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Dive into the research topics where Silvia Raspanti is active.

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Featured researches published by Silvia Raspanti.


Journal of Endocrinological Investigation | 2001

False serum calcitonin high levels using a non-competitive two-site IRMA

Mariasilvia Tommasi; Alessandro Brocchi; A. Cappellini; Silvia Raspanti; Massimo Mannelli

Dual site antibody-base immunoassays are commonly used in clinical laboratories to quantify the CT serum concentrations as a specific and sensitive marker of medullary thyroid carcinoma (MTC). Heterophile antibodies can interfere with these assays, however, and cause erroneous results. In order to avoid this interference, immobilized and conjugated antibodies from two different animal species or immunoreactive antibody fragments, as well as the addition of non-immune globulins, are generally included among the assay reagents. We describe the case of a 73-year-old man affected by a multinodular goiter, who showed high basal CT plasma levels as measured by a monoclonal antibody based IRMA. The finding of negative results for the presence of MTC at fine needle aspiration (FNA) and the mild increase observed in plasma CT during a pentagastrin (Pg) stimulation test, suggested that the high CT levels might depend on a cross-reaction with heterophilic antibodies. In fact, after the addition of the heterophilic blocking tube (HBT) to each specimen, the CT levels markedly decreased by more than 80% (average decrease±SE= 87.6±2.668%). Such a decrease strongly suggests that in our case the routinely used F(ab’)2 fragments were unable to eliminate all of the interference and that the elevated serum CT levels might have been caused by human heterophilic antibodies. In conclusion, these results indicate a novel cause of CT false positivity, suggesting that high serum CT levels, when combined with a slight increase during Pg stimulation, should be critically interpreted in view of the possible presence of heterophilic antibodies in the specimens.


European Heart Journal | 2014

Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial

Giampaolo Cerisano; Piergiovanni Buonamici; Renato Valenti; Roberto Sciagrà; Silvia Raspanti; Alberto Santini; Nazario Carrabba; Emilio Vincenzo Dovellini; Roberta Romito; Alberto Pupi; Paolo Colonna; David Antoniucci

AIMS Experimental studies suggest that doxycycline attenuates post-infarction remodelling and exerts protective effects on myocardial ischaemia/reperfusion injury. However, the effects of the drug in the clinical setting are unknown. The aim of this study was to examine the effect of doxycycline on left ventricular (LV) remodelling in patients with acute ST-segment elevation myocardial infarction (STEMI) and LV dysfunction. METHODS AND RESULTS Open-label, randomized, phase II trial. Immediately after primary percutaneous coronary intervention, patients with STEMI and LV ejection fraction < 40% were randomly assigned to doxycycline (100 mg b.i.d. for 7 days) in addition to standard therapy, or to standard care. The echo LV end-diastolic volumes index (LVEDVi) was determined at baseline and 6 months. (99m)Tc-Sestamibi-single-photon emission computed tomography infarct size and severity were assessed at 6 months. We calculated a sample size of 110 patients, assuming that doxycycline may reduce the increase in the LVEDVi from baseline to 6 months > 50% compared with the standard therapy (statistical power > 80% with a type I error = 0.05). The 6-month changes in %LVEDVi were significant smaller in the doxycycline group than in the control group [0.4% (IQR: -16.0 to 14.2%) vs.13.4% (IQR: -7.9 to 29.3%); P = 0.012], as well as infarct size [5.5% (IQR: 0 to 18.8%) vs. 10.4% (IQR: 0.3 to 29.9%) P = 0.052], and infarct severity [0.53 (IQR: 0.43-0.62) vs. 0.44 (IQR: 0.29-0.60), P = 0.014], respectively. CONCLUSION In patients with acute STEMI and LV dysfunction, doxycycline reduces the adverse LV remodelling for comparable definite myocardial infarct size (NCT00469261).


Journal of Medicinal Chemistry | 2010

Click-chemistry-derived triazole ligands of arginine-glycine-aspartate (RGD) integrins with a broad capacity to inhibit adhesion of melanoma cells and both in vitro and in vivo angiogenesis.

Andrea Trabocchi; Gloria Menchi; Nicoletta Cini; Francesca Bianchini; Silvia Raspanti; Anna Bottoncetti; Alberto Pupi; Lido Calorini; Antonio Guarna

A click chemistry approach was applied for the discovery of triazole-based arginine-glycine-aspartate (RGD) mimetics by Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction, which showed binding affinity properties toward α(v)β(3)/α(v)β(5) integrins. Biological assays showed compound 18 capable of binding α(v)β(3) integrin with nanomolar affinity according to a two-sites model, and molecular modeling studies revealed a peculiar π-stacking interaction between the triazole ring and Tyr178 side chain. Accordingly, compound 18 inhibited the adhesion of integrin-expressing human melanoma cells to RGD-containing proteins of the extracellular matrix, such as vitronectin, fibronectin, and osteopontin, and also angiogenesis in in vitro and in vivo experimental models. The relevant biological effects exerted by compound 18 suggest its potential application as an antiangiogenic agent in the diagnosis and therapy of tumors where α(v)β(3) integrin expression is up-regulated.


Journal of Medicinal Chemistry | 2008

Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based αVβ3/αVβ5 Integrin Binders Embedding 4-Aminoproline Residues

Franca Zanardi; Paola Burreddu; Gloria Rassu; Luciana Auzzas; Lucia Battistini; Claudio Curti; Andrea Sartori; Giuseppe Nicastro; Gloria Menchi; Nicoletta Cini; Anna Bottoncetti; Silvia Raspanti; Giovanni Casiraghi

The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha Vbeta 3/alpha Vbeta 5 integrin binders [IC 50 h (alpha Vbeta 3) 0.03-5.12 nM; IC 50 h (alpha Vbeta 5) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5- 12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N (alpha)-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5- 7 and 9- 11, showed moderate yet significant selectivity toward the alpha Vbeta 3 receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha Vbeta 3 complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.


British Journal of Pharmacology | 1995

Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion

Emanuela Masini; M. Lupini; Laura Mugnai; Silvia Raspanti; P. F. Mannaioni

1 Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea‐pigs and from hearts subjected to regional ischaemia and reperfusion. 2 In guinea‐pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration‐dependent fashion. At the highest concentration studied (10−6 m), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3 The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NGmonomethyl‐L‐arginine (l‐NMMA, 10−4 m), an inhibitor of nitric oxide synthase (NOS). 4 The endothelium‐dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L‐NMMA (10−4 m). 5 In guinea‐pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6 Reperfusion‐induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7 The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed.


Immunopharmacology | 1994

Platelet aggregation and histamine release by immunological stimuli

Emanuela Masini; Maria Grazia Bello; Silvia Raspanti; Tatiana Bani Sacchi; Enrico Maggi; Pier Francesco Mannaioni

Platelet aggregation and histamine release were evaluated in normal and IgE pretreated human platelets exposed in vitro to IgE, anti-IgE and thrombin. The response of platelets from atopic donors directly stimulated with anti-IgE was also evaluated. Histamine release was measured by fluorimetric analysis of histamine content in platelets and in supernatants. The morphology of platelets exposed to immunological and non-immunological stimuli was recorded using an electron microscope. A detectable amount of histamine was measured in quiescent platelets. Their exposure to varying concentrations of thrombin produces a progressive aggregation which runs parallel to histamine release. The effects were significantly enhanced in platelets pretreated with IgE. Incubation of normal platelets with increasing concentrations of IgE myeloma protein, or with anti-human IgE antibody was ineffective on both aggregation and histamine release. However, incubation of platelets passively sensitized with IgE-myeloma protein with different concentrations of anti-human IgE antibody produces a concentration-dependent increase both in aggregation and histamine release. The same effects were obtained using platelets from atopic donors directly stimulated with anti-IgE. The electron microscopic pattern of platelet aggregation induced by thrombin was indistinguishable from that evoked by anti-IgE in IgE pretreated platelets. Loratadine, a non-sedative H1-receptor blocker, significantly abated platelet aggregation and histamine release induced by anti-IgE in IgE pretreated platelets.


Journal of Medicinal Chemistry | 2012

125I-Radiolabeled Morpholine-Containing Arginine–Glycine–Aspartate (RGD) Ligand of αvβ3 Integrin As a Molecular Imaging Probe for Angiogenesis

Francesca Bianchini; Nicoletta Cini; Andrea Trabocchi; Anna Bottoncetti; Silvia Raspanti; Eleonora Vanzi; Gloria Menchi; Antonio Guarna; Alberto Pupi; Lido Calorini

In this paper, using a hybrid small-animal Micro SPECT/CT imaging system, we report that a new (125)I-Cilengitide-like RGD-cyclopentapeptide, containing d-morpholine-3-carboxylic acid, interacts in vivo with α(v)β(3) integrin expressed by melanoma cells. Images clearly show that the (125)I-compound has the capacity to monitor the growth of a melanoma xenograft. Indeed, retention of the labeled ligand in the tumor mass has a good tumor/background ratio, and a significant reduction of its uptake was observed after injection of unlabeled ligand. These results suggest that the use of (125)I-labeled morpholine-based RGD-cyclopentapeptides targeting α(v)β(3) positive tumors may play a role in future therapeutic strategies.


Inflammation Research | 1994

Nitric oxide modulates cardiac and mast cell anaphylaxis

Emanuela Masini; F. Gambassi; M. G. Di Bello; Laura Mugnai; Silvia Raspanti; P. F. Mannaioni

Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release of histamine with a long-lasting release of nitrite (NO2−), an oxidation product of NO.NG-monomethyl-l-arginine (MeArg, 300 μM) increased the severity of cardiac anaphylaxis, as shown by the decrease in the coronary flow and by a prolonged duration of antigen-induced arrhythmias. Concomitantly, MeArg increased the release of histamine while decreasing the release of nitrite. Sodium nitroprusside (NaNP, 10−5–10−4M) reduced the severity of cardiac anaphylaxis by increasing coronary flow and shortening the duration of antigen-induced arrhythmias. Concomitantly, NaNP decreased the release of histamine while increasing the release of nitrite. In mast cells isolated from actively sensitized guinea-pigs, the release of histamine elicited by specific antigen was increased by MeArg and decreased by NaNP.In conclusion, endogenous and exogenous NO antagonizes the effect of vasoconstrictor mediators released after antigen challenge and plays a protective role in anaphylactic reactions “in vitro”,


Bioorganic & Medicinal Chemistry | 2009

Morpholine-based RGD-cyclopentapeptides as αvβ3/αvβ5 integrin ligands: Role of configuration towards receptor binding affinity

Nicoletta Cini; Andrea Trabocchi; Gloria Menchi; Anna Bottoncetti; Silvia Raspanti; Alberto Pupi; Antonio Guarna

Two c[RGDfX] cyclopeptides, having either L- or D-morpholine-3-COOH (Mor) as the X amino acid were developed as ligands for alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed only d-Mor-containing cyclopentapeptide capable to bind alpha(v)beta(3) integrin with a low nanomolar affinity according to a two-site model, thus revealing a connection between the configuration of Mor and the preferred binding to alpha(v)beta(3) integrin. Conformational analysis showed different structural preferences for the two peptides induced by the two enantiomeric cyclic amino acids, suggesting a role of the stereochemistry of Mor on the overall peptide conformation and on the presentation of the pharmacophoric Arg and Asp side chains.


International Archives of Allergy and Immunology | 1992

Platelet Histamine: Characterization of the Proaggregatory Effect of Histamine in Human Platelets

P. F. Mannaioni; M. G. Di Bello; Silvia Raspanti; F. Gambassi; Laura Mugnai; Emanuela Masini

Minute amounts of histamine and a discrete histamine-forming capacity was present in quiescent human platelets. Aggregation of human platelets induced by thrombin was concomitant with the release of h

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