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Fiorella Calabrese

Publications and source records attributed to Fiorella Calabrese.

At least 37 records · Page 2Linked to original sources
PubMed2004

Prostate carcinoma and green tea: (-)epigallocatechin-3-gallate inhibits inflammation-triggered MMP-2 activation and invasion in murine TRAMP model.

Green tea infusion has been shown to inhibit metastatic spreading of the transgenic adenocarcinoma of mouse prostate (TRAMP). Investigation on the molecular mechanisms triggered by the main green tea flavonoid, (-)epigallocatechin-3-gallate (EGCG), shows that EGCG restrains TRAMP-C1 cell proliferation in a dose-dependent manner, at concentrations (IC(50) < 0.2 microM) equivalent to those measured in the plasma of moderate green-tea drinkers. Up to 10 microM, EGCG does not modify the cell-surface immuno-localization of MMP-2, one of the invasion-instrumental proteinases; but while in default culture conditions these cells secrete mainly pro-MMP-2, in the presence of reconstituted basement membrane (Matrigel) they release almost exclusively pro-MMP-9. In contrast, when stimulated to traverse Matrigel toward a chemo-attractant, in addition to pro-MMP-9, they secrete pro-MMP-2. In the presence of 0.2 microM EGCG, only the level of the latter is markedly lowered in the conditioned medium, in parallel with the invasive behavior (>50%). In vivo, s.c. injection of TRAMP-C1 cells dispersed in Matrigel gives origin to a tumor mass, whose growth is not inhibited by green-tea regimen. This growth is contained greater than two-thirds by LPS-triggered polymorpho-nuclear phagocyte (PMN) recruitment but this effect is abolished by green tea. Nevertheless, while tumor-released pro-MMP-2 is activated by co-incubation of TRAMP-C1 cells with PMNs, in the presence of 10 microM EGCG the activation is almost abolished. These results suggest that inflammatory involvement of prostate carcinoma could be efficaciously prevented by green tea with a concomitant lowering of the invasive potential.

Adenocarcinoma↗
PubMed2004

Intramyocyte detection of Epstein-Barr virus genome by laser capture microdissection in patients with inflammatory cardiomyopathy.

BACKGROUND: The causal role of Epstein-Barr virus (EBV) in inflammatory cardiomyopathy (IC) is still unclear, because this virus is present in latently infected circulating B lymphocytes in 90% of adults. Laser capture microdissection (LCM) has been applied on endomyocardial biopsy samples from patients with IC to assess the presence of EBV genome in separately dissected lymphocytes and myocytes. METHODS AND RESULTS: Among 142 patients with cardiac dilation and dysfunction and a histological and immunohistochemical diagnosis of myocarditis, 44 had a myocardial viral infection detected by polymerase chain reaction on frozen endomyocardial biopsy samples. In 9 of them, the virus detected was EBV. LCM was performed on 5-microm-thick paraffin sections of EBV-infected hearts. Lymphocytes and myocytes were microdissected and analyzed separately by polymerase chain reaction analysis on DNA extracted from the collected cells. Blood and myocardial samples from patients with positive and negative serology for EBV were used as controls. EBV genome was detected in myocytes but not in infiltrating lymphocytes of patients, nor in myocardial samples from controls. Despite full conventional antifailure therapy, a progressive cardiac dilation and dysfunction was documented in patients with EBV-related IC at a mean of 31+/-14 months of follow-up. CONCLUSIONS: Intramyocyte detection of EBV can be obtained by LCM in up to 6.3% of patients with IC. This supports a cytopathic EBV role and suggests the opportunity for an antiviral/immunomodulatory therapy.

Adult↗
PubMed2004

Hyperforin inhibits cancer invasion and metastasis.

Hyperforin (Hyp), the major lipophilic constituent of St. John's wort, was assayed as a stable dicyclohexylammonium salt (Hyp-DCHA) for cytotoxicity and inhibition of matrix proteinases, tumor invasion, and metastasis. Hyp-DCHA triggered apoptosis-associated cytotoxic effect in both murine (C-26, B16-LU8, and TRAMP-C1) and human (HT-1080 and SK-N-BE) tumor cells; its effect varied, with B16-LU8, HT-1080, and C-26 the most sensitive (IC50 = 5 to 8 micromol/L). At these concentrations, a marked and progressive decline of growth was observed in HT-1080 cells, whereas untransformed endothelial cells were only marginally affected. Hyp-DCHA inhibited in a dose-dependent and noncompetitive manner various proteinases instrumental to extracellular matrix degradation; the activity of leukocyte elastase was inhibited the most (IC50 = 3 micromol/L), followed by cathepsin G and urokinase-type plasminogen activator, whereas that of the matrix metalloproteinases (MMPs) 2 and 9 showed an IC50 > 100 micromol/L. Nevertheless, inhibition of extracellular signal-regulated kinase 1/2 constitutive activity and reduction of MMP-2 and MMP-9 secretion was triggered by 0.5 micromol/L Hyp-DCHA to various degrees in different cell lines, the most in C-26. Inhibition of C-26 and HT-1080 cell chemoinvasion (80 and 54%, respectively) through reconstituted basement membrane was observed at these doses. Finally, in mice that received i.v. injections of C-26 or B16-LU8 cells, daily i.p. administration of Hyp-DCHA-without reaching tumor-cytotoxic blood levels-remarkably reduced inflammatory infiltration, neovascularization, lung weight (-48%), and size of experimental metastases with C-26 (-38%) and number of lung metastases with B16-LU8 (-22%), with preservation of apparently healthy and active behavior. These observations qualify Hyp-DCHA as an interesting lead compound to prevent and contrast cancer spread and metastatic growth.

Adenocarcinoma↗
PubMed2004

Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model of human disease.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. METHODS AND RESULTS: ARVC was diagnosed in 23 boxer dogs (12 male; 9.1+/-2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n=8) and the left ventricle (LV) (n=11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4+/-18.8% versus 13.8+/-3.4%, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6+/-19.2% versus 84.8+/-3.8% in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n=14, 61%) and LV (n=16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. CONCLUSIONS: We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.

Animals↗
PubMed2004

Acute rejection and graft survival in renal transplanted patients with viral diseases.

Transplanted patients are susceptible to viral infections; thus, the aim of this study was to evaluate the features of acute rejections and the outcome of the renal graft in transplanted patients with herpes virus diseases. Renal biopsies from 30 renal transplanted patients undergoing early acute rejection (type IA and IB according to the Banff 97 classification) were evaluated. In total, 15 of these patients experienced cytomegalovirus (CMV) or Epstein-Barr virus disease within the first year following transplantation (group I) and 15 patients showed no evidence of viral infection (group II). No significant differences between the groups in terms of age, male/female ratio, living/cadaveric donor ratio, cold ischemia time, HLA A-B matching, pretransplant panel reactive antibody test, occurrence of post-transplant tubular necrosis, plasma levels of cyclosporin A and mean percent increase of serum creatinine at the time of the biopsy were observed. In group I biopsies, the mean number of interstitial plasma cells, as well as the mean number of CD79a-positive cells (B lymphocytes and plasma cells) was significantly higher than in group II (P<0.01 and <0.01, respectively). There was a positive correlation between the number of infections and the number of plasma cells (P<0.05). In transplanted patients, CMV can trigger the formation of anti-endothelial cell antibodies, which have been proposed to play a role in antibody-mediated rejections. We investigated whether a deposition of C4d, a marker of antibody-mediated reactions, was present in renal peritubular capillaries. In group I C4d deposition was found in five cases, while in group II it was not observed (P<0.05). In group I, 7/15 patients developed chronic allograft nephropathy vs 1/15 patients in group II (P<0.05). The estimated 1-, 5- and 8-year cumulative graft survival rates were 80, 66 and 57%, respectively, in group I, while in group II the estimated 8-year cumulative survival rate was 100% (P<0.05). In conclusion, acute rejection biopsies of patients with viral infections displayed plasma cell infiltrates and, in several cases, C4d deposition. Our study suggests a role of B lymphocytes in the pathology of these rejections and confirms the association between viral infections and poor graft survival.

Adult↗
PubMed2004

Overexpression of tumor necrosis factor (TNF)alpha and TNFalpha receptor I in human viral myocarditis: clinicopathologic correlations.

Proinflammatory cytokines, including tumor necrosis factor (TNF)alpha, have been recognized as important physiopathogenetic factors in the initiation and continuation of inflammatory cardiomyopathies. Experimental and preliminary human studies have demonstrated that TNFalpha plays a crucial role in enteroviral-induced myocarditis. In this study, we investigated the expression of TNFalpha and both its receptors (TNFRI and TNFRII) in both viral and nonviral myocarditis. Myocardial expression of TNFalpha was then correlated with different clinical and pathologic findings. TNFalpha expression was investigated in endomyocardial biopsies obtained from 38 patients with myocarditis and from eight control subjects by using reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry. Viral etiology was diagnosed by PCR in 20 cases: enterovirus in seven, Epstein-Barr virus in four, hepatitis C virus in three, adenovirus in two, influenza virus in two, cytomegalovirus in one, and double infection adenovirus and enterovirus in one. Immunohistochemistry was also used to analyze both TNFalpha receptors (RI and RII). A semiquantitative analysis was employed (score 0-3) for necrosis, inflammation, fibrosis and immunohistochemical findings. TNFalpha mRNA and TNFalpha protein were significantly more present in viral myocarditis than in nonviral myocarditis (16/20 vs 3/18, P=0.001). Remarkable immunostaining was observed for both receptors, particularly TNFRI. Histological analysis revealed that myocardial necrosis (mean score 1.89 vs 1.15, P=0.01) and cellular infiltration (mean score 2.26 vs 1.78, P=0.05) were more prominent in TNFalpha-positive cases. Among TNFalpha-positive cases, the greater TNFalpha mRNAs, the more impaired was cardiac function. Our findings suggest that the expression of TNFalpha may play an important role in the pathogenesis of viral myocarditis of any etiology and may influence the severity of cardiac dysfunction. Cytokine effects are more strictly linked to overexpression of TNFRI.

Adolescent↗
PubMed2004

Alterations in the coagulation profile in renal pig-to-monkey xenotransplantation.

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this model. Variable degrees of compensated consumptive coagulopathy were observed in each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels consistent with thrombin generation and fibrin formation were recorded. There was no consumption of the main clotting inhibitors (including antithrombin) or a progressive, severe drop in fibrinogen levels and platelet counts, although grafts were left in situ. After transplantation, D-dimer levels remained persistently high, so they were of limited value in defining this coagulopathy. At post mortem, no cases of multiorgan involvement typical of overt DIC were observed. The lack of a rapid postoperative recovery of clotting inhibitor levels after transplantation was invariably associated with early poor outcome. This study shows that AHXR is associated with various degrees of compensated consumptive coagulopathy in our pig-to-primate model. No clear relationship was found between coagulation parameter levels and graft outcome.

Animals↗
PubMed2004

Ureteral stenosis in HDAF pig-to-primate renal xenotransplantation: a phenomenon related to immunological events?

The aim of this study was to analyze the incidence of ureteral stenosis in a life-supporting human decay-accelerating factor (hDAF) transgenic pig-to-cynomolgus monkey kidney transplantation model and determine the role of possible immunological events in its pathogenesis. Thirty consecutive bi-nephrectomized cynomolgus monkeys received a kidney from hDAF transgenic pigs with or without a ureteral stent. Four monkeys were euthanized prematurely after transplantation. In the remaining 26 cases, the mean survival was 24 +/- 19 days. Except in one case, there was a close relationship between ureter and kidney in terms of type and severity of rejection. There were six ureteral stenoses; five were repaired by stent positioning and resurgery extended survival for an additional 16 +/- 10 days. The stenotic ureters showed diffuse acute humoral xenograft rejection (AHXR), while all cases with no or only focal signs of ureteral rejection never revealed ureteral obstruction. Use of a ureteral stent extends the survival of a xenografted primate, thereby helping to clarify the immunological events surrounding the onset of AHXR in kidneys in long-term xenograft recipients.

Animals↗
PubMed2003

Myocarditis and inflammatory cardiomyopathy: microbiological and molecular biological aspects.

Myocarditis is an inflammatory disease of the myocardium associated with cardiac dysfunction. The natural history of myocarditis is frequently characterised by the evolution in dilated cardiomyopathy. Due to its variable clinical manifestation from latent to very severe clinical forms, such as acute congestive heart failure and sudden death, its prevalence is still unknown and probably underestimated. In spite of the development of various diagnostic modalities, early and definite diagnosis of myocarditis still depends on the detection of inflammatory infiltrates in endomyocardial biopsy specimens according to the Dallas criteria. Routine application of immunohistochemistry, used for identification and characterisation of inflammatory cell populations, has now significantly increased the sensistivity of the diagnosis of inflammatory cardiomyopathy. Various molecular techniques, such as PCR, gene sequencing and real-time PCR, often applied on the same endomyocardial specimen, have become an essential part of the diagnostic armamentarium for rapid, specific and sensitive identification of infective agents. The correct application of molecular techniques will allow increasingly more information to be obtained: new epidemiology, new patient risk stratification and overall more appropriate medical treatment.

Adolescent↗
PubMed2003

Airway inflammation in childhood asthma.

Airway pathology has been extensively investigated in adulthood asthma, whereas only few studies examined bronchial biopsies in childhood asthma. To evaluate the airway pathology in children with asthma, we analyzed bronchial biopsies obtained from 23 children undergoing bronchoscopy for clinical indications other than asthma. Nine had mild/moderate asthma. Six had atopy without asthma, and eight had no atopy or asthma. We measured basement membrane thickness and quantified the number of eosinophils, mast cells, neutrophils, macrophages, T lymphocytes, and positive cells for transforming growth factor-beta1 (TGF-beta1) and its receptors I and II (TGFbeta-RI and TGFbeta-RII) in subepithelium. Children with asthma had an increase in basement membrane thickness and in the number of eosinophils compared with control subjects, but not compared with children with atopy. They also had a decreased expression of TGFbeta-RII compared with both those with atopy and control subjects. In children with asthma, the number of eosinophils correlated negatively with TGFbeta-RII and positively with symptom duration. In conclusion, airway eosinophilia and basement membrane thickening, which are the pathologic features that are characteristic of adulthood asthma, are already present in children with mild asthma, and even in children with atopy without asthma. Moreover, in children with asthma but not in children with atopy without asthma, there is a downregulation of TGFbeta-RII.

Adolescent↗
PubMed2003

Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis.

Neutrophils play an essential role in host defense and inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Green tea has been claimed to exert anti-inflammatory properties through unknown molecular mechanisms. We have previously shown that the most abundant catechin of green tea, (-)epigallocatechin-3-gallate (EGCG), strongly inhibits neutrophil elastase. Here we show that 1) micromolar EGCG represses reactive oxygen species activity and inhibits apoptosis of activated neutrophils, and 2) dramatically inhibits chemokine-induced neutrophil chemotaxis in vitro; 3) both oral EGCG and green tea extract block neutrophil-mediated angiogenesis in vivo in an inflammatory angiogenesis model, and 4) oral administration of green tea extract enhances resolution in a pulmonary inflammation model, significantly reducing consequent fibrosis. These results provide molecular and cellular insights into the claimed beneficial properties of green tea and indicate that EGCG is a potent anti-inflammatory compound with therapeutic potential.

Administration, Oral↗
PubMed2003

Immunosuppressive therapy for active lymphocytic myocarditis: virological and immunologic profile of responders versus nonresponders.

BACKGROUND: The beneficial effect of immunosuppressive treatment on myocarditis is still controversial, possibly because the immunologic and virological profile of potential candidates is largely unknown. METHODS AND RESULTS: Out of 652 biopsied patients, 112 had a histological diagnosis of active lymphocytic myocarditis; 41 of these 112 patients were characterized by progressive heart failure despite conventional therapy and were treated with prednisone and azathioprine for 6 months. All were resubmitted to cardiac catheterization, angiography, and endomyocardial biopsy at 1 and 6 months and followed-up for 1 year. A total of 21 patients responded with prompt improvement in left ventricular ejection fraction from 25.7+/-4.1% to 47.1+/-4.4% and showed evidence of healed myocarditis at control biopsy. Conversely, 20 patients failed to respond and showed a histological evolution toward dilated cardiomyopathy: 12 remained stationary, 3 underwent cardiac transplantation, and 5 died. We retrospectively performed a polymerase chain reaction on frozen endomyocardial tissue for the most common cardiotropic viruses and assessed circulating serum cardiac autoantibodies. Viral genomes were present in biopsy specimens of 17 nonresponders (85%), including enterovirus (n=5), Epstein-Barr virus (n=5) adenovirus (n=4), both adenovirus and enterovirus (n=1), influenza A virus (n=1), parvovirus-B19 (n=1), and in 3 responders, who were all positive for hepatitis C virus. Cardiac autoantibodies were present in 19 responders (90%) and in none of the nonresponders. CONCLUSIONS: In patients with active lymphocytic myocarditis, those with circulating cardiac autoantibodies and no viral genome in the myocardium are the most likely to benefit from immunosuppression. The beneficial effect of immunosuppression in hepatitis C virus myocarditis suggests a relevant immunomediated component of damage.

Adolescent↗
PubMed2003

Successful treatment of enterovirus-induced myocarditis with interferon-alpha.

No randomized, placebo-controlled studies have investigated interferon-alpha therapy in enterovirus-proven myocarditis. This report describes 2 patients with enterovirus-induced myocarditis (1 with associated Churg-Strauss syndrome) who at follow-up endomyocardial biopsy showed clinical and hemodynamic improvement and viral clearance (using polymerase chain reaction) after interferon-alpha therapy.

Adult↗
PubMed2003

Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey renal xenotransplantation.

Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a life-supporting kidney from human decay-accelerating factor transgenic pigs were administered MTX intravenously according to three different regimens. All the animals also received cyclosporine A and steroids. In addition, mycophenolate sodium (MPS) was administered post-operatively in two of the three groups of transplanted animals. At clinically relevant concentrations, MTX is able in vitro to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After intravenous administration, moreover, exposure of cynomolgus monkeys to MTX appeared to be higher than had been previously reported in baboons. Graft function was observed in the transplanted animals, which survived from 0 to 41 days. All but two animals revealed acute humoral rejection in the explanted graft and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It was unrelated to the administration of MPS and associated with severe histopathological signs of enteritis. This study demonstrates that the pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between non-human primate species. In vitro, MTX has immunosuppressive properties in the cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons. We conclude that MTX is scarcely effective as an immunosuppressant, be it for induction or maintenance, in pig-to-cynomolgus monkey renal xenotransplantation.

Animals↗
PubMed2003

Coronary thrombosis and sudden death after an enteroviral infection. Case report.

We report the case of a 26-year-old man who died suddenly 9 days after an episode of flu. Microscopic examination of the left anterior descending coronary artery showed an eccentric fibroatheromatic plaque complicated by thrombosis, endothelial erosion and extensive T-cell and macrophage infiltration. Frozen sections of the thrombotic coronary segment, analysed for different infective agents by polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR, showed positive amplification for an enteroviral genome. Enteroviral infection may play an important role in coronary plaque instability and may precipitate thrombotic occlusion.

Adult↗
PubMed2003

Parenchymal transforming growth factor beta-1: its type II receptor and Smad signaling pathway correlate with inflammation and fibrosis in chronic liver disease of viral etiology.

BACKGROUND AND AIMS: Transforming growth factor-beta (TGF-beta) system is involved in the control of cell growth and extracellular matrix formation. Previous studies in patients with chronic liver disease have shown that increased TGF-beta expression significantly correlates with the degree of hepatic fibrosis. The aim of our study was to define TGF-beta system expression in hepatic parenchymal cells and its significance in patients with differing extents of chronic liver disease of viral etiology. METHODS: Expression of TGF-beta 1, TGF-beta 1 type II receptor (TGF-beta RII) and the Smad signaling pathway was evaluated in consecutive liver sections of 77 patients with chronic liver disease (65 HCV positive and 12 HBV positive). Results were correlated with histological scores and apoptotic activity. RESULTS: TGF-beta 1 was demonstrated in the liver of 30/56 (53.6%) patients with chronic hepatitis and 20/21 (95%) patients with cirrhosis, but in none of the 20 normal livers. Positive cytokine reaction was seen both in stromal cells and hepatocytes. Expression of TGF-beta RII and Smad proteins showed a distribution pattern similar to that of TGF-beta, with a direct correlation in terms of immunoreactivity extent. A significant correlation was found between parenchymal expression of TGF-beta system and inflammatory and fibrosis scores. No correlation was found with apoptotic index and other morphological, clinical or virological parameters. CONCLUSIONS: The TGF-beta system is up-regulated at the ligand, receptor and signaling level in the liver of patients with more active disease. The strong expression of TGF-beta and the Smad pathway in parenchymal cells suggests that hepatocytes, in addition to mesenchymal cells, may play an important role in the progression of liver disease.

Adolescent↗