RESUMO
Focal cortical dysplasias (FCDs) are a frequent cause of epilepsy. It has been reported that up to 40% of them cannot be visualized with conventional magnetic resonance imaging (MRI). The main objective of this work was to evaluate by means of a retrospective descriptive observational study whether the automated brain segmentation is useful for detecting FCD. One hundred and fifty-five patients, who underwent surgery between the years 2009 and 2016, were reviewed. Twenty patients with FCD confirmed by histology and a preoperative segmentation study, with ages ranging from 3 to 43â¯years (14 men), were analyzed. Three expert neuroradiologists visually analyzed conventional and advanced MRI with automated segmentation. They were classified into positive and negative concerning visualization of FCD by consensus. Of the 20 patients evaluated with conventional MRI, 12 were positive for FCD. Of the negative studies for FCD with conventional MRI, 2 (25%) were positive when they were analyzed with automated segmentation. In 13 of the 20 patients (with positive segmentation for FCD), cortical thickening was observed in 5 (38.5%), while pseudothickening was observed in the rest of patients (8, 61.5%) in the anatomical region of the brain corresponding to the dysplasia. This work demonstrated that automated brain segmentation helps to increase detection of FCDs that are unable to be visualized in conventional MRI images.
Assuntos
Encéfalo/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Adolescente , Adulto , Encéfalo/patologia , Encéfalo/cirurgia , Criança , Pré-Escolar , Epilepsia/patologia , Epilepsia/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Malformações do Desenvolvimento Cortical/patologia , Malformações do Desenvolvimento Cortical/cirurgia , Estudos Retrospectivos , Adulto JovemRESUMO
Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.
Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Glucocorticoides/administração & dosagem , Transplante de Rim , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/patologia , Criança , Feminino , Fator de Crescimento de Fibroblastos 23 , Seguimentos , Glucocorticoides/efeitos adversos , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Falência Renal Crônica/cirurgia , Proteínas Klotho , Masculino , Proteínas de Membrana , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
The in vitro process of chondrogenic differentiation of mesenchymal stem cells (MSCs) induces a pre-apoptotic hypertrophic phenotype, guided by the active status of the WNT/ßcatenin pathway. To achieve a stable chondrocyte phenotype for cartilage tissue engineering, it is necessary to gain a better understanding of specific genes that regulate the cartilage tissue phenotype. RNA sequencing (RNA-seq) analysis of tissue samples from bone, cartilage, growth plate and muscle show that Dickkopf-1 (DKK1), a natural WNT canonical signaling inhibitor, is expressed in cartilage tissue. This observation reinforces the concept that inhibition of the WNT/ßcatenin pathway is critical for preventing avoid chondrocyte hypertrophy in vitro. We used two doses of DKK1 in a pellet cell culture system to inhibit the terminal differentiation of chondrocytes derived from bone marrow mesenchymal stem cells (MSCs). Bone marrow MSCs were cultured in chondrogenic induction medium with 50 and 200â¯ng/ml of DKK1 for 21â¯days. The highest doses of DKK1 reduce ßcatenin expression and nuclear localization at day 21, concomitant with reduced expression and activity of hypertrophy markers collagen type X (COL10A1) and alkaline phosphatase (ALPL), thus decreasing the pre-hypertrophic chondrocyte population. Furthermore, DKK1 stimulated expression of collagen type II (COL2A1) and glycosaminoglycans (GAGs), which represent healthy articular cartilage markers. We conclude that exogenous DKK1 impedes chondrocyte progression into a prehypertrophic stage and stimulates expression of healthy articular cartilage markers by blocking the WNT/ßcatenin pathway. Hence, DKK1 may promote a mature healthy articular cartilage phenotype and facilitate cartilage tissue engineering for joint repair.
Assuntos
Biomarcadores/análise , Células da Medula Óssea/patologia , Condrócitos/patologia , Condrogênese , Hipertrofia/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/patologia , Adulto , Apoptose , Células da Medula Óssea/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrócitos/metabolismo , Feminino , Humanos , Hipertrofia/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual , Adulto JovemRESUMO
Osteosarcoma is the most common malignant bone tumor in children and adolescents. Metastasis and poor responsiveness to chemotherapy in osteosarcoma correlates with over-expression of the runt-related transcription factor RUNX2, which normally plays a key role in osteogenic lineage commitment, osteoblast differentiation, and bone formation. Furthermore, WNT/ß-catenin signaling is over-activated in osteosarcoma and promotes tumor progression. Importantly, the WNT/ß-catenin pathway normally activates RUNX2 gene expression during osteogenic lineage commitment. Therefore, we examined whether the WNT/ß-catenin pathway controls the tumor-related elevation of RUNX2 expression in osteosarcoma. We analyzed protein levels and nuclear localization of ß-catenin and RUNX2 in a panel of human osteosarcoma cell lines (SAOS, MG63, U2OS, HOS, G292, and 143B). In all six cell lines, ß-catenin and RUNX2 are expressed to different degrees and localized in the nucleus and/or cytoplasm. SAOS cells have the highest levels of RUNX2 protein that is localized in the nucleus, while MG63 cells have the lowest RUNX2 levels which is mostly localized in the cytoplasm. Levels of ß-catenin and RUNX2 protein are enhanced in HOS, G292, and 143B cells after treatment with the GSK3ß inhibitor SB216763. Furthermore, small interfering RNA (siRNA)-mediated depletion of ß-catenin inhibits RUNX2 expression in G292 cells. Thus, WNT/ß-catenin activation is required for RUNX2 expression in at least some osteosarcoma cell types, where RUNX2 is known to promote expression of metastasis related genes. J. Cell. Biochem. 118: 3662-3674, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Neoplasias Ósseas/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Proteínas de Neoplasias/biossíntese , Osteossarcoma/metabolismo , Via de Sinalização Wnt , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica , Proteínas de Neoplasias/genética , Osteossarcoma/genética , Osteossarcoma/patologiaRESUMO
Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohns disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.
Assuntos
Humanos , Masculino , Adulto Jovem , Neoplasias Peritoneais/complicações , Doença de Crohn/complicações , Mesotelioma Cístico/complicações , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/patologia , Mesotelioma Cístico/cirurgia , Mesotelioma Cístico/patologiaRESUMO
BACKGROUND: Medial patellofemoral ligament (MPFL) is the main restrictor of lateral shifting of the patella, contributing by 60 % in the first 20° flexion of the knee. MPFL reconstruction has been performed in order to restore the stability of the patella with good results.Lyophilized Gracilis tendon allograft (LGA) compared to Cryopreserved Gracilis tendon allograft (CGA) has a lower cost, does not require to maintain cooling chain or preparation. The purpose of this study is to compare the histological and biomechanical characteristics of an experimental model of reconstruction of the MPFL in porcine patellas with LGA versus CGA. METHODS: Randomized controlled experimental study in porcine model conducted on 36 porcine patellas in which 18 were intervened with LGA and 18 were intervened with CGA. The confluent tunnel technique was used for MPFL reconstruction. Maximum tensile force, allograft elongation and stiffness of the construct were measured. The cellularity and collagen tissue distribution were evaluated in the allografts. The histological and biomechanical characteristics of the LGA were compared to those of the CGA. RESULTS: The median of the maximum tensile force for the LGA group was 299.63 N and 280.86 N for the CGA group (p = 0.45). The median of the stiffness was 57.86 N/mm for the LGA and 54.23 N/mm for the CGA (p = 0.2). The median of the elongation for the LGA was 5.95 mm and 6.12 mm for the CGA (p = 0,29). The bone bridge failed in 88.88 % of the constructs with LGA and 94.44 % in those with CGA (p = 0.5). CONCLUSIONS: No differences were observed between the LGA group and the CGA group in maximum tensile force, elongation, stiffness, site of rupture and histological characteristics. The use of a lyophilized Gracilis tendon allograft for MPFL reconstruction confers the same histological and biomechanical characteristics as a cryopreserved Gracilis tendon allograft.
RESUMO
Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohns disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.
Assuntos
Doença de Crohn/complicações , Mesotelioma Cístico/complicações , Neoplasias Peritoneais/complicações , Humanos , Masculino , Mesotelioma Cístico/patologia , Mesotelioma Cístico/cirurgia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Adulto JovemRESUMO
Sarcomatoid squamous carcinoma (ESC) is a rare esophageal neoplasm, with a clinical, etiological and pathological behavior that differs from squamous cancer. From the histological point of view it has a dual configuration. The squamous epithelial component is usually limited to small areas, while the major part is constituted by mesenchymatous (sarcomatoid) polypoid tissue. Treatment is esophagectomy or total esophagogastrectomy depending on the tumor location. Early detection is critical in terms of survival. For large lesions, preoperative chemo-radiotherapy can be considered. We report a 78-year-old male presenting with dysphagia. An upper gastrointestinal endoscopy showed a tumor located below the cardia. The patient was subjected to a total esophageal and gastric resection. In a second operation, the digestive transit was reconstituted in 2 steps. The pathology report informed a sarcomatoid squamous carcinoma. After 18 months of follow up, the patient is ambulatory.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Idoso , Biópsia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
Congenital unilateral overgrowth of the upper extremity affecting only the muscle tissue is rare. We describe on the clinical, histopathological, and neuroimaging findings in a 6-year-old girl with a congenital, non-progressive muscle enlargement of the entire left upper limb with an ipsilateral hand deformity. No cutaneous stigmata or additional features were detected. Sanger sequencing for the AKT1, PIK3CA, and PTEN genes identified an activating c.3140A>G, p.H1047R mutation in the PIK3CA gene from the affected muscle DNA. We demonstrate that isolated congenital muscular upper limb overgrowth with aberrant hand muscles is another condition related genetically to the PIK3CA-related overgrowth spectrum.
Assuntos
Deformidades Congênitas da Mão/enzimologia , Deformidades Congênitas da Mão/genética , Músculo Esquelético/anormalidades , Mutação/genética , Fosfatidilinositol 3-Quinases/genética , Sequência de Bases , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Deformidades Congênitas da Mão/diagnóstico por imagem , Humanos , Hipertrofia , Recém-Nascido , Imageamento por Ressonância Magnética , Dados de Sequência Molecular , Músculo Esquelético/patologia , RadiografiaRESUMO
Sarcomatoid squamous carcinoma (ESC) is a rare esophageal neoplasm, with a clinical, etiological and pathological behavior that differs from squamous cancer. From the histological point of view it has a dual configuration. The squamous epithelial component is usually limited to small areas, while the major part is constituted by mesenchymatous (sarcomatoid) polypoid tissue. Treatment is esophagectomy or total esophagogastrectomy depending on the tumor location. Early detection is critical in terms of survival. For large lesions, preoperative chemo-radiotherapy can be considered. We report a 78-year-old male presenting with dysphagia. An upper gastrointestinal endoscopy showed a tumor located below the cardia. The patient was subjected to a total esophageal and gastric resection. In a second operation, the digestive transit was reconstituted in 2 steps. The pathology report informed a sarcomatoid squamous carcinoma. After 18 months of follow up, the patient is ambulatory.