Tuning of polyurethane foam mechanical and thermal properties using ball-milled cellulose.

Cystalline-Cc and ultra-milled Amorphous-Ca cellulose were used as reactive filler to tune the performances of composite polyurethane-cellulose-foams, PUC. The effect of Cc and Ca on chemo-physical and mechanical properties of PUC was analysed through FTIR, morphological analysis, thermal conductivity and compression measurements. FTIR results show that, both Cc and Ca react with isocyanate through the OH functional groups contributing to the formation of a tough cellulose-polyurethane network. Morphological observations show that the addition of both Cc and Ca induces a decrease of average cell-size compared to the pristine-PU, thus confirming that they act as nucleating agent. In addition, the better dispersion of the Ca in the polyol, with respect to Cc induces, a finer cell leading to a reduction of the thermal conductivity around 33 % (for the composite loaded with 20 %wt-Ca) with respect to pristine-PU. Finally, the addition of Ca highly reactive modifies the mechanical behaviour from rigid-brittle to semi-rigid.

Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery.

OBJECTIVE: Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. METHODS: A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. RESULTS: In total, 61 neonates were included, median gestational age at 39 weeks (range 31-42) and weight at 3000 grams (1400-4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. CONCLUSION: Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group.

Randomized trial of early erythropoietin supplementation after preterm birth: Iron metabolism and outcome.

BACKGROUND: Excess of iron and oxidant injury shortly after birth may be associated with neonatal morbidities in preterm infants. AIMS: The aim was to determine whether administration of erythropoietin without iron supplementation decreases iron load and morbidity. STUDY DESIGN AND SUBJECTS: In a randomized trial, we administered erythropoietin (EPO 250IU/kg daily during the first 6days of life) or placebo to 39 preterm infants (BW 700-1500g, GA≤30.0weeks). OUTCOME MEASURES: The iron status, postnatal morbidities and follow-up at the age of two years were investigated. RESULTS: In all, 21 EPO- and 18 placebo-treated infants were recruited. A requirement of red blood cell transfusions during first 28days was similar between the study groups. EPO treatment decreased total serum iron concentration (p=0.035). EPO supplementation had no significant effect on serum transferrin receptors or reactive non-protein-bound iron. There were no differences in neonatal morbidity or in survival without major neurological abnormality at two years of age. CONCLUSIONS: A 6-day course of EPO decreased the iron load in preterm infants. There was no change in reactive, non-protein bound iron plasma levels and no influence on the outcomes during early childhood. Whether the neurocognitive effects of early EPO treatment can be detectable later in childhood remained to be verified.

Use of fetal analgesia during prenatal surgery.

OBJECTIVE: Recent progresses in fetal surgery have raised concern on fetal pain, its long-term consequences and the risks of sudden fetal movements induced by pain. In several studies, surgeons have directly administered opioids to the fetus, while others have considered sufficient the maternally administered analgesics. We performed a review of the literature to assess the state of the art. METHODS: We performed a PubMed search to retrieve the papers that in the last 10 years reported studies of human fetal surgery and that described whether any fetal analgesia was administered. RESULTS: We retrieved 34 papers. In three papers, the procedure did not hurt the fetus, being performed on fetal annexes, in two papers, it was performed in the first half of pregnancy, when pain perception is unlikely. In 10 of the 29 remaining papers, fetal surgery was performed using direct fetal analgesia, while in 19, analgesia was administered only to the mother. In most cases, fetal direct analgesia was obtained using i.m. opioids, and muscle relaxant. Rare drawbacks on either fetuses or mothers due to fetal analgesia were reported. CONCLUSION: Fetal direct analgesia is performed only in a minority of cases and no study gives details about fetal reactions to pain. More research is needed to assess or exclude its possible long-term drawbacks, as well as the actual consequences of pain during surgery.

Antioxidant effects of potassium ascorbate with ribose therapy in a case with Prader Willi Syndrome.

Oxidative stress (OS) is involved in several human diseases, including obesity, diabetes, atherosclerosis, carcinogenesis, as well as genetic diseases. We previously found that OS occurs in Down Syndrome as well as in Beckwith-Wiedemann Syndrome (BWS). Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder, characterized by obesity, atherosclerosis and diabetes mellitus type 2, pathologies in which a continuous and important production of free radicals takes place. We verified the presence of OS by measuring a redox biomarkers profile including total hydroperoxides (TH), non protein-bound iron (NPBI), thiols (SH), advanced oxidation protein products (AOPP) and isoprostanes (IPs). Thus we introduced in therapy an antioxidant agent, namely potassium ascorbate with ribose (PAR), in addition to GH therapy and we monitored the redox biomarkers profile for four years. A progressive decrease in OS biomarkers occurred until their normalization. In the meantime a weight loss was observed together with a steady growth in standards for age and sex.

Functional maturation of neocortex: a base of viability.

The term "viability" is not simply a synonymous with being "born alive," but is closely related to the capability of having a "meaningful life" and having a reasonable period of survival. The definition of "viability" is generally based on two major criteria: the biological, which takes into consideration the maturity of the foetus, and the epidemiological, which is based on the survival rates reported in literature. The neuromaturation of the cerebral cortex is a dynamic process promoted by the subplate, a transient population of neurons that guides the development of cortical and thalamocortical connections. These connections are for example fundamental for cortical processing of sensory information and mental processes. The first thalamocortical and cortico-cortical connections grows at 23-24 postconceptional weeks, which coincides with the age limit for premature baby survival.

Exposure to electromagnetic fields from laptop use of "laptop" computers.

Portable computers are often used at tight contact with the body and therefore are called "laptop." The authors measured electromagnetic fields (EMFs) laptop computers produce and estimated the induced currents in the body, to assess the safety of laptop computers. The authors evaluated 5 commonly used laptop of different brands. They measured EMF exposure produced and, using validated computerized models, the authors exploited the data of one of the laptop computers (LTCs) to estimate the magnetic flux exposure of the user and of the fetus in the womb, when the laptop is used at close contact with the woman's womb. In the LTCs analyzed, EMF values (range 1.8-6 µT) are within International Commission on Non-Ionizing Radiation (NIR) Protection (ICNIRP) guidelines, but are considerably higher than the values recommended by 2 recent guidelines for computer monitors magnetic field emissions, MPR II (Swedish Board for Technical Accreditation) and TCO (Swedish Confederation of Professional Employees), and those considered risky for tumor development. When close to the body, the laptop induces currents that are within 34.2% to 49.8% ICNIRP recommendations, but not negligible, to the adult's body and to the fetus (in pregnant women). On the contrary, the power supply induces strong intracorporal electric current densities in the fetus and in the adult subject, which are respectively 182-263% and 71-483% higher than ICNIRP 98 basic restriction recommended to prevent adverse health effects. Laptop is paradoxically an improper site for the use of a LTC, which consequently should be renamed to not induce customers towards an improper use.

Inhibition of rapamycin-induced autophagy causes necrotic cell death associated with Bax/Bad mitochondrial translocation.

Rapamycin, a lipophilic macrolide antibiotic, has been found to reduce injury in different models of neurodegenerative disorders. We have previously shown that in neonatal rats subjected to hypoxia-ischemia (HI) the neuroprotective effect of rapamycin was associated with increased autophagy and decreased caspase-3 activation. We show here that the strong reduction of caspase-3 activation after rapamycin was due, at least in part, to its effect on the intrinsic apoptotic mitochondrial pathway because after rapamycin treatment there was a marked reduction of Bax and Bad translocation to mitochondria, cytochrome c release, and caspase-3 activation. Poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and the number of terminal dUDP nick-end labeling (TUNEL)-positive cells were also reduced. To assess how the antiapoptotic effect of rapamycin was linked to the strong autophagy signal induced by the drug, we blocked the formation of autophagosomes with 3-methyladenine (3MA). 3MA administered 10 min after rapamycin, elicited again Bax and Bad translocation to the mitochondria but did not cause cytochrome c release and caspase-3 activation. After 3MA treatment, cells underwent necrotic cell death. These data indicate that rapamycin administered before HI prevents the apoptotic signaling taking place through the mitochondrial pathway. We hypothesize that rapamycin confers a preconditioning-like protection and suggest that caution is necessary before using pharmacological agents targeting autophagy in neuroprotection because they could interfere with endogenous protective mechanisms.

Physiopathological effects of the NO donor 3-morpholinosydnonimine on rat cortical synaptosomes.

The NO donor 3-Morpholinosydnonimine (SIN-1) releases NO in the presence of molecular oxygen. In this study, we evaluated the effect of SIN-1 on mitochondria of rat cortical synaptosomes. We demonstrated in vitro that the amount of ONOO(-) generated and H(2)O(2) formation directly correlated with SIN-1 concentration. The mean oxygen consumption by synaptosomal mitochondria was approximately 3.8 nmol of O(2) min(-1) mg(-1) protein, which decreased significantly in the presence of SIN-1 1 mM to 2.5 nmol O(2) min(-1) mg(-1). This decrease was not modified by catalase or Trolox, demonstrating that ONOO(-) was responsible for the effect. The same concentration of SIN-1 caused a significant decrease of ATP production by synaptosomal mitochondria and depolarized the mitochondrial membrane. Moreover, ROS production increased progressively and was completely inhibited by pre-incubation of synaptosomes with Trolox. Finally, phosphatidylserine was externalized and, at the same time, intrasynaptosomal lactate dehydrogenase decreased confirming both, the external membrane breakdown after the addition of SIN-1 and the damage to the synaptosomes.

Electromagnetic fields produced by incubators influence heart rate variability in newborns.

BACKGROUND: Incubators are largely used to preserve preterm and sick babies from postnatal stressors, but their motors produce high electromagnetic fields (EMFs). Newborns are chronically exposed to these EMFs, but no studies about their effects on the fragile developing neonatal structure exist. AIM: To verify whether the exposure to incubator motor electric power may alter autonomous nervous system activity in newborns. MATERIAL AND METHODS: Heart rate variability (HRV) of 43 newborns in incubators was studied. The study group comprised 27 newborns whose HRV was studied throughout three 5-minute periods: with incubator motor on, off, and on again, respectively. Mean HRV values obtained during each period were compared. The control group comprised 16 newborns with constantly unrecordable EMF and exposed to changes in background noise, similar to those provoked by the incubator motor. RESULTS: Mean (SD) total power and the high-frequency (HF) component of HRV increased significantly (from 87.1 (76.2) ms2 to 183.6 (168.5) ms2) and the mean low-frequency (LF)/HF ratio decreased significantly (from 2.0 (0.5) to 1.5 (0.6)) when the incubator motor was turned off. Basal values (HF = 107.1 (118.1) ms2 and LF/HF = 1.9 (0.6)) were restored when incubators were turned on again. The LF spectral component of HRV showed a statistically significant change only in the second phase of the experiment. Changes in background noise did not provoke any significant change in HRV. CONCLUSION: EMFs produced by incubators influence newborns' HRV, showing an influence on their autonomous nervous system. More research is needed to assess possible long-term consequences, since premature newborns may be exposed to these high EMFs for months.

Ante partum bed rest and unexplained infantile crying.

AIM: The aim of this study was to assess whether bed rest during pregnancy is a risk factor for infantile colics. METHODS: In a previous paper a questionnaire was administered to 86 women (43 of whom had stayed in bed during pregnancy for a mean of 3.4+/-1.2 months, and 43 were controls) about the clinical history and the present state of their 11-15 year old babies. In the present paper we traced these women and assessed the presence/absence of unexplained infant crying (UIC, infantile colic), diagnosed by a physician in the first year of life of these children. Forty mothers answered the inquiry, and we compared their answers with 40 control mothers. RESULTS: Babies born after maternal bed rest during pregnancy had a higher incidence of UIC than the control group (26/40 vs 11/40; P=0.0015). No significant correlation was found between UIC and allergies or between UIC and maternal or artificial breast feeding. CONCLUSIONS: Our retrospective study shows a possible association between bed rest and UIC: further studies, including other important variables (stress, drugs, smoking) are needed.

Non protein bound iron concentrations in amniotic fluid.

OBJECTIVES: To investigate whether amniotic fluid concentrations of non protein bound iron (NPBI) vary with growth in healthy fetuses and also offer a reference curve in the second trimester of pregnancy. DESIGN AND METHODS: Amniotic fluid concentrations of NPBI were measured by HPLC in 118 women with physiological singleton pregnancies, who underwent amniocentesis for fetal karyotype between weeks 15 and 18 of gestation. RESULTS: NPBI increased progressively from weeks 14--15 to weeks 15--16, peaking at 17--18 weeks of gestation. NPBI values regressed positively with gestational age (GA). Multiple linear regression analysis between NPBI, as dependent variable, and various fetal parameters, as independent variables, showed a statistically significant regression coefficient with GA, bi-parietal diameter and transverse cerebellar diameter. CONCLUSIONS: The present data constitutes the first quantification of NPBI concentrations in amniotic fluid under physiological conditions. Correlations with GA and ultrasound fetal biometry suggest that NPBI may play a role in fetal growth.

Reduction of exposure of newborns and caregivers to very high electromagnetic fields produced by incubators.

The aims of this paper is to measure whether ferromagnetic panels sufficiently reduce the high electromagnetic fields (EMF) to which newborns are exposed in incubators and to which caregivers are exposed when working near the incubators. We measured EMF at mattress level in three neonatal incubators with and without ferromagnetic panels between the electric motor and the mattress. We then measured the EMF at the level of the maximum emission point for caregivers, i.e., near the display panel. The ferromagnetic panels were (a) 5 mm thick iron, (b), (c), (d) respectively, one, two, and three sheets of 0.3 mm thick mu-metal. The weight of iron sheet was 4 g/cm2, and mu-metal 0.2 g/cm2. The use of the ferromagnetic panels significantly reduced the EMF. No significant difference in attenuation was recorded using one, two, or, three sheets of mu-metal, or a single sheet of iron. One, two, and three sheets of mu-metal reduced EMFs by 77%, 82%, and 84.3%, respectively; the reduction with iron was 80%. EMF values measured in incubators were higher than those to which the general population is exposed. The use of ferromagnetic panels significantly reduces the level of EMFs to which neonates and caregivers are exposed.

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.

Encephalocraniocutaneous lipomatosis (Haberland syndrome) with bilateral cutaneous and visceral involvement.

Encephalocraniocutaneous lipomatosis, or Haberland syndrome, is a rare congenital neurocutaneous disease. It is characterized clinically by unilateral lipomatous hamartomata of the scalp, eyelid, and outer globe of the eye, ipsilateral porencephalic cysts with cortical atrophy, cranial asymmetry, marked developmental delay and mental retardation. This syndrome should be distinguished from other mosaic neurocutaneous phenotypes such as as Delleman syndrome, Schimmelpenning syndrome, Goltz syndrome, Goldenhar syndrome and Proteus syndrome. Here we report a case of Haberland syndrome with bilateral involvement which underscores the extreme heterogeneity of clinical presentation of this and related syndromes.

Oxidant injury in neonatal erythrocytes during the perinatal period.

UNLABELLED: It has been known for many decades that oxidative stress leads to oxidation of hemoglobin and damage to the erythrocyte membrane. More recently, the factors involved in denaturating of membrane proteins and lipid peroxidation have been investigated in detail, as well as the mechanism of reactive oxygen species formation in red cells. Oxidative stress depletes adenosine triphosphate (ATP) and adenine nucleotides, whereas adenosine monophosphate (AMP) deaminase seems to depress energy metabolism by blocking the salvage pathway of purine nucleotides. Depletion of ATP and activation of AMP deaminase are related to calcium ion concentrations. Denaturating of membrane proteins generally precedes lipid peroxidation and consequent phagocytosis due to caspase activation. Extensive investigations demonstrated the key role of oxidative stress and iron release in a reactive form causing membrane protein damage via the Fenton reaction and hydroxyl radical production. In the absence of efficient protection by antioxidant factors and other molecules such as flavonoids, oxidative stress is responsible for the release of iron in reactive form, predisposing red cells to hemolysis through the formation of senescence antigen. Other well-known sources of oxidative stress in red cells are free radical production outside the red cell by activated phagocytes, endothelial metabolism, hyperoxia, ischemia-reperfusion and the arachidonic acid cascade. CONCLUSION: The recent insight into the mechanism of oxidative injury of red cells and evidence of relationships between erythrocyte oxidative stress and hypoxia suggest that increased hemolysis is induced by severe hypoxia and acidosis in the fetus as well as the newborn.

New biomarkers of fetal-neonatal hypoxic stress.

UNLABELLED: The complex pathophysiological mechanisms underlying perinatal hypoxia make it difficult to define early markers of severe hypoxia-ischemia encephalopathy. However, as progress in the development of neuroprotective therapeutic measures continues, the early identification of neonates at risk of severe hypoxic-ischemic encephalopathy is an important goal for appropriate decision making. Although the timing of perinatal hypoxic brain damage may vary and is sometimes unknown, high levels of non-protein-bound iron and high nucleated red blood cell counts in cord blood indicate an antepartum origin of neurological impairment, because they can occur only as a consequence of a pre-existing asphyxic event. CONCLUSION: The combined assessment of nucleated red blood cells and non-protein-bound iron at birth seems extremely useful for the early identification of newborns at high risk of brain damage. Activin A also seems to be a reliable marker of perinatal hypoxia. Prospective long-term follow-up studies are needed to verify their predictive role.

Early neonatal brain injury in histologic chorioamnionitis.

The relation between clinical or histologic chorioamnionitis and early neonatal adverse neurologic outcome was investigated (n = 483). Histologic, but not clinical, evidence of chorioamnionitis was found to be a significant predictor of periventricular echodensity (odds ratio, 2.4; 95% CI, 1.8-3.2), echolucency (3.3; 1.9-5.6), ventriculomegaly (2.7; 1.8-4.2), intraventricular hemorrhage > or =3 (3.5; 2.4-5.2), and seizures (2.3; 1.4-3.7).

EEG in assessing hydroxycobalamin therapy in neonatal methylmalonic aciduria with homocystinuria.

We performed serial electroencephalograms (EEG) in a newborn with methylmalonic aciduria and homocystinuria to assess the effects of hydroxycobalamin (OHcbl) therapy on the CNS. Diagnosis was made at 22 days of age: she had torpor, failure to thrive and hypotonia of the limbs, and intermittent opisthotonus. The first EEG, performed on the first day of therapy, showed abnormal and immature transients, low voltage and very long flat periods in the discontinuous part of the tracing. These features quickly improved during therapy. After 13 days of OHcbl therapy, the EEG tracing became normal for conceptional age and showed normal sleep phases with only minor anomalies; only mild hypotonia still remained and biochemical parameters normalized. The decrease in blood homocysteine (index of blood detoxification) was statistically correlated to the reduction of the length of flat periods in EEG (p < 0.01). In conclusion, changes in neonatal EEG, particularly the length of interburst periods in the intermittent part of the tracing, appeared to be a reliable index for evaluating drug effectiveness in methylmalonic aciduria and homocystinuria.