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Biomedical subjects

Diego Gazzolo

Publications and source records attributed to Diego Gazzolo.

32 records · Page 2Linked to original sources

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.

Blotting, Western↗

Measurement of urinary S100B protein concentrations for the early identification of brain damage in asphyxiated full-term infants.

BACKGROUND: Perinatal asphyxia is a major cause of mortality and morbidity. To date there are no reliable methods to detect which infants will develop brain damage after asphyxia insult. We investigated whether measurements of urine levels of S100B in asphyxiated full-term newborns may be a useful tool for early detection of postasphyxia brain damage. METHODS: A prospective study of 38 infants with perinatal asphyxia and 96 control subjects, recruited at 3 tertiary departments of neonatology between April 1, 1999, and July 31, 2001. Routine laboratory variables, neurologic patterns, and urine concentrations of S100B protein were determined at 4 predetermined time points (first urination and 12, 24, and 72 hours after birth). The concentrations of S100B protein in urine were measured using an immunoluminometric assay. The results were correlated with the presence or absence of neurologic abnormalities at age 12 months. RESULTS: S100B protein levels were significantly higher in samples collected at all monitoring times from new-borns with abnormal neurologic findings on follow-up (first urination, 1.92 +/- 0.33 micro g/L; 12 hours, 2.78 +/- 1.71 micro g/L; 24 hours, 4.75 +/- 4.08 micro g/L; 72 hours, 5.93 +/- 1.63 micro g/L) than in samples from those without (first urination, 0.24 +/- 0.06 micro g/L; 12 hours, 0.13 +/- 0.06 micro g/L; 24 hours, 0.21 +/- 0.07 micro g/L; 72 hours, 0.12 +/- 0.04 micro g/L) or from healthy infants (first urination, 0.11 +/- 0.01 micro g/L; 12 hours, 0.12 +/- 0.03 micro g/L; 24 hours, 0.12 +/- 0.02 micro g/L; 72 hours, 0.12 +/- 0.02 micro g/L) (P<.001 for all). An S100B concentration cutoff of 0.28 micro g/L at first urination had a sensitivity of 100% and a specificity of 87.3% for predicting the development of abnormal neurologic findings on follow-up. The sensitivity and specificity of measurements obtained between 12 and 72 hours were up to 100% and 98.2%, respectively. CONCLUSION: Longitudinal S100B protein measurements in urine soon after birth are a useful tool to identify which asphyxiated infants are at risk of long-term neurologic sequelae.

Adult↗

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.

Adult↗

S100B testing in pregnancy.

Follow-up studies have shown that the vast majority of neurological abnormalities present during childhood can have a prenatal or perinatal origin. It is relevant, therefore, to investigate the timing of adverse insults in the search for measures of prevention. However, such knowledge is still incomplete and subject to debate. Until recently, clinical-laboratory assessment was based essentially on biochemical aspecific parameters, ultrasound and Doppler patterns, and the determination of blood pH and gases. However, the measurement of brain constituents may offer a direct indicator of cell damage in the nervous system. The S100B protein, a calcium-binding protein highly concentrated in the nervous system, appears to meet the criteria required of such a marker in prenatal and perinatal medicine for its reproducible, simple and sensible measurements. Results in high-risk pregnancies demonstrated that S100B concentration increased in amniotic fluid and in cord blood of fetuses with brain damage. In addition, S100B protein has been also usefully employed to monitor the effects of maternal-antenatal therapy, such as NO and glucocorticoid administration. It appears also to be relevant that a neurotrophic role has been hypothesized for the protein, which in fact exhibits in amniotic fluid, in cord blood and in placenta patterns of concentration related to the gestational age.

Amniotic Fluid↗

Ontogenetic localization and distribution of S-100beta protein in human placental tissues.

OBJECTIVE: To investigate whether S-100beta, a brain-specific protein found in amniotic fluid and fetal circulation, is present in fetoplacental tissues throughout gestation. METHODS: S-100beta protein localization and concentration were assessed in placentae, fetal membranes, and cord vessels. Tissues were obtained from 40 pregnant women at different gestational ages: first trimester (n = 10), second trimester (n = 10), early third trimester (n = 10), and late third trimester (n = 10). RESULTS: In the placenta, S-100beta was localized in villous and intermediate trophoblast cells. The intensity of immunostaining and protein concentration increased with advancing gestation. S-100beta protein was also present in amnion, trophoblast, and decidual cells of fetal membranes, and in endothelial cells of umbilical vessels at all gestational ages. CONCLUSION: This study demonstrated that fetoplacental tissues contain S-100beta protein, suggesting that these tissues may, at least in part, be responsible for the high level found in the fetal circulation. Although the significance of placental S-100beta is unknown, this origin should be taken into account when this protein is used as a marker of brain injury in the fetus or infant at birth.

Blotting, Western↗

S100B protein is increased in asphyxiated term infants developing intraventricular hemorrhage.

OBJECTIVE: To establish whether S100B protein may be useful in the early detection of intraventricular hemorrhage in asphyxiated term infants. DESIGN: Case-control study. PATIENTS: Twenty full-term newborns with intraventricular hemorrhage, 20 asphyxiated infants without intraventricular hemorrhage, and 80 normal newborns. INTERVENTIONS: Routine laboratory variables and neurologic patterns were assessed at birth after 12 and 72 hrs. Ultrasound imaging and middle cerebral artery Doppler velocimetry pulsatility index were recorded at 12 and 72 hrs after birth. S100B protein blood concentrations were determined at 12 hrs. MEASUREMENTS AND MAIN RESULTS: S100B protein levels were significantly higher in samples collected from newborns who developed intraventricular hemorrhage (1.87 +/- 0.60 microg/L) than from those who did not develop intraventricular hemorrhage (0.72 +/- 0.39 microg/L) or from normal infants (0.66 +/- 0.31 microg/L). Multiple logistic regression analysis showed a significant correlation between circulating S100B protein concentrations and the occurrence of intraventricular hemorrhage. CONCLUSIONS: This study suggests that elevated S100B protein represents a useful tool for the early detection of intraventricular hemorrhage in the postasphyxia period when clinical examination and cerebral ultrasound might still be silent.

Asphyxia↗

Circulating S100beta protein is increased in intrauterine growth-retarded fetuses.

To determine whether S100beta, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n = 10) or abnormal (n = 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100beta protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100beta proteins in umbilical plasma levels were higher (p < 0.05) in IUGR patients (121.8 +/- 70.4 fmol/mL) than in control patients (54.7 +/- 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 +/- 55.2 fmol/mL). Fetal S100beta concentrations correlated with middle cerebral artery pulsatility index (r = -0.536, p < 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r = 0.469, p < 0.03). No difference in the localization or intensity of S100beta staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100beta protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period.

Adult↗

S100B protein in biological fluids: a tool for perinatal medicine.

The diagnosis of perinatal insults currently relies on adequate documentation of general medical and obstetric factors and on radiologic and laboratory assessments. The measurement of brain constituents such as S100B protein may offer an alternative and direct indicator of cell damage in the nervous system when clinical and radiologic assessments are still silent and has the additional advantage of providing a quantitative indicator of the extent of brain lesions. S100B protein has been measured by several immunoassays in biological fluids (i.e., cerebrospinal fluid, blood, amniotic fluid, and urine) from fetuses and newborns at high risk of perinatal brain damage. S100B protein in biological fluids increased at an early stage when standard monitoring procedures were still silent in the study populations that later developed brain damage. S100B concentration was also significantly correlated with the extent of brain lesions. S100B protein appears to satisfy the criteria for a marker for brain injuries in perinatal medicine: (a) simple to perform measurements with good reproducibility; (b) detection in a variety of biological fluids, possibly reducing perinatal stress related to testing; (c) possible use in longitudinal monitoring because of its 1-h half-life; and (d) well-established use as an early and quantitative marker of brain lesions/damage. Finally, because of the neurotrophic role putatively played by S100B, its measurement in biological fluids at pre-/perinatal ages makes it a candidate for the laboratory evaluation of brain maturation.

Animals↗

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.

Amniotic Fluid↗

S100B blood levels correlate with rewarming time and cerebral Doppler in pediatric open heart surgery.

BACKGROUND: Brain hyperthermia, accompanying the rewarming phase of cardiopulmonary bypass (CPB), has been involved in the genesis of postoperative brain damage. Blood S100B levels are emerging as a marker of brain distress, and could offer a reliable monitoring tool at different times during and after open heart surgery. METHODS: Thirty-two patients undergoing repair of congenital heart disease with CPB and deep hypothermic circulatory arrest (DHCA) were monitored by S100B blood levels and middle cerebral artery Doppler velocimetry pulsatility index (MCA PI) before, during, and after surgical procedure at five predetermined time-points. RESULTS: Both S100B and MCA PI significantly increased, MCA PI values exhibiting a peak at the end of surgery time-point (p > 0.05), while S100B blood levels were increased at the end of CPB (p < 0.05). Multivariate analysis, with S100B levels measured at the end of CPB as dependent variable, showed a positive significant correlation with MCA PI (p = 0.04), with the CPB and the rewarming duration (p = 0.03 and p = 0.009, respectively). CONCLUSIONS: The present results show a significant correlation between a biochemical marker of brain damage and an index of increased cerebrovascular resistance, with higher levels during the rewarming CPB phase in pediatric open heart surgery.

Blood Volume↗