Campolo Dott. Jonica

Pubblicazioni su PubMed

• Cancer Risk in Patients With Congenital Heart Disease Exposed to Radiation From Cardiac Procedures.
  J Am Coll Cardiol

  2023 Mar;81(11):1133-1134. doi: 10.1016/j.jacc.2022.12.028.
  
  Borghini Andrea, Campolo Jonica, Annoni Giuseppe, Giuli Valentina, Sicari Rosa, Peretti Alessio, Mercuri Antonella, Picano Eugenio, Andreassi Maria Grazia
  
  
  
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• Congenital Heart Disease and the Risk of Cancer: An Update on the Genetic Etiology, Radiation Exposure Damage, and Future Research Strategies.
  J Cardiovasc Dev Dis

  2022 Aug;9(8):. doi: 245.
  
  Campolo Jonica, Annoni Giuseppe, Giaccardi Marzia, Andreassi Maria Grazia
  
  Abstract
  
  Epidemiological studies have shown an increased prevalence of cancer in patients with congenital heart disease (CHD) as compared with the general population. The underlying risk factors for the acquired cancer risk remain poorly understood, and shared genetic anomalies and cumulative radiation exposure from repeated imaging and catheterization procedures may be contributing factors. In the present review, we provide an update on the most recent literature regarding the associations between CHD and cancer, with a particular focus on genetic etiology and radiation exposure from medical procedures. The current evidence indicates that children with CHD may be a high-risk population, already having the first genetic "hit", and, consequently, may have increased sensitivity to ionizing radiation from birth or earlier. Future research strategies integrating biological and molecular measures are also discussed in this article.
  
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• Biochemical but not imaging parameters are predictive of outcome in septic shock: a pilot study.
  Cardiovasc Ultrasound

  2022 Mar;20(1):6. doi: 6.
  
  Belli Oriana E, Campolo Jonica, Vallerio Paola, Musca Francesco, Moreo Antonella, Maloberti Alessandro, Parolini Marina, Bonacchini Luca, Monti Gianpaola, De Gasperi Andrea, Fumagalli Roberto, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND:
  Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome.
  
  METHODS:
  Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress.
  
  RESULTS:
  The multivariate Cox's proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000-1.034; P?=?0.049). An angiopoietin-2 concentrations ? of 33,418?pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%.
  
  CONCLUSIONS:
  Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting.
  
  © 2022. The Author(s).
  
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• Gender-Specific Behaviour in Obesity Stages I-II: Imbalance of Aminothiol Status and Adipomyokine Profile in Subjects with Different Insulin Resistance Severity.
  Oxid Med Cell Longev

  2021 ;2021():9713582. doi: 9713582.
  
  Campolo Jonica, Corradi Ettore, Parolini Marina, Di Guglielmo Maria Luisa, Rizzardi Alice, Dellanoce Cinzia, Tarlarini Patrizia, Cattaneo Marina, Scioscioli Elena, Trivella Maria Giovanna, De Maria Renata
  
  Abstract
  
  The hyperproduction of oxidative stress and inflammatory biomarkers, which is paralleled by decreased levels of antioxidant and anti-inflammatory mediators, is part of cellular mechanisms that contribute to the disruption of metabolic homeostasis in obesity. Whether gender-specific alterations and gender-restricted associations in these biomarkers underlie the increased cardiometabolic risk in men compared to women is unclear. We enrolled 31 women and 29 men, aged ?50 and ?70 years and with body?mass?index ? 30 and
  Copyright © 2021 Jonica Campolo et al.
  
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• Triglycerides and low HDL cholesterol predict coronary heart disease risk in patients with stable angina.
  Sci Rep

  2021 Oct;11(1):20714. doi: 20714.
  
  Caselli Chiara, De Caterina Raffaele, Smit Jeff M, Campolo Jonica, El Mahdiui Mohammed, Ragusa Rosetta, Clemente Alberto, Sampietro Tiziana, Clerico Aldo, Liga Riccardo, Pelosi Gualtiero, Rocchiccioli Silvia, Parodi Oberdan, Scholte Arthur, Knuuti Jhuani, Neglia Danilo,
  
  Abstract
  
  We assessed whether high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, expressed by an increased TG/HDL-C ratio, predict coronary atherosclerotic disease (CAD) outcomes in patients with stable angina. We studied 355 patients (60?±?9 years, 211 males) with stable angina who underwent coronary computed tomography angiography (CTA), were managed clinically and followed for 4.5?±?0.9 years. The primary composite outcome was all-cause mortality and non-fatal myocardial infarction. At baseline, the proportion of males, patients with metabolic syndrome, diabetes and obstructive CAD increased across TG/HDL-C ratio quartiles, together with markers of insulin resistance, hepatic and adipose tissue dysfunction and myocardial damage, with no difference in total cholesterol or LDL-C. At follow-up, the global CTA risk score (HR 1.06, 95% confidence interval (CI) 1.03-1.09, P?=?0.001) and the IV quartile of the TG/HDL-C ratio (HR 2.85, 95% CI 1.30-6.26, P?0.01) were the only independent predictors of the primary outcome. The TG/HDL-C ratio and the CTA risk score progressed over time despite increased use of lipid-lowering drugs and reduction in LDL-C. In patients with stable angina, high TG and low HDL-C levels are associated with CAD related outcomes independently of LDL-C and treatments.Trial registration. EVINCI study: ClinicalTrials.gov NCT00979199, registered September 17, 2009; SMARTool study: ClinicalTrials.gov NCT04448691, registered June 26, 2020.
  
  © 2021. The Author(s).
  
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• Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD.
  Front Immunol

  2021 ;12():683028. doi: 683028.
  
  Kanoni Stavroula, Kumar Satish, Amerikanou Charalampia, Kurth Mary Jo, Stathopoulou Maria G, Bourgeois Stephane, Masson Christine, Kannt Aimo, Cesarini Lucia, Kontoe Maria-Spyridoula, Milanovi? Maja, Roig Francisco J, Beribaka Mirjana, Campolo Jonica, Jiménez-Hernández Nuria, Milo?evi? Nata?a, Llorens Carlos, Smyrnioudis Ilias, Francino M Pilar, Mili? Nata?a, Kaliora Andriana C, Trivella Maria Giovanna, Ruddock Mark W, Medi?-Stojanoska Milica, Gastaldelli Amalia, Lamont John, Deloukas Panos, Dedoussis George V, Visvikis-Siest Sophie
  
  Abstract
  
  UNLABELLED:
  Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ? 30 kg/m) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene ( associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene ( and the sphingolipid transporter-1 gene () associated with hemoglobin levels, the transforming growth factor-beta-induced gene () and the micro-RNA 129-1 ( associated with IL-6 and the granzyme B gene () associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.
  
  CLINICAL TRIAL REGISTRATION:
  ClinicalTrials.gov, identifier NCT03135873.
  
  Copyright © 2021 Kanoni, Kumar, Amerikanou, Kurth, Stathopoulou, Bourgeois, Masson, Kannt, Cesarini, Kontoe, Milanovi?, Roig, Beribaka, Campolo, Jiménez-Hernández, Milo?evi?, Llorens, Smyrnioudis, Francino, Mili?, Kaliora, Trivella, Ruddock, Medi?-Stojanoska, Gastaldelli, Lamont, Deloukas, Dedoussis and Visvikis-Siest.
  
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• Effect of Mastiha supplementation on NAFLD: The MAST4HEALTH Randomised, Controlled Trial.
  Mol Nutr Food Res

  2021 May;65(10):e2001178. doi: 10.1002/mnfr.202001178.
  
  Amerikanou Charalampia, Kanoni Stavroula, Kaliora Andriana C, Barone Angela, Bjelan Mladen, D'Auria Giuseppe, Gioxari Aristea, Gosalbes María José, Mouchti Sofia, Stathopoulou Maria G, Soriano Beatriz, Stojanoski Stefan, Banerjee Rajarshi, Halabalaki Maria, Mikropoulou Eleni V, Kannt Aimo, Lamont John, Llorens Carlos, Marascio Fernando, Marascio Miriam, Roig Francisco J, Smyrnioudis Ilias, Varlamis Iraklis, Visvikis-Siest Sophie, Vukic Milan, Milic Natasa, Medic-Stojanoska Milica, Cesarini Lucia, Campolo Jonica, Gastaldelli Amalia, Deloukas Panos, Trivella Maria Giovanna, Francino M Pilar, Dedoussis George V,
  
  Abstract
  
  SCOPE:
  Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD.
  
  METHODS AND RESULTS:
  Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ? 35 kg m and BMI > 35 kg m ), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo.
  
  CONCLUSION:
  Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients.
  
  © 2021 Wiley-VCH GmbH.
  
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• Correction to: Correlates of olfactory impairment in middle-aged non-diabetic Caucasian subjects with stage I-II obesity.
  Eur Arch Otorhinolaryngol

  2021 Jun;278(6):2055. doi: 10.1007/s00405-021-06618-7.
  
  Campolo Jonica, Corradi Ettore, Rizzardi Alice, Parolini Marina, Dellanoce Cinzia, Di Guglielmo Maria Luisa, Tarlarini Patrizia, Cattaneo Marina, Trivella Maria Giovanna, De Maria Renata
  
  
  
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• Early intra-aortic balloon pump in acute decompensated heart failure complicated by cardiogenic shock: Rationale and design of the randomized Altshock-2 trial.
  Am Heart J

  2021 Mar;233():39-47. doi: 10.1016/j.ahj.2020.11.017.
  
  Morici Nuccia, Marini Claudia, Sacco Alice, Tavazzi Guido, Cipriani Manlio, Oliva Fabrizio, Rota Matteo, De Ferrari Gaetano Maria, Campolo Jonica, Frigerio Gianfranco, Valente Serafina, Leonardi Sergio, Corrada Elena, Bottiroli Maurizio, Grosseto Daniele, Cacciavillani Luisa, Frigerio Maria, Pappalardo Federico,
  
  Abstract
  
  BACKGROUND:
  Cardiogenic shock (CS) is a systemic disorder associated with dismal short-term prognosis. Given its time-dependent nature, mechanical circulatory support may improve survival. Intra-aortic balloon pump (IABP) had gained widespread use because of the easiness to implant and the low rate of complications; however, a randomized trial failed to demonstrate benefit on mortality in the setting of acute myocardial infarction. Acute decompensated heart failure with cardiogenic shock (ADHF-CS) represents a growing resource-intensive scenario with scant data and indications on the best management. However, a few data suggest a potential benefit of IABP in this setting. We present the design of a study aimed at addressing this research gap.
  
  METHODS AND DESIGN:
  The Altshock-2 trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with ADHF-CS will be randomized to early IABP implantation or to vasoactive treatments. The primary end point will be 60 days patients' survival or successful bridge to heart replacement therapy. The key secondary end point will be 60-day overall survival; 60-day need for renal replacement therapy; in-hospital maximum inotropic score, maximum duration of inotropic/vasopressor therapy, and maximum sequential organ failure assessment score. Safety end points will be in-hospital occurrence of bleeding events (Bleeding Academic Research Consortium >3), vascular access complications and systemic (noncerebral) embolism. The sample size for the study is 200 patients.
  
  IMPLICATIONS:
  The Altshock-2 trial will provide evidence on whether IABP should be implanted early in ADHF-CS patients to improve their clinical outcomes.
  
  Copyright © 2020 Elsevier Inc. All rights reserved.
  
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• Correlates of olfactory impairment in middle-aged non-diabetic Caucasian subjects with stage I-II obesity.
  Eur Arch Otorhinolaryngol

  2021 Jun;278(6):2047-2054. doi: 10.1007/s00405-020-06442-5.
  
  Campolo Jonica, Corradi Ettore, Rizzardi Alice, Parolini Marina, Dellanoce Cinzia, Di Guglielmo Maria Luisa, Tarlarini Patrizia, Cattaneo Marina, Trivella Maria Giovanna, De Maria Renata
  
  Abstract
  
  PURPOSE:
  This study evaluates among middle-aged subjects with obesity the prevalence of olfactory impairment (OI) with respect to normative values and its correlation with body composition, cognition, sleep quality, and inflammation.
  
  METHODS:
  In 60 (31 women, 29 men) volunteers with a body mass index???30 to ??40 kg/m, aged???50 to???70 years, we assessed olfaction by the Sniffin' Stick test. We measured anthropometrics, body composition and metabolic profiles and evaluated cognition by the MiniMental State Examination (MMSE) and sleep disturbances by the Insomnia Severity Index (ISI). Patients were classified into two groups according to a total olfactory score (odor Threshold, Discrimination, Identification, TDI) below or above the 25th percentile from age and gender-adjusted normative data.
  
  RESULTS:
  Overall, 25 subjects (42%) had OI (TDI?25th percentile). The largest differences between subjects with and without OI were observed in discrimination and identification scores, with a large overlap in olfactory threshold. Subjects with an abnormal TDI showed significantly higher fat mass index, ISI scores and urinary neopterin and lower MMSE scores than those without OI. By multivariable logistic regression, MMSE, ISI score and urinary neopterin were significantly associated to OI.
  
  CONCLUSIONS:
  Among middle-aged subjects with stage I and II obesity, OI is highly prevalent and is independently associated with poor self-reported sleep quality, lower cognition scores and higher levels of the inflammatory marker neopterin.
  
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• Blood Monocyte Phenotype Fingerprint of Stable Coronary Artery Disease: A Cross-Sectional Substudy of SMARTool Clinical Trial.
  Biomed Res Int

  2020 ;2020():8748934. doi: 8748934.
  
  Sbrana Silverio, Campolo Jonica, Clemente Alberto, Bastiani Luca, Cecchettini Antonella, Ceccherini Elisa, Caselli Chiara, Neglia Danilo, Parodi Oberdan, Chiappino Dante, Smit Jeff M, Scholte Arthur J, Pelosi Gualtiero, Rocchiccioli Silvia
  
  Abstract
  
  BACKGROUND AND AIMS:
  Atherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at different stages of coronary atherosclerosis in stable coronary artery disease (CAD) patients.
  
  METHODS:
  73 patients with chronic coronary syndrome were evaluated by CT coronary angiography (CTCA) and classified by maximal diameter stenosis of major vessels into three groups of CAD severity: CAD1 (no CAD/minimal CAD, ° = 30), CAD2 (non-obstructive CAD, ° = 21), and CAD3 (obstructive CAD, ° = 22). Flow cytometry for CD14, CD16, and CCR2 was used to quantify Mon1, Mon2, and Mon3 subsets. Expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, and CXCR4 was also measured. Adhesion molecules and cytokines were quantified by ELISA.
  
  RESULTS:
  Total cell count and fraction of Mon2 were higher in CAD2 and CAD3 compared to CAD1. By multivariate regression analysis, Mon2 cell fraction and Mon2 expression of CX3CR1, CD18, and CD16 showed a statistically significant and independent increase, parallel to stenosis severity, from CAD1 to CAD2 and CAD3 groups. A similar trend was also present for CX3CR1 and HLA-DR expressions on total monocyte population. A less calcified plaque composition was associated to a higher Mon2 expression of CD16 and higher TNF- levels. IL-10 levels were lower at greater stenosis severity, while the IFN-/IL-10 ratio, a marker of a systemic pro-inflammatory imbalance, was directly correlated to stenosis degree and number of noncalcified plaques.
  
  CONCLUSIONS:
  The results of this study suggest that a specific pattern of inflammation-correlated monocyte marker expression is associated to higher stenosis severity and less calcified lesions in stable CAD. The clinical trial Identifier is NCT04448691.
  
  Copyright © 2020 Silverio Sbrana et al.
  
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• Urinary neopterin, a new marker of the neuroinflammatory status in amyotrophic lateral sclerosis.
  J Neurol

  2020 Dec;267(12):3609-3616. doi: 10.1007/s00415-020-10047-7.
  
  Lunetta Christian, Lizio Andrea, Gerardi Francesca, Tarlarini Claudia, Filippi Massimo, Riva Nilo, Tremolizzo Lucio, Diamanti Susanna, Dellanoce Cinzia Carla, Mosca Lorena, Sansone Valeria Ada, Campolo Jonica
  
  Abstract
  
  OBJECTIVE:
  To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS.
  
  METHODS:
  We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALS patients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival.
  
  RESULTS:
  Urinary neopterin was significantly higher in pALS (263.90 [198.71-474.90]) compared to MS (155.28 [131.74-190.38], p?=??.001), OND patients (205.60 [158.96-299.41], p?=?0.04) and HC (169.55 [134.91-226.10], p?.001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r?=?- 0.46, p?.001) and its subscores (bulbar r?=?- 0.34, p?=?0.002; motor r?=?- 0.33, p?=?0.003; respiratory r?=?- 0.53, p?.001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation.
  
  CONCLUSIONS:
  Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin's potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.
  
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• Irisin and markers of metabolic derangement in non-diabetic Caucasian subjects with stage I-II obesity during early aging.
  PLoS One

  2020 ;15(2):e0229152. doi: e0229152.
  
  Campolo Jonica, Corradi Ettore, Rizzardi Alice, Parolini Marina, Dellanoce Cinzia, Di Guglielmo Maria Luisa, Tarlarini Patrizia, Cattaneo Marina, Trivella Maria Giovanna, De Maria Renata
  
  Abstract
  
  Irisin concentrations are decreased in subjects with overt diabetes and upregulated in those with obesity or impaired fasting glucose. However, gender-balanced data in older populations, in whom risk factors commonly culminate in overt cardiovascular disease, are scarce. We assessed in non-diabetic Caucasian subjects with stage I-II obesity in the early aging range (50 to 70 years), the relationship between irisin, body composition and markers of metabolic derangement by gender. In 60 (31 women, 29 men) non-diabetics with a body mass index ?30 - ?40 kg/m2, we measured anthropometrics and body composition (Air Displacement Plethysmography). We assayed lipid and glucose profile by routine methods, plasma irisin by ELISA and measured insulin resistance by the HOMA index. Irisin levels were higher in women than in men (161 [105-198]) vs 83 [33-115] ng/ml, P
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• Computing of Low Shear Stress-Driven Endothelial Gene Network Involved in Early Stages of Atherosclerotic Process.
  Biomed Res Int

  2018 ;2018():5359830. doi: 5359830.
  
  Vozzi Federico, Campolo Jonica, Cozzi Lorena, Politano Gianfranco, Di Carlo Stefano, Rial Michela, Domenici Claudio, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  In the pathogenesis of atherosclerosis, a central role is represented by endothelial inflammation with influx of chemokine-mediated leukocytes in the vascular wall. Aim of this study was to analyze the effect of different shear stresses on endothelial gene expression and compute gene network involved in atherosclerotic disease, in particular to homeostasis, inflammatory cell migration, and apoptotic processes.
  
  METHODS:
  HUVECs were subjected to shear stress of 1, 5, and 10 dyne/cm in a Flow Bioreactor for 24 hours to compare gene expression modulation. Total RNA was analyzed by Affymetrix technology and the expression of two specific genes (CXCR4 and ICAM-1) was validated by RT-PCR. To highlight possible regulations between genes and as further validation, a bioinformatics analysis was performed.
  
  RESULTS:
  At low shear stress (1 dyne/cm) we observed the following: (a) strong upregulation of CXCR4; (b) mild upregulation of Caspase-8; (c) mild downregulation of ICAM-1; (d) marked downexpression of TNFAIP3. Bioinformatics analysis showed the presence of network composed by 59 new interactors (14 transcription factors and 45 microRNAs) appearing strongly related to shear stress.
  
  CONCLUSIONS:
  The significant modulation of these genes at low shear stress and their close relationships through transcription factors and microRNAs suggest that all may promote an initial inflamed endothelial cell phenotype, favoring the atherosclerotic disease.
  
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• A serving of blueberry (V. corymbosum) acutely improves peripheral arterial dysfunction in young smokers and non-smokers: two randomized, controlled, crossover pilot studies.
  Food Funct

  2017 Nov;8(11):4108-4117. doi: 10.1039/c7fo00861a.
  
  Del Bo' Cristian, Deon Valeria, Campolo Jonica, Lanti Claudia, Parolini Marina, Porrini Marisa, Klimis-Zacas Dorothy, Riso Patrizia
  
  Abstract
  
  Several studies have documented the important role of polyphenol-rich foods in the modulation of vascular remodelling and function. This study aimed to evaluate the capacity of a single portion of blueberry (V. corymbosum) to acutely improve peripheral arterial dysfunction in a group of young volunteers. Twenty-four healthy males (12 non-smokers and 12 smokers) were recruited for two different randomized, controlled, crossover pilot acute studies. In the first study, non-smokers were exposed to a control treatment (C; 300 mL of water with sugar) and a blueberry treatment (BB; 300 g of blueberry). In the second study, smokers underwent 3 different protocols: (1) - smoking treatment (S); (2) - control treatment (CS; 300 mL of water with sugar + smoking); (3) - blueberry treatment (BS; 300 g of blueberry + smoking). Each treatment (1 day long) was separated by a one week washout period. Blood pressure, peripheral arterial function (reactive hyperemia index, RHI, a marker of endothelial function) and arterial stiffness (digital augmentation index, dAix and dAix normalized by considering a heart rate of 75 bpm, dAix@75) were measured before and after each treatment. In the first study, the consumption of blueberry and control treatment acutely increased peripheral arterial function in the group of non-smokers. The improvement in RHI was higher and significantly different after blueberry treatment compared to the control treatment (54.8 ± 8.4% BB vs. 28.2 ± 8.3% C; p = 0.01). No effects were observed for markers of arterial stiffness, blood pressure and heart rate. Acute cigarette smoke significantly increased blood pressure and heart rate, while no significant effect was registered in peripheral arterial function and stiffness. The intake of blueberry and control treatment before a cigarette did not counteract the increase in blood pressure and heart rate, while it significantly improved peripheral arterial function. In particular, a significant increase was observed following BS (35.2 ± 7.5% RHI; p = 0.02) and CS treatments (34.6 ± 11.9% RHI; p = 0.02) when compared to only smoking treatment. No difference between BS and CS was detected. In conclusion, the intake of blueberry and control treatments acutely improved peripheral arterial dysfunction both in smoker and in non-smoker subjects. Further studies should be performed to confirm the results obtained and reveal the potential mechanisms of blueberry in the improvement of endothelial function.
  
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• Medium-term effect of sublingual l-glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors.
  Nutrition

  2017 Jun;38():41-47. doi: 10.1016/j.nut.2016.12.018.
  
  Campolo Jonica, Bernardi Stefano, Cozzi Lorena, Rocchiccioli Silvia, Dellanoce Cinzia, Cecchettini Antonella, Tonini Annamaria, Parolini Marina, De Chiara Benedetta, Micheloni Gianpaolo, Pelosi Gualtiero, Passino Claudio, Giannattasio Cristina, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF).
  
  METHODS:
  We enrolled 16 healthy men with CVRF in a double-blinded, randomized placebo-controlled crossover study. At each visit, blood samples were collected for biochemistry analyses and peripheral endothelial function (reactive hyperemia index [RHI]) and stiffness were measured by Endo-PAT2000.
  
  RESULTS:
  In the overall population, a decrease in total and low-density lipoprotein cholesterol was highlighted after L-GSH supplementation compared with placebo (P = 0.023 and P = 0.04, respectively). On the contrary, no difference was observed in RHI and oxidative stress markers between L-GSH and placebo in the study population. However, seven participants with baseline abnormal RHI (?1.67) compared with those with normal RHI showed a significant reduction of arterial stiffness after L-GSH administration, (P = 0.007 and P = 0.037, respectively).
  
  CONCLUSIONS:
  Supplementation of L-GSH compared with placebo influences the lipid profile of patients with CVRF. Sublingual L-GSH may represent a valid prevention of vascular damage in patients with CVRF and endothelial dysfunction.
  
  Copyright © 2017 Elsevier Inc. All rights reserved.
  
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• Intra- and interday repeatability of peripheral arterial function: suitability and potential limitations.
  Microcirculation

  2016 Oct;23(7):503-511. doi: 10.1111/micc.12300.
  
  Del Bo' Cristian, Deon Valeria, Porrini Marisa, Campolo Jonica, Parolini Marina, Riso Patrizia
  
  Abstract
  
  OBJECTIVE:
  This study aimed to investigate the inter-and intraday repeatability of RHI measured by Endo-PAT in healthy volunteers.
  
  METHODS:
  Interday RHI repeatability was tested in two consecutive days in a group of 31 male subjects. Intraday repeatability was investigated at baseline and after 2 and 4 hour in a group of 16 volunteers. Data were evaluated by analysis of variance. Bland-Altman plot, CV, CR, and ICC were measured.
  
  RESULTS:
  While interday RHI repeatability was found to be reliable (CV: 6.0%; CR: 0.51; ICC: 0.77), multiple evaluations within the same day significantly (P<.001 affected rhi of the measurement cr: icc: in particular a significant increase occurred at hour compared to p and baseline>
  CONCLUSIONS:
  RHI showed good interday but poor intraday repeatability. Multiple evaluations increased RHI especially in subjects with endothelial dysfunction who improved or reversed their impairment. These results show the potential limitations of multiple Endo-PAT measurements within the same day and the importance of standardizing the protocols before RHI evaluations.
  
  © 2016 John Wiley & Sons Ltd.
  
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• Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.
  J Neurol Sci

  2016 Nov;370():167-172. doi: 10.1016/j.jns.2016.09.050.
  
  Campolo Jonica, De Maria Renata, Cozzi Lorena, Parolini Marina, Bernardi Stefano, Proserpio Paola, Nobili Lino, Gelosa Giorgio, Piccolo Immacolata, Agostoni Elio C, Trivella Maria G, Marraccini Paolo
  
  Abstract
  
  OBJECTIVES:
  We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD.
  
  METHODS:
  We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin).
  
  RESULTS:
  Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016).
  
  CONCLUSIONS:
  Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD.
  
  Copyright © 2016 Elsevier B.V. All rights reserved.
  
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• Biological and proteomic characterization of a composite mesh for abdominal wall hernia treatment: Reference Study.
  J Biomed Mater Res B Appl Biomater

  2017 Oct;105(7):2045-2052. doi: 10.1002/jbm.b.33749.
  
  Vozzi Federico, Guerrazzi Ilenia, Campolo Jonica, Cozzi Lorena, Comelli Laura, Cecchettini Antonella, Rocchiccioli Silvia, Domenici Claudio
  
  Abstract
  
  AIMS:
  The industrial development of a product requires performing a deep analysis to highlight its characteristics useful for future design. The clinical use of a product stimulates knowledge improvement about it in a constant effort of progress. This work shows the biological characterization of CMC composite mesh. CMC polypropylene prosthesis was seeded with Human fibroblast BJ. Samples (cells and medium) were collected at different time points in order to perform different analysis: inflammatory markers quantification; collagens immunohistochemistry; matrix metalloproteinases zimography; extracellular matrix proteomic profile.
  
  FINDINGS:
  CMC presented a good cell viability rate and cell growth during the 21 days. The inflammatory profile showed an initial secretion of anti-inflammatory IL-10 and a final increase of pro-inflammatory IL-6. Immunocytochemistry highlighted a similar Collagen type I/type III ratio. The proteomic analysis evidenced the ECM protein content profile composed, mainly, by collagens, fibronectin, laminin. MMPs resulted both expressed when in contact to mesh.
  
  CONCLUSIONS:
  CMC shows a good cell biocompatibility and growth. The increase of pro-inflammatory markers could stimulate proliferation, influencing the integration process in human body. Proteomics highlights the ECM modulation by CMC. An integrated investigation of these biological analyses with mechanical data should improve the design process of a new product. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2045-2052, 2017.
  
  © 2016 Wiley Periodicals, Inc.
  
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• A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defence and oxidative stress in healthy volunteers following cigarette smoking.
  Mutagenesis

  2016 Mar;31(2):215-24. doi: 10.1093/mutage/gev079.
  
  Del Bo' Cristian, Porrini Marisa, Campolo Jonica, Parolini Marina, Lanti Claudia, Klimis-Zacas Dorothy, Riso Patrizia
  
  Abstract
  
  We previously reported that a portion of blueberries reversed endothelial dysfunction induced by acute cigarette smoking. Since smoking-induced endothelial dysfunction is associated with a condition of oxidative stress, we evaluated whether the observed effect was mediated by modulation of markers of oxidative stress and antioxidant defence. Fourteen out of 16 male healthy smokers previously enrolled, participated in a three-armed randomized controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300g of blueberries) + smoking (one cigarette); control treatment (300ml of water with sugar) + smoking (one cigarette). The cigarette was smoked 100min after blueberry/control/water consumption. Each treatment was separated by 1 week of washout period. Plasma vitamin (C, B12 and folate) and aminothiol concentrations, endogenous [formamidopyrimidine-DNA glycosylase (FPG)-sensitive sites] and oxidatively induced DNA damage (resistance to H2O2-induced DNA damage) in peripheral blood mononuclear cells (PBMCs) were measured at baseline and 20, 60, 90, 120min and 24h after smoking. On the whole, analysis of variance did not show a significant effect of treatment on the modulation of markers of oxidative stress and antioxidant defence but revealed an effect of time for plasma concentrations of vitamin C (P = 0.003), B12 (P 0.05) and H2O2-induced DNA damage (P > 0.05) in PBMCs. In conclusion, the consumption of a single blueberry portion failed to modulate markers of oxidative stress and antioxidant defence investigated in our experimental conditions. Further studies are necessary to elucidate this finding and help clarifying the mechanisms of protection of blueberries against smoking-induced endothelial dysfunction.
  
  © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
  
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• Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein.
  Clin Chem Lab Med

  2015 Aug;53(9):1359-66. doi: 10.1515/cclm-2014-0633.
  
  Caruso Raffaele, Caselli Chiara, Cozzi Lorena, Campolo Jonica, Viglione Federica, Parolini Marina, Nonini Sandra, Trunfio Salvatore, D'Amico Andrea, Pelosi Gualtiero, Giannessi Daniela, Marraccini Paolo, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  In left ventricular assist device (LVAD) recipients, plasma levels of interleukin (IL)-6 are associated with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles, reflecting post-operative risk. However, it is not clear how the cardiac level of IL-6, detectable on the tissue samples at the time of implantation, can contribute to predict the post-operative outcome.
  
  METHODS:
  In 40 LVAD recipients, blood and myocardial samples from LV-apex were collected at the time of implantation to assess plasma and cardiac IL-6 levels. Serum C-reactive protein (CRP) levels were considered as inflammatory variable routinely used in LVAD-based therapy.
  
  RESULTS:
  Cardiac IL-6 levels did not correlate with either plasma IL-6 levels (R=0.296, p=0.063) and tissue IL-6 mRNA expression (R=-0.013, p=0.954). Contrary to what happened for the plasma IL-6 and CRP, no differences were observed in cardiac IL-6 levels with respect to INTERMACS profiles (p=0.090). Furthermore, cardiac IL-6 concentrations, unlike IL-6 and CRP circulating levels, were not correlated with the length of intensive care unit stay and hospitalization.
  
  CONCLUSIONS:
  Cardiac IL-6 levels do not contribute to improve risk profile of LVAD recipients in relation to clinical inpatient post-implantation. Instead, plasma IL-6 and serum CRP concentrations are more effective in predicting the severity of the clinical course in the early phase of LVAD therapy.
  
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• A single serving of blueberry (V. corymbosum) modulates peripheral arterial dysfunction induced by acute cigarette smoking in young volunteers: a randomized-controlled trial.
  Food Funct

  2014 Dec;5(12):3107-16. doi: 10.1039/c4fo00570h.
  
  Del Bo' Cristian, Porrini Marisa, Fracassetti Daniela, Campolo Jonica, Klimis-Zacas Dorothy, Riso Patrizia
  
  Abstract
  
  Cigarette smoking causes oxidative stress, hypertension and endothelial dysfunction. Polyphenol-rich foods may prevent these conditions. We investigated the effect of a single serving of fresh-frozen blueberry intake on peripheral arterial function and arterial stiffness in young smokers. Sixteen male smokers were recruited for a 3-armed randomized-controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300 g of blueberry) + smoking; control treatment (300 mL of water with sugar) + smoking. Each treatment was separated by one week of wash-out period. The blood pressure, heart rate, peripheral arterial function (reactive hyperemia and Framingham reactive hyperemia), and arterial stiffness (digital augmentation index, digital augmentation index normalized for a heart rate of 75 bpm) were measured before and 20 min after smoking with Endo-PAT2000. Smoking impaired the blood pressure, heart rate and peripheral arterial function, but did not affect the arterial stiffness. Blueberry consumption counteracted the impairment of the reactive hyperemia index induced by smoking (-4.4 ± 0.8% blueberry treatment vs. -22.0 ± 1.1% smoking treatment, p
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• Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy.
  Circ Cardiovasc Genet

  2014 Dec;7(6):760-70. doi: 10.1161/CIRCGENETICS.113.000384.
  
  Schmitz Boris, De Maria Renata, Gatsios Dimitris, Chrysanthakopoulou Theodora, Landolina Maurizio, Gasparini Maurizio, Campolo Jonica, Parolini Marina, Sanzo Antonio, Galimberti Paola, Bianchi Michele, Lenders Malte, Brand Eva, Parodi Oberdan, Lunati Maurizio, Brand Stefan-Martin
  
  Abstract
  
  BACKGROUND:
  Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters.
  
  METHODS AND RESULTS:
  Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic (P
  CONCLUSIONS:
  We demonstrated that rule induction algorithms can successfully be applied for the classification of heart failure patients in CRT responder and nonresponder status using clinical and genetic parameters. Our analysis included information on alleles and genotypes of 4 genetic loci, rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11), pathophysiologically associated with remodeling of the failing ventricle.
  
  © 2014 American Heart Association, Inc.
  
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• Effects of sapropterin on endothelium-dependent vasodilation in patients with CADASIL: a randomized controlled trial.
  Stroke

  2014 Oct;45(10):2959-66. doi: 10.1161/STROKEAHA.114.005937.
  
  De Maria Renata, Campolo Jonica, Frontali Marina, Taroni Franco, Federico Antonio, Inzitari Domenico, Tavani Alessandra, Romano Silvia, Puca Emanuele, Orzi Francesco, Francia Ada, Mariotti Caterina, Tomasello Chiara, Dotti Maria Teresa, Stromillo Maria Laura, Pantoni Leonardo, Pescini Francesca, Valenti Raffaella, Pelucchi Claudio, Parolini Marina, Parodi Oberdan,
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients.
  
  METHODS:
  In a 24-month, multicenter randomized, double-blind, placebo-controlled trial, CADASIL patients aged 30 to 65 years were randomly assigned to receive placebo or sapropterin 200 to 400 mg BID. The primary end point was change in the reactive hyperemia index by peripheral arterial tonometry at 24 months. We also assessed the safety and tolerability of sapropterin. Analysis was done by intention-to-treat.
  
  RESULTS:
  The intention-to-treat population included 61 patients. We found no significant difference between sapropterin (n=32) and placebo (n=29) in the primary end point (mean difference in reactive hyperemia index by peripheral arterial tonometry changes 0.19 [95% confidence interval, -0.18, 0.56]). Reactive hyperemia index by peripheral arterial tonometry increased after 24 months in 37% of patients on sapropterin and in 28% on placebo; however, after adjustment for age, sex, and clinical characteristics, improvement was not associated with treatment arm. The proportion of patients with adverse events was similar on sapropterin and on placebo (50% versus 48.3%); serious adverse events occurred in 6.3% versus 13.8%, respectively.
  
  CONCLUSIONS:
  Sapropterin was safe and well-tolerated at the average dose of 5 mg/kg/day, but did not affect endothelium-dependent vasodilation in CADASIL patients.
  
  CLINICAL TRIAL REGISTRATION URL:
  https://www.clinicaltrialsregister.eu. Unique identifier: 2007-004370-55.
  
  © 2014 American Heart Association, Inc.
  
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• Relationship between early inflammatory response and clinical evolution of the severe multiorgan failure in mechanical circulatory support-treated patients.
  Mediators Inflamm

  2014 ;2014():281790. doi: 281790.
  
  Caruso Raffaele, Campolo Jonica, Verde Alessandro, Botta Luca, Cozzi Lorena, Parolini Marina, Milazzo Filippo, Nonini Sandra, Martinelli Luigi, Paino Roberto, Marraccini Paolo, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified.
  
  METHODS:
  Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53?MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA).
  
  RESULTS:
  During MCS treatment, 32 patients experienced moderate MOFS (tSOFA?11; A group), while 21 patients experienced severe MOFS (tSOFA???11) with favorable (B group) or adverse (n = 13, C group) outcomes. At preimplant, higher values of left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were the only parameter independently associated with A group. In C group, during the first postoperative week, high levels of interleukin-8 (IL-8) and tumor necrosis factor (TNF)-?, and an increase of neopterin and adhesion molecules, precede tSOFA worsening and exitus.
  
  CONCLUSIONS:
  The MCS patients of C group show an excessive release to IL-8 and TNF-?, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS.
  
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• Vascular injury post stent implantation: different gene expression modulation in human umbilical vein endothelial cells (HUVECs) model.
  PLoS One

  2014 ;9(2):e90213. doi: e90213.
  
  Campolo Jonica, Vozzi Federico, Penco Silvana, Cozzi Lorena, Caruso Raffaele, Domenici Claudio, Ahluwalia Arti, Rial Michela, Marraccini Paolo, Parodi Oberdan
  
  Abstract
  
  To explore whether stent procedure may influence transcriptional response of endothelium, we applied different physical (flow changes) and/or mechanical (stent application) stimuli to human endothelial cells in a laminar flow bioreactor (LFB) system. Gene expression analysis was then evaluated in each experimental condition. Human umbilical vein endothelial cells (HUVECs) were submitted to low and physiological (1 and 10 dyne/cm(2)) shear stress in absence (AS) or presence (PS) of stent positioning in a LFB system for 24 h. Different expressed genes, coming from Affymetrix results, were identified based on one-way ANOVA analysis with p values 3 in modulus. Low shear stress was compared with physiological one in AS and PS conditions. Two major groups include 32 probes commonly expressed in both 1AS versus 10AS and 1PS versus 10PS comparison, and 115 probes consisting of 83 in addition to the previous 32, expressed only in 1PS versus 10PS comparison. Genes related to cytoskeleton, extracellular matrix, and cholesterol transport/metabolism are differently regulated in 1PS versus 10PS condition. Inflammatory and apoptotic mediators seems to be, instead, closely modulated by changes in flow (1 versus 10), independently of stent application. Low shear stress together with stent procedure are the experimental conditions that mainly modulate the highest number of genes in our human endothelial model. Those genes belong to pathways specifically involved in the endothelial dysfunction.
  
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• Is the oxidant/antioxidant status altered in CADASIL patients?
  PLoS One

  2013 ;8(6):e67077. doi: e67077.
  
  Campolo Jonica, De Maria Renata, Mariotti Caterina, Tomasello Chiara, Parolini Marina, Frontali Marina, Inzitari Domenico, Valenti Raffaella, Federico Antonio, Taroni Franco, Parodi Oberdan
  
  Abstract
  
  The altered aggregation of proteins in non-native conformation is associated with endoplasmic reticulum derangements, mitochondrial dysfunction and excessive production of reactive oxygen species. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary systemic vasculopathy, caused by NOTCH3 mutations within the receptor extracellular domain, that lead to abnormal accumulation of the mutated protein in the vascular wall. NOTCH3 misfolding could cause free radicals increase also in CADASIL. Aim of the study was to verify whether CADASIL patients have increased oxidative stress compared to unrelated healthy controls. We enrolled 15 CADASIL patients and 16 gender- and age-matched healthy controls with comparable cardiovascular risk factor. Blood and plasma reduced and total aminothiols (homocysteine, cysteine, glutathione, cysteinylglycine) were measured by HPLC and plasma 3-nitrotyrosine by ELISA. Only plasma reduced cysteine (Pr-Cys) and blood reduced glutathione (Br-GSH) concentrations differed between groups: in CADASIL patients Br-GSH levels were higher (p = 0.019) and Pr-Cys lower (p = 0.010) than in controls. No correlation was found between Br-GSH and Pr-Cys either in CADASIL patients (rho 0.25, P = 0.36) or in controls (rho -0.15, P = 0.44). Conversely, 3-nitrotyrosine values were similar in CADASIL and healthy subjects (p = 0.82). The high levels of antioxidant molecules and low levels of oxidant mediators found in our CADASIL population might either be expression of an effective protective action against free radical formation at an early stage of clinical symptoms or they could suggest that oxidative stress is not directly involved in the pathogenesis of CADASIL.
  
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• A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers.
  Nutr Res

  2013 Mar;33(3):220-7. doi: 10.1016/j.nutres.2012.12.009.
  
  Del Bó Cristian, Riso Patrizia, Campolo Jonica, Møller Peter, Loft Steffen, Klimis-Zacas Dorothy, Brambilla Ada, Rizzolo Anna, Porrini Marisa
  
  Abstract
  
  It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H(2)O(2)-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P
  Copyright © 2013 Elsevier Inc. All rights reserved.
  
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• Genetic variants of the renin-angiotensin-aldosterone system and reverse remodeling after cardiac resynchronization therapy.
  J Card Fail

  2012 Oct;18(10):762-8. doi: 10.1016/j.cardfail.2012.07.008.
  
  De Maria Renata, Landolina Maurizio, Gasparini Maurizio, Schmitz Boris, Campolo Jonica, Parolini Marina, Sanzo Antonio, Galimberti Paola, Bianchi Michele, Brand Stefan-Martin, Parodi Oberdan, Lunati Maurizio
  
  Abstract
  
  BACKGROUND:
  Reverse remodeling (RR) after cardiac resynchronization therapy (CRT) is associated with favorable clinical outcomes in heart failure (HF). The renin-angiotensin-aldosterone system (RAAS) is involved in the remodeling process.
  
  METHODS AND RESULTS:
  We assessed the association between RR and 8 common RAAS gene variants, which were determined by TaqMan assays, in 156 outpatients with chronic HF. RR was defined as a >15% decrease in left ventricular end systolic volume (LVESV) at 9 (interquartile range 7-12) months after CRT. We matched 76 patients who did not show RR (RR-) to 80 RR+ control subjects by age, sex, HF etiology, New York Heart Association (NYHA) functional class and left ventricular ejection fraction (LVEF). The frequency of the minor allele of the NR3C2 gene (rs5522 C/T), encoding the mineralocorticoid receptor, was higher in RR- than in RR (24/126 vs 10/150; P value after false discovery rate correction: <.0193 conversely lvesv decreased significantly less after crt in carriers of the nr3c2 minor c allele .02 adjustment for age sex nyha functional class previous myocardial infarction atrial fibrillation and lvef rr- remained independently associated with carriage ratio confidence interval>
  CONCLUSIONS:
  The association of RR- after CRT with a common polymorphism in the mineralocorticoid receptor gene involved in aldosterone signaling suggests a possible role for variants in RAAS genes in progressive LV function decline, despite apparently effective CRT.
  
  Copyright © 2012 Elsevier Inc. All rights reserved.
  
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• Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors.
  Eur J Nutr

  2013 Apr;52(3):949-61. doi: 10.1007/s00394-012-0402-9.
  
  Riso Patrizia, Klimis-Zacas Dorothy, Del Bo' Cristian, Martini Daniela, Campolo Jonica, Vendrame Stefano, Møller Peter, Loft Steffen, De Maria Renata, Porrini Marisa
  
  Abstract
  
  PURPOSE:
  Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease.
  
  METHODS:
  Eighteen male volunteers (ages 47.8 ± 9.7 years; body mass index 24.8 ± 2.6 kg/m²) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed.
  
  RESULTS:
  Wild blueberry drink intake significantly reduced the levels of endogenously oxidized DNA bases (from 12.5 ± 5.6 % to 9.6 ± 3.5 %, p ? 0.01) and the levels of H?O?-induced DNA damage (from 45.8 ± 7.9 % to 37.2 ± 9.1 %, p ? 0.01), while no effect was found after the PL drink. No significant differences were detected for markers of endothelial function and the other variables under study.
  
  CONCLUSIONS:
  In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial function.
  
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• Plasma total cysteine and cardiovascular risk burden: action and interaction.
  ScientificWorldJournal

  2012 ;2012():303654. doi: 303654.
  
  De Chiara Benedetta, Sedda Valentina, Parolini Marina, Campolo Jonica, De Maria Renata, Caruso Raffaele, Pizzi Gianluigi, Disoteo Olga, Dellanoce Cinzia, Corno Anna Rosa, Cighetti Giuliana, Parodi Oberdan
  
  Abstract
  
  We hypothesized that redox analysis could provide sensitive markers of the oxidative pathway associated to the presence of an increasing number of cardiovascular risk factors (RFs), independently of type. We classified 304 subjects without cardiovascular disease into 4 groups according to the total number of RFs (smoking, hypertension, hypercholesterolaemia, hyperhomocysteinaemia, diabetes, obesity, and their combination). Oxidative stress was evaluated by measuring plasma total and reduced homocysteine, cysteine (Cys), glutathione, cysteinylglycine, blood reduced glutathione, and malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1 RF, 31% in 2 RF, and 16% in ? 3 RF. By multivariable ordinal regression analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068; 95% CI = 1.027-1.110, P = 0.002). Total RF burden is associated with increased total Cys levels. These findings support a prooxidant effect of Cys in conjunction with RF burden, and shed light on the pathophysiologic role of redox state unbalance in preclinical atherosclerosis.
  
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• Severity of oxidative stress and inflammatory activation in end-stage heart failure patients are unaltered after 1 month of left ventricular mechanical assistance.
  Cytokine

  2012 Jul;59(1):138-44. doi: 10.1016/j.cyto.2012.04.018.
  
  Caruso Raffaele, Verde Alessandro, Campolo Jonica, Milazzo Filippo, Russo Claudio, Boroni Chiara, Parolini Marina, Trunfio Salvatore, Paino Roberto, Martinelli Luigi, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  This study investigates the impact of early left ventricular (LV)-mechanical unloading on systemic oxidative stress and inflammation in terminal heart failure patients and their impact both on multi organ failure and on intensive care unit (ICU) stay. Circulating levels of urinary 15-isoprostane-F(2t) (8-epi-PGF2(?)) and pro-inflammatory markers [plasma interleukin (IL)-6, IL-8, and urinary neopterin, a monocyte activation index] were analyzed in 20 healthy subjects, 22 stable end-stage heart failure (ESHF) patients and in 23 LV assist device (LVAD) recipients at pre-implant and during first post-LVAD (PL) month. Multi-organ function was evaluated by total Sequential Organ Failure Assessment (tSOFA) score. In LVAD recipients the levels of oxidative-inflammatory markers and tSOFA score were higher compared to other groups. After device implantation 8-epi-PGF2(?) levels were unchanged, while IL-6, and IL-8 levels increased during first week, and at 1month returned to pre-implant values, while neopterin levels increased progressively during LVAD support. The tSOFA score worsened at 1 PL-week with respect to pre-implant value, but improved at 1 PL-month. The tSOFA score related with IL-6 and IL-8 levels, while length of ICU stay related with pre-implant IL-6 levels. These data suggest that hemodynamic instability in terminal HF is associated to worsening of systemic inflammatory and oxidative milieu that do not improve in the early phase of hemodynamic recovery and LV-unloading by LVAD, affecting multi-organ function and length of ICU stay. This data stimulate to evaluate the impact of inflammatory signals on long-term outcome of mechanical circulatory support.
  
  Copyright © 2012 Elsevier Ltd. All rights reserved.
  
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• Impaired vasoreactivity in mildly disabled CADASIL patients.
  J Neurol Neurosurg Psychiatry

  2012 Mar;83(3):268-74. doi: 10.1136/jnnp-2011-300080.
  
  Campolo Jonica, De Maria Renata, Frontali Marina, Taroni Franco, Inzitari Domenico, Federico Antonio, Romano Silvia, Puca Emanuele, Mariotti Caterina, Tomasello Chiara, Pantoni Leonardo, Pescini Francesca, Dotti Maria Teresa, Stromillo Maria Laura, De Stefano Nicola, Tavani Alessandra, Parodi Oberdan
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare genetic disease caused by NOTCH3 gene mutations. A dysfunction in vasoreactivity has been proposed as an early event in the pathogenesis of the disease. The aim of this study was to verify whether endothelium dependent and/or independent function is altered in CADASIL patients with respect to controls.
  
  METHODS:
  Vasoreactivity was studied by a non-invasive pletismographic method in 49 mildly disabled CADASIL patients (30-65 years, 58% male, Rankin scale ?2) and 25 controls. Endothelium dependent vasodilatation was assessed by reactive hyperaemia (flow mediated dilation-peripheral arterial tone (FMD-PAT)) and endothelium independent vasoreactivity by glyceryl trinitrate (GTN) administration (GTN-PAT).
  
  RESULTS:
  Patients and controls showed comparable age, gender and cardiovascular risk factor distribution. GTN-PAT values were significantly lower in CADASIL patients (1.54 (1.01 to 2.25)) than in controls (1.89 (1.61 to 2.59); p=0.041). FMD-PAT scores did not differ between patients and controls (1.88 (1.57 to 2.43) vs 2.08 (1.81 to 2.58); p=0.126) but 17 CADASIL patients (35%) had FMD-PAT scores below the fifth percentile of controls. FMD-PAT and GTN-PAT values correlated both in controls (?=0.648, p
  CONCLUSIONS:
  The impaired vasoreactivity observed in CADASIL patients highlights the fact that both endothelial and smooth muscle functional alterations may already be present in mildly disabled subjects. The improvement in vascular function could be a new target for pharmacological trials in CADASIL patients.
  
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• Relationship between myocardial redox state and matrix metalloproteinase activity in patients on left ventricular assist device support.
  Circ J

  2011 ;75(10):2387-96.
  
  Caruso Raffaele, Caselli Chiara, Boroni Chiara, Campolo Jonica, Milazzo Filippo, Cabiati Manuela, Russo Claudio, Parolini Marina, Giannessi Daniela, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Redox aminothiols have been reported to modulate the activity of recombinant metalloproteinases (MMP). The aim of the present study was to investigate the effects of myocardial redox state on the activities of MMP-2 and -9 implicated in cardiac remodeling in end-stage heart failure patients supported by left ventricular assist device (LVAD).
  
  METHODS AND RESULTS:
  During heart transplant (HT) surgery, myocardial specimens (MS) from right ventricular walls and LV walls were obtained from 7 LVAD recipients (LVAD group, MS n=35) and from 7 stable HT candidates on medical therapy (MT group, MS n=35). Myocardial MMP-2 and -9 activities and expression, tissue inhibitor of MMP (TIMP)-1 and -4, transforming growth factor (TGF)-?1 and aminothiol concentrations were measured. MMP-2 and -9 activities were evaluated also by incubating MS with different amounts of reduced and oxidized glutathione (GSH). MMP-2 and -9 activities and expression were lower in the LVAD group, whereas myocardial TIMP-1 and -4 concentrations were comparable to those of MT patients. Higher GSH and TGF-?1 concentrations were found in LVAD-recipients. Only GSH concentrations were inversely related to MMP-2 and -9 activities. In vitro, GSH had an inhibitory effect on MMP-2 and -9 activities.
  
  CONCLUSIONS:
  LVAD recipients show reduced myocardial MMP-2 and -9 activities and expression when compared to medically treated patients. Changes of myocardial redox state, predominantly GSH-dependent, appear to modulate MMP-2 and -9 activities by an inhibitory effect dependent on thiol content. These data support a role of GSH cycle in modulating the extracellular matrix in end-stage heart failure patients supported by LVAD.
  
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• Early expression of pro- and anti-inflammatory cytokines in left ventricular assist device recipients with multiple organ failure syndrome.
  ASAIO J

  2010 ;56(4):313-8. doi: 10.1097/MAT.0b013e3181de3049.
  
  Caruso Raffaele, Trunfio Salvatore, Milazzo Filippo, Campolo Jonica, De Maria Renata, Colombo Tiziano, Parolini Marina, Cannata Aldo, Russo Claudio, Paino Roberto, Frigerio Maria, Martinelli Luigi, Parodi Oberdan
  
  Abstract
  
  To assess whether the combined evaluation of total Sequential Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVAD, we analyzed plasma interleukin (IL)-6, IL-8, IL-10, IL-1ra, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and urine neopterin levels before (day 0) and at 4 hours, 1, 3, 7, 14, and 30 days after LVAD implant in 23 recipients. Eight patients died of MOFS between days 7 and 30 (nonsurvivors). At preimplant, only blood urea nitrogen and age were higher in nonsurvivors than survivors. At 4 hours, IL-8, IL-10, and IL1-ra levels were higher in nonsurvivors than in survivors; t-SOFA was also higher and peaked on day 3 in nonsurvivors. Only IL-8 levels on day 1 were significantly associated with a t-SOFA > or =10 on day 3 (odds ratio 1.10, 95% confidence interval 1.01-1.21, p = 0.04). Neopterin, marker of monocyte activation, increased significantly only in nonsurvivors (p
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• Automated APTT cycle for the rapid identification of plasma prekallikrein deficiency.
  Thromb Res

  2010 Aug;126(2):e152-3. doi: 10.1016/j.thromres.2010.02.004.
  
  Corno Anna Rosa, Campolo Jonica, Redaelli Rosaria, Caimi Teresa Maria, Mostarda Giovanni, Morra Enrica, Nichelatti Michele
  
  
  
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• Plasma glutathione levels are independently associated with gamma-glutamyltransferase activity in subjects with cardiovascular risk factors.
  Free Radic Res

  2008 Feb;42(2):135-41. doi: 10.1080/10715760701836821.
  
  Sedda Valentina, De Chiara Benedetta, Parolini Marina, Caruso Raffaele, Campolo Jonica, Cighetti Giuliana, De Maria Renata, Sachero Aldo, Donato Luigi, Parodi Oberdan
  
  Abstract
  
  To investigate whether GGT (gamma-glutamyltransferase) is associated to specific redox patterns. GGT, total and reduced aminothiols and malondialdehyde, were measured in 150 subjects (83 males, 48 (39-56) years), with none, one or more risk factors. By univariable analysis GGT was positively associated with age (p =0.001), male gender (p
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• Aminothiol redox alterations in patients with chronic heart failure of ischaemic or non-ischaemic origin.
  J Cardiovasc Med (Hagerstown)

  2007 Dec;8(12):1024-8.
  
  Campolo Jonica, Caruso Raffaele, De Maria Renata, Parolini Marina, Oliva Fabrizio, Roubina Elena, Cighetti Giuliana, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  Oxidative stress plays a role in the progression of chronic heart failure (CHF), but whether and how ischaemic heart disease (IHD) or non-IHD aetiology may account for differential redox alterations is currently unclear. We assessed the relation between thiol redox state and lipid peroxidation, as a marker of oxidative stress, in patients with CHF of ischaemic or non-ischaemic origin.
  
  METHODS:
  Blood reduced glutathione, plasma total and reduced cysteine, cysteinylglycine, homocysteine, glutathione, plasma alpha-tocopherol, ascorbic acid, and free malondialdehyde were assessed in 43 CHF heart transplant candidates (24 IHD and 19 non-IHD) and 30 controls matched for age, gender and number of atherosclerotic risk factors.
  
  RESULTS:
  Reduced cysteine was increased in CHF patients compared with controls. The highest levels were found in IHD versus non-IHD patients versus controls. Malondialdehyde levels were significantly higher in IHD patients than in controls, whereas antioxidant vitamins did not differ among the three groups.
  
  CONCLUSIONS:
  Specific abnormalities in the thiol pattern are associated with heart failure aetiology in CHF patients. Our findings point to the possible role of reduced cysteine in the progression of chronic IHD to heart failure status, as an additional pro-oxidant stimulus for worsening oxidative stress.
  
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• Glutamate-cysteine ligase polymorphism, hypertension, and male sex are associated with cardiovascular events. Biochemical and genetic characterization of Italian subpopulation.
  Am Heart J

  2007 Dec;154(6):1123-9.
  
  Campolo Jonica, Penco Silvana, Bianchi Elena, Colombo Laura, Parolini Marina, Caruso Raffaele, Sedda Valentina, Patrosso Maria Cristina, Cighetti Giuliana, Marocchi Alessandro, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Glutathione (GSH) is an important intravascular scavenger that protects endothelial cells from atherosclerosis. However, it is still unknown whether cardiovascular (CV) events are associated with metabolic and genetic factors, linked to GSH synthesis in an Italian subpopulation, and if a glutamate-cysteine ligase polymorphism within the catalytic subunit (GCLC) could affect blood and plasma GSH concentrations.
  
  METHODS:
  One hundred subjects, with or without CV risk factors, were enrolled to evaluate plasma and erythrocyte redox status (GSH, homocysteine, cysteine, cysteinylglycine), antioxidant vitamins (alpha-tocopherol and ascorbate), malondialdehyde, a lipid peroxidation product, and the presence of the GCLC-129 C/T polymorphism; an experimental hyperhomocysteinemia after methionine-induced stimulation of transsulfuration pathway was performed in 91% of enrolled subjects. Clinical, biochemical, and genetic variables were correlated with the presence of CV events (myocardial infarction, transient ischemic attacks, and stroke).
  
  RESULTS:
  By multiple logistic regression analysis, male sex (P = .027), hypertension (P = .001), and GCLC C/T genotype (P = .009) were the only variables associated with events. Plasma alpha-tocopherol content decreased postmethionine in the T allele subjects compared with wild type (P for time x group interaction = .001). Plasma-reduced GSH level was higher in C/T than in C/C genotype subjects at both time points (P for group = .03), whereas intracellular GSH concentration did not differ between the 2 genotype groups either at baseline or postmethionine.
  
  CONCLUSIONS:
  GCLC T allele, together with hypertension and male sex, is associated with CV events in our study population. Moreover, after stimulation of transsulfuration, intracellular GSH content is preserved in T allele subjects, probably by increases in GSH turnover and export, and consumption of alpha-tocopherol.
  
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• Pre-operative redox state affects 1-month survival in patients with advanced heart failure undergoing left ventricular assist device implantation.
  J Heart Lung Transplant

  2007 Nov;26(11):1177-81.
  
  Caruso Raffaele, Garatti Andrea, Sedda Valentina, Milazzo Filippo, Campolo Jonica, Colombo Tiziano, Catena Emanuele, Cighetti Giuliana, Russo Claudio, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Left ventricular assist device (LVAD) implantation has proven effective as a bridge to transplantation in end-stage heart failure patients (ESHFPs), although survival during device support is critical. Oxidative stress has been implicated in the development of heart failure, but the influence of redox state on in-hospital post-LVAD outcome has not been clarified.
  
  METHODS AND RESULTS:
  In this report we describe the oxidant/anti-oxidant profiles of 15 ESHFPs before LVAD placement, 5 of whom did not survive to 1 month, and in 30 subjects without cardiac disease, representing the control group.
  
  CONCLUSIONS:
  Preliminary findings suggest that adequate activity of the GPx-1-based anti-oxidant system before device placement is associated with patient survival up to 1 month, despite comparable baseline oxidative stress in patients who both survived and died (within 2 weeks post-LVAD).
  
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• Low plasma glutathione levels after reperfused acute myocardial infarction are associated with late cardiac events.
  Coron Artery Dis

  2007 Mar;18(2):77-82.
  
  De Chiara Benedetta, Mafrici Antonio, Campolo Jonica, Famoso Gabriella, Sedda Valentina, Parolini Marina, Cighetti Giuliana, Lualdi Alessandro, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  To clarify whether an altered redox state persists in the subacute phase of myocardial infarction and if specific redox patterns are associated with later cardiac events.
  
  METHODS:
  Ninety-seven patients [80 men, median 63 (interquartile range, 53, 69) years] with a first acute myocardial infarction, with (53%) or without ST segment elevation, treated with successful percutaneous interventions, were tested at 5-6 days after admission for plasma alpha-tocopherol, ascorbic acid, total and reduced homocysteine, cysteine, glutathione, cysteinylglycine and blood-reduced glutathione, all assessed by high-pressure liquid chromatography. Free malondialdehyde was evaluated by gas chromatography. A subgroup of 14 patients had adjunctive blood samples within 1 h and at 72 h after angioplasty. Blood samples from 44 patients matched for age, sex, and risk factors served as controls. Patients were followed up for median 15 (interquartile range, 9, 17) months for cardiac events.
  
  RESULTS:
  All plasma-reduced aminothiols, vitamins and plasma total glutathione were significantly lower in myocardial infarction at 5-6 days than in controls. In the 14 myocardial infarction patients sampled repeatedly, plasma-reduced glutathione, cysteinylglycine, total glutathione, and alpha-tocopherol significantly decreased, whereas blood-reduced glutathione, total homocysteine, and cysteine significantly increased over time. During follow-up, 20 of 97 (21%) patients had adverse cardiac events. Multivariate analysis revealed that only plasma-reduced glutathione was independently associated with events (hazard ratio 0.42, 95% confidence interval 0.18-0.99, P=0.04).
  
  CONCLUSIONS:
  Acute myocardial infarction patients have an altered redox state at 5-6 days after successful reperfusion with respect to controls. Low plasma levels of reduced glutathione at discharge are associated with cardiac events at follow-up.
  
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• Plasma cysteine and glutathione are independent markers of postmethionine load endothelial dysfunction.
  Clin Biochem

  2007 Feb;40(3-4):188-93.
  
  Parodi Oberdan, De Chiara Benedetta, Baldassarre Damiano, Parolini Marina, Caruso Raffaele, Pustina Linda, Parodi Guido, Campolo Jonica, Sedda Valentina, Baudo Francesco, Sirtori Cesare
  
  Abstract
  
  OBJECTIVES:
  Oxidative stress caused by acute hyperhomocysteinemia impairs endothelial function in human arteries. We sought to identify markers of endothelial dysfunction during methionine-induced hyperhomocysteinemia.
  
  DESIGN AND METHODS:
  35 subjects underwent flow-mediated dilation (FMD) of the brachial artery by high-resolution ultrasonography and fasting blood samples before and 3 h postmethionine load (PML). Clinical, conventional biochemical, and redox status (plasma total and reduced homocysteine, glutathione, cysteine, cysteinylglycine, ascorbic acid, alpha-tocopherol, free malondialdehyde, blood glutathione) data were sequentially entered into an univariate and multivariate stepwise linear regression analysis to evaluate their relation with the dependent variable FMD.
  
  RESULTS:
  Median [interquartile range] FMD decreased from 4.1% [2.8-6.3] to 3.2% [0.7-4.3] PML (P=0.02). At the multivariate analysis PML total cysteine (beta=-0.008, P=0.002) and glutathione (beta=0.21, P=0.005) were the only independent variables associated with FMD after methionine, adjusted for baseline FMD.
  
  CONCLUSIONS:
  Elevated plasma total cysteine and decreased plasma total glutathione levels were associated with abnormal FMD PML. Cysteine and glutathione are stronger markers of endothelial dysfunction than clinical and all other biochemical variables explored.
  
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• Methionine challenge paradoxically induces a greater activation of the antioxidant defence in subjects with hyper- vs. normohomocysteinemia.
  Free Radic Res

  2006 Sep;40(9):929-35.
  
  Campolo Jonica, De Chiara Benedetta, Caruso Raffaele, De Maria Renata, Sedda Valentina, Dellanoce Cinzia, Parolini Marina, Cighetti Giuliana, Penco Silvana, Baudo Francesco, Parodi Oberdan
  
  Abstract
  
  To determine whether hyperhomocysteinemia induced post-methionine loading (PML) is associated with different response in the aminothiol redox state and oxidative stress vs. normohomocysteinemia, we assessed PML plasma thiols, vitamins, free malondialdehyde (MDA), and blood reduced glutathione (GSH) in 120 consecutive subjects (50 [35-56] years, 83 males), divided into two groups according to PML plasma total Hcy or = 35 microM (Group 2, n = 55). In the group as a whole, plasma reduced cysteine and cysteinylglycine, blood reduced GSH (all p for time = 0.0001) and plasma total GSH (p for time = 0.001) increased from baseline to PML. MDA values were unchanged. Group 1 and 2 differed in blood reduced GSH (p for group = 0.004, higher in Group 2), and MDA levels (p for group = 0.024, lower in Group 2). The oxidative stress induced by methionine challenge seems to be opposed by scavenger molecules activation, namely GSH, and lipid peroxidation does not increase. This mechanism paradoxically appears to be more efficient in hyperhomocysteinemic subjects.
  
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• Blood glutathione as independent marker of lipid peroxidation in heart failure.
  Int J Cardiol

  2007 Apr;117(1):45-50.
  
  Campolo Jonica, De Maria Renata, Caruso Raffaele, Accinni Roberto, Turazza Fabio, Parolini Marina, Roubina Elèna, De Chiara Benedetta, Cighetti Giuliana, Frigerio Maria, Vitali Ettore, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Aminothiols have a critical function as intracellular redox buffers and constitute furthermore an important extracellular redox system. Lipid peroxidation is increased in chronic heart failure (CHF), but the contribution of each thiol to oxidative stress in this syndrome has not been evaluated.
  
  AIM:
  To assess the correlation between blood and plasma concentrations of aminothiols and lipid peroxidation as marker of oxidative stress in CHF patients.
  
  METHODS:
  Blood reduced glutathione (GSH), plasma total and reduced cysteine, cysteinylglycine, homocysteine, GSH, alpha-tocopherol, ascorbic acid, and free malondialdehyde (MDA) were assessed in samples obtained from 26 CHF heart transplant candidates and 26 age- and gender-matched controls with atherosclerotic risk factors and no history of cardiovascular disease. Results are expressed as median and interquartile range (I-III).
  
  RESULTS:
  MDA levels were significantly higher in CHF patients than in controls [1.03 (0.56-1.60) microM vs. 0.70 (0.40-0.83) microM, p=0.006]. Blood reduced GSH concentrations were significantly higher [662 (327-867) microM vs. 416 (248-571) microM, p=0.016], while alpha-tocopherol levels were significantly lower [15 (13-19) microM vs. 21 (17-32) microM, p=0.001] in CHF patients than in controls. By multivariate logistic regression analysis, the only independent predictors of lipid peroxidation, as expressed by MDA levels > or = 1.00 microM, were increased blood GSH concentrations (OR 1.003 per unit, 95% CI 1.001 to 1.006, p=0.008), ischemic (OR 20, 95% CI 2.6 to 155, p=0.004) and non ischemic CHF etiology (OR 11, 95% CI 1.3 to 99, p=0.026).
  
  CONCLUSIONS:
  Abnormalities in intracellular GSH cycling are associated to increased lipid peroxidation in CHF.
  
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• Effect of homocysteine lowering by 5-methyltetrahydrofolate on redox status in hyperhomocysteinemia.
  J Cardiovasc Pharmacol

  2006 Apr;47(4):549-55.
  
  Caruso Raffaele, Campolo Jonica, Sedda Valentina, De Chiara Benedetta, Dellanoce Cinzia, Baudo Francesco, Tonini Annamaria, Parolini Marina, Cighetti Giuliana, Parodi Oberdan
  
  Abstract
  
  The endothelial dysfunction induced by hyperhomocysteinemia can be reversed by 5-methyltetrahydrofolate (5-MTHF) via homocysteine (Hcy) lowering. An additive antioxidant action of 5-MTHF has been suggested to ameliorate endothelial dysfunction through increased nitric oxide production and superoxide radical scavenging, independent of Hcy lowering. The aim of the study was to assess whether 5-MTHF affects the redox state in hyperhomocysteinemia. We examined the effect of 3 months of oral 5-MTHF treatment (15 mg/day) on the redox pattern in 48 hyperhomocysteinemic subjects compared to 24 untreated hyperhomocysteinemic subjects. By analysis of variance with repeated measures in the 72 subjects, 5-MTHF markedly decreased plasma total Hcy (p-tHcy; P = 0.0001) and blood-total glutathione (GSH; b-tGSH; P = 0.002). By multivariate linear regression in the treated subjects, p-tHcy changes from baseline to 3 months (adjusted by baseline p-tHcy levels) correlated only with changes in reduced cysteinylglycine (P = 0.001). The effects of treatment on Hcy lowering and GSH metabolism were greater in medium than in moderate hyperhomocysteinemia. In conclusion, high-dose 5-MTHF treatment for 3 months ensures marked Hcy lowering to normal values even in subjects with high Hcy levels, and should be the treatment of choice in medium hyperhomocysteinemia. Furthermore, 5-MTHF shows a favorable interaction with GSH metabolism.
  
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• Blood glutathione as a marker of cardiac allograft vasculopathy in heart transplant recipients.
  Clin Transplant

  2005 Jun;19(3):367-71.
  
  De Chiara Benedetta, Bigi Riccardo, Campolo Jonica, Parolini Marina, Turazza Fabio, Masciocco Gabriella, Frigerio Maria, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx). Between immunologic and non-immunologic factors, reactive oxygen species generation has been proposed as pathogenetic mechanism. This study was aimed at evaluating redox status in HTx recipients and verifying whether it could be independently associated with CAV.
  
  METHODS:
  Fifty-five consecutive male HTx recipients, median [interquartile range] age 60 yr [50, 64], underwent angiography 67 months [21, 97] after HTx to assess CAV, defined as significant stenosis in >or=1 epicardial vessel or any distal vessel attenuation. All patients underwent blood sampling 89 months [67, 119] after HTx for biochemical (glucose, creatinine, total and LDL cholesterol, and cyclosporin levels) and redox evaluation [plasma reduced and total homocysteine, cysteine, cysteinylglycine, glutathione, blood reduced glutathione (GSH(bl)) and vitamin E]. Univariate Odds Ratios (OR) with 95% confidence interval (95% CI, highest vs. lowest quartile) were estimated on the basis of a logistic regression analysis between clinical, conventional biochemical and redox data. Only the significant variables at univariate entered into multivariate analysis.
  
  RESULTS:
  CAV was documented in 15 (27%) patients. Univariate analysis showed that time from HTx to angiography (OR 3.97, 95% CI 1.15-14, p = 0.03) and GSH(bl) (OR 0.31, 95% CI: 0.14-0.70, p = 0.005) were significantly associated with CAV. However, multivariate analysis revealed GSH(bl) as the only independent predictor of CAV (OR 0.31, 95% CI: 0.13-0.74, p = 0.008).
  
  CONCLUSIONS:
  In HTx recipients reduced levels of GSH(bl) are independently associated with CAV. Given its potent intracellular scavenger properties, GSH(bl) may serve as a marker of antioxidant defence consumption, favouring CAV development.
  
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• Critical study of preanalytical and analytical phases of adenine and pyridine nucleotide assay in human whole blood.
  Anal Biochem

  2004 Jul;330(1):43-51.
  
  Caruso Raffaele, Campolo Jonica, Dellanoce Cinzia, Mariele Rosina, Parodi Oberdan, Accinni Roberto
  
  Abstract
  
  Intracellular redox and energetic status play a crucial role in cardiovascular diseases and metabolic disorders. The physiological status of reducing agents, such as NADPH and NADH, and of high-energy molecules, such as ATP, is required for antioxidant system activity. For these reasons, an accurate measurement of adenine and pyridine nucleotides is fundamental. In this study we examined the preanalytical phase of reduced pyridine (RPN) and adenine and oxidized pyridine (AOPN) nucleotide assay in human whole blood. Different experimental conditions were applied to RPN alkaline and AOPN acid extracts to find the best analytical performance. Our results show that a good RPN and AOPN linearity (r from 0.994 to 0.999), recovery (near to 100%), and precision (coefficient of variation
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• Analytical performance and method comparison study of the total homocysteine fluorescence polarization immunoassay (FPIA) on the AxSYM analyzer.
  Clin Chem Lab Med

  2004 Feb;42(2):228-34.
  
  Lonati Silvia, Novembrino Cristina, Ippolito Silvia, Accinni Roberto, Galli Claudio, Troonen Hugo, Campolo Jonica, Della Noce Cinzia, Lunghi Giovanna, Catena Fabrizia Bamonti
  
  Abstract
  
  A fluorescence polarization immunoassay (FPIA) has been commercially released for routine large-scale testing of total homocysteine (tHcy) on the AxSYM analyzer. We evaluated the analytical performance of the AxSYM tHcy FPIA and compared it with the well established high-performance liquid chromatography (HPLC) and IMx tHcy FPIA methods. Homocysteine concentrations were measured by AxSYM and IMx tHcy FPIA and by a rapid isocratic HPLC method with fluorescence detection. Coefficient of variation (CV) of total imprecision for AxSYM tHcy was
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• Myocardial lactate metabolism in relation to preoperative regional wall motion and to early functional recovery after coronary revascularization.
  J Cardiothorac Vasc Anesth

  2003 Aug;17(4):478-85.
  
  Bortone Franco, Mazzoni Maurizio, Repossini Alberto, Campolo Jonica, Ceriani Roberto, Devoto Emmanuela, Parolini Marina, De Maria Renata, Arena Vincenzo, Parodi Oberdan
  
  Abstract
  
  OBJECTIVE:
  To evaluate myocardial lactate metabolism as a marker of functional status after surgical coronary revascularization.
  
  DESIGN:
  Single-center, prospective, cohort study.
  
  SETTING:
  Tertiary care teaching hospital.
  
  PARTICIPANTS:
  Fifty patients with stable angina, ejection fraction >0.40, undergoing coronary artery bypass surgery for multiple-vessel disease.
  
  MEASUREMENTS AND MAIN RESULTS:
  Before (T1) and 30 minutes (T2) after coronary artery bypass grafting, the authors simultaneously sampled blood from artery and coronary sinus to determine myocardial lactate dynamics and performed transesophageal echocardiography (TEE) to assess segmental wall motion. Wall motion score index (WMSI) was calculated with an online/offline comparison. At T2, WMSI improved from 1.40 +/- 0.31 to 1.17 +/- 0.23 (p = 0.0001). Preoperatively, 2 patterns of lactate balance were found: 39 patients were lactate extractors (17% +/- 10%) and 11 were lactate producers (-11% +/- 11%). At T2, lactate metabolism was shifted towards a pattern opposite to the baseline: delta lactate extraction was -8% +/- 16% in extractors at T1 versus 7% +/- 9% in producers at T1 (p = 0.003). Changes in WMSI were not correlated with changes in lactate utilization. No single preoperative variable predicted postoperative WMSI or its changes from baseline. Cardiopulmonary bypass (CPB) time was the only significant predictor of postoperative lactate extraction by multivariate regression (r = -0.46, p = 0.001): at T2, patients in the highest CPB time quartile showed frank lactate production (-6% +/- 13%) when compared with those in the lowest quartile (15% +/- 11%, p = 0.005). However, postoperative WMSI was similar in different CPB time groups.
  
  CONCLUSIONS:
  Myocardial lactate metabolism pattern is not associated with functional status before and early after successful coronary revascularization. CPB time was the only significant predictor of postoperative lactate extraction. Measurement of lactate does not appear to be a valuable tool to assess the coupling of myocardial regional function and metabolism in the setting of coronary artery surgery and mild-to-moderate functional impairment.
  
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• Newborn screening of homocystinuria: quantitative analysis of total homocyst(e)ine on dried blood spot by liquid chromatography with fluorimetric detection.
  J Chromatogr B Analyt Technol Biomed Life Sci

  2003 Mar;785(2):219-26.
  
  Accinni Roberto, Campolo Jonica, Parolini Marina, De Maria Renata, Caruso Raffaele, Maiorana Andrea, Galluzzo Cino, Bartesaghi Silvia, Melotti Davide, Parodi Oberdan
  
  Abstract
  
  Identification of homocystinuric newborns is hindered by the pitfalls of neonatal screening programs. We propose a fluorimetric HPLC method with a rapid pre-analytical step for homocysteine determination from neonatal dried blood spot cards. Homocysteine in blood spots sampled among 2000 healthy newborns on living day 4, averaged 2.92+/-2.07 microM (range 0.4-7.5). In eight homocystinuric control children, mean values were 61.71+/-52.84 microM (range 18.9-145.7). The method showed a good linearity (r=0.999), precision (RSD
  Copyright 2002 Elsevier Science B.V.
  
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