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OBJECTIVE: To investigate tyrosine kinase inhibitors (TKI) and gold nanorods (AuNRs) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma (RCC) mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urological cancers. Likewise, the use of nanoparticles in photothermal tumour ablation, although early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNRs and activated with photothermal ablation have shown significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model. MATERIALS AND METHODS: Immunologically naïve nude mice (athymic nude-Foxn1nu ) were injected subcutaneously bilaterally in both flanks (n = 36) with 2.5 × 106 cells of a human metastatic renal cell carcinoma cell line (RCC 786-O). Subcutaneous xenograft tumours developed into 1-cm palpable nodules. AuNRs encapsulated in human serum albumin protein (HSA) nanoparticles were synthesised with or without a TKI and injected directly into the tumour nodule. Irradiation was administered with an 808-nm light-emitting diode laser for 6 min. Mice were humanely killed 14 days after irradiation; tumours were excised, formalin fixed, paraffin embedded, and evaluated for size and the percentage of necrosis by a genitourinary pathologist. The untreated contralateral flank tumours were used as controls. RESULTS: In mice that did not receive irradiation, TKI alone yielded 4.2% tumour necrosis on the injected side and administration of HSA-AuNR-TKI alone yielded 11.1% necrosis. In the laser-ablation models, laser ablation alone yielded 62% necrosis and when paired with HSA-AuNR there was 63.4% necrosis. The combination of laser irradiation and HSA-AuNR-TKI had cell kill rate of 100%. CONCLUSIONS: In the absence of laser irradiation, TKI treatment alone or when delivered via nanoparticles produced moderate necrosis. Irradiation with and without gold particles alone also improves tumour necrosis. However, when irradiation is paired with gold particles and drug-loaded nanoparticles, the combined therapy showed the most significant and synergistic complete tumour necrosis of 100% (P < 0.05). This study illustrates the potential of combination nanotechnology as a new approach in the treatment of urological cancers.
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Carcinoma de Células Renais/terapia , Ouro/administração & dosagem , Neoplasias Renais/terapia , Terapia a Laser , Nanotecnologia , Nanotubos , Proteínas Tirosina Quinases/administração & dosagem , Técnicas de Ablação , Animais , Terapia Combinada , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Nus , Resultado do TratamentoRESUMO
PURPOSE: We sought to develop a reproducible TGF-ß1 injection technique to induce urethral fibrosis in the rat urethra. MATERIALS AND METHODS: A total of 32 male Sprague Dawley® rats weighing 300 to 350 gm were anesthetized with ketamine/xylazine intraperitoneally. Using a 5 mm penoscrotal incision the rat urethra was exposed. In the experimental group varying doses of TGF-ß1 (5, 10 and 25 µg) were injected in each side of the urethral wall. Normal saline infiltration was used in the sham treated group. Rats were sacrificed 2 and 4 weeks following TGF-ß1 injection. Urethral specimens were stained with hematoxylin and eosin, and Masson trichrome, and Western blot evaluations were performed. Normal and strictured urethral tissues from patients were collected and evaluated in the same fashion. RESULTS: There was no evidence of urethral wall thickening or fibrosis in the sham treated group. Varied histological evidence of fibrosis was noted in all experimental groups. There was a significant increase in collagen type I expression 2 weeks after injection of 5, 10 and 25 µg TGF-ß1. Collagen type III expression was significantly increased 2 weeks after injecting 10 and 25 µg of TGF-ß1, which persisted to 28 days after injection. CONCLUSIONS: TGF-ß1 injection can successfully generate a reproducible rat model of urethral spongiofibrosis. This technique is simple, inexpensive and reproducible. Our series is a proof of concept study. Additional studies in larger animals are needed to further confirm our findings.
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Modelos Animais de Doenças , Fator de Crescimento Transformador beta1/administração & dosagem , Uretra/patologia , Estreitamento Uretral/induzido quimicamente , Animais , Fibrose/induzido quimicamente , Injeções , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The objectives of this review are to discuss the current literature and summarise some of the promising areas with which nanotechnology may improve urological care. A Medline literature search was performed to elucidate all relevant studies of nanotechnology with specific attention to its application in urology. Urological applications of nanotechnology include its use in medical imaging, gene therapy, drug delivery, and photothermal ablation of tumours. In vitro and animal studies have shown initial encouraging results. Further study of nanotechnology for urological applications is warranted to bridge the gap between preclinical studies and translation into clinical practice, but nanomedicine has shown significant potential to improve urological patient care.
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Nanomedicina/métodos , Urologia/métodos , Animais , HumanosRESUMO
PURPOSE: This systematic review was done to compare the effectiveness of infection retardant coated inflatable penile prostheses vs noncoated devices. MATERIALS AND METHODS: We systematically reviewed PubMed® and Galileo® to identify all relevant case studies. The postoperative infection incidence rate was compared for coated and noncoated inflatable penile prostheses to determine whether coating the implant affects the rate of surgical implant infection. RESULTS: Included in analysis were 14 clinical case studies in a total of 9,910 patients with a first time implant, including 5,214 inflatable penile prostheses without an infection retardant coating and 4,696 coated inflatable penile prostheses impregnated with minocycline/rifampin (3,158), rifampin/gentamycin immersion (181), vancomycin/gentamycin immersion (181) and a hydrophilic coating only (1,176). For noncoated vs coated prostheses the infection rate was 2.32% vs 0.89% (p <0.01), including 0.63%, 0.55%, 4.42% and 1.11% for minocycline/rifampin, rifampin/gentamycin immersion, vancomycin/gentamycin immersion and hydrophilic coatings, respectively. CONCLUSIONS: This analysis documents a significant advantage of using coated compared to noncoated inflatable penile prostheses to prevent postoperative device infection. Infection retardant coatings that allow antibiotics to elute off the device components decrease the incidence of device infection by approximately 50%. Future studies must address novel techniques, such as preventing bacterial adhesion, to further decrease infectious etiologies.
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Antibacterianos/administração & dosagem , Prótese de Pênis , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/prevenção & controle , Materiais Revestidos Biocompatíveis , Humanos , Incidência , Masculino , Desenho de PróteseRESUMO
INTRODUCTION: Penile implant surgery continues to be an important option for men with erectile dysfunction. Advancements in technology of implants have contributed to improved survival from mechanical breakdown. Prosthesis infection remains a serious adverse event. For the last 8 years, the Titan implant (Coloplast Corporation, Minneapolis, MN, USA) has been available with an infection-retardant polyvinylpyrrolidone coating. AIM: To compare the infection rates between coated three-piece inflatable penile prostheses (IPPs) with the previous non-coated model. MAIN OUTCOME MEASURES: Infection-related revisions reported in the physician-generated, manufacturer-tabulated patient information forms (PIFs). METHODS: PIFs reported into the voluntary, post-market registry of Coloplast Corporation from July 14, 2000 to September 30, 2011 were retrospectively reviewed. Infection-related revisions entered into the product evaluation database for coated and non-coated IPPs were compared. Data were analyzed using Pearson's chi-squared test. RESULTS: The database included 36,391 PIFs related to primary IPP implantation. At 11 years of follow-up, 4.6% (7,031) of non-coated IPPs were removed or replaced due to infections, whereas 1.4% (29,360) of hydrophilic-coated implants reported replacements due to device infections. The hydrophilic coating of the IPP components makes the device slippery and prevents bacterial attachment. The hydrophilic coating allows rapid absorption of antibiotics in an aqueous solution and allows these water-soluble antibiotics to elute off the device into the implant spaces. Unfortunately, information pertaining to what agents were used in the studies patients was not tabulated. The rate of revision due to device infection was reduced 69.56% in patients with hydrophilic-coated IPPs (P<0.001). CONCLUSION: To the best of our knowledge, this is the longest post-marketing registry report related to IPP infections. At 8 years of follow-up, the hydrophilic-coated IPPs demonstrated a significant reduction in revision rates due to infection when compared with the 11-year follow-up of non-coated implants. Since there was no information or uniformity of antibiotics used in the soaking solution, it is uncertain which antibiotic selection provided the best results. In vitro testing against known infectious agents may further benefit IPP patients by reducing the prosthesis infection rate.
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Prótese de Pênis/efeitos adversos , Prótese de Pênis/estatística & dados numéricos , Infecções Relacionadas à Prótese/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
This study reports, for the first time, development of tyrosine kinase inhibitor-loaded, thermosensitive liposomes (TKI/TSLs) and their efficacy for treatment of renal cell carcinoma when triggered by focused ultrasound (FUS). Uptake of these nanoparticles into renal cancer cells was visualized with confocal and fluorescent imaging of rhodamine B-loaded liposomes. The combination of TKI/TSLs and FUS was tested in an in vitro tumor model of renal cell carcinoma. According to MTT cytotoxic assay and flow cytometric analysis, the combined treatment led to the least viability (23.4% ± 2.49%, p < 0.001), significantly lower than that observed from treatment with FUS (97.6% ± 0.67%, not significant) or TKI/TSL (71.0% ± 3.65%, p < 0.001) at 96 h compared to control. The importance of this unique, synergistic combination was demonstrated in viability experiments with non-thermosensitive liposomes (TKI/NTSL + FUS: 58.8% ± 1.5% vs. TKI/TSL + FUS: 36.2% ± 1.4%, p < 0.001) and heated water immersion (TKI/TSL + WB43°: 59.3% ± 2.91% vs. TKI/TSL + FUS: 36.4% ± 1.55%, p < 0.001). Our findings coupled with the existing use of FUS in clinical practice make the proposed combination of targeted chemotherapy, nanotechnology, and FUS a promising platform for enhanced drug delivery and cancer treatment.
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Carcinoma de Células Renais/metabolismo , Liberação Controlada de Fármacos , Temperatura Alta , Neoplasias Renais/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Ondas Ultrassônicas , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Humanos , Neoplasias Renais/tratamento farmacológico , Lipossomos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos da radiação , Resultado do TratamentoRESUMO
PURPOSE: To identify variations in renal function and histology between Caucasian Americans (CA) and African Americans (AA) undergoing robotic nephron-sparing surgery (NSS). METHODS: A retrospective chart review was performed on patients who underwent NSS. Multivariate analysis identified factors affecting postoperative estimated glomerular filtration rate (eGFR). Histology was re-reviewed by pathology to confirm papillary type. RESULTS: A total of 331 patients underwent NSS: CA (n = 212), AA (n = 105), Hispanic (n = 10), and other (n = 4). AA average age (60.1 years) was lower than CA (62.3 years) (P < .001), with a higher proportion of AA women (46%) than CA (37%) (P = .021). AA had a higher incidence of diabetes (58.2%) and hypertension (93.9%). Preoperative average eGFR was similar: 70.35 mL/min for AA versus 69.06 mL/min for CA. Average postoperative eGFR was 50.59 mL/min for AA and 57.85 mL/min for CA. Postoperative creatinine increased more in AA (0.44 mg/dL) versus CA (0.33 mg/dL) (P < .001) even when stratified by pathological stage. Clear cell renal cell carcinoma (RCC) was the most common histology with AA (45%) and CA (60%). A greater than 2-fold higher incidence of papillary RCC was observed in AA (31%) versus CA (13%). AA exhibited a greater proportion of high-grade or type 2 papillary RCC (40% and 30%) versus CA (25% and 13%). CONCLUSIONS: AA patients were treated at a younger age, with a larger proportion of women. Postoperatively, AA experienced a greater increase in serum creatinine. Final histology demonstrated greater papillary RCC incidence in AA and increased likelihood for type 2 papillary RCC, a more aggressive histology.
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Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Rim/fisiopatologia , Procedimentos Cirúrgicos Urológicos/métodos , Adolescente , Adulto , Negro ou Afro-Americano , Idoso , Carcinoma de Células Renais/etnologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/patologia , Neoplasias Renais/etnologia , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , População Branca , Adulto JovemRESUMO
INTRODUCTION: We sought to evaluate the therapeutic effect of adi-pose tissue-derived stem cells (ADSCs) in a rat model of urethral fibrosis. METHODS: Eighteen (18) male Sprague-Dawley rats (300â350 g) were divided into three groups: (1) sham (saline injection); (2) urethral fibrosis group (10 µg transforming growth factor beta 1 (TGF-ß1) injection); and (3) ADSCs group (10 µg TGF-ß1 injection plus 2 × 105 ADSCs). Rat ADSCs were harvested from rat inguinal fat pads. All study animals were euthanized at two weeks after urethral injection. Following euthanasia, rat urethral tissue was harvested for histologic evaluation. Type I and III collagen levels were quantitated by Western blot analysis. RESULTS: TGF-ß1 injection induced significant urethral fibrosis and increased collagen type I and III expression (p<0.05). Significant decrease in submucosal fibrosis and collagen type I and III expression were noted in the ADSCs group compared with the urethral fibrosis group (p<0.05). TGF-ß1 induced fibrotic changes were ameliorated by injection of ADSCs. CONCLUSIONS: Local injection of ADSCs in a rat model of urethral fibrosis significantly decreased collagen type I and III. These findings suggest that ADSC injection may prevent scar formation and potentially serve as an adjunct treatment to increase the success rate of primary treatment for urethral stricture disease. Further animal and clinical studies are needed to confirm these results.
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OBJECTIVE: To detect and measure surgeons' head movement during laparoscopic simulator performance to determine whether expert surgeons have economy of motion in their head movement, including change of direction, compared with intermediate and novice surgeons. We investigated head movement as an objective tool for assessment of laparoscopic surgical skill and its potential use for assessing novice surgeons' progress on the learning curve. DESIGN: After obtaining institutional review board approval, medical students, urology residents, and attending staff surgeons from an academic institution were recruited. Participants were grouped by level of experience and performed tasks on the Electronic Data Generation for Evaluation laparoscopic simulator. Surgeons wore a commercially available wireless electroencephalogram monitor as a flexible, adjustable, and lightweight headband with 7 sensors-2 forehead sensors, 2 ear sensors, and 3 reference sensors. The headband incorporates a 3-axis accelerometer enabling head movement quantification. A variance analysis was used to compare the average head movement acceleration data between each group. SETTING: Tulane University Medical Center, New Orleans, LA, an academic medical center and the principal teaching hospital for Tulane University School of Medicine. PARTICIPANTS: A total of following 19 participants were recruited for the study and stratified by surgical experience into novice (n = 6), intermediate (n = 9), and expert (n = 4) laparoscopy groups: 6 medical students, 9 urology residents (postgraduate years 1 to5), and 4 attending urologists, respectively. RESULTS: Analysis of the average acceleration rate of head movement showed statistically significant differences among groups on both the vertical axis (p = 0.006) and horizontal axis (p = 0.018) in the laparoscopic suturing task. This demonstrated the ability to distinguish between experts and novice laparoscopic surgeons. The average acceleration among groups did not demonstrate statistical significance on the vertical axis (p = 0.078) and horizontal axis (p = 0.077) in the peg transfer task. This may be in response to the ease of the task. The analysis of the forward-backward axis or depth perception also showed no significant differences between groups. CONCLUSION: Accelerometer-based motion analysis of head movement appears to be a useful tool to evaluate laparoscopic skill development of surgeons in terms of their economy of motion, and it could potentially be used for ergonomic assessment of training in the future, and progression on the learning curve.
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Competência Clínica , Educação Médica/métodos , Movimentos da Cabeça , Laparoscopia/educação , Acelerometria , Humanos , Louisiana , Inquéritos e Questionários , Análise e Desempenho de TarefasRESUMO
To characterize and evaluate human serum albumin-encapsulated nanoparticles for drug delivery of a tyrosine kinase inhibitor combined with induction of photothermal ablation combination therapy of renal cell carcinoma (RCC), nanoparticles of varying preparations and concentrations were characterized via zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using clear cell RCC cell line RCC 786-0, a human metastatic carcinoma. Target temperatures of >50°C were consistently attained by 0.1 and 0.05 µM concentrations of irradiated human serum albumin nanoparticle-gold nanorods (HSAP-AuNRs). Irradiated trials of HSAP-AuNRs demonstrated significantly decreased cell viabilities compared with nonirradiated "dark" controls (p < 0.01). Increasing loaded masses of sorafenib (SRF) also significantly decreased relative cell viability of RCC (p < 0.05). Photothermal ablation using HSAP-AuNRs is capable of inducing significant hyperthermia while the loading of SRF further enhances cytotoxicity relative to treatment with HSAP-AuNRs alone. HSAP-AuNR-SRFs have the potential to be an effective, novel combination treatment for advanced RCC.
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Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cumarínicos/química , Composição de Medicamentos , Ouro , Humanos , Neoplasias Renais/patologia , Lasers , Nanotubos , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Albumina Sérica/química , Solubilidade , SorafenibeRESUMO
PURPOSE: To assess determinants of performance applying the tasks of the Basic Laparoscopic Urologic Surgery (BLUS) skills curriculum administered at a single institution. METHODS: After obtaining institutional review board approval, fourth-year medical students, urology residents (postgraduate year 1-5), and staff attending surgeons from an academic institution were recruited. Participants were grouped by level of experience and evaluated on 4 different BLUS modules testing fundamental laparoscopic techniques from September 2012 to September 2013. Task completion time (TCT) and missed objectives were compared with previous laparoscopic experience, amount of endourological training, and scores obtained through the EDGE simulator. RESULTS: TCTs among the participants were slower and accrued greater errors in the novice group (n = 10) than in the intermediate-level (n = 9) and expert-level (n = 9) groups. Completion times on the peg transfer were 213.4, 128.1, and 108.7 seconds (p < 0.05); on the circle cutting were 182.4, 128.3, and 97.2 seconds (p < 0.05); on the clip application were 44.4, 43.2, and 38.1 seconds (p = 0.08); and on the suturing were 286.1, 177.3, and 123.6 seconds (p < 0.05) for novice, intermediate, and expert groups, respectively. When past laparoscopic numbers of participants were compared with TCTs, a positive correlation of R(2) = 0.39 was seen, signifying a relationship between number of laparoscopic cases and TCT outcomes. CONCLUSION: Performance on the EDGE simulator device during the BLUS modules significantly correlated with the amount of laparoscopic experience. Increase in the years of experience and number of laparoscopic cases led to faster and more accurate TCTs.
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Competência Clínica , Educação Médica/métodos , Laparoscopia/educação , Treinamento por Simulação/métodos , Procedimentos Cirúrgicos Urológicos/educação , Adulto , Currículo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 µM from 24 to 96 h, respectively. At maximum dosage and time (15 µM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 µM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.
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1,2-Dipalmitoilfosfatidilcolina/análogos & derivados , Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Portadores de Fármacos , Neoplasias Renais/tratamento farmacológico , Ácido Láctico/química , Nanopartículas , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Ácido Poliglicólico/química , 1,2-Dipalmitoilfosfatidilcolina/química , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Química Farmacêutica , Quitosana/química , Relação Dose-Resposta a Droga , Humanos , Interações Hidrofóbicas e Hidrofílicas , Neoplasias Renais/patologia , Cinética , Lipossomos , Nanotecnologia , Niacinamida/química , Niacinamida/farmacologia , Compostos de Fenilureia/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Sorafenibe , Tecnologia Farmacêutica/métodosRESUMO
PURPOSE: To measure gamma and alpha brain wave activity as a measurement of concentration and stress levels during surgical simulator performance of laparoscopic tasks to determine if expert surgeons have different brain activity patterns compared with intermediate and novice surgeons. MATERIALS AND METHODS: After obtaining Institutional Review Board approval, 1st and 2nd year medical students, urology residents (PGY2-PGY5), and attending urologists from one institution were recruited. Participants were stratified by level of experience and performed laparoscopic tasks on the EDGE laparoscopic simulator. Subjects were evaluated for concentration and stress levels using the electroencephalography (EEG) data extracted from the MUSE(™) headband. The MUSE software developer kit (SDK) allowed quantification of gamma and alpha waves during each task. An analysis of variance was used to compare concentration and stress levels between groups. RESULTS: A total of 19 participants were recruited for the study and stratified by surgical experience into novice, intermediate, and expert laparoscopy groups: 6 medical students, 9 urology residents, and 4 attending urologists, respectively. Concentration and stress were quantified by calculating the area under the curve of the gamma and alpha EEG wave tracings. Stress was significantly lower in the attending urologists compared with the residents and medical students during the laparoscopic suturing and trended toward significance in the peg transfer task (P = 0.0003, P = 0.069). Concentration was significantly higher in the expert group compared with the less experienced groups during both the peg and suture tasks (P = 0.036, P = 0.0039). CONCLUSIONS: EEG brain activity in more experienced surgeons reveals a significant increase in concentration levels with a decrease in stress during simulated laparoscopic tasks compared with novices. This information may correlate with increased proficiency as well as provide objective feedback of progress along the learning curve with the MUSE SDK.
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Atenção/fisiologia , Ondas Encefálicas/fisiologia , Docentes de Medicina , Internato e Residência , Laparoscopia/educação , Estresse Psicológico/fisiopatologia , Estudantes de Medicina , Análise e Desempenho de Tarefas , Urologia/educação , Ritmo alfa/fisiologia , Eletroencefalografia , Ritmo Gama/fisiologia , Humanos , Curva de Aprendizado , Treinamento por Simulação , Software , SuturasRESUMO
OBJECTIVE: To evaluate the treatment effect of collagenase Clostridium histolyticum (CCH) in a rat model of urethral fibrosis. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats (300-350 g) were divided into 5 groups. The rat urethra was injected with normal saline in the sham group and, in the other 4 groups, the rat urethra was injected with 10 µg of transforming growth factor beta 1 to create fibrosis of the urethra. Two weeks following transforming growth factor beta 1 injection, the rats were injected with varying doses of CCH or vehicles, depending on their group. The rats were then euthanized at 4 weeks after CCH or vehicle injection. Urethral tissue was harvested for histologic and molecular analyses. Type I and III collagen levels were evaluated by Western blot analysis. RESULTS: There was urethral fibrosis and to significant increase in collagen type I and III expressions in the urethral fibrosis group compared with the sham group (P <.05). Urethral injection of CCH appeared to be safe and significantly reduce urethral fibrosis as well as collagen type I and III expressions in the high-dose CCH treatment groups when compared with the treatment control group (P <.01). CONCLUSION: This study demonstrated a beneficial effect of CCH injections in a rat model of urethral fibrosis. These findings suggest a potential role for CCH as a therapeutic option in urethral stricture patients and warrant further investigation.
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Colagenase Microbiana/uso terapêutico , Uretra/patologia , Estreitamento Uretral/tratamento farmacológico , Animais , Modelos Animais de Doenças , Fibrose/diagnóstico , Fibrose/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Uretra/efeitos dos fármacosRESUMO
Disorders of ejaculation are the most common form of sexual dysfunction. The ejaculatory reflex consists of two phases: emission and expulsion. Premature ejaculation (PE) can arise from overactivity of the smooth muscles responsible for ejaculation. On the other side of the spectrum, delayed ejaculation occurs when an individual is unable to either reach orgasm within an adequate time frame or experiences no ejaculation. While premature ejaculation and to a lesser degree delayed ejaculation have been recognized for quite some time, no FDA approved treatment has been developed. Since both types of ejaculatory dysfunction have an underlying neuro-muscular component, this may be a target for future treatment strategies. We thereby hypothesize that modulation of the rhythmic contraction of the ejaculatory smooth muscles with either a Sirt3 activator or inhibitor may prove beneficial in treating either premature or delayed ejaculation.
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Ductos Ejaculatórios/metabolismo , Músculo Liso/metabolismo , Ejaculação Precoce/tratamento farmacológico , Sirtuína 3/metabolismo , Trifosfato de Adenosina/metabolismo , Ductos Ejaculatórios/efeitos dos fármacos , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Sirtuína 3/antagonistas & inibidoresRESUMO
OBJECTIVE: To investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on erectile and penile vascular function in the rat. METHODS: The effect of chronic treatment with escitalopram (0.286 mg/kg/day) on change in intracavernosal pressure, maximum intracavernosal pressure/mean arterial pressure, and area under the intracavernosal pressure curve in response to cavernosal nerve stimulation was measured. The effect of chronic escitalopram treatment on endothelial-dependent relaxant responses was investigated in isolated mesenteric and internal pudendal resistance arteries. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and nitric oxide synthase levels were determined with enzymatic assay and Western blot, respectively. RESULTS: Chronic treatment with escitalopram resulted in a significant reduction in the erectile response to cavernosal nerve stimulation without an effect on the response to intracavernosal injection of the nitric oxide donor sodium nitroprusside. The decrease in erectile function was associated with marked increases in NADPH oxidase activity in the corpora cavernosa. Treatment with escitalopram also caused a significant reduction in the relaxant response to acetylcholine in isolated internal pudendal and mesenteric resistance arteries without altering the response to sodium nitroprusside. The decreased response to acetylcholine in the isolated vascular segments was associated with a marked increase in NADPH oxidase activity that was corrected by treatment with the NAPDH oxidase inhibitor apocynin. CONCLUSION: The inhibitory effects of escitalopram on erectile and vascular function were not accompanied by a change in endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase expression, or endothelial nitric oxide synthase activity, suggesting that the inhibitory effect is caused by a decrease in nitric oxide bioavailability mediated by increased NADPH oxidase and reactive oxygen species production.