Biomedical subjects

G Buonocore

Publications and source records attributed to G Buonocore.

At least 37 records · Page 2Linked to original sources

PubMed2001

Red blood cell involvement in fetal/neonatal hypoxia.

Free radical release plays an important role in the development of brain injury following hypoxic-ischemic encephalopathy. It causes endothelial cell damage and anomalies in NMDA receptors, synaptosome structure and astrocyte function. Mitochondrial dysfunctions caused by asphyxia, reperfusion after ischemia, arachidonic acid cascade, catecholamine metabolism and phagocyte activation are known sources of reactive oxygen species, particularly the superoxide anion (O2(-)). O2(-) mainly induces peroxidation by the Fenton/Haber Weiss reaction or via iron-oxygen complexes. Since both reactions require reactive heavy metals, non-protein-bound iron (NPBI) is essential for the induction of lipid peroxidation. Experimental studies have demonstrated the neurotoxicity of iron in ischemia-reperfusion. Normal axonal transport of brain iron is also reported to be disrupted in hypoxia-ischemia, leading to a buildup of iron in the white matter. The free iron content of erythrocytes (ICRBC) is considered a marker of oxidative stress. Free iron release is accompanied by the oxidation of membrane proteins and the appearance of senescent antigen, as measured by autologous IgG binding. Our preliminary results suggest a significant positive correlation between plasma free iron and the number of nucleated red cells in cord blood, currently considered a reliable index of lasting intrauterine asphyxia but also possessing a high predictive value for poor neurodevelopmental outcome. The rate of erythropoiesis and the entity of ICRBC are related to the degree of asphyxia and the probability of neurological impairment. Since even an increase in NPBI during asphyxia is related to a poor outcome, iron released by red cells could possibly also contribute to NPBI levels.

Asphyxia Neonatorum↗

PubMed2001

Sensorial saturation: an effective analgesic tool for heel-prick in preterm infants: a prospective randomized trial.

Pain is traumatic for preterm infants and can damage their CNS. We wanted to assess whether multisensorial stimulation can be analgesic and whether this effect is only due to oral glucose or sucking. We performed a randomized prospective study, using a validated acute pain rating scale to assess pain during heel-prick combined with five different procedures: (A) control, (B) 10% oral glucose plus sucking, (C) sensorial saturation (SS), (D) oral water, and (E) 10% oral glucose. SS is a multisensorial stimulation consisting of delicate tactile, vestibular, gustative, olfactory, auditory and visual stimuli. Controls did not receive any analgesia. We studied 85 heel-pricks (5 per baby) performed for routine blood samples in 17 preterm infants (28-35 weeks of gestational age). We applied in random order in each patient the five procedures described above and scored pain. SS and sucking plus oral glucose have the greater analgesic effect with respect to no intervention (p < 0.001). The effect of SS is statistically better than that of glucose plus sucking (p < 0.01). SS promotes interaction between nurse and infant and is a simple effective form of analgesia for the NICU.

Analgesia↗

PubMed2001

Cyclooxygenase-2 immunoreactivity in the ischemic neonatal human brain. An autopsy study.

Cyclooxygenase-2 (COX-2) is known to be expressed in rat brain and up-regulated by ischemia. The administration of COX inhibitors before as well as soon after the ischemic insult reduces the extension of cerebral damage in rats. Overexpression of COX-2 has also been shown in the ischemic brain of adult human patients, while no information concerning COX-2 expression in neonatal ischemia is available. Intrapartum asphyxia and perinatal brain injury may result in cerebral palsy, mental retardation or epilepsy. COX-2 expression in the brain of neonates delivered after severe birth asphyxia was investigated using immunohistochemistry. Meningeal vessel walls of term and preterm babies widely expressed COX-2 immunoreactivity, as did periventricular large vessels in preterms. A number of brain cells (mature and immature cortical, periventricular and basal ganglia neurons, and oligodendrocytes of the cerebral white matter in brains from term neonates) also expressed COX-2. The present findings suggest that COX-2 may take part in enhancing neonatal brain damage via different mechanisms, such as those involving excitotoxicity and production of reactive oxygen species.

Acute Disease↗

PubMed2001

[Free radicals and brain damage in newborns with hypoxic-ischemic lesion].

Free radicals (FR) are highly reactive chemical molecules containing one or more unpaired electrons. Oxygen-derived free radicals, collectively termed reactive oxygen species (ROS), are normally produced in living organisms. When over produced, they are major mediators of cell and tissue injury. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress in vivo is a degenerative process due to the over production and propagation of FR reactions. FR reactions lead to oxidation of lipids, proteins, polysaccharides and to DNA damage. Newborns and particularly preterm infants are very susceptible to FR oxidative damage. In these subjects, there is evidence of an imbalance between antioxidant and oxidant-generating systems enhancing oxidant injury.

Brain Damage, Chronic↗

PubMed2000

Acute thymic involution in fetuses and neonates with chorioamnionitis.

Chorioamnionitis represents the leading cause of preterm birth and related pathologic conditions as well as of fetal death and frequently occurs in symptom-free mothers. Recent radiologic findings have indicated that thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis. However, an accurate morphologic description of the thymus gland in fetuses and neonates with chorioamnionitis is lacking, although it is known that infection and other stress processes may cause lymphocyte depletion in the thymuses of infants and older babies (acute stress involution). We describe morphologic modifications in the thymus of fetuses with histologically proven chorioamnionitis and newborn infants with chorioamnionitis and proven sepsis. The main findings included (1) decreased organ volume (ANOVA, P < .0024); (2) reduced corticomedullary ratio (P < 10(-6)); (3) significant changes in the relationship between thymic parenchyma and thymic interstitial tissue with resulting increased organ complexity (P = .03); (4) severe reduction of thymocytes; and (5) other degenerative processes such as monocyte/macrophage infiltration of Hassall's bodies. These results indicate that chorioamnionitis, with or without sepsis, is associated with significant morphologic modifications in the thymus. We wish to note that the described thymic pathology is only one aspect of the fetal systemic inflammatory response syndrome with which chorioamnionitis is associated.

Abortion, Spontaneous↗

PubMed2000

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.

Electroencephalography↗

PubMed2000

Total hydroperoxide and advanced oxidation protein products in preterm hypoxic babies.

Previous studies have shown that plasma lipoproteins are a common target of free radical-induced oxidative stress in hypoxic newborn infants. In contrast to lipids, the reaction of proteins with various oxidants during hypoxia has not been extensively studied. We tested the hypothesis that tissue hypoxia results in increased production of protein oxidation in cord blood of preterm newborns. Heparinized blood samples of 39 hypoxic and 16 control preterm newborns were obtained from the umbilical vein, after cord clamping immediately after delivery. Plasma levels of total hydroperoxide (TH), advanced oxidation protein products (AOPP), hypoxanthine (Hx), xanthine (Xa), and uric acid (UA) were measured. Higher Hx, Xa, UA, TH, and AOPP levels were found in hypoxic newborn infants than in controls. Statistically significant correlations were observed between: TH and Hx (r = 0.54, p = 0.003, n = 28), AOPP and Hx (r = 0.64, p = 0.0001, n = 27), and TH and AOPP plasma levels (r = 0.50, p = 0.02, n = 21). In summary, TH, AOPP, Hx, Xa, and UA production is increased in fetal blood during hypoxia. The more severe the hypoxia, the higher the lipid and protein damage by free radicals.

Blood Proteins↗

PubMed2000

[Pre- and post-natal corticosteroids: side effects].

It is well known that prenatal steroid therapy (ST) reduces the mortality rate and the incidence of respiratory distress syndrome and intraventricular haemorrhage in premature infants. The benefits and safety of repeated courses of antenatal ST are doubtful due to possible side effects in the mother and baby. Experimental studies in animals have shown that multiple courses of antenatal ST have deleterious effects on lung growth and organisation, brain myelination, hypothalamic-pituitary-adrenal function and retina development. In humans, exposure to multiple courses of antenatal ST is associated with small head circumference at birth and increased incidence of maternal endometritis and early-onset neonatal sepsis. When administered soon after birth, ST may enable a reduction in ventilator settings and facilitate weaning from mechanical ventilation, but although associated with rapid improvement in lung function, it does not modify mortality or long-term outcome and has many acute side effects. Deleterious effects on lung maturation and neuro-developmental outcome, including cerebral palsy, have also been reported. The paucity of follow-up data is a major problem, and further prospective trials are needed.

Adrenal Cortex Hormones↗

PubMed1999

Nucleated red blood cell count at birth as an index of perinatal brain damage.

OBJECTIVE: The prognostic value of the nucleated red blood cell count at birth with respect to perinatal brain damage and neonatal outcome was assessed in infants at high risk of having neurologic damage. STUDY DESIGN: The nucleated red blood cell count at birth, pulsed Doppler ultrasonography in the cerebral arteries, cranial fontanelle sonograms, and neurodevelopmental status were evaluated in 337 newborn infants. RESULTS: The nucleated red blood cell count at birth was significantly higher (1) in neonates with abnormal Doppler ultrasonographic parameters for the cerebral arteries at 48 to 72 hours after birth than in healthy neonates, (2) in 6-month-old infants with sequelae of hypoxic-ischemic encephalopathy than in healthy infants, and (3) in 3-year-old children with abnormal developmental status than in those with no abnormalities at follow-up. Significant correlations were observed between the nucleated red blood cell count and gestational age, Apgar score at 1 and 5 minutes, pH, base deficit, fraction of inspired oxygen, blood oxygen content, and birth weight. CONCLUSIONS: The nucleated red blood cell count at birth not only reflects a response of the infant to perinatal hypoxia but is also a reliable index of perinatal brain damage.

Apgar Score↗

PubMed1999

Hypoxic response of synaptosomal proteins in term guinea pig fetuses.

Early events in the hypoxia-induced response trigger tyrosine phosphorylation cascades involving a large number of enzymes and substrates. The resolving power of advanced two-dimensional gel electrophoresis, followed by immunoblotting with specific antibodies to phosphotyrosine, has been used to analyze hypoxia-induced modifications in guinea pig brain synaptosomes. These procedures, in conjunction with computer-aided image analysis, are useful in the differential display of gene products, providing comparison at the level of posttranslationally modified products. Studies were performed in cerebral cortical synaptosomes from three normoxic and three hypoxic newborn guinea pigs. To filter off background noise consisting of nonreproducible migrating protein spots, only reproducible features of electrophoretic patterns were considered. Immunoreactivity patterns obtained with anti-phosphotyrosine antibodies proved to be different in normoxic and hypoxic synaptosomes: of a total of 130 immunoreactive spots, 49 were tyrosine-phosphorylated in hypoxic synaptosomes only and 20 in the normoxic ones only. Our data suggest that hypoxia extensively remodels the signaling pathway by switching off tyrosine phosphorylation of some cellular components (i.e., alpha-internexin) and switching on tyrosine phosphorylation of some other proteins (i.e., heat shock cognate 70, aconitase, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and pyruvate kinase).

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1998

Intraerythrocyte nonprotein-bound iron and plasma malondialdehyde in the hypoxic newborn.

Intraerythrocyte nonprotein-bound iron (INPBI), malondialdehyde (MDA), and hypoxanthine plasma levels (HxPL), were determined by high-pressure liquid chromatography in 138 randomly selected newborn infants with gestational ages ranging from 23 to 42 weeks at birth and on fourth day of life. MDA plasma levels were significantly higher in cord and fourth-day blood samples of preterm babies than term infants as well as babies born by emergency Caesarean section than babies born by vaginal delivery and in intubated than in nonintubated newborns. Highly significant correlations both in cord blood and fourth-day blood samples were observed between MDA plasma levels and gestational age, birth weight, Apgar score at 1 min and 5 min, HxPL, pH, base deficit, and INPBI content. Multiple regression analysis identified HxPL as the best single predictor of MDA plasma levels in cord blood, and INPBI content in fourth-day blood as the best single predictor of MDA plasma levels in fourth-day blood. The results indicate that red cells and plasma lipoproteins are a common target of free radical-induced oxidative stress during hypoxia.

Erythrocytes↗

PubMed1998

Effect of deferoxamine and allopurinol on non-protein-bound iron concentrations in plasma and cortical brain tissue of newborn lambs following hypoxia-ischemia.

Reduction of non-protein-bound iron (NPBI) using iron chelators may attenuate hypoxia-ischemia-induced reperfusion injury of the brain. This study investigated whether administration of low-dose deferoxamine and allopurinol, both having NPBI-chelating properties, reduced hypoxia-ischemia-induced NPBI formation in plasma effluent from the brain and in cerebral cortical tissue. Twenty-one newborn lambs underwent severe hypoxia-ischemia. Upon reperfusion and reoxygenation the lambs received either a placebo (n = 7), or deferoxamine 2.5 mg/kg (n = 7) or allopurinol 20 mg/kg (n = 7). The post-hypoxic-ischemic NPBI levels in plasma were significantly lower after deferoxamine but not after allopurinol as compared to placebo-treated lambs. Cortical NPBI levels in both deferoxamine and allopurinol-treated lambs were significantly lower than NPBI levels in placebo-treated lambs. We conclude that deferoxamine effectively lowers NPBI in plasma effluent from the brain, and that both, deferoxamine and allopurinol, lower NPBI in cortical brain tissue.

Allopurinol↗

PubMed1998

Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle.

OBJECTIVE: Antioxidant enzymes are an important part of the defence mechanisms against free radical damage. Little is known, however, about the relationship between sex steroid hormones and cellular antioxidant systems. We have investigated the effect of physiological sex steroid changes on the erythrocyte antioxidant glutathione peroxidase (GSH-Px) activity during the menstrual cycle in a population of healthy normomenorrhoic women. DESIGN: Prospective, controlled. PATIENTS: Ten normally cycling women (age range: 19-28 years; mean: 23.3 years) were recruited for alternate-day blood sampling from the first day of one menstrual bleed until the first day of the subsequent menstrual phase. MEASUREMENTS: Plasma was analysed for LH, FSH, oestradiol (E2) and progesterone (P4) concentrations. Erythrocyte GSH-Px activity was evaluated on the same days in all subjects. Pyruvate-kinase (PK) activity, as an index of red blood cell population age, was also determined. RESULTS: All the women examined had a normal ovulatory cycle, as indicated by the hormone plasma pattern. Cycle length was standardized on the basis of the preovulatory E2 peak. Significant cycle phase-related changes in GSH-Px (P < 0.03) were observed, with higher GSH-Px activity levels being found from the later follicular to early luteal phase as compared to early follicular phase (chi 2 = 8.53, P < 0.001 and chi 2 = 5.54, P < 0.002, respectively). A significant positive correlation was observed between mean E2 and GSH-Px cycle-related changes (r = 0.78, P = 0.001). Conversely, no significant cycle phase-dependent variations were detected in PK. CONCLUSIONS: The findings support the hypothesis that physiological ovarian E2 production during the menstrual cycle may play an important role in regulating erythrocyte glutathione peroxidase activity.

Adult↗

PubMed1998

Hypoxia-induced free iron release in the red cells of newborn infants.

Heparinized blood samples were obtained at birth from 164 newborn infants (101 full term; 63 preterm). Intra-erythrocyte free iron concentration and hypoxanthine plasma levels were determined by high-pressure liquid chromatography. Intra-erythrocyte free iron concentration was higher in preterm than in full term babies (p < 0.0001) and adults (p < 0.0001). Statistically significant correlations were observed between intra-erythrocyte free iron concentration and hypoxanthine levels (r = 0.66; p = 0.0001), pH (r = -0.76; p = 0.0001), base excess (r = -0.79; p = 0.0001), and gestational age (r = -0.44; p = 0.0001) in both infant populations. Multiple regression analysis between intra-erythrocyte free iron concentration in cord blood, as an independent variable, and Apgar score at 1 min, pH, base excess, hypoxanthine values, FiO2 needed for resuscitation immediately after delivery, and gestational age, as dependent variables, identified hypoxanthine levels (p = 0.0003; partial F-test = 15.4) as the best single predictor of intra-erythrocyte free iron concentration. In conclusion, hypoxia induces intra-erythrocyte free iron release, and therefore enhances the risk of oxidative injury due to hydroxyl radical generation.

Adult↗

PubMed1998

Inflammatory pathogenesis of cortical polymicrogyria: an autopsy study.

Polymicrogyria, a cortical abnormality usually classified among neuron migration disorders, is characterized by different etiologies and pathogeneses. Recently, it has been proposed that polymicrogyria could be acquired as a consequence of a lasting damage to the developing brain. In this study, we test the hypothesis that an infection in the fetal adnexa may give rise to distant brain defects and eventually polymicrogyria. Thirty-two fetuses spontaneously aborted for extensive ascending chorioamnionitis at 15-26 wk of gestation were evaluated. Control subjects were represented by 8 fetuses aborted at 15-24 wk of gestation. A complete autopsy was carried out between 4 and 12 h after fetal expulsion. We found different histologic alterations in the primitive cortical architecture, both isolated and combined (undulation of the cortical ribbon, untimely cortical folding/molecular layer fusion, and neuronal loss). A total of 25 cases presented one or more of the above-described morphologic alterations in the brain (78%). On the contrary, similar alterations were never observed in any of the control brains (p=0.019). Our findings indicate that chorioamnionitis significantly impairs brain cortex morphogenesis. Such neuron damage may be caused by an unspecific, indirect mechanism of injury to the developing cortex involving hypoxia and free radical generation. The reported brain abnormalities may even evolve into polymicrogyria in surviving fetuses.

Abortion, Spontaneous↗

PubMed1997

Bronchopulmonary dysplasia of the premature baby: an immunohistochemical study.

Prematurely born infants who required assisted ventilation may develop chronic lung disease or bronchopulmonary dysplasia (BPD). The cells involved in the reparative process of the premature lung are not well defined. The repair of injured tissues is a highly standardized process and the most important cells are activated (modulated) fibroblasts (myofibroblasts). A key cytokine in controlling repair is transforming growth factor-beta (TGF-beta). To characterize the cells involved in the repair process of the premature lung, we employed immunocytochemical techniques and examined the lungs of 39 autopsied premature babies who had neonatal respiratory distress syndrome (RDS). All were treated in neonatal intensive care units and required mechanical ventilation and supplemental oxygen; all survived for at least 12 hours. Antibodies were employed against vimentin, alpha-smooth muscle (alpha-SM) actin, total muscle actin, desmin, MAC387, and TGF-beta. Our study indicates that myofibroblasts are normally present along terminal airways in the developing lung. These cells increase in number some days after lung injury, form bundles of cells encircling terminal air spaces, and acquire desmin contractile filaments shortly thereafter. Myofibroblasts do not lose their contractile filaments with time, suggesting a conversion to smooth muscle metaplasia. The proliferation and migration of such myofibroblasts at sites of lung injury is associated with the presence of TGF-beta. These findings suggest that myofibroblasts play an important role in premature lung repair. They may point the way to experimental and clinical trials that will identify drugs antagonistic to TGF-beta (or other cytokines). Such antagonists may protect the neonates who are at high risk of developing BPD.

Acute Disease↗

PubMed1997

Neonatal onset of hyperornithinemia-hyperammonemia-homocitrullinuria syndrome with favorable outcome.

We report on a neonate with hyperammonemic coma in whom hyperornithinemia-hyperammonemia-homocitrullinuria syndrome was diagnosed. Appropriate treatment led to rapid clinical and metabolic improvement. The incorporation of 14C-ornithine on cultured fibroblasts confirmed the diagnosis. At the age of 18 months, the patient is in excellent clinical condition.

Amino Acid Metabolism, Inborn Errors↗

PubMed1997

Effects of estradiol and medroxyprogesterone-acetate treatment on erythrocyte antioxidant enzyme activities and malondialdehyde plasma levels in amenorrhoic women.

Plasma levels of 17 beta-estradiol (E2) and malondialdehyde and erythrocyte antioxidant enzyme [superoxide dismutase, catalase, and glutathione-peroxidase (GSH-Px)] activities were evaluated in 20 healthy eumenorrhoic women (EW) on day 7 of the menstrual cycle and in 48 secondary hypothalamic amenorrhea patients (AP) (time 0). The AP were randomly divided into four subgroups of 12 subjects and treated with transdermal E2 for 30 days (subgroup A), oral medroxyprogesterone-acetate for 30 days (subgroup B), and transdermal E2 plus medroxyprogesterone-acetate for 30 days (subgroup C). The fourth subgroup acted as control. E2 and malondialdehyde plasma levels and superoxide dismutase, catalase, and GSH-Px activities were evaluated in subgroups A, B, and C on day 30 of therapy and in the control subgroup. GSH-Px activity was significantly higher in EW than in AP at time 0. A statistically significant increase in E2 plasma levels and GSH-Px activity was observed in subgroups A and C on day 30 of treatment, and there was a significant positive correlation between E2 plasma levels and GSH-Px activity in both subgroups. After a month of treatment, erythrocyte GSH-Px activity in subgroups A and C was not significantly different from that observed in EW. After a month of treatment, no significant variation was found in subgroup B nor in the control group. These results strongly suggest that when plasma E2 is restored to physiological levels in AP, it stimulates erythrocyte GSH-Px activity. Progesterone therapy did not induce significant modifications.

Adult↗