Parolini Dott.ssa Marina

Pubblicazioni su PubMed

• The burden of radiation exposure in congenital heart disease: the Italian cohort profile and bioresource collection in HARMONIC project.
  Ital J Pediatr

  2024 May;50(1):100. doi: 100.
  
  Campolo Jonica, Annoni Giuseppe, Vignati Gabriele, Peretti Alessio, Papa Marco, Colombo Paola Enrica, Muti Gaia, Parolini Marina, Borghini Andrea, Giaccardi Marzia, Ait-Alì Lamia, Picano Eugenio, Andreassi Maria Grazia
  
  Abstract
  
  BACKGROUND:
  The European-funded Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) project aims to improve knowledge on the effects of medical exposure to ionizing radiation (IR) received during childhood. One of its objectives is to build a consolidated European cohort of pediatric patients who have undergone cardiac catheterization (Cath) procedures, with the goal of enhancing the assessment of long-term radiation-associated cancer risk. The purpose of our study is to provide a detailed description of the Italian cohort contributing to the HARMONIC project, including an analysis of cumulative IR exposure, reduction trend over the years and an overview of the prospective collection of biological samples for research in this vulnerable population.
  
  METHODS:
  In a single-center retrospective cohort study, a total of 584 patients (323 males) with a median age of 6 (2-13) years, referred at the Pediatric Cardiology in Niguarda Hospital from January 2015 to October 2023, were included. Biological specimens from a subset of 60 patients were prospectively collected for biobanking at baseline, immediately post-procedure and after 12 months.
  
  RESULTS:
  Two hundred fifty-nine (44%) patients were under 1 year old at their first procedure. The median KAP/weight was 0.09 Gy·cm/kg (IQR: 0.03-0.20), and the median fluoroscopy time was 8.10 min (IQR: 4.00-16.25). KAP/weight ratio showed a positive correlation with the fluoroscopy time (Spearman's rho?=?0.679, p?0.001). Significant dose reduction was observed either after implementation of an upgraded technology system and a radiation training among staff. The Italian cohort includes 1858 different types of specimens for Harmonic biobank, including blood, plasma, serum, clot, cell pellet/lymphocytes, saliva.
  
  CONCLUSIONS:
  In the Italian Harmonic cohort, radiation dose in cardiac catheterization varies by age and procedure type. An institution's radiological protection strategy has contributed to a reduction in radiation dose over time. Biological samples provide a valuable resource for future research, offering an opportunity to identify potential early biomarkers for health surveillance and personalized risk assessment.
  
  © 2024. The Author(s).
  
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• Exploiting routine laboratory test to identify primary severe hypertriglyceridaemic patients in a large Italian hospital.
  Eur J Prev Cardiol

  2024 Aug;31(10):e71-e74. doi: 10.1093/eurjpc/zwae056.
  
  Pavanello Chiara, Pazzucconi Franco, Parolini Marina, Turri Marta, Mombelli Giuliana Germana, Castiglione Sofia, Alberti Antonia, De Maria Renata, Calabresi Laura
  
  
  
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• Influence of Chromosome 9p21.3 rs1333049 Variant on Telomere Length and Their Interactive Impact on the Prognosis of Coronary Artery Disease.
  J Cardiovasc Dev Dis

  2023 Sep;10(9):. doi: 387.
  
  Borghini Andrea, Mercuri Antonella, Campolo Jonica, Parolini Marina, Ndreu Rudina, Turchi Stefano, Andreassi Maria Grazia
  
  Abstract
  
  BACKGROUND:
  Both telomere shortening and the chromosome 9p21.3 (Chr9p21) rs1333049 (G/C) variant are involved in coronary artery disease (CAD) risk, likely affecting mechanisms related to cell cycle arrest and vascular senescence. The aim of the study was to examine the link between Chr9p21 rs1333049 variant and leucocyte telomere length (LTL), as well as their interactive effect on the risk of major adverse cardiovascular events (MACEs).
  
  METHODS:
  A cohort of 472 patients with angiographically proven and clinically stable CAD were included in the study. At baseline, the LTL, biochemical parameters, and genotype analysis of Chr9p21 rs1333049 variant were measured in all patients. The primary endpoint of this study was the occurrence of MACE defined as a composite of coronary-related death, nonfatal MI, and coronary revascularization.
  
  RESULTS:
  On multivariable linear regression analysis, age ( = 0.02) and Chr9p21 rs1333049 variant ( = 0.002) were the only independent predictors of LTL levels. Carriers of the CC genotype of this SNP had shorter telomeres than GC carriers ( = 0.02) and GG carriers ( = 0.0005). After a follow-up with a mean period of 62 ± 19 months, 90 patients (19.1%) had MACE. Short LTL was an independent prognostic factor of MACE incidence (HR:2.2; 95% CI: 1.3-3.7; = 0.005) after adjustment for potential confounders. There was a significant interaction ( = 0.01) between the LTL and rs1333049 variant, with patients with risk-allele C and short LTL having a higher risk (HR:5.8; 95% CI: 1.8-19.2; = 0.004).
  
  CONCLUSION:
  A strong relationship between LTL and Chr9p21 rs1333049 variant was identified, and they interactively affect the risk of poor prognosis in CAD patients.
  
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• Clinical and Biological Predictors of Cancer Incidence and Mortality in Patients with Stable Coronary Artery Disease.
  Int J Mol Sci

  2023 Jul;24(13):. doi: 11091.
  
  Campolo Jonica, Borghini Andrea, Parolini Marina, Mercuri Antonella, Turchi Stefano, Andreassi Maria Grazia
  
  Abstract
  
  Clinical and epidemiological evidence has recently revealed a link between coronary artery disease (CAD) and cancer. Shared risk factors and common biological pathways are probably involved in both pathological conditions. The aim of this paper was to evaluate whether and which conventional risk factors and novel circulating biomarkers could predict cancer incidence and death in patients with CAD. The study included 750 CAD patients, who underwent blood sampling for the evaluation of systemic inflammatory indexes (NLR and SII) and specific biomarkers of oxidative damage (leukocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)). Study participants were followed up for a mean of 5.4 ± 1.2 years. Sixty-seven patients (8.9%) developed cancer during the follow-up time, and nineteen (2.5%) died of cancer. Cox multivariable analysis revealed that age (HR = 1.071; 95% CI: 1.034-1.109;
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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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• 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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• 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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• 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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• Systematic Lab Knowledge Integration for Management of Lipid Excess in High-Risk Patients: Rationale and Design of the SKIM LEAN Project.
  Front Big Data

  2018 ;1():4. doi: 4.
  
  Pavanello Chiara, Parolini Marina, Alberti Antonia, Carenini Michele, Maino Paolo, Mombelli Giuliana, Pazzucconi Franco, Origgi Gianni, Orsi Federica, Trivella Maria Giovanna, Calabresi Laura, De Maria Renata
  
  Abstract
  
  SKIM LEAN aims at exploiting Electronic Health Records (EHRs) to integrate knowledge derived from routine laboratory tests with background analysis of clinical databases, for the identification and early referral to specialist care, where appropriate, of patients with hypercholesterolemia, who may be inadequately controlled according to their cardiovascular (CV) risk level. SKIM LEAN addresses gaps in care that may occur through the lack of coordination between primary and specialist care, incomplete adherence to clinical guidelines, or poor patient's compliance to the physician's prescriptions because of comorbidities or drug side effects. Key project objectives include: (1) improved health professionals' competence and patient empowerment through a two-tiered educational website for general practitioners (GPs) and patients, and (2) implementation of a hospital-community shared care pathway to increase the proportion of patients at high/very-high CV risk (Familial Hypercholesterolemia, previous CV events) who achieve target LDL cholesterol (LDL-C) levels. Thanks to a close collaboration between clinical and information technology partners, SKIM LEAN will fully exploit the value of big data deriving from EHRs, and filter such knowledge using clinically-derived algorithms to risk-stratify patients. Alerts for GPs will be generated with interpreted test results. GPs will be able to refer patients with uncontrolled LDL-C within the shared pathway to the lipid or secondary prevention outpatient clinics of NIG hospital. Metrics to verify the project achievements include web-site visits, the number of alerts generated, numbers of patients referred by GPs, the proportion of secondary prevention patients who achieve LDL-C 50% decrease from baseline.
  
  Copyright © 2018 Pavanello, Parolini, Alberti, Carenini, Maino, Mombelli, Pazzucconi, Origgi, Orsi, Trivella, Calabresi and De Maria.
  
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• Galectin-3 and outcomes after anterior-wall myocardial infarction treated by primary percutaneous coronary intervention.
  Biomark Med

  2018 Jan;12(1):21-26. doi: 10.2217/bmm-2017-0178.
  
  Di Tano Giuseppe, Caretta Giorgio, De Maria Renata, Bettari Luca, Parolini Marina, Testa Sophie, Pirelli Salvatore
  
  Abstract
  
  AIM:
  Galectin-3 (Gal-3), a biomarker of inflammation, tissue repair and fibrogenesis, is associated to left ventricular remodeling after ST-elevated myocardial infarction (STEMI), but its relation with long-term outcomes is unclear.
  
  METHODS:
  In 103 consecutive patients with a first anterior STEMI treated by primary angioplasty, we assayed Gal-3 and NT-proBNP.
  
  RESULTS:
  Age was 65 (56-76) years, 28% were women. During 18 ± 13 months, 20 patients (19.4%) died or were admitted for heart failure. After adjustment for age, gender, renal and ventricular function, troponin, NT-proBNP and Gal-3 independently predicted the combined end point (hazard ratio: 1.11; 95% CI: 1.05-1.17; per 1 ng/ml increase). Event-free survival was 42.3 versus 93.5% for Gal-3? versus
  CONCLUSION:
  Among anterior STEMI patients, early postangioplasty Gal-3 levels may be useful for risk stratification.
  
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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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• Galectin-3 predicts left ventricular remodelling after anterior-wall myocardial infarction treated by primary percutaneous coronary intervention.
  Heart

  2017 Jan;103(1):71-77. doi: 10.1136/heartjnl-2016-309673.
  
  Di Tano Giuseppe, Caretta Giorgio, De Maria Renata, Parolini Marina, Bassi Laura, Testa Sophie, Pirelli Salvatore
  
  Abstract
  
  OBJECTIVES:
  Despite modern reperfusion therapies, left ventricular remodelling (LVR) occurs frequently after an ST-elevated myocardial infarction (STEMI) and represents a strong predictor of mortality and heart failure. Galectin-3 (Gal-3), a novel biomarker involved in inflammation, tissue repair and fibrogenesis, might be a valuable predictor of LVR.
  
  METHODS:
  We enrolled consecutively admitted patients with a first anterior STEMI and left anterior descending artery occlusion treated by primary percutaneous coronary intervention (pPCI). Gal-3, N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography and cardiovascular events were evaluated 48?hours after admission, at 1 and 6?months. LVR was defined as a ?15% increase in LV end-systolic volume.
  
  RESULTS:
  We recruited 103 patients (28% women, aged 64.6±12?years, LV ejection fraction 47±11%). Median baseline Gal-3 and NT-proBNP levels were 13.2?ng/mL (10.8-17.1 ng/mL) and 2132 pg/mL (1019-4860?pg/mL) respectively. During 6?months of follow-up, 4 patients dropped out, 7 died and 26 (28.3%) of the 92 survivors developed LVR (LVR+). LVR+ patients had higher Gal-3 levels at baseline, 1 and 6?months than LVR- (p
  CONCLUSION:
  Gal-3 serum levels measured during hospitalisation could be clinically useful in predicting LVR among patients admitted with anterior STEMI treated by pPCI.
  
  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
  
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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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• Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant" patients during acute coronary syndrome.
  Mediators Inflamm

  2015 ;2015():710123. doi: 710123.
  
  Caruso Raffaele, Rocchiccioli Silvia, Gori Anna Maria, Cecchettini Antonella, Giusti Betti, Parodi Guido, Cozzi Lorena, Marcucci Rossella, Parolini Marina, Romagnuolo Ilaria, Citti Lorenzo, Abbate Rosanna, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel.
  
  MATERIAL AND METHODS:
  Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ?70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined.
  
  RESULTS:
  Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFN?, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased.
  
  CONCLUSIONS:
  In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.
  
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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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• 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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• [Screening of asymptomatic left ventricular systolic dysfunction in a population sample at high cardiovascular risk in Lombardy (Italy): the DAVID-Berg study].
  G Ital Cardiol (Rome)

  2014 May;15(5):313-22. doi: 10.1714/1563.17033.
  
  Gavazzi Antonello, De Maria Renata, Grosu Aurelia, Iacovoni Attilio, Fontana Alessandra, Gori Mauro, Ferrari Paola, Canova Paolo, Calabrese Alice, Filippi Alessandro, Rutili Maria Rosaria, Donzelli Luigi, Parolini Marina, Senni Michele
  
  Abstract
  
  BACKGROUND:
  Prevalence of asymptomatic left ventricular systolic dysfunction (ALVSD) increases with age and cardiovascular (CV) risk exposure. Early diagnosis and treatment allow reducing heart failure and fatal and non-fatal event rates. Data on ALVSD prevalence in Italy are still scarce and ALVSD remains commonly under-diagnosed in primary care, where diagnostic facilities are limited. Among subjects at high CV risk in primary care, we assessed the prevalence of ALVSD and the relative predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the Framingham Heart Failure Risk Score (FHFRS).
  
  METHODS:
  Records of 4047 subjects aged 55-80 years, without history, symptoms or signs of heart failure, registered at three primary care practices in Lombardy, Northern Italy, were reviewed; 623 subjects at high CV risk underwent visit, ECG, echocardiography, NT-proBNP and FHFRS calculation.
  
  RESULTS:
  ALVSD, defined as left ventricular ejection fraction
  CONCLUSIONS:
  In subjects at high CV risk in primary care, prevalence of ALVSD is 5.3%; for diagnosis NT-proBNP adds predictive value to the FHFRS and is equivalent to the combination of FHFRS and ECG. Because of its practical advantages, NT-proBNP might be routinely used for ALVSD screening in primary care.
  
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• Effect of 10-day broccoli consumption on inflammatory status of young healthy smokers.
  Int J Food Sci Nutr

  2014 Feb;65(1):106-11. doi: 10.3109/09637486.2013.830084.
  
  Riso Patrizia, Vendrame Stefano, Del Bo' Cristian, Martini Daniela, Martinetti Antonia, Seregni Ettore, Visioli Francesco, Parolini Marina, Porrini Marisa
  
  Abstract
  
  This study evaluated the effects of 10-day broccoli (250?g/day) intake on dietary markers and markers of inflammations in young male smokers. A dietary intervention study with a repeated measures crossover design was conducted. Circulating levels of carotenoids, folate, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-?), interleukin 6 (IL-6), interleukin 6 receptor (IL-6sR) and adiponectin were measured. Broccoli intake significantly increased plasma levels of folate (+17%) and lutein (+39%), while no significant effect was observed for TNF-?, IL-6, IL-6sR or adiponectin. Plasma CRP decreased by 48% (post-hoc analysis, p??0.05) following broccoli diet; this resulted to be independent from the plasma variations in lutein and folate. An inverse correlation between lycopene, TNF-? and IL-6sR was observed at baseline. In conclusion, broccoli consumption may reduce CRP levels in smokers, consistent with epidemiologic observations that fruit and vegetable intake is associated with lower circulating CRP concentrations.
  
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• Natriuretic peptides and the Framingham risk score for screening of asymptomatic left ventricular systolic dysfunction in high-risk patients in primary care. The DAVID-BERG study.
  Int J Cardiol

  2013 Oct;168(5):5093-5. doi: 10.1016/j.ijcard.2013.07.260.
  
  Iacovoni Attilio, De Maria Renata, Gavazzi Antonello, Grosu Aurelia, Fontana Alessandra, Guideri Silvia, Gori Mauro, Ferrari Paola, Filippi Alessandro, Rutili Maria Rosaria, Donzelli Luigi, Parolini Marina, Senni Michele
  
  
  
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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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• 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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• 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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• Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients.
  J Heart Lung Transplant

  2012 Jun;31(6):625-33. doi: 10.1016/j.healun.2012.02.006.
  
  Caruso Raffaele, Verde Alessandro, Cabiati Manuela, Milazzo Filippo, Boroni Chiara, Del Ry Silvia, Parolini Marina, Vittori Claudia, Paino Roberto, Martinelli Luigi, Giannessi Daniela, Frigerio Maria, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Inflammatory mechanisms are associated with worse prognosis in end-stage heart failure (ESHF) patients who require left ventricular assist device (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles describe patient condition at pre-implant and outcome. This study assessed the relationship among inflammation patterns and INTERMACS profiles in LVAD recipients.
  
  METHOD:
  Thirty ESHF patients undergoing LVAD implantation as bridge to transplant were enrolled. Blood and urine samples were collected pre-operatively and serially up to 2 weeks post-operatively for assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function was evaluated by the total sequential organ failure assessment (tSOFA) score. Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive care unit (ICU) length of stay.
  
  RESULTS:
  Fifteen patients had INTERMACS profiles 1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6 levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6 levels.
  
  CONCLUSIONS:
  The INTERMACS profiles reflect the severity of the pre-operative inflammatory activation and the post-implant inflammatory response, affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may contribute to poor outcome in patients with severe INTERMACS profile.
  
  Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
  
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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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• A case for assessment of oscillatory breathing during cardiopulmonary exercise test in risk stratification of elderly patients with chronic heart failure.
  Int J Cardiol

  2012 Feb;155(1):115-9. doi: 10.1016/j.ijcard.2011.02.033.
  
  Scardovi Angela Beatrice, De Maria Renata, Ferraironi Alessandro, Gatto Laura, Celestini Andrea, Forte Silvia, Parolini Marina, Sciarretta Sebastiano, Ricci Roberto, Guazzi Marco
  
  Abstract
  
  UNLABELLED:
  The prognostic value of exercise oscillatory breathing (EOB) during cardiopulmonary test (CPX) has been described in young chronic heart failure (HF) patients. We assessed the prognostic role of EOB vs other clinical and ventilatory parameters in elderly HF patients performing a maximal CPX.
  
  METHODS AND RESULTS:
  We prospectively followed-up 370 HF outpatients ? 65 years after a symptom limited CPX. We tested the predictive value of clinical and ventilatory parameters for all-cause mortality and a composite of all-cause mortality and HF hospitalizations. Median age was 74 years, 51% had ischemic heart disease, 25% NYHA class III; ejection fraction was 41% [34-50]. Peak oxygen consumption (PVO(2)) was 11.9 [9.9-14] mL/kg/min, the slope of the regression line relating ventilation to CO(2) output, (VE/VCO(2) slope) was 33.9 [29.8-39.2]. EOB was found in 58% of patients. At follow-up, 84 patients died and overall 158, using a time-to-first event approach, met the composite end-point. Independent predictors of all-cause mortality were CPX EOB and the ratio of VE/VCO(2) slope to peak VO(2), hemoglobin, creatinine and body mass index. The area under the ROC curve (AUC) of the Cox multivariable model was 0.80 (95% CI 0.73 to 0.87). Independent predictors of the composite end-point were EOB, VE/VCO(2) slope, hemoglobin and HF admissions in the previous year (Model AUC 0.75) (95% CI 0.69 to 0.81).
  
  CONCLUSIONS:
  Among elderly HF patients, EOB prevalence is higher than middle-aged cohorts. EOB and the ratio of VE/VCO(2) slope to peak VO(2) resulted the strongest ventilatory predictor of all-cause mortality, independent of ventricular function.
  
  Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
  
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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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• Prognostic value of brain natriuretic peptide and enhanced ventilatory response to exercise in patients with chronic heart failure.
  Intern Emerg Med

  2008 Dec;3(4):331-7. doi: 10.1007/s11739-008-0163-x.
  
  Scardovi Angela Beatrice, De Maria Renata, Celestini Andrea, Coletta Claudio, Aspromonte Nadia, Perna Silvia, Parolini Marina, Ricci Roberto
  
  Abstract
  
  Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) 35) was found in 67 patients (43%). During 759 +/- 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO(2) slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.
  
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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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• Myocardial perfusion imaging evidence of functionally complete revascularization by minimally invasive direct coronary artery bypass in 2-vessel coronary artery disease.
  J Nucl Cardiol

  2007 ;14(6):860-8.
  
  De Maria Renata, Repossini Alberto, Dabdoob Wafer, Parolini Marina, Cianci Vincenzo, Bestetti Alberto, Binetti Giorgio, Arena Vincenzo, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Whether patency of a second diseased vessel still impacts myocardial perfusion when complete revascularization of the left anterior descending coronary artery (LAD) territory has been achieved is currently undetermined. In patients with 2-vessel coronary artery disease and complex LAD lesions, we evaluated the impact of single LAD or integrated revascularization on single photon emission computed tomography-assessed reversible myocardial ischemia.
  
  METHODS AND RESULTS:
  Thirty-five candidates for revascularization with double-vessel disease including the LAD and a preoperative stress single photon emission computed tomography study were studied. Revascularization was performed by minimally invasive direct coronary artery bypass (MIDCAB) alone (n = 15) or by an integrated procedure with second-vessel angioplasty, either soon after surgery (n = 13) or at 2 months (n = 7), according to the extent of reversible perfusion defects in the second vessel territory. At 1 year, the total ischemic area decreased from 9.3 +/- 5.1 to 0.8 +/- 1.5 in MIDCAB-only patients and from 8.2 +/- 4.9 to 1.6 +/- 2.9 in the integrated group (P = .87 for treatment and P
  CONCLUSIONS:
  In 2-vessel coronary artery disease involving the LAD, MIDCAB alone achieves, in a substantial proportion of patients, functionally complete revascularization even in the nonrevascularized second vessel territory.
  
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• Multiparametric risk stratification in patients with mild to moderate chronic heart failure.
  J Card Fail

  2007 Aug;13(6):445-51.
  
  Scardovi Angela Beatrice, De Maria Renata, Coletta Claudio, Aspromonte Nadia, Perna Silvia, Cacciatore Giuseppe, Parolini Marina, Ricci Roberto, Ceci Vincenzo
  
  Abstract
  
  BACKGROUND:
  Whether brain natriuretic peptide (BNP) combined with cardiopulmonary exercise test (CPx) and echocardiographic findings improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is unclear.
  
  METHODS AND RESULTS:
  A total of 244 consecutive stable outpatients, median age of 71 (62-76) years, with New York Heart Association (NYHA) Class I-III HF and left ventricular ejection fraction (LVEF) or = 35) was found in 90 patients (37%) During 18 (9-37) follow-up months, 80 patients died or were admitted for worsening HF (33%). In addition to simple bedside clinical variables (NYHA Class III, creatinine clearance, hemoglobin), BNP levels were predictive of outcome (HR 1.35 [1.12-1.63]). However, both RFP (HR 3.36 [2.09-5.41]) and a steeper minute ventilation-carbon dioxide output slope (HR 1.50 [1.19-1.88]) outperformed BNP as prognostic markers. Patients with both RFP and EVR had a 7.30 (95% CI 4.02-13.25) HR for death or HF-admission versus subjects with neither predictor.
  
  CONCLUSIONS:
  This study highlights the importance of a multiparametric approach for optimal risk stratification in the elderly with mild-to-moderate HF. Patients at high risk should undergo closer follow-up and be carefully evaluated for different therapeutic options, including nonpharmacologic treatment.
  
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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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• Long-term outcome of survivors of prolonged intensive care treatment after cardiac surgery.
  Ann Thorac Surg

  2006 Dec;82(6):2080-7.
  
  Mazzoni Maurizio, De Maria Renata, Bortone Franco, Parolini Marina, Ceriani Roberto, Solinas Costantino, Arena Vincenzo, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  The relative impact of perioperative risk profile and postoperative complications on long-term outcome in cardiac surgical patients is currently unclear. The aim of this work was to assess the relative predictive value of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Sequential Organ Failure Assessment (SOFA) on long-term event-free survival in this patient population.
  
  METHODS:
  Preoperative and postoperative variables, EuroSCORE and SOFA, 30-day mortality, and long-term mortality or hospital admission for cardiovascular events were assessed in 115 consecutive cardiac surgical patients in whom multiorgan dysfunction syndrome developed postoperatively.
  
  RESULTS:
  Mean age was 70 +/- 8 years, 41% were women, EuroSCORE averaged 7.87 +/- 3.99, and postoperative stay in the intensive care unit was 10.3 +/- 8.2 days. In-hospital 30-day mortality was 10.4% (n = 12). During 1998 person-months follow-up, 12 (11.6%) of 103 patients discharged alive died, and 46 (44.7%) met the combined end point of all-cause death or cardiovascular admission. By Cox multivariate analysis, maximum SOFA (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.34 to 3.51) and maximum cardiovascular score (HR, 2.35; 95% CI, 1.22 to 4.51) independently predicted all-cause mortality. EuroSCORE (HR, 1.33; 95% CI, 1.01 to 1.76), maximum cardiovascular score (HR 2.09; 95% CI 1.41 to 3.10), and maximum liver score (HR 2.67; 95% CI, 1.46 to 4.86) were independently associated with the combined end point.
  
  CONCLUSIONS:
  High-risk cardiac surgical patients with postoperative multiorgan dysfunction syndrome show excess mortality and cardiovascular morbidity after hospital discharge. Combined preoperative and postoperative risk stratification identifies patients with the highest likelihood of death or early readmission.
  
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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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• [Prognostic value of serial measurements of left ventricular function and exercise performance in chronic heart failure].
  Rev Esp Cardiol

  2006 Sep;59(9):905-10.
  
  Moreo Antonella, de Chiara Benedetta, Cataldo Gabriella, Piccalò Giacomo, Lobiati Elisabetta, Parolini Marina, Frigerio Maria, Ciliberto Guglielma Rita, Mauri Francesco
  
  Abstract
  
  INTRODUCTION AND OBJECTIVES:
  The prognostic value of a single measurement of ejection fraction and peak oxygen uptake in chronic heart failure has been extensively investigated. The aim of our study was to evaluate the prognostic significance of serial changes in ejection fraction and exercise performance in moderate to severe chronic heart failure.
  
  METHODS:
  182 patients (156 men, 53 [47-58] years) underwent echocardiography and cardiopulmonary exercise testing at baseline and after 10 [8-12] months. Most patients had idiopathic dilated cardiomyopathy (69%) and all patients presented left ventricular ejection fraction
  RESULTS:
  During follow-up 18 patients (9.9%) died and 14 (7.7%) underwent heart transplantation. Baseline ejection fraction (HR, 0.94, 95% CI, 0.89-0.98 P=.006) and mitral regurgitation (HR, 4.22, 95% CI, 1.63-10.92, P=.003), and delta (second examination-baseline) ejection fraction (HR, 0.93, 95% CI, 0.88-0.98, P=.01) were the only significant variables at univariate analysis. Both ejection fraction and delta ejection fraction remained independently associated with events at multivariate analysis. The prognostic power significantly increased between a model including ejection fraction alone and another one including ejection fraction plus delta ejection fraction.
  
  CONCLUSIONS:
  In clinically stable patients with chronic heart failure, ejection fraction and its changes were independently associated with outcome; on the contrary, serial cardiopulmonary exercise testing did not provide significant prognostic value. Baseline plus changes in ejection fraction showed better prognostic performance than baseline ejection fraction alone.
  
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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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• An unusual cause of pulmonary edema: acute rupture of noncoronary sinus of valsalva aneurysm into the left atrium.
  J Am Soc Echocardiogr

  2006 Jul;19(7):938.e9-11.
  
  Moreo Antonella, De Chiara Benedetta, Bruschi Giuseppe, Tarelli Giuseppe, Parolini Marina, Mauri Francesco
  
  Abstract
  
  We present the case of a patient admitted to hospital with pulmonary edema and atrial fibrillation. The transthoracic echocardiogram showed noncoronary sinus of Valsalva aneurysm ruptured into the left atrium, with a turbulent flow directed toward the left atrium floor and the pulmonary vein, which explained the clinical presentation. Echocardiography played a crucial role in identification of the cause and correct therapeutic approach.
  
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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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• Early detection of cardiac dysfunction in thalassemic patients by radionuclide angiography and heart rate variability analysis.
  Eur J Haematol

  2005 Jun;74(6):517-22.
  
  De Chiara Benedetta, Crivellaro Wilma, Sara Roberto, Ruffini Livia, Parolini Marina, Fesslovà Vlasta, Carnelli Vittorio, Fiorentini Cesare, Parodi Oberdan
  
  Abstract
  
  BACKGROUND:
  Cardiac dysfunction remains the major cause of death in beta-thalassemia. Aim of this study was to assess early myocardial damage in thalassemic patients with no symptoms or echocardiographic evidence of dysfunction at routine monitoring.
  
  METHODS:
  Twenty patients (seven females; median 25 yr [first quartile 22,third quartile 28]) with beta-thalassemia underwent radionuclide angiography (RNA) at rest and during low-dose dobutamine infusion (5-10 gamma/kg/min). Right and left ventricular ejection fractions (EF) were determined by first-pass method and gated equilibrium acquisition, respectively. Twenty-four-hour Holter monitoring with time-domain heart rate variability (HRV) assessment and echocardiographic follow-up (21 months [5,27]) were performed.
  
  RESULTS:
  Eleven patients showed regional wall motion abnormalities at RNA; left ventricular EF, HR and diastolic measurements significantly increased after dobutamine infusion. Patients with abnormal RNA right ventricular EF (n = 8,
  CONCLUSIONS:
  Right ventricular dysfunction and abnormal HRV may represent the early features of cardiac disease in thalassemic patients with no evidence of ventricular dysfunction at routine evaluation.
  
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• Myofiberbreak-up: a marker of ventricular fibrillation in sudden cardiac death.
  Int J Cardiol

  2005 Apr;100(3):435-41.
  
  Baroldi Giorgio, Silver Malcom D, Parolini Marina, Pomara Cristoforo, Turillazzi Emanuela, Fineschi Vittorio
  
  Abstract
  
  BACKGROUND:
  Electrophysiologically, ventricular fibrillation is defined as a "chaotic, random, asynchronous electrical activity of the ventricles due to repetitive re-entrant excitation and/or rapid focal discharge". To this point its morphological equivalent has not been defined.
  
  MATERIAL AND METHOD:
  Several groups of different diseases and types of accidental death in normal subjects were studied. A complete autopsy was performed and the hearts were examined in 432 cases. A total of 16 myocardial samples per heart were processed for histological examination and sections were stained by haematoxylin and eosin or by specific stains. The frequency, location and extent of myocellular segmentation (stretching and/or rupture) of intercalated discs and associated changes of myocardial bundles and single myocells were investigated. A quantitative analysis was performed and the data were processed for statistical evaluation.
  
  RESULTS:
  The frequency of MFB was maximal in coronary (88%) and Chagas (76%) groups followed by the intracranial brain haemorrhage group (52%). The extent of myofiberbreak-up was maximal in coronary/Chagas groups followed by intracranial haemorrhage and transplant groups.
  
  CONCLUSIONS:
  No correlation was seen between gender, age, heart weight, degree of coronary atherosclerosis, myocardial fibrosis, survival and MFB. If our postulate is correct, finding MFB in the myocardium might allow the diagnosis of a malignant arrhythmia followed by cardiac arrest due to ventricular fibrillation even in the absence of clinical information (sudden death out-of-hospital).
  
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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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• Prognostic value of contractile response during high-dose dipyridamole echocardiography test in heart transplant recipients.
  J Heart Lung Transplant

  2003 May;22(5):526-32.
  
  Ciliberto Guglielma Rita, Parodi Oberdan, Cataldo Gabriella, Mangiavacchi Maurizio, Alberti Antonia, Parolini Marina, Frigerio Maria
  
  Abstract
  
  BACKGROUND:
  Coronary allograft vasculopathy (CAV) remains a main factor limiting long-term survival after heart transplantation (HTX). The diagnosis of CAV is still based on serial coronary angiography. In this study, we evaluated the prognostic value of high-dose dipyridamole echocardiography in HTX.
  
  METHODS:
  Sixty-eight patients underwent dipyridamole echocardiography within 48 hours of their scheduled annual coronary angiography. Coronary allograft vasculopathy was defined as CAV 1 (focal or diffuse stenosis or=50%). Wall-motion score index (WMSI) was evaluated at rest and after dipyridamole administration.
  
  RESULTS:
  Results of coronary angiography were normal in 43 patients (63%), showed CAV 1 in 11 (16%), and showed CAV 2 in 14 (21%). Rest wall motion was normal in 39 patients and abnormal in 29. After dipyridamole administration, wall motion remained normal in all 39 (Group 1, no CAV in 34 and CAV 1 in 5). Of 29 patients with rest wall-motion abnormalities, all reversed to normal after dipyridamole in 8 patients (Group 2, no CAV in 7 and CAV 1 in 1) and remained or worsened in 21 (Group 3, CAV 2 in 14 and no CAV or CAV 1 in 7). During follow-up (6 +/- 3 years), 15 patients had major cardiac events: 11 occurred in Group 3, whereas 4 occurred in Groups 1 and 2. Wall motion at rest and after dipyridamole administration and CAV were independent predictors for cardiac events; only dipyridamole WMSI >1 remained significant (p
  CONCLUSIONS:
  Dipyridamole echocardiography is a simple, non-invasive test that after HTX may identify patients with altered wall motion who deserve stricter surveillance.
  
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• Frequency and extent of contraction band necrosis in orthotopically transplanted human hearts. A morphometric study.
  Int J Cardiol

  2003 Apr;88(2-3):267-78.
  
  Baroldi Giorgio, Silver Malcom D, De Maria Renata, Parolini Marina, Turillazzi Emanuela, Fineschi Vittorio
  
  Abstract
  
  BACKGROUND:
  The aims of the present study are to quantify forms of myocardial and coronary changes found at postmortem and to discuss their significance in relation to causes of death and cardiac arrest in orthotopic transplanted human hearts.
  
  METHODS:
  The examined material included (1) 46 orthotopic transplanted human hearts and, as "controls", hearts from (2) 25 sudden/unexpected coronary death cases, 38 patients with acquired immunodeficiency syndrome, 34 subjects with "silent" Chagas' disease who died suddenly, 27 non cardiac patients who died from intracranial hemorrhage due to a ruptured cerebral aneurysm and 45 healthy subjects dead from head trauma.
  
  RESULTS:
  Contraction band necrosis was observed in 85% of transplanted hearts, 66% of AIDS cases and in 100% Chagas' disease, 89% intracranial hemorrhage, 71% sudden coronary death, and 18% normal head trauma cases. Foci of lymphocytic infiltrate were present in 89% of transplanted heart, 50% AIDS, 100% Chagas' disease, 37% intracranial hemorrage and 64% head trauma groups. An allograft coronary vasculopathy was observed in four transplanted hearts with a survival greater than 202 days. In another 12 cases, who survived more than one year, atherosclerosis was the only coronary lesion found. No relation was observed between coronary lesions of any degree of stenosis and myocardial injuries.
  
  CONCLUSIONS:
  In the group studied acute rejection was the least frequent cause (2%) of graft failure at any time following transplantation and coronary vasculopathy a questionable cause of it in four cases. Rather, contraction band necrosis as an expression of catecholamine myotoxicity seemed to play a role in graft failure related to increased myocardial catecholamine sensitivity after global denervation.
  
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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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