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Biomedical subjects

F Michetti

Publications and source records attributed to F Michetti.

At least 19 recordsLinked to original sources
PubMed2005

How does human stem cell therapy influence gene expression after liver injury? Microarray evaluation on a rat model.

BACKGROUND: Tissue homeostasis is guaranteed by stem proliferating reserve, depending on dynamic changes in gene expression. A high plasticity is shown by the haematopoietic stem cells, potential source for liver regeneration. AIM: We aimed to evaluate the gene expression modifications induced by human haematopoietic stem cell therapy after liver injury in rats. SUBJECTS: Rats were sorted as follows: (A) human-haematopoietic stem cell injection after allyl alcohol liver damage; (B) only haematopoietic stem cell injection; (C) only allyl alcohol injection; and (D) sacrifice without any treatment. METHODS: Livers, spleens and bone marrows were analysed with flow-cytometry. Livers were also studied by reverse-transcription PCR, histology, immunohistochemistry and microarray analysis; selected genes were confirmed by real-time PCR. RESULTS: In subset A, haematopoietic stem cells were selectively recruited by liver, with respect to the group B, and they improved the liver regeneration process compared to group C. As regards microarrays, haematopoietic stem cell infusion upregulates 265 genes and downregulates 149 genes. Differentially regulated genes belong to a broad range of functional pathways, including proliferation, differentiation, adhesion/migration and transcripts related to oval-cell activation. Real-time PCR validated array results. CONCLUSIONS: Our study confirmed the capacity of haematopoietic stem cells to contribute to liver regeneration. Moreover, microarray analysis led to the identification of genes whose regulation strongly correlates with a more efficient process of liver repair after haematopoietic stem cell injection.

Animals↗
PubMed2004

Gamma-aminobutyric acidergic interneuron vulnerability to aging in canine prefrontal cortex.

The aged dog is considered a promising model for examining molecular and cellular processes involved in a variety of human neurological disorders. By using the canine counterpart of senile dementia of the Alzheimer's type (ccSDAT), we investigated the specific vulnerability of the gamma-aminobutyric acid (GABA) cortical subset of interneurons, characterized by their calcium-binding protein content, to neuronal death. Dogs representing a large variety of breeds were classified into three groups: young control, aged control, and ccSDAT. In all dogs, the general distribution and cell typology of parvalbumin-, calretinin-, and calbindin-positive neurons were found to be similar to those in the human. As in Alzheimer's disease patients, neurons displaying parvalbumin or calretinin immunoreactivity were resistant and the calbindin-positive ones depleted. Together with aging, amyloid deposition in its early phase (stage II) participates in this specific neuronal death, but with a lower potency. In conclusion, our data provide evidence that preservation of GABAergic cortical interneurons has to be focused on the early stage of beta-amyloid deposition. We also demonstrate the usefulness of dogs of all breeds for investigating the early phases of human brain aging and Alzheimer's disease.

Aging↗
PubMed2004

A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury.

BACKGROUND: Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. AIMS: In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. METHODS: We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. CONCLUSIONS: We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.

Animals↗
PubMed2003

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.

Adrenergic alpha-Antagonists↗
PubMed2002

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.

Calcium-Binding Proteins↗
PubMed2002

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.

Blood Flow Velocity↗
PubMed2000

Prognostic significance of the Ca(2+) binding protein S100A2 in laryngeal squamous-cell carcinoma.

We investigated by immunocytochemistry the expression of the Ca(2+) binding protein S100A2 in 62 cases of laryngeal squamous-cell carcinoma (SCC). S100A2 was detected in 18/19 (95%) low-grade tumors and in 22/43 (51%) high-grade tumors, which were partially keratinizing. The remaining 21/43 (49%) high-grade tumors were non-keratinizing, anaplastic tumors and clearly S100A2-negative. In normal laryngeal squamous epithelium and in laryngeal SCC, S100A2 expression was strictly associated with that of cytokeratins 14 (P = 0.0002) and 17 (P = 0.0021), suggesting an association of S100A2 expression and cell commitment to squamous differentiation. A correlation was found between S100A2 tumor positivity and longer relapse-free (P = 0.0005) and overall (P = 0.0095) survival.

Analysis of Variance↗
PubMed1999

Elevated S100 blood level as an early indicator of intraventricular hemorrhage in preterm infants. Correlation with cerebral Doppler velocimetry.

The aim of this study was to assess the use of S100 protein in blood as a means of identifying preterm infants at risk of intraventricular hemorrhage. In 25 preterm newborns, S100 blood concentrations were measured by an immunoradiometric assay during the first 48 h. Cerebral Doppler velocimetry waveform patterns were also tested at the time the blood sample was taken, when clinical and cerebral ultrasound scanning were still normal. Of the 25 newborns studied, 14 were controls and 11 developed intraventricular hemorrhage as revealed by ultrasound scanning more than 72 h after birth, and clinically confirmed by neurological examination on the seventh day of follow-up. S100 blood concentrations were significantly higher (P<0.002) in infants with intraventricular hemorrhage than in control infants and also correlated significantly (r=0.81, P<0.003) with the grade of hemorrhage. A significant correlation (r=0.70, P<0.05) between the S100 blood concentration and the middle cerebral artery pulsatility index was also observed. The present data show that S100 blood concentrations offer a measurable parameter of brain lesion in preterm infants before a radiological assessment of hemorrhage can be performed, when clinical symptoms may be silent and preventive/therapeutic action could be especially useful.

Blood Flow Velocity↗
PubMed1998

Neuronal subpopulations of developing rat hippocampus containing different calcium-binding proteins behave distinctively in trimethyltin-induced neurodegeneration.

The present study investigates, by immunocytochemistry, the behavior of different neuronal subpopulations of the developing rat hippocampus, selectively labeled by the calcium-binding proteins calbindin D28-k (CB), parvalbumin (PV), and calretinin (CR), in neurodegenerative processes induced by the neurotoxicant trimethyltin (TMT). Previous studies on adult rats indicated that CB-immunoreactive (IR) neurons were affected by TMT, while PV- and CR-IR neurons were selectively spared. The present findings show that only CR-IR neurons are spared in developing rats, and in addition the number of CR-IR neurons are significantly higher in the DG of treated animals. On the contrary, PV-IR neurons, spared in adult rats, were affected by TMT during development. CB-IR neurons were affected also in developing rats, as in adults. The different postnatal time-courses of calcium-binding protein expression in relationship to the time of TMT administration (presence of CR but absence of PV) could have a role in the different behavior of CR- and PV-IR cells in developing rats.

Animals↗
PubMed1997

Calretinin-containing neurons in trimethyltin-induced neurodegeneration in the rat hippocampus: an immunocytochemical study.

The present study uses immunocytochemistry to investigate the behavior of the calretinin (CR)-containing neuronal subpopulation (interneurons) of the rat hippocampus in neurodegenerative processes induced by the neurotoxicant trimethyltin. Cell counts of CR-immunolabeled interneurons indicated that these cells are spared by the neurotoxicant-induced degeneration, characterized by a generalized neuronal loss, as shown by quantitative analysis after cresyl violet staining.

Animals↗
PubMed1996

Parvalbumin-immunoreactive neurons are not affected by trimethyltin-induced neurodegeneration in the rat hippocampus.

The present study investigates, by immunocytochemistry, the behavior of different neuronal subpopulations of the rat hippocampus in neurodegenerative processes induced by the neurotoxicant trimethyltin. The calcium-binding proteins calbindin and parvalbumin are used as selective markers of different neuronal subpopulations. The effects of the neurotoxicant were apparent 21 days after a single i.p. administration with severe neuronal loss, which was significant in CAI and CA3, as revealed by cell counts after cresyl violet staining. Immunolabeling with calbindin D28-k (CB) and parvalbumin (PV) indicated severe cell loss of CB-containing neurons, essentially reflecting the generalized neuronal loss, while PV-containing neurons appeared to be selectively spared by the neurotoxicant-induced degeneration.

Animals↗
PubMed1994

Effects of intraluminal acidification on oesophageal motor activity.

This study assessed the effect of prolonged intraluminal acidification on the motor activity of the entire oesophageal body (under controlled conditions). Intraoesophageal pressures were recorded in 13 endoscopy negative subjects with gastro-oesophageal reflux disease in whom saline, HC1 0.1 N, and saline solutions were infused (1.5 ml/min) blindly in the oesophageal body, 6 cm distal to the upper oesophageal sphincter for three consecutive periods of 45 minutes each. These findings were compared with those of a control group. Intraoesophageal acidification caused an increase in the deglutition frequency (p < 0.02), the occurrence of multipeaked waves (p < 0.04) as well as a decrease of the propagating velocity (p < 0.04) of the primary peristaltic contractions. Furthermore, intraoesophageal acidification determined an increase, at all levels of the oesophagus, of the duration (p < 0.04) and, more noticeable in the proximal oesophageal body, of the amplitude (p < 0.02) of primary peristaltic contraction waves. In conclusion prolonged intraoesophageal acidification can considerably affect frequency of deglutition, morphology, and propagating patterns of primary peristaltic contractions. This study shows that these effects are independent from volume distension of the oesophagus and supports the presence of acid sensitive receptors in the oesophageal mucosa.

Adult↗