G Ciabattoni

Università degli Studi G. d'Annunzio Chieti e Pescara, Chieta, Abruzzo, Italy

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Publications (196)1170.37 Total impact

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    ABSTRACT: Techniques are described in detail for the radioimmunological measurement of prostaglandin (PG) E2 and F2α in human urine. 50 ml urine samples are extracted with an organic solvent system and then purified by silicic acid column chromatography. The overall recovery after extraction and purification, calculated with labeled as well as unlabeled compounds, is in the order of 70%. The column eluates are assayed at 1:12–1:60 dilution in the “standard diluent” of the assay: 8 pg PGE2.or PGF2a/ml of whole urine represents the lowest measurable concentration. A urine blank and a solvent blank were evaluated separately, subjecting 50 ml of urine obtained from an indomethacin treated subject (“PG-free” urine) or 50 ml of distilled water, respectively, to the extraction-purification procedures. Both were found not to interfere with the antigen-antibody reaction. Urinary PG-like immunoreactivity (LI) was characterized in terms of immunochemical and thin-layer chromatographic (TLC) behavior. Both urinary PGE2-LI and PGF2α-LI behaved as authentic PGE2 and PGF2α, upon dilution and on TLC. In 33 healthy female subjects (aged 19–58 yr), urinary excretion rates averaged 178 ± 80 (mean ± SD) ng/day for PGE2 and 498 ± 181 ng/day for PGF2α. In a group of 8 healthy men, both PGE2 and PGF2α crexcretion rates were higher and more scattered than the female values. When two healthy women were given indomethacin (200 mg/day), urinary PGE2 and PGF2α dropped to undetectable levels during the 4th day of drug therapy. I ntravenous injection of furosemide (50 mg) in a female volunteer was followed by an immediate rise of urinary sodium, PGE2, PGF2α and PGE2/PGF2α ratio and plasma renin activity. Ina 10 year old girl with Bartter’s syndrome, urinary PG excretion rate was elevated with a 3 times higher than normal PGE2/PGF2α ratio. Indomethacin therapy resulted in a prompt drop of PG excretion rate and of plasma renin activity. These results show that a combi nation of adequate purification steps and antisera with optimal characteristics provides a reliable method for measuring PGE2 and PGF2α in urine, and therefore a valuable tool to further our knowledge of the physiology and physiopathology of the renal PG-system.
    Journal of endocrinological investigation 04/2014; 2(2):173-182. · 1.65 Impact Factor
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    ABSTRACT: The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F2α and 11-dehydro-thromboxane (TX)B2 (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF2α and 11-dehydro-TXB2 were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF2α (p<0.0001) and 11-dehydro-TXB2 (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF2α excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF2α and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.
    Thrombosis and Haemostasis 07/2012; 108(3):533-42. · 5.76 Impact Factor
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    ABSTRACT: Metabolomics could provide new insights into the pathophysiology of cystic fibrosis (CF) by identifying profiles of endogenous metabolites. To investigate whether metabolomics of exhaled breath condensate could discriminate between patients with unstable CF, stable CF and healthy subjects, and whether selected metabolites were responsible for between-group differences. Twenty-nine patients with stable CF, 24 with unstable CF and 31 healthy subjects (age 9-24 years) participated in a cross-sectional study. Metabolomics was performed with high-resolution nuclear magnetic resonance spectroscopy. Partial least squares-discriminant analysis was used as classifier. The results were validated in a second independent study. Intraclass correlation coefficients for between-day and technical repeatability were 0.93 and 0.96, respectively. Bland-Altman analysis showed good within-day repeatability. Correct classification rate of CF (n=53) vs. healthy subjects (n=31) was 96% (R2=0.84; Q2=0.79). Model validation with a testing sample set obtained from subjects not included in the primary analysis (23 CF and 25 healthy subjects) showed a sensitivity of 91% and a specificity of 96%. The classification rate of stable CF (n=29) vs. unstable CF patients (n=24) was 95% (R2=0.82; Q2=0.78). Model external validation in 14 patients with stable CF and 16 with unstable CF showed a sensitivity of 86% and a specificity of 94%. Ethanol, acetate, 2-propanol and acetone were most discriminant between patients with CF and healthy subjects, whereas acetate, ethanol, 2-propanol and methanol were the most important metabolites for discriminating between patients with stable and unstable CF. Nuclear magnetic resonance spectroscopy of exhaled breath condensate is reproducible, discriminates patients with CF from healthy subjects and patients with unstable CF from those with stable CF, and identifies the metabolites responsible for between-group differences.
    Thorax 11/2011; 67(3):222-8. · 8.38 Impact Factor
  • American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado; 05/2011
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    ABSTRACT: We examined the time-dependent effects of atorvastatin and rosuvastatin on in vivo oxidative stress and platelet activation, to assess whether these phenomena are related to any pleiotropic effect of any statin or to their LDL-lowering effect. We also asked whether the presence of specific allele frequencies in carriers of the 3'UTR/lectin-like oxidized LDL receptor-1 (LOX-1) polymorphism may influence the effect of either statin. We included 60 hypercholesterolemic subjects, previously screened for LOX-1 3'UTR polymorphism, randomized, according to genetic profile (15 T and 15 C carriers for each arm), to atorvastatin 20mg/day or rosuvastatin 10mg/day. After 8 weeks, atorvastatin and rosuvastatin were associated with comparable, significant reductions in LDL cholesterol (40.8% and 43.6%, respectively), plasma hs-CRP (9.5% vs. 13.8%), urinary 11-dehydro-thromboxane (TX) B(2) (38.9% vs. 27.1%) and 8-iso-prostaglandin (PG) F(2α) (39.4% vs. 19.4%). The impact of rosuvastatin or atorvastatin on CRP, 8-iso-PGF(2α), and 11-dehydro-TXB(2) did not differ according to the LOX-1 haplotype. On multiple regression analyses, only CRP and LDL were independent predictors of 11-dehydro-TXB(2), and only LDL was a significant predictor of 8-iso-PGF(2α). Both atorvastatin and rosuvastatin cause comparable reductions of thromboxane-dependent platelet activation, lipid peroxidation and inflammation. The presence of 3'UTR/LOX-1 polymorphism does not affect the changes induced by either statin.
    Atherosclerosis 11/2010; 214(1):122-8. · 3.71 Impact Factor
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    ABSTRACT: Thromboxane (TX) biosynthesis by platelets and other cells in response to inflammatory triggers may provide a link between chronic inflammatory disease and atherothrombosis in rheumatoid arthritis (RA). In this study, we investigated the determinants of TX biosynthesis in RA, with particular reference to enhanced oxidative stress, receptor for advanced glycation end-products (RAGE) hyperactivity, and anti-tumor necrosis factor (TNF) treatment. Fifty-four patients with RA and 20 healthy subjects were recruited and a cross-sectional comparison of urinary 11-dehydro-TXB(2), 8-iso-PGF(2alpha), and plasma endogenous secretory RAGE (esRAGE) levels was performed between patients and controls. Urinary 11-dehydro-TXB(2) was significantly higher in RA patients than in healthy controls [425 (309-592) vs 233 (158-327) pg/mg creatinine, P<0.0001]. Furthermore, urinary 8-iso-PGF(2alpha) [323 (221-515) vs 172 (91-292) pg/mg creatinine, P<0.0001] and plasma esRAGE [155 (100-240) vs 377 (195-486) pg/ml, P=0.001] were higher and lower, respectively, in patients than in controls. A direct correlation was found between urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) only in patients not on anti-TNF therapy (r=0.420, P=0.021). Conversely, patients on anti-TNF therapy showed significantly lower urinary 8-iso-PGF(2alpha) [284 (201-373) vs 404 (241-539) pg/mg creatinine, P=0.043] but not 11-dehydro-TXB(2) than anti-TNF-treated subjects, with esRAGE as the only independent predictor of 11-dehydro-TXB(2) in this group of patients (adjusted R(2)=0.496, beta=-0.725, SEM=0.025, P=0.001). In conclusion, we provide biochemical evidence of enhanced TX biosynthesis in patients with RA, driven, at least in part, by lipid peroxidation. Treatment with anti-TNF agents may blunt isoprostane generation in the absence of significant effects on TX biosynthesis. We suggest that RAGE hyperactivity may escape TNF blockade, thus contributing to persistent TX biosynthesis in this setting.
    Free Radical Biology and Medicine 09/2010; 49(5):857-64. · 5.27 Impact Factor
  • American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans; 05/2010
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    ABSTRACT: Analysis of exhaled breath by biosensors discriminates between patients with asthma and healthy subjects. An electronic nose consists of a chemical sensor array for the detection of volatile organic compounds (VOCs) and an algorithm for pattern recognition. We compared the diagnostic performance of a prototype of an electronic nose with lung function tests and fractional exhaled nitric oxide (FENO) in patients with atopic asthma. A cross-sectional study was undertaken in 27 patients with intermittent and persistent mild asthma and in 24 healthy subjects. Two procedures for collecting exhaled breath were followed to study the differences between total and alveolar air. Seven patients with asthma and seven healthy subjects participated in a study with mass spectrometry (MS) fingerprinting as an independent technique for assessing between group discrimination. Classification was based on principal component analysis and a feed-forward neural network. The best results were obtained when the electronic nose analysis was performed on alveolar air. Diagnostic performance for electronic nose, FENO, and lung function testing was 87.5%, 79.2%, and 70.8%, respectively. The combination of electronic nose and FENO had the highest diagnostic performance for asthma (95.8%). MS fingerprints of VOCs could discriminate between patients with asthma and healthy subjects. The electronic nose has a high diagnostic performance that can be increased when combined with FENO. Large studies are now required to definitively establish the diagnostic performance of the electronic nose. Whether this integrated noninvasive approach will translate into an early diagnosis of asthma has to be clarified. Trial registration: EUDRACT https://eudralink.emea.europa.eu; Identifier: 2007-000890-51; and clinicaltrials.gov; Identifier: NCT00819676.
    Chest 04/2010; 137(4):790-6. · 7.13 Impact Factor
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    ABSTRACT: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE). Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001). Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.
    Journal of Thrombosis and Haemostasis 04/2010; 8(4):828-37. · 6.08 Impact Factor
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    ABSTRACT: Thromboembolism is a relatively common complication of chronic heart failure (HF) and the place of antiplatelet therapy is uncertain. We characterized the rate of thromboxane and prostacyclin biosynthesis in chronic HF of ischemic origin, with the aim of separating the influence of HF on platelet activation from that of the underlying ischemic heart disease (IHD). We compared urinary 11-dehydro-thromboxane (TX)B(2), 2,3 dinor 6-keto-PGF(1alpha,) 8-iso-prostaglandin (PG)F(2alpha), and plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), asymmetric dimethylarginine (ADMA), and soluble CD40 ligand (sCD40L), in 84 patients with HF secondary to IHD, 61 patients with IHD without HF and 42 healthy subjects. HF patients not on aspirin had significantly higher urinary 11-dehydro-TXB(2) as compared with healthy subjects (P < 0.0001) and IHD patients not on aspirin (P = 0.028). They also showed significantly higher 8-iso-PGF(2alpha) (P = 0.018), NT-pro-BNP (P = 0.021) and ADMA (P < 0.0001) than IHD patients not on aspirin. HF patients on low-dose aspirin had significantly lower 11-dehydro-TXB(2) (P < 0.0001), sCD40L (P = 0.007) and 2,3-dinor-6-keto-PGF(1alpha) (P = 0.005) than HF patients not treated with aspirin. HF patients in NYHA classes III and IV had significantly higher urinary 11-dehydro-TXB(2) than patients in classes I and II, independently of aspirin treatment (P < 0.05). On multiple linear regression analysis, higher NT-pro-BNP levels, lack of aspirin therapy and sCD40L, predicted 11-dehydro-TXB(2) excretion rate in HF patients (R(2) = 0.771). Persistent platelet activation characterizes HF patients. This phenomenon is related to disease severity and is largely suppressable by low-dose aspirin. The homeostatic increase in prostacyclin biosynthesis is impaired, possibly contributing to enhanced thrombotic risk in this setting.
    Journal of Thrombosis and Haemostasis 02/2010; 8(5):914-22. · 6.08 Impact Factor
  • Paolo Montuschi, Peter J Barnes, Giovanni Ciabattoni
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    ABSTRACT: Oxidative stress is functionally involved in the pathophysiology of lung diseases including asthma and chronic obstructive pulmonary disease. 8-Isoprostane, which is derived from free radical-catalyzed peroxidation of arachidonic acid, is one of the most reliable biomarkers of oxidative stress. Exhaled breath condensate (EBC) is a completely noninvasive method for collecting airway secretions. We developed a specific and sensitive radioimmunoassay (RIA) that has been applied to the measurement of 8-isoprostane in EBC. This RIA for 8-isoprostane has been validated using high performance liquid chromatography. Measurement of 8-isoprostane in EBC is a useful noninvasive technique for exploring the role of oxidative stress in lung diseases. This technique might provide important insights into the understanding of the clinical pharmacology of antioxidants and might be useful for monitoring the effects of pharmacological therapy.
    Methods in molecular biology (Clifton, N.J.) 01/2010; 594:73-84. · 1.29 Impact Factor
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    ABSTRACT: United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral and nasal FENO concentrations were increased in children with PER, IA, mA and MA when compared with HCs. Nasal 8-isoprostane was higher in EBC of children with PER and asthma than in HCs. Oral and nasal LTB4 were higher in EBC of children with PER and mA than in HCs. Oral and nasal PGE2 concentrations were higher in EBC of children with PER than in HCs. Positive correlations between oral and nasal biomarkers were found in IA for LTB4 and PGE2, in mA for FENO, 8-isoprostane, LTB4 and PGE2, and in MA for PGE2. No correlations were observed in children with PER and HCs. Our results suggest that non-invasive markers of inflammation and oxidative stress might be useful to study the relationships between oral and nasal compartments in allergic children with PER and concomitant asthma with the aim of defining the UAD.
    International journal of immunopathology and pharmacology 01/2010; 23(4):1211-9. · 2.99 Impact Factor
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    ABSTRACT: We tested whether cyclooxygenase 2 (COX-2) expression and unacetylated COX-1 in newly formed platelets might contribute to persistent thromboxane (TX) biosynthesis in aspirin-treated essential thrombocythemia (ET). Forty-one patients on chronic aspirin (100 mg/day) and 24 healthy subjects were studied. Platelet COX-2 expression was significantly increased in patients and correlated with thiazole orange-positive platelets (r = 0.71, P < .001). The rate of TXA(2) biosynthesis in vivo, as reflected by urinary 11-dehydro-TXB(2) (TXM) excretion, and the maximal biosynthetic capacity of platelets, as reflected by serum TXB(2), were higher in patients compared with aspirin-treated healthy volunteers. Serum TXB(2) was significantly reduced by the selective COX-2 inhibitor NS-398 added in vitro. Patients were randomized to adding the selective COX-2 inhibitor, etoricoxib, or continuing aspirin for 7 days. Etoricoxib significantly reduced by approximately 25% TXM excretion and serum TXB(2). Fourteen of the 41 patients were studied again 21 (+/- 7) months after the first visit. Serum TXB(2) was consistently reduced by approximately 30% by adding NS398 in vitro, while it was completely suppressed with 50 microM aspirin. Accelerated platelet regeneration in most aspirin-treated ET patients may explain aspirin-persistent TXA(2) biosynthesis through enhanced COX-2 activity and faster renewal of unacetylated COX-1. These findings may help in reassessing the optimal antiplatelet strategy in ET.
    Blood 11/2009; 115(5):1054-61. · 9.78 Impact Factor
  • Thrombosis Research 08/2009; 125(4):362-4. · 3.13 Impact Factor
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    ABSTRACT: Air pollution is associated with respiratory symptoms, lung function decrements, and hospitalizations. However, there is little information about the influence of air pollution on lung injury. In this study we investigated acute effects of air pollution on pulmonary function and airway oxidative stress and inflammation in asthmatic children. We studied 182 children with asthma, 9-14 years of age, for 4 weeks. Daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, and particulate matter < or = 2.5 microm in aerodynamic diameter (PM(2.5)) were monitored from two stations. Once a week we measured spirometry and fractional exhaled nitric oxide (FeNO), and determined thiobarbituric acid reactive substances (TBARS) and 8-isoprostane--two oxidative stress markers--and interleukin-6 (IL-6) in breath condensate. We tested associations using mixed-effects regression models, adjusting for confounding variables. Interquartile-range increases in 3-day average SO2 (5.4 ppb), NO2 (6.8 ppb), and PM(2.5) (5.4 microg/m3) were associated with decreases in forced expiratory flow between 25% and 75% of forced vital capacity, with changes being -3.1% [95% confidence interval (CI), -5.8 to -0.3], -2.8% (95% CI, -4.8 to -0.8), and -3.0% (95% CI, -4.7 to -1.2), respectively. SO2, NO2, and PM(2.5) were associated with increases in TBARS, with changes being 36.2% (95% CI, 15.7 to 57.2), 21.8% (95% CI, 8.2 to 36.0), and 24.8% (95% CI, 10.8 to 39.4), respectively. Risk estimates appear to be larger in children not taking corticosteroids than in children taking corticosteroids. O3 (5.3 ppb) was not associated with health end points. FeNO, 8-isoprostane, and IL-6 were not associated with air pollutants. Air pollution may increase airway oxidative stress and decrease small airway function of asthmatic children. Inhaled corticosteroids may reduce oxidative stress and improve airway function.
    Environmental Health Perspectives 05/2009; 117(4):668-74. · 7.26 Impact Factor
  • American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California; 04/2009
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    ABSTRACT: This study was conducted to assess the thromboxane (TX) dependence of biochemical and functional indexes used to monitor the effect of low-dose aspirin. Functional assays of the antiplatelet effects of low-dose aspirin variably reflect the TX-dependent component of platelet aggregation. Previous studies of aspirin resistance were typically based on a single determination of platelet aggregation. We assessed the TXB(2) dependence of biochemical and functional indexes, as well as their intersubject and intrasubject variability during administration of the drug and after its withdrawal in 48 healthy volunteers randomized to receive aspirin 100 mg daily for 1 to 8 weeks. Serum TXB(2) was uniformly suppressed by 99% of baseline. Urinary 11-dehydro-TXB(2), arachidonic acid-induced aggregation, and VerifyNow Aspirin (Accumetrics Inc., San Diego, California) showed stable, incomplete inhibition (65%, 80%, and 35%, respectively). Adenosine diphosphate- and collagen-induced aggregation was highly variable and poorly affected by aspirin, with an apparent time-dependent reversal. Inhibition of platelet cyclooxygenase activity was nonlinearly related to inhibition of platelet aggregation. Platelet function largely recovered by day 3 post-aspirin, independently of treatment duration. With any functional assay, occasionally "resistant" subjects were found to be "responders" on previous or subsequent determinations. Platelet cyclooxygenase activity, as reflected by serum TXB(2) levels, is uniformly and persistently suppressed by low-dose aspirin in healthy subjects. However, the effect of aspirin is variably detected by functional assays, potentially leading to misclassification of "responder" as "resistant" phenotypes owing to poor reproducibility of functional measurements. The nonlinearity of the relationship between inhibition of TX production and inhibition of platelet function has important clinical implications.
    Journal of the American College of Cardiology 03/2009; 53(8):667-77. · 14.09 Impact Factor
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    ABSTRACT: Microalbuminuria is a predictor of adverse outcome in hypertension. We evaluated in vivo platelet activation, by urinary 11-dehydro-thromboxane (TX)B(2) and plasma P-selectin, in hypertensives with or without microalbuminuria, and its possible association with oxidative stress, by urinary 8-iso-prostaglandin (PG)F(2a) and endothelial dysfunction. Sixty essential hypertensive patients with (n=30) or without (n=30) microalbuminuria, and 30 controls were studied. Endothelial function was assessed by nitric oxide products, intercellular adhesion molecule (ICAM)-1 and asymmetric dimethylarginine (ADMA) levels. Urinary 11-dehydro-TXB(2) excretion was higher in microalbuminuric (median 805 pg/mg creatinine) compared to non-microalbuminuric patients or controls (414 and 291 pg/mg, respectively; p<0.0001). Plasma P-selectin was significantly higher in patients with microalbuminuria (median 136 ng/ml) as compared to those without microalbuminuria or controls (85 and 65 ng/ml; p<0.0001). Urinary 8-iso-PGF(2a) excretion was also enhanced in microalbuminuric (median 279 pg/mg creatinine) compared to non-microalbuminuric patients or controls (157 and 146 pg/mg, respectively; p<0.0001). A significant impairment in endothelial function was found in microalbuminuric patients, with decreased nitric oxide and increased ICAM-1 and ADMA levels. Multivariate regression analysis showed that urinary 8-iso-PGF(2a) excretion (beta=0.49; p<0.0001) and microalbuminuria (beta=0.36; p<0.001) were independently related to 11-dehydro-TXB(2) in hypertensives. Vitamin E supplementation (900 mg daily for 1 month) in 10 hypertensives with microalbuminuria was associated with normalization in median 11-dehydro-TXB(2) and 8-iso-PGF(2a). We conclude that lipid peroxidation is a major determinant of persistent platelet activation in hypertensive patients with microalbuminuria.
    Free Radical Biology and Medicine 01/2009; · 5.27 Impact Factor
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    ABSTRACT: We measured 8-isoprostane, a biomarker of oxidative stress, and prostaglandin (PG) E(2) in exhaled breath condensate in 36 stable and 14 unstable cystic fibrosis (CF) patients, and in 15 healthy age-matched controls. We studied the relationships of these eicosanoids with clinical, radiological, and systemic inflammatory parameters. Compared with controls [15.5 (11.5-17.0) pg/ml] exhaled 8-isoprostane was increased in stable CF patients [30.5 (25.3-36.0) pg/ml, P<0.001]. Unstable CF patients had higher exhaled 8-isoprostane levels [47.5 (44.0-50.0) pg/ml, P<0.001] than stable CF patients. Unlike PGE(2), exhaled 8-isoprostane was negatively correlated with FEV(1) (r=-0.67; P<0.0001; r=-0.63; P<0.02) and Shwachman score (r=-0.43, P=0.012; r=-0.58, P=0.031) and positively correlated with Chrispin-Norman score (r=0.51, P<0.002; r=0.56, P=0.039) in stable and unstable CF patients, respectively. No correlation was observed with C-reactive protein. Compared with controls [41.0 (29.0-50.0) pg/ml], exhaled PGE(2) was also elevated in stable [72.0 (64.3-81.8) pg/ml, P<0.001) and, to a greater extent, in unstable CF patients [83.0 (74.3-91.3) pg/ml, P<0.001). In patients with CF, exhaled 8-isoprostane and PGE(2) could be a useful marker of disease severity.
    Free Radical Biology and Medicine 09/2008; 45(6):913-9. · 5.27 Impact Factor
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    ABSTRACT: Exercise-induced bronchoconstriction (EIB) in the asthmatic child is associated with persistent airway inflammation and poor disease control. EIB could arise partly from airway oxidative stress. Exhaled breath condensate (EBC) levels of 8-isoprostane (IsoP), which is a known marker of oxidative stress, might therefore be helpful for monitoring asthma noninvasively. We recruited 46 asthmatic children and adolescents 6 to 17 years of age (29 boys), all of whom underwent lung function testing, measurement of the fractional concentration of exhaled nitric oxide (FENO), and collection of EBCs for 8-IsoP measurement before and after exercise challenge. FENO was measured before exercise and 5 min and 20 min after exercise. Spirometry was repeated 1, 5, 10, 15, and 20 min after exercise. Baseline 8-IsoP levels (but not baseline FENO levels) correlated with the fall in FEV(1) 5 min after exercise (r = - 0.47; p = 0.002). 8-IsoP levels measured after exercise remained unchanged from baseline levels; conversely, FENO levels decreased in parallel with the decline in FEV(1) at 5 min (r = 0.44; p = 0.002). The mean baseline 8-IsoP concentrations were higher in patients with EIB (n = 12) than in those without EIB (n = 34; 44.9 pg/mL [95% confidence interval (CI), 38.3 to 51.5] vs 32.3 pg/mL [95% CI, 27.6 to 37.0], respectively; p < 0.01). No difference was found in the mean baseline FENO between groups (with EIB group: 38.7 ppb; 95% CI, 24.5 to 61.1; without EIB group: 29.1 ppb; 95% CI, 22.0 to 38.4). Increased 8-IsoP concentrations in EBC samples of asthmatic children and adolescents with EIB suggest a role for oxidative stress in bronchial hyperreactivity.
    Chest 09/2008; 135(1):66-73. · 7.13 Impact Factor

Publication Stats

7k Citations
1,170.37 Total Impact Points


  • 1990–2012
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Dipartimento di Medicina e Scienze dell'Invecchiamento
      Chieta, Abruzzo, Italy
  • 2010
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 1983–2010
    • Catholic University of the Sacred Heart
      • Institute of Pharmacology
      Milano, Lombardy, Italy
  • 2009
    • Santo Spirito Hospital, Casale Monferrato
      Casale, Piedmont, Italy
  • 2008
    • Ospedale Pediatrico Bambino Gesù
      Roma, Latium, Italy
  • 1987–2008
    • Sapienza University of Rome
      • Department of Medicine
      Roma, Latium, Italy
  • 2004
    • Istituto Dermopatico dell'Immacolata
      Roma, Latium, Italy
  • 2003
    • University of Padova
      Padua, Veneto, Italy
  • 2000
    • Università degli Studi di Messina
      Messina, Sicily, Italy
  • 1999
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 1997–1999
    • Erasmus Universiteit Rotterdam
      • Department of Neurology
      Rotterdam, South Holland, Netherlands
    • Università degli Studi di Perugia
      • Department of Internal Medicine
      Perugia, Umbria, Italy
  • 1988–1993
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
  • 1980–1991
    • The Catholic University of America
      Washington, Washington, D.C., United States