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Biomedical subjects

F Bruni

Publications and source records attributed to F Bruni.

At least 19 recordsLinked to original sources
PubMed2006

Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment.

BACKGROUND: Oxidized-LDL (ox-LDL) are involved in atherothrombosis by induction of endothelial dysfunction and thrombosis. The specific receptor lectin-like oxidized-LDL receptor-1 (LOX-1) is expressed in endothelial cells, monocytes and platelets. LOX-1 gene allelic variants (3'UTR/T) have been related with cardiovascular events and reduced anti-platelet activity induced by statins. OBJECTIVES: To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention. PATIENTS/METHODS: The present was a retrospective study performed in 751 white hypercholesterolemic subjects treated with increasing doses of atorvastatin (n=382, 247 male, 135 female) or simvastatin (n=369, 244 male, 125 female) up to 4 years, whose LDL target was 3.36 mmol/L according to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATPIII). Single nucleotide polymorphism were evaluated by allelic discrimination assays (PCR), lipid profile by enzymatic-colorimetric methods and C-reactive protein (CRP) by a nephelometric technique. RESULTS: Twenty-three non-ST elevation (NSTEMI) and eleven ST-elevation myocardial infarction (STEMI) were encountered in the observational period without differences between treatments (p=0.175) and sex (p=0.139). Each symptomatic subject (10 reaching the appropriate LDL target and 24 with still undesirable LDL) had the 3'UTR/T allelic variant (adjusted O.R. 4.63, 95% C.I. 3.46-6.70, p<0.0001). Among patients not reaching LDL target the C allele resulted protective with respect to T carriers (p<0.00001). Also, similar changes of CRP resulted in different event rate between T and C carriers (p<0.001) in the whole cohort. CONCLUSIONS: In the studied population LOX-1 genetic variants influence cardiovascular risk reduction induced by statins also in patients not reaching the LDL target. The previously described LOX-1-related antithrombotic actions of both statins employed could have a specific role in what observed, suggesting a genetic influence in statins LDL-lowering partially related actions.

Aged↗
PubMed2006

Eigen versus Zundel complexes in HCl-water mixtures.

There is an ongoing debate on the nature of hydration of the hydrogen ion, H+ in solution, and the extent to which Eigen or Zundel complexes occur. Here, our previous neutron diffraction data on a solution of 1:9 HCl in water are reanalyzed using a new starting hypothesis for the Monte Carlo simulation of the data. Either bare H+ ions, all H3O+ ions, or all H5O2 + ions are allowed in the simulation box together with the water and chlorine ions. All three simulations give a satisfactory fit to the experimental data. From the simulation with simple H+ ions, it is found that all H+ ions form one strong and very short hydrogen bond with water molecules and that on average 75% of them also engage in a second, slightly longer hydrogen bond. This result can be interpreted alternatively either in terms of the formation of a high percentage of asymmetric Zundel complexes or in terms of the formation of distorted H3O+ ions, which in turn form two or three hydrogen bonds, respectively, with neighboring molecules opposite their unbonded hydrogen sites (thus forming Eigen complexes). Therefore the new analysis is not inconsistent with our previous conclusion that the solution consists primarily of Eigen complexes, but does highlight the difficulty of making a clear distinction between Eigen and Zundel complexes due to the continuous random network of hydrogen bonds formed between water and hydrated protons. The role of hydrogen ion to chloride counterion contacts is also discussed in these solutions.

Journal Article↗
PubMed2005

Ions in water: the microscopic structure of concentrated hydroxide solutions.

Neutron-diffraction data on aqueous solutions of hydroxides, at solute concentrations ranging from 1 solute per 12 water molecules to 1 solute per 3 water molecules, are analyzed by means of a Monte Carlo simulation (empirical potential structure refinement), in order to determine the hydration shell of the OH- in the presence of the smaller alkali metal ions. It is demonstrated that the symmetry argument between H+ and OH- cannot be used, at least in the liquid phase at such high concentrations, for determining the hydroxide hydration shell. Water molecules in the hydration shell of K+ orient their dipole moment at about 45 degrees from the K+-water oxygen director, instead of radially as in the case of the Li+ and Na+ hydration shells. The K+-water oxygen radial distribution function shows a shallower first minimum compared to the other cation-water oxygen functions. The influence of the solutes on the water-water radial distribution functions is shown to have an effect on the water structure equivalent to an increase in the pressure of the water, depending on both ion concentration and ionic radius. The changes of the water structure in the presence of charged solutes and the differences among the hydration shells of the different cations are used to present a qualitative explanation of the observed cation mobility.

Journal Article↗
PubMed2005

Glassy behavior of a percolative water-protein system.

We show that is possible to look at the glass transition as a percolation transition in phase space. This study has been carried out on a hydrated globular enzyme for which the thermodynamic transition and the percolative transition could have a functional significance. The approach adopted is based on the identity of roles played respectively by the glass transition temperature T(o) and the critical hydration threshold h(c) for the percolation of protons on the surface and through the protein, given that dynamical arrest is observed at temperatures and hydration below T(o) and h(c). Theoretical predictions for temperature dependence of the nonexponentiality parameter, beta(KWW) , appearing in the KWW relaxation function, indicate that at high temperatures, beta(KWW) remains insensitive to temperature changes, whereas in the vicinity of the glass transition, beta(KWW) is linearly increasing with temperature. The low temperature limit of beta(KWW) is about 1/3 and its temperature-independent behavior starts at 1.23 T(g): both predictions have been verified in the present study.

Computer Simulation↗
PubMed2005

Structural and functional abnormality of systemic microvessels in cardiac syndrome X.

BACKGROUND AND AIM: Microvascular damage of coronary bed has been considered the main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced ischemic ST-segment changes and angiographically normal coronary arteries). Previous studies have demonstrated that vascular abnormalities are not confined to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of a generalized microvascular disturbance in cardiac syndrome X, we performed a morphologic and functional study of systemic microcirculation in patients with syndrome X compared to normal subjects. METHODS AND RESULTS: Microvessels were evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and conjunctival observation sites which explore micro and paramicrocirculation; biohumoral study included markers of inflammation and of endothelial function, coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed several morphologic changes (present in high percent of patients with syndrome X and not in controls) and significant quantitative alterations (capillary density, granular flow score, alterations of vessel profile, length of capillary loop branches and of arteriole/venule diameter) which indicated a severe alteration of whole vessel structure and an important rearrangement of microvascular disposition. In a similar way, the humoral study showed some significant changes of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated with inflammatory response. CONCLUSIONS: We conclude that patients with cardiac syndrome X exhibited some structural and functional alterations of systemic microvasculature; the pattern is similar to that detected in systemic inflammatory diseases and suggests a vascular lesion of inflammatory type. The same changes could be operating also in coronary microvessels of patients with syndrome X.

Angina Pectoris↗
PubMed2005

Atorvastatin reduces platelet-oxidized-LDL receptor expression in hypercholesterolaemic patients.

BACKGROUND: Oxidized-LDL (ox-LDL) are proatherogenic and platelet-activating molecules. Atorvastatin reduces platelet activity before cholesterol-lowering action. CD36 and lectin-like oxidized-LDL receptor-1 (LOX-1) are specific ox-LDL receptors expressed also in platelets. This study was planned to address whether the possible rapid effect of atorvastatin on platelets could be related to modulation of ox-LDL receptors. MATERIALS AND METHODS: Forty-eight hypercholesterolaemic subjects requiring statin treatment (atorvastatin 20 mg day(-1)) after an ineffective diet regimen were evaluated for complete lipid-profile (chromogenic); P-selectin (P-sel), CD36 and LOX-1 expression (cytofluorimetric detection); circulating and platelet-associated ox-LDL (ox- and Pox-LDL, ELISA); and intracellular citrullin recovery (iCit, HPLC) at baseline and 3, 6 and 9 days after inclusion in the study. Moreover, we studied 48 normal controls matched for sex and age. RESULTS: Platelet activity expressed by P-sel (in resting and thrombin-activated cells), CD36 and LOX-1 were increased in hypercholesterolaemic subjects (all P < 0.01). Atorvastatin induced a reduction of CD36 at 6 days (P < 0.05); and P-sel in resting (P < 0.001) and activated cells (P < 0.001) and LOX-1 were reduced at 9 days (all P < 0.001) in association with decreased Pox-LDL (P < 0.001) and increased iCit (P < 0.01). All data were obtained before a significant reduction of LDL and ox-LDL was achieved (P = 0.109 and 0.113). DISCUSSION: Present data suggest that platelet deactivation by atorvastatin is related to CD36 and LOX-1 expression reduction before significant LDL changes. Moreover, the modulation of LOX-1 can be considered a self-relevant antiatherothrombotic action of atoravastin owing to the important role of this receptor in the ox-LDL-mediated vascular damage.

Adult↗
PubMed2004

Ions in water: the microscopic structure of a concentrated HCl solution.

A neutron diffraction experiment with isotopic H/D substitution on a concentrated HCl/H2O solution is presented. The full set of partial structure factors is extracted, by combining the diffraction data with a Monte Carlo simulation. This allows us to investigate both the changes of the water structure in the presence of ions and their solvation shell, overcoming the limitations of standard diffraction experiments. It is found that the interaction with the solutes affects the tetrahedral network of hydrogen bonded water molecules, in a manner similar to the application of an external pressure to pure water, although HCl seems less effective than other solutes, such as NaOH, at the same concentration. Consistent with experimental and theoretical data, the number of water molecules in the solution is not sufficient to completely dissociate the acid molecule. As a consequence, both dissociated H+ and Cl- ions and undissociated HCl molecules coexist in the sample, and this mixture is correctly reproduced in the simulation box. In particular, the hydrated H+ ions, forming a H3O+ complex, participate in three strong and short hydrogen bonds, while a well-defined hydration shell is found around the chlorine ion. These results are not consistent with the findings of early diffraction experiments on the same system and could only be obtained by combining high quality experimental data with a proper computer simulation.

Journal Article↗
PubMed2004

Ions in water: the microscopic structure of concentrated NaOH solutions.

A neutron diffraction experiment with isotopic H/D substitution on four concentrated NaOH/H(2)O solutions is presented. The full set of partial structure factors is extracted, by combining the diffraction data with a Monte Carlo simulation. These allow to investigate both the changes of the water structure in the presence of ions and their solvation shells. It is found that the interaction with the solute affects the tetrahedral network of hydrogen bonded water molecules in a manner similar to the application of high pressure to pure water. The solvation shell of the OH(-) ions has an almost concentration independent structure, although with concentration dependent coordination numbers. The hydrogen site coordinates a water molecule through a weak bond, while the oxygen site forms strong hydrogen bonds with a number of molecules that is on the average very close to four at the higher water concentrations and decreases to about three at the lowest one. The competition between hydrogen bond interaction and Coulomb forces in determining the orientation of water molecules within the cation solvation shell is visible in the behavior of the g(NaHw)(r) function

Journal Article↗
PubMed2004

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function.

We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a more-marked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.

Aged↗
PubMed2004

Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.

BACKGROUND: Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation. METHODS: Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment. RESULTS: PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05). CONCLUSIONS: The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.

Adult↗
PubMed2003

Structure and dynamics of water confined in silica hydrogels: X-ray scattering and dielectric spectroscopy studies.

We have used a sol-gel technique to obtain optically transparent hydrogels in which water is confined within a 3D silica matrix. In this work we report X-ray scattering and dielectric spectroscopy measurements on samples having different aging times and compare them with previously obtained results with near-infrared (NIR) absorption spectroscopy. X-ray scattering at room temperature enables to characterize the structure and size of the matrix pores and the non-uniform distribution of water inside the hydrogel. Broad band dielectric spectroscopy in the temperature range 130-280 K enables to study water dynamics. In aged hydrogels two relaxations are clearly evident and show characteristic temperature dependence. The faster relaxation has an Arrhenius behavior in the whole temperature range investigated with an activation enthalpy of approximately 50 kJ/mol; it is attributed to water molecules strongly interacting with the silica matrix. The slower relaxation has a markedly non-Arrhenius behavior which can be fitted with a Vogel-Fulcher-Tamman (VFT) relation with critical temperature of approximately 100 K and activation enthalpies of 35 and 95 kJ/mol at 300 and 170 K respectively; it is attributed to water molecules within the pores that do not interact strongly with the matrix and behave collectively. The VFT temperature dependence of the dielectric relaxation time suggests that this water does not crystallize, in agreement with previous results from NIR spectroscopy.

Journal Article↗
PubMed2003

T cell activation and enhanced apoptosis in non-ST elevation myocardial infarction.

Recent studies have shown that inflammation plays a major role in coronary plaque destabilization and in the induction of thrombosis in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte activation and apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with age-matched healthy controls. We considered T cell subpopulations, T cell surface HLA-DR and CD69 expression (evaluated by flow cytometry), lymphomonocyte spontaneous apoptosis (evaluated by ELISA), and IL2 production (evaluated by ELISA) in peripheral blood within 6 hours of onset of NSTEMI. We also investigated Fas expression on T cells (evaluated by flow cytometry) and FasL mRNA (evaluated by RT-PCR), as well as Fas functionality. In NSTEMI patients we found a significant increase of HLADR+ CD3+ and CD69+CD4+ cells. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and was associated with an increased expression of Fas, an increased susceptibility to Fas agonist (CH11), and a normal production of IL2 in cell cultures. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that peripheral lymphocytes are activated in NSTEMI and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Apoptosis↗
PubMed2003

Different effect induced by treatment with several statins on monocyte tissue factor expression in hypercholesterolemic subjects.

Platelets and monocytes are involved in atherothrombosis via tissue factor expression. Moreover, they are activated in hypercholesterolemia, a classic risk factor for atherothrombosis. Cholesterol-lowering drugs (statins) reduce cardiovascular risk either by decreasing cholesterol or non-lipidic actions, such as platelet and monocyte activity. The aim of our study was to evaluate the effect of several statins on platelet and monocyte activity in hypercholesterolemic subjects. Platelet activity (P-selectin, cytofluorimetric detection), tissue factor levels (ELISA) and activity (detected in whole blood and cellular preparations by a specific clotting assay) were measured in hypercholesterolemic subjects (41 males, 23 females, aged 34-65 years, total cholesterol 6.86+/-0.60 mmol/l) treated with atorvastatin 10 mg, simvastatin 20 mg, fluvastatin 40 mg, or pravastatin 40 mg for 6 weeks. P-selectin and tissue factor expression in whole blood and isolated cells were increased in hypercholesterolemic subjects with respect to controls (all P<0.001). Simvastatin, atorvastatin, and fluvastatin reduced monocyte procoagulant activity in whole blood and P-selectin (P<0.01). Tissue factor antigen and activity in isolated cells were further reduced (all P<0.05) independently of cholesterol lowering. Pravastatin decreased tissue factor expression in whole blood in direct relationship to reduction of P-sel and cholesterol (P<0.05). Our data show a different impact of several statins on monocyte tissue factor expression in whole blood, suggesting a possible role of decreased platelet activity and a direct action on monocytes. In contrast, pravastatin decreased monocyte procoagulant activity with relation to cholesteroldependent modifications of platelet function.

Adult↗
PubMed2003

Microvascular assessment in Behçet disease: videocapillaroscopic study.

The aim of this study was to evaluate microvascular assessment in patients with Behcet disease (BD) by means of an intravital videocapillaroscopic study. Sixteen BD patients were compared with an equivalent group of healthy subjects matched for age and sex. Videocapillaroscopy (VCP) was performed in peripheral areas and in conjunctiva, and morphological and quantitative parameters were assessed. In both areas VCP showed several morphological alterations (microaneurysms, megacapillaries, desertification areas) detectable in a high percentage of patients; quantitatively we found significant changes of incisuring and sludging score, of capillary loop intermediate branch length (in peripheral areas) and of arteriole/venule diameter (in conjunctiva). Therefore, vessel involvement included both the number and the whole vessel structure and was seen both in peripheral and conjunctival areas when the two different vascular beds of micro- and paramicrocirculation were examined. We conclude that an important rearrangement of microcirculation is detectable in BD and that VCP may have diagnostic and prognostic value, providing qualitative and quantitative information able to define the systemic extension of vascular damage and the degree of vessel wall alteration.

Adult↗
PubMed2002

Cardiac papillary fibroelastoma: an unusual source of cerebral embolism solved with local fibrinolysis.

Fibroelastoma is an infrequent tumor affecting mainly cardiac valves. Before echocardiography, it was an occasional autoptic finding. With the development of ultrasonographic techniques, it is currently possible to carry out diagnosis in vivo. We report the case of a young woman with cerebral ischemia who was successfully treated by intra-arterial fibrinolysis with complete clinical resolution. Transesophageal echocardiography (TEE) identified a papillary fibroelastoma on the posterior leaflet of the mitral valve. Surgical excision of the tumor was performed. Sudden cerebral or peripheral embolization is frequently linked to thrombotic material which surrounds the neoplasm, and thus can be successfully treated with local fibrinolysis.

Female↗
PubMed2002

Relationship between serum complement and different lipid disorders.

Inflammatory and lipid factors share an important role in atherosclerosis. Recent studies showed the concomitant presence and increase of complement components and lipids both in the atherosclerotic plaque and the circulating blood. The aim of this study was to examine the relationship between the complement system and lipid disorders. We evaluated the circulating complement terminal complex C5b-9, a clear sign of complement activation, in three groups of 30 patients the first with hypercholesterolemia, the second with hypertriglyceridemia (associated with low values of HDL-cholesterol), the third with low levels of HDL-cholesterol compared with an equivalent group of matched normolipemic subjects. We found a significant increase of sC5b-9 in each group of patients compared with controls. The mean sC5b-9 level in the hypercholesterolemic population was 366.2 +/- 141.2 ng/ml (P<0.01), 395.4 +/- 118.2 ng/ml in the hypertrygliceridemic group (P<0.01), 414.8 +/- 126.4 ng/ml in the low HDL-chol subjects (P<0.01), and 182.0 +/- 40.8. ng/ml in the control group. Regression analysis showed a significant direct correlation between sC5b-9 and triglycerides (r=0.64), and a significant inverse correlation between sC5b-9, HDL-chol (r=-0.74), and apo-A1 (r=-0.68); no significant relationship was found between sC5b-9 and cholesterol. We suggest that complement activation is associated with the various lipid disorders and is more important in those dyslipidemic conditions in which other factors may be involved. In particular, hypertriglyceridemia may be associated with endothelial and fibrinolytic disturbances, and the decrease of HDL may induce the failure of the regulatory proteins transported by the same HDL.

Adult↗
PubMed2002

Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure.

BACKGROUND: Recent studies have shown that carvedilol therapy in patients with heart failure improves clinical outcome and survival, however, the effects of such treatment on left cardiac morphology and function in elderly patients with severe heart failure has not been widely studied. AIM: The purpose of this study was to establish the effect of carvedilol at short- and long-term on left ventricular size and performance with mono- and two-dimensional echocardiography, in subjects with dilated cardiomyopathy, NYHA III functional class, low LV ejection fraction (EF < 35%) and mean age of > 70 years. METHODS: We studied 48 patients, previously randomized to treatment with either carvedilol or placebo, and we performed echocardiographic evaluation at the start, and after 3 and 12 months. Left ventricular diameters, LV mass and fractional shortening were calculated by Deveraux formula; left ventricular volumes and ejection fraction were measured by area-length formula; pulmonary pressure was calculated by tricuspid reflow. RESULTS: After 3 months, only LV end-diastolic diameter was lower in the carvedilol group compared to the placebo group. Nevertheless, after 12 months, patients on carvedilol treatment showed a LV geometric and functional improvement compared to placebo. We found significant differences in: diastolic (P < 0.01) and systolic diameters (P < 0.001); on LV mass (P < 0.002); on LV systolic volume (P < 0.03); and on LV ejection fraction (P<0.01). Pulmonary pressure was also reduced in beta-blocker subjects (P < 0.001). CONCLUSIONS: Carvedilol therapy for 12 months reduced LV diameters and volumes. Thus, improving cardiac remodeling and LV systolic function in elderly patients with severe heart failure. Several months of therapy are required for these favorable effects to occur, as these changes do not occur in the short term.

Adrenergic beta-Antagonists↗