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Highlights • The article refers to the implementation of a disinfection protocol for neonatal incubators in a "Neonatal Pediatric Unit". • Neonatal incubators have been recognized as a source of microorganisms potentially involved in the diffusion of HAIs. • A proper use of disinfectants and the education of the cleaning staff are essential for an effective disinfection protocol. Abstract Background The role of environmental cleaning as an effective measure to contain the diffusion of Healthcare Associated Infections (HAIs) has already been demonstrated. Among medical devices, neonatal incubators have been recognized as a source of pathogens involved in the spread of HAIs. Aim of the study was to assess the efficacy of a disinfection protocol for neonatal incubators. Methods The cross sectional study took place in the "Neonatal Pediatric Unit" of the Teaching Hospital of Siena: twenty incubators, used for critical newborns, were swabbed in 13 sampling points before and after the implementation of the disinfection protocol. Sanitation procedures were performed by trained staff, implementing the product Umonium38® Neutralis as disinfectant. Different culture media for the identification of the microbial contamination were adopted: plates were incubated for the proper time and the results were referred to Colony Forming Units (CFUs)/swab per point. Descriptive statistical analysis was performed. It was also evaluated the 95% confidence interval (C.I.) of the mean and the percentage of CFUs reduction by the bootstrap bias corrected and accelerated resampling method. Results Matched points analyzed were 313. The average CFUs percentage of reduction was 93.5% [C.I. 90.6–95.9%]: it was higher, 97.0% [C.I. 94.1–99.1%], in points placed inside the incubators structure compared to the 88.4% [C.I. 83.6–93.0%] obtained outside. Conclusion The disinfection protocol achieved good results. Routine surveillance and supervision of the various aspects of the disinfection processes (procedures, staff and disinfectants) could guarantee a safe environment during the first days of babies' life, avoiding harmful conditions for the newborns' health. [ABSTRACT FROM AUTHOR]

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+6 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. [ABSTRACT FROM AUTHOR]

Summary: Oxygen has a central role in the evolution of complex life on Earth mainly because of the biochemical symmetry of oxygenic photosynthesis and aerobic respiration that can maintain homeostasis within our planet biosphere. Oxygen can also produce toxic molecules, reactive oxygen species (ROS). ROS is a collective term that includes both oxygen radicals and certain oxidizing agents that are easily converted into radicals. They can be produced from both endogenous and exogenous substances. ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. They can be considered a double-edged sword because on the one hand oxygen-dependent reactions and aerobic respiration have significant advantages but, on the other, overproduction of ROS has the potential to cause damage. [Copyright &y& Elsevier]

Summary: Oxidative stress plays an important role in causing organ injury in the compromised fetus and neonate. Recent experimental research and clinical studies have clarified important pathways in the production of reactive oxygen and nitrogen species. Free radicals are involved in causing cerebral damage after perinatal hypoxia–ischemia affecting membrane lipids, proteins, and DNA. Anti-oxidant strategies can be used as add-on neuroprotective therapy after perinatal oxidative stress. Selective inhibitors of neuronal and inducible nitric oxide synthase, allopurinol, melatonin, and erythropoietin are among the first compounds that are ready for clinical trials. [Copyright &y& Elsevier]

Perinatal oxidative stress (OS) is involved in the physiopathology of many pregnancy-related disorders and is largely responsible for cellular, tissue and organ damage that occur in the perinatal period especially in preterm infants, leading to the so-called "free-radicals related diseases of the newborn". Reliable biomarkers of lipid, protein, DNA oxidation and antioxidant power in the perinatal period have been demonstrated to show specificity for the disease, to have prognostic power or to correlate with disease activity. Yet potential clinical applications of oxidative stress biomarkers in neonatology are still under study. Overcoming the technical and economic difficulties that preclude the use of OS biomarkers in the clinical practice is a challenge that needs to be overcome to identify high-risk subjects and to predict their short- and long-term outcome. Cord blood, urine and saliva represent valid and ethically acceptable biological samples for investigations in the perinatal period. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is characterized by multiple metabolic processes to allow proper foetal development and ensure adequate stores. Little is known about the interactions between maternal and foetal metabolism during the last phase of pregnancy. Metabolomic offers potential to discover changes in maternal metabolism in pregnancy and their relation to the newborn metabolic status.Objective: In this study we tested the hypothesis that metabolomic status in newborns at birth depends upon the metabolomic profile of their mothers in the last phase of pregnancy.Study Design: Urine samples were collected from 36 pregnant women three weeks before delivery and from 21 healthy term newborns within 48 h after birth. Urines were analysed using proton nuclear magnetic resonance (1H NMR) spectroscopy and NMR urine spectra were evaluated through Principal Components Analysis.Results: The first component of the PCA analysis showed two distinct metabolic groups: pregnant women and newborns. A significant correlation was found between urine metabolic profiles of newborns and those of their mothers.Conclusion: Urine metabolomic profiles of newborns at birth mirrors that of their mothers in the last phase of pregnancy. The metabolomic approach appears to be crucial to understand the maternal effects on foetal programming and infant outcomes. [ABSTRACT FROM AUTHOR]

The dynamic field of perinatology entails ever-increasing search for molecular mechanisms of neonatal diseases, especially in the domain of fetal growth and neurodevelopmental outcome. There is an urgent need for new molecular biomarkers, to early identify newborn at high risk for developing diseases and to provide new treatment targets. The interest in biomarkers of oxidative stress in perinatal period have begun to grow in the last century, when it was evidenced the importance of the free radicals generation underlying the various disease conditions. To date, interesting researches have been carried out, representing milestones for implementation of oxidative stress biomarkers in perinatal medicine. Use of a panel of "oxidative stress biomarkers", particularly non protein bound iron, advanced oxidative protein products and isoprostanes, may provide valuable information regarding functional pathways underlying free radical mediated diseases of newborns and their early identification and prevention. Here, we will review recent advances and the current knowledge on the application of biomarkers of oxidative stress in neonatal/perinatal medicine including novel biomarker discovery, defining yet unrecognized biologic therapeutic targets, and linking of oxidative stress biomarkers to relevant standard indices and long-term outcomes. Image 1 • Oxidative stress may induce perinatal permanent tissues alterations and damage. • A panel of "oxidative stress biomarkers" may identify evolution of tissues dysfunction. • Early identification of oxidative stress related diseases now might be possible. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that an initial fraction of inspired oxygen (FiO2) of 30% during resuscitation of preterm infants results in less oxidative stress and is associated with improved clinical outcomes compared with an FiO2 of 65%. Study design: Preterm infants of gestational age <32 weeks (n = 193) were randomized to start resuscitation with either 30% oxygen (low-oxygen group) or 65% oxygen (high-oxygen group), after which the FiO2 was adjusted based on oxygen saturation values. The primary outcome was bronchopulmonary dysplasia (BPD) assessed at 36 weeks postmenstrual age. Secondary outcomes included major neonatal illnesses and markers of oxidative stress. Results: The median gestational age of included infants was 286/7 weeks (IQR, 265/7-303/7 weeks). The incidence of BPD was not significantly different between the low-oxygen and high-oxygen groups (24% vs 17%; P = .15). The FiO2 in both groups was adjusted to a mean of 40% by 7 minutes in the low-oxygen group and by 11 minutes in the high-oxygen group. No differences in markers of oxidative stress were noted between groups. Conclusion: Initial supplementation of preterm infants with 30% oxygen during the fetal-to-neonatal transition is as safe as 65% oxygen, with no differences in oxidative stress markers or BPD. [Copyright &y& Elsevier]

Abstract: This research studied, 25 adult patients who underwent physical therapy to assess the analgesic effect of distraction with the use of music during physical therapy. Patients randomly underwent physical therapy once with music provided by an iPod and once without music. In both sessions patients underwent identical physical procedures. At end of both sessions patients filled in 5-item questionnaire where they scored pain and other parameters, such as stress, enjoyment, interaction, and satisfaction, on 10-cm visual analog scale. The mean scores (range, 0-10) of the two sessions were statistically compared. Mean pain scores were significantly lower (p = .031) during the session in which patients received music (4.8 ± 2.5) than during the session without music (5.8 ± 2.3). The other items of the questionnaire did not disclose any statistically significant difference when the sessions with versus without music were compared. Enjoyment (8.5 ± 1.6), interaction (8.3 ± 1.9), and satisfaction (8.6 ± 1.7) scores with music did not significantly differ in the sessions without music (8.5 ± 2.1, 8.5 ± 1.9, and, 8.5 ± 1.5, respectively); mean stress score was, 3.9 in both sessions. The conclusion of the study is that music provided through a portable media player has an analgesic effect. This can be an effective analgesic strategy during painful physical therapy. [Copyright &y& Elsevier]

Iron, to be redox cycling active, has to be released from its macromolecular complexes (ferritin, transferrin, hemoproteins, etc.). Iron is released from hemoglobin or its derivatives in a nonprotein-bound, desferrioxamine-chelatable form (DCI) in a number of conditions in which the erythrocytes are subjected to oxidative stress. Such conditions can be related to toxicological events (haemolytic drugs) or to physiological situations (erythrocyte ageing, reproduced in a model of prolonged aerobic incubation), but can also result from more subtle circumstances in which a state of ischemia-reperfusion is imposed on erythrocytes (e.g., childbirth). The released iron could play a central role in oxidation of membrane proteins and senescent cell antigen (SCA) formation, one of the major pathways for erythrocyte removal. Iron chelators able to enter cells (such as ferrozine, quercetin, and fluor-benzoil-pyridoxal hydrazone) prevent both membrane protein oxidation and SCA formation. The increased release of iron observed in β-thalassemia patients and newborns (particularly premature babies) suggests that fetal hemoglobin is more prone to release iron than adult hemoglobin. In newborns the release of iron in erythrocytes is correlated with plasma nonprotein-bound iron and may contribute to its appearance. [Copyright &y& Elsevier]

Survival of preterm very low birthweight infants resulted in high risk for developmental cognitive deficits, poor academic achievement, and behaviour disorders. While numerous studies evaluated the prevalence of neurodevelopmental disability in early childhood, poor literature is available for infants born very low birthweight in adulthood. Fifty-five young adults born preterm (mean age: 18 ± 2.42 years; <33 weeks of gestational age and/or with birth weight <1500 g) were enrolled. The Verbal Intelligence Quotient (vIQ), Performance Intelligence Quotient (pIQ) and Total Intelligence Quotient (tIQ) were assessed through the Wechsler Adult Intelligence Scale – Revised (WAIS-R). Personality profiles were investigated using Rorschach test. Both WAIS-R and Rorschach scores were subsequently compared to 13 matched controls born at term. Data were analysed with the SPSS v20 for Windows statistical package. Young adults born preterm showed lower IQ scores than young adults born at term: tIQ 90.95 ± 22.46 versus 108.77 ± 16.14, p = 0.006; vIQ 89.85 ± 21.85 versus 107.69 ± 18.33, p = 0.009, and pIQ 92.40 ± 22.90 versus 108.31 ± 14.52, p = 0.011. No differences emerged in personality profile as most subjects showed adequate internal resources in both groups, but a trend towards anxiety and insecurity were identified in young adult born preterm. Young adults born preterm show psychological fragility and lower cognitive pattern than young adults born at term. Data support the need of an early psychological intervention that could help these individuals at greater risk to face a young society that is changing and that necessarily requires stronger internal resources. [ABSTRACT FROM AUTHOR]

Abstract: 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 12–36h) underwent hypoxia until the base excess reached −20mmol/L or the mean arterial blood pressure dropped below 15mm Hg. They were randomly assigned to receive resuscitation with 21, 40, or 100% oxygen for 30min 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 30min, 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. [Copyright &y& Elsevier]

According to increasing evidence, hypothermia can significantly improve outcomes in term neonates manifesting asphyxic insult and hypoxic-ischemic encephalopathy. Oxidative stress plays a key role in hypoxic-ischemic and inflammatory brain injuries. We investigated the impact of hypothermia on oxidative stress in babies with hypoxic-ischemic encephalopathy. Term infants were randomly selected for treatment with moderate whole body hypothermia or standard care on normothermia, after perinatal asphyxia. Total hydroperoxides as biochemical markers of oxidative stress, and C-reactive protein as a marker of inflammation, were assayed in blood samples drown at 6, 12, 24, 48, and 72 postnatal hours. In both hypothermic and normothermic groups, total hydroperoxides and C-reactive protein exhibited a continuous increase in the first days after birth. Nevertheless, a tendency was evident for slower and smaller elevations of total hydroperoxides and C-reactive protein in hypothermic compared with normothermic infants. A significant correlation was observed between total hydroperoxides and C-reactive protein in all patients, indicating an association between inflammation and oxidative stress during asphyxia. The slower increase and lower peaks of total hydroperoxides in the hypothermic group support the hypothesis that postasphyxic oxidative stress may be reduced by hypothermia. [Copyright &y& Elsevier]

Abstract: Objective: We assessed the effects of three different parenteral lipid emulsions (long-chain triacylglycerols, medium-chain/long-chain triacylglycerols, olive oil) on lipid peroxidation in preterm infants. The hypothesis to be tested was that preterm infants receiving the olive oil–based lipid emulsion would undergo less peroxidation than preterm infants receiving lipid emulsions based on long- or medium-chain triacylglycerols. The secondary aim was to evaluate whether the lipid peroxidation persists beyond the cessation of parenteral nutrition (PN). Methods: A randomized controlled trial was designed. Thirty-six consecutive preterm infants (gestational age 28–33 wk) were enrolled in the study. Preterm infants were randomized to receive one of the three emulsions within the first 24h of life. Plasma F2-isoprostanes (F2-Ip) and total radical-trapping antioxidant potential (TRAP) were determined at baseline, on day 7 of PN, and on day 7 after stopping PN. Results: The F2-Ip and TRAP concentrations were not statistically different within and among the three groups at any time of the study. No significant interaction effect between the type of lipid emulsion administered and the repeated values of F2-Ip and TRAP was found. F2-Ip values showed a trend to decrease throughout the study in all the three groups. Conclusion: No significant difference in oxidative stress of preterm infants was detected according to the type of lipid emulsion received. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are degenerative disorders of muscle. Although the mechanisms underlying muscle degeneration are still uncertain, oxidative-damage has been proposed to play a key role. Isoprostanes are markers of free radical-catalyzed lipid peroxidation; the aim of our study was to evaluate plasma isoprostane levels in group of patients affected by Duchenne and Becker muscular dystrophies. PF2-isoprostane levels were measured by colorimetric enzyme immunoassay in the plasma of 17 patients with DMD and 24 with BMD. When compared to a group of healthy controls, affected patients showed significantly higher plasma levels of isoprostanes (p =0.001). When patients were stratified according to the clinical diagnosis, isoprostane levels were not statistically different between DMD and BMD patients. In conclusion whether the condition of oxidative stress found in plasma depends on the degenerative process occurring in muscles or on different mechanisms, such as the release of myoglobin in the blood, should be ascertained. However, our study confirms that oxidative stress findings in DMD/BMD patients are effectively present at the plasma levels. The condition of oxidative stress might act as an adjunctive cause of extra-muscular cell damage to which these patients are exposed for their entire life. [Copyright &y& Elsevier]

Abstract: Aim: To assess inter-observer reliability of two of the most widely used pain scales for newborns. Background: More than 30 scales exist to assess neonatal pain, but they are rarely used because they are too complicated or unreliable. Method: We scored pain level in two groups of babies during a heelprick. The first group of 20 premature babies (mean gestational age: 34.2±1.2 weeks) was studied using the PIPP scale, and the second group of 20 term babies (mean gestational age: 39.5±0.9 weeks) with the NIPS scale. We compared the pain scores assigned by the nurse who took the blood sample (nurse A) and those assigned by another who was present during heelprick (nurse B) with those assigned by a nurse who later watched the video clip of the procedure (nurse C). We chose the latter as “objective” score, because in this case the scorer could watch the recorded event several times, timing and scoring it thoroughly. Finding: NIPS: 8/20 scores were different between nurse A and nurse C, but only in one case was this difference greater than 2 (Cohen''s K =0.60). In the case of nurse B, there were 12/20 differences with respect to the score assigned by nurse C but only one baby was assigned a score that differed by more than 2 (Cohen''s K =0.30). PIPP: 16/20 scores were different between nurse A and nurse C; in 9 cases this difference was more than 2 (Cohen''s K =0.10). In the case of nurse B, differences with respect to the score assigned by nurse C occurred in 17/20 cases and for six babies the difference in score was more than 2 (Cohen''s K =0.16). Conclusion: Our results indicate a higher inter-observer reliability of NIPS than PIPP, though NIPS did not have a very high inter-observer agreement score. Caregivers who use them to assess pain in real time at the cribside should be aware of the limits we have highlighted in this study. [Copyright &y& Elsevier]

Abstract: Background: : Premature rupture of membranes (PROM) is caused by collagen damage in the chorioamniotic sac leading to tearing. Reactive oxygen species (ROS) may be the cause of collagen damage. Isoprostanes (F2-IP) are produced by ROS attack on polyunsaturated fatty acids and are sensitive and specific biomarkers of lipid-peroxidation in vivo. Aim: : To verify whether oxidative stress occurs in pregnancies associated with preterm PROM. Methods: : F2-IPs were measured in amniotic fluid of 16 pregnancies with preterm PROM (Group II) and 97 without PROM (Group I). Results: : F2-IP concentrations (pg/mL) were significantly higher in group II than group I (p <0.0001). The ROC curve showed a sensitivity of 100% and a specificity of 84.5% at a cut-off of 124.4 pg/mL. Conclusions: : An association exists between oxidative stress in pregnancy and preterm PROM. The detection of amniotic fluid F2-IP concentrations seems to be a reliable predictive index of risk of preterm PROM. [Copyright &y& Elsevier]

Abstract: Nerve cells, especially synaptosomes, are very susceptible to hypoxia and the subsequent oxidative stress. In this paper, we examined the effects of hypoxia (93% N2:2% O2:5% CO2, v/v/v) on rat cortical synaptosomes by evaluating modifications of synaptosomal mitochondrial respiration rate and ATP production, membrane potential, intrasynaptosomal mitochondrial Ca2+ concentration ([Ca2+]i), and desferoxamine-chelatable free iron and esterified F2-isoprostane levels after different periods of hypoxia and after 30 min of reoxygenation. Oxygen consumption decreased significantly during 120 min of hypoxia and was restored after reoxygenation. At the same time, ATP production decreased and remained significantly lower even after reoxygenation. This involved a depolarization of the synaptosomal mitochondrial membrane, although the [Ca2+]i remained practically unchanged. Indeed, iron and F2-isoprostane levels, representing useful prediction markers for neurodevelopmental outcome, increased significantly after hypoxia, and there was a strong correlation between the two variables. On the whole our results indicate that synaptosomal mitochondria undergo mitoptosis after 2 h of hypoxia. [Copyright &y& Elsevier]

Abstract: Background: : Oxidative stress has recently been found to play a key role in post-ischemic kidney damage. We tested the hypothesis that oxidative kidney damage due to perinatal hypoxia in preterm newborns is associated with an increased production of oxidative free radicals in plasma. Methods: : Blood and urine samples were obtained at birth and on days 7 and 14, from 55 preterm newborns, without any known congenital abnormalities. Total hydroperoxides (TH) and advanced oxidation protein products (AOPP) as indices of oxidative stress, xanthine (Xa) and hypoxanthine (Hx) as indices of hypoxia, α1-microglobulin and N-acetyl-β-d-glucosaminidase (NAG) as indices of kidney damage were assayed. Results: : Statistically significant correlations (p <0.05) were found between biochemical markers of hypoxia, oxidative stress and proximal tubules damage at days 7 and 14. Conclusions: : Perinatal oxidative stress is associated with a variable degree of kidney damage detectable at birth and continuing up to 14 days. [Copyright &y& Elsevier]

Since birth-induced oxidative stress (OS) results in the removal of erythrocytes from the blood stream, we studied the binding of autologous IgG to erythrocyte band 3 dimers (the 170-kDa band, which marks the erythrocytes for removal) in preterm and term newborns and in adults. The 170-kDa band was present in as much as 74% of preterm, in 21% of term newborns, and in 10% of adults. During erythrocyte ageing “in vitro” (0, 24, and 48 h aerobic incubation), the appearance of the band occurred much faster with erythrocytes from newborns (particularly preterm) than with those from adults. When the blots for the 170-kDa band were quantified by scanning densitometry, it was seen that the 0 time values were significantly higher in preterm compared to term and adult values. After aerobic incubation a progressive increase in the optical density was observed in each group and the densities were higher in preterm than in the other groups. The course of iron release during the various incubations was analogous to that of the 170-kDa band blots, and significant correlations were found at 0 and 48 h. Methemoglobin formation roughly paralleled iron release. Esterified F2-isoprostanes (markers of OS) and O2•− production in the nonincubated (0 time) erythrocytes were much higher in newborn (preterm and term) than in adult erythrocytes. Plasma free F2-isoprostanes were significantly higher in preterms than in terms and in terms than in adults. Plasma non-protein-bound iron (NPBI) was higher in preterm than in term newborns and not detectable in adults. In conclusion dimers of band 3 with autologous IgG are found under conditions in which OS can be detected in erythrocytes or in plasma: namely in newborns or in aged erythrocytes. [Copyright &y& Elsevier]

Abstract: Isoprostanes are markers of free radical-catalyzed lipid peroxidation. Evidence suggests that oxidative stress occurs in pregnancies with fetal growth restriction (FGR). The aim of this study was to analyze F2-isoprostanes in amniotic fluid of FGR pregnancies. We tested the hypothesis that F2-isoprostanes are reliable markers to distinguish FGR pregnancies from normal ones and appropriate-for-gestational-age (AGA) from small-for-gestational-age (SGA) newborns. F2-isoprostanes levels were measured by colorimetric enzyme immunoassay in the amniotic fluid of 77 pregnancies with normal fetal growth (group I) and 37 with FGR (group II). Fetal biometry and Doppler measurements were obtained using an ATL HDI 3000 ultrasound system. Isoprostanes were higher in group II than group I. The ROC curve distinguished group I from group II, showing 100% sensitivity and 88.3% specificity at a cutoff of 94 pg/ml. There were no statistical differences in isoprostanes levels between AGA and SGA newborns in group II. The area under the ROC curve drawn to distinguish AGA and SGA newborns showed a sensitivity of 100% and a specificity of 72.3% at a cutoff of 94 pg/ml. The relative risk index indicated a 8.05 times higher risk of birth weight below the 3rd percentiles in group II than in group I. High isoprostanes concentrations can be detected in the amniotic fluid of FGR pregnancies and the assay of isoprostanes in amniotic fluid is a reliable assessment of fetal oxidative stress. Common use of this predictive marker in obstetrics will improve the ability of clinicians to identify those fetuses who will be born SGA or with a birth weight below the 25th percentile. [Copyright &y& Elsevier]

Abstract: Objectives:: S100B is an acidic calcium-binding protein of the EF-hand family present in the central nervous system, where it is concentrated in glial cells. It has been suggested to act as a cytokine with neurotrophic effects at physiological concentrations. Design and methods:: S100B concentration was assessed in saliva by western blot analysis and an immunoluminometric assay. A reference curve of the protein was established in 216 preterm and term newborns. Results:: S100B levels were significantly higher in saliva taken from the preterm group, and the highest S100B levels were found in newborns who were delivered in the earlier weeks of gestation, exhibiting a progressive decrease nearer to term. S100B concentration in saliva was correlated with gestational age (r = −0.69; P < 0.001). Conclusions:: The present study offers data consistent with the putative neurotrophic role of S100B and suggests the usefulness of saliva in the clinical monitoring of S100B levels. [Copyright &y& Elsevier]

F2-isoprostanes, prostaglandin F2-like compounds formed by free radical-catalyzed lipid peroxidation, are considered the most reliable markers of oxidative stress. It has been repeatedly suggested that newborns are exposed to conditions of oxidative stress resulting from the change from a low oxygen pressure in utero to a high oxygen pressure at birth. We measured the levels of F2-isoprostanes in plasma of newborns by gas chromatography/mass spectrometry and we found that F2-isoprostanes are significantly higher in term newborns compared to healthy adults. The greatest values were found in preterm newborns in whom F2-isoprostanes are even higher than in term babies. Moreover a significant inverse correlation was found between the plasma levels of isoprostanes and the gestational age. A quite normal level of isoprostanes was found in the mothers both at delivery and during pregnancy. Placental total F2-isoprostanes (sum of free plus esterified) were significantly higher in preterm compared to term deliveries and such a difference might account for the difference in plasma isoprostanes. Plasma non-protein-bound iron is higher in preterm than in term newborns, even if no correlation was found with plasma F2-isoprostanes. Erythrocyte desferrioxamine-chelatable iron content (0 time) and release (24 h of aerobic incubation) are higher in newborns than in adults and in preterm than in term newborns, but again no correlation was found with plasma F2-isoprostanes. The marked increase in plasma isoprostanes suggests that oxidative stress is a feature of the physiopathological changes seen in the perinatal period. [Copyright &y& Elsevier]

Activin-A is expressed by human endometrium, and the actions are counteracted by follistatin, its binding protein. We evaluated the endometrial mRNA and peptide expression of follistatin-related gene (FLRG), a protein that binds activin-A, preventing its interaction.By reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, FLRG expression was evaluated in tissues collected at early proliferative (EP; n=8) and late proliferative (LP; n=8); early secretory (ES; n=9) and late secretory (LS; n=10); and in pregnancy, maternal decidua (MD; n=12). FLRG mRNA was expressed by all samples, and semi-quantitative analysis showed that FLRG expression was significantly (P<0.001) higher in MD.FLRG was strongly immunolocalized in epithelial cells of glands and vessel walls (cytoplasma and nucleus), but only in the stromal cells nucleus. In MD, FLRG immunostaining was found in the nucleus and cytoplasm of vessel endothelium, gland epithelial, and decidualized stromal cells.In conclusion, FLRG is expressed by the human endometrium, and the different cellular localization suggests novel putative functions. [Copyright &y& Elsevier]