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  • Article: Plaque-infiltrating T lymphocytes in patients with carotid atherosclerosis: an insight into the cellular mechanisms associated to plaque destabilization.
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    ABSTRACT: AIM: Inflammation plays a crucial role in the progression of atherosclerotic plaques. The aim of the present study was to investigate phenotypic and functional characteristics of plaque-infiltrating T lymphocytes associated with a complicated phenotype of carotid atherosclerotic lesions. METHODS: Atherosclerotic plaques were obtained from 17 patients undergoing carotid endarterectomy and cultured to isolate infiltrating T lymphocytes. Blood samples were obtained from patients and from 20 sex- and age-matched healthy subjects. The presence of lymphocytes (CD3+ cells) within atherosclerotic plaques was determined by immunohistochemistry. Phenotypic characteristics and intracellular cytokine expression of plaque-infiltrating and circulating T lymphocytes were determined by flow cytometry. Cytokine levels in supernatants from infiltrating T cell cultures were evaluated by enzyme-linked immunosorbent assay. RESULTS: A higher number of CD3+ cells was detected in complicated than in uncomplicated plaques. Complicated plaques had higher percentages of tumor necrosis factor (TNF)-α- and interferon (IFN)-γ- positive cells than uncomplicated ones, especially in CD4+ subpopulation. In patients the percentages of TNF-α-positive cells were higher in infiltrating than in circulating lymphocyte samples. Intracellular TNF-α, IFN-γ, interleukin (IL)-4 and IL-10 expression resulted higher in circulating lymphocyte samples from patients than in those from healthy subjects. Supernatants of infiltrating T cell cultures from complicated plaques showed higher levels of TNF-α and lower levels of IL-4 than those from uncomplicated plaques. CONCLUSION: Our data provide new information on the presence of increased percentages of pro-inflammatory T lymphocytes in complicated plaques with respect to uncomplicated ones and support the concept of the key role played by activated T cells in the progression of atherosclerotic lesions.
    The Journal of cardiovascular surgery 05/2012; · 1.56 Impact Factor
  • Article: Criteria for histopathologic diagnosis of aortic disease consensus statement from the SIAPEC-IAP study group of "cardiovascular pathology" in collaboration with the association for Italian cardiovascular pathology.
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    ABSTRACT: Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery. The principal aims of the project are defining histopathological diagnostic criteria, standard nomenclature and classification, methodology and reporting of histopathological study and handling of aortic specimens. In addiction, some current issues and new knowledge emerging from basic aortic research are debated, with the aim of promoting a "modern" and up-to-date view of aortic pathology.
    Pathologica 02/2012; 104(1):1-33.
  • Article: Teaching anatomical pathology in the undergraduate curriculum in medicine: the experience of 'C Course', Sapienza University, Rome.
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    ABSTRACT: INTRODUCTION: The aim of the present article is to describe how Anatomical Pathology is taught in 'C Course' undergraduate Curriculum and to outline the benefits of such an organization. SETTING ANALYSIS: 'C Course' is one of the six undergraduate curricula in Medicine within Sapienza University of Rome, focused on integrated teaching and medical education activities. ORIGINAL EXPERIENCE: In 'C Course', the learning objectives of Anatomical Pathology have been subdivided in four areas: i) an 'early contact' aimed to provide a 'clinical trigger' to students learning basic sciences; ii) a methodological background intended to help students understand the role of pathology in the comprehension of disease mechanisms; iii) the full body of systemic pathology, taught within inter-disciplinary courses devoted to each apparatus; iv) a latest approach, aimed to explain the role of anatomical pathology in diagnosis, grading and staging of tumours, and in the detection of predictive markers. DISCUSSION: Our teaching organization represents a unusual experience in the Italian setting, allowing students to grasp the concept that anatomical pathology can give many contributions to their overall formation: as a trigger for basic sciences, as a central way of understanding etiology, behavior, and diagnostic pathways, and to predict the outcome of any disease, and as a powerful diagnostic and prognostic means to guide therapy. This approach is well perceived by students, whose questionnaires gave the course an above average score, and offers a valuable output in term of students' knowledge, as assessed by their performance in the area of Anatomical Pathology in the National Progress Test.
    Pathologica 04/2011; 103(2):27-31.
  • Article: 2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology.
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    ABSTRACT: The Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology have produced this position paper concerning the current role of endomyocardial biopsy (EMB) for the diagnosis of cardiac diseases and its contribution to patient management, focusing on pathological issues, with these aims: • Determining appropriate EMB use in the context of current diagnostic strategies for cardiac diseases and providing recommendations for its rational utilization • Providing standard criteria and guidance for appropriate tissue triage and pathological analysis • Promoting a team approach to EMB use, integrating the competences of pathologists, clinicians, and imagers.
    Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 12/2011; 21(4):245-74. · 1.63 Impact Factor
  • Article: Morphologic evidence of diffuse vascular damage in human and in the experimental model of ethylmalonic encephalopathy.
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    ABSTRACT: Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1, a mitochondrial sulphur dioxygenase. By studying a suitable mouse model, we found that loss of ETHE1 leads to accumulation of sulphide, which is a poison for COX and other enzymatic activities thus accounting for the main features of EE. We report here the first autopsy case of a child with a genetically confirmed diagnosis of EE, and compare the histological, histochemical and immunohistochemical findings with those of the constitutive Ethe1 (-/-) mice. In addition to COX depleted cells, widespread endothelial lesions of arterioles and capillaries of the brain and gastrointestinal tract were the pathologic hallmarks in both organisms. Our findings of diffuse vascular damage of target critical organs are in keeping with the hypothesis that the pathologic effects of ETHE1 deficiency may stem from high levels of circulating hydrogen sulphide rather than the inability of specific organs to detoxify its endogenous production.
    Journal of Inherited Metabolic Disease 10/2011; 35(3):451-8. · 3.58 Impact Factor

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