Publications by authors named "Fabrizio Proietti"

32 Publications

PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.

J Cell Mol Med 2020 05 17;24(10):5565-5577. Epub 2020 Apr 17.

Department of Medical Biotechnologies, University of Siena, Siena, Italy.

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.
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http://dx.doi.org/10.1111/jcmm.15213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214180PMC
May 2020

Sacubitril/valsartan: preliminary experience in post-acute stabilized patients with reduced ejection fraction heart failure.

Curr Med Res Opin 2019 03;35(sup1):17-20

a UO Cardiologia , Aurelia Hospital , Rome , Italy.

Introduction: We investigated the effectiveness of sacubitril/valsartan by performing laboratory tests and a 6-minute walking test (6-MWT) at 1 and 6 months after treatment initiation.

Methods: We evaluated patients admitted to our Cardiology Department, stabilized after an episode of acute decompensated heart failure (HF), who were considered eligible for sacubitril/valsartan therapy. Therapy was initiated after interrupting angiotensin-converting enzyme (ACE) inhibitors for at least 36 h or after the last dose of an angiotensin receptor blocker (ARB). In naïve patients, we initiated a low dose of sacubitril/valsartan combination following patient stabilization. Before discharge, a 6-MWT was performed to evaluate patient's functional capacity, measuring total walked distance (in meters), oxygen saturation and heart rate at the beginning and at the end of the test; Borg Scale was applied to evaluate the intensity of dyspnoea. After discharge, follow-up visits at 1 and 6 months, 2D-echocardiography, blood tests and 6-MWT were performed to re-evaluate the efficacy of the treatment.

Results: A total of 14 patients (85.7% males) were included. Mean age was 66.0 ± 10.3 years. Body mass index (BMI) was 29.9 ± 4.7 kg/m. There were no differences in creatinine at admission compared with values at 1 and 6 months. Mean left ventricular ejection fraction (LVEF) was 28.7 ± 4.7% at baseline and increased to 33.5 ± 6.6% and 38.0 ± 2.9% at 1 and 6 months, respectively (p = .028). Total distance covered at 6-MWT increased over the study period (baseline: 227.4 ± 62.8 m; 6 months: 257.3 ± 65.2 m, p = .317) although the increase was not statistically significant.

Conclusions: The present experience showed that angiotensin receptor-neprilysin inhibitor (ARNi) might represent a new valuable therapeutic strategy, even at the earlier stages of stabilized acute HF. Therefore, we suggest a clinical practice algorithm, to consider before discharge, which should be validated by further analyses.
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http://dx.doi.org/10.1080/03007995.2019.1576485DOI Listing
March 2019

Identification of a panel of cytokines in neonates with hypoxic ischemic encephalopathy treated with hypothermia.

Cytokine 2018 11 22;111:119-124. Epub 2018 Aug 22.

Department of Molecular and Developmental Medicine, General Hospital "Santa Maria alle Scotte", University of Siena, Italy.

Purpose: Inflammation is a crucial but understudied mechanism of neuronal injury after hypoxia-ischemia. The aim was to identify a panel of cytokines involved in brain injury in neonates with hypoxic ischemic encephalopathy (HIE).

Methods: Ten newborns with HIE undergoing to therapeutic hypothermia (TH, HIE Group) and 8 healthy newborns (CTRL Group) were enrolled. For the HIE group, 5 samples were collected: between 0 and 6 h of life (time 1), 12 h (time 2), 24 h (time 3), 48 h (time 4) and 96 h of life (time 5). For the CTRL group, one sample was collected. A panel of 48 inflammatory cytokines was determined in all samples. Data were analyzed using multivariate statistical analysis (Principal component analysis, PCA) RESULTS: 17 cytokines, among 48 analyzed, were found to be significantly different, initially, between the CTRL and HIE groups: 12 with reported pro-inflammatory effects and 5 with reported anti-inflammatory effects. In the HIE group cytokines showed a decreasing trend during the TH and at the end of treatment comparable to the CTRL group. IL-18 did demonstrate a slight increase at time 3 during HT but decreased steadily at sampling times, 4 and 5.

Conclusions: Our data demonstrates that many pathways of the inflammatory cascade are activated following hypoxic-ischemic injury. This information will increase our understanding of changes in cytokines over time in neonates with HIE undergoing TH.
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http://dx.doi.org/10.1016/j.cyto.2018.08.011DOI Listing
November 2018

The Free Radical Diseases of Prematurity: From Cellular Mechanisms to Bedside.

Oxid Med Cell Longev 2018 24;2018:7483062. Epub 2018 Jul 24.

Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

During the perinatal period, free radicals (FRs) are involved in several physiological roles such as the cellular responses to noxia, the defense against infectious agents, the regulation of cellular signaling function, and the induction of a mitogenic response. However, the overproduction of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS) which represents a deleterious process and an important mediator of damage to the placenta and the developing fetus. After birth, OS can be magnified by other predisposing conditions such as hypoxia, hyperoxia, ischemia, hypoxia ischemia-reperfusion, inflammation, and high levels of nonprotein-bound iron. Newborns are particularly susceptible to OS and oxidative damage due to the increased generation of FRs and the lack of adequate antioxidant protection. This impairment of the oxidative balance has been thought to be the common factor of the so-called "free radical related diseases of prematurity," including retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, kidney damage, and oxidative hemolysis. In this review, we provide an update focused on the factors influencing these diseases refining the knowledge about the role of OS in their pathogenesis and the current evidences of such relationship. Mechanisms governing FR formation and subsequent OS may represent targets for counteracting tissue damage.
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http://dx.doi.org/10.1155/2018/7483062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081521PMC
October 2018

Regional differences of hypothermia on oxidative stress following hypoxia-ischemia: a study of DHA and hypothermia on brain lipid peroxidation in newborn piglets.

J Perinat Med 2018 Dec;47(1):82-89

Department of Pediatric Research, Institute of Surgical Research, University of Oslo, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Background Oxidative stress plays an important part in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) and is reliably measured through prostanoids following lipid peroxidation of polyunsaturated fatty acids (PUFAs). The aim of the study is to measure oxidative stress in the prefrontal cortex, white matter and hippocampus in the brains of hypoxic-ischemic piglets treated with docosahexaenoic acid (DHA) and therapeutic hypothermia (TH) and investigate the additive effects of DHA on hypothermia by factorial design. Methods Fifty-five piglets were randomized as having severe global hypoxia (n=48) or not (sham, n=7). Hypoxic piglets were further randomized: vehicle (VEH), DHA, VEH+hypothermia (HT) or HT+DHA. A total of 5 mg/kg DHA was given intravenously 210 min after the end of hypoxia. Brain tissues were analyzed using liquid chromatography triple quadrupole mass spectrometry technique (LC-MS). A two-way analysis of variance (ANOVA) was performed with DHA and HT as main effects. Results In the white matter, we found main effects of DHA on DH-isoprostanes (P=0.030) and a main effect of HT on F4-neuroprostanes (F4-NeuroPs) (P=0.007), F2-isoprostanes (F2-IsoPs) (P=0.043) and DH-isoprostanes (P=0.023). In the cortex, the ANOVA analysis showed the interactions of main effects between DHA and HT for neurofuranes (NeuroFs) (P=0.092) and DH-isoprostanes (P=0.015) as DHA significantly reduced lipid peroxidation in the absence of HT. DHA compared to VEH significantly reduced NeuroFs (P=0.019) and DH-isoprostanes (P=0.010). No differences were found in the hippocampus. Conclusion After severe hypoxia, HT reduced lipid peroxidation in the white matter but not in the cortical gray matter. HT attenuated the reducing effect of DHA on lipid peroxidation in the cortex. Further studies are needed to determine whether DHA can be an effective add-on therapy for TH.
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http://dx.doi.org/10.1515/jpm-2017-0355DOI Listing
December 2018

Early Prediction of Hypoxic-Ischemic Brain Injury by a New Panel of Biomarkers in a Population of Term Newborns.

Oxid Med Cell Longev 2018 28;2018:7608108. Epub 2018 Jun 28.

Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

This research paper is aimed at evaluating the predictive role of a default panel of oxidative stress (OS) biomarkers for the early identification of infants at high risk of HIE and their validation through the correlation with MRI findings. A multicenter prospective observational study was performed between March 2012 and April 2015 in two European tertiary NICUs. Eighty-four term infants at risk for HIE (pH < 7, BE < -13 mmol/L, and 5' Apgar < 5) were enrolled. Three were excluded for chromosomal abnormalities and one due to lack of blood samples. The final population was divided according to the severity of perinatal hypoxia into 2 groups: mild/moderate HIE and severe HIE. Advanced oxidation protein products (AOPP), non-protein-bound iron (NPBI), and F2-isoprostanes (F2-IsoPs) were measured in blood samples at P1 (4-6 hours), P2 (24-72 hours), and P3 (5 days), in both groups. MRIs were scored for the severity of brain injury, using a modified Barkovich score. The mean GA was 39.8 weeks (SD 1.4) and the mean birth weight 3538 grams (SD 660); 37 were females and 43 males. Significantly lower 5' Apgar score, pH, and BE and higher Thompson score were found in group II compared to group I at birth. Group II showed significantly higher AOPP and NPBI levels than group I (mean (SD) AOPP: 15.7 (15.5) versus 34.1 (39.2), = 0.033; NPBI 1.1 (2.5) versus 3.9 (4.4), = 0.013) soon after birth (P1). No differences were observed in OS biomarker levels between the two groups at P2 and P3. A regression model, including adjustment for hypothermia treatment, gender, and time after birth, showed that AOPP levels and male gender were both risk factors for higher brain damage scores (AOPP: OR 3.6, 95% CI (1.1-12.2) and gender: OR 5.6, 95% CI (1.2-25.7), resp.). Newborns with severe asphyxia showed higher OS than those with mild asphyxia at birth. AOPP are significantly associated with the severity of brain injury assessed by MRI, especially in males.
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http://dx.doi.org/10.1155/2018/7608108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046131PMC
October 2018

Rooming-in Reduces Salivary Cortisol Level of Newborn.

Mediators Inflamm 2018 8;2018:2845352. Epub 2018 Mar 8.

Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

Background: Rooming-in practice improves breastfeeding and reduces newborn stress reactivity. When this modality is not available, partial rooming-in after birth can be considered. Salivary cortisol levels (SCLs) are considered reliable biomarkers to indicate stress.

Objective: To test the hypothesis that rooming-in duration impacts neonatal stress response in hospitalized newborns.

Design/methods: Forty term newborns, enrolled in the Neonatology and Obstetrics Nursing, C.G. Ruesch, Naples, Italy, were divided, according to the mother's choice, into the study (SG; = 20) and control (CG; = 20) groups if they received full (24 hs) or partial (14 hs) rooming-in care, respectively. Saliva samples were collected from all babies between 7:00 a.m. and 8:00 a.m. of the 3rd day of life by using oral swab. Salivary cortisol levels were measured using an enzyme immunoassay kit (Salimetrics LLC, PA, USA).

Results: A statistically significant difference in the SCLs between SG and CG was found (median: 258 ng/dl versus 488.5 ng/dl; = 0.048).

Conclusions: Data support the practice of full rooming-in care compared with partial rooming-in. The rooming-in duration clearly reduces SCLs and likely neonatal stress. These lower SCLs may have long-term positive effects reducing the risk of metabolic syndrome, high blood pressure, and cognitive and behavioural changes.
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http://dx.doi.org/10.1155/2018/2845352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863308PMC
September 2018

Melatonin Pharmacokinetics Following Oral Administration in Preterm Neonates.

Molecules 2017 Dec 1;22(12). Epub 2017 Dec 1.

Department of Molecular and Developmental Medicine, University of Siena, Viale Bracci, 53100 Siena, Italy.

Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm infants. Preterm newborns were enrolled 24-72 h after birth, and randomly assigned to three groups receiving a single bolus of 0.5 mg·kg melatonin, or 3 boluses of 1 or 5 mg·kg of melatonin at 24-h intervals. Blood samples were collected before and at selective times after melatonin administration. The half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve (AUC) from 10.48 to 118.17 µg·mL·h. Our results indicate a different pharmacokinetic profile in premature newborns, compared to adults and experimental animals. The high peak plasma concentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to obtain and maintain high serum concentrations using a single administration of melatonin repeated every 12/24 h.
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http://dx.doi.org/10.3390/molecules22122115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149762PMC
December 2017

Oxidative Stress Biomarkers: Establishment of Reference Values for Isoprostanes, AOPP, and NPBI in Cord Blood.

Mediators Inflamm 2017 23;2017:1758432. Epub 2017 Apr 23.

Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

Oxidative stress (OS) is a common pathogenic factor involved in the onset of several diseases in humans, from immunologic disorders to malignancy, being a serious public health problem. In perinatal period, OS has been associated with adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are mediated by increased production of free radicals (FRs) following various mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation, mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism. FRs have short half-life, and their measurement in vivo is faced with many challenges. However, oxyradical derivatives are stable and thus may be measured and monitored repeatedly. The quantification of OS is based on the measurement of specific biomarkers in biologic fluids and tissues, which reflect induced oxidative damage to lipids, proteins, and DNA. Prostanoids, non-protein-bound iron (NPBI), and advanced oxidation protein products (AOPP) are actually considered truly specific and reliable for neonatal injury. Defining reference values for these biomarkers is necessary to investigate their role in neonatal diseases or also to evaluate the success of treatments. In this work, we wanted to define laboratory reference values for biomarkers of OS in a healthy population of term newborns.
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http://dx.doi.org/10.1155/2017/1758432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420435PMC
March 2018

DHA Reduces Oxidative Stress after Perinatal Asphyxia: A Study in Newborn Piglets.

Neonatology 2017 1;112(1):1-8. Epub 2017 Feb 1.

Department of Pediatric Research, University of Oslo, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Background: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurological morbidity in infants and children. Oxidative stress due to free radical formation and the initiation of abnormal oxidative reactions appears to play a key role. Docosahexanoic acid (DHA), a main component of brain membrane phospholipids, may act as a neuroprotectant after hypoxia-ischemia by regulating multiple molecular pathways and gene expression.

Objectives: The aims of this study were to test the hypothesis that DHA provides significant protection against lipoperoxidation damage in the cerebral cortex and hippocampus in a neonatal piglet model of severe hypoxia-reoxygenation.

Methods: Newborn piglets, Noroc (LYLD), were subjected to severe global hypoxia. One group was resuscitated with ambient air (21% group, n = 11) and another also received 5 mg/kg of DHA 4 h after the end of hypoxia (21% DHA group, n = 10). After 9.5 h, tissues from the prefrontal cortex and hippocampus were sampled and the levels of isoprostanes, neuroprostanes, neurofurans, and F2-dihomo-isoprostanes were determined by the liquid chromatography triple quadrupole mass spectrometry technique.

Results: Lipid peroxidation biomarkers were significantly lower in both the cortex and hippocampus in the DHA-treated group compared with the untreated group.

Conclusions: The present study demonstrates that DHA administration after severe hypoxia in newborn piglets has an antioxidative effect in the brain, suggesting a protective potential of DHA if given after injuries to the brain.
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http://dx.doi.org/10.1159/000454982DOI Listing
April 2018

Rheumatic Heart Disease Predisposing to Embolic Myocardial Infarction: A Multimodality Imaging Approach.

Int J Angiol 2016 Dec 23;25(5):e4-e7. Epub 2013 Jul 23.

Operative Unit of Cardiology and Cardiac Intensive Care Unit, Aurelia Hospital, Rome, Italy.

We report a clinical case of a 45-year-old male with a diagnosis of inferior myocardial infarction and previous history of rheumatic fever during his childhood. Coronary angiography demonstrated normal coronary arteries. Transthoracic echocardiogram showed hypokinetic left ventricular inferolateral wall and mitral stenosis; furthermore, speckle tracking analysis revealed reduction of global longitudinal strain involving the inferior wall. A three-dimensional transesophaegeal echocardiography, performed to better characterize the anatomy of the valve and to find possible source of embolic infarct in an enlarged left atrium, showed rheumatic valvular involvement. Cardiac magnetic resonance confirmed the ischemic damage and also provided prognostic information. A multimodality imaging approach should be mandatory in patients with acute myocardial infarction and normal coronary angiography, to define possible sources of embolic infarction and to quantify myocardial damage.
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http://dx.doi.org/10.1055/s-0033-1349676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5186263PMC
December 2016

Placental histological examination and the relationship with oxidative stress in preterm infants.

Placenta 2016 10 26;46:72-78. Epub 2016 Aug 26.

Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

Background: Prenatal conditions of enhanced oxidative stress (OS) linked to inflammation or hypoxia have been associated with impaired fetal growth and preterm delivery. Little is known regarding biomarkers of OS in the cord blood of preterm infants and placental histological patterns.

Objectives: To test the hypothesis that placental lesions indicating chorioamnionitis (CA) or vascular underperfusion (VU) are associated with increased OS in the offspring.

Methods: 120 neonates born below 29 weeks of gestational age (GA) were enrolled. Histological characteristics of placentas from their mothers were classified as normal (CTRL group), histological CA (HCA) and vascular underperfusion (VU). Serum concentrations of isoprostanes (IsoPs), non-protein bound iron (NPBI) and advanced oxidative protein products (AOPP), were determined in cord blood.

Results: IsoPs, NPBI and AOPP were significantly increased in HCA group compared to CTRL group. The multivariable regression model, adjusted for GA, maternal age, parity, maternal diabetes, maternal obesity and presence/absence of fetal growth restriction (FGR), showed a significant association between the presence of HCA and increased OS biomarkers levels in cord blood (IsoPs: p = 0.006; NPBI: p = 0.014; AOPP: p = 0.007). Placental VU lesions were significantly associated with higher umbilical IsoPs, NPBI and AOPP levels (IsoPs: p = 0.008; NPBI: p = 0.002; AOPP: p = 0.040). In the cases of placental VU lesions associations were also found between high AOPP levels and low GA (p = 0.002) and the presence of fetal growth restriction (p = 0.014).

Conclusions: Placental lesions indicating inflammation or impaired perfusion are associated with higher cord blood levels of OS biomarkers explaining the fetal susceptibility to oxidative injury and the need of antioxidant protection.
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http://dx.doi.org/10.1016/j.placenta.2016.08.084DOI Listing
October 2016

Antioxidant strategies in genetic syndromes with high neoplastic risk in infant age.

Tumori 2014 Nov-Dec;100(6):590-9

Oxidative stress plays a key role in carcinogenesis. Oxidative damage to cell components can lead to the initiation, promotion and progression of cancer. Oxidative stress is also a distinctive sign in several genetic disorders characterized by a cancer predisposition such as ataxia-telangiectasia, Fanconi anemia, Down syndrome, Beckwith-Wiedemann syndrome and Costello syndrome. Taking into account the link between oxidative stress and cancer, the capacity of antioxidant agents to prevent or delay neoplastic development has been tested in various studies, both in vitro and in vivo, with interesting and promising results. In recent years, research has been conducted into the molecular mechanisms linking oxidative stress to the pathogenesis of the genetic syndromes we consider in this review, with the resulting identification of possible new therapeutic targets. The aim of this review is to focus on the oxidative mechanisms intervening in carcinogenesis in cancer-prone genetic disorders and to analyze the current status and future prospects of antioxidants.
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http://dx.doi.org/10.1700/1778.19256DOI Listing
May 2015

A metabolomic study of preterm and term human and formula milk by proton MRS analysis: preliminary results.

J Matern Fetal Neonatal Med 2014 Oct;27 Suppl 2:27-33

Department of Molecular and Developmental Medicine, University of Siena , Siena , Italy and.

Objective: To investigate changes in global metabolic profile between: 1 - breast milk and formula milk, 2 - breast milk from mothers delivering at different gestational age (GA) collected within one week from delivery, and then week by week until term equivalent age.

Methods: Proton magnetic resonance spectroscopy (MRS) was used to analyze the water-soluble and lipid fractions extracted from 50 milk samples, 46 human milk at different GA, from 23 weeks of gestation until term equivalent age and four different formula milks.

Results: The formula milk for premature infants was the most similar to breast milk of preterm babies. Breast milk showed higher lactose concentrations than formula milk, that conversely presented higher galactose 1-phosphate and maltose concentrations. Mother's milk of very preterm babies (23-25 wks of GA) showed a different metabolic profile from preterm infants ≥29 wks of GA with a subsequent trend to similarity around the 30th week of post-natal age. Breast milk from preterm infants of 29-34 wks, collected up to 40 wks of post-natal age showed a temporal change over the first three weeks of lactation, approaching to zero with the achievement of term age.

Conclusions: Metabolome is a promising tool to study human and artificial milk global metabolic profile.
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http://dx.doi.org/10.3109/14767058.2014.955958DOI Listing
October 2014

Melatonin reduces endoplasmic reticulum stress and preserves sirtuin 1 expression in neuronal cells of newborn rats after hypoxia-ischemia.

J Pineal Res 2014 Sep 15;57(2):192-9. Epub 2014 Jul 15.

Department of Biomolecular Sciences, University of Urbino 'Carlo Bo', Urbino, Italy.

Conditions that interfere with the endoplasmic reticulum (ER) functions cause accumulation of unfolded proteins in the ER lumen, referred to as ER stress, and activate a homeostatic signaling network known as unfolded protein response (UPR). We have previously shown that in neonatal rats subjected to hypoxia-ischemia (HI), melatonin administration significantly reduces brain damage. This study assessed whether attenuation of ER stress is involved in the neuroprotective effect of melatonin after neonatal HI. We found that the UPR was strongly activated after HI. Melatonin significantly reduced the neuron splicing of XBP-1 mRNA, the increased phosphorylation of eIF2α, and elevated expression of chaperone proteins GRP78 and Hsp70 observed after HI in the brain. CHOP, which plays a convergent role in the UPR, was reduced as well. Melatonin also completely prevented the depletion of SIRT-1 induced by HI, and this effect was observed in the same neurons that over-express CHOP. These results demonstrate that melatonin reduces ER stress induced by neonatal HI and preserves SIRT-1 expression, suggesting that SIRT-1, due to its action in the modulation of a wide variety of signaling pathways involved in neuroprotection, may play a key role in the reduction of ER stress and neuroprotection observed after melatonin.
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http://dx.doi.org/10.1111/jpi.12156DOI Listing
September 2014

Increased autophagy reduces endoplasmic reticulum stress after neonatal hypoxia-ischemia: role of protein synthesis and autophagic pathways.

Exp Neurol 2014 May 12;255:103-12. Epub 2014 Mar 12.

Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Via S. Chiara 27, 61029 Urbino, Italy. Electronic address:

The endoplasmic reticulum (ER) stress can result from several pathological conditions that perturb ER homeostasis and is characterized by accumulation of unfolded proteins in the ER lumen. To cope with ER stress, cells activate the unfolded protein response (UPR), a protein quality control mechanism aimed at restoring homeostasis. The present study was undertaken to characterize the UPR after neonatal hypoxia/ischemia (HI) and its crosstalk with autophagy. After HI, there was a significant increase of GRP78 and Hsp70 expression, phosphorylation of eIF2α, Xbp-1 mRNA splicing and CHOP expression, revealing severe ER stress and UPR. Increasing autophagy with rapamycin (Rap) significantly reduced the UPR. Rap did not further increase the eIF2α phosphorylation and p70S6 kinase (p70S6K) inactivation induced by HI. After autophagy activation, however, there was a clear co-localization between monodansylcadaverine (MDC)-positive autophagosome-like structures and the ribosomal protein S6 (RPS6), indicating the presence of ribosomes in autophagosomes (ribophagy). We found that the autophagy inhibitor 3-methyladenine administered after Rap treatment completely reverted the increased phosphorylation of eIF2α and p70S6K inactivation, and blocked the formation of autophagosome-like structures restoring the UPR. These results demonstrate that the UPR is strongly activated after neonatal HI. Over-activation of autophagy significantly reduces this response, highlighting the relevance of the cross-talk between ER and the autophagy machinery in this important pathological condition. Furthermore, the presence of ribosome subunits in autophagosome-like structures suggests that increased ribosome turnover through autophagy (ribophagy) may represent an additional mechanism involved in the neuroprotective effect observed after autophagy over-activation.
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http://dx.doi.org/10.1016/j.expneurol.2014.03.002DOI Listing
May 2014

A rare case of concurrent multichamber thrombosis complicated by cardioembolic stroke in a reversible postpartum thyrotoxic cardiomyopathy.

BMJ Case Rep 2013 Mar 7;2013. Epub 2013 Mar 7.

Operative Unit of Cardiology and Intensive Care, Aurelia Hospital, Rome, Italy.

We describe a rare case of cardiac multichamber thrombosis in a young woman admitted with heart failure and atrial fibrillation, who was later found to have reversible postpartum thyrotoxic cardiomyopathy. A transoesophageal echocardiogram demonstrated a patent foramen ovalis with an over-riding thrombus. The clinical scenario was complicated by a cardioembolic stroke upon spontaneous restoration of sinus rhythm.
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http://dx.doi.org/10.1136/bcr-2012-008452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618705PMC
March 2013

Antioxidant effects of potassium ascorbate with ribose in costello syndrome.

Anticancer Res 2013 Feb;33(2):691-5

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Viale Mario Bracci 36, 53100, Siena, Italy.

Background: Costello syndrome is a rare genetic condition characterized by coarse facies, short stature, loose folds of skin especially on hands and feet, severe feeding difficulties and failure to thrive. Other features include cardiac anomalies, developmental disability and increased risk of neoplasms. Given the link between oxidative stress (OS) and carcinogenesis, we tested the hypothesis that OS occurs in this syndrome, supposing its role both in cancer development and in other clinical features.

Patients And Methods: We describe four cases with Costello syndrome in which we verified the presence of OS by measuring a redox biomarker profile including total hydroperoxides, non-protein-bound iron, advanced oxidation protein products, thyols, carbonyl groups and isoprostanes. Thus, we introduced an antioxidant agent, namely potassium ascorbate with ribose (PAR) into the therapy and monitored the redox profile every three months to verify its efficacy.

Results: A progressive decrease in OS biomarkers occurred, together with an improvement in the clinical features of the patients.

Conclusion: OS was proven in all four cases of Costello syndrome. The antioxidant therapy with PAR demonstrated positive effects. These promising results need further research to confirm the relevance of OS and the efficacy of PAR therapy in Costello syndrome.
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February 2013

Resuscitation with supplementary oxygen induces oxidative injury in the cerebral cortex.

Free Radic Biol Med 2012 Sep 24;53(5):1061-7. Epub 2012 Jul 24.

Department of Pediatric Research, University of Oslo, Oslo University Hospital, Rikshospitalet, N-0424 Oslo, Norway.

Isoprostanes, neuroprostanes, isofurans, and neurofurans have all become attractive biomarkers of oxidative damage and lipid peroxidation in brain tissue. Asphyxia and subsequent reoxygenation cause a burst of oxygen free radicals. Isoprostanes and isofurans are generated by free radical attacks of esterified arachidonic acid. Neuroprostanes and neurofurans are derived from the peroxidation of docosahexanoic acid, which is abundant in neurons and could therefore more selectively represent oxidative brain injury. Newborn piglets (age 12-36 h) underwent hypoxia until the base excess reached -20 mmol/L or the mean arterial blood pressure dropped below 15 mm Hg. They were randomly assigned to receive resuscitation with 21, 40, or 100% oxygen for 30 min and then ventilation with air. The levels of isoprostanes, isofurans, neuroprostanes, and neurofurans were determined in brain tissue (ng/g) isolated from the prefrontal cortex using gas chromatography-mass spectrometry (GC/MS) with negative ion chemical ionization (NICI) techniques. A control group underwent the same procedures and observations but was not submitted to hypoxia or hyperoxia. Hypoxia and reoxygenation significantly increased the levels of isoprostanes, isofurans, neuroprostanes, and neurofurans in the cerebral cortex. Nine hours after resuscitation with 100% oxygen for 30 min, there was nearly a 4-fold increase in the levels of isoprostanes and isofurans compared to the control group (P=0.007 and P=0.001) and more than a 2-fold increase in neuroprostane levels (P=0.002). The levels of neuroprostanes and neurofurans were significantly higher in the piglets that were resuscitated with supplementary oxygen (40 and 100%) compared to the group treated with air (21%). The significance levels of the observed differences in neuroprostanes for the 21% vs 40% comparison and the 21% vs 100% comparison were P<0.001 and P=0.001, respectively. For neurofurans, the P values of the 21% vs 40% comparison and the 21% vs 100% comparison were P=0.036 and P=0.025, respectively. Supplementary oxygen used for the resuscitation of newborns increases lipid peroxidation in brain cortical neurons, a result that is indicative of oxidative brain damage. These novel findings provide new knowledge regarding the relationships between oxidative brain injury and resuscitation with oxygen.
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http://dx.doi.org/10.1016/j.freeradbiomed.2012.07.022DOI Listing
September 2012

Is newborn melatonin production influenced by magnetic fields produced by incubators?

Early Hum Dev 2012 Aug 14;88(8):707-10. Epub 2012 Mar 14.

Department of Pediatrics, Obstetrics and Reproduction Medicine, University of Siena, Viale M. Bracci 16, Siena, Italy.

Background: During permanence in most incubators, newborns are very close to the electric engine, which represents a source of electromagnetic fields (EMF). Previous studies demonstrated a decrease in melatonin production in adults and animals exposed to EMF.

Aims: To assess melatonin production in a group of newborns exposed to EMF, and to evaluate whether removing the babies from the source of MF can affect melatonin production.

Study Design And Subjects: We have recruited 28 babies (study group), who had spent at least 48 h in incubator where we had previously assessed the presence of significant EMF. We have measured their mean 6-hydroxy-melatonin-sulfate (6OHMS) urine excretion at the end of their permanence in the incubators, and compared it with their mean 6OHMS excretion after having been put in cribs, where EMF are below the detectable limit (<0.1mG). We have also measured urine 6OHMS twice, with an interval of 48h, in a control group of 27 babies who were not exposed to EMF during both samples.

Results: Mean 6OHMS/cr values were respectively 5.34±4.6 and 7.68±5.1ng/mg (p=0.026) when babies were exposed to EMF in incubators, and after having been put in the crib. In the control group, mean 6OHMS/cr values in the first and in the second sample were respectively 5.91±5.41 vs 6.17±3.94ng/mg (p=0.679).

Conclusions: The transitory increase in melatonin production soon after removing newborns from incubators demonstrates a possible influence of EMF on melatonin production in newborns. Further studies are needed to confirm these data.
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http://dx.doi.org/10.1016/j.earlhumdev.2012.02.015DOI Listing
August 2012

Development of a fast and simple LC-MS/MS method for measuring the F2-isoprostanes in newborns.

J Matern Fetal Neonatal Med 2012 Apr;25 Suppl 1:114-8

AB Sciex, Brugherio, Italy.

Background: Quantification of F(2)-IsoPs isomer has been regarded as the "gold standard" to assess oxidative stress status in various adult and neonatal human diseases. These methods require high amounts of plasma.

Objective: To develop a fast and simple LC-MS/MS method for measuring F(2)-isoprostanes in newborns.

Methods: A sample of heel blood (0.4 mL) was collected in a tube containing EDTA was collected from 20 term healthy newborns. For measurements, the tandem mass spectrometer has been run in multiple reaction monitoring (MRM) with the electrospray source operating in negative ion mode, and by exploiting the transitions m/z 353.3 > 193.2 for F2-IsoPs and 357.3 > 197.2 for the internal standard d4-8-iso PGF2α.

Results: The concentration of F(2)-IsoPs (in pg/mL) in the collected cord bloods was 60.50 ± 25.04 (mean ± S.D.). No statistical difference was found between male (57.09 ± 19.69) and female (64.67 ± 31.13) concentrations. The overall efficiency of the extraction has been over 80%, while the recovery on spiked samples has been around 94% for spikes of 100 pg/mL with a C.V. of 7.7%.

Conclusions: We developed a suitable method for large-scale studies with a reduced sample requirement as it is mandatory in neonatal age. Small samples and quick answers are very useful in Neonatology allowing early diagnosis and preventive treatments' strategies of free radical related diseases of the newborn.
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http://dx.doi.org/10.3109/14767058.2012.664856DOI Listing
April 2012

May oxidative stress biomarkers in cord blood predict the occurrence of necrotizing enterocolitis in preterm infants?

J Matern Fetal Neonatal Med 2012 Apr 6;25 Suppl 1:128-31. Epub 2012 Mar 6.

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy.

Introduction: Oxidative stress (OS) is strongly involved in the pathogenesis of many preterm newborn diseases; this is due to the low efficiency of neonatal antioxidant systems unable to counteract the harmful effects of free radicals (FRs). Hypoxic-ischemic events and inflammation, involved in necrotizing enterocolitis (NEC) pathogenesis, are responsible of the overproduction of FRs, generating OS.

Aim: To test the hypotesis that OS markers levels in cord blood may early identify the newborns at high risk to develop NEC.

Materials And Methods: 332 preterm newborns of gestational age (GA) between 24 and 33 week and birth weight (BW) between 460 and 2540 g were consecutively recruited in three european neonatal intensive care units. Markers of potential OS risk: non-protein bound iron (NPBI), and markers of FRs damage: advanced oxidation protein products (AOPP) and total hydroperoxides (TH), were measured in the cord blood. Associations between NEC and OS markers were checked through inferential analysis.

Results: Out of 332 preterm babies, 29 developed NEC. Babies with NEC had a BW and a GA significantly lower than healthy babies. AOPP, TH and NPBI cord blood levels were significantly higher in babies with NEC than in babies without (respectively mean AOPP = 28.05 ± 21 vs 15.80 ± 7.14; p < 0.05; TH = 154.48 ± 84.67 vs 107.40 ± 61.01; p < 0.05; NPBI = 2.21 ± 3.98 vs 0.95 ± 1.59; p < 0.05).

Conclusions: The determination of OS biomarkers in cord blood can be useful in identifying babies at high risk for NEC and in devising new strategies to ameliorate perinatal outcome.
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http://dx.doi.org/10.3109/14767058.2012.663197DOI Listing
April 2012

Beckwith-Wiedemann syndrome: potassium ascorbate with ribose therapy in a syndrome with high neoplastic risk.

Anticancer Res 2011 Nov;31(11):3973-6

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Viale Mario Bracci 36, 53100 Siena, Italy.

Background: Beckwith-Wiedemann Syndrome (BWS) is a genomic imprinting disorder characterized by overgrowth and increased risk of malignancy. We studied the oxidative stress (OS) pattern of our patients with BWS and administered, for the first time, potassium ascorbate with ribose (PAR) once a day as long-term therapy in order to correct the effects induced by free radicals.

Patients And Methods: We describe the clinical features of three patients examined every three months in our clinic. OS was ascertained by measuring a panel of OS biomarkers: non-protein-binding iron, total hydroperoxides, advanced oxidation protein products, isoprostanes, carbonyl groups and thiols. After the presence of OS was established, treatment with PAR was started at the dosage of 300 mg of Potassium Bicarbonate and 150 mg of Ascorbic Acid in aqueous solution and changes occurring in OS biomarkers were followed dosing every three months.

Results: Our patients showed higher levels of OS biomarkers than controls at the time of diagnosis. There was a reduction in OS biomarker values for all three patients with treatment. No primary or secondary neoplastic disease was observed in 9 months of follow-up.

Conclusion: This is the first report showing OS occurring in BWS. No drug until this report has been published showing efficacy against OS in any cancer. Given the limited number of patients, care must be taken to mitigate enthusiasm. We are collecting data for a large number of BWS patients to confirm these preliminary results.
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November 2011

[Feasibility and safety of immediately returning patients transferred for percutaneous coronary intervention in a large metropolitan area].

G Ital Cardiol (Rome) 2010 Oct;11(10):783-8

U.O. di Cardiologia Interventistica, Dipartimento di Scienze Cardiovascolari, European Hospital, Roma.

Background: Hospitals without percutaneous coronary intervention (PCI) capabilities are used to transfer patients who need coronary angiography and/or PCI to other centers. In order to optimize economic resources and hospital bed management, PCIs might be performed with an in-service organization, with re-transfer to the community hospital immediately after the procedure. The aim of our study was to evaluate the safety of a consecutive, unselected series of in-service PCIs compared to PCIs performed in patients admitted to hospitals with cath-lab capabilities.

Methods: During 2008, 1030 PCI procedures were performed at the European Hospital and Aurelia Hospital: 905 in patients admitted to a hospital with PCI capabilities (Group I) and 125 (12%) with an in-service strategy (Group II) referring from the Città di Roma Hospital. All treatment protocols were preventively uniformed and standardized.

Results: The two groups were statistically comparable in terms of baseline clinical characteristics and/or procedural findings, with the exception for older age (66 +/- 10 vs 70 +/- 10 years, p = 0.004) and a higher prevalence of acute coronary syndromes (56 vs 88%, p < 0.001) and femoral vascular access (94 vs 98%, p = 0.03) in Group II. The rate of left ventricular ejection fraction < or = 35% (20 vs 13%, p = 0.06), multivessel PCI (23 vs 19%, p = 0.4), and glycoprotein IIb/IIIa inhibitor use (15 vs 13%, p = 0.5) was similar between the two groups. Among patients treated with an in-service strategy, 2 (1.6%) were not transferred to the community hospital, because of hemodynamic instability. The in-hospital rate of major clinical events (death for cardiovascular causes, cerebrovascular events, urgent revascularization, stent thrombosis) was 0.75% and 0.8% (p = 0.8), 1.8% and 1% (p = 0.4) for periprocedural myocardial infarction, 1.7% and 1.9% (p = 0.5) for major bleeding, 1.1% and 1.6% (p = 0.6) for vascular complications, in Group I and II, respectively. Left ventricular dysfunction was the only independent predictor of major clinical events (p = 0.003).

Conclusions: A strategy of in-service organization for PCI presents a similar rate of in-hospital clinical events and complications compared to an overnight stay into a hospital with PCI capabilities. Such a strategy may be utilized in order to optimize economic resources and hospital bed management.
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October 2010

Isoprostane levels in urine of preterm newborns treated with ibuprofen for patent ductus arteriosus closure.

Pediatr Nephrol 2011 Jan 15;26(1):105-9. Epub 2010 Oct 15.

Department of Pediatrics, Obstetrics and Reproductive Medicine, Division of Neonatology, University of Siena, Siena, Italy.

Patent ductus arteriosus (PDA) is the most common cardiovascular abnormality of the preterm infant usually treated with ibuprofen (IBU). PDA is strictly related to oxidative stress (OS) in neonates. This study tests the hypothesis that OS occurs in neonates with PDA and that IBU treatment reduces OS. Forty-three preterm babies with gestational age (GA) <33 weeks were studied prospectively. Three urine samples were collected: at time 0 (before starting treatment), time 1 (after pharmacological PDA closure), and time 2 (7 days after the end of treatment) in all patients. OS was studied by measuring urinary isoprostane (IPs) levels. The results showed significant changes in urinary IP levels from time 0 to time 2 (Kruskal-Wallis, p=0.047). Time trend showed a significant decrease in IPs from time 0 to time 1 after IBU therapy (p=0.0067). This decrease was followed by an increase in IPs levels 7 days after treatment. IBU therapy for PDA closure reduced the risk of OS related to free-radical (FR) generation. This antioxidant effect of IBU may be beneficial in preterm babies with PDA who are at high risk for OS.
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http://dx.doi.org/10.1007/s00467-010-1651-6DOI Listing
January 2011

Oxidative stress in children affected by epileptic encephalopathies.

J Neurol Sci 2011 Jan 6;300(1-2):103-6. Epub 2010 Oct 6.

Department of Pediatrics, Obstetrics, Gynecology and Reproductive Medicine, University of Siena, Viale M. Bracci, 53100, Siena, Italy.

Oxidative stress may lead to abnormal peroxidation of membrane lipids, oxidation of sulfhydryl groups and disruption of nucleic acids. Experimental and clinical studies suggested that free radicals may be involved in the pathogenesis of epilepsy. Three groups of patients were considered in the study. Group 1 (N=34) included patients affected by epileptic encephalopathy; Group 2 (N=31) included those affected by idiopathic epilepsy syndromes and under valproic acid (VPA) monotherapy, and Group 3 (N=22) represented by healthy controls. All patients and healthy children underwent blood withdrawals to evaluate redox status by measuring levels of F2-isoprostanes (F2-iso), advanced oxidative protein products (AOPP), non-protein binding iron (NPBI), thiols (-SH groups), and total hydroperoxides (TH). In comparison to the controls, Group 1 patients showed significantly higher plasma levels of F2-iso, AOPP, and TH. By contrast, no differences there were in the plasma NPBI concentrations. Again, no statistical differences there were in the plasma levels of the oxidative stress markers between patients from Group 2 and normal subjects. Our study showed that patients with epileptic encephalopathy have increased levels of oxidative stress markers. By contrast, normal redox status was observed in patients with idiopathic epilepsy syndromes under long-term VPA monotherapy.
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http://dx.doi.org/10.1016/j.jns.2010.09.017DOI Listing
January 2011

Oxidative damage induced by herbicides is mediated by thiol oxidation and hydroperoxides production.

Free Radic Res 2010 Aug;44(8):891-906

Dipartimento di Biologia Molecolare, Università degli Studi di Siena, via Fiorentina 1, 53100 Siena (SI), Italy.

Toxicological and environmental issues are associated with the extensive use of agricultural pesticides, although the knowledge of their toxic effects as commercial formulations is still far from being complete. This work investigated the impact of three herbicides as commercial formulations on the oxidative status of a wild type Saccharomyces cerevisiae strain. With yeast being a well-established model of eukaryotic cells, especially as far as regards the stress response, these results may be indicative of potential damages on higher eukaryotes. It was found that herbicide-mediated toxicity towards yeast cells could be the result of an increased production of hydroperoxides (like in the case of the herbicides Pointer and Silglif) or advanced oxidation protein products and lipid peroxidation (especially in the case of the herbicide Proper Energy). Through a redox-proteomic approach it was found also that, besides a common signature, each herbicide showed a specific pattern for protein thiols oxidation.
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http://dx.doi.org/10.3109/10715762.2010.489111DOI Listing
August 2010

Effects of epidural and systemic maternal analgesia in term infants: the NoPiL study.

Front Biosci (Elite Ed) 2010 Jun 1;2:1514-9. Epub 2010 Jun 1.

Department of Surgical and Medical Critical Care, Section of Neonatology, University Hospital of Florence, Florence, Italy.

The aim of the No Pain in Labour (NoPiL) study was to evaluate the stress and clinical outcome of infants vaginally born without maternal analgesia and after maternal epidural or systemic analgesia. We studied 120 healthy term infants, 41 in the no analgesia group, 38 in the epidural analgesia group, and 41 in the systemic analgesia group. Cortisol, beta-endorphin, oxidative stress markers (ie: total hydroperoxide (TH) and advanced oxidation protein products (AOPP)), interleukin-1beta (IL-1beta), and interleukin-8 (IL-8) cytokines were measured in arterial cord blood samples. Infants in the 3 groups had similar Apgar score, cord blood pH and occurrence of hypoglycaemia, hyperbilirubinemia, and respiratory depression. Cortisol and endorphin plasma levels did not differ in the groups, nor did TH and AOPP values. IL-1beta and IL-8 cytokine were higher in infants born after maternal epidural analgesia than in other groups. Short-term outcome and stress were similar in infants vaginally born without maternal analgesia and after epidural and systemic analgesia. The possible implications of the highest interleukin levels in the epidural analgesia group deserve further study.
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http://dx.doi.org/10.2741/e210DOI Listing
June 2010

Early identification of the risk for free radical-related diseases in preterm newborns.

Early Hum Dev 2010 Apr 13;86(4):241-4. Epub 2010 May 13.

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy.

Background: Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as 'free radical-related diseases' (FRD).

Aim: This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients And Methods: 168 preterm newborns of GA: 24-32weeks (28.09+/-1.99); and BW: 470-2480 gr (1358.11+/-454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results: The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p=0.000, OR=1.025, 95%CI=1.013-1.038; p=0.014, OR=1.092, 95%CI=1.018-1.172; p=0.007, OR=1.26995%CI=1.066-1.511).

Conclusions: Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.
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http://dx.doi.org/10.1016/j.earlhumdev.2010.03.008DOI Listing
April 2010

Effects of lutein on oxidative stress in the term newborn: a pilot study.

Neonatology 2010 7;97(1):36-40. Epub 2009 Jul 7.

Division of Neonatology, Department of Pediatrics, Obstetrics and Reproductive Medicine, Policlinico Le Scotte University of Siena, Siena, Italy.

Background: Oxidative stress (OS) plays a crucial role in pathological conditions during the early neonatal period. The newborns are susceptible to oxidative damage due to high metabolic rate and low levels of antioxidant enzymes. Lutein has been found to have protective functions in adult humans as antioxidant.

Aim: To evaluate the effects of lutein on OS in newborns. We tested the hypothesis that lutein would act both by increasing antioxidant capacity and inhibiting OS.

Methods: This was a randomized, double-blind, placebo-controlled, single-center study. 20 healthy term newborns were assigned to receive lutein or placebo (lutein and control group, respectively) at 12 and 36 h after birth. Total hydroperoxides (TH), as marker of OS, and biological antioxidant potential (BAP), as marker of antioxidant power, were detected on cord blood and at 48 h of life in all babies.

Results: TH significantly increased from birth to 48 h in the control group (p = 0.02), but not in the lutein group. In the lutein group, BAP significantly increased after 48 h (p = 0.02), showing a strengthening of antioxidant activity due to lutein. At 48 h of life, compared with those in the control group, neonates assigned to receive lutein had significantly lower TH levels (p = 0.04) and higher BAP levels (p = 0.028).

Conclusions: Lutein administration in newborns increases the levels of BAP decreasing TH. The enhancement of antioxidant activity in plasma clearly results in protecting newborn from perinatal OS. These preliminary results, adding a new contribution in antioxidant strategies, strongly require to be confirmed by RCT.
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http://dx.doi.org/10.1159/000227291DOI Listing
March 2010