Fiorella Calabrese

University of Padova, Padua, Veneto, Italy

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Publications (135)700.53 Total impact

  • Clinical and Molecular Allergy 12/2015; 13(1). DOI:10.1186/s12948-015-0022-z · 1.39 Impact Factor
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    ABSTRACT: Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment. Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues. Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control. \Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.
    BMC Musculoskeletal Disorders 04/2015; 16(1):103. DOI:10.1186/s12891-015-0555-9 · 1.90 Impact Factor
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    ABSTRACT: Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC). Adipose tissue directly stimulates tumor progression independently from body mass index (BMI), but the mechanisms are not fully understood. We studied the morphological, histological and molecular characteristics of peritumoral and distal adipose tissue of 60 patients with EAC, to investigate whether depot-specific differences affect tumor behavior. We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients. We treated OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and we observed increased mRNA levels of leptin and adiponectin receptors, as well as two key regulator genes of epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (α-SMA) and E-cadherin. This effect was greater in cells treated with CM from peritumoral adipose tissue of patients with nodal metastasis and was partially blunted by a leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct effect on the progression of EAC by secreting depot-specific paracrine factors, and leptin is a key player in this crosstalk.
    Oncotarget 03/2015; · 6.63 Impact Factor
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    ABSTRACT: The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the synovial hypervascularity in PsA.
    Clinical Rheumatology 02/2015; DOI:10.1007/s10067-015-2894-1 · 1.77 Impact Factor
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    ABSTRACT: Background Xenotransplantation is a potential answer to the current organ shortage, but the risk of infections related to overimmunosuppression is an important parameter that may predict the recipient's long-term survival. Cytomegalovirus (CMV) in xenotransplanted and immunosuppressed primates is a well-known cause of disease particularly affecting the gastrointestinal (GI) tract and a zoonotic concern.Methods Post-mortem sera and tissues from 45 immunosuppressed and xenografted Macaca fascicularis were evaluated for CMV using antisera specific for the immediate early 1 (IE1), anti-RhCMV, and QPCR for virus.ResultsSerological analysis showed 100% positivity for the presence of CMV antibodies following the application of a specific test designed for RhCMV. Five of 45 primates showed typical lesions of CMV infection in the GI tract, including neutrophilic enteritis and inclusion bodies. Molecular analysis confirmed the presence of recipient's CMV in the tissues with CMV histopathology. Porcine CMV from the donor animals was not found in any of the CMV-specific IHC-positive recipients.Conclusion The presence of active CMV infection in animals intended for xenograft experiments can lead to severe gastrointestinal lesions that could impact the overall aims of the study. In such cases, the animals should be investigated using appropriate (non-human primate-specific) diagnostic tools prior to use and treated aggressively with state-of-the-art antiviral therapy.
    Xenotransplantation 02/2015; 22(2). DOI:10.1111/xen.12153 · 1.78 Impact Factor
  • Fiorella Calabrese, Francesca Lunardi, Helmut Popper
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    ABSTRACT: The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.
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    ABSTRACT: Rationale: α1-antitrypsin (AAT) is a potent protease inhibitor which deficiency is associated with the presence of emphysema. An imbalance of elastase/antielastase, along with an innate inflammation in the lung, is believed to cause lung destruction in α1-antitrypsin deficiency (AATD). It is now apparent that AAT has important immune regulatory roles that would be lost in AATD, yet adaptive immune responses in the lung have not been investigated in patients with AATD. Objectives: To assess the adaptive immune response in severe AATD emphysema and compare it to that present in "usual" COPD . Methods: The immune inflammatory response in explanted lungs from 10 subjects with AATD was characterized and quantified and the results compared to 26 subjects with "usual" COPD, 17 smoking and 11 non-smoking controls with normal lung function. Results: Lymphoid follicles (LF) in AATD and "usual" COPD were markedly increased when compared to control groups. Molecular analysis of B-lymphocytes in LF showed predominantly mono/oligoclonality. LF number correlated with FEV1/FVC. B-lymphocytes, CD4+ and CD8+ T-lymphocytes were significantly increased in AATD and "usual" COPD when compared to control groups. IL-32, an important cytokine in induction of autoimmunity, was markedly upregulated in AATD and "usual" COPD. Conclusions: An important adaptive immune inflammation, comprising B, CD4+, CD8+ lymphocytes and mono/oligoclonal lymphoid follicles, is a prominent feature in AATD. These results change the paradigm of the mechanism of AATD-induced emphysema from a pure elastase/antielastase imbalance to a much more complex one involving the adaptive immune system, similarly to what occurs in "usual" COPD.
    American Journal of Respiratory and Critical Care Medicine 11/2014; 191(4). DOI:10.1164/rccm.201403-0529OC · 11.99 Impact Factor
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    ABSTRACT: Objectives Adenocarcinoma comprises a group of diseases with heterogeneous clinical and molecular characteristics. COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients. Our aim was to study COPD-associated adenocarcinoma phenotypes mainly focusing on morphological and molecular aspects, in comparison to smoke-related cancer without COPD. Materials and Methods From 2010 to 2013, 54 patients with adenocarcinoma (20 COPD and 34 smokers) were prospectively studied. Each patient underwent a complete clinical and instrumental assessment. Morphological studies included analysis of growth pattern, cell proliferation (Ki-67/MIB1 expression) and parameters of intra-and peri-tumoural remodeling (inflammation, fibrosis and necrosis). Genetic analysis of EGFR and KRAS mutations was also performed. Results The two groups were comparable for the main demographic and biohumoral parameters except for increased blood basophil cell count in the COPD group. Compared to COPD, tumours of smokers presented an increased percentage of solid component (median: 20% vs 5%, p = 0.02), a reduced percentage of lepidic pattern (median: 0% vs 10%, p = 0.06) and higher Ki-67/MIB1 median value (55% vs 30%, p = 0.02). In multivariate analysis lepidic and solid histological pattern were significantly influenced by clinical group (p = 0.03 and 0.05, respectively). Concerning EGFR mutation, no differences were found between groups while KRAS mutation presented a trend of higher percentage in smokers compared to COPD (41% vs 20%, p = NS). Adenocarcinoma with KRAS mutation showed a higher value of Ki-67/MIB1 (65% vs 35%, p = 0.048) and prevalent solid pattern (35% vs 10%, p = 0.019) in comparison to wild-type form. Conclusions COPD-related adenocarcinoma presents molecular and morphological features of lower aggressiveness (increased lepidic component, reduced solid pattern, lower cell proliferation and less frequent KRAS mutation) compared to smokers. Different molecular mechanisms could be associated with the development of COPD associated cancer.
    Lung Cancer 10/2014; 86(3). DOI:10.1016/j.lungcan.2014.10.004 · 3.74 Impact Factor
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    ABSTRACT: Objectives To evaluate the role of CT and PET/CT in patients with thymic cancer and thymoma at initial staging.Methods We retrospectively reviewed CT and PET/CT scans of 26 patients with a thymic cancer (n=9) or thymoma (n=17). Chest CT findings documented were qualitative and quantitative. Both qualitative and semiquantitative data were recovered by PET/CT. The outcome of all patients was retrieved by clinical chart or follow-up. The comparisons among histological entities, outcome and qualitative data from CT and PET/CT were made by a non-parametric analysis.ResultsPET/CT resulted positive in 15/17 patients with thymoma. CT was available in 5/9 (56%) patients with thymic cancer and in 3/17 with thymoma. All quantitative CT parameters were significantly higher in patients with thymic cancer than thymoma (maximum axial diameter: 45vs.20mm, maximum longitudinal diameter: 69vs.21mm and volume: 77.91vs.4.52ml; all p<0.05). Conversely, only metabolic tumor volume (MTV) and total lesion glycolysis were significantly different in patients with thymic cancer than the counterpart (126.53vs.6.03cm3 and 246.05vs.20.32, respectively; both p<0.05). After a median follow-up time of 17.45 months, four recurrences of disease occurred: three in patients with thymic cancer and one with a type B2 thymoma. Follow-up data were lost in three subjects. CT volume in patients with recurrent disease was 102.19ml vs. a median value of 62.5ml in six disease-free patients. MTV was higher in recurrent than disease-free patient subset (143.3vs.81.13cm3), although not statistically significant (p=0.075).Conclusion From these preliminary results emerged that both morphological and metabolic volume can be useful from a diagnostic and prognostic point of view in thymic cancer and thymoma patients. A large multi-center clinical trial experience for confirming the findings of this study seems mandatory.
    10/2014; DOI:10.1111/1759-7714.12197
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    ABSTRACT: We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970T>A) in GTF2I at high frequency in type A thymomas, a relatively indolent subtype. In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified. Therefore, GTF2I mutation correlated with better survival. GTF2I β and δ isoforms were expressed in TETs, and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas carried a higher number of mutations than thymomas (average of 43.5 and 18.4, respectively). Notably, we identified recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1, in thymic carcinomas. These findings will complement the diagnostic assessment of these tumors and also facilitate development of a molecular classification and assessment of prognosis and treatment strategies.
    Nature Genetics 06/2014; 46(8). DOI:10.1038/ng.3016 · 29.65 Impact Factor
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    ABSTRACT: We report a rare case of an incidental diagnosis of necrotizing sarcoid granulomatosis (NSG) in a 60-year-old non smoker male. The patient was admitted to the hospital for sudden back pain. Chest X-ray revealed areas of parenchymal consolidation and high resolution computed tomography demonstrated a pulmonary nodular pattern without any lymph node enlargement. All laboratory and pulmonary function tests were normal. Bronchoscopy with bronchoalveolar lavage showed no sign of infection or specific inflammation. The diagnosis of NSG was made by histopathological examination of a lung surgical biopsy and by excluding other causes of granulomatous disease. In pauci/asymptomatic patients, as was our case, therapy is not necessary with a good prognosis and complete recovery. NSG is a rare systemic disease lying in between sarcoidosis and Wegener's granulomatosis with a benign clinical course that should always be kept in mind in patients with nodular pulmonary lesions even with subclinical or uncommon features.
    12/2013; 59(9). DOI:10.4187/respcare.02842
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    ABSTRACT: The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed. In addition, TG males showed higher expression of mTOR in the liver. Liver histology showed age-dependent increase of steatosis and decrease of glycogen storage in both groups and none of the animals developed neoplastic lesions. In conclusion, the gain in life span observed in SB3-transgenic mice could be determined by multiple mechanisms, including the decrease of circulating IL-6 and the modulation of ageing genes in the liver.
    Scientific Reports 10/2013; 4. DOI:10.1038/srep04330 · 5.58 Impact Factor
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    ABSTRACT: The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed. In addition, TG males showed higher expression of mTOR in the liver. Liver histology showed age-dependent increase of steatosis and decrease of glycogen storage in both groups and none of the animals developed neoplastic lesions. In conclusion, the gain in life span observed in SB3-transgenic mice could be determined by multiple mechanisms, including the decrease of circulating IL-6 and the modulation of ageing genes in the liver.
    Scientific Reports 10/2013; 3:3056. DOI:10.1038/srep03056 · 5.58 Impact Factor
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    ABSTRACT: Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. Only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. In human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. The detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential graft rejection. In this study, the presence and the significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which kidney function was supported only by the transplanted organ. Eight bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) were transplanted with a single kidney from α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for human CD39, CD55, CD59, and α1,2-fucosyltransferase. In addition to hematological and biochemical analyses, quantitative and qualitative analysis of proteinuria was evaluated by urinary protein-to-creatinine ratio (UPC ratio) and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE), respectively. The main hematological and biochemical changes recorded after transplantation were a progressive anemia and a severe and progressive decrease in total proteins. In urine samples, the UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation, but bands consistent with mixed (i.e., tubular and glomerular) proteinuria were observed in all samples collected post-transplantation. The study of clinicopathological changes in cynomolgus monkey renal xenograft recipients provides a valid help in monitoring the health conditions in the post-transplant period. Moreover, the evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey renal xenograft recipients may be considered a valid, inexpensive, and less time-consuming method than more sophisticated techniques in monitoring proteinuria. Proteinuria and presence of low molecular weight (LMW) proteins were consistently found in urine after transplantation, independent of fluctuations in renal function.
    Xenotransplantation 09/2013; 20(6). DOI:10.1111/xen.12063 · 1.78 Impact Factor
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    ABSTRACT: We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target.
    Cell metabolism 06/2013; 17(6):988-99. DOI:10.1016/j.cmet.2013.04.019 · 16.75 Impact Factor
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    ABSTRACT: Objectifs Cette étude réalisée en ouvert est basée sur une approche translationnelle dans le but de détecter les changements cliniques, à l’imagerie et des biomarqueurs synoviaux dans le liquide synovial (LS) et le tissu synovial (TS) dans la spondyloarthropathie périphérique (SpA) après l’inhibition intra-articulaire (IA) du tumor necrosis factor (TNF)-α par des injections répétées d’etanercept (E). Méthodes Vingt-sept patients présentant une synovite résistante du genou ont reçu quatre injections IA bihebdomadaires d’E (12,5 mg). Le critère d’évaluation principal était l’indice du genou de Thompson (THOMP) et les critères secondaires étaient représentés par l’indice articulaire du genou (IAG), la protéine C-réactive (CRP), le health assessment questionnaire-disability index (HAQ-DI), l’épaisseur maximale de la synoviale (EMS) évaluée par échographie et imagerie par résonnance magnétique (IRM) de contraste, le taux sérique des cellules mononucléaires dans les TS – CD45+ et – CD31+, le taux dans le LS d’interleukine-1β (IL-1β), le récepteur antagoniste de l’IL-1 (IL-1Ra) et d’IL-6 à l’inclusion et à la fin de l’étude. Résultats À la fin de l’étude, les données cliniques, de l’imagerie ainsi que les biomarqueurs ont été tous significativement réduits et améliorés comparativement aux données à l’inclusion. Il y avait une corrélation significative entre la clinique, l’imagerie et les biomarqueurs. (la CRP avec le THOMP, l’IAG, le HAQ-DI et le taux d’IL-1Ra ; l’EMS à l’écho avec l’IAG, le TS-CD45+ avec le THOMP, IAG, TS-CD31+ et LS-IL-1β ; le LS-IL-6 avec le THOMP, IAG, LS-IL-1β, ou IL-1Ra). Conclusions Cette étude en « preuve de concept » a démontré une amélioration précoce des scores locaux et systémiques, de l’épaisseur synoviale mesurée par IRM et échographie, et de l’expression des biomarqueurs synoviaux. Le CD45+, CD31+ dans le TS et l’IL-6 et IL-1β dans le LS peuvent être considérés comme des biomarqueurs potentiels dans la réponse de la SpA périphérique à un agent anti-TNF-α IA.
    Revue du Rhumatisme 03/2013; 80(2):149–156. DOI:10.1016/j.rhum.2012.09.015
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    ABSTRACT: Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed. Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice. A higher frequency of virus positive cases was found in IPF patients than in controls (0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (0.01), poorer performance in the six minute walking test (6MWT; 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (0.002 and 0.004) and higher TGF-β expression (0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (0.03), poorer performance in the 6MWT (0.008) and PGD ( = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients. Herpesviral infections may contribute to the development of PH in IPF patients.
    PLoS ONE 02/2013; 8(2):e55715. DOI:10.1371/journal.pone.0055715 · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding.METHODS The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH(2)O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features.RESULTSAfter applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen.CONCLUSIONS This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.
    Interactive Cardiovascular and Thoracic Surgery 02/2013; DOI:10.1093/icvts/ivt029 · 1.11 Impact Factor
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    ABSTRACT: Acute liver failure (ALF) is characterized by severe neurological complications, known as acute hepatic encephalopathy, where brain ammonia and inflammatory processes play a dominant role. In experimental models of acute liver failure SERPINB3 was found significantly increased in microglia, the intrinsic immune cells of the central nervous system. The aim of the present study was to investigate the extent of brain tissue damage and the inflammatory milieu in experimental acute liver failure using a SERPINB3-transgenic mouse model. C57BL/6J wild-type and transgenic mice were inoculated with acetaminophen or phosphate-buffered saline and sacrificed 20 h postinjection. Proliferation and apoptotic activity were analyzed in brain tissue by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique. The expression of cytokines was analysed in brain and liver tissue by real time polymerase chain reaction and in the corresponding serum samples using a Bio-Plex system. Acetaminophen induced a significantly lower body temperature and shorter survival in transgenic than in wild-type mice, despite liver function was similar in both groups. The brain of transgenic mice, expressing SERPINB3 positivity in microglia, showed increased glial cell number, associated to significant lower apoptotic death events, compared with wild-type mice. In mice injected with acetaminophen, remarkably higher values of cytokines mRNA were observed in the liver of both groups, with a trend toward higher values in transgenic animals. In brain tissue similar increase of tumor necrosis factor-α was detected in transgenic and wild-type mice, while IL-10 mRNA increased only in the wild-type group. A remarkable increase of circulating Th1 cytokines was detected in serum of transgenic mice, while in the wild-type group they remained rather unchanged. These figures were associated with lower levels of granulocyte macropage colony-stimulating factor, despite similar increase of IL-10 values in both groups. In conclusion, in acute liver failure SERPINB3 determines an enhanced inflammatory background, mainly mediated by higher levels of Th1 proinflammatory cytokines.
    Experimental Biology and Medicine 12/2012; 237(12):1474-82. DOI:10.1258/ebm.2012.012135 · 2.23 Impact Factor
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    ABSTRACT: In the WHO 1996 classification of cardiomyopathies, myocarditis is defined as an "inflammatory disease of the myocardium associated with cardiac dysfunction" and is listed among "specific cardiomyopathies". Myocarditis is diagnosed on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria, and molecular techniques are recommended to identify viral etiology. Infectious, autoimmune, and idiopathic forms of inflammatory cardiomyopathy are recognized that may lead to dilated cardiomyopathy. According to Dallas criteria, myocarditis is diagnosed in the setting of an "inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes, not typical of ischemic damage associated with coronary artery disease". The majority of experts in the field agree that an actual increase in sensitivity of EMB has now been reached by using immunohistochemistry together with histology. A value of >14 leukocytes/mm(2) with the presence of T lymphocytes >7 cells/mm(2) has been considered a realistic cut off to reach a diagnosis of myocarditis. The development of molecular biological techniques, particularly amplification methods like polymerase chain reaction (PCR) or nested-PCR, allows the detection of low copy viral genomes even from an extremely small amount of tissue such as in EMB specimens. Positive PCR results obtained on EMB should always be accompanied by a parallel investigation on blood samples collected at the time of the EMB. According to the recent Association for European Cardiovascular Pathology guidelines, optimal specimen procurement and triage indicates at least three, preferably four, EMB fragments, each 1-2 mm in size, that should immediately be fixed in 10 % buffered formalin at room temperature for light microscopic examination. In expected focal myocardial lesions, additional sampling is recommended. Moreover, one or two specimens should be snap-frozen in liquid nitrogen and stored at -80 °C or alternatively stored in RNA-later for possible molecular tests or specific stains. A sample of peripheral blood (5-10 ml) in EDTA or citrate from patients with suspected myocarditis allows molecular testing for the same viral genomes sought in the myocardial tissue.
    Heart Failure Reviews 10/2012; DOI:10.1007/s10741-012-9355-6 · 3.99 Impact Factor

Publication Stats

3k Citations
700.53 Total Impact Points

Institutions

  • 2003–2015
    • University of Padova
      • Department of Cardiac, Thoracic and Vascular Sciences
      Padua, Veneto, Italy
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
  • 2009
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
  • 2007
    • Venetian Institute of Molecular Medicine
      Padua, Veneto, Italy
  • 1996–2007
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 2006
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1996–2005
    • It-Robotics
      Vicenza, Veneto, Italy
  • 2004
    • The Ohio State University
      Columbus, Ohio, United States
    • Amedeo Avogadro University of Eastern Piedmont
      Novara, Piedmont, Italy