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Biomedical subjects

G Raciti

Publications and source records attributed to G Raciti.

At least 19 recordsLinked to original sources
PubMed2005

Isotopic scaling and the symmetry energy in spectator fragmentation.

Isotopic effects in the fragmentation of excited target residues following collisions of 12C on (112,124)Sn at incident energies of 300 and 600 MeV per nucleon were studied with the INDRA 4pi detector. The measured yield ratios for light particles and fragments with atomic number Z < or = 5 obey the exponential law of isotopic scaling. The deduced scaling parameters decrease strongly with increasing centrality to values smaller than 50% of those obtained for the peripheral event groups. Symmetry-term coefficients, deduced from these data within the statistical description of isotopic scaling, are near gamma = 25 MeV for peripheral and gamma < 15 MeV for central collisions.

Journal Article↗
PubMed2005

Incidence of prostate cancer in Sicily: results of a multicenter case-findings protocol.

OBJECTIVE: To establish the incidence of prostate cancer (PCa) in Sicily in patients who entered an early detection protocol. METHODS: From February 2002 to February 2004, 16,298 subjects aged 40-75 entered the protocol. Patients with suspicious DRE, PSA>10 ng/ml, PSA<or=2.5 ng/ml, from 2.6 to 4 ng/ml or from 4.1 to 10 ng/ml with F/T PSA of <or=15%, <or=20% and <or=25% respectively underwent needle biopsy according to an extensive protocol. RESULTS: 3266 patients were eligible for biopsy; PSA was <or=4 in 12.7% and <or=10 ng/ml in 63.9% of patients. A PCa was found in 1171 cases (36.9%) with a relationship between PCa incidence and PSA and age respectively (chi2-test, p<0.0001); 51.8% of patients with PCa had a PSA<10 and 8.8% a PSA<4 ng/ml; 49% were clinically staged as T1c. The estimated odds ratios for each age group showed increased risk for PCa in the fourth decade with PSA between 2.6 and 4 ng/ml (12.5 times higher) and in the fifth decade with PSA between 4.1 and 10 ng/ml (6.2 times higher). CONCLUSIONS: Age and serum PSA levels are the major risk factors for PCa. On their basis it is possible to modulate the most suitable timing for early diagnosis in individual patients.

Adult↗
PubMed2003

Cystamine inhibits transglutaminase and caspase-3 cleavage in glutamate-exposed astroglial cells.

Although the precise role of transglutaminase in cell death is unknown, several findings demonstrate that tissue transglutaminase selectively accumulates in cells undergoing apoptosis both in vivo and in vitro. Calcium-dependent transglutaminase reactions are also implicated in several neurodegenerative diseases, including alterations in the release of excitatory amino acids. One prevalent theme in cell damage induced by excitotoxic stimuli in different regions of the CNS is that apoptosis may be executed by intracellular caspase proteases. Furthermore, the presence of functional ion channel-gated receptors in glial cells suggests that also astrocytes can be susceptible to glutamate's toxic effects. In this study, we demonstrated that prolonged exposure to glutamate (100 microM) of cultured astrocytes caused an increase in the expression of tissue transglutaminase (tTG). This effect was prevented by preincubation with GYKI 52466, an antagonist of AMPA/KA receptors. Glutamate exposure also promoted an increase in caspase-3 compared with control cultures. Confocal laser microscopy analysis demonstrated the presence of activated caspase-3 in the cytoplasm as well as in the nucleus. The inhibition of TG-catalyzed reactions by cystamine (1 mM) blocked the activation pathway of caspase-3, with an evident reduction of enzyme cleavage. These results suggest that glutamate increased both TG and caspase-3 in astroglial cells early in the excitotoxin-induced events.

Animals↗
PubMed2003

Glutamate-induced increases in transglutaminase activity in primary cultures of astroglial cells.

Glutamate exposure of astroglial cells caused ligand-gated channel receptor activation, associated with excitotoxic cell response. We investigated the effects of 24 h glutamate exposure on transglutaminase in astrocytes primary cultures at 7, 14, and 21 days in vitro (DIV). Increases in enzyme activity were observed as a function of cell differentiation stage in glutamate-treated cultures. These effects were significantly reduced when GYKI 52466, an AMPA/KA receptors inhibitor, was added to the culture medium prior to incubation with glutamate. Microscopy observation on transglutaminase-mediated, fluorescent dansylcadaverine incorporation in living cells was consistent with these results. Western blotting analysis with monoclonal antibody showed that glutamate also up-regulated tissue transglutaminase expression, which reached the highest values in 14 DIV cultures. Confocal laser scanning microscopy analysis of immunostained astroglial cells showed a mainly cytoplasmic localisation of the enzyme both in control and treated cultures; nevertheless, counterstaining with the nuclear dye acridine orange demonstrated the presence of tissue transglutaminase also into the nucleus of glutamate-exposed and 21 DIV cells. The increases in enzyme expression and localisation in the nucleus of glutamate-treated astroglial cells may be part of biochemical alterations induced by excitotoxic stimulus.

Animals↗
PubMed2001

A 3D QSAR study of monoamino oxidase-B inhibitors using the chemical function based pharmacophore generation approach.

A molecular modelling study was performed using the CATALYST software package on a dataset of 100 thiosemicarbazide and thiazole derivatives acting as MAO-B irreversible inhibitors in order to, (i) better elucidate the possible role of the ligand features which are significant for binding and (ii) generate chemical features based pharmacophore models which were subsequently used as 3D queries for database searching. Based on known MAO-B inhibitors, pharmacophore hypotheses were created in order to find similarities between the thiazoles and thiosemicarbazides and identify the key sub-structures most likely to be significant for high MAO-B inhibitory activity.

Animals↗
PubMed2000

Fragment kinetic energies and modes of fragment formation

Kinetic energies of light fragments ( A</=10) from the decay of target spectators in 197Au+197Au collisions at 1000 MeV per nucleon have been measured with high-resolution telescopes at backward angles. Except for protons and apart from the observed evaporation components, the kinetic-energy spectra exhibit slope temperatures of about 17 MeV, independent of the particle species, but not corresponding to the thermal or chemical degrees of freedom at breakup. It is suggested that these slope temperatures may reflect the intrinsic Fermi motion and thus the bulk density of the spectator system at the instant of becoming unstable.

Journal Article↗
PubMed1999

Cortical benign fibromatous tumor (fibroma) of the kidney.

Benign fibromatous tumor (BFT), also named 'fibroma', is a distinctive clinico-pathologic entity occurring in epididymis, spermatic cord, paratesticular structures, testis, renal peripelvis and rarely in renal parenchyma. We report the first case of a BFT (fibroma) located in the cortex of the kidney, and a critical review on the topic is provided. Tumor was found incidentally at autopsy as a small cortical nodule. With the increasing use of radiological imaging of the abdomen, it is likely that an increased number of incidental and asymptomatic benign renal tumors will be diagnosed. We underline that BFT (fibroma) should be considered in the preoperative differential diagnosis of renal cortical nodules.

Actins↗
PubMed1999

Thiazole derivatives as inhibitors of purified bovine liver mitochondrial monoamine oxidase-B: structure-activity relationships and theoretical study.

Structure-activity relationships were performed on a new series of thiazole derivatives which selectively inactivate monoamine oxidase-B (MAO-B), purified from mitochondrial beef liver. All of the synthesized and tested compounds showed non-competitive inhibition, suggesting the formation of a stable adduct between the tertiary amine function, linked to the thiazolyl derivatives and the active site of the enzyme. The mechanism of MAO-B inhibition is discussed in terms of the Ionization Potential of the amine nitrogen atom and the conformational flexibility of the inhibitors.

Animals↗
PubMed1996

Growth conditions influence DNA methylation in cultured cerebellar granule cells.

Growth conditions influenced DNA methylation in cultured cerebellar granule cells, as indicated by immunocytochemical analysis with monoclonal antibodies raised against 5-methylcytidine. In cultures grown under suboptimal conditions, i.e. in medium containing 10 instead of 25 mM K+, a substantial reduction in both the number of immunopositive cells and the intensity of immunostaining occurred at 4 days in vitro (DIV), a time which preceded the appearance of the morphological features of apoptosis. These results suggest that a reduction in DNA methylation is one of the biochemical events associated with the 'condemned phase' of apoptosis, in which granule cells grown under suboptimal conditions become committed to death.

Animals↗
PubMed1996

Structure-activity studies on monoamine oxidase inhibitors by calorimetric and quantum mechanical calculations.

Structure-activity relationship studies were carried out on a new series of hydrazino-thiosemicarbazide derivatives, which inhibit monoamino oxidase (MAO). Fifty-five compounds were synthesized and tested "in vitro" for their inhibitory effects on rat liver mitochondrial MAO. The most efficient MAO inhibitors were the benzylidene derivatives (sequence: see text] where R is the piperonyl radical and ethyl or isopropyl substituents are in R1 position. Correlation of MAO activity with hydrophobic, electronic and steric properties of tested compounds, evaluated by means of Quantum Mechanical calculations and calorimetric analysis (DSC) suggest that electronic and steric parameters give a better fit than hydrophobicity with the biological activity.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Activation of class II or III metabotropic glutamate receptors protects cultured cortical neurons against excitotoxic degeneration.

Trans-1-aminocyclopentane-1,3-dicarboxylic acid, a mixed agonist of all metabotropic glutamate receptor (mGluR) subtypes, is known to produce either neurotoxic or neuroprotective effects. We have therefore hypothesized that individual mGluR subtypes differentially affect neurodegenerative processes. Selective agonists of subtypes which belong to mGluR class II or III, such as (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV) (specific for subtypes mGluR4, 6 or 7), were highly potent and efficacious in protecting cultured cortical neurons against toxicity induced by either a transient exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. In contrast, agonists that preferentially activate class I mGluR subtypes (mGluR1 or 5), such as quisqualate or trans-azetidine-2,3-dicarboxylic acid, were inactive. DCG-IV was still neuroprotective when applied to cultures after the toxic pulse with NMDA. This delayed rescue effect was associated with a reduction in the release of endogenous glutamate, a process that contributes to the maturation of neuronal damage. We conclude that agonists of class II or III mGluRs are of potential interest in the experimental therapy of acute or chronic neurodegenerative disorders.

Animals↗
PubMed1995

Inhibition of rat liver mitochondrial monoamine oxidase by hydrazine-thiazole derivatives: structure-activity relationships.

The purpose of this research is to study the relationship between chemical structure and inhibitory activity of some hydrazine-thiazole derivatives on rat liver mitochondria monoamine oxidase (MAO). Forty-five compounds belonging to three series of hydrazine-thiazole derivatives, with either alkylic or arylic substituents in the thiazole ring, were tested. The highest inhibitory activity was observed with piperonyl derivatives 25 and 40, which contain a 4-methyl group in the thiazole nucleus. The structure-activity relationship of MAO inhibitors was established in relation to hydrophobic, electronic and steric hindrance parameters. A mechanism of enzyme inhibition was proposed based on the calculation of HOMO energies.

Animals↗
PubMed1994

Correlation between monoamino oxidase inhibitor activity of some thiazol-2-ylhydrazines and their interaction with dipalmitoylphosphatidylcholine liposomes.

A calorimetric investigation has been carried out on the influence exerted by some 1-(alkoxybenzoyl)-2-(4-substituted thiazolyl-2-yl)hydrazines, possessing monoamine oxidase inhibitory (MAOI) activity, on the thermotropic behavior of model membranes constituted by dipalmitoylphosphatidylcholine (DPPC) vesicles. Attention was paid to evaluate how structural variations of drugs may influence drug-lipid interaction. The examined drugs were found to modify the gel to liquid-crystal phase transition of DPPC liposomes, by causing a shift of the transition temperature (Tm) toward lower values and a negligible variation in the enthalpy changes (delta H). The different effects on DPPC thermotropic behavior of these MAOI drugs could be considered in terms of different substituents on the molecule's backbone. The calorimetric results were related to drug's MAO inhibitory activity measured by fluorescence techniques and the apparent distribution coefficient of the compounds in water/n-octanol. A hypothesis on a correlation between a drug's structure, inhibitory activity, and membrane interaction has been suggested.

1,2-Dipalmitoylphosphatidylcholine↗