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1.
Clin Radiol ; 75(10): 798.e1-798.e11, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32712007

RESUMO

AIM: To investigate the role of diffusion-weighted imaging (DWI), T2-weighted (W) imaging, and apparent diffusion coefficient (ADC) histogram analysis before, during, and after neoadjuvant chemoradiotherapy (CRT) in the prediction of pathological response in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Magnetic resonance imaging (MRI) at 1.5 T was performed in 43 patients with LARC before, during, and after CRT. Tumour volume was measured on both T2-weighted (VT2W) and on DWI at b=1,000 images (Vb,1,000) at each time point, hence the tumour volume reduction rate (ΔVT2W and ΔVb,1,000) was calculated. Whole-lesion (three-dimensional [3D]) first-order texture analysis of the ADC map was performed. Imaging parameters were compared to the pathological tumour regression grade (TRG). The diagnostic performance of each parameter in the identification of complete responders (CR; TRG4), partial responders (PR; TRG3) and non-responders (NR; TRG0-2) was evaluated by multinomial regression analysis and receiver operating characteristics curves. RESULTS: After surgery, 11 patients were CR, 22 PR, and 10 NR. Before CRT, predictions of CR resulted in an ADC value of the 75th percentile and median, with good accuracy (74% and 86%, respectively) and sensitivity (73% and 82%, respectively). During CRT, the best predictor of CR was ΔVT2W (-58.3%) with good accuracy (81%) and excellent sensitivity (91%). After CRT, the best predictors of CR were ΔVT2W (-82.8%) and ΔVb, 1,000 (-86.8%), with 84% accuracy in both cases and 82% and 91% sensitivity, respectively. CONCLUSIONS: The median ADC value at pre-treatment MRI and ΔVT2W (from pre-to-during CRT MRI) may have a role in early and accurate prediction of response to treatment. Both ΔVT2W and ΔVb,1,000 (from pre-to-post CRT) can help in the identification of CR after CRT.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico por imagem , Neoplasia Residual/patologia , Compostos Organometálicos , Neoplasias Retais/terapia , Sensibilidade e Especificidade , Carga Tumoral
2.
Clin Radiol ; 74(4): 259-267, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739715

RESUMO

AIM: To assess whether there is a significant difference in perfusion parameters between benign and malignant prostatic lesions, focusing on semi-quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and presence of late gadolinium enhancement (LGE). MATERIAL AND METHODS: Three hundred and thirteen patients who underwent multiparametric MRI (mpMRI) of the prostate and with available corresponding histology (prostatectomy or biopsy) were selected retrospectively for this study. The MRI protocol consisted of multiplanar T2-and diffusion-weighted imaging, DCE and delayed axial T1 images. Images were reviewed independently by two radiologists for LGE assessment and Prostate Imaging - Reporting and Data System (PI-RADS) scoring. For each lesion, semi-quantitative analysis of DCE-MRI was performed and the following data were evaluated: time to peak, wash-in rate, wash-out rate, brevity of enhancement, and area under the curve. The presence or absence of LGE in delayed axial T1 images was assessed qualitatively. MRI results were compared to histology. The presence of significant prostate cancer was based both on Epstein criteria (SPC) and Gleason score (GS ≥7). RESULTS: SPC and Gleason score ≥7 tumours showed significant lower time to peak and brevity of enhancement (p<0.001) with higher wash-in rate (p=0.001). LGE was observed in 152/313 (49%) cases; among them 103/152 (68%) did not show SPC whereas 49/152 (32%) had SPC (p<0.001). The presence of LGE determined a risk reduction of SPC resulting as an independent predictor at multivariate analysis (logOR=-0.78, SE 0.33, p=0.02). CONCLUSION: Semi-quantitative perfusion analysis and LGE may help to predict the presence/absence of a significant prostate tumour and represent a promising tool to improve mpMRI diagnostic performance.


Assuntos
Meios de Contraste , Gadolínio , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias da Próstata/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Reprodutibilidade dos Testes
3.
Clin Radiol ; 73(10): 911.e1-911.e7, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30029837

RESUMO

AIM: To evaluate whether perfusion heterogeneity of rectal cancer prior to chemoradiotherapy (CRT) using histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative parameters can predict response to treatment. MATERIALS AND METHODS: Twenty-one patients with histologically proven rectal adenocarcinoma were enrolled prospectively. All patients underwent 1.5 T DCE-MRI before CRT. Tumour volumes were drawn on Ktrans and Ve maps, using T2-weighted (W) images as reference, and the following first-order texture parameters of Ve and Ktrans values were extracted: 25th, 50th, 75th percentile, mean, standard deviation, skewness, and kurtosis. After CRT, patients underwent surgery and according with Rödel's tumour regression grade (TRG), they were classified as poor responders "non-GR" (TRG 0-2) and good responders "GR" (TRG 3-4). Differences between GR and non-GR in DCE-MRI first-order texture parameters were evaluated using the Mann-Whitney test, and their role in the prediction of response was investigated using receiver operating characteristic (ROC) curve analysis. RESULTS: Sixteen (76%) patients were classified as GR and five (24%) were non-GR. Skewness and kurtosis of Ve was significantly higher in non-GR (4.886±1.320 and 36.402±24.486, respectively) than in GR patients (1.809±1.280, p=0.003 and 6.268±8.130, p= 0.011). Ve skewness <3.635 was able to predict GR with an area under the ROC curve (AUC) of 0.988, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Ve kurtosis <21.095 was able to predict response with an AUC of 0.963, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Other parameters were not different between groups or predictors of response. CONCLUSION: Ve skewness and kurtosis seem to be promising in the prediction of response to CRT in rectal cancer patients.


Assuntos
Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Curva ROC , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
4.
Clin Radiol ; 73(6): 555-563, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29459138

RESUMO

AIM: To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. RESULTS: Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%). CONCLUSION: MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Quimiorradioterapia Adjuvante/métodos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Estudos Prospectivos , Neoplasias Retais/patologia , Resultado do Tratamento , Carga Tumoral
5.
Am J Transplant ; 16(6): 1812-26, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26695701

RESUMO

Islet autotransplantation (IAT) is usually performed in patients undergoing pancreatic surgery for chronic pancreatitis. In the present series, IAT was offered also to patients undergoing pancreatic surgery for both nonmalignant and malignant diseases, having either completion pancreatectomy as treatment for severe pancreatic fistulas (n = 21) or extensive distal pancreatectomy for neoplasms of the pancreatic neck (n = 19) or pancreatoduodenectomy because of the high risk of pancreatic fistula (n = 32). Fifty-eight of 72 patients who were eligible to this broader spectrum of indication actually received IAT. There was no evidence of a higher-than-expected rate of major complications for pancreatectomy. Forty-five patients receiving IAT were still alive at the time of the last scheduled follow-up (1375 ± 365 days). Eighteen (95%) of 19 and 11 (28%) of 39 patients reached insulin independence after partial or total pancreatectomy, respectively. The metabolic results were dependent on the transplanted islet mass. Thirty-one of 58 patients had malignant diseases of the pancreas or periampullary region, and only three patients developed ex novo liver metastases after IAT (median follow-up 914 ± 382 days). Our data demonstrate the feasibility, efficacy, and safety of IAT for a broader spectrum of clinical indications beyond chronic pancreatitis.


Assuntos
Sobrevivência de Enxerto , Transplante das Ilhotas Pancreáticas , Pancreatectomia , Pancreatopatias/cirurgia , Pancreatite Crônica/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo , Resultado do Tratamento
6.
Am J Transplant ; 14(1): 202-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24219129

RESUMO

The aim of this study was to investigate liver microvascular adaptation following the intraportal infusion of pancreatic islets (pancreatic islet transplantation [islet-tx]) in diabetic patients using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI was performed before and 7 days after islet-tx in six diabetic patients. Initial area under curve (AUC60) and volume transfer coefficient (Ktrans) were assessed as markers of liver perfusion. Clinical and metabolic monthly follow-up was performed in all patients, considering fasting C-peptide and ß-score as main indices of graft function. High variability in the response of liver microvasculature to islet infusion was observed: two patients showed a significant reduction in liver perfusion after transplantation (pt.2: AUC60 = -23.4%, Ktrans = -31.7%; pt.4: AUC60 = -23.7%, Ktrans = -27.9%); three patients did not show any significant variation of liver perfusion and one patient showed a significant increase (pt.3: AUC60 = +31%, Ktrans = +42.8%). Interestingly, a correlation between DCE-MRI parameters and indices of graft function was observed and, in particular, both patients with DCE-MRI evidence of posttransplantation liver perfusion reduction experienced premature graft failure. Our preliminary study demonstrated that DCE-MRI may identify different adaptive responses of liver microvasculature in patients submitted to islet-tx. These different responses could have an impact on islet engraftment, although reported findings need confirmation from larger studies.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante das Ilhotas Pancreáticas/métodos , Fígado/irrigação sanguínea , Adulto , Idoso , Feminino , Humanos , Fígado/fisiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Microvasos/anatomia & histologia , Pessoa de Meia-Idade
7.
J Clin Ultrasound ; 42(2): 116-20, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23657871

RESUMO

Atherosclerotic renal artery stenosis is a frequent cause of arterial hypertension and/or allograft dysfunction after kidney transplantation and is usually located at the iliac artery anastomosis. Fibromuscular dysplasia is a less frequent, nonatherosclerotic, vascular disease, inducing stenosis at the proximal/mid-distal part of the renal artery. We report the case of a 44-year-old woman, in whom serum creatinine concentration increased and arterial hypertension developed 3 months after renal transplantation. Color Doppler ultrasonography showed a low arterial resistance index and prolonged acceleration time in the interlobar arteries, and a significantly increased peak systolic velocity at the mid third of the renal artery, demonstrating hemodynamically significant stenosis. Percutaneous transluminal angioplasty allowed stenosis correction and was followed by creatinine concentration and arterial blood pressure normalization.


Assuntos
Displasia Fibromuscular/diagnóstico por imagem , Transplante de Rim , Complicações Pós-Operatórias/diagnóstico por imagem , Obstrução da Artéria Renal/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Feminino , Displasia Fibromuscular/etiologia , Humanos , Obstrução da Artéria Renal/etiologia , Doadores de Tecidos
10.
Radiol Med ; 116(4): 564-74, 2011 Jun.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-21431301

RESUMO

PURPOSE: This study evaluated the methods, technical aspects and impact of preoperative radiological guidance in radioguided occult lesion localisation (ROLL) for single nonpalpable breast lesions. MATERIALS AND METHODS: A total of 288 patients underwent ROLL before surgery. Human serum albumin macroaggregates labelled with 3.7-7.4 MBq of technetium(99) were injected into the lesion. In the case of ultrasonographic guidance (221/288 patients), inoculum positioning resulted in a change of echogenicity at the lesion site. In the case of mammographic guidance (67/288 patients), iodinated contrast medium was injected following the radiotracer for subsequent mammographic evaluation. Patients underwent surgery within 24 h from ROLL. A gamma-detecting probe was used to locate the lesion during surgery and guide its removal. After excision, the specimen was examined by either ultrasonography or mammography to verify complete lesion removal before histological evaluation. RESULTS: The lesion was correctly localised in 281/288 patients (97.5%). One ROLL procedure failed because surgery could not be performed within 24 h and the radioactivity decayed. Of the six incorrect localisations, 2 were due to the radiological guidance and 4 to technetium(99) dispersion. CONCLUSIONS: Radiological guidance in ROLL ensured the outcome of the procedure of localisation and removal of single, nonpalpable breast lesions in the majority of cases.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Radiografia Intervencionista , Compostos Radiofarmacêuticos , Agregado de Albumina Marcado com Tecnécio Tc 99m , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Meios de Contraste , Feminino , Humanos , Injeções Intradérmicas , Pessoa de Meia-Idade , Palpação , Cintilografia , Agregado de Albumina Marcado com Tecnécio Tc 99m/administração & dosagem , Ultrassonografia de Intervenção
11.
J Exp Med ; 190(9): 1351-6, 1999 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-10544206

RESUMO

The mechanisms that govern leukocyte transmigration through the endothelium are not yet fully defined. Junctional adhesion molecule (JAM) is a newly cloned member of the immunoglobulin superfamily which is selectively concentrated at tight junctions of endothelial and epithelial cells. A blocking monoclonal antibody (BV11 mAb) directed to JAM was able to inhibit monocyte transmigration through endothelial cells in in vitro and in vivo chemotaxis assays. In this study, we report that BV11 administration was able to attenuate cytokine-induced meningitis in mice. The intravenous injection of BV11 mAb significantly inhibited leukocyte accumulation in the cerebrospinal fluid and infiltration in the brain parenchyma. Blood-brain barrier permeability was also reduced by the mAb. We conclude that JAM may be a new target in limiting the inflammatory response that accompanies meningitis.


Assuntos
Anticorpos Monoclonais/farmacologia , Moléculas de Adesão Celular/imunologia , Quimiotaxia/imunologia , Leucócitos/imunologia , Meningite/imunologia , Animais , Barreira Hematoencefálica/imunologia , Encéfalo/imunologia , Citocinas/farmacologia , Modelos Animais de Doenças , Eosinófilos/metabolismo , Imunofluorescência , Inflamação/imunologia , Interleucina-1/farmacologia , Moléculas de Adesão Juncional , Meningite/líquido cefalorraquidiano , Camundongos , Microscopia de Fluorescência , Monócitos/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/farmacologia
12.
Diabet Med ; 27(8): 960-4, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20653756

RESUMO

AIMS: Few longitudinal imaging studies of liver-engrafted islets after islet transplantation are available for islet-transplant-alone (ITA) and islet-after-kidney (IAK) transplanted patients. Particularly controversial is the link between islet function and the appearance of islet-induced liver focal fatty changes. Aims of this study were to assess liver focal fatty changes at ultrasound after islet transplantation and their relationship with islet function. METHODS: The timing of first ultrasound detection of liver focal fatty changes and the prevalence and duration of these changes were assessed in 30 IAK transplanted patients, in five ITA patients and, retrospectively, in full-, partial- and no-function groups, according to islet function evaluated 1 year after transplantation. Patients with persistent ultrasound detected liver focal fatty changes underwent liver biopsy. Ultrasound positive and negative patients with functioning islets were compared for islet-function and C-peptide-levels during the follow-up. Variations of cholesterol/triglycerides and other metabolic parameters were also recorded at 1 year. RESULTS: Liver focal fatty changes at ultrasound were found in 12 patients (10/30 IAK, 2/5 ITA). First detection was at 6 months in eight cases and at 12 months in four cases. Liver ultrasound changes were of more than 1 year duration in eight cases. Steatosis was found histologically in 8/8 patients. At 12 months, liver ultrasound changes were detected to a greater extent in patients with partial islet function (10/12, eight IAK, two ITA) compared with patients with full islet function. C-peptide-levels were significantly lower in ultrasound-positive than in ultrasound-negative patients. At 18 months, ultrasound- positive patients were more prone to worsening of their function (9/12) compared with ultrasound-negative patients (3/18). No statistically significant differences of cholesterol/triglycerides levels were found in either the total number of patients or the IAK and ITA patients. CONCLUSIONS: Liver focal fatty changes at ultrasound (steatosis) after islet transplantation in IAK and ITA patients may represent an early sign of altered graft function.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Fígado Gorduroso/patologia , Transplante das Ilhotas Pancreáticas , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Diabetes Mellitus Tipo 1/terapia , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia
13.
Am J Transplant ; 9(10): 2372-82, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19681816

RESUMO

Islet transplantation is an effective therapy for restoring normoglycemia in type-1 diabetes, but long-term islet graft function is achieved only in a minority of cases. Noninvasive magnetic resonance imaging of pancreatic islets is an attractive option for "real-time" monitoring of graft evolution. So far, previous studies have been performed in the absence of a standardized labeling procedure and, besides a feasibility study in patients, the effectiveness and safety of various labeling approaches were tested only with high field magnets (4.7 T). In this study, we addressed: (a) standardization of a labeling procedure for human islets with clinically-approved contrast agent Endorem, (b) safety aspects of labeling related to inflammation and (c) quality of imaging both at 7 T and 1.5 T. We have highlighted that the ratio of Endorem/islet is crucial for reproducible labeling, with a ratio of 2.24 ug/IEQ, allowing successful in vivo imaging both with 1.5 T and 7.0 T magnets up to 143 days after intrahepatic transplant. With this standardized labeling procedure, labeled islets are neither inflamed nor more susceptible to inflammatory insults than unlabeled ones. This report represents an important contribution towards the development of a standardized and safe clinical protocol for the noninvasive imaging of transplanted islets in humans.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante das Ilhotas Pancreáticas , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Animais , Meios de Contraste , Diabetes Mellitus Tipo 1/fisiopatologia , Estudos de Viabilidade , Perfilação da Expressão Gênica , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes
14.
Diabet Med ; 26(9): 847-54, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19719704

RESUMO

AIMS: Studies have pointed to insulin resistance as a pathogenic factor in fatty liver. Although pancreatic B-cell function is believed to be involved, its role is unclear. This study was undertaken to test whether fasting C-peptide, an index of fasting B-cell function, was related to intra-hepatic fat (IHF) content in non-diabetic humans. METHODS: We assessed, retrospectively, fasting plasma C-peptide concentration in 31 patients with fatty liver and 62 individuals without fatty liver. The IHF content was measured by proton magnetic resonance spectroscopy ((1)H-MRS), while insulin sensitivity was estimated based on fasting plasma glucose and insulin with the homestasis model assessment (HOMA) 2 method. RESULTS: Age, sex and body mass index (BMI) were not different between groups. Patients with fatty liver had higher fasting insulin (P < 0.01), C-peptide (P < 0.005) and lower insulin sensitivity (HOMA2-%S). Fasting insulin alone explained 14% of the IHF content variability (P < 0.001); inclusion of fasting C-peptide in multivariate regression explained up to 32% (P < 0.001). A subgroup analysis was performed by matching 1 : 1 for HOMA2-%S. These data were analysed by conditional logistic regression which showed that, when HOMA2-%S was matched between groups, fasting C-peptide remained the only significant predictor of fatty liver. CONCLUSIONS: Non-diabetic individuals with fatty liver are characterized by increased fasting plasma C-peptide concentration, irrespective of their insulin resistant state.


Assuntos
Linfócitos B/fisiologia , Glicemia/metabolismo , Peptídeo C/metabolismo , Fígado Gorduroso/metabolismo , Resistência à Insulina/fisiologia , Adulto , Jejum/fisiologia , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Valores de Referência , Estudos Retrospectivos
15.
J Cell Biol ; 135(2): 497-510, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8896605

RESUMO

Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE-cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE-cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen-reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE-cadherin distribution was affected by PMN adhesion to the vessel wall in vivo too. This work suggests that PMN adhesion could trigger intracellular signals in EC that possibly regulate VE-cadherin /catenin complex disorganization. This effect could increase EC permeability and facilitate PMN transmigration during the acute inflammatory reaction.


Assuntos
Adesão Celular , Endotélio Vascular/fisiologia , Junções Intercelulares/fisiologia , Neutrófilos/fisiologia , Transativadores , Western Blotting , Caderinas/análise , Caderinas/fisiologia , Células Cultivadas , Proteínas do Citoesqueleto/análise , Proteínas do Citoesqueleto/fisiologia , Desmoplaquinas , Endopeptidases/metabolismo , Endotélio Vascular/ultraestrutura , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Junções Intercelulares/ultraestrutura , Neutrófilos/ultraestrutura , Veias Umbilicais , alfa Catenina , beta Catenina , gama Catenina
16.
Horm Metab Res ; 41(11): 840-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19598076

RESUMO

This study examined the impact of L-acetylcarnitine treatment on metabolic parameters and body composition in patients with lipodystrophy syndrome secondary to antiretroviral treatment in human immunodeficiency virus (HIV) infection. A total of 9 HIV-1 infected patients with lipodystrophy syndrome (4F/5M, age 41+/-5 years, HIV duration 8+/-2 years, BMI 23.7+/-3.4 kg/m(2), on protease inhibitors and nucleoside analogue Reverse Transcriptase inhibitors) were evaluated before and after 8 months of therapy with L-acetylcarnitine (2 g/die) and 9 matched healthy subjects served as control subjects. In all patients fasting plasma glucose, insulin concentrations (for evaluation of surrogate indexes of insulin sensitivity), lipid profile, lipid oxidation (by indirect calorimetry), body composition (by DEXA), and intramyocellular triglyceride (IMCL) content of the calf muscles (by (1)H NMR spectroscopy) were assessed. After this therapy, in HIV-1 patients, the IMCL content of the soleus had significantly decreased (p=0.03). Plasma FFAs (0.79+/-0.31 to 0.64+/-0.25; p<0.05) and Respiratory Quotient (0.83+/-0.18 to 0.72+/-0.16; p<0.03) also decreased. Insulin sensitivity was significantly lower prior (HOMA-IS 0.56+/-0.30) and nonstatistically different than controls after therapy (0.72+/-0.49 vs. 0.78+/-0.42) whilst the percentage of fat in the legs increased (p=0.05). Eight months of L-acetylcarnitine treatment increased lipid oxidation, decreased intramyocellular triglyceride content, and induced a more physiological distribution of fat deposits.


Assuntos
Acetilcarnitina/uso terapêutico , Composição Corporal/efeitos dos fármacos , Síndrome de Lipodistrofia Associada ao HIV/tratamento farmacológico , Adulto , Glicemia , Estudos de Casos e Controles , Feminino , Síndrome de Lipodistrofia Associada ao HIV/sangue , Humanos , Insulina/sangue , Lipídeos/sangue , Pessoa de Meia-Idade
17.
Eur J Vasc Endovasc Surg ; 37(4): 395-400, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19230726

RESUMO

OBJECTIVE: To evaluate the feasibility of the Adamkiewicz artery (AKA) detection by multidetector computed tomography (CT) data analysis without the need of a dedicated workstation, using low-cost hardware and the freeware OsiriX. METHODS: CT scans of 67 patients undergoing a thoracic or thoraco-abdominal aortic procedure between April 2006 and August 2008 were evaluated with respect to detection rate and AKA level and side using the OsiriX software version 3.2 on Mac OS X computer and compared to results obtained by standard workstation analysis, in a fully blinded analysis. The results were also compared with data compiled from a review of the English-language literature on this topic. RESULTS: (1) AKA identification showed a substantial agreement of 85.07% between the methods (k=0.636). (2) The comparison of AKA level showed a substantial agreement (weighted k=0.661), with consensus in 70.14%. (3) From the literature review, we found that recognition of the AKA was achieved in 466 of 555 cases (83.96%). (4) In 384 (83.3%) cases the AKA originated from a left intercostal artery. (5) The proposed method and literature-compiled data showed a similar AKA level distribution. CONCLUSIONS: Noninvasive AKA location with open-source software and low-cost hardware is feasible. The OsiriX software allows to effectively navigate through CT data not only to study the aorta, but also to detect the AKA, as in the case of the standard method and the literature data. Its availability and ease of use may contribute to make identification of the AKA part of the routine evaluation of CT scans in patients with aortic disease, even where dedicated workstations are not available, with potential benefits for planning therapeutic procedures.


Assuntos
Angiografia/métodos , Processamento de Imagem Assistida por Computador , Software , Medula Espinal/irrigação sanguínea , Medula Espinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/cirurgia , Falso Aneurisma/cirurgia , Aorta Abdominal/cirurgia , Aorta Torácica/cirurgia , Aneurisma Aórtico/cirurgia , Meios de Contraste/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Iopamidol/administração & dosagem , Iopamidol/análogos & derivados , Masculino , Pessoa de Meia-Idade
18.
Abdom Imaging ; 34(4): 514-22, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18587612

RESUMO

In patients affected by periampullary tumors, surgical resection represents the only treatment with curative intent. Preoperative evaluation of vascular involvement is necessary to avoid surgical treatments unable of curative intent resection. The aim of our update article is to assess the performance of multidetector computed tomography (MDCT), endoscopic ultrasonography (EUS), and color Doppler ultrasonography (CDU) in the evaluation of vascular involvement of major peripancreatic vessels, in periampullary tumors, analyzing the current and past literature.


Assuntos
Ampola Hepatopancreática/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Meios de Contraste , Endossonografia , Artéria Hepática , Humanos , Interpretação de Imagem Assistida por Computador , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/patologia , Veia Porta , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores
19.
Mol Biol Cell ; 10(1): 9-22, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9880323

RESUMO

Cadherins are cell-cell adhesion receptors whose adhesive function requires their association with the actin cytoskeleton via proteins called catenins. The small guanosine triphosphatases (GTPases), Rho and Rac, are intracellular proteins that regulate the formation of distinct actin structures in different cell types. In keratinocytes and in other epithelial cells, Rho and Rac activities are required for E-cadherin function. Here we show that the regulation of cadherin adhesiveness by the small GTPases is influenced by the maturation status of the junction and the cellular context. E-cadherin localization was disrupted in mature keratinocyte junctions after inhibition of Rho and Rac. However, an incubation of 2 h was required after GTPase inhibition, when compared with newly established E-cadherin contacts (30 min). Regarding other cadherin receptors, P-cadherin was effectively removed from mature keratinocytes junctions by blocking Rho or Rac. In contrast, VE-cadherin localization at endothelial junctions was independent of Rho/Rac activity. We demontrate that the insensitivity of VE-cadherin to inhibition of Rho and Rac was not due to the maturation status of endothelial junction, but rather the cellular background: when transfected into CHO cells, the localization of VE-cadherin was perturbed by inhibition of Rho proteins. Our results suggest that the same stimuli may have different activity in regulating the paracellular activity in endothelial and epithelial cells. In addition, we uncovered possible roles for the small GTPases during the establishment of E-cadherin-dependent contacts. In keratinocytes, Rac activation by itself cannot promote accumulation of actin at the cell periphery in the absence of cadherin-dependent contacts. Moreover, neither Rho nor Rac activation was sufficient to redistribute cadherin molecules to cell borders, indicating that redistribution results mostly from the homophilic binding of the receptors. Our results point out the complexity of the regulation of cadherin-mediated adhesion by the small GTPases, Rho and Rac.


Assuntos
Caderinas/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Actinas/metabolismo , Animais , Adesão Celular , Diferenciação Celular , Células Cultivadas , Ativação Enzimática , GTP Fosfo-Hidrolases/antagonistas & inibidores , Humanos , Junções Intercelulares/metabolismo , Queratinócitos/citologia , Queratinócitos/metabolismo , Células L , Camundongos
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 4161-4164, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28269199

RESUMO

An accurate detection of myocardial scar using Cardiac CT may have a strong clinical impact; however, the main drawback is the insufficient contrast to noise ratio of delayed iodine enhanced (DIE) CT images, which makes its accurate segmentation (manual as well as automatic) difficult. In this work, we investigate texture parameters applied on the different scans in order to obtain the scans and features that best differentiates normal from scarred myocardium. The experiments on 7 cases of myocarditis show the accuracy of the parameter energy in all scans, as well as the good performance of the angiographic scan (having higher spatial resolution) with different parameters for the segmentation propose. Moreover, the best performance was obtained on the baseline scan for the energy feature, with an accuracy of 94%.


Assuntos
Miocardite/diagnóstico , Tomografia Computadorizada por Raios X , Algoritmos , Desfibriladores Implantáveis , Coração/diagnóstico por imagem , Humanos , Miocardite/diagnóstico por imagem , Miocardite/terapia
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