Showing papers by "University of Perugia published in 1995"

Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study.

Abstract: Objective: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. Design: Cross-cultural correlation study. Setting/Participants: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. Main Outcome Measures: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. Results: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%;P=.0001), flavonoid intake (8%;P=.01), and percentage of smokers per cohort (9%;P=.03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. Conclusions: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality. (Arch Intern Med. 1995;155:381-386)

Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study

Abstract: Objective. —To compare the relationship between serum total cholesterol and long-term mortality from coronary heart disease (CHD) in different cultures. Design. —Total cholesterol was measured at baseline (1958 through 1964) and at 5- and 10-year follow-up in 12 467 men aged 40 through 59 years in 16 cohorts located in seven countries: five European countries, the United States, and Japan. To increase statistical power six cohorts were formed, based on similarities in culture and cholesterol changes during the first 10 years of follow-up. Main Outcome Measures. —Relative risks (RRs), estimated with Cox proportional hazards (survival) analysis, for 25-year CHD mortality for cholesterol quartiles and per 0.50-mmol/L (20-mg/dL) cholesterol increase. Adjustment was made for age, smoking, and systolic blood pressure. Results. —The age-standardized CHD mortality rates in the six cohorts ranged from 3% to 20%. The RRs for the highest compared with the lowest cholesterol quartile ranged from 1.5 to 2.3, except for Japan's RR of 1.1. For a cholesterol level of around 5.45 mmol/L (210 mg/dL), CHD mortality rates varied from 4% to 5% in Japan and Mediterranean Southern Europe to about 15% in Northern Europe. However, the relative increase in CHD mortality due to a given cholesterol increase was similar in all cultures except Japan. Using a linear approximation, a 0.50-mmol/L (20-mg/dL) increase in total cholesterol corresponded to an increase in CHD mortality risk of 12%, which became an increase in mortality risk of 17% when adjusted for regression dilution bias. Conclusion. —Across cultures, cholesterol is linearly related to CHD mortality, and the relative increase in CHD mortality rates with a given cholesterol increase is the same. The large difference in absolute CHD mortality rates at a given cholesterol level, however, indicates that other factors, such as diet, that are typical for cultures with a low CHD risk are also important with respect to primary prevention. (JAMA. 1995;274:131-136)

Vasoactive peptide levels in the plasma of young migraine patients with and without aura assessed both interictally and ictally.

Abstract: We measured, by RIA methods, ictal and interictal levels of substance P (SP), calcitonin-gene related peptide (CGRP) and neurokinin A (NKA) in the plasma of 30 young migraine patients with aura (MPA) and 45 migraine patients without aura (MWA), and compared the results with those of 30 age-matched controls. There were no significant differences between the levels of these vasoactive peptides in the control group and the levels in both migraine groups studied in headache-free periods. An elevation of CGRP levels in plasma was found during attacks in MPA and, to a lesser extent, in MWA (p < 0.03 and p < 0.05, respectively). A significant increase in NKA levels was also demonstrated in the MPA and MWA groups (p < 0.02 and p < 0.04, respectively). These data suggest, although indirectly, that CGRP and NKA could be involved in the pathogenesis of migraine attacks in juvenile migraine patients.

Stochastic resonance as a bona fide resonance

Abstract: Stochastic resonance in a bistable potential is fully characterized as a synchronization effect of the hopping mechanism induced by the external periodic bias. Most notably, synchronization is shown to attain a maximum by increasing the forcing frequency close to the relevant switching rate, thus revealing a bona fide resonant process.

On the spatial organization of soil moisture fields

Abstract: We examine the apparent disorder which seems to characterize the spatial structure of soil moisture by analyzing large-scale experimental data. Specifically, we address the statistical structure of soil moisture fields under different scales of observation and find unexpected results. The variance of soil moisture follows a power law decay as function of the area at which the process is observed. The spatial correlation remains unchanged with the scale of observation and follows a power law decay typical of scaling processes. Soil moisture also shows clear scaling properties on its spatial clustering patterns. A well-defined organization of statistical character is found to exist in soil moisture patterns linking a large range of scales through which the process manifests itself and impacts other processes. We suggest that such scaling properties are crucial to our current understanding and modeling of the dynamics of soil moisture in space and time.

The motogenic and mitogenic responses to HGF are amplified by the Shc adaptor protein

Abstract: The receptor of Hepatocyte Growth Factor-Scatter Factor (HGF) is a tyrosine kinase which regulates cell motility and growth. After ligand-induced tyrosine phosphorylation, the HGF receptor associates with the Shc adaptor, via the SH2 domain. Site-directed mutagenesis of the HGF receptor indicates that phosphotyrosines Y1349VHV and Y1356VNV can work as docking sites for Shc. The Kd of this interaction, measured in real time using synthetic phosphopeptides and recombinant Shc on a BIAcore biosensor, is 150 nm for both sites. After stimulation of the HGF receptor, Shc is phosphorylated on Y317VNV, generating an high affinity binding site for Grb2 (Kd = 15 nM). This duplicates the high affinity binding site for Grb2 present on the HGF receptor (Y1356VNV). Thus HGF stimulation can trigger the Ras pathway by recruiting Grb2 both directly through the receptor, and indirectly, through Shc. Overexpression of wild-type Shc, but not of the Y317-->F mutant, enhances cell migration and growth in response to HGF. These data show that Shc is a relevant substrate of the HGF receptor, and works as an 'amplifier' of the motogenic as well as of the mitogenic response.

Downregulation by cryptococcal polysaccharide of tumor necrosis factor alpha and interleukin-1 beta secretion from human monocytes.

Abstract: The regulation by Cryptococcus neoformans encapsulation of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) production by human monocytes was investigated. By using encapsulated and acapsular C. neoformans, we demonstrated that both strains induce cytokine production, although the acapsular strain was a better stimulator than the thinly encapsulated strain. The cytokine levels produced by cells stimulated by the two strains were lower and followed a different kinetic than those stimulated by lipopolysaccharide (LPS). Purified capsular polysaccharide inhibits TNF-alpha secretion induced by LPS or acapsular C. neoformans. In contrast, no regulator effect on IL-1 beta was observed when LPS was used. The secretory response of these cytokines follows different pathways of macrophage activation; in fact, complete inhibition of TNF-alpha does not affect IL-1 beta production and vice versa. These data indicate that purified capsular polysaccharide of C. neoformans could contribute to the in vivo progress of cryptococcosis by suppressing cytokine production of macrophages and suggest that a therapeutic approach to address the suppressive effect of cryptococal polysaccharide could be devised.

Occupational hand dermatitis in hospital environments.

Abstract: Health care personnel form the 5th category at major occupational risk of skin disease in Italy. The aim of this study was to assess the prevalence and clinical relevance of contact dermatitis in a group of 1301 employees of the Perugia Monteluce Hospital (658 females and 643 males; mean age 39.8 years) who answered a self-administered questionnaire elaborated by the authors. The subjects with anamnestic hand dermatitis and/or atopic mucosal reactions were clinically examined and submitted to skin tests (patch and/or prick tests). Contact dermatitis of the hands and/or forearms occurred in 21.2% and was significantly more frequent (p < 0.001) in women, subjects under 31 years of age, workers in internistic and surgical fields, cleaners and nurses. In the majority of cases (94.9%), the lesions were irritant in origin and mainly related to disinfectants (especially, chlorhexidine gluconate and glutaraldehyde) and gloves (latex proteins and starch glove powder, rather than accelerators and additives of rubber). Finally, atopy seemed to favour the onset of hand dermatitis. The importance of these results for preventive measures of contact dermatitis in hospital employees is discussed.

Activation of Class II or III Metabotropic Glutamate Receptors Protects Cultured Cortical Neurons Against Excitotoxic Degeneration

Abstract: Trans-1-aminocyclopentane-1,3-dicarboxylic acid, a mixed agonist of all metabotropic glutamate receptor (mGluR) subtypes, is known to produce either neurotoxic or neuroprotective effects. We have therefore hypothesized that individual mGluR subtypes differentially affect neurodegenerative processes. Selective agonists of subtypes which belong to mGluR class II or III, such as (2s, 1′R,2′R,3′R)-2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV) (specific for subtypes mGluR2 or 3) or L-2-amino-4-phosphonobutanoate and L-serine-O-phosphate (specific for subtypes mGluR4, 6 or 7), were highly potent and efficacious in protecting cultured cortical neurons against toxicity induced by either a transient exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. In contrast, agonists that preferentially activate class I mGluR subtypes (mGluR1 or 5), such as quisqualate or trans-azetidine-2,3-dicarboxylic acid, were inactive. DCG-IV was still neuroprotective when applied to cultures after the toxic pulse with NMDA. This delayed rescue effect was associated with a reduction in the release of endogenous glutamate, a process that contributes to the maturation of neuronal damage. We conclude that agonists of class II or III mGluRs are of potential interest in the experimental therapy of acute or chronic neurodegenerative disorders.

Origin of the fumarolic fluids of Vulcano island, Italy and implications for volcanic surveillance

Abstract: Variations in δD and δ18O values with H2O contents and outlet temperatures indicate that the fumaroles of La Fossa crater have discharged mixtures of magmatic water and marine hydrothermal water, since 1979. The contribution of meteoric water was low in the period 1979–1982 and very low afterwards. The δ18O values of the marine-hydrothermal component of +5 to +7.2‰ are due to isotopic exchange with the 18O-rich silicates of the rocks under high-temperature and low-permeability conditions. The δ18O value of the magmatic end-member is generally +3.5 to +4.3‰, although values as high as +5.5 to +6.5‰ were reached in the summer of 1988, when magma degassing appears to have extended into the core of the magma body. The δD values of the end-member were close to -20‰, typical of andesitic waters. Both the isotopic values and chemical data strongly support a ‘dry’ model, consisting of a central magmatic gas column and a surrounding hydrothermal envelope, in which marine hydrothermal brines move along limited fracture zones to undergo total evaporation on approaching the conduits of magmatic fluids. The vents at the eastern and western boundaries of the fumarolic field are fed by fluids whose pressure is governed by the coexistence of vapor, liquid and halite, giving rise to a high risk of phreato magmatic explosions, should magma penetrate into these wet environments. Most La Fossa eruptions were triggered by an initial hydrothermal blast and continued with a series of phreatomagmatic explosions. The fluids discharged by the Forgia Vecchia fumaroles are mixed with meteoric water, which is largely evaporated, although subordinate loss of condensed steam may be responsible for scrubbing most of the acidic gas species. The temperatures and pressures, and the risk of a sudden pressure increase, are low. A boiling hydrothermal aquifer at 230° C is present underneath the Baia di Levante beach. This area has a minor risk of hydrothermal explosions.

Surgical treatment of craniopharyngiomas: an evaluation of the transsphenoidal and pterional approaches.

Abstract: FIFTY-SEVEN PATIENTS WITH craniopharyngiomas underwent a total of 64 operations. Their clinical follow-up ranged from 2.5 to 15.5 years, with a mean follow-up of 6.5 years. A transsphenoidal approach was used in 35 patients (61%), whereas 22 (39%) were operated on using a pterional approach

Interleukin-4 and -10 exacerbate candidiasis in mice.

Abstract: Neutralization of endogenous interleukin (IL)-4 or IL-10 in mice with Candida albicans infection initiates or accelerates development of a T helper (Th)1-associated protective response. Here, we report the effect of IL-4 and IL-10 administration on the course of systemic or gastrointestinal (GI) candidiasis and on the development of Th immunity using yeast/host combinations that result either in Th1-associated self-limiting infection (healer mice) or in Th2-associated progressive disease (nonhealer mice). Treatment with IL-4 or IL-10 greatly exacerbated the course of systemic infection in nonhealer mice and rendered healer mice, inoculated with attenuated yeast cells, susceptible to infection. Under the latter conditions of yeast challenge and IL-4/IL-10 administration, the development of a fatal disease was associated with inhibition of IL-12 production and detection of progressive Th2 cell dominance. In contrast, in healer mice allowed to resolve their infections and to develop long-lived anti-candidal resistance, the expression of this acquired resistance was not impaired by IL-4 and/or IL-10, as shown by the outcome of reinfection with virulent yeast cells. In the GI model of infection, both IL-4 and IL-10 were found to exacerbate the course of infection and to induce the appearance of CD4+ T cells producing high levels of IL-4 and IL-10 in Peyer's patches. These findings demonstrate that exogenous IL-4 and IL-10 may greatly affect the development of Th responses to C. albicans in vivo, but do not modify the expression of established and predominant Th1 cell reactivity.

Ondansetron Clinical Pharmacokinetics

Abstract: Ondansetron is a potent and highly selective serotonin 5-HT3-receptor antagonist which has demonstrated important antiemetic activity and good tolerability in the prevention of chemotherapy-induced nausea and vomiting. Ondansetron is completely and rapidly absorbed from the gastrointestinal tract after oral administration, and does not accumulate with repeated oral administration. Owing to hepatic first-pass metabolism, its bioavailability is only about 60% compared with ondansetron administered by infusion over 15 minutes. Bioavailability is slightly increased when administered after a standard meal, and is not influenced by coadministration of antacids; a slightly enhanced bioavailability has been observed in patients with cancer. Since the time to reach peak concentration is 0.5 to 2 hours after oral ingestion, the drug should be administered at least 30 minutes before chemotherapy. Possible alternative ways of administration of ondansetron include intramuscular, subcutaneous and rectal administration, and oral controlled-release formulations. Ondansetron is widely distributed (volume of distribution approximately 160L) and binds moderately (70 to 76%) to plasma proteins; the elimination half-life averages approximately 3.8 ± 1 hours. Clearance occurs by hepatic metabolism (95%) rather than renal excretion. Metabolites do not play a role in the activity of the drug, and there is no evidence of genetic polymorphic metabolism. Although aging is associated with decreased clearance and increased bioavailability, dosage adjustments are not required for the elderly, and may be necessary only in patients with severe hepatic impairment. Chemotherapeutic agents do not seem to modify the pharmacokinetics of ondansetron. There remains the question of whether control of emesis is related to systemic availability of ondansetron and, in consequence, the optimal dose and schedule of ondansetron is still to be identified with certainty.

Constitutive phosphorylation of Shc proteins in human tumors

Abstract: The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed cells. In tumor cells with known TK gene alterations Shc proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive Shc phosphorylation was found in primary cell cultures and normal tissues. In 14 of 27 tumor cell lines with no reported TK alterations, Shc proteins were constitutively phosphorylated and formed stable complexes with novel tyrosine-phosphorylated polypeptides. Ten distinct Shc-associated phosphoproteins were identified with molecular weights ranging from 30 to 200 kDa. In a subset of carcinoma cell lines, phosphorylated Shc proteins complexed with a p175 phosphoprotein that was identified as the constitutively activated EGFR. In one glioblastoma cell line, a Shc-associated p190 was identified as the activated PDGFR. In 13 of 14 acute leukemia samples phosphorylated Shc proteins were constitutively complexed with a p140 phosphoprotein. Some of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively activated TKs and that the analysis of Shc phosphorylation allow the identification of tumors with constitutive TK activation.

Facts, myths and legends on the prime industrial microorganism.

Abstract: Archaic speculations and firmly established legends regarding the origin of the yeast Saccharomyces cerevisiae and related species are revisited in light of past and recent ecological evidence pointing to a strict association with artificial, man-made environments such as wineries and fermentation plants. The nomenclature within this industrially important group is also discussed in view of the modifications imposed from application of molecular techniques to classification.