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Biomedical subjects

Fabrizio Michetti

Publications and source records attributed to Fabrizio Michetti.

At least 19 recordsLinked to original sources
PubMed2006

Urinary S100B protein concentrations are increased in intrauterine growth-retarded newborns.

BACKGROUND: Intrauterine growth retardation is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect brain damage in these patients. METHODS: We conducted a case-control study in tertiary NICUs from December 2001 to December 2003 with 42 intrauterine growth retardation infants and 84 controls. Routine laboratory variables, neurologic outcome at 7-day follow-up, ultrasound imaging, and urine concentrations of S100B protein were determined at 5 time points. Urine S100B levels were measured by an immunoluminometric assay at first urination, 24, 48, and 72 hours, and 7 days after birth. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling. RESULTS: S100B protein was significantly higher at all of the monitoring time points in urine taken from intrauterine growth retardation newborns than in control infants. When intrauterine growth retardation infants were corrected for the presence of abnormal (group A) or normal (group B) neurologic examination 7 days after birth, S100B was significantly higher at all of the predetermined monitoring time points in group A infants than in group B or controls. At a cutoff of 7.37 multiples of median at first urination, S100B achieved a sensitivity of 95% and a specificity of 99.1% as a single marker for predicting an adverse neurologic outcome. Twenty of 126 patients had neurologic abnormalities, making an overall prevalence of the disease in our population of 15.9% (pretest probability). With respect to the performance of S100B in predicting brain damage, its positive and negative predictive values were 91.0% and 99.0%, respectively. CONCLUSIONS: Increased urine S100B protein levels in intrauterine growth retardation newborns in the first week after birth suggest the presence of brain damage reasonably because of intrauterine hypoxia. Longitudinal S100B protein measurements soon after birth are a useful tool to identify which intrauterine growth retardation infants are at risk of possible neurologic sequelae.

Biomarkers↗
PubMed2006

Canine cognitive deficit correlates with diffuse plaque maturation and S100beta (-) astrocytosis but not with insulin cerebrospinal fluid level.

Like humans, canines develop with aging beta-amyloid (Abeta) plaques and a progressive cognitive deficit on tasks similar to those used in diagnosis and follow-up of Alzheimer's disease. Owing to that, dogs are quite unique to investigate the early events taking place in the diffuse Abeta plaque maturation and its relationship with cognitive deficit. The aim of the present investigation was to study the link between the diffuse Abeta plaque maturation and the astro- and microglial reactivity. The involvement of insulin and beta-subunit of S100 protein (S100beta) overexpression in the process was also investigated. Abeta plaques were measured and counted in prefrontal cortex of 16 pet dogs of different breeds, weight and sex, classified as control and with a light or severe cognitive deficit. A correlation between canine graded cognitive deficit, diffuse plaque maturation, and S100beta (-) astrocytosis, but not with cerebrospinal fluid insulin level, was found that may reflect the very early events of Abeta deposition in Alzheimer's disease.

Aging↗
PubMed2006

High maternal blood S100B concentrations in pregnancies complicated by intrauterine growth restriction and intraventricular hemorrhage.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with perinatal mortality and with neurologic damage from intraventricular hemorrhage (IVH). We investigated whether S100B, a neural protein found in high concentrations after cell injury in the nervous system, is increased in serum of women whose pregnancies are complicated by IUGR and whose newborns develop IVH. We also explored the prognostic accuracy of maternal serum S100B for IVH in the newborn. METHODS: We conducted a case-control study of 106 pregnancies complicated by IUGR, including a subgroup (n = 26) who developed IVH after birth, and 212 unaffected pregnancies matched for gestational age. Ultrasound examination, Doppler velocimetry patterns (in the utero-placental vessels and middle cerebral artery), and maternal blood collection were performed before birth; cerebral ultrasound and neurologic examinations were performed after birth. RESULTS: S100B was higher (P <0.001) in IUGR pregnancies complicated by IVH than in those that were not and in controls. At a cutoff of 0.72 microg/L, sensitivity was 100% [95% confidence interval (95% CI), 87%-100%] and specificity was 99.3% (97.5%-99.9%) for prediction of IVH (area under the ROC curve, 0.999). The prevalence of IVH was 8.2% in the whole study population, 93% (95% CI, 83.6%-100%) in those with maternal S100B >0.72 microg/L, and 0% (0%-2.5%) in those with maternal S100B <0.72 microg/L. CONCLUSION: For prediction of IVH, measurements of maternal S100B may be useful at times before clinical, laboratory, and ultrasound patterns can identify risk of IVH.

Case-Control Studies↗
PubMed2006

Systemic endotoxin administration results in increased S100B protein blood levels and periventricular brain white matter injury in the preterm fetal sheep.

OBJECTIVE: Intrauterine infection is suggested to cause perinatal brain white matter injury. The aim of the present study was to clarify, whether intravenous application of endotoxin results in neuropathological findings and increased blood levels of the S100B protein, which is a consolidated marker of brain injury. METHODS: Twenty-one fetal sheep were chronically catheterized at a mean gestational age of 107+/-1 days (0.7 of gestation). Three days after surgery fetuses received either 100 (n = 9), 500 (n = 5) or 2500 ng (n = 1) lipopolysaccharide (LPS; E. coli; O127:B8, Sigma-Aldrich) or 2 ml 0.9% saline (n = 6) i.v. S100B protein blood levels were assessed before during and after LPS or placebo administration. Brain damage was evaluated by light microscopy. Selected areas of the periventricular white matter were also examined by electron microscopy. RESULTS: Histopathological screening revealed no evidence for cortical neuronal cell damage in both groups. However, LPS treatment resulted in inflammatory infiltrates in all animals and cystic lesions in the periventricular brain white matter in two fetuses. On electron micrographs, infiltrate forming cells appeared to be activated microglia. S100B protein blood levels were significantly higher in the LPS group at 1h (p < 0.01) after LPS injection, peaking at 3h (p < 0.001) and returning to baseline between 12 and 72 h. CONCLUSION: Intravenous application of endotoxin caused focal periventricular brain white matter injury, inflammation and an increase in S100B protein release. It is suggested that longitudinal investigations of S100B protein blood levels offer a tool for the early detection of white matter injury.

Animals↗
PubMed2005

S100b counteracts effects of the neurotoxicant trimethyltin on astrocytes and microglia.

Central nervous system degenerative diseases are often characterized by an early, strong reaction of astrocytes and microglia. Both these cell types can play a double role, protecting neurons against degeneration through the synthesis and secretion of trophic factors or inducing degeneration through the secretion of toxic molecules. Therefore, we studied the effects of S100B and trimethyltin (TMT) on human astrocytes and microglia with two glial models, primary cultures of human fetal astrocytes and a microglia cell line. After treatment with 10(-5) M TMT, astrocytes showed morphological alterations associated with an increase in glial fibrillary acidic protein (GFAP) expression and changes in GFAP filament organization. Administration of S100B before TMT treatment prevented TMT-induced changes in morphology and GFAP expression. A decrease in inducible nitric oxide synthase expression was observed in astrocytes treated with TMT, whereas the same treatment induced iNOS expression in microglia. In both cases, S100B prevented TMT-induced changes. Tumor necrosis factor-alpha mRNA expression in astrocytes was not modified by TMT treatment, whereas it was increased in microglia cells. S100B pretreatment blocked the TMT-induced increase in TNF-alpha expression in microglia. To trace the mechanisms involved in S100B activity, the effect of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-kappaB) activation, and of PD98059, an inhibitor of MEK-ERK1/2, were investigated. Results showed that the protective effects of S100B against TMT toxicity in astrocytes depend on NF-kappaB, but not on ERK1/2 activation. These results might help in understanding the role played by glial cells in brain injury after exposure to chemical neurotoxicants and support the view that S100B may protect brain cells in case of injury. (c) 2005 Wiley-Liss, Inc.

Astrocytes↗
PubMed2005

Enhanced neurogenesis during trimethyltin-induced neurodegeneration in the hippocampus of the adult rat.

The occurrence of neurogenesis in the hippocampus of the adult rat during trimethyltin (TMT)-induced neurodegeneration was investigated using bromodeoxyuridine (BrdU). Fifteen days after TMT intoxication, BrdU-labeled cells were significantly more numerous in the hippocampus of treated animals, gradually decreasing towards the control value 21 days after intoxication in the dentate gyrus (DG), while in the CA3/hilus region BrdU-labeled cells were still more numerous in TMT-treated rats. In order to investigate the fate of newly-generated cells double labeling experiments using neuronal or glial markers were performed. Colocalization of the neuronal marker NeuN was detected in many BrdU-positive cells in the DG, while in the CA3/hilus region no colocalization of NeuN and BrdU could be observed. No colocalization of BrdU and the astroglial marker GFAP or the microglial marker OX-42 was detected either in the DG and or in the CA3/hilus region. The results indicate an enhancement of endogenous neurogenesis in the hippocampus during TMT-induced neurodegeneration, with the development of a subpopulation of regenerated cells into neurons in the DG, while in the CA3/hilus region the population of newly-generated cells should be regarded as undifferentiated.

Animals↗
PubMed2005

S100B protein levels in saliva: correlation with gestational age in normal term and preterm newborns.

OBJECTIVES: S100B is an acidic calcium-binding protein of the EF-hand family present in the central nervous system, where it is concentrated in glial cells. It has been suggested to act as a cytokine with neurotrophic effects at physiological concentrations. DESIGN AND METHODS: S100B concentration was assessed in saliva by western blot analysis and an immunoluminometric assay. A reference curve of the protein was established in 216 preterm and term newborns. RESULTS: S100B levels were significantly higher in saliva taken from the preterm group, and the highest S100B levels were found in newborns who were delivered in the earlier weeks of gestation, exhibiting a progressive decrease nearer to term. S100B concentration in saliva was correlated with gestational age (r = -0.69; P < 0.001). CONCLUSIONS: The present study offers data consistent with the putative neurotrophic role of S100B and suggests the usefulness of saliva in the clinical monitoring of S100B levels.

Biomarkers↗
PubMed2005

S100B protein in urine of preterm newborns with ominous outcome.

Prematurity is an important cause of perinatal death, and no reliable biochemical/biophysical markers exist to identify newborns with an increased mortality risk. We aimed to use S100B concentrations in urine as an early indicator of risk of neonatal death. We did a cross-sectional study using urine obtained from 165 preterm newborns, of whom 11 suffered neonatal death within the first week, 121 displayed no overt neurologic syndrome, and 33 suffered neonatal hypoxia and intraventricular hemorrhage (IVH) but not ominous outcome. Urine S100B concentrations were determined at four time-points and corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Ultrasound imaging was assessed within the first 72 h from birth. In infants that died within the first week, S100B levels in urine were already higher than controls at first urination and increased progressively between the 24 and 96-h time-points. Multiple logistic regression analysis showed a significant correlation between urine S100B protein concentrations and the occurrence of neonatal death. An S100B concentration cut-off of 12.93 MoM at first urination had a sensitivity of 100% and a specificity of 97.8% for predicting an ominous outcome. The positive predictive value was 78.6%, the negative predictive value was 100%. Measurement of urine S100B protein levels in preterm newborns could be useful to identify newborns at higher risk of neonatal death.

Female↗
PubMed2004

Trimethyltin-induced differential expression of PAR subtypes in reactive astrocytes of the rat hippocampus.

Thrombin, its main inhibitor (protease nexin-1) and its related receptors (protease-activated receptors, PAR-1,-2, -3, -4) were studied in rat hippocampus following administration of trimethyltin (TMT), a neurotoxin inducing neuronal degeneration and reactive gliosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry revealed that while expression of prothrombin and protease nexin-1 did not change significantly in TMT-treated hippocampi, PARs (in particular PAR-1 and to a lesser extent PAR-2 and PAR-3) were upregulated in reactive astrocytes, suggesting their involvement in neurodegeneration and in the consequent response of the nervous tissue.

Animals↗
PubMed2004

Expression of astrocytic nestin in the rat hippocampus during trimethyltin-induced neurodegeneration.

In this study we used an immunocytochemical approach to study nestin expression in the rat hippocampus during trimethyltin-induced neurodegeneration at different time points (5, 10, 15, 21 and 50 days) after intoxication. Nestin is transiently expressed by a subpopulation of astroglial cells strictly associated with pyramidal neurons in those hippocampal areas severely affected by degeneration. This observation shows that cerebral tissue re-expresses this developmental protein during neurodegenerative diseases in early stages of astroglial activation.

Animals↗
PubMed2004

Levels of S100B protein are higher in mature human milk than in colostrum and milk-formulae milks.

BACKGROUND & AIMS: Human milk is believed to contain biological factors involved in the regulation of newborn growth, including brain development. Recently, it has also been shown to contain the calcium-binding S100B protein, regarded as a neurotrophic factor. The present study investigates the concentrations of this protein in colostrum, human milk at different levels of maturation and in milk-formulae. METHODS: Samples for S100B measurements were collected from human colostrum (on day 1 after birth), from transition milk (on post-delivery days 7 and 14) and from mature milk (on day 30 after delivery) in 14 healthy women and from 14 milk-formulae. The S100B protein levels were measured using a commercially available specific immunoluminometric assay. RESULTS: Mean S100B protein levels were significantly higher in mature human milk (117.9+/-36.7 microg/l) than in transition milk at 14 days (106.7+/-38.1 microg/l) and at 7 days (92.7+/-37.8 microg/l), colostrum (74.6+/-37.6 microg/l) or milk-formulae (24.8+/-19.5 microg/l) (P<0.001, for all). A correlation between human milk S100B levels and the gestational age at which samples were obtained was also found (r=0.39; P<0.01). CONCLUSIONS: These findings, possibly related to S100B's neurotrophic role, offers useful information to the investigation of the role of S100B protein in brain maturation.

Adult↗
PubMed2004

Urinary S100B protein measurements: A tool for the early identification of hypoxic-ischemic encephalopathy in asphyxiated full-term infants.

OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect which infants will develop brain damage after asphyxia insult. DESIGN AND SETTING: Prospective study conducted in three tertiary departments of neonatology from December 1999 to July 2002. PARTICIPANTS: A total of 44 infants with perinatal asphyxia and 68 control infants. INTERVENTION: Routine laboratory variables, neurologic patterns, ultrasound imaging, and urine concentrations of S100B protein were determined at nine time points. MAIN OUTCOME MEASURES: The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, and 72 hrs after birth. The results were correlated with the presence or absence of hypoxic-ischemic encephalopathy. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling. RESULTS: S100B protein levels were significantly higher in samples collected at all monitoring time points from newborns with perinatal asphyxia with or without hypoxic-ischemic encephalopathy than in samples from normal infants (all p <.001). When asphyxiated infants were subdivided according to the presence of mild or absence of hypoxic-ischemic encephalopathy (group A) and of moderate or severe hypoxic-ischemic encephalopathy (group B), S100B levels were significantly higher at all the predetermined monitoring time points in group B infants than group A or control infants (all p <.001). An S100B concentration cutoff of 0.41 microg/L at first urination had a sensitivity of 91.3% and a specificity of 94.6% for predicting the development of hypoxic-ischemic encephalopathy. The sensitivity and specificity of measurements obtained from 4 to 72 hrs after birth were up to 100% and 98.8%, respectively. CONCLUSIONS: Longitudinal S100B protein measurements in urine soon after birth are a useful tool to identify which asphyxiated infants are at risk of hypoxic-ischemic encephalopathy and its possible neurologic sequelae.

Asphyxia Neonatorum↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗