Predictors of Ominous Outcome in Infants Undergone to Cardiac Surgery and Cardiopulmonary by-Pass: S100B Protein.

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined time-points before during and after surgery. In all CHD children, S100B values showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the surgical procedure. Moreover, S100B concentrations in CHD death group were significantly higher (P<0.01) than controls at all monitoring time-points. The ROC curve analysis showed that S100B measured before surgical procedure was the best predictor of perioperative death, among a series of clinical and laboratory parameters, reaching at a cut-off of 0.1 µg/L a sensitivity of 100% and a specificity of 63.7%. The present data suggest that in CHD infants biochemical monitoring in the perioperative period is becoming possible and S100B can be include among a series of parameters for adverse outcome prediction.

Acute and chronic immunomodulatory changes in rat liver after fetal and perinatal asphyxia.

Hypoxic-ischemic encephalopathy (HIE) caused by fetal and perinatal asphyxia is an important cause of mortality in the neonatal period. Not only will asphyxia affect the brain but also other organs such as the liver and kidneys. Interestingly, it has been shown that liver damage is proportional to the severity of the asphyctic insult, implying an association between liver impairment and HIE. Accordingly, we investigated in an established rat model the acute and chronic hepatic response to both fetal (FA) and perinatal asphyxia (PA). In addition, we assessed whether fetal asphyctic preconditioning (PC) would have any beneficial effect on the liver. Inflammation, ceramide signaling and hepatocellular damage were analyzed in the livers of newborn and adult rats at several short- and long-term time points after both FA and PA. We found that although FA induced an acute inflammatory response, apoptotic mRNA levels and oxidative DNA damage were decreased at 96 h post FA. Whereas increased IL-6 and IL-10 mRNA levels were observed after PA, the combination of FA and PA (PC) attenuated the inflammatory response. Moreover, 6 h after PA anti-apoptotic genes were downregulated and associated with less lipid peroxidation, while preconditioned animals were comparable to controls. In summary, asphyctic PC seems to have an acute protective effect on the liver by modulating the inflammatory, apoptotic and anti-oxidative response. More insight into the hepatic response to asphyxia is necessary, as disturbed hepatic function is associated with metabolic diseases in later life.

Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Adjunctive effect of chlorhexidine antiseptics in mechanical periodontal treatment: first results of a preliminary case series.

OBJECTIVES: The aim of the present case series was to evaluate the clinical and microbiological effects of a single session of mechanical and manual scaling and root planing (SRP) combined with the use of two different chlorhexidine formulations in the treatment for generalized chronic periodontitis. METHODS: Ten patients affected by chronic periodontal disease with periodontal probing depth (PPD) ≥ 5 mm were treated with SRP plus local chlorhexidine. In each patient, similar teeth, treated with SRP with the adjunctive use of chlorhexidine digluconate and dihydrochloride or chlorhexidine gluconate, respectively, were selected and assigned to a test and a control group. In both groups, PPD, bleeding on probing (BOP) parameters, total bacterial counts (TBC) and quality of periodontal bacteria at time 0 and 6 weeks after treatment were measured. RESULTS: PPD significantly decreased over time both in the test and in the control group; however, no significant differences between the two groups were observed. BOP and TBC were significantly lower in the test than in the control group 6 weeks after treatment. In the post-treatment revaluation, a significant decrease both in the treatment and in the control group, for each of the single periodontal pathogens, was observed. CONCLUSION: In this study--a preliminary case series with small sample size and short follow-up--the adjunctive use of chlorhexidine (CHX) to SRP resulted in clinical and microbiological benefits in the treatment for generalized chronic periodontitis. A CHX gel formulation consisting of CHX digluconate and CHX dihydrochloride seems to lead some additional benefits over SRP plus CHX gluconate in the short term. Additional investigations are needed to evaluate the effectiveness of this antiseptic therapy.

Selective serotonin reuptake inhibitors in pregnancy.

The use of antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), during pregnancy is rapidly increasing. To date, the effects of SSRI on pregnant women and fetuses are controversial and still a matter of debate. Although a number of studies have shown that these antidepressants are not teratogenic, some of them have reported an increase of congenital malformations after antenatal exposure to SSRIs. Moreover, fetal behavior is affected by these drugs, 30% of infants suffer from neonatal withdrawal symptoms and long term sequelae have not yet been excluded. Since there are no clear guidelines for SSRI treatment in pregnancy, potential risks must be balanced against the effects of untreated maternal depression. Treatment with SSRIs before and during pregnancy should only be considered in case of real necessity. Milder forms of depression should be treated with alternative methods. In this paper we have reviewed the literature on effects of SSRIs on embryonic, fetal and infant development.

[Markers of brain injury in non-invasive biological fluids]. / Markers of brain injury in non-invasive biological fluids.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular autoregulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present article is aimed at investigating the role of dosage biochemical markers in non-invasive biological fluids such as S100B, a calcium binding protein, activin A, a protein expressed in Central nervous System (CNS).

Antioxidant properties of anesthetics: the biochemist, the surgeon and the anesthetist.

General anesthesia can impair immunological defense mechanisms while inducing an inflammatory reaction. Generalized inflammatory reactions involve leucocytes which in turn release inflammatory mediators and free oxygen radicals. General anesthetics include a series of gaseous and intravenous sedative-hypnotic agents indicated for induction and maintenance of general anesthesia as well as for sedation of intubated, mechanically ventilated adults in intensive care units (ICU). Some anesthetics, such as propofol, are characterized by a phenolic structure similar to that of alpha-tocopherol, and exhibit antioxidant properties that have been demonstrated both in vitro and in vivo. Similarly, other anesthetics show antioxidant and protective roles but this mechanism is to be related to their ability to induce antioxidant enzyme (i.e., heme oxygenase-1). The aim of the present review is to evaluate the antioxidant properties of anesthetics in various experimental models and if they may be considered efficient therapeutic tools in counteracting oxidative stress during general anesthesia and sedation in ICU.

Nitric oxide test during cardiac catheterization decreases the serum concentrations of S100B protein in adult patients with idiopathic pulmonary hypertension.

OBJECTIVE: Cardiac catheterization (CC) is a life-threatening procedure in adult patients. Complicated by idiopathic arterial pulmonary hypertension (IPAH), there is a potential risk of central nervous system (CNS) damage. We measured serum levels of a well-established brain damage marker, namely S100B, collected before, during and after CC in adult patients in whom the nitric oxide (NO) test had been performed. MATERIAL AND METHODS: In 12 adult patients who had undergone CC for IPAH diagnosis, we recorded clinical and standard monitoring procedures (laboratory variables and echocardiographic patterns) and serum concentrations of S100B before (time 0), during (time 1) and after the NO test (time 2) and at 24 h after (time 3) the procedure in samples obtained from the systemic and pulmonary circulation. Patients were subdivided into NO test responders (n=6) and non-responders (n=6). Neurological evaluation was performed at admission and at discharge from hospital. RESULTS: Adult patients subjected to CC showed no overt neurological injury at discharge from hospital. No significant differences (p > 0.05 for all) in S100B serum levels between groups at times 0, 1 and 3 have been shown independently from the sampling site. It was noteworthy that the concentration of protein in the responders group at time 2 was significantly decreased (p < 0.05, for all) compared to the responder group and to baseline values. A significant correlation was found between arterial oxygen partial pressure and individual S100B concentration in the pulmonary and systemic bloodstream in the entire study group (R = -0.66 and R = 0.71, respectively; p < 0.05, for both). CONCLUSIONS: The data suggest that S100B protein assessment, as well as the NO test, may be useful when monitoring possible CNS damage during CC in patients with IPAH, and may also be valuable in relation to brain functions, especially when performed as an emergency procedure in severely hypoxic patients.

Role of carbon monoxide and biliverdin in renal ischemia/reperfusion injury.

Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin/bilirubin with a concurrent release of iron. There is strong evidence that HO activity and products play a major role in renoprotection, however the exact molecular mechanisms underlying the beneficial effects exerted by this pathway are not fully understood. This review is aimed at illustrating the possible mechanism/s by which HO is renoprotective in the context of ischemia/reperfusion. We will first analyze the effects of exogenous administration of bilirubin/biliverdin and CO and then describe their biological activities once generated endogenously following stimulation of the HO pathway by either pharmacological means or gene targeting-mediated approaches.

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.

Phentolamine administration increases blood S100B protein levels in pediatric open-heart surgery patients.

AIM: Phentolamine administration during open-heart surgery shortens the cooling and rewarming phases of cardiopulmonary bypass (CPB) and hastens weaning from mechanical ventilation and extubation. Data on the effects of phentolamine on cerebral circulation and function in this setting are lacking. This study reports the cerebral effects of phentolamine using blood S100B protein levels and the middle cerebral artery pulsatility index (MCA PI). METHODS: Sixty pediatric patients undergoing congenital heart disease repair were randomly assigned to receive either phentolamine 0.2 mg kg(-1) i.v. (n = 30) or placebo (n = 30) before the cooling and rewarming phases of CPB. Samples for S100B measurement were collected at seven predetermined time-points before, during and after surgery. MCA PI values were recorded at the same times as sampling. RESULTS: S100B blood levels were higher in the phentolamine-treated group than in controls after rewarming (3.53 +/- 1.88 vs 1.58 +/- 0.53 microg l(-1); p < 0.001), remained persistently higher at the end of surgery (2.95 +/- 0.91 vs 0.79 +/- 0.21 microg l(-1); p < 0.001) and returned to normal ranges 12 h later than in the placebo group (p > 0.05). MCA PI values were also significantly higher at the end of surgery in the phentolamine-treated group (1.83 +/- 0.50 vs 1.22 +/- 0.34; p < 0.01). Cooling and rewarming times were shorter in the phentolamine-treated group (p < 0.01, for all). CONCLUSION: Despite improved peripheral vasodilatation and perfusion, phentolamine administration in pediatric open-heart surgery is correlated with increased cerebrovascular resistance and brain damage.

S100B protein cord blood levels and development of fetal behavioral states: a study in normal and small-for-dates fetuses.

OBJECTIVE: We aimed to determine whether S100B protein levels in cord blood and the development of fetal behavioral states were altered and interrelated in small-for-dates (SFD) fetuses. METHODS: Umbilical cord blood samples were collected from 12 SFD fetuses with normal umbilical artery (UA) Doppler findings, from six SFD fetuses with abnormal Doppler waveform patterns and from 36 controls matched for gestational age. S100B protein levels were measured by means of a specific radioimmunoassay. Fetal behavioral state recordings were made before delivery by Cesarean section and data were expressed as percentage of quiet sleep coincidence (C1F), of activity state coincidence (C2-4F) and of no coincidence (NOC). Flow velocimetry waveforms were recorded from the uterine artery, UA and fetal middle cerebral artery (MCA). RESULTS: Mean S100B protein levels in umbilical plasma were significantly higher in the six SFD infants with abnormal prenatal Doppler findings (3.31 +/- 0.65 microg/l) than in SFD infants with normal Doppler findings (1.56 +/- 0.35 microg/l) and in controls (1.23 +/- 0.43 microg/l). Similarly in these fetuses NOC was higher and C2F significantly lower (p < 0.05), but there was no significant difference in C1F. S100B concentrations were correlated with the UA pulsatility index (PI) (r = 0.78, p < 0.01), with the MCA PI (r = -0.78, p < 0.01) and with the UA PI/MCA PI ratio (r = 0.80, p < 0.01). Also, NOC and C2F percentages were correlated with the UA PI (r = 0.61, p < 0.01 and r = -0.61, p < 0.01, respectively), with the MCAPI (r = -0.72, p < 0.001 and r = 0.66, p < 0.01, respectively), and with the UA PI/MCA PI ratio (r = 0.60, p < 0.01 and r = -0.54, p < 0.05, respectively). NOC was also correlated with S100B protein (r = 0.48, p < 0.05); the correlation of S100B protein and C2F almost reached significance (r = -0.47, p < 0.05). CONCLUSIONS: This study provides evidence of a relationship between a biochemical marker of brain development and/or integrity and the development of fetal behavioral states, offering additional information on brain maturation in normal and high-risk pregnancies.

Maternal nitric oxide supplementation increases adrenomedullin concentrations in growth retarded fetuses.

Nitric oxide (NO) and adrenomedullin (AM) are both involved in the regulation of fetoplacental circulation in human pregnancy. The aim of this study was to investigate the effect of maternal NO supplementation in pregnancies complicated by intrauterine growth retardation (IUGR) on maternal and fetal NO and AM concentrations and their correlation with uteroplacental and fetal blood flow. We studied 20 pregnant women with IUGR and impaired uteroplacental blood flow between 27 and 35 weeks of gestation randomly selected to receive either transdermal glyceryl trinitrate or placebo. Maternal NO metabolites (NOx) and AM concentrations did not change before and after NO treatment. AM levels were significantly higher in growth retarded fetuses whose mothers received NO donors (114.1 +/- 17.6 pg/ml) than in untreated fetuses (59.8 +/- 38.6 pg/ml), whereas NO treatment did not affect significantly fetal NOx levels. Fetal AM correlated with middle cerebral artery pulsatility index in untreated IUGR but not in NO treated pregnancies.

Elevated S100B protein as an early indicator of intracranial haemorrhage in infants subjected to extracorporeal membrane oxygenation.

UNLABELLED: The aim of this investigation was to verify whether plasma S100B could be a useful tool in identifying which infants subjected to extracorporeal membrane oxygenation (ECMO) might develop intracranial haemorrhage (ICH). A case-control study of eight infants who developed ICH during ECMO was conducted. Plasma samples collected daily after ECMO insertion were assessed for S100B and compared with those obtained from eight infants supported by ECMO who did not develop ICH. Cerebral ultrasound and Doppler velocimetry waveform patterns in the middle cerebral artery (MCA PI) were also recorded at the same time as blood sampling. S100B blood concentrations were significantly higher in the group of infants with ICH 72 h before any signs of haemorrhage could be detected by ultrasound (ICH: 2.91 +/- 0.91 microg/L vs. control: 0.53 +/- 0.15 microg/L), reaching their peak at day 6, when cerebral ultrasound scan patterns were suggestive of intracranial haemorrhage (ICH: 3.50 +/- 1.03 microg/L vs. control: 0.66 +/- 0.27 microg/L) (p < 0.05, for both). The highest S100B levels were observed in the three ICH infants who expired during the ECMO procedure (3.43 microg/L, 4.0 microg/L, 4.12 microg/L, respectively). MCA PI values in the ICH group were also significantly higher, but only 24 h before any ultrasound pattern of bleeding was detected (ICH: 2.31 +/- 0.22 vs control: 1.81 +/- 0.24) (p < 0.05). CONCLUSION: This study suggests that blood S100B measurement could be a promising tool for the identification of infants at risk of ICH when imaging assessment and clinical symptoms of haemorrhage might still be silent.

Circulating adrenomedullin is increased in preterm newborns developing intraventricular hemorrhage.

Adrenomedullin is a novel vasoactive peptide that participates in cerebral blood flow regulation and circulates in human plasma. To verify whether plasma adrenomedullin is able to identify preterm newborns at risk of intraventricular hemorrhage (IVH), we performed a case-control study. Plasma samples collected within 6 h after birth in 24 preterm newborns who developed IVH, as diagnosed at 72 h, were assessed for adrenomedullin and compared with those obtained from 48 preterm newborns, matched for gestational age, who did not develop IVH. Cerebral ultrasound and Doppler velocimetry waveform patterns in the middle cerebral artery were also recorded at the time of blood sampling. Adrenomedullin blood concentrations and middle cerebral artery pulsatility index values were significantly higher in infants developing IVH (20.1 +/- 4.5 fmol/mL and 1.71 +/- 0.21 fmol/mL, respectively) than in controls (7.5 +/- 3.0 fmol/mL and 1.49 +/- 0.19 fmol/mL, respectively). Adrenomedullin blood concentrations correlated with middle cerebral artery pulsatility index (r = -0.77, p < 0.01) and with the grade of IVH extension (r = 0.83, p < 0.01). This study suggests that adrenomedullin blood concentration might be a promising tool for identifying preterm infants at risk of IVH immediately after birth, when imaging assessment and clinical symptoms of hemorrhage are still silent.

Kangaroo care improves post-extubation cardiorespiratory parameters in infants after open heart surgery.

UNLABELLED: The aim of this investigation was to study whether kangaroo care could be helpful in full-term infants subjected to cardiac postoperative intensive care during the early post-extubation hours. Kangaroo care was performed at 2-h intervals in the first 12 h after extubation in 5 male infants and assessed by cardiorespiratory parameters. Results showed that, during kangaroo care, heart rate (123 +/- 4 vs 128 +/- 5 bpm), respiratory frequency (43 +/- 3 vs 51 +/- 5 breath pm), transcutaneous carbon dioxide (46 +/- 2 vs 50 +/- 4 mmHg) and central venous pressure (11 +/- 0.8 vs 12 +/- 1.2 mmHg) significantly decreased (p <0.05 for all), while oxygen saturation (78 +/- 6 vs 74 5 mmHg) and transcutaneous oxygen pressure increased (42 +/- 2 vs 38 +/- 3 mmHg) (p < 0.05 for all). CONCLUSION: We conclude that kangaroo care might be a useful technique contributing to stabilization of the cardiorespiratory status in postoperative paediatric cardiac intensive care.