Pierluigi Bruschettini

Pediatric Concentrations of S100B Protein in Blood: Age- and Sex-related Changes

The term S100 refers to members of a multigenic family of calcium-modulated proteins, mostly of low molecular mass (∼10 000 Da), first identified as a protein fraction detectable in the brain and called S100 because of its solubility in a solution of 100 g/L ammonium sulfate (1). The protein seems to be most abundant in glial cells, although its presence in neuronal subpopulations has also been reported (2)(3). The biological role of this protein within the cell populations that contain it has not been completely elucidated. The possibility of an extracellular biological role for S100B, which, secreted by astrocytes as a cytokine, may have a neurotrophic effect during both development and nerve regeneration at physiologic (nmol/L) concentrations, appears particularly interesting (4)(5)(6)(7). Recent studies conducted in perinatal medicine that showed a correlation between S100B protein measured in several biological fluids (i.e., amniotic fluid, cord blood, and urine) and gestational age (8)(9)(10) appear consistent with a neurotrophic role for the protein. The present study offers a reference curve for S100B protein in peripheral blood from the postnatal period to 15 years of age in healthy pediatric patients. Between April 1997 and July 2000, we routinely collected blood samples for S100B measurement from healthy children admitted to our Institute for routine day-hospital investigations. All of the children were delivered at term without perinatal complications, and their clinical history, from birth to the time of blood sampling, was negative for neurologic abnormalities and comorbidities. We recruited a total of 1004 healthy children (males, n = 482; females, n = 522) whose ages ranged from 1 month to 15 years of age (mean, 8 years). On admission to the study, all of the patients were checked against routine clinical and laboratory indices, …

Amniotic fluid S100B protein in mid-gestation and intrauterine fetal death

Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of alpha fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case-control study in 758 healthy women undergoing amniocentesis at mid-gestation, of whom 12 had a spontaneous intrauterine fetal death before 28 weeks, and 746 matched controls. Concentrations were corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Concentrations of S100B, but not alpha fetoprotein, were significantly higher (p<0.0001) in women who later had spontaneous fetal death (median 4.431 MoM [95%CI 3.605-6.197]) than in controls (1.000 MoM [1.062-1.121]). Sensitivity, specificity, and positive and negative predictive values of S100B as a diagnostic test were 100%, suggesting that measurement of this protein at amniocentesis could be useful to identify at-risk women.

Human milk contains S100B protein

The present study constitutes the first finding of the calcium-binding protein S100B and of its mRNA in human milk, as revealed by a quantitative immunoluminometric assay, by Western blot analysis and by reverse transcription-polymerase chain reaction (RT-PCR) assay followed by restriction enzyme digestion. The concentration of S100B in milk is markedly higher than that observed in other biological fluids such as cord blood, peripheral blood, urine, cerebrospinal fluid and amniotic fluid. This finding could be related to a possible trophic role, which has been hypothesized for the protein.

Amniotic fluid levels of S100B protein in normal and trisomy-21 foetuses.

BACKGROUND The human chromosome 21 has been shown to contain the gene for the beta subunit of the S100B protein. The present case-control study was aimed at investigating whether overproduction of S100B protein is detectable in the amniotic fluid of foetuses with trisomy-21. METHODS Measurements of S100B in amniotic fluid samples from 14 pregnant women with trisomy-21 foetuses were compared with those obtained from 182 physiological pregnancies. S100B was measured in the samples using an immunoluminometric assay (LIA-mat Sangtec 100). RESULTS Our results showed that S100B protein amniotic fluid levels were significantly higher in trisomy-21 foetuses (0.83+/-0.21 microg/l) than in controls (0.51+/-0.22 microg/l) (p<0.05). CONCLUSION The present finding supports the notion that the expression of S100B is increased in trisomy-21 foetuses; it also constitutes a prerequisite basis for a possible involvement of the protein in pathogenic processes associated with trisomy-21, and/or for its potential employment as a diagnostic tool.

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 μg l‐1; p < 0.001), remained persistently higher at the end of surgery (2.95 ± 0.91 vs 0.79 ± 0.21 μg 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).

Saliva S100B in professional sportsmen: High levels at resting conditions and increased after vigorous physical activity

BACKGROUND Neurological dysfunction is a key medical concern in professional sportsmen (PSM). We investigated whether saliva S100B concentrations in PSM and healthy controls are modified before and after training. METHODS We conducted a case-control-study in 75 patients (25 PSM vs 50 controls) in which S100B saliva concentrations were expressed as absolute values and percentage of change (%) from samples drawn before (T0) and after (T1) training. RESULTS No differences (P>0.05) between groups were found regarding clinical, monitoring and laboratory parameters. S100B both in PSM and controls was higher at T1 when compared to T0 (P<0.01). In PSM, S100B was higher than controls (P<0.001) at T0 and T1. S100B% at T0-T1 was higher (P<0.001) in PSM and in controls and between PSM and controls (P<0.001). CONCLUSIONS Increased saliva S100B levels in PSM before and after training suggest a paracrine/autocrine proteins role connected to stressing activity, which becomes especially evident in PSMs.

S100B Protein Concentrations in Amniotic Fluid Are Higher in Monoamniotic than in Diamniotic Twins and Singleton Pregnancies

S100B is an acidic calcium-binding protein of the EF-hand family present in the central nervous system, where it is located mainly in glial cells (1). It has been suggested that the protein is involved in various cellular functions, but precisely which is still a matter of debate. The protein has been found to act at physiologic concentrations as a cytokine with a neurotrophic role in experimental models, in cell cultures, and in biological fluids such as cord blood, peripheral blood, and urine (1)(2)(3)(4). This hypothesis has been corroborated by measurements of S100B protein in amniotic fluid in the second trimester of pregnancy (5). The present work, following from an earlier study, investigates amniotic fluid S100B concentrations in twins. We performed a case-control study (between January 1998 and June 2002) of 49 women with physiologic twin pregnancies (27 monoamniotic and 22 diamniotic) who underwent amniocentesis to exclude chromosomal abnormalities between the 15th and 18th weeks of gestation (mean, 16.5 weeks). The control group consisted of 490 singleton pregnancies matched for gestational age and weight at sampling and normal neonatal outcome (5 control fetuses for each twin fetus). Appropriate fetal growth was defined by the presence of ultrasonographic signs (when biparietal diameter and abdominal circumference were between the 10th and 90th percentiles) according to the normograms of Campbell and Thoms (6) and by postnatal confirmation of a birth weight between the 10th and 90th percentiles according to our population standards after correction for maternal height, weight, and parity and the sex of the newborns. Exclusion criteria included intrauterine growth retardation; gestational hypertension; diabetes and infections; fetal malformations; chromosomal abnormalities; maternal exposure to alcohol, cocaine, or smoke; perinatal asphyxia; and dystocia. The local ethics committee approved the study protocol, and the parents of the fetuses examined gave …

Doppler velocimetry and behavioural state development in relation to perinatal outcome in pregnancies complicated by gestational diabetes

Seventy-one pregnancies complicated by gestational diabetes and 100 healthy pregnancies were monitored on two occasions (between 27th-32nd and 33rd-36th week of gestation) by behavioural state analysis (1F coincidence; 2F coincidence) and umbilical artery Doppler velocimetry (UA) (Resistance Index, RI). The purpose of our study was to determine if the development of behavioural states and Doppler velocimetry: (1) differ between normal and gestational diabetic cases; (2) in gestational diabetic cases, are they related to the degree of abnormality of the maternal oral glucose tolerance test (OGTT)?; and (3) are they predictors of perinatal outcome? (i.e. emergency caesarean section; low Apgar scores; respiratory distress syndrome; neonatal hypoglycaemia and neurological abnormality in the neonate and/or at 4 months of age). Our findings suggest that: (1) results on behavioral state development and Doppler velocimetry were significantly different in gestational diabetic cases; (2) infants of women with gestational diabetes who are neurologically abnormal during the newborn period, had a poor development of coincidence 2F during fetal life and had neonatal hypoglycaemia more often than infants with a normal neurological outcome; (3) in cases with abnormal neurological outcome, the maternal diabetes was more severe than in those cases with normal outcome.

Pregnancy-induced hypertension, antihypertensive drugs and the development of fetal behavioural states

In 21 pregnancies complicated by pregnancy-induced hypertension (PIH) which was treated by antihypertensive drugs (labetalol, nifedipine), fetal behavioural recordings (quiet state, C1F; active state, C2F; no coincidence, NOC) and Doppler measurements of blood flow velocity in the umbilical artery (UA) (resistance index, RI) were made on two occasions (27-32 and 33-36 weeks of gestation). Data were compared to those of a control group of normally grown fetuses (n = 96); in 15 cases we were able to match fetuses from the study group for age (+/- 1 week) and weight (+/- 150 g) at birth with fetales from a control group. It was the aim of this study to investigate if there are disturbances in the development of fetal behavioural states and if possible disturbances are due to poor fetal growth or to antihypertensive therapy. Our results show that in PIH treated by antihypertensive drugs, there are disturbances in the development of fetal behavioural states with higher percentages of NOC and C1F, lower percentages of C2F, and higher UA RI values. These disturbances are mainly due to coexisting placental impairment and poor fetal growth rather than to nifedipine or labetalol therapy, although these drugs may cause some redistribution of states.

Predictors of perinatal outcome in intrauterine growth retardation: a long term study.

UNLABELLED Fifty-three intrauterine retarded fetuses (IUGR) and seventy-five healthy pregnancies were monitored by neurobehavioural profile (quiet state or S1F and activity state or S2F percentages) and umbilical artery Doppler velocimetry (UA RI) on two occasions between the 27th-32nd and the 33rd-36th week of gestation. The aims of the present study were the following 1) to relate S1F, S2F and RI to mild and severe IUGR 2) to relate behavioural state analysis and UA Doppler velocimetry to the following perinatal outcomes: Cesarean section (CS); Preterm delivery (PD); small for gestational age (SGA); Apgar score at 1st and 5th min < 7; Respiratory Distress Syndrome (RDS); Neurological Injury (NI) (evaluated at the birth, the 4th, the 8th and the 12th month of life). 3) to establish the best predictors of perinatal outcome with these monitoring parameters by a stepwise computerized processing. Our results suggest: 1) mild IUGR, characterized by a progressive increase in peripheral vascular resistances, positive diastolic peak flow (RI: 0.72 +/- 0.01; mean +/- SD), is associated with gradual increase in S1F (12.51 +/- 2.84; mean +/- SD) and a decrease in S2F (27.51 +/- 2.81; mean +/- SD) percentages; 2) severe IUGR, characterized by zero or negative diastolic peak flow (UA RI-->1), is associated with a significant increase in S1F (21.32 +/- 12.11; mean +/- SD) and a decrease in S2F percentages (30.93 +/- 20.35; mean +/- SD). IN CONCLUSION S1F is the best predictor of severe IUGR and significant for all the perinatal outcomes selected; S2F is the best predictor of mild IUGR and significant for SGA; UA RI is the best parameter for recognizing mild IUGR and evolution to severe IUGR.