specific survival (CSS) (HR = 3.58, 95% CI = 1.70-7.55) and a higher cancer-specific mortality (CSM) (HR = 2.20, 95% CI = 1.06-3.82) than those cases without PNI. This meta-analysis and systematic review demonstrated the predictive role of PNI in ILNM, CSS, and CSM for PC patients.


Assuntos
Canal Inguinal/patologia , Linfonodos/patologia , Neoplasias Penianas/diagnóstico , Pênis/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Canal Inguinal/inervação , Canal Inguinal/cirurgia , Linfonodos/inervação , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Razão de Chances , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Neoplasias Penianas/cirurgia , Pênis/inervação , Pênis/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
15.
Zhonghua Nan Ke Xue ; 24(6): 483-490, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30173451

RESUMO

Objective: To investigate the protective effect of human urine-derived stem cells (USCs) on erectile function and cavernous structure in rats with cavernous nerve injury (CNI). METHODS: Sixty adult male SD rats with normal sexual function were randomly divided into four groups of equal number: sham operation, bilateral CNI (BCNI) model control, phosphate buffered saline (PBS), and USC. The BCNI model was established in the latter three groups of rats by clamping the bilateral cavernous nerves. After modeling, the rats in the PBS and USC groups were treated by intracavernous injection of PBS at 200 µl and USCs at 1×106/200 µl PBS respectively for 28 days. Then, the maximum intracavernous pressure (mICP) and the ratio of mICP to mean arterial pressure (mICP/MAP) of the rats were calculated by electrical stimulation of the major pelvic ganglions, the proportion of nNOS- or NF200-positive nerve fibers in the total area of penile dorsal nerves determined by immunohistochemical staining, the levels of endothelial cell marker eNOS, smooth muscle marker α-SMA and collagen I detected by Western blot, and the smooth muscle to collagen ratio and the cell apoptosis rate in the corpus cavernosum measured by Masson staining and TUNEL, respectively. RESULTS: After 28 days of treatment, the rats in the USC group, as compared with those in the PBS and BCNI model control groups, showed significant increases in the mICP (ï¼»81 ± 9.9ï¼½ vs ï¼»31 ± 8.3ï¼½ and ï¼»33 ± 4.2ï¼½ mmHg, P <0.05), mICP/MAP ratio (0.72 ± 0.05 vs 0.36 ± 0.03 and 0.35 ± 0.04, P <0.05), the proportions of nNOS-positive nerve fibers (ï¼»11.31 ± 4.22ï¼½% vs ï¼»6.86 ± 3.08ï¼½% and ï¼»7.29 ± 4.84ï¼½% , P <0.05) and NF200-positive nerve fibers in the total area of penile dorsal nerves (ï¼»27.31 ± 3.12ï¼½% vs ï¼»17.38 ± 2.87ï¼½% and ï¼»19.49 ± 4.92ï¼½%, P <0.05), the eNOS/GAPDH ratio (0.52 ± 0.08 vs 0.31 ± 0.06 and 0.33 ± 0.07, P <0.05), and the α-SMA/GAPDH ratio (1.01 ± 0.09 vs 0.36 ± 0.05 and 0.38 ± 0.04, P <0.05), but a remarkable decrease in the collagen I/GAPDH ratio (0.28 ± 0.06 vs 0.68 ± 0.04 and 0.70 ± 0.10, P <0.05). The ratio of smooth muscle to collagen in the corpus cavernosum was significantly higher in the USC than in the PBS and BCNI model control groups (17.91 ± 2.86 vs 7.70 ± 3.12 and 8.21 ± 3.83, P <0.05) while the rate of cell apoptosis markedly lower in the former than in the latter two (3.31 ± 0.83 vs 9.82 ± 0.76, P <0.01; 3.31 ± 0.83 vs 9.75 ± 0.91, P <0.05). CONCLUSIONS: Intracavernous injection of USCs can protect the erectile function of the rat with cavernous nerve injury by protecting the nerves, improving the endothelial function, alleviating fibrosis and inhibiting cell apoptosis in the cavernous tissue.


Assuntos
Disfunção Erétil/prevenção & controle , Ereção Peniana/fisiologia , Pênis/inervação , Transplante de Células-Tronco/métodos , Actinas/análise , Animais , Pressão Arterial , Colágeno/análise , Modelos Animais de Doenças , Masculino , Óxido Nítrico Sintase Tipo I/análise , Óxido Nítrico Sintase Tipo III/análise , Nervo Pudendo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Solução Salina/administração & dosagem , Células-Tronco , Urina/citologia
16.
Neurourol Urodyn ; 37(8): 2551-2559, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30187971

RESUMO

AIMS: Rhabdosphincter (RS) muscle injury occurs during prostatectomy, and is a leading cause of stress urinary incontinence (SUI). Current SUI treatments engender significant side effects, which negatively impact patient quality of life. Thus an unmet need exists to develop novel RS regeneration methods. We have shown that Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and we have developed novel peptide amphiphile nanofiber hydrogel delivery of SHH protein to the penis to regenerate smooth muscle after prostatectomy induced injury. If similar SHH signaling mechanisms regulate RS muscle homeostasis, this innovative technology may be adapted for RS regeneration post-prostatectomy. We examine the SHH pathway in human RS muscle. METHODS: Human RS obtained during radical cystoprostatectomy (n = 13), underwent SHH pathway analysis. Primary cultures were established (n = 5), and RS cells were treated with SHH protein, SHH inhibitor, or PBS (control). Immunohistochemical analysis for SHH pathway, skeletal muscle actin, and trichrome stain were performed. RS growth was quantified at 3 and 6 days. RESULTS: SHH, it is receptors patched and smoothened, and transcriptional activators, GLI proteins, were identified in human RS muscle. At 3 and 6 days, RS cells increased 62% and 78% (P = 0.0001) with SHH treatment and decreased 40% (P = 0.0001) and 18% (P = 0.039) with SHH inhibition. CONCLUSIONS: The SHH pathway was identified in human RS. RS growth increased with SHH treatment, indicating intervention may be possible to enhance RS regeneration, and impact SUI. Peptide amphiphile delivery of SHH may be applicable for RS regeneration and SUI prevention.


Assuntos
Proteínas Hedgehog , Músculo Liso/inervação , Músculo Liso/fisiopatologia , Pênis/inervação , Pênis/fisiopatologia , Incontinência Urinária por Estresse/fisiopatologia , Actinas/metabolismo , Apoptose , Técnicas de Transferência de Genes , Homeostase , Humanos , Hidrogéis , Masculino , Nanofibras , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Cultura Primária de Células , Prostatectomia/efeitos adversos , Incontinência Urinária por Estresse/terapia
17.
Ann Plast Surg ; 81(5): 571-575, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29994881

RESUMO

PURPOSE: The lack of erogenous sensitivity in the neovagina is one of the major shortcomings for patients undergoing male-to-female genital confirmation surgery. Remnant fibers of the dorsal nerve of the penis (DNP) after clitroplasty can potentially be used for a second neurovascular pedicle flap for intravaginal erogenous sensation. METHODS: An anatomic dissection of the DNP was performed in 10 male frozen pelvises to identify major trunks and their branches. Lateral branches of DNP were preserved for a sensate "O" pedicle flap for the vagina. The number of main branches in the lateral dorsal aspect of the penis was calculated to ensure sufficient erogenous innervation to the vagina. Cross sections of the penis were used for histological analysis. Optimal width and length of the new sensate flap were described. RESULTS: There were 1, 2, and 3 main branches in the lateral compartment in 2 (20%), 6 (30.7%), and 2 (42.8%) cadavers, respectively. A sensate pedicle flap from the lateral aspect of the glans penis with a mean width of 1.14 cm (range, 0.9-1.28 cm) ensured at least one main branch of the DNP for erogenous sensitivity of the vagina. This sensate vaginal flap and its neurovascular pedicle had a mean length of 9.8 cm (range, 8.7-10.3 cm) allowing its inset into the anterior vaginal canal. CONCLUSION: Lateral branches of the DNP can be preserved for a pedicle sensate flap to the vagina, which can provide patients with an erogenous vaginal "spot" during male-to-female confirmation surgery.


Assuntos
Pênis/inervação , Sensação/fisiologia , Procedimentos de Readequação Sexual/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/inervação , Estruturas Criadas Cirurgicamente/irrigação sanguínea , Estruturas Criadas Cirurgicamente/inervação , Vagina/irrigação sanguínea , Vagina/inervação , Cadáver , Feminino , Humanos , Masculino
18.
J Sex Med ; 15(7): 958-965, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29960630

RESUMO

BACKGROUND: MicroRNAs (miRs) were found to be dysregulated in erectile dysfunction (ED) related to aging, type 2 diabetes mellitus, and vasculogenic abnormalities. However, miR expression in ED after radical prostatectomy (RP) is not known. AIM: To detect abnormal miR expression in post-RP ED and analyze target genes and pathways. METHODS: 16 Sprague Dawley rats were divided into bilateral cavernous nerve crush (BCNC) and control groups. 4 weeks after surgery, erectile function and histological change in the corpus cavernosum were evaluated. Total RNA from 3 rats from each group was isolated and processed to analyze the miR expression profiling by RNA sequencing. The top 10 up-regulated miR profiles were chosen directly and further validated in another 5 rats per each group by quantitative real-time polymerase chain (PCR) reaction. The target genes were predicted by online databases, including: TargetScan, mirwalk, miRanda, miRDB, and DIANA. The enrichment analysis of gene ontology-term analysis and Kyoto Encyclopedia of Genes and Genomes were performed by DAVID database. OUTCOMES: Intra-cavernosal pressure, mean arterial pressure, smooth muscle content, and miR expression were measured. RESULTS: Compared to the control group, the BCNC group had decreased intra-cavernosal/mean arterial pressure ratio and smooth muscle marker (α-smooth muscle actin). The sequence results showed that 124 miR expression dysregulated in the BCNC group, in which 122 miR expression were up-regulated. Of the 122 miRs, 21 miR expressions were increased above 2-fold. Among the top 10 up-regulated miRs, 4 miRs (miR-101a, miR-138, miR-338, and miR-142) levels were finally validated for over-expression by quantitative (PCR) reaction. The gene ontology analysis results showed that these 4 miRs could regulate the processes of cell apoptosis, fibrosis, endothelium, and smooth muscle cells function. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed the target genes were involved in 7 pathways related to ED. CLINICAL TRANSLATION: Our findings provide novel insights into post-RP ED that may stimulate further studies to develop miR targeted therapy or damage detection for ED. STRENGTHS & LIMITATIONS: To our knowledge, this is the first study to identify the miR profiling and function in the BCNC rat model. The rat model might not represent the human condition and the miR was only detected at 1 period. Besides that, there is a high probability of false positives for RNA sequence results. CONCLUSION: 4 dysregulated miRs were found in the BCNC rat model, which may be related to post-RP ED by regulating apoptosis, fibrosis, endothelial, and smooth muscle cells. Liu C, Cao Y, Ko TC, et al. The Changes of MicroRNA Expression in the Corpus Cavernosum of a Rat Model With Cavernous Nerve Injury. J Sex Med 2018;15:958-965.


Assuntos
MicroRNAs/biossíntese , Pênis/lesões , Pênis/inervação , Prostatectomia/efeitos adversos , Animais , Apoptose/fisiologia , Diferenciação Celular , Endotélio/metabolismo , Fibrose/fisiopatologia , Masculino , Músculo Liso/metabolismo , Miócitos de Músculo Liso/metabolismo , Compressão Nervosa , Ratos , Ratos Sprague-Dawley , Traumatismos do Sistema Nervoso/fisiopatologia , Regulação para Cima
19.
Nanomedicine ; 14(7): 2087-2094, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30037776

RESUMO

Erectile dysfunction (ED) critically impacts quality of life in prostatectomy, diabetic and aging patients. The underlying mechanism involves cavernous nerve (CN) damage, resulting in ED in 80% of prostatectomy patients. Peptide amphiphile (PA) nanofiber hydrogel delivery of sonic hedgehog (SHH) protein to the injured CN, improves erectile function by 60% at 6 weeks after injury, by an unknown mechanism. We hypothesize that SHH is a regulator of neurite formation. SHH treatment promoted extensive neurite formation in uninjured and crushed CNs, and SHH inhibition decreased neurites >80%. Most abundant neurites were observed with continuous SHH PA treatment of crushed CNs. Once induced with SHH, neurites continued to grow. SHH rescued neurite formation when not given immediately. SHH is a critical regulator of neurite formation in peripheral neurons under uninjured and regenerative conditions, and SHH PA treatment at the time of injury/prostatectomy provides an exploitable avenue for intervention to prevent ED.


Assuntos
Sistemas de Liberação de Medicamentos , Proteínas Hedgehog/administração & dosagem , Hidrogéis/administração & dosagem , Nanofibras/química , Neuritos/fisiologia , Pênis/inervação , Fragmentos de Peptídeos/administração & dosagem , Animais , Proteínas Hedgehog/química , Hidrogéis/química , Masculino , Neuritos/efeitos dos fármacos , Neurogênese , Pênis/efeitos dos fármacos , Fragmentos de Peptídeos/química , Ratos , Ratos Sprague-Dawley
20.
Asian J Androl ; 20(5): 442-447, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30004040

RESUMO

Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury (CNI) by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage (2 × 105 cells) of ADSCs for intracavernous injection (ICI) and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs (NanoADSCs) were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.


Assuntos
Disfunção Erétil/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Pênis/inervação , Traumatismos dos Nervos Periféricos/complicações , Animais , Rastreamento de Células , Modelos Animais de Doenças , Disfunção Erétil/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
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