PubMed Health⌕ Search

Biomedical subjects

V Conte

Publications and source records attributed to V Conte.

At least 19 recordsLinked to original sources

Hippocampal vulnerability following traumatic brain injury: a potential role for neurotrophin-4/5 in pyramidal cell neuroprotection.

Traumatic brain injury (TBI) causes selective hippocampal cell death, which is believed to be associated with cognitive impairment observed both in clinical and experimental settings. Although neurotrophin administration has been tested as a strategy to prevent cell death following TBI, the potential neuroprotective role of neurotrophin-4/5 (NT-4/5) in TBI remains unknown. We hypothesized that NT-4/5 would offer neuroprotection for selectively vulnerable hippocampal neurons following TBI. Measurements of NT-4/5 in rats subjected to lateral fluid percussion (LFP) TBI revealed two-threefold increases in the injured cortex and hippocampus in the acute period (1-3 days) following brain injury. Subsequently, the response of NT-4/5 knockout (NT-4/5(-/-)) mice to controlled-cortical impact TBI was investigated. NT-4/5(-/-) mice were more susceptible to selective pyramidal cell loss in Ahmon's corn (CA) subfields of the hippocampus following TBI, and showed impaired motor recovery when compared with their brain-injured wild-type controls (NT-4/5(wt)). Additionally, we show that acute, prolonged administration of recombinant NT-4/5 (5 microg/kg/day) prevented up to 50% of the hippocampal CA pyramidal cell death following LFP TBI in rats. These results suggest that post-traumatic increases in endogenous NT-4/5 may be part of an adaptive neuroprotective response in the injured brain, and that administration of this neurotrophic factor may be useful as a therapeutic strategy following TBI.

Animals↗

The ratio between arterio-venous PCO2 difference and arterio-jugular oxygen difference as estimator of critical cerebral hypoperfusion.

AIM: The aim of this study was to evaluate the arterio-venous difference in carbon dioxide tension (DPCO2) and the ratio between DPCO2 and arterio-jugular oxygen difference (AJDO2) as indicators of compensated or uncompensated cerebral hypoperfusion. METHODS: Cerebral blood flow (CBF) was reduced stepwise in 6 pigs by inducing intracranial hypertension with consequently cerebral perfusion pressure (CPP) reduction: CBF 100%, 50-60 % of baseline, 20-30% of baseline. Intracranial pressure (ICP), mean arterial pressure (MAP), CPP and CBF (laser-Doppler method) were continuously recorded. Superior sagittal sinus was punctured for the determination of AJDO2 and DPCO2. RESULTS: CBF impairment was accompanied by changes in AJDO2 from 6.03 +/- 1.21 vol% to 7.32 +/- 1.30 vol%, up to 8.07 +/- 1.32 vol% (P < 0.01), in DPCO2 from 12.17 +/- 3.25 mmHg to 16 +/- 4.12 mmHg, up to 26.5 +/- 6.41 mmHg (P < 0.01), and DPCO2/AJDO2 ratio from 2.05 +/- 0.39 to 2.06 +/- 0.72 up to 3.41 +/- 1.09 in the 3 phases (P < 0.05). CONCLUSIONS: When CBF declines AJDO2 increases, indicating greater extraction of O2 to satisfy aerobic metabolism. However, this mechanism can no longer compensate once a critical CBF threshold is reached. DPCO2 rises slowly during moderate CBF reduction because of defective washout; the rise is steeper during marked CBF impairment when anaerobic metabolism takes place. During cerebral hypoperfusion the venous blood gases and acid base variables mirror the degree of cerebral perfusion. In particular the DPCO2, and the DPCO2/ AJDO2 ratio may be useful markers of critical brain hypoperfusion.

Animals↗

Mini-TEPCs for radiation therapy.

A mini-tissue-equivalent proportional-counter (TEPC) has been constructed to study the possibility to manufacture mini-counters without field-shaping tubes for radiation therapy. The mini-TEPC can be assembled with and without field-shaping tubes. It can be equipped with a mini-alpha source for a precise lineal energy calibration. After the positive conclusions of this study, a slim TEPC has been designed and constructed. The slim TEPC has an external diameter of only 2.7 mm. It has been tested with therapeutic proton beams and gamma ray sources.

Equipment Design↗

Microdosimetric investigation at the therapeutic proton beam facility of CATANA.

Proton beams (62 Mev) are used by the Laboratori Nazionali del Sud of the Italian Institute of Nuclear Physics to treat eye melanoma tumours at the therapeutic facility called CATANA. A cylindrical slim tissue-equivalent proportional counter (TEPC) of 2.7 mm external diameter has been used to compare the radiation quality of two spread-out Bragg peaks (SOBP) at the CATANA proton beam.

Algorithms↗

Design of a 10 nm electron collector for a track-nanodosimetric counter.

Recently we have developed a track-nanodosimetric counter, which is a gas detector that measures the distributions of electrons induced by a charged particle in nanometric volumes of tissue equivalent matter, positioned at different distances from the track. Sites equivalent to 20 and 24 nm were defined by means of an electron collector, which is a system of electrodes enclosing an almost wall-less cylindrical volume. In this paper, we present the design of a new electron collector that is able to simulate a volume as small as 10 nm in diameter.

Algorithms↗

Experimental equivalent cluster-size distributions in nanometric volumes of liquid water.

Ionisation cluster-size distributions in nanometric volumes of liquid water were determined for alpha particles at 4.6 and 5.4 MeV by measuring cluster-size frequencies in small gaseous volumes of nitrogen or propane at low gas pressure as well as by applying a suitable scaling procedure. This scaling procedure was based on the mean free ionisation lengths of alpha particles in water and in the gases measured. For validation, the measurements of cluster sizes in gaseous volumes and the cluster-size formation in volumes of liquid water of equivalent size were simulated by Monte Carlo methods. The experimental water-equivalent cluster-size distributions in nitrogen and propane are compared with those in liquid water and show that cluster-size formation by alpha particles in nitrogen or propane can directly be related to those in liquid water.

Algorithms↗

BNCT microdosimetry at the tapiro reactor thermal column.

A thermal column is available for dosimetric and radiobiological studies by the fast reactor TAPIRO, located at the ENEA research centre Casaccia. The TAPIRO neutron field has been studied (in the frame of LNL BNCT project) with a tissue-equivalent proportional counter, which has worked alternatively with an ordinary tissue-equivalent cathode and with a boron-enriched cathode. Measurements have been performed with polyethylene caps of different thickness. Both the absorbed dose and the microdosimetric-calculated biological effective dose show a maximum at approximately 0.5 mg cm(-2) of depth. The different dose components have been calculated and the results are discussed.

Body Burden↗

Age-dependent synuclein pathology following traumatic brain injury in mice.

Synucleins (Syn), a family of synaptic proteins, includes alpha-Syn, which plays a pivotal role in Parkinson's disease and related neurodegenerative diseases (synucleinopathies) by forming distinct brain pathologies (Lewy bodies and neurites). Since traumatic brain injury (TBI) is a poorly understood risk factor for Parkinson's disease, we examined the effects of TBI in the young and aged mouse brain on alpha-, beta-, and gamma-Syn. Immunohistochemical analysis showed that brains from sham-injured young and aged mice had normal alpha- and beta-Syn immunoreactivity (IR) in neuropil of cortex, striatum, and hippocampus with little or no gamma-Syn IR. At 1 week post TBI, the aged mouse brain showed a transient increase of alpha- and beta-Syn IR in the neuropil as well as an induction of gamma-Syn IR in subcortical axons. This was associated with strong labeling of striatal axon bundles by antibodies to altered or nitrated epitopes in alpha-Syn as well as by antibodies to inducible nitric oxide synthase. However, these TBI-induced changes disappeared by 16 weeks post TBI, and altered Syn IR was not seen in young mice subjected to TBI nor in alpha-Syn knockout mice while Western blots confirmed that TBI induced transient alterations of alpha-Syn in the mouse brains. This model of age-dependent TBI-induced transient alterations in alpha-Syn provides an opportunity to examine possible links between TBI and mechanisms of disease in synucleinopathies.

Aging↗

Ionization-cluster distributions of alpha-particles in nanometric volumes of propane: measurement and calculation.

The probability of the formation of ionization clusters by primary alpha-particles at 5.4 MeV in nanometric volumes of propane was studied experimentally and by Monte Carlo simulation, as a function of the distance between the center line of the particle beam and the center of the target volume. The volumes were of cylindrical shape, 3.7 mm in diameter and height. As the investigations were performed at gas pressures of 300 Pa and 350 Pa, the dimensions of the target volume were equivalent to 20.6 nm or 24.0 nm in a material of density 1.0 g/cm(3). The dependence of ionization-cluster formation on distance was studied up to values equivalent to about 70 nm. To validate the measurements, a Monte Carlo model was developed which allows the experimental arrangement and the interactions of alpha-particles and secondary electrons in the counter gas to be properly simulated. This model is supplemented by a mathematical formulation of cluster size formation in nanometric targets. The main results of our study are (i) that the mean ionization-cluster size in the delta-electron cloud of an alpha-particle track segment, decreases as a function of the distance between the center line of the alpha-particle beam and the center of the sensitive target volume to the power of 2.6, and (ii) that the mean cluster size in critical volumes and the relative variance of mean cluster size due to delta-electrons are invariant at distances greater than about 20 nm. We could imagine that the ionization-cluster formation in nanometric volumes might in future provide the physical basis for a redefinition of radiation quality.

Biophysics↗

Cerebral veno-arterial pCO2 difference as an estimator of uncompensated cerebral hypoperfusion.

The aim of the present study was to assess the veno-arterial difference in pCO2 (delta pCO2) as an indicator of ischemia compared to the arteriovenous O2 difference (AVDO2). Staircase cerebral blood flow (CBF) reductions were obtained in seven domestic pigs by inducing intracranial hypertension: CBF 100%, 50-60% of baseline, 20-30% of baseline. ICP, MAP, CPP and CBF (Laser-Doppler method) were continuously recorded. The superior sagittal sinus was punctured to determine AVDO2 and delta pCO2. AVDO2 was 5.9 (+/- 1.78, range 3.3-7.4), 7.01 (+/- 1.31, range 5-8.9) and 8.17 (+/- 1.51, range 6.0-11.3) ml/100 ml in the three CBF steps (p = 0.001). CBF impairment was accompanied by the following increases in delta pCO2: from 10 (+/- 4, range 4-15) mmHg to 14.5 (+/- 4.11, range 10-27) mmHg, and to 31.2 (+/- 9.0, range 17-39) mmHg (p < 0.001). When CBF declines AVDO2 increases, indicating greater extraction of O2 to satisfy the aerobic metabolism. However, this mechanism can no longer compensate once a critical CBF threshold is reached. delta pCO2 rises slowly during moderate CBF reduction because of defective washout; the rise is impressive during marked CBF impairment when anaerobic metabolism takes place with proton buffering in CO2 and H2O. Therefore, when the brain's ability to compensate for low blood flow is exceeded, CO2 production outweighs O2 extraction.

Animals↗

Stereoselective halogenations of alkenes and alkynes in ionic liquids.

[reaction: see text]. Room-temperature ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium bromide, and 1-butyl-3-methylimidazolium chloride, are used as "green" recyclable alternative to chlorinated solvents for the stereoselective halogenation of alkenes and alkynes.

Journal Article↗

Vanadium catalyzed reduction of dioxygen to hydrogen peroxide: an oscillating process.

In acid isopropanol/water solution and aerobic conditions, (Bu)4N+VO3- in the presence of an initial amount of H2O2, catalyzes the autoxidation of isopropanol to acetone and the contextual dioxygen reduction to hydrogen peroxide, which accumulates in solution. We have observed that, in the system under examination, the build-up of H2O2 concentration shows an oscillatory behavior. Speciation of the peroxovanadium complexes in iPrOH/H2O has been explored with the combined use of 51V NMR, UV-Vis and ESI-MS techniques.

2-Propanol↗

Models for the active site of vanadium-dependent haloperoxidases: insight into the solution structure of peroxo vanadium compounds.

A combined use of electrospray ionization-mass spectrometry (ESI-MS), 51V NMR spectroscopy and ab initio calculations has been proved to be a powerful tool for obtaining direct information of the structure and the chemistry of peroxo vanadates in solutions. The analysis of acid solutions containing monoperoxo vanadates showed the occurrence of exchange reactions between solvent molecules in the coordination sphere of the metal. On the other hand, bisperoxo vanadates appear to be less prone to coordinate more than one water or alcohol molecule. The bisperoxo complex [VO5]- in the presence of histidine and histidine-like ligands, at near neutral conditions, has been studied. Coordination of one and two molecules of ligand is observed affording [VO5L]- and [VO5L2]-, respectively. Characterization of these species has been obtained by MSn experiments, which allowed us to distinguish specific fragmentations of the peroxidic moiety.

Binding Sites↗

Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes.

Myostatin is a recently identified member of the transforming growth factor-beta family of regulatory factors, also known as growth and differentiation factor 8 (GDF8). The nucleotide sequence of human myostatin was determined in 40 individuals. The invariant promoter contains a consensus MyoD binding site, and the coding sequence contains five missense substitutions in conserved amino acid residues (A55T, K153R, E164K, P198A, and I225T). Two of these, A55T in exon 1 and K153R in exon 2, are polymorphic in the general population with significantly different allele frequencies in Caucasians and African Americans (P < 0.001). Neither of the common polymorphisms had a significant impact on muscle mass response to strength training in either Caucasians or African Americans, although skewed allele frequencies preclude detection of small effects. These allelic variants provide markers for examining association between the myostatin gene and interindividual variation in muscle mass and differences in loss of muscle mass with aging.

Amino Acid Substitution↗

[The indications and controversies for the use of corticosteroids in respiratory deficits in the multiple-trauma patient].

The rational use of corticosteroids in terms of doses, timing and methods of administration, has proved useful in management of the effects of morbidity and mortality in respiratory insufficiency in multiple trauma patients. MPSS (methyl prednisone sodium succinate) is the drug of choice because, compared to other steroids, it penetrates lung tissue more easily (as demonstrated using autoradiographic techniques). The effect of reducing permeability, shown by MPSS, is more marked in the first 6 hours, followed by a progressive diminution. For this reason, it is advisable to administer the drug every 6-8 hours, irrespective of T 1/2 (12-36 h). However, in syndromes of post-traumatic respiratory distress, corticosteroid therapy is only symptomatic, namely it reduces short term mortality, but does not influence the prognosis in the event of persistent microembolism. On the other hand, it is important not to overlook the disadvantages and possible damaging effects linked to the use of corticosteroids in multiple trauma patients. With regard to the use of "alternative" type or support treatments to corticosteroids, the lack of markers documented using atraumatic and reliable techniques hinders the development and clinical application of specific and effective antioxidising treatments. However, alongside the perfection of methods of detecting markers, among the antioxidant drugs, a decisive contribution is expected from the lazaroids or 21-aminosteroids (synthesis steroids). With powerful scavenger activity and antioxidant properties (twice those of MPSS), the lazaroids can provide more suitable solutions to the complex therapeutic problems of these patients, also because they lack glucocorticoid and mineralocorticoid activity.

Adrenal Cortex Hormones↗

Serum silicon levels are elevated in women with silicone gel implants.

The metabolic fate of silicone gel leaked into the body from an implant is unknown. In this study, serum from 72 women with silicone gel breast implants and 55 control women was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon. Samples were processed using materials free of silicon. The mean silicon level in controls was 0.13 +/- 0.07 mg/l (range 0.06-0.35 mg/l), while in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/l (range 0.06-0.87 mg/l) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/l), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw or the number of years with implants and silicon levels. The results suggest that elevations of serum silicon are seen in many women with silicone gel breast implants. The kinetics of this elevation and the actual chemical species of the measured silicon remain to be determined.

Adult↗