Showing papers by "University of Perugia published in 2001"

Prognostic significance of endothelial dysfunction in hypertensive patients.

Abstract: Background— Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown. Methods and Results— Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events incl...

Three Months versus One Year of Oral Anticoagulant Therapy for Idiopathic Deep Venous Thrombosis

Abstract: Background In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial. Methods Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up. Results The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant ...

Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection.

Abstract: Objectives To identify variables predictive of nonadherence to highly active antiretroviral therapy (HAART) and to assess whether self-reported symptoms or medication side effects are related to adherence. Design Cross-sectional multicenter study Adherence Italian Cohort Naive Antiretrovirals [AdICONA] within the Italian Cohort Naive Antiretrovirals (ICONA). Methods Participants receiving HAART completed a 16-item self-administered questionnaire to assess nonadherence in the last 3 days as well as the type and intensity of 24 common HIV- and HAART-related symptoms experienced during the last 4 weeks. Results From May 1999 to March 2000, 358 persons were enrolled: 22% reported nonadherence and were less likely to have HIV RNA Conclusions In addition to patient characteristics, medication-related variables, and reasons for nonadherence, patient-reported symptoms and medication side effects were significantly associated with adherence to HAART.

Radiation hard silicon detectors—developments by the RD48 (ROSE) collaboration

Abstract: The RD48 (ROSE) collaboration has succeeded to develop radiation hard silicon detectors, capable to withstand the harsh hadron fluences in the tracking areas of LHC experiments. In order to reach this objective, a defect engineering technique was employed resulting in the development of Oxygen enriched FZ silicon (DOFZ), ensuring the necessary O-enrichment of about 2×1017 O/cm3 in the normal detector processing. Systematic investigations have been carried out on various standard and oxygenated silicon diodes with neutron, proton and pion irradiation up to a fluence of 5×1014 cm−2 (1 MeV neutron equivalent). Major focus is on the changes of the effective doping concentration (depletion voltage). Other aspects (reverse current, charge collection) are covered too and the appreciable benefits obtained with DOFZ silicon in radiation tolerance for charged hadrons are outlined. The results are reliably described by the “Hamburg model”: its application to LHC experimental conditions is shown, demonstrating the superiority of the defect engineered silicon. Microscopic aspects of damage effects are also discussed, including differences due to charged and neutral hadron irradiation.

Ozone quenching properties of isoprene and its antioxidant role in leaves.

Abstract: Isoprene is formed in and emitted by plants and the reason for this apparent carbon waste is still unclear. It has been proposed that isoprene stabilizes cell and particularly chloroplast thylakoid membranes. We tested if membrane stabilization or isoprene reactivity with ozone induces protection against acute ozone exposures. The reduction of visible, physiological, anatomical, and ultrastructural (chloroplast) damage shows that clones of plants sensitive to ozone and unable to emit isoprene become resistant to acute and short exposure to ozone if they are fumigated with exogenous isoprene, and that isoprene-emitting plants that are sensitive to ozone do not suffer damage when exposed to ozone. Isoprene-induced ozone resistance is associated with the maintenance of photochemical efficiency and with a low energy dissipation, as indicated by fluorescence quenching. This suggests that isoprene effectively stabilizes thylakoid membranes. However, when isoprene reacts with ozone within the leaves or in a humid atmosphere, it quenches the ozone concentration to levels that are less or non-toxic for plants. Thus, protection from ozone in plants fumigated with isoprene may be due to a direct ozone quenching rather than to an induced resistance at membrane level. Irrespective of the mechanism, isoprene is one of the most effective antioxidants in plants.

Adenosine deaminase: Functional implications and different classes of inhibitors

Abstract: Adenosine deaminase (ADA) is an enzyme of the purine metabolism which catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. This ubiquitous enzyme has been found in a wide variety of microorganisms, plants, and invertebrates. In addition, it is present in all mammalian cells that play a central role in the differentiation and maturation of the lymphoid system. However, despite a number of studies performed to date, the physiological role played by ADA in the different tissues is not clear. Inherited ADA deficiency causes severe combined immunodeficiency disease (ADA-SCID), in which both B-cell and T-cell development is impaired. ADA-SCID has been the first disorder to be treated by gene therapy, using polyethylene glycol-modified bovine ADA (PEG-ADA). Conversely, there are several diseases in which the level of ADA is above normal. A number of ADA inhibitors have been designed and synthesized, classified as ground-state and transition-state inhibitors. They may be used to mimic the genetic deficiency of the enzyme, in lymphoproliferative disorders or immunosuppressive therapy (i.e., in graft rejection), to potentiate the effect of antileukemic or antiviral nucleosides, and, together with adenosine kinase, to reduce breakdown of adenosine in inflammation, hypertension, and ischemic injury.

Left Ventricular Hypertrophy as an Independent Predictor of Acute Cerebrovascular Events in Essential Hypertension

Abstract: Background It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension. Methods and Results A total of 2363 initially untreated hypertensive patients (mean age 51±12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m2). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG c...

Neutrophils are primary source of O2 radicals during reperfusion after prolonged myocardial ischemia.

Abstract: Although many studies document oxygen radical formation during ischemia-reperfusion, few address the sources of radicals in vivo or examine radical generation in the context of prolonged ischemia. In particular, the contribution of activated neutrophils remains unclear. To investigate this issue, we developed a methodology to detect radicals without interfering with blood-borne mechanisms of radical generation. Dogs underwent aorta and coronary sinus catheterization. No chemicals were infused; instead, blood was drawn into syringes prefilled with a spin trap and analyzed by electron paramagnetic resonance spectroscopy. After 90 min of coronary artery occlusion, transcardiac concentration of oxygen radicals rose severalfold 10 min after reflow and remained significantly elevated for at least 1 h. Radicals were mostly derived from neutrophils, as shown by marked reduction after the administration of 1) neutrophil NADPH oxidase inhibitors and 2) a monoclonal antibody (R15.7) against neutrophil CD18 adhesion molecule. Reduction of radical generation by R15.7 was also associated with a significantly smaller infarct size and no-reflow areas. Thus our data demonstrate that neutrophils are a major source of oxidants in hearts reperfused in vivo after prolonged ischemia and that antineutrophil interventions can effectively prevent the increase in oxygen radical concentration during reperfusion.

Normal faults, normal friction?

Abstract: Debate continues as to whether normal faults may be seismically active at very low dips (d , 308) in the upper continental crust. An updated compilation of dip estimates (n 5 25) has been prepared from focal mechanisms of shallow, intracontinental, normal-slip earthquakes (M . 5.5; slip vector raking 90 86 308 in the fault plane) where the rupture plane is unambiguously discriminated. The dip distribution for these moderate-to-large normal fault ruptures extends from 658 . d . 308, corresponding to a range, 258 , ur , 608, for the reactivation angle between the fault and inferred vertical s1. In a comparable data set previously obtained for reverse fault ruptures (n 5 33), the active dip distribution is 108 , d5u r , 608. For vertical and horizontal s1 trajectories within extensional and compressional tectonic regimes, respectively, dip-slip reactivation is thus restricted to faults oriented at ur # 608 to inferred s1. Apparent lockup at ur 608 in each dip distribution and a dominant 30 86 58 peak in the reverse fault dip distribution, are both consistent with a friction coefficient ms 0.6, toward the bottom of Byerlee’s experimental range, though localized fluid overpressuring may be needed for reactivation of less favorably oriented faults.

Different Prognostic Impact of 24-Hour Mean Blood Pressure and Pulse Pressure on Stroke and Coronary Artery Disease in Essential Hypertension

Abstract: Background—We tested the hypothesis that the steady and pulsatile components of blood pressure (BP) exert a different influence on coronary artery disease and stroke in subjects with hypertension. ...

IL-6 Inhibits the Tolerogenic Function of CD8α+ Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase

Abstract: The outcome of dendritic cell (DC) presentation of tumor and/or self peptides, including P815AB (a tumor peptide of murine mastocytoma cells) and NRP-A7 (a synthetic peptide mimotope recognized by diabetogenic T cells), may depend on a balance between the activities of immunogenic (CD8α−) and tolerogenic (CD8α+) DC. By virtue of their respective actions on CD8− and CD8+ DC, IL-12 and IFN-γ have functionally opposing effects on peptide presentation by the CD8− DC subset, and IFN-γ-activated CD8+ DC mediate tolerogenic effects that prevail over the adjuvant activity of IL-12 on CD8− DC. We have previously shown that CD40 ligation abrogates the tolerogenic potential of CD8+ DC, an effect associated with an impaired capacity of the CD40-modulated and IFN-γ-treated DC to degrade tryptophan and initiate T cell apoptosis in vitro. We report here that IL-6 may both replace (upon administration of the recombinant cytokine) and mediate (as assessed by the use of neutralizing Abs) the effect of CD40 ligation in ablating the tolerogenic activity of CD8+ DC. The activity of IL-6 includes down-regulation of IFN-γR expression in the CD8+ DC subset and correlates to a reduced ability of these cells to metabolize tryptophan and initiate T cell apoptosis in vitro.

Characterization of Non-Starter Lactic Acid Bacteria from Italian Ewe Cheeses Based on Phenotypic, Genotypic, and Cell Wall Protein Analyses

Abstract: Non-starter lactic acid bacteria (NSLAB) were isolated from 12 Italian ewe cheeses representing six different types of cheese, which in several cases were produced by different manufacturers. A total of 400 presumptive Lactobacillus isolates were obtained, and 123 isolates and 10 type strains were subjected to phenotypic, genetic, and cell wall protein characterization analyses. Phenotypically, the cheese isolates included 32% Lactobacillus plantarum isolates, 15% L. brevis isolates, 12% L. paracasei subsp. paracasei isolates, 9% L. curvatus isolates, 6% L. fermentum isolates, 6% L. casei subsp. casei isolates, 5% L. pentosus isolates, 3% L. casei subsp. pseudoplantarum isolates, and 1% L. rhamnosus isolates. Eleven percent of the isolates were not phenotypically identified. Although a randomly amplified polymorphic DNA (RAPD) analysis based on three primers and clustering by the unweighted pair group method with arithmetic average (UPGMA) was useful for partially differentiating the 10 type strains, it did not provide a species-specific DNA band or a combination of bands which permitted complete separation of all the species considered. In contrast, sodium dodecyl sulfate-polyacrylamide gel electrophoresis cell wall protein profiles clustered by UPGMA were species specific and resolved the NSLAB. The only exceptions were isolates phenotypically identified as L. plantarum and L. pentosus or as L. casei subsp. casei and L. paracasei subsp. paracasei, which were grouped together. Based on protein profiles, Italian ewe cheeses frequently contained four different species and 3 to 16 strains. In general, the cheeses produced from raw ewe milk contained a larger number of more diverse strains than the cheeses produced from pasteurized milk. The same cheese produced in different factories contained different species, as well as strains that belonged to the same species but grouped in different RAPD clusters.

Detecting leaks in pressurised pipes by means of transients

Abstract: Reliable and quick techniques are needed to locate and estimate leaks in pressurised pipe systems in order to reduce water loss as much as possible. The aim of the present paper is to show that the...

Proteinase-activated receptor 2 is an anti-inflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis

Abstract: The proteinase-activated receptor 2 (PAR-2) is a member of a family of G protein-coupled receptors for proteases. Proteases cleave PARs within the extracellular N-terminal domains to expose tethered ligands that bind to and activate the cleaved receptors. PAR-2 is highly expressed in colon in epithelial and neuronal elements. In this study we show that PAR-2 activation prevents the development and induces healing of T helper cell type 1-mediated experimental colitis induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. A role for PAR-2 in the protection against colon inflammation was explored by the use of SLIGRL-NH(2), a synthetic peptide that corresponds to the mouse tethered ligand exposed after PAR-2 cleavage. TNBS-induced colitis was dose-dependently reduced by the administration of SLIGRL-NH(2), whereas the scramble control peptide, LSIGRL-NH(2), was uneffective. This beneficial effect was reflected by increased survival rates, improvement of macroscopic and histologic scores, decrease in mucosal content of T helper cell type 1 cytokines, protein, and mRNA, and a diminished myeloperoxidase activity. SLIGRL-NH(2), but not the scramble peptide, directly inhibited IFN-gamma secretion and CD44 expression on lamina propria T lymphocytes. Protection exerted by PAR-2 in TNBS-treated mice was reverted by injecting mice with a truncated form of calcitonin gene-related peptide and by sensory neurons ablation with the neurotoxin capsaicin. Collectively, these studies show that PAR-2 is an anti-inflammatory receptor in the colon and suggest that PAR-2 ligands might be effective in the treatment of inflammatory bowel diseases.

S100B expression in and effects on microglia.

Abstract: We evaluated the intracellular and extracellular biological role of S100B protein with respect to microglia. S100B, which belongs to the multigenic family of Ca2+-binding proteins, is abundant in astrocytes where it is found diffusely in the cytoplasm and is associated with membranes and cytoskeleton constituents. S100B protein is also secreted by astrocytes and acts on these cells to stimulate nitric oxide secretion in an autocrine manner. However, little is known about the relationship between S100B and microglia. To address this issue, we used primary microglia from newborn rat cortex and the BV-2 microglial cell line, a well-established cell model for the study of microglial properties. S100B expression was assessed by immunofluorescence in primary microglia and by RT-PCR, Western blotting, and immunofluorescence in BV-2 cells. S100B was found in microglia in the form of a filamentous network as well as diffusely in the cytoplasm and associated with intracellular membranes. S100B relocated around phagosomes during BV-2 phagocytosis of opsonized Cryptococcus neoformans. Furthermore, interferon-γ (IFN-γ) treatment caused cell shape changes and redistribution of S100B, and downregulation of S100B mRNA expression in BV-2 cells. Treatment of BV-2 cells with nanomolar to micromolar amounts of S100B resulted in increased IFN-γ–induced expression of inducible nitric oxide synthase mRNA as well as nitric oxide secretion. Taken together, these data suggest a possible role for S100B in the accomplishment/regulation of microglial cell functions. GLIA 33:131–142, 2001. © 2001 Wiley-Liss, Inc.

Optical and radio variability of the BL Lacertae object AO 0235+16: A possible 5-6 year periodicity

Abstract: The BL Lacertae object AO 0235+16 is well known for its extreme optical and radio variability. New optical and radio data have been collected in the last four years by a wide international collaboration, which conrm the intense activity of this source: on the long term, overall variations of 5 mag in the R band and up to a factor 18 in the radio fluxes were detected, while short-term variability up to 0:5 mag in a few hours and 1: 3m ag in one day was observed in the optical band. The optical data also include the results of the Whole Earth Blazar Telescope (WEBT) rst-light campaign organized in November 1997, involving a dozen optical observatories. The optical spectrum is observed to basically steepen when the source gets fainter. We have investigated the existence of typical variability time scales and of possible correlations between the optical and radio emissions by means of visual inspection and Discrete Correlation Function (DCF) analysis. On the long term, the autocorrelation function of the optical data shows a double-peaked maximum at 4100{4200 days (11:2{11:5 years), while a double-peaked maximum at 3900{4200 days (10:7{11:5 years) is visible in the radio autocorrelation functions. The existence of this similar characteristic time scale of variability in the two bands is by itself an indication of optical-radio correlation. A further analysis by means of Discrete Fourier Transform (DFT) technique and folded light curves reveals that the major radio outbursts repeat quasi-regularly with a periodicity of5:7 years, i.e. half the above time scale. This period is also in agreement with the occurrence of some of the major optical outbursts, but not all of them. Visual inspection and DCF analysis of the optical and radio light curves then reveal that in some cases optical outbursts seem to be simultaneous with radio ones, but in other cases they lead the radio events. Moreover, a deep inspection of the radio light curves suggests that in at least two occasions (the 1992{1993 and 1998 outbursts) flux variations at the higher frequencies may have led those at the lower ones.

Dose-Response Study of Recombinant Factor VIIa/Tissue Factor Inhibitor Recombinant Nematode Anticoagulant Protein c2 in Prevention of Postoperative Venous Thromboembolism in Patients Undergoing Total Knee Replacement

Abstract: Background—With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. Methods and Results—This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7±2) and confirmed symptomatic venous thromboembolism recorded ≤48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding ≤72 h...