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2.
BMJ Case Rep ; 16(9)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723090

RESUMO

Anastomosing haemangioma is a rare subtype of haemangioma, a benign vascular tumour. Its rarity stems from its low incidence and difficulty in obtaining an accurate diagnosis. In addition, its histological resemblance to malignant neoplasms may lead to unnecessary overtreatment. Here, we report the case of an asymptomatic male patient with a slight increase in kidney function who underwent an abdominal ultrasound and a CT scan for suspected renal cell carcinoma. Subsequently, the patient underwent laparoscopic left radical nephrectomy. Histological analysis revealed an anastomosing haemangioma. The patient is currently asymptomatic with no relapse or imaging progression. We also present a literature review on anastomosing haemangioma.


Assuntos
Carcinoma de Células Renais , Hemangioma , Neoplasias Renais , Neoplasias Vasculares , Masculino , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Hemangioma/diagnóstico por imagem , Hemangioma/cirurgia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Nefrectomia
4.
J Surg Case Rep ; 2022(9): rjac419, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36196128

RESUMO

Entero-neovesical fistula is a rare complication of orthotopic ileal neobladder after radical cystectomy occurring in <2% of cases. Surgical treatment is usually required and includes open resection of the affected bowel tract and reconstitution of bowel transit. Here we present a case of a laparoscopic treatment of entero-to-neobladder fistula 8 years after laparoscopic radical cystectomy to demonstrate the feasibility and safety of minimally invasive treatment (Supplementary Video). To the best of our knowledge, this is the first report of minimally invasive treatment of entero-neobladder fistula.

5.
Arch Ital Urol Androl ; 94(1): 32-36, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35352522

RESUMO

OBJECTIVES: Multiparametric magnetic resonance imaging (mpMRI) is a useful tool to diagnose prostate cancer (PCa) but its cost is not negligible. In order to reduce costs and minimize time to diagnosis, it is necessary to establish which patients benefit the most from doing mpMRI prior to prostate biopsy (PB). Our aim was to test if mpMRI still predicts PCa and clinically significant PCa (csPCa) in patients with high clinical suspicion of cancer, defined as prostate specific antigen (PSA) > 10 ng/ml, PSA-Density (PSAD) > 0.15 ng/ml/cc or suspicious digital rectal examination (DRE). MATERIALS AND METHODS: We retrospectively collected data on 206 patients who underwent mpMRI before PB at our Department from January 2017 to July 2018. mpMRI results were classified using Prostate Imaging Reporting and Data System (PI-RADS) version 2. In primary analysis, we evaluated the association of mpMRI with PCa and csPCa and stratified this model for low and high clinical suspicion of cancer. In secondary analysis, we determined the rate of negative PB results in patients with high suspicion of cancer and compared theses rates with those obtained if only those with PI-RADS 3-5 would be biopsied. RESULTS: In primary analysis and overall, mpMRI was predictive of PCa and csPCa. In stratified analysis, mpMRI was still significantly associated with csPCa in patients with PSA > 10 ng/ml and PSAD > 0.15 ng/ml/cc, but not in those with suspicious DRE. In secondary analysis, negative result rates were lower if only patients with PI-RADS 3-5 were biopsied, even in subgroups with high suspicion of cancer based on PSA and PSAD. In patients with suspicious DRE, however, the rate of negative results did not change significantly if only patients with PI-RADS 3-5 were biopsied. CONCLUSIONS: mpMRI is still useful in predicting csPCa in patients with PSA > 10 ng/mL and PSAD > 0.15 ng/ml/cc. If DRE is suspicious, though, mpMRI might be no longer useful in the prediction of PCa.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Biópsia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos
6.
Sci Rep ; 10(1): 14688, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895458

RESUMO

Benign prostate hyperplasia is a dysfunctional disease with an elevated prevalence. Despite the accepted impact of aging and testosterone (TES) in its pathophysiology, its aetiology remains unknown. Recent studies described that serotonin (5-HT) inhibits benign prostate growth through the modulation of the androgen receptor, in the presence of TES. Accordingly, this work aimed to determine the impact of castration and TES replacement in plasmatic and prostatic 5-HT regulation. C57BL/6 mice were submitted to surgical castration and divided into three groups, continually exposed to either vehicle or different TES doses for 14 days. Plasmatic 5-HT concentration was measured before and after castration, and after TES reintroduction. Finally, total prostatic weight and intra-prostatic 5-HT were determined in the different groups. Our results demonstrate that mice prostate exhibits high 5-HT tissue levels and that intra-prostatic total 5-HT was independent of castration or TES reintroduction, in all studied groups. Also, 5-HT plasmatic concentration significantly increased after castration and then normalized after TES administration. Our findings revealed that mice prostate has a high 5-HT content and that total prostatic 5-HT levels do not depend on androgens' action. On the other hand, castration induced a significant increase in plasmatic 5-HT concentration, raising the hypothesis that androgens might be regulating the production of extra-prostatic 5-HT.


Assuntos
Hipogonadismo/patologia , Próstata/patologia , Hiperplasia Prostática/patologia , Serotonina/análise , Testosterona/farmacologia , Animais , Castração , Modelos Animais de Doenças , Hipogonadismo/sangue , Hipogonadismo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Próstata/efeitos dos fármacos , Próstata/metabolismo , Hiperplasia Prostática/sangue , Hiperplasia Prostática/metabolismo , Serotonina/sangue , Serotonina/metabolismo , Testosterona/administração & dosagem , Testosterona/metabolismo
7.
Front Oncol ; 9: 465, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214506

RESUMO

Re-staging transurethral resection, the so-called repeat TUR (Re-TUR), is mandatory in case of incomplete first transurethral resection of bladder tumor (TURBT). In completely resected high grade T1 tumors, Re-TUR is recommended but question remains whether it provides advantages in terms of recurrence-free survival (RFS), progression-free survival (PFS), and cancer specific survival (CSS). The present study aimed to determine whether Re-TUR improves such outcomes in patients with completely resected high-grade T1 bladder cancer (BC). We queried our prospectively maintained database to identify patients with completely resected high-grade T1 BC who underwent (Group A) or not (Group B) Re-TUR before starting intravesical instillations of Bacillus Calmette-Guerin (BCG). The impact of Re-TUR as well as of other tested variables on RFS, PFS, and CSS was tested by Kaplan-Meier method and Log-rank testing. A total of 118 patients underwent Re-TUR, which pointed out no BC in 61 (51.7%), NMIBC in 54 (45.8%) and pT2 disease in 3 (2.5%). The 3 patients with pT2 disease underwent cystectomy, whereas all others were offered BCG treatment. Forty-two patients refused BCG treatment while 2 did not complete it; therefore, Group A (Re-TUR before BCG treatment) consisted of 71 patients whereas Group B consisted of 40 patients who refused Re-TUR but completed BCG treatment. Mean follow-up was 60 months (range 12-142). Kaplan-Meier curves and Log-rank testing showed no difference in RFS, PFS and CSS between patients who had (Group A) or had not (Group B) Re-TUR before starting BCG treatment. Our findings suggest that a Re-TUR in patients with a completely resected high-grade T1 BC does not translate into a better oncological outcome. Given its impact on both patients and healthcare system, the need for Re-TUR in completely resected high grade T1 BC should be further investigated into the framework of a randomized study.

8.
Int J Surg Case Rep ; 53: 238-241, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30428440

RESUMO

INTRODUCTION: Vesicoureteral reflux (VUR) corresponds to the reflux of urine from the bladder into the upper urinary system. It can be a congenital or an acquired anomaly and although its incidence is high in children it is uncommon in the adult life. One of its presentations in the adult population is the presence of recurrent Pyelonephritis. CASE PRESENTATION: Here we report a case of an adult patient with repetitive uncomplicated pyelonephritis caused by VUR. VUR was successfully managed endoscopically with subureteral injection of a bulking agent. A literature review of adult presenting VUR was performed. DISCUSSION: The first presentation of VUR in the adult life is rare. One of the most typical presentation is the presence of recurrent uncomplicated Pyelonephritis. Although no guidelines exists to study the presence of VUR in adult patients with Pyelonephritis, in the presence of several recurrent episodes of Pyelonephritis we should think in VUR as a possible cause. Even in adults, endoscopic management of VUR is an effective treatment with low morbidity. CONCLUSION: VUR can first present in the adult life, with recurrent episodes of UTI. The diagnosis is a suspicious one and is confirmed by VUCG. VUR in adults can be effectively managed with endoscopic injection of bulking agents.

9.
Minerva Urol Nefrol ; 70(6): 624-629, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30160385

RESUMO

BACKGROUND: In urology, lasers are used in a variety of endoscopic procedures such as ureteroscopy and retrograde renal surgery for stone fragmentation of urinary calculi and ablation of urothelial tumors. To perform these procedures, guidewires are used as a preliminary safe-mainstay for referencing the urinary tract. This study aims to determine the effect of two different lasers: holmium:YAG (Ho:YAG) and thulium:YAG (Tm:YAG) lasers on metal guidewires with PTFE coating (PTFE), nitinol guidewires with hydrophilic coating (Hydrophilic) and nitinol guidewires with hydrophilic listed coating (Zebra). METHODS: Different combinations of frequency (5, 10 and 12 Hz) and energy per pulse (0.5, 1.5, and 2.6 J) of Ho:YAG laser were applied on the three kinds of guidewires in two experiments (50 J vs. 100 J of total energy). For the Tm:YAG laser three power levels (5, 35, and 70 W) with a total energy of 100 J were applied to the guidewires. The degree of damage (0 to 5) of the guidewire was assessed after each laser application. RESULTS: A higher degree of injury of guidewires was related to higher values of total energy used for the Ho:YAG laser (P=0.036), and to higher values of power applied with the Tm:YAG (P=0.051). The most resistant guidewire to Ho:YAG laser energy was Zebra, followed by PTFE and Hydrophilic (P<0.001). With the Tm:YAG laser, PTFE guidewire appears to be the most resistant and the Hydrophilic the most fragile, although without reaching the statistical significance (P=0.223). CONCLUSIONS: Both lasers revealed a harmful effect on the three tested guidewires. There was an association between the degree of injury and the amount of Ho:YAG laser energy and Tm:YAG laser power. The guidewire Zebra proved to be the safest when using Ho:YAG laser and the PTFE guidewire the most resistant to laser Tm:YAG. Further studies are necessary to confirm these results.


Assuntos
Lasers/efeitos adversos , Desenho de Equipamento , Humanos , Terapia a Laser , Lasers de Estado Sólido , Litotripsia a Laser/efeitos adversos , Ureteroscopia/efeitos adversos , Urologia/instrumentação
10.
Acta Med Port ; 31(2): 101-108, 2018 Feb 28.
Artigo em Português | MEDLINE | ID: mdl-29596769

RESUMO

INTRODUCTION: Smoking is an important risk factor for the development, recurrence and progression of bladder cancer. Our aim was to analyze smoking habits after diagnosis in bladder cancer patients. Additionally, we evaluated patient knowledge about smoking as a risk factor and the urologist role in promoting abstinence. MATERIAL AND METHODS: A cross-sectional, observational and descriptive study was performed in bladder cancer patients, diagnosed between January 2013 and September 2015 (n = 160) in Braga Hospital, in Portugal. RESULTS: Smoking history was present in 71.9% of the sample, with 21.9% current smokers, (40.7% of abstinence after diagnosis). Smoking was acknowledged as a risk factor by 74.4% of the sample, with only 51.3% of ever smokers and 24.4% of non-smokers recognizing smoking as the leading risk factor (p = 0.008). The presence of other household smokers were significantly higher in patients who continued smoking (40%) than in ex-smokers after diagnosis (4.2%) (p = 0.005). The majority of smokers at diagnosis (83.1%) were advised to quit by their urologist, but only one smoker (1.7%) was offered any specific intervention to aid in cessation. DISCUSSION: Smoking is not recognized as the leading risk factor for bladder cancer. This limited awareness, associated with the known difficulties in quitting smoking and the observed lack of smoking cessation interventions, may account for the high current smoking prevalence, albeit in line with other studies. CONCLUSION: This study highlights the need for efficient smoking cessation programs directed to bladder cancer patients.


Introdução: O tabagismo é um importante fator de risco para o desenvolvimento, recorrência e progressão do cancro da bexiga. Este estudo pretendia analisar os hábitos tabágicos após o diagnóstico em doentes com cancro da bexiga. Adicionalmente, foi avaliado o reconhecimento do tabagismo como fator de risco e a atuação médica na promoção da cessação tabágica. Material e Métodos: Estudo transversal, observacional e descritivo realizado em doentes com cancro da bexiga, diagnosticados entre janeiro de 2013 e setembro de 2015 (n = 160) no Hospital de Braga. Resultados: História tabágica estava presente em 71,9% da amostra, com 21,9% de tabagismo atual (40,7% de abstinência após o diagnóstico). O tabagismo foi reconhecido como fator de risco por 74,4% dos doentes, mas apenas 51,3% dos doentes com história tabágica e 24,4% dos não fumadores referem o tabagismo como a principal causa etiológica (p = 0,008). A presença de outros fumadores em casa foi significativamente maior em doentes que mantiveram tabagismo (40%) do que em ex-fumadores após o diagnóstico (4,2%) (p = 0,005). A maioria dos fumadores (83,1%) refere ter sido aconselhada a deixar de fumar, mas apenas um (1,7%) recebeu apoio específico para a cessação. Discussão: O tabagismo não é adequadamente reconhecido como a principal etiologia de cancro da bexiga. Este desconhecimento, aliado à reconhecida dificuldade na abstinência tabágica e ao défice de estratégias promotoras de cessação tabágica observados, poderá justificar a elevada prevalência de fumadores atuais, todavia, em linha com outros estudos. Conclusão: Este estudo evidencia a necessidade de programas de cessação tabágica eficientes dirigidos a pacientes com cancro da bexiga.


Assuntos
Abandono do Hábito de Fumar/estatística & dados numéricos , Neoplasias da Bexiga Urinária , Idoso , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias da Bexiga Urinária/diagnóstico
11.
J Surg Educ ; 75(3): 828-835, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29031522

RESUMO

BACKGROUND: Since the end of the XIX century, teaching of surgery has remained practically unaltered until now. With the dawn of video-assisted laparoscopy, surgery has faced new technical and learning challenges. Due to technological advances, from Internet access to portable electronic devices, the use of online resources is part of the educational armamentarium. In this respect, videos have already proven to be effective and useful, however the best way to benefit from these tools is still not clearly defined. AIMS: To assess the importance of video-based learning, using an electronic questionnaire applied to residents and specialists of different surgical fields. METHODS: Importance of video-based learning was assessed in a sample of 141 subjects, using a questionnaire distributed by a GoogleDoc online form. RESULTS: We found that 98.6% of the respondents have already used videos to prepare for surgery. When comparing video sources by formation status, residents were found to use Youtube significantly more often than specialists (p < 0.001). Additionally, residents placed more value on didactic illustrations and procedure narration than specialists (p < 0.001). On the other hand, specialists prized surgeon's technical skill and the presence of tips and tricks much more than residents (p < 0.001). CONCLUSION: Video-based learning is currently a hallmark of surgical preparation among residents and specialists working in Portugal. Based on these findings we believe that the creation of quality and scientifically accurate videos, and subsequent compilation in available video-libraries appears to be the future landscape for video-based learning.


Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina/métodos , Internato e Residência/métodos , Especialidades Cirúrgicas/educação , Inquéritos e Questionários , Gravação em Vídeo , Feminino , Humanos , Aprendizagem , Masculino , Melhoria de Qualidade
12.
Sci Rep ; 7(1): 15428, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29133842

RESUMO

Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT's inhibitory mechanism is also present in human cells of normal prostate and BPH, namely in cell lines expressing AR when treated with testosterone. In both models, 5-HT's inhibitory mechanism was replicated by specific agonists of 5-Htr1a and 5-Htr1b. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type, whereas 5-HT treatment restored the prostate weight and AR levels. As 5-HT is decreased in BPH, we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a new therapeutic target for BPH.


Assuntos
Próstata/patologia , Hiperplasia Prostática/patologia , Receptores Androgênicos/metabolismo , Serotonina/metabolismo , Animais , Animais Recém-Nascidos , Linhagem Celular , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Masculino , Camundongos , Camundongos Knockout , Células Neuroendócrinas/metabolismo , Células Neuroendócrinas/patologia , Técnicas de Cultura de Órgãos , Tamanho do Órgão/efeitos dos fármacos , Próstata/citologia , Próstata/efeitos dos fármacos , Próstata/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , Ratos , Receptores 5-HT1 de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Testosterona/metabolismo , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo , Regulação para Cima
13.
Cell Physiol Biochem ; 35(1): 104-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25547331

RESUMO

UNLABELLED: BACKGROUND/ AIMS: The knowledge of the molecular network that governs fetal lung branching is an essential step towards the discovery of novel therapeutic targets against pulmonary pathologies. Lung consists of two highly branched systems: airways and vasculature. Ephrins and its receptors, Eph, have been implicated in cardiovascular development, angiogenesis and vascular remodeling. This study aims to clarify the role of these factors during lung morphogenesis. METHODS: Ephrins-B1, -B2 and receptor EphB4 expression pattern was assessed in fetal rat lungs between 15.5 and 21.5 days post-conception, by immunohistochemistry. Fetal rat lungs were harvested at 13.5 dpc, cultured during 4 days and treated with increasing doses of ephrins-B1 and -B2 and the activity of key signaling pathways was assessed. RESULTS: Ephrin-B1 presents mesenchymal expression, whereas ephrin-B2 and its receptor EphB4 were expressed by the epithelium. Both ephrins stimulated pulmonary branching. Moreover, while ephrin-B1 did not affect the pathways studied, ephrin-B2 supplementation decreased activity of JNK, ERK and STAT. This study characterizes the expression pattern of ephrins-B1, -B2 and EphB4 receptor throughout rat lung development. CONCLUSION: Our data highlight a possible role of ephrins as molecular stimulators of lung morphogenesis. Moreover, it supports the idea that classical vascular factors might play a role as airway growth promoters.


Assuntos
Efrina-B1/metabolismo , Efrina-B2/metabolismo , Pulmão/crescimento & desenvolvimento , Animais , Células Cultivadas , Desenvolvimento Embrionário , Efrina-B1/genética , Efrina-B1/farmacologia , Efrina-B2/genética , Efrina-B2/farmacologia , Epitélio/metabolismo , Feminino , Feto/metabolismo , Feto/patologia , Técnicas In Vitro , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Morfogênese , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor EphB4/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Urology ; 82(6): 1444-50, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24094658

RESUMO

OBJECTIVE: To compare the last generation of 3-dimensional imaging (3D) vs standard 2-dimensional imaging (2D) laparoscopy. MATERIALS AND METHODS: A prospective observational study was conducted during the 4th Minimally Invasive Urological Surgical Week Course held in Braga (Portugal) in April 2013. The course participants and faculty were asked to perform standardized tasks in the dry laboratory setting and randomly assigned into 2 study groups; one starting with 3D, the other with 2D laparoscopy. The 5 tasks of the European Training in Basic Laparoscopic Urological Skills were performed. Time to complete each task and errors made were recorded and analyzed. An end-of-study questionnaire was filled by the participants. RESULTS: Ten laparoscopic experts and 23 laparoscopy-naïve residents were included. Overall, a significantly better performance was obtained using 3D in terms of time (1115 seconds, interquartile range [IQR] 596-1469 vs 1299 seconds, IQR 620-1723; P = .027) and number of errors (2, IQR 1-3 vs 3, IQR 2-5.5; P = .001). However, the experts were faster only in the "peg transfer" task when using the 3D, whereas naïves improved their performance in 3 of the 5 tasks. A linear correlation between level of experience and performance was found. Three-dimensional imaging was perceived as "easier" by a third of the laparoscopy-naïve participants (P = .027). CONCLUSION: Three-dimensional imaging seems to facilitate surgical performance of urologic surgeons without laparoscopic background in the dry laboratory setting. The advantage provided by 3D for those with previous laparoscopic experience remains to be demonstrated. Further studies are needed to determine the actual advantage of 3D over standard 2D laparoscopy in the clinical setting.


Assuntos
Competência Clínica , Imageamento Tridimensional , Laparoscopia/métodos , Procedimentos Cirúrgicos Urológicos , Humanos , Laparoscopia/educação , Estudos Prospectivos , Procedimentos Cirúrgicos Urológicos/educação
15.
PLoS One ; 8(6): e67607, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23826327

RESUMO

The glycoprotein 130 (gp130) dependent family of cytokines comprises interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin M (OSM). These cytokines share the membrane gp130 as a common signal transducer. Recently, it was demonstrated that IL-6 promotes, whereas LIF inhibits fetal lung branching. Thus, in this study, the effects on fetal lung morphogenesis of the other classical members of the gp130-type cytokines (IL-11, CLC, CNTF, CT-1 and OSM) were investigated. We also provide the first description of these cytokines and their common gp130 receptor protein expression patterns during rat lung development. Fetal rat lung explants were cultured in vitro with increasing concentrations of IL-11, CLC, CNTF, CT-1 and OSM. Treated lung explants were morphometrically analyzed and assessed for MAPK, PI3K/AKT and STAT3 signaling modifications. IL-11, which similarly to IL-6 acts through a gp130 homodimer receptor, significantly stimulated lung growth via p38 phosphorylation. On the other hand, CLC, CNTF, CT-1 and OSM, whose receptors are gp130 heterodimers, inhibited lung growth acting in different signal-transducing pathways. Thus, the present study demonstrated that although cytokines of the gp130 family share a common signal transducer, there are specific biological activities for each cytokine on lung development. Indeed, cytokine signaling through gp130 homodimers stimulate, whereas cytokine signaling through gp130 heterodimers inhibit lung branching.


Assuntos
Receptor gp130 de Citocina/metabolismo , Citocinas/metabolismo , Pulmão/embriologia , Pulmão/metabolismo , Animais , Apoptose , Proliferação de Células , Feminino , Espaço Intracelular/metabolismo , Pulmão/citologia , Modelos Biológicos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
16.
PLoS One ; 7(1): e30517, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22291973

RESUMO

BACKGROUND: Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are members of the family of the glycoprotein 130 (gp130)-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. METHODOLOGY/PRINCIPAL FINDINGS: LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. CONCLUSIONS/SIGNIFICANCE: The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching.


Assuntos
Feto/metabolismo , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/fisiologia , Pulmão/embriologia , Pulmão/metabolismo , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Fator Inibidor de Leucemia/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/fisiologia , Técnicas de Cultura de Órgãos , Organogênese/genética , Organogênese/fisiologia , Gravidez , Alvéolos Pulmonares/embriologia , Alvéolos Pulmonares/metabolismo , Ratos , Ratos Sprague-Dawley
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