Alessandro Lupi | AOU Maggiore della Carità (original) (raw)

Papers by Alessandro Lupi

Journal of cardiovascular medicine (Hagerstown, Md.), Jan 21, 2015

Coronary inflammation and healing influence outcomes of diabetic patients treated with Percutaneo... more Coronary inflammation and healing influence outcomes of diabetic patients treated with Percutaneous coronary revascularization (PCI). Stents covered with biodegradable polymers (bp) may offer advantages over nonerodible polymer ones, because polymer reabsorption extinguish coronary inflammation and favours healing. Aim of our study was to assess the safety and efficacy of bp-biolimus-eluting stent (bp-BES) in a large series of consecutive diabetic patients. From 2009 to 2013 we retrospectively enrolled consecutive diabetic patients treated with PCI and bp-BES implantation. Primary end points were target lesion revascularization (TLR) and stent thrombosis rates. Study cohort counted 747 patients. Multivessel disease was present in 48.2% with a mean stent/patient ratio of 1.860.78. During the hospital stay no stent thrombosis occurred. At 3-year follow-up we observed a 1.5% cumulative incidence of cardiac death, 1.1% of myocardial infarction and 6.3% of TLR. Stent thrombosis occurred ...

Biochemia medica, 2015

The aim of this study was to identify clinical variables which may be independently associated wi... more The aim of this study was to identify clinical variables which may be independently associated with positivity of a cardiac troponin I (cTnI) assay in a large population of patients admitted to the emergency department (ED). 3166 subjects, with at least two troponin I tests ordered within 6 hours in the ED, were studied. Patient data were statistically analyzed to identify clinical associations with increased values of Troponin I. Although patients with diagnosis of acute coronary syndrome displayed troponin I values significantly higher than those of other groups, positivity to troponin I (> 40 ng/L) was also observed in patients with other clinical conditions. In multivariate analysis, age, elevated heart rate and electrocardiographyc changes were independently associated with troponin I positivity at admission. In the whole study population troponin I positivity exhibited high sensitivity and negative predictive value, counterbalanced by low specificity and limited positive pr...

Recent Patents on Medical Imaging, 2014

ABSTRACT Imaging of the coronary circulation is a critical clinical topic, as only the best knowl... more ABSTRACT Imaging of the coronary circulation is a critical clinical topic, as only the best knowledge of coronary anatomy allows efficacious and safe coronary interventions [1]. However this is a fast moving field, with new techniques continuously added to the inventory of the cardiologists and with new evidence supporting such techniques continuously accumulating in literature [2]. Such needs largely justify the present monothematic issue which collects up to date information regarding coronary multimodality imaging. The backbone of coronary imaging, coronary angiography, is turning to the trans-radial approach, which offers important advantages both in terms of patient satisfaction and prognosis. This topic is tackled by the review by Rognoni et al. [3], describing the principles of quantitative coronary angiography, a robust method that nowadays allows researchers to assess the impact of the process of atherosclerosis on the lumen of the coronary artery and to establish over time whether an intervention attenuates progression or regression of atherosclerotic disease. In this paper the latest developments of computer assisted assessment of coronary artery luminograms are described and the limitations and difficulties related to interpretation of the angiographic information are discussed. The probably most dynamic field of cardiac and coronary imaging is constituted by the tomographic imaging techniques, among which cardiac and coronary CT-scan and cardiac magnetic resonance are gaining more and more favor to assess cardiac and coronary anatomy as well as the consequences of coronary artery disease, myocardial ischemia and necrosis. CT-scan of coronary arteries are becoming better and better in selecting patients for subsequent coronary interventions with magnificent 3- D reconstructions of the whole coronary tree. These topics are widely discussed by the reviews of Schaffer et al. [4]. Finally, the most exciting evolution has involved the invasive coronary imaging: IVUS, with particular attention to newer development of the technique, that is to say radiofrequency IVUS (virtual histology) for vulnerable coronary plaques detection; fractional flow reserve, which adds to coronary angiography fundamental functional information to guide coronary interventions; and finally optical coherence tomography which with its amazing resolution power can detect stent endothelization with details comparable to an histological examination. These fields are exhaustively covered in the reviews of Barbieri et al. [5] and the paper from the group of Imperial College of London lead by Prof Di Mario [6]. To finally turn the readers’ attention to the clinical point of view, the reviews of Lupi et al. [7] and Nardi et al. [8] address two of the most exciting imaging problems in the clinical cardiology, the search for vulnerable coronary plaques and the detection of cardioembolic sources.

BioMed Research International, 2014

Several studies have already demonstrated that the incomplete polymerization of resin-based denta... more Several studies have already demonstrated that the incomplete polymerization of resin-based dental materials causes the release of monomers which might affect cell metabolism. The aim of this study was to investigate the effects of triethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, urethane dimethacrylate, and 2-hydroxyethyl methacrylate on (1) cellular energy metabolism, evaluating oxygen consumption rate, glucose consumption, glucose 6-phosphate dehydrogenase activity, and lactate production, and (2) cellular redox status, through the evaluation of glutathione concentration and of the activities of enzymes regulating glutathione metabolism. Methods. Human pulp cells were used and oxygen consumption was measured by means of a Clark electrode. Moreover, reactive oxygen species production was quantified. Enzymatic activity and glucose and lactate concentrations were determined through a specific kit. Results. Triethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, and 2-hydroxyethyl methacrylate induced a decrease in oxygen consumption rate, an enhancement of glucose consumption, and lactate production, whilst glucose 6-phosphate dehydrogenase and glutathione reductase activity were not significantly modified. Moreover, the monomers induced an increase of reactive oxygen species production with a consequent increase of superoxide dismutase and catalase enzymatic activities. A depletion of both reduced and total glutathione was also observed. Conclusion. The obtained results indicate that dental monomers might alter energy metabolism and glutathione redox balance in human pulp cells.

To compare the acute performance of the PLLA ABSORB Bioresorbable Vascular Scaffold (BVS) with se... more To compare the acute performance of the PLLA ABSORB Bioresorbable Vascular Scaffold (BVS) with second generation metallic drug eluting stents (DES) in complex coronary artery lesions.

Luminescence, 2008

In the last years the studies regarding the biocompatibility of dental materials investigate, in ... more In the last years the studies regarding the biocompatibility of dental materials investigate, in addition to the classic cytotoxic tests, the interactions between the materials and the host cells to better explain the causes of the adverse effects observed sometimes in the clinical practice. In the present study the ability of diurethane dimethacrylate (DUDMA) and 1,4-butanediol dimethacrylate (BDDMA) methacrylic monomers present in dental composite resins to alter the functionality of peripheral blood monocytes (PBMs) and polymorphonucleate cells (PMNs) was examined. These cells are involve in the biological response to materials and in the host ability to respond to bacteria. The results obtained suggest that the examined methacrylates induce a relevant decrease of PBMs oxidative burst whereas the basal ROS production is only slightly decreased. In PMNs DUDMA induces a decrease of both basal and stimulated ROS production. BDDMA, on the contrary, it does not alter total oxidative burst in presence of stimulus while induces a statistically significant decrease of basal ROS production. Moreover this monomer alters the reaction kinetics of stimulated ROS production. The reported finding seems to indicate that this molecule could be able to stabilize PMNs in resting state and maximize their stimulated activity.

Luminescence, 2006

Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are... more Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are photo-polymerized, but this reaction is never complete, so release of uncured monomers in the periapical tissues and in biological fluids may happen and, potentially, alter the repair of pulpal and of periapical lesions by interfering with local phagocytes. The aim of this study was the evaluation of the functional activity of the monocyte-macrophage system after incubation with methacrylic monomers. The oxidative burst of two cellular systems was analysed using the chemiluminescence technique. Data were collected and statistically analysed. Monomers were found to reduce the in vitro oxidative burst of phagocytes independently from their cytotoxicity. These findings demand further evaluation of the effects of oxidative burst alteration in monocyte-macrophage function and may prompt the inclusion of the described chemiluminescence test in biocompatibility preliminary studies of dental materials.

Journal of Proteome Research, 2004

Thirteen samples of human normal whole saliva were analyzed by RP-HPLC-ESI-MS and MALDI-TOF-MS to... more Thirteen samples of human normal whole saliva were analyzed by RP-HPLC-ESI-MS and MALDI-TOF-MS to investigate the basic proline-rich protein complex. Between known basic-PRPs the P-B, P-C (or IB-8b), P-D (or IB-5), P-E (or IB-9), P-F (or IB-8c), P-H (or IB-4), IB-6, II-2, IB-1, and IB-8a glucosylated were identified, whereas the II-1, IB-7, PA, and D1-A peptides were not detected. Some detected masses not attributable to known basic-PRPs were putatively ascribed to II-2 and IB-1 nonphosphorylated, II-2 and IB-1 missing the C-terminal arginine residue, and the 1-62 fragment of IB-6, named P-J peptide. A correlation matrix analysis revealed a cluster of correlation among all the basic PRPs (apart from the P-B peptide) which is in agreement with their common parotid origin.

Journal of Dentistry, 2007

Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacryla... more Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Helvetica Chimica Acta, 1984

265. Biogenetic-Type Total Synthesis of (f)-2-Deoxystemodinone ... Summary A biogenetic-type tota... more 265. Biogenetic-Type Total Synthesis of (f)-2-Deoxystemodinone ... Summary A biogenetic-type total synthesis of (&)-2-deoxystemodinone (l), by solvolytic rear-rangement of the 1-methylbicyclo[2.2.2] oct-2-yl methanesulfonate 4, is described. ... We have previously ...

Helvetica Chimica Acta, 1983

... by Rinaldo Marini Bettolo" and Pietro Tagliatesta Centro di Studio del CNR per la Chimic... more ... by Rinaldo Marini Bettolo" and Pietro Tagliatesta Centro di Studio del CNR per la Chimica delle Sostanze Organiche Naturali, Dipartimento di Chimica, Facolta di Scienze Matematiche ... 1 1981, 1386; c) RL Cargill, DF Bushey, JR Dalton, PS Prasad, RD Dyer & J. Bordner, J . Org. ...

Free Radical Research, 2000

... Page 4. 4 B. TAVAZZI et al. 200 and 300 nm, and equipped with a Kromasil C-18, 5~tm particle ... more ... Page 4. 4 B. TAVAZZI et al. 200 and 300 nm, and equipped with a Kromasil C-18, 5~tm particle size, 250 x4.6mm column (Eka Chemicals AB, Bohus, Sweden), provided of its own guard-column. ... RESULTS System (1) for ROS Generation ...

European Journal of Pediatrics, 1997

European Journal of Oral Sciences, 2009

The polymerization of methacrylates present in dental composite resins is never complete (1), and... more The polymerization of methacrylates present in dental composite resins is never complete (1), and when monomers such as triethyleneglycol dimethacrylate (TEGDMA), 2-hydroxyethylmethacrylate (HEMA), bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA), 1,4-butanediol dimethacrylate (BDDMA), urethane dimethacrylate (UDMA), or others are converted to the high-molecular-weight networked solid, residual unreacted monomers remain trapped in the structure (2). The incomplete conversion causes, along with a reduction in the mechanical strength (3), the release of monomers, the presence of which may result in adverse effects in the organism [i.e. allergic reactions (4), systemic toxicity, cytotoxicity (5), estrogenicity, cell cycle alteration (6), and mutagenicity (1, 7, 8)]. As the intracellular mechanisms of the aforesaid effects are still not completely clear, we decided to investigate the biochemical interactions between methacrylates and human cells. In particular, we studied the behaviour of BDDMA and UDMA because their cytotoxicity and the mechanisms underlying it are poorly known. To avoid interference owing to synergistic and/or antagonistic effects often observed in methacrylate mixtures (9), we chose to employ pure monomer compounds.

ELECTROPHORESIS, 2003

Binding of Zn 21 to bacitracin A 1 was studied by capillary electrophoresis in water/ 2,2,2-trifl... more Binding of Zn 21 to bacitracin A 1 was studied by capillary electrophoresis in water/ 2,2,2-trifluoroethanol (70/30 v/v) at different apparent pH values in order to estimate the association constant of metal, the acidic dissociation constants and the Stokes radii of both free and bounded peptide in apolar environment. The Stokes radii of the free peptide species were compared with those in aqueous solution, as obtained in a recent study performed by our group, indicating that apolar environment stabilizes bacitracin A 1 in a conformational structure with the lateral chain of apolar amino acids exposed on the external surface. This conformation of the macrocyclic dodecapeptide is ready to interact with Zn 21 ion, as pointed out by the strong increase of the association constant measured in water/2,2,2-trifluoroethanol with respect to the value obtained in aqueous solution. In addition, whereas Zn 21 ion binding in aqueous solution provides a sensible reduction of peptide Stokes radius, no sensible variations following to ion binding were observed in hydro-organic solution. The present results suggest that the apolar environment, rather than the metal ion binding, could be responsible for the conformational transition that brings bacitracin A 1 towards its biologically active structure.*

ELECTROPHORESIS, 2002

The general properties of dendrimers and in particular their electrolytic characteristics that ar... more The general properties of dendrimers and in particular their electrolytic characteristics that are relevant in electrokinetic separations, are described. In order to confirm theoretical considerations on commercial dendrimer charge and hydrodynamic radius, several capillary zone electrophoresis (CZE) experiments were performed. Electrophoretic mobilities measured at different pH values indicated a sensible increase of dendrimer hydrodynamic radius at pH values lower than 2.5. This was probably due to the Coulombic repulsion of charged amine groups of the inner dendrimer shells. The principal reasons that should address the use of dendrimers as pseudostationary phases in micellar electrokinetic chromatography (MEKC) are discussed. Moreover, a survey of different separations performed utilizing dendrimers in MEKC as well as of several future plausible uses of various classes of dendrimers is presented.

ELECTROPHORESIS, 2004

Thermodynamics of the binding of Ni 21 , Cu 21 and Zn 21 to bacitracin A 1 was studied by capilla... more Thermodynamics of the binding of Ni 21 , Cu 21 and Zn 21 to bacitracin A 1 was studied by capillary electrophoresis measuring the peptide effective mobility at different pH in the presence of increasing concentration of the three ligands. The affinity follows the order Ni 21 . Cu 21 . Zn 21 , with association constant values of (2.3 6 0.1)610 4 , (4.9 6 0.2)610 3 , and (1.5 6 0.1)610 3 M 21 , respectively. The only model able to rationalize mobility data implies that metal ion binds to the P 0 peptide form. Moreover, mobility values indicated a change of bacitracin A 1 acidic properties on Ni 21 and Cu 21 binding, with a shift of the pK a of N-terminal Ile-1 from 7.6 to about 5 and of the pK a of the d-amino group of D-Orn-7 from 9.7 to about 7. Even though on Zn 21 binding a shift of the N-terminal Ile-1 pK a was observed, restrictions in the pH range suitable for investigation, due to precipitation phenomena, did not allow establish if the shift of D-Orn-7 lateral chain pK a also occurred. Nonetheless, if present, the shift should be limited to the 7.8-9.7 range. Mobility data indicated that the Stokes radius of the complexes is ca. 3 Å lower than that of the free peptide. The present results indicate that metal-ion binding to bacitracin A 1 is more complex than previously assumed.

ELECTROPHORESIS, 2003

Measurements by capillary electrophoresis (CE) of bacitracin A 1 effective mobility at different ... more Measurements by capillary electrophoresis (CE) of bacitracin A 1 effective mobility at different pH values permitted to estimate the five acidic dissociation constants and the Stokes radii at different protonation stages of the macrocyclic dodecapeptide. The pK a values were 3.6 and 4.4 for the two carboxylic groups of the lateral chains of D-Asp-11 and D-Glu-4, respectively, 6.4 for the aza-atom of the imidazole ring of His-10, 7.6 for the amino group of N-terminal Ile-1 and 9.7 for the d-amino group of D-Orn-7, very close to the values obtained by other researchers by titration experiments. In agreement with a rigid macrocyclic structure the Stokes radii of different protonated forms ranged only between 14.3 and 14.8 Å. Best fitting procedures performed on experimental mobility measured at two different pH values (5.50 and 6.72) in the presence of increasing Zn 12 concentration allowed confirming the model that assumes the binding of Zn 12 to P 0 peptide form with a 1.5610 3 M 21 intrinsic association constant. Following to Zn 12 binding, the pK a of the amino group of N-terminal Ile-1 is shifted from 7.6 to 5.9 and the Stokes radius is reduced of about 3 Å. The mean charge of the bacitracin A 1 -Zn 12 complex resulted 11.67 and 11.12 at pH 5.50 and 6.72, respectively. These results suggest that the amino group of N-terminal Ile-1 is not essential for Zn 12 binding.

Dental Materials, 2011

d e n t a l m a t e r i a l s 2 7 ( 2 0 1 1 ) e87-e98 a v a i l a b l e a t w w w . s c i e n c e... more d e n t a l m a t e r i a l s 2 7 ( 2 0 1 1 ) e87-e98 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . i n t l . e l s e v i e r h e a l t h . c o m / j o u r n a l s / d e m a GSH Metabolism HPLC-MS Capillary electrophoresis a b s t r a c t Objectives. Methacrylic monomers are released, from dental composite resins, either into the oral cavity or in pulpal tissues, where they can cause local or systemic adverse effects. The mechanisms of these effects are not well understood, probably because such molecules can act at different levels also inducing a depletion of intracellular glutathione (GSH). GSH can detoxify methacrylates by conjugating their ␣,␤-unsaturated carbon-carbon moiety to the thiol group, with the catalysis of glutathione S-transferases (GST). This reaction determines a GSH cellular depletion and belongs to the metabolism of ␣,␤-unsaturated esters, protecting the body against the toxic effects of electrophiles. On the basis of the above considerations, this work aim is to set up a method for the detection of the adducts formed by methacrylic monomers with GSH in cells using HPLC coupled to mass spectrometry (HPLC-MS) and micellar electrokinetic capillary chromatography (MECK) techniques. Methods and results. Adducts of glutathione with triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA) were incontrovertibly identified by HPLC-MS and MECK in human gingival fibroblasts and erythrocytes, both outside and inside cells. Molecular docking simulations of HEMA and TEGDMA in the experimental structure of glutathione S-transferase, are also reported to rationalize the effectiveness of such enzyme in the catalysis of the above described reaction.

Biomaterials, 2010

Cytotoxicity of the dental resin monomer 2-hydroxyethyl methacrylate (HEMA) and the protective ef... more Cytotoxicity of the dental resin monomer 2-hydroxyethyl methacrylate (HEMA) and the protective effects of N-acetyl cysteine (NAC) on monomer-induced cell damage are well demonstrated. The aim of our study was to analyze the hypothesis that the protection of NAC from HEMA cytotoxicity might be due to direct NAC adduct formation. To this end, using HPLC we first measured the actual intracellular HEMA concentrations able to cause toxic effects on 3T3-fibroblasts and then determined the decrease in intracellular and extracellular HEMA levels in the presence of NAC. In addition, by capillary electrophoresis coupled with mass spectrometry analysis (CE-MS), we evaluated NAC-HEMA adduct formation. HEMA reduced 3T3 cell vitality in a dose-and time-dependent manner. The concentration of HEMA inside the cells was 15-20 times lower than that added to the culture medium for cell treatment (0-8 mmol/L). In the presence of 10 mmol/L NAC, both intracellular and extracellular HEMA concentrations greatly decreased in conjunction with cytotoxicity. NAC-HEMA adducts were detected both in the presence and absence of cells. Our findings suggest that the in vitro detoxification ability of NAC against HEMA-induced cell damage occurs through NAC adduct formation. Moreover, we provide evidence that the actual intracellular concentration of HEMA able to cause cytotoxic effects is at least one magnitude lower than that applied extracellularly.

Journal of cardiovascular medicine (Hagerstown, Md.), Jan 21, 2015

Coronary inflammation and healing influence outcomes of diabetic patients treated with Percutaneo... more Coronary inflammation and healing influence outcomes of diabetic patients treated with Percutaneous coronary revascularization (PCI). Stents covered with biodegradable polymers (bp) may offer advantages over nonerodible polymer ones, because polymer reabsorption extinguish coronary inflammation and favours healing. Aim of our study was to assess the safety and efficacy of bp-biolimus-eluting stent (bp-BES) in a large series of consecutive diabetic patients. From 2009 to 2013 we retrospectively enrolled consecutive diabetic patients treated with PCI and bp-BES implantation. Primary end points were target lesion revascularization (TLR) and stent thrombosis rates. Study cohort counted 747 patients. Multivessel disease was present in 48.2% with a mean stent/patient ratio of 1.860.78. During the hospital stay no stent thrombosis occurred. At 3-year follow-up we observed a 1.5% cumulative incidence of cardiac death, 1.1% of myocardial infarction and 6.3% of TLR. Stent thrombosis occurred ...

Biochemia medica, 2015

The aim of this study was to identify clinical variables which may be independently associated wi... more The aim of this study was to identify clinical variables which may be independently associated with positivity of a cardiac troponin I (cTnI) assay in a large population of patients admitted to the emergency department (ED). 3166 subjects, with at least two troponin I tests ordered within 6 hours in the ED, were studied. Patient data were statistically analyzed to identify clinical associations with increased values of Troponin I. Although patients with diagnosis of acute coronary syndrome displayed troponin I values significantly higher than those of other groups, positivity to troponin I (> 40 ng/L) was also observed in patients with other clinical conditions. In multivariate analysis, age, elevated heart rate and electrocardiographyc changes were independently associated with troponin I positivity at admission. In the whole study population troponin I positivity exhibited high sensitivity and negative predictive value, counterbalanced by low specificity and limited positive pr...

Recent Patents on Medical Imaging, 2014

ABSTRACT Imaging of the coronary circulation is a critical clinical topic, as only the best knowl... more ABSTRACT Imaging of the coronary circulation is a critical clinical topic, as only the best knowledge of coronary anatomy allows efficacious and safe coronary interventions [1]. However this is a fast moving field, with new techniques continuously added to the inventory of the cardiologists and with new evidence supporting such techniques continuously accumulating in literature [2]. Such needs largely justify the present monothematic issue which collects up to date information regarding coronary multimodality imaging. The backbone of coronary imaging, coronary angiography, is turning to the trans-radial approach, which offers important advantages both in terms of patient satisfaction and prognosis. This topic is tackled by the review by Rognoni et al. [3], describing the principles of quantitative coronary angiography, a robust method that nowadays allows researchers to assess the impact of the process of atherosclerosis on the lumen of the coronary artery and to establish over time whether an intervention attenuates progression or regression of atherosclerotic disease. In this paper the latest developments of computer assisted assessment of coronary artery luminograms are described and the limitations and difficulties related to interpretation of the angiographic information are discussed. The probably most dynamic field of cardiac and coronary imaging is constituted by the tomographic imaging techniques, among which cardiac and coronary CT-scan and cardiac magnetic resonance are gaining more and more favor to assess cardiac and coronary anatomy as well as the consequences of coronary artery disease, myocardial ischemia and necrosis. CT-scan of coronary arteries are becoming better and better in selecting patients for subsequent coronary interventions with magnificent 3- D reconstructions of the whole coronary tree. These topics are widely discussed by the reviews of Schaffer et al. [4]. Finally, the most exciting evolution has involved the invasive coronary imaging: IVUS, with particular attention to newer development of the technique, that is to say radiofrequency IVUS (virtual histology) for vulnerable coronary plaques detection; fractional flow reserve, which adds to coronary angiography fundamental functional information to guide coronary interventions; and finally optical coherence tomography which with its amazing resolution power can detect stent endothelization with details comparable to an histological examination. These fields are exhaustively covered in the reviews of Barbieri et al. [5] and the paper from the group of Imperial College of London lead by Prof Di Mario [6]. To finally turn the readers’ attention to the clinical point of view, the reviews of Lupi et al. [7] and Nardi et al. [8] address two of the most exciting imaging problems in the clinical cardiology, the search for vulnerable coronary plaques and the detection of cardioembolic sources.

BioMed Research International, 2014

Several studies have already demonstrated that the incomplete polymerization of resin-based denta... more Several studies have already demonstrated that the incomplete polymerization of resin-based dental materials causes the release of monomers which might affect cell metabolism. The aim of this study was to investigate the effects of triethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, urethane dimethacrylate, and 2-hydroxyethyl methacrylate on (1) cellular energy metabolism, evaluating oxygen consumption rate, glucose consumption, glucose 6-phosphate dehydrogenase activity, and lactate production, and (2) cellular redox status, through the evaluation of glutathione concentration and of the activities of enzymes regulating glutathione metabolism. Methods. Human pulp cells were used and oxygen consumption was measured by means of a Clark electrode. Moreover, reactive oxygen species production was quantified. Enzymatic activity and glucose and lactate concentrations were determined through a specific kit. Results. Triethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, and 2-hydroxyethyl methacrylate induced a decrease in oxygen consumption rate, an enhancement of glucose consumption, and lactate production, whilst glucose 6-phosphate dehydrogenase and glutathione reductase activity were not significantly modified. Moreover, the monomers induced an increase of reactive oxygen species production with a consequent increase of superoxide dismutase and catalase enzymatic activities. A depletion of both reduced and total glutathione was also observed. Conclusion. The obtained results indicate that dental monomers might alter energy metabolism and glutathione redox balance in human pulp cells.

To compare the acute performance of the PLLA ABSORB Bioresorbable Vascular Scaffold (BVS) with se... more To compare the acute performance of the PLLA ABSORB Bioresorbable Vascular Scaffold (BVS) with second generation metallic drug eluting stents (DES) in complex coronary artery lesions.

Luminescence, 2008

In the last years the studies regarding the biocompatibility of dental materials investigate, in ... more In the last years the studies regarding the biocompatibility of dental materials investigate, in addition to the classic cytotoxic tests, the interactions between the materials and the host cells to better explain the causes of the adverse effects observed sometimes in the clinical practice. In the present study the ability of diurethane dimethacrylate (DUDMA) and 1,4-butanediol dimethacrylate (BDDMA) methacrylic monomers present in dental composite resins to alter the functionality of peripheral blood monocytes (PBMs) and polymorphonucleate cells (PMNs) was examined. These cells are involve in the biological response to materials and in the host ability to respond to bacteria. The results obtained suggest that the examined methacrylates induce a relevant decrease of PBMs oxidative burst whereas the basal ROS production is only slightly decreased. In PMNs DUDMA induces a decrease of both basal and stimulated ROS production. BDDMA, on the contrary, it does not alter total oxidative burst in presence of stimulus while induces a statistically significant decrease of basal ROS production. Moreover this monomer alters the reaction kinetics of stimulated ROS production. The reported finding seems to indicate that this molecule could be able to stabilize PMNs in resting state and maximize their stimulated activity.

Luminescence, 2006

Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are... more Methacrylates are present in dental composite resins used in clinical practice. Methacrylates are photo-polymerized, but this reaction is never complete, so release of uncured monomers in the periapical tissues and in biological fluids may happen and, potentially, alter the repair of pulpal and of periapical lesions by interfering with local phagocytes. The aim of this study was the evaluation of the functional activity of the monocyte-macrophage system after incubation with methacrylic monomers. The oxidative burst of two cellular systems was analysed using the chemiluminescence technique. Data were collected and statistically analysed. Monomers were found to reduce the in vitro oxidative burst of phagocytes independently from their cytotoxicity. These findings demand further evaluation of the effects of oxidative burst alteration in monocyte-macrophage function and may prompt the inclusion of the described chemiluminescence test in biocompatibility preliminary studies of dental materials.

Journal of Proteome Research, 2004

Thirteen samples of human normal whole saliva were analyzed by RP-HPLC-ESI-MS and MALDI-TOF-MS to... more Thirteen samples of human normal whole saliva were analyzed by RP-HPLC-ESI-MS and MALDI-TOF-MS to investigate the basic proline-rich protein complex. Between known basic-PRPs the P-B, P-C (or IB-8b), P-D (or IB-5), P-E (or IB-9), P-F (or IB-8c), P-H (or IB-4), IB-6, II-2, IB-1, and IB-8a glucosylated were identified, whereas the II-1, IB-7, PA, and D1-A peptides were not detected. Some detected masses not attributable to known basic-PRPs were putatively ascribed to II-2 and IB-1 nonphosphorylated, II-2 and IB-1 missing the C-terminal arginine residue, and the 1-62 fragment of IB-6, named P-J peptide. A correlation matrix analysis revealed a cluster of correlation among all the basic PRPs (apart from the P-B peptide) which is in agreement with their common parotid origin.

Journal of Dentistry, 2007

Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacryla... more Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Helvetica Chimica Acta, 1984

265. Biogenetic-Type Total Synthesis of (f)-2-Deoxystemodinone ... Summary A biogenetic-type tota... more 265. Biogenetic-Type Total Synthesis of (f)-2-Deoxystemodinone ... Summary A biogenetic-type total synthesis of (&)-2-deoxystemodinone (l), by solvolytic rear-rangement of the 1-methylbicyclo[2.2.2] oct-2-yl methanesulfonate 4, is described. ... We have previously ...

Helvetica Chimica Acta, 1983

... by Rinaldo Marini Bettolo" and Pietro Tagliatesta Centro di Studio del CNR per la Chimic... more ... by Rinaldo Marini Bettolo" and Pietro Tagliatesta Centro di Studio del CNR per la Chimica delle Sostanze Organiche Naturali, Dipartimento di Chimica, Facolta di Scienze Matematiche ... 1 1981, 1386; c) RL Cargill, DF Bushey, JR Dalton, PS Prasad, RD Dyer & J. Bordner, J . Org. ...

Free Radical Research, 2000

... Page 4. 4 B. TAVAZZI et al. 200 and 300 nm, and equipped with a Kromasil C-18, 5~tm particle ... more ... Page 4. 4 B. TAVAZZI et al. 200 and 300 nm, and equipped with a Kromasil C-18, 5~tm particle size, 250 x4.6mm column (Eka Chemicals AB, Bohus, Sweden), provided of its own guard-column. ... RESULTS System (1) for ROS Generation ...

European Journal of Pediatrics, 1997

European Journal of Oral Sciences, 2009

The polymerization of methacrylates present in dental composite resins is never complete (1), and... more The polymerization of methacrylates present in dental composite resins is never complete (1), and when monomers such as triethyleneglycol dimethacrylate (TEGDMA), 2-hydroxyethylmethacrylate (HEMA), bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA), 1,4-butanediol dimethacrylate (BDDMA), urethane dimethacrylate (UDMA), or others are converted to the high-molecular-weight networked solid, residual unreacted monomers remain trapped in the structure (2). The incomplete conversion causes, along with a reduction in the mechanical strength (3), the release of monomers, the presence of which may result in adverse effects in the organism [i.e. allergic reactions (4), systemic toxicity, cytotoxicity (5), estrogenicity, cell cycle alteration (6), and mutagenicity (1, 7, 8)]. As the intracellular mechanisms of the aforesaid effects are still not completely clear, we decided to investigate the biochemical interactions between methacrylates and human cells. In particular, we studied the behaviour of BDDMA and UDMA because their cytotoxicity and the mechanisms underlying it are poorly known. To avoid interference owing to synergistic and/or antagonistic effects often observed in methacrylate mixtures (9), we chose to employ pure monomer compounds.

ELECTROPHORESIS, 2003

Binding of Zn 21 to bacitracin A 1 was studied by capillary electrophoresis in water/ 2,2,2-trifl... more Binding of Zn 21 to bacitracin A 1 was studied by capillary electrophoresis in water/ 2,2,2-trifluoroethanol (70/30 v/v) at different apparent pH values in order to estimate the association constant of metal, the acidic dissociation constants and the Stokes radii of both free and bounded peptide in apolar environment. The Stokes radii of the free peptide species were compared with those in aqueous solution, as obtained in a recent study performed by our group, indicating that apolar environment stabilizes bacitracin A 1 in a conformational structure with the lateral chain of apolar amino acids exposed on the external surface. This conformation of the macrocyclic dodecapeptide is ready to interact with Zn 21 ion, as pointed out by the strong increase of the association constant measured in water/2,2,2-trifluoroethanol with respect to the value obtained in aqueous solution. In addition, whereas Zn 21 ion binding in aqueous solution provides a sensible reduction of peptide Stokes radius, no sensible variations following to ion binding were observed in hydro-organic solution. The present results suggest that the apolar environment, rather than the metal ion binding, could be responsible for the conformational transition that brings bacitracin A 1 towards its biologically active structure.*

ELECTROPHORESIS, 2002

The general properties of dendrimers and in particular their electrolytic characteristics that ar... more The general properties of dendrimers and in particular their electrolytic characteristics that are relevant in electrokinetic separations, are described. In order to confirm theoretical considerations on commercial dendrimer charge and hydrodynamic radius, several capillary zone electrophoresis (CZE) experiments were performed. Electrophoretic mobilities measured at different pH values indicated a sensible increase of dendrimer hydrodynamic radius at pH values lower than 2.5. This was probably due to the Coulombic repulsion of charged amine groups of the inner dendrimer shells. The principal reasons that should address the use of dendrimers as pseudostationary phases in micellar electrokinetic chromatography (MEKC) are discussed. Moreover, a survey of different separations performed utilizing dendrimers in MEKC as well as of several future plausible uses of various classes of dendrimers is presented.

ELECTROPHORESIS, 2004

Thermodynamics of the binding of Ni 21 , Cu 21 and Zn 21 to bacitracin A 1 was studied by capilla... more Thermodynamics of the binding of Ni 21 , Cu 21 and Zn 21 to bacitracin A 1 was studied by capillary electrophoresis measuring the peptide effective mobility at different pH in the presence of increasing concentration of the three ligands. The affinity follows the order Ni 21 . Cu 21 . Zn 21 , with association constant values of (2.3 6 0.1)610 4 , (4.9 6 0.2)610 3 , and (1.5 6 0.1)610 3 M 21 , respectively. The only model able to rationalize mobility data implies that metal ion binds to the P 0 peptide form. Moreover, mobility values indicated a change of bacitracin A 1 acidic properties on Ni 21 and Cu 21 binding, with a shift of the pK a of N-terminal Ile-1 from 7.6 to about 5 and of the pK a of the d-amino group of D-Orn-7 from 9.7 to about 7. Even though on Zn 21 binding a shift of the N-terminal Ile-1 pK a was observed, restrictions in the pH range suitable for investigation, due to precipitation phenomena, did not allow establish if the shift of D-Orn-7 lateral chain pK a also occurred. Nonetheless, if present, the shift should be limited to the 7.8-9.7 range. Mobility data indicated that the Stokes radius of the complexes is ca. 3 Å lower than that of the free peptide. The present results indicate that metal-ion binding to bacitracin A 1 is more complex than previously assumed.

ELECTROPHORESIS, 2003

Measurements by capillary electrophoresis (CE) of bacitracin A 1 effective mobility at different ... more Measurements by capillary electrophoresis (CE) of bacitracin A 1 effective mobility at different pH values permitted to estimate the five acidic dissociation constants and the Stokes radii at different protonation stages of the macrocyclic dodecapeptide. The pK a values were 3.6 and 4.4 for the two carboxylic groups of the lateral chains of D-Asp-11 and D-Glu-4, respectively, 6.4 for the aza-atom of the imidazole ring of His-10, 7.6 for the amino group of N-terminal Ile-1 and 9.7 for the d-amino group of D-Orn-7, very close to the values obtained by other researchers by titration experiments. In agreement with a rigid macrocyclic structure the Stokes radii of different protonated forms ranged only between 14.3 and 14.8 Å. Best fitting procedures performed on experimental mobility measured at two different pH values (5.50 and 6.72) in the presence of increasing Zn 12 concentration allowed confirming the model that assumes the binding of Zn 12 to P 0 peptide form with a 1.5610 3 M 21 intrinsic association constant. Following to Zn 12 binding, the pK a of the amino group of N-terminal Ile-1 is shifted from 7.6 to 5.9 and the Stokes radius is reduced of about 3 Å. The mean charge of the bacitracin A 1 -Zn 12 complex resulted 11.67 and 11.12 at pH 5.50 and 6.72, respectively. These results suggest that the amino group of N-terminal Ile-1 is not essential for Zn 12 binding.

Dental Materials, 2011

d e n t a l m a t e r i a l s 2 7 ( 2 0 1 1 ) e87-e98 a v a i l a b l e a t w w w . s c i e n c e... more d e n t a l m a t e r i a l s 2 7 ( 2 0 1 1 ) e87-e98 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . i n t l . e l s e v i e r h e a l t h . c o m / j o u r n a l s / d e m a GSH Metabolism HPLC-MS Capillary electrophoresis a b s t r a c t Objectives. Methacrylic monomers are released, from dental composite resins, either into the oral cavity or in pulpal tissues, where they can cause local or systemic adverse effects. The mechanisms of these effects are not well understood, probably because such molecules can act at different levels also inducing a depletion of intracellular glutathione (GSH). GSH can detoxify methacrylates by conjugating their ␣,␤-unsaturated carbon-carbon moiety to the thiol group, with the catalysis of glutathione S-transferases (GST). This reaction determines a GSH cellular depletion and belongs to the metabolism of ␣,␤-unsaturated esters, protecting the body against the toxic effects of electrophiles. On the basis of the above considerations, this work aim is to set up a method for the detection of the adducts formed by methacrylic monomers with GSH in cells using HPLC coupled to mass spectrometry (HPLC-MS) and micellar electrokinetic capillary chromatography (MECK) techniques. Methods and results. Adducts of glutathione with triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA) were incontrovertibly identified by HPLC-MS and MECK in human gingival fibroblasts and erythrocytes, both outside and inside cells. Molecular docking simulations of HEMA and TEGDMA in the experimental structure of glutathione S-transferase, are also reported to rationalize the effectiveness of such enzyme in the catalysis of the above described reaction.

Biomaterials, 2010

Cytotoxicity of the dental resin monomer 2-hydroxyethyl methacrylate (HEMA) and the protective ef... more Cytotoxicity of the dental resin monomer 2-hydroxyethyl methacrylate (HEMA) and the protective effects of N-acetyl cysteine (NAC) on monomer-induced cell damage are well demonstrated. The aim of our study was to analyze the hypothesis that the protection of NAC from HEMA cytotoxicity might be due to direct NAC adduct formation. To this end, using HPLC we first measured the actual intracellular HEMA concentrations able to cause toxic effects on 3T3-fibroblasts and then determined the decrease in intracellular and extracellular HEMA levels in the presence of NAC. In addition, by capillary electrophoresis coupled with mass spectrometry analysis (CE-MS), we evaluated NAC-HEMA adduct formation. HEMA reduced 3T3 cell vitality in a dose-and time-dependent manner. The concentration of HEMA inside the cells was 15-20 times lower than that added to the culture medium for cell treatment (0-8 mmol/L). In the presence of 10 mmol/L NAC, both intracellular and extracellular HEMA concentrations greatly decreased in conjunction with cytotoxicity. NAC-HEMA adducts were detected both in the presence and absence of cells. Our findings suggest that the in vitro detoxification ability of NAC against HEMA-induced cell damage occurs through NAC adduct formation. Moreover, we provide evidence that the actual intracellular concentration of HEMA able to cause cytotoxic effects is at least one magnitude lower than that applied extracellularly.