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Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT.
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Sistemas de Liberação de Medicamentos , Géis , Poloxâmero , Vagina , Feminino , Animais , Administração Intravaginal , Poloxâmero/química , Vagina/efeitos dos fármacos , Progesterona/administração & dosagem , Progesterona/química , Reologia , Camundongos , Cremes, Espumas e Géis Vaginais/administração & dosagem , GravidezRESUMO
Vaginal atrophy affects up to 57% of post-menopausal women, with symptoms ranging from vaginal burning to dysuria. Estradiol hormone replacement therapy may be prescribed to alleviate these symptoms, though many vaginal products have drawbacks including increased discharge and local tissue toxicity due to their hypertonic nature. Here, we describe the development and characterization of a Pluronic F127-coated estradiol nanosuspension (NS) formulation for improved vaginal estradiol delivery. We compare the pharmacokinetics to the clinical comparator vaginal cream (Estrace) and demonstrate increased delivery of estradiol to the vaginal tissue. We utilized ovariectomized (OVX) mice as a murine model of post-menopausal vaginal atrophy and demonstrated equivalent efficacy in vaginal re-epithelialization when dosed with either the estradiol NS or Estrace cream. Further, we demonstrate compatibility of the estradiol NS with vaginal bacteria in vitro. We demonstrate that a Pluronic F127-coated estradiol NS may be a viable option for the treatment of post-menopausal vaginal atrophy.
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Introduction: Mucus in the female reproductive tract acts as a barrier that traps and eliminates pathogens and foreign particles via steric and adhesive interactions. During pregnancy, mucus protects the uterine environment from ascension of pathogens and bacteria from the vagina into the uterus, a potential contributor to intrauterine inflammation and preterm birth. As recent work has demonstrated the benefit of vaginal drug delivery in treating women's health indications, we sought to define the barrier properties of human cervicovaginal mucus (CVM) during pregnancy to inform the design of vaginally delivered therapeutics during pregnancy. Methods: CVM samples were self-collected by pregnant participants over the course of pregnancy, and barrier properties were quantified using multiple particle tracking. 16S rRNA gene sequencing was performed to analyze the composition of the vaginal microbiome. Results: Participant demographics differed between term delivery and preterm delivery cohorts, with Black or African American participants being significantly more likely to delivery prematurely. We observed that vaginal microbiota is most predictive of CVM barrier properties and of timing of parturition. Lactobacillus crispatus dominated CVM samples showed increased barrier properties compared to polymicrobial CVM samples. Discussion: This work informs our understanding of how infections occur during pregnancy, and directs the engineering of targeted drug treatments for indications during pregnancy.
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Microbiota , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , RNA Ribossômico 16S/genética , Vagina/microbiologia , Muco , Microbiota/genéticaRESUMO
Objective: to evaluate the performance statistics of average flow (Qave), voiding time (Vtime), and time to maximum flow (TQmax), in addition to maximum flow (Qmax), for diagnosis of infravesical obstruction. Methods: we reviewed urodynamic studies performed in men > 40 years. Obstruction was considered a grade 3-6 in the Schäfer nomogram. Sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and the receiver operator characteristic (ROC) curve were calculated for the different components of free uroflowmetry. Results: we analyzed 432 studies. Patients with obstruction had lower values of Qmax and Qave, and higher values of Vtime and TQmax. Considering different thresholds, Qmax had sensitivity, specificity, LR + and LR- values of 12-83%, 50-97%, 1.7-4.46 and 0.32-0.9, respectively; Qave had sensitivity, specificity, LR + and LR- values of 65-95%, 21-66%, 1.22-1.94 and 0.19-0.53, respectively; Vtime had sensitivity, specificity, LR + and LR- values of 49-85%, 26-67%, 1.15-1.54, and 0.57-0.74, respectively; TQmax had a sensitivity, specificity, LR + and LR- of 36-81%, 22-72%, 1.04-1.33 and 0.85-0.87, respectively. The areas under the ROC curves for Qmax, Qave, Vtime and TQmax were 0.75 (95% CI = 0.71-0.79, p < 0.001), 0.71 (95% CI = 0.66-0.75, p < 0.001), 0.62 (95% CI = 0.57-0.67, p < 0.001) and 0.55 (95% CI = 0.5-0.6, p = 0.03), respectively. Conclusions: Qave, Vtime, and TQmax showed a statistically significant discriminatory capacity to predict infravesical obstruction, and therefore they have clinical value as a complement to the information provided by Qmax.
Objetivo: evaluar las estadísticas de desempeño del flujo promedio (Qave), el tiempo de evacuación (Vtime) y el tiempo hasta el flujo máximo (TQmax), además del flujo máximo (Qmax), para el diagnóstico de obstrucción infravesical. Métodos: revisamos urodinamias realizadas en hombres > 40 años. La obstrucción se consideró un grado 3-6 en el nomograma de Schäfer. Se calcularon la sensibilidad, la especificidad, la razón de verosimilitud positiva (LR +), la razón de verosimilitud negativa (LR-) y la curva característica operativa del receptor (ROC) para los diferentes componentes de la flujometría libre. Resultados: analizamos 443 estudios. Los pacientes con obstrucción tenían valores más bajos de Qmax y Qave, y valores más altos de Vtime y TQmax. Considerando diferentes umbrales, el Qmax tuvo valores de sensibilidad, especificidad, LR + y LR- de 12-83%, 50-97%, 1.7-4.46 y 0.32-0.9, respectivamente; Qave tuvo valores de sensibilidad, especificidad, LR + y LR- de 65-95%, 21-66%, 1.22-1.94 y 0.19-0.53, respectivamente; Vtime tuvo valores de sensibilidad, especificidad, LR + y LR- de 49-85%, 26-67%, 1.15-1.54 y 0.57-0.74, respectivamente; TQmax tuvo una sensibilidad, especificidad, LR + y LR- de 36-81%, 22-72%, 1.04-1.33 y 0.85-0.87, respectivamente. Las áreas bajo las curvas ROC para Qmax, Qave, Vtime y TQmax fueron 0,75 (95% CI = 0.71-0.79, p < 0,001), 0.71 (95% CI = 0.66-0.75, p < 0,001), 0.62 (95% CI = 0.57-0.67, p < 0,001) y 0.55 (95% CI = 0.5-0.6, p = 0.03), respectivamente. Conclusiones: Qave, Vtime y TQmax mostraron una capacidad discriminatoria estadísticamente significativa para predecir la obstrucción infravesical, por lo que tienen valor clínico como complemento de la información proporcionada por el Qmax.
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Humanos , Masculino , Adulto , Transtornos Urinários/diagnósticoRESUMO
OBJECTIVE: To evaluate the impact on continence rate during 1-year follow-up of a preservation technique that included nonligation of the dorsal vascular complex and sparing of the puboprostatic ligaments and the endopelvic fascia during laparoscopic radical prostatectomy. MATERIAL AND METHODS: Information from 30 patients who underwent the preservation technique was prospectively collected and compared with data from 60 patients who underwent the nonpreservation traditional technique. A single surgeon performed all procedures. RESULTS: Demographic and preoperative characteristics were similar. The mean patient age was 59 years in both groups. All patients were stage cT1c or cT2. Operative time was significantly lower in the preservation technique group (229.6 vs. 262.7 minutes, P < .001). There were no significant differences in intraoperative bleeding, discharge hemoglobin level, blood transfusion rate, length of hospitalization, and drop in the hemoglobin level. The probability of continence recovery was significantly higher in the preservation technique group than in the traditional technique group (hazard ratio = 0.50, 95% CI = 0.31-0.81). The continence rate (0 pads/day) for the preservation technique group versus the traditional technique group at 1, 3, 6, and 12 months was, respectively, 53.3% versus 30% (P = .031), 90% versus 45% (P < .001), 90% versus 63.3% (P = .008), and 96.6% versus 78.3% (P = .024). There were no significant differences between the groups regarding potency and oncologic outcomes. CONCLUSION: Nonligation of the dorsal vascular complex and preservation of the puboprostatic ligaments and the endopelvic fascia improved urinary continence compared with the traditional nonpreservation technique, with no impact in terms of bleeding and oncologic outcomes.
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The current COVID-19 pandemic is a public health emergency that has seriously affected mental health in the general population. Both, studies on previous epidemics and those conducted during the current pandemic have reported a wide range of psychosocial consequences and multiple psychological symptoms as a result of said outbreaks, and among these problems, sleep/wake cycle alterations stand out. Publications addressing this phenomenon have consistently reported that nearly a third of people who experience social isolation develop insomnia, which, in turn, is an important predictor for mental disorders that affect people's functionality, including anxiety disorders, depression and post-traumatic stress disorder. This reflection paper aims to describe the effects that social isolation may have on sleep in the context of the current COVID-19 pandemic.
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We investigated the association between varicocele and benign prostatic hyperplasia in men over the age of 40 years. A total of 296 outpatients were evaluated. Prostate volume was measured with transrectal ultrasound. Varicocele was diagnosed by physical examination and ultrasound. Prostatic hyperplasia was defined as prostate volume greater than or equal to 40 ml. Two groups were compared: patients with prostate volume less than 40 ml and patients with prostate volume greater than or equal to 40 ml. There was a statistically significant difference between the groups in terms of mean age, post-void residual, International Prostate Symptom Score and PSA. The percentage of patients with clinical varicocele in the group with a volume less than 40 ml and the group with a volume equal to or greater than 40 ml was 38.2% and 47.7% respectively (p = .12). There were no differences between the two groups in the percentage of patients with clinical or subclinical varicocele (43.2% vs. 52.2%, respectively, p = .12). No differences were found in the percentage of patients with varicocele when comparing men with prostates smaller than 40 ml and greater than or equal to 40 ml.
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Hiperplasia Prostática , Varicocele , Adulto , Humanos , Masculino , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/epidemiologia , Ultrassonografia , Varicocele/diagnóstico por imagem , Varicocele/epidemiologiaRESUMO
Inflammation contributes to nearly 4 million global premature births annually. Here, we used a mouse model of intrauterine inflammation to test clinically used formulations, as well as engineered nanoformulations, for the prevention of preterm birth (PTB). We observed that neither systemic 17a-hydroxyprogesterone caproate (Makena) nor vaginal progesterone gel (Crinone) was sufficient to prevent inflammation-induced PTB, consistent with recent clinical trial failures. However, we found that vaginal delivery of mucoinert nanosuspensions of histone deacetylase (HDAC) inhibitors, in some cases with the addition of progesterone, prevented PTB and resulted in delivery of live pups exhibiting neurotypical development. In human myometrial cells in vitro, the P4/HDAC inhibitor combination both inhibited cell contractility and promoted the anti-inflammatory action of P4 by increasing progesterone receptor B stability. Here, we demonstrate the use of vaginally delivered drugs to prevent intrauterine inflammation-induced PTB resulting in the birth of live offspring in a preclinical animal model.
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Preparações Farmacêuticas , Nascimento Prematuro , Caproato de 17 alfa-Hidroxiprogesterona , Animais , Feminino , Nanomedicina , Gravidez , Nascimento Prematuro/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Progesterona , ProgestinasRESUMO
Abstract The 2019 coronavirus pandemic (COVID-19) is a public health emergency of international concern, which poses a major challenge to mental health as a result of its unprecedented impact in this 21st century. Research in past epidemics has revealed a deep and wide range of psychosocial consequences at the individual and collective level. There are multiple associated psychological disturbances, ranging from isolated symptoms to complex disorders with marked impairment of functionality, such as insomnia, anxiety, depression, and post-traumatic stress disorder. Therefore, it is necessary for mental health services to develop strategies that allow them to react skillfully and provide support to health workers and the affected population so as to reduce the psychological impact as well as the development of psychiatric symptoms. The purpose of this reflection article is to show the possible consequences on the mental health of the population as a result of social isolation due to the COVID-19 pandemic.
Resumen La pandemia por coronavirus 2019 (COVID-19) es una emergencia de salud pública de preocupación internacional, con impactos sin precedentes en el siglo XXI y hoy representa un gran desafío a la salud mental. Estudios en epidemias anteriores han revelado una profunda y amplia gama de consecuencias psicosociales a nivel individual y comunitario durante los brotes. Son múltiples las alteraciones psicológicas asociadas, que van desde síntomas aislados hasta trastornos complejos, con un deterioro marcado de la funcionalidad, como insomnio, ansiedad, depresión y trastorno por estrés postraumático. En este contexto es necesario que las entidades de salud mental desarrollen estrategias que permitan reaccionar con destreza y que logren un soporte al personal de salud y a la población afectada, en aras de reducir el impacto psicológico y de los síntomas psiquiátricos. Este artículo de reflexión tiene por objetivo mostrar las posibles consecuencias en la salud mental de la población, como resultado del aislamiento social debido a la pandemia de la COVID-19.
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Humanos , Isolamento Social , COVID-19 , Ansiedade , Transtornos de Estresse Pós-Traumáticos , Saúde Mental , Coronavirus , Depressão , Epidemias , Distúrbios do Início e da Manutenção do SonoRESUMO
Preterm birth (PTB) affects nearly 15 million infants each year. Of these PTBs, >25% are a result of inflammation or infection. Animal models have improved our understanding of the mechanisms leading to PTB. Prior work has described induction of intrauterine inflammation in mice with a single injection of lipopolysaccharide (LPS). Herein, we have improved the reproducibility and potency of LPS in the model using two injections distal to the cervix. An in vivo imaging system revealed more uniform distribution of Evans Blue Dye using a double distal injection (DDI) approach compared with a single proximal injection (SPI). Endotoxin concentrations in vaginal lavage fluid from SPI dams were significantly higher than from DDI dams. At equivalent LPS doses, DDI consistently induced more PTB than SPI, and DDI showed a linear dose-response, whereas SPI did not. Gene expression in myometrial tissue revealed increased levels of inflammatory markers in dams that received LPS DDI compared with LPS SPI. The SPI group showed more significant overexpression in cervical remodeling genes, likely due to the leakage of LPS from the uterine horns through the cervix. The more reliable PTB induction and uniform uterine exposure provided by this new model will be useful for further studying fetal outcomes and potential therapeutics for the prevention of inflammation-induced PTB.
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Modelos Animais de Doenças , Inflamação/complicações , Lipopolissacarídeos/toxicidade , Miométrio/patologia , Nascimento Prematuro/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Animais , Feminino , Inflamação/induzido quimicamente , Inflamação/patologia , Camundongos , Miométrio/efeitos dos fármacos , Miométrio/imunologia , Gravidez , Nascimento Prematuro/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Útero/efeitos dos fármacosRESUMO
Preterm birth (PTB) is a significant global problem, but few therapeutic options exist. Vaginal progesterone supplementation has been demonstrated to reduce PTB rates in women with a sonographic short cervix, yet there has been little investigation into the most effective dose or delivery form. Further, vaginal products like progesterone gel often contain excipients that cause local toxicity, irritation, and leakage. Here, we describe the development and characterization of a mucoinert vaginal progesterone nanosuspension formulation for improved drug delivery to the female reproductive tract. We compare the pharmacokinetics and pharmacodynamics to the clinical comparator progesterone gel in pregnant mice and demonstrate increased vaginal absorption and biodistribution via the uterine first-pass effect. Importantly, the unique plasma progesterone double peak observed in humans, reflecting recirculation from the uterus, was also observed in pregnant mice with vaginal dosing. We adapted a mouse model of progesterone withdrawal that was previously believed to be incompatible with testing the efficacy of exogenous progestins, and are first to demonstrate efficacy in preventing preterm birth with vaginal progesterone in this model. Further, improved vaginal progesterone delivery by the nanosuspension led to increased efficacy in PTB prevention. Additionally, we identified histological and transcriptional evidence of cervical and uterine toxicity with a single vaginal administration of the clinical gel that are absent after dosing with the mucoinert nanosuspension formulation. We demonstrate that a progesterone formulation that is designed for improved vaginal progesterone absorption and vaginal biocompatibility could be more effective for PTB prevention.
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Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Administração Intravaginal , Animais , Animais Recém-Nascidos , Feminino , Humanos , Camundongos , Nanogéis/química , Veículos Farmacêuticos/química , Gravidez , Progesterona/farmacocinética , Progesterona/uso terapêutico , Progestinas/farmacocinética , Progestinas/uso terapêutico , Distribuição Tecidual , Cremes, Espumas e Géis Vaginais/químicaRESUMO
HIV pre-exposure prophylaxis (PrEP) strategies have the potential to prevent millions of incident HIV infections each year. However, the efficacy of PrEP strategies has been plagued by issues of non-adherence, likely because of the difficulty in motivating otherwise healthy people to adhere to treatment regimens that require significant behavioral changes and daily discipline. An alternative approach to PrEP is to focus on strategies that fit in to normal, and even desirable, sexual behaviors, such as the use of cleansing enemas by men who have sex with men (MSM) prior to receptive anal intercourse (RAI). Here, we describe preclinical efforts toward optimizing a tenofovir (TFV)-based enema formulation for rectal PrEP. Using a murine model, we compared the plasma and tissue pharmacokinetics of TFV and various TFV prodrugs, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and hexadecyloxypropyl tenofovir (CMX157), after dosing as enema formulations with varying osmolality and ion content. We observed that the enema vehicle composition played a more important role than the TFV prodrug properties in achieving rapid and therapeutically relevant tenofovir diphosphate (TFV-DP) concentrations in mouse colorectal tissue. Our results support the next steps, which are further preclinical (non-human primate) and clinical development of a hypo-osmolar TFV enema product for rectal PrEP.
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Anti-Infecciosos/farmacologia , Pró-Fármacos/farmacologia , Reto/efeitos dos fármacos , Tenofovir/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Administração Retal , Alanina , Animais , Fármacos Anti-HIV/farmacologia , Enema/métodos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Homossexualidade Masculina , Masculino , Camundongos , Organofosfatos/farmacologia , Organofosfonatos/farmacologia , Profilaxia Pré-Exposição/métodos , Minorias Sexuais e de GêneroRESUMO
Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder that affects more than 1 million individuals in the USA. Local therapy with enema formulations, such as micronized budesonide (Entocort®), is a common strategy for treating patients with distally active IBD. However, we hypothesize that micronized particulates are too large to effectively penetrate colorectal mucus, limiting the extent of drug delivery to affected tissues prior to clearance. Here, we describe the development of a budesonide nanosuspension (NS) with the appropriate surface coating and size to enhance penetration of colorectal mucus and ulcerated colorectal tissues. We demonstrate that model fluorescent polystyrene (PS) particles â¼200 nm in size with a muco-inert Pluronic F127 coating provide enhanced mucosal distribution and tissue penetration in mice with trinitrobenzenesulfonic acid (TNBS)-induced IBD compared to model 2 µm PS particles coated with polyvinylpyrollidone (PVP), the stabilizer used in the clinical micronized budesonide formulation. We then used a wet-milling process to develop a budesonide NS formulation with a muco-inert Pluronic F127 coating (particle size â¼230 nm), as well as a budesonide microsuspension (MS) stabilized with PVP (particle size â¼2 µm). Using an acute TNBS mouse model of IBD, we show that daily budesonide NS enema treatment resulted in a significant reduction in the macroscopic (decreased colon weight) and microscopic (histology score) symptoms of IBD compared to untreated controls or mice treated daily with the budesonide MS enema. Further, we show that the budesonide NS enema treated mice had a significantly reduced number of inflammatory macrophages and IL-ß producing CD11b + cells in colon tissue compared to untreated controls or mice treated with the budesonide MS enema. We conclude that the nano-size and muco-inert coating allowed for enhanced local delivery of budesonide, and thus, a more significant impact on local colorectal tissue inflammation.
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Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Budesonida/administração & dosagem , Budesonida/farmacocinética , Sistemas de Liberação de Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Nanopartículas/metabolismo , Animais , Colo/metabolismo , Composição de Medicamentos , Enema , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Muco/metabolismo , Poloxâmero/metabolismo , Poliestirenos/metabolismo , Suspensões , Ácido Trinitrobenzenossulfônico/metabolismoRESUMO
Here we evaluate the potential for local administration of a small molecule FOLH1/GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) as a novel treatment for inflammatory bowel disease (IBD). We found that FOLH1/GCPII enzyme activity was increased in the colorectal tissues of mice with TNBS-induced colitis, and confirmed that 2-PMPA inhibited FOLH1/GCPII enzyme activity ex vivo. In order to maximize local enema delivery of 2-PMPA, we studied the effect of vehicle tonicity on the absorption of 2-PMPA in the colon. Local administration of 2-PMPA in a hypotonic enema vehicle resulted in increased colorectal tissue absorption at 30min compared to 2-PMPA administered in an isotonic enema vehicle. Furthermore, local delivery of 2-PMPA in hypotonic enema vehicle resulted in prolonged drug concentrations for at least 24h with minimal systemic exposure. Finally, daily treatment with the hypotonic 2-PMPA enema ameliorated macroscopic and microscopic symptoms of IBD in the TNBS-induced colitis mouse model, indicating the potential of FOLH1/GCPII inhibitors for the local treatment of IBD.
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Colite/tratamento farmacológico , Enema , Glutamato Carboxipeptidase II/antagonistas & inibidores , Doenças Inflamatórias Intestinais/tratamento farmacológico , Compostos Organofosforados/administração & dosagem , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Glutamato Carboxipeptidase II/metabolismo , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos BALB C , Compostos Organofosforados/sangue , Compostos Organofosforados/farmacocinética , Compostos Organofosforados/uso terapêutico , Ácido TrinitrobenzenossulfônicoRESUMO
Objetivo: La extensión de la linfadenectomía durante la prostatectomía radical es objeto de reciente controversia. Evaluamos nuestros resultados iniciales con una linfadenectomía pélvica extendida laparoscópica en pacientes con carcinoma de próstata de alto riesgo. Métodos: La linfadenectomía pélvica extendida laparoscópica fue realizada en 9 pacientes con carcinoma de próstata localizado. El abordaje fue transperitoneal. La disección incluyó los ganglios localizados en la fosa obturatriz y sobre los vasos ilíacos externos e internos. Resultados: La disección extendida fue unilateral en 6 pacientes y bilateral en 3. El tiempo operatorio promedio de la disección unilateral fue 45 minutos. No hubo conversión a cirugía abierta. No hubo complicaciones relacionadas con la linfadenectomía. El número promedio de ganglios extraídos fue 17 con la disección bilateral y 9 con la disección unilateral. No se detectaron metástasis a ganglios linfáticos. Conclusión: La linfadenectomía pélvica extendida es un procedimiento viable en nuestra clínica a través de un abordaje extraperitoneal.
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Masculino , Excisão de Linfonodo , Laparoscopia , Neoplasias da Próstata/cirurgia , Prostatectomia/classificação , Prostatectomia/instrumentaçãoRESUMO
La prostatectomía radical laparoscópica se ha posicionado como Propósito: una alternativa válida para el manejo del carcinoma localizado de próstata. Reportamos nuestra experiencia inicial con 104 procedimientos. Métodos: Un total de 104 pacientes fueron intervenidos. La edad promedio fue 65 años (rango 43-75). El PSA promedio fue 8.2 (rango 2.3-25). Todos los pacientes tuvieron un tumor estadío cT1 o cT2. El abordaje fue transperitoneal o extraperitoneal. Los pasos del procedimiento son: incisión de la fascia endopélvica, ligadura del plejo venoso anterior, disección del cuello vesical, movilización de las vesículas seminales, disección de la cara posterior de la próstata, sección de los pedículos laterales con o sin preservación de los paquetes neurovasculares, disección del plejo venoso dorsal y el ápex, y anastomosis uretrovesical con sutura continua. Durante las últimas 22 cirugías se realizó una modificación consistente en una preservación anterior de la fascia pélvica lateral (preservación del "Velo de Afrodita"). Resultados: El tiempo operatorio promedio fue 223 minutos (rango: 120-400) y la pérdida de sangre promedio fue 443 cc (rango 150-1500). Hubo conversión a cirugía abierta en cuatro pacientes (3.8 por cien ). Se encontraron márgenes positivos en 26 pacientes (25 por cien ). La distribución por estadío patológico fue pT2a 31 pacientes (29.8 por cien ), pT2b 52 pacientes (50 por cien ) y pT3 21 pacientes (20 por cien ). 59 pacientes completan un seguimiento mayor de 12 meses, de los cuales permanecen 56 (94 por cien ) sin usar protector. Entre los pacientes con preservación bilateral de los paquetes neurovasculares y seguimiento mayor de 12 meses, se encuentra que el 63 por cien de ellos logra erecciones adecuadas. Después de un seguimiento promedio de 13.8 meses (rango 1-34), se encuentra recurrencia bioquímica en el 24 por cien de los pacientes...