Biomedical subjects

G Grossi

Publications and source records attributed to G Grossi.

At least 19 recordsLinked to original sources

PubMed2005

Fragmentation studies of relativistic iron ions using plastic nuclear track detectors.

We measured fluence and fragmentation of high-energy (1 or 5 A GeV) 56Fe ions accelerated at the Alternating Gradient Synchrotron or at the NASA Space Radiation Laboratory (Brookhaven National Laboratory, NY, USA) using solid-state CR-39 nuclear track detectors. Different targets (polyethylene, PMMA, C, Al, Pb) were used to produce a large spectrum of charged fragments. CR-39 plastics were exposed both in front and behind the shielding block (thickness ranging from 5 to 30 g/cm2) at a normal incidence and low fluence. The radiation dose deposited by surviving Fe ions and charged fragments was measured behind the shield using an ionization chamber. The distribution of the measured track size was exploited to distinguish the primary 56Fe ions tracks from the lighter fragments. Measurements of projectile's fluence in front of the shield were used to determine the dose per incident particle behind the block. Simultaneous measurements of primary 56Fe ion tracks in front and behind the shield were used to evaluate the fraction of surviving iron projectiles and the total charge-changing fragmentation cross-section. These physical measurements will be used to characterize the beam used in parallel biological experiments.

Aluminum↗

PubMed2005

Modelled microgravity does not modify the yield of chromosome aberrations induced by high-energy protons in human lymphocytes.

The aim was to evaluate the effect of modelled microgravity on radiation-induced chromosome aberrations (CAs). G0 peripheral blood lymphocytes were exposed to 60 MeV protons or 250 kVp X-rays in the dose range 0-6 Gy, and allowed to repair DNA damage for 24 h under either normal gravity or microgravity modelled by the NASA-designed rotating-wall bioreactor. Cells were then stimulated to proliferate by phytohaemagglutinin (PHA) under normal gravity conditions and prematurely condensed chromosomes were harvested after 48 h. CAs were scored in chromosomes 1 and 2 by fluorescence in-situ hybridization. Proliferation gravisensitivity was examined by cell growth curves and by morphological evaluation of mitogen-induced activation. Cell replication rounds were monitored by bromodeoxyuridine labelling. Modelled microgravity markedly reduced PHA-mediated lymphocyte blastogenesis and cell growth. However, no significant differences between normal gravity and modelled microgravity were found in the dose-response curves for the induction of aberrant cells or total interchromosomal exchange frequency. Rotating-wall bioreactor-based microgravity reproduced space-related alterations of mitogen stimulation in human lymphocytes but did not affect the yield of CAs induced by low-linear energy transfer radiation.

Cell Proliferation↗

PubMed2005

Cytogenetic effects of high-energy iron ions: dependence on shielding thickness and material.

We report results for chromosomal aberrations in human peripheral blood lymphocytes after they were exposed to high-energy iron ions with or without shielding at the HIMAC, AGS and NSRL accelerators. Isolated lymphocytes were exposed to iron ions with energies between 200 and 5000 MeV/nucleon in the 0.1-1-Gy dose range. Shielding materials consisted of polyethylene, lucite (PMMA), carbon, aluminum and lead, with mass thickness ranging from 2 to 30 g/cm2. After exposure, lymphocytes were stimulated to grow in vitro, and chromosomes were prematurely condensed using a phosphatase inhibitor (calyculin A). Aberrations were scored using FISH painting. The yield of total interchromosomal exchanges (including dicentrics, translocations and complex rearrangements) increased linearly with dose or fluence in the range studied. Shielding decreased the effectiveness per unit dose of iron ions. The highest RBE value was measured with the 1 GeV/nucleon iron-ion beam at NSRL. However, the RBE for the induction of aberrations apparently is not well correlated with the mean LET. When shielding thickness was increased, the frequency of aberrations per particle incident on the shield increased for the 500 MeV/nucleon ions and decreased for the 1 GeV/nucleon ions. Maximum variation at equal mass thickness was obtained with light materials (polyethylene, carbon or PMMA). Variations in the yield of chromosomal aberrations per iron particle incident on the shield follow variations in the dose per incident particle behind the shield but can be modified by the different RBE of the mixed radiation field produced by nuclear fragmentation. The results suggest that shielding design models should be benchmarked using both physics and biological data.

Chromosome Aberrations↗

PubMed2004

Chromosomal aberrations induced by high-energy iron ions with shielding.

Biophysical models are commonly used to evaluate the effectiveness of shielding in reducing the biological damage caused by cosmic radiation in space flights. To improve and validate these codes biophysical experiments are needed. We have measured the induction of chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to 500 MeV/n iron ion beams (dose range 0.1-1 Gy) after traversing shields of different material (lucite, aluminium, or lead) and thickness (0-11.3 g/cm2). For comparison, cells were exposed to 200 MeV/n iron ions and to X-rays. Chromosomes were prematurely condensed by a phosphatase inhibitor (calyculin A) to avoid cell-cycle selection produced by the exposure to high-LET heavy-ion beams. Aberrations were scored in chromosomes 1, 2, and 4 following fluorescence in situ hybridization. The fraction of aberrant lymphocytes has been evaluated as a function of the dose at the sample position, and of the fluence of primary 56Fe ions hitting the shield. The influence of shield thickness on the action cross-section for the induction of exchange-type aberrations has been analyzed, and the dose average-LET measured as a function of the shield thickness. These preliminary results prove that the effectiveness of heavy ions is modified by shielding, and the biological damage is dependent upon shield thickness and material.

Aluminum↗

PubMed2003

Biological dosimetry in Russian and Italian astronauts.

Large uncertainties are associated with estimates of equivalent dose and cancer risk for crews of long-term space missions. Biological dosimetry in astronauts is emerging as a useful technique to compare predictions based on quality factors and risk coefficients with actual measurements of biological damage in-flight. In the present study, chromosomal aberrations were analyzed in one Italian and eight Russian cosmonauts following missions of different duration on the MIR and the international space station (ISS). We used the technique of fluorescence in situ hybridization (FISH) to visualize translocations in chromosomes 1 and 2. In some cases, an increase in chromosome damage was observed after flight, but no correlation could be found between chromosome damage and flight history, in terms of number of flights at the time of sampling, duration in space and extra-vehicular activity. Blood samples from one of the cosmonauts were exposed in vitro to 6 MeV X-rays both before and after the flight. An enhancement in radiosensitivity induced by the spaceflight was observed.

Astronauts↗

PubMed2002

The treatment of functional dyspepsia with red pepper.

AIM: : To decrease the intensity of dyspeptic symptoms by impairing the visceral nociceptive C-type fibres with capsaicin, contained in red pepper powder. METHODS: : The study was performed on 30 patients with functional dyspepsia and without gastro-oesophageal reflux disease and irritable bowel syndrome. After a 2-week washout period, 15 patients received, before meals randomly and in a double-blind manner, 2.5 g/day of red pepper powder for 5 weeks, and 15 patients received placebo. A diary sheet was given to each patient to record, each day, the scores of individual and overall symptom intensity, which subsequently were averaged weekly and over the entire treatment duration. RESULTS: : The overall symptom score and the epigastric pain, fullness and nausea scores of the red pepper group were significantly lower than those of the placebo group, starting from the third week of treatment. The decrease reached about 60% at the end of treatment in the red pepper group, whilst placebo scores decreased by less than 30%. CONCLUSIONS: : Red pepper was more effective than placebo in decreasing the intensity of dyspeptic symptoms, probably through a desensitization of gastric nociceptive C-fibres induced by its content of capsaicin. It could represent a potential therapy for functional dyspepsia.

Adult↗

PubMed2001

Phonological processing in visual rhyming: a developmental erp study.

We employed a visual rhyming priming paradigm to characterize the development of brain systems important for phonological processing in reading. We studied 109 righthanded, native English speakers within eight age groups: 7-8, 9-10, 11-12, 13-14, 15-16, 17-18, 19-20, and 21-23. Participants decided whether two written words (prime-target) rhymed (JUICE-MOOSE) or not (CHAIR-MOOSE). In similar studies of adults, two main event-related potential (ERP) effects have been described: a negative slow wave to primes, larger over anterior regions of the left hemisphere and hypothesized to index rehearsal of the primes, and a negative deflection to targets, peaking at 400-450 msec, maximal over right temporal-parietal regions, larger for nonrhyming than rhyming targets, and hypothesized index phonological matching. In this study, these two ERP effects were observed in all age groups; however, the two effects showed different developmental timecourses. On the one hand, the frontal asymmetry to primes increased with age; moreover, this asymmetry was correlated with reading and spelling scores, even after controlling for age. On the other hand, the distribution and onset of the more posterior rhyming effect (RE) were stable across age groups, suggesting that phonological matching relied on similar neural systems across these ages. Behaviorally, both reaction times and accuracy improved with age. These results suggest that different aspects of phonological processing rely on different neural systems that have different to developmental timecourses.

Evoked Potentials↗

PubMed2001

1,5-Benzodiazepine tricyclic derivatives exerting anti-inflammatory effects in mice by inhibiting interleukin-6 and prostaglandinE(2)production.

The 1,4- and the 1,5-benzodiazepines (BDZ) are commonly used as anxiolytic and anticonvulsive drugs. It has been suggested that they influence, particularly through stimulation of peripheral BDZ receptors, some immune cell properties such as pro-inflammatory cytokine production. The availability of a new class of [1,2,4]triazolo[4,3-a][1,5]benzodiazepine derivatives (compounds IV), endowed with anti-inflammatory and/or analgesic properties but no anti-pentylenetetrazole activity, prompted us to investigate in more detail the anti-inflammatory properties of three selected compounds IV (N,N-dimethyl-1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benz- odiazepin-5-amine; N,N-dibutyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amine; 1-methyl-N,N-dimethyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amine) and one structurally related compound (1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one). These BDZ derivatives have lost their affinity for the central and peripheral BDZ receptors. The in vivo effect on leukocyte migration of these compounds was investigated by using the mouse air-pouch model of local inflammation. Compounds A and B, significantly inhibited the carrageenan-induced leukocyte recruitment in a dose-dependent manner starting from the dose of 50 mgkg(-1), whereas compound C was effective only at the higher dose of 100 mgkg(-1). Compound D did not exert such effects at any of the doses considered. The effect of compounds A, B and C on leukocyte recruitment was paralleled by a significant inhibition of interleukin-6 and prostaglandin E(2)production in the exudate, similarly to indomethacin, and by a partial reduction of vascular permeability. These features may be relevant for the design and development of innovative anti-inflammatory molecules among the 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amine derivatives.

Analgesics↗

PubMed2001

On the radiosensitivity of man in space.

Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space.

Aerospace Medicine↗

PubMed2001

Analysis of all-in-one parenteral nutrition admixtures by liquid chromatography and laser diffraction: study of stability.

All-in-one parenteral nutrition admixtures are complex lipid emulsions (oil/water) which require absolute sterility, stability and no precipitates. Particle diameter must be in the range 0.4--1 microm in order to mime the size of chylomicra. Added vitamins must not degrade during infusion time (24 h). In this study, the physicochemical stability of parenteral nutrition admixtures was tested in the course of time at different storage temperatures. Two liquid chromatographic methods, based on solid phase extraction (SPE), were developed for fat-soluble vitamin determination. Stability studies were carried out on three industrial lipid emulsions and on six compounded all-in-one admixtures. They were stored at three different temperatures: 4 degrees C (storage), 25 degrees C (compounding) and 37 degrees C (infusion); then they were analyzed at starting time and at 24, 48 and 72 h after compounding. Particle diameter was determined by means of Laser Particle Sizer Analysette 22, which uses laser diffraction technique (light scattering -- reverse Fourier optics). Fat-soluble vitamins (retinol palmitate and alpha-, delta-, gamma-tocopherol) were determined in admixtures with a branded vitamin compound called Idroplurivit Liofilizzato. Samples were extracted by SPE on C(18) cartridges, then they were separated by reversed-phase liquid chromatography (LC) and detected by ultraviolet detection (retinol palmitate) and electrochemical detection (tocopherols). Laser diffraction analysis pointed out that particle size did not change in the course of time at the tested temperatures. LC analysis showed that vitamins interact each other and degrade after compounding at different times and storage temperatures; only retinol palmitate is stable at 37 degrees C. Retinol palmitate recovery was 98%, coefficient of variation (CV) 5.4%, detection limit 25 microg/l, limit of quantitation 75 microg/l and there were not interfering substances. Tocopherols average recovery was 99%, CV 3.5%, detection limit 15 ng/l and limit of quantitation 50 ng/l. In conclusion, all-in-one parenteral admixtures were proved to be physically stable under analysis conditions, but degradation of retinol palmitate and tocopherols requires admixtures with vitamins to be infused within 24 h after compounding.

Chromatography, Liquid↗

PubMed2001

Antioxidants and total peroxyl radical-trapping ability of olive and seed oils.

The presence of the oxidized and reduced forms of ubiquinones Q(9) and Q(10) was determined in commercial extra virgin olive and seed oils, where the amounts of alpha- and gamma-tocopherols and beta-carotene were also quantitated. Very high concentrations of ubiquinones were found in soybean and corn oils. Furthermore, the total antioxidant capability of each oil was evaluated by measuring total radical-trapping antioxidant parameters (TRAP) in tert-butyl alcohol and using egg lecithin as the oxidizable substrate. These values decreased in the order sunflower > corn > peanut > olive; the highest TRAP, which was found in sunflower oil, was related to the very high amount of alpha-tocopherol. Olive oil, because of the low content of alpha-tocopherol, exhibited a TRAP value approximately one-third that of sunflower oil. TRAP values of corn and soybean oils, in which low amounts of alpha-tocopherol but very high contents of gamma-tocopherol and reduced ubiquinones were present, were intermediate. gamma-Tocopherol exhibited a poor ability of trapping peroxyl radicals in tert-butyl alcohol. This behavior was probably due to the effects of the solvent on the rate of hydrogen abstraction from this phenol.

Antioxidants↗

PubMed2001

Inactivation of human cells exposed to fractionated doses of low energy protons: relationship between cell sensitivity and recovery efficiency.

Within the framework of radiation biophysics research in the hadrontherapy field, split-dose studies have been performed on four human cell lines with different radiation sensitivity (SCC25, HF19, H184B5 F5-1 M10, and SQ20B). Low energy protons of about 8 and 20 keV/micron LET and gamma-rays were used to study the relationship between the recovery ratio and the radiation quality. Each cell line was irradiated with two dose values corresponding to survival levels of about 5% and 1%. The same total dose was also delivered in two equal fractions separated by 1.5, 3, and 4.5 hours. A higher maximum recovery ratio was observed for radiosensitive cell lines as compared to radioresistant cells. The recovery potential after split doses was small for slow protons, compared to low-LET radiation. These data show that radiosensitivity may not be related to a deficient recovery, and suggest a possible involvement of inducible repair mechanisms.

Cell Line↗

PubMed2001

Cell inactivation by beryllium, boron and carbon ions at the low-energy irradiation facility of the Naples University.

The 3MV HVEC TTT-3 Tandem accelerator at the University of Naples, already used for radiobiological studies with protons and alpha particles, was set up for irradiation of biological samples with low energy carbon, boron, and beryllium beams. Radiobiological characterisation and study of these ion beams is essential in hadrontherapy (correction of hadrotherapy) to understand, for example, the possible biological effect of the target fragmentation products. Furthermore in space radiation biology we need to know the biological effects of heavy ions, a component of cosmic radiation that can contribute to the radiobiological risk when long sojourns in space are concerned. V79 Chinese hamster cells were irradiated with the different ions and the resulting cell inactivation data are reported.

Animals↗

PubMed2001

A model of radiation-induced myelopoiesis in space.

Cell Survival↗

PubMed2001

Effect of space radiation on expression of apoptosis-related genes in endometrial cells: a preliminary study.

In this paper we present some preliminary results on alteration of gene expression caused by radiation on human endometrial cells. To this purpose, we have studied the modulation of the expression of the bcl-2 gene family in two cell lines following irradiations with low energy protons and gamma-rays from a 60Co. The two epithelial cell strains, namely AN3Ca and HEC1B cells, both obtained from human neoplastic endometrial tissues, grow in culture and continue to maintain some differentiated functions typical of the original tissue. Indeed, these cells, that can be considered as representative of different stages of cellular transformation of endometrium. Because their epithelial nature and rapid growth, the expression of genes related to the maintenance of the cellular homeostasis (correction of omeostasis), as the pro and anti-apoptotic ones, is expected to be susceptible to changes in environment, including radiation. The effects have been evaluated in terms of both cell survival and changes in the expression of pro- and anti apoptotic proteins. Even though the data reported above can not be considered complete and/or definitive, nevertheless, in whole, they confirm that these cells may constitute a suitable model system to study, at molecular level, the effects of cosmic radiation on endometrium. Further observation, ensuing from these preliminary data, is that endometrial cells present different sensitivity to radiation in regard to its 'quality' and 'dosage', in accord to the original stage of differentiation.

Apoptosis↗

PubMed2000

Elevated plasma homocysteine levels in centenarians are not associated with cognitive impairment.

BACKGROUND: Previous reports have shown elevated plasma total homocysteine (tHcy) levels in elderly person with impaired cognition. OBJECTIVE: To study the association between cognitive status and plasma tHcy levels in centenarians. DESIGN: Cross-sectional survey. SETTING: Centenarians living in two northern Italian provinces. PARTICIPANTS: Thirteen cognitively normal centenarians, ten cognitively impaired not-demented centenarians, and 34 demented centenarians with a clinical diagnosis of Alzheimer's disease (AD). MEASUREMENTS: Blood levels of homocysteine's biological determinants vitamin B12, folate, and vitamin B6. RESULTS: Elevated plasma tHcy levels (>17 micromol/l) were common in the general population (77% of normal centenarians, 100% of cognitively impaired not-demented centenarians, 82% of AD centenarians). Demented centenarians had the lowest folate serum levels. Low or borderline vitamin B12 serum levels (<221 pmol/l) and low vitamin B6 plasma levels (<11.7 nmol/l) were found in 33 and 66% of all centenarians independently of cognitive status. Among demented centenarians only plasma tHcy correlated inversely with both serum vitamin B12 and folate. No significant difference was found for plasma tHcy levels among the three diagnostic groups, even after adjusting for B vitamin levels. CONCLUSIONS: Hyperhomocysteinemia is very common among centenarians, probably due to vitamin deficiencies, but does not seem to be associated with cognitive impairment.

Aged↗

PubMed2000

1,8-Naphthyridines IV. 9-substituted N,N-dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4]triazolo[4,3-a][1, 8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities.

The title compounds (8) were synthesized through the cyclocondensation of the corresponding N-substituted 4-amino-2-chloro-1,8-naphthyridine-3-carboxamides (4) with the proper hydrazides, in order to evaluate their anti-inflammatory and anti-aggressive properties. Several compounds 8 exhibited high anti-inflammatory activity (carrageenin-induced paw edema assay in the rat) along with appreciable anti-aggressive properties (isolation-induced aggressiveness test in mice). With respect to anti-inflammatory activity, the most active compounds (8n and 8c) produced a 61% edema inhibition at the 25 mg/kg dose, and 50 or 35% inhibition, respectively, at the 12.5 mg/kg dose. The structure-activity relationships are discussed.

Aggression↗

PubMed2000

Synthesis, antiplatelet activity and comparative molecular field analysis of substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones, their congeners and isosteric analogues.

2-(1-Piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (5a) is a recently described in vitro inhibitor of human platelet aggregation which specifically inhibits the activity of high affinity cAMP phosphodiesterase. A number of substitution derivatives, isosteres, and analogues of 5a were now synthesized and tested in vitro for their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen, or the Ca2+ ionophore A23187. Among the most effective compounds, the 6-methyl, 8-methyl and 6,8-dimethyl derivatives of 5a resulted nearly as active as the lead when platelet aggregation was induced by ADP or A23187, but less active when collagen was the inducer. On the basis of present results and those previously obtained by us in this and 2-aminochromone structural fields, we have developed a statistically significant 3-D QSAR model, using comparative molecular field analysis (CoMFA), describing the variation of the antiplatelet activity in terms of molecular steric and electrostatic potential changes.

Humans↗