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Biomedical subjects

M Bonini

Publications and source records attributed to M Bonini.

At least 19 recordsLinked to original sources

Rhinitis and asthma in athletes: an ARIA document in collaboration with GA2LEN.

This consensus document is aimed at reviewing evidence that the rhinitis-asthma links have peculiar features in athletes. Beside a review of epidemological data on the high prevalence of rhinitis and asthma in athletes, the effects on intense physical exercise on the immune system and repiratory functions are discussed, with special reference to the role of allergens and pollutants. In extending the Allergic Rhinitis and its Impact on Asthma (ARIA) recommendations to athletes, the issue is addressed of adapting diagnosis and management to criteria set by the International Olympic Committee (IOC) and regulations adopted by the World Anti-Doping Agency (WADA).

Asthma↗

Synergistic effects of some metals contaminating mussels on the cytotoxicity of the marine toxin okadaic acid.

Okadaic acid (OA), a marine toxin is cytotoxic and promotes tumours in mouse skin. It is a specific and potent inhibitor of protein synthesis and also inhibits phosphatases A1 and A2 in vitro. In the present study, we investigated the influence of metals found at acceptable levels in mussels as environmental pollutants on the cytotoxicity of OA in Vero cells. Among the metals found in mussels (Mytilus edulis), the most represented, in terms of molar quantities per gram of dried weight are aluminium (230 nmol/g), copper (58 nmol/g), lead (16 nmol/g), mercury (14 nmol/g) and cadmium (7.4 nmol/g). A solution containing these five metals Al(3+), Cu(2+), Pb(2+), Hg(2+) and Cd(2+) combined at the concentrations detected in mussels, stimulated protein synthesis (+25%, P < 0.01), whereas different dilutions of this solution in the presence of okadaic acid (15 ng/ml, i.e. 18.7 x 10(-9) M) increased the percentage of protein synthesis inhibition from 35 to 79%. The metals also increased the lactate dehydrogenase (LDH) release into the medium and the lipid peroxidation induced by this algal toxin. In addition, these metals reduced the cell viability for an incubation period of 24 h especially at the two higher concentrations. These results indicate that metals (Al(3+), Cu(2+), Pb(2+), Hg(2+), Cd(2+)) in concentration ranges largely below the acceptable levels, synergistically increase the cytotoxicity of low concentrations of OA in cultured cells.

Animals↗

Oxygen reactive radicals production in cell culture by okadaic acid and their implication in protein synthesis inhibition.

Okadaic acid (OA), a diarrhetic shellfish toxin is a potent promoter of tumours in mouse skin and a specific inhibitor of protein phosphatases 1 and 2A. Recently it has been shown that OA inhibited protein synthesis in a cell-free system, with 50% inhibitory concentration of 6.3x10(-12) M but the mechanism whereby this inhibition is mediated was still unclear. In the present study, the effect of OA on protein synthesis in Vero cell cultures was investigated. Protein synthesis was inhibited by OA alone in Vero cells in a concentration-dependent manner (IC50=27 ng/ml i.e. 3. 3x10(-8) M). Since OA also induced lipid peroxidation and likely oxygen reactive radicals, it was interesting to know whether these radicals impair the protein synthesis process. Therefore, SOD+catalase known as scavenger of active oxygen radicals were added in the culture medium in the presence of OA and labelled leucine. These enzymes partially prevented the inhibition of protein synthesis induced by OA, indicating that the formation of high reactive oxygen free radicals could be one of the pathways this marine toxin induces its toxicity. Since the prevention by SOD+catalase was only partial (the IC50 increased from 27 ng/ml to 48 ng/ml i.e. 3.3x10(-8) M to 5.9x10(-8) M) it was speculated that the production of oxygen reactive radical scavengered by SOD+catalase is not the main mechanism whereby OA induces its cytotoxicity. Vitamins E and C completely prevent the lipid peroxidation induced by OA in cells, but failed to reduce the inhibition of protein synthesis to the same level, indicating that a more specific mechanism might be responsible for protein synthesis inhibition. That is the hyperphosphorylation of elongation factor EF-2 in the protein synthesis machinery. However our results pointed to lipid peroxidation being a precocious phenomenon following the OA exposure, since a concentration with enhanced MDA production was lower than that inducing significant cellular protein synthesis inhibition.

Animals↗

Transplacental passage of aluminum from pregnant mice to fetus organs after maternal transcutaneous exposure.

Aluminum is present in tap water, antiperspirants and cosmetics up to 20%. Teratogenicity of aluminium was clearly identified after per os or intravenous administration. Malformations and other alterations by aluminium intoxication were evaluated in fetus. In the present study, we investigated the possible transplacental passage of aluminium and its accumulation in the tissue after cutaneous uptake. Female Swiss mice received aluminium chloride by cutaneous way (0.4 micrograms/day) during 20 days of gestation. The samples were assayed for aluminium quantification by graphite furnace atomic absorption with Zeeman correction. This treatment led to an increase of aluminum in maternal and fetus samples (serum, amniotic fluid and organs) as compared to controls.

Aluminum↗

Inhibition of protein synthesis in a cell-free system and Vero cells by okadaic acid, a diarrhetic shellfish toxin.

Okadaic acid, a diarrhetic shellfish toxin, is a potent promoter of tumors in mouse skin and a specific inhibitor of protein phosphatases 1 and 2A. In the present study, we investigated its effects on protein synthesis in Vero cells and rabbit reticulocyte lysate. Protein synthesis was inhibited by okadaic acid in Vero cells in a concentration-dependent manner (IC50 = 3.3 x 10(8) M-1). DNA synthesis was also inhibited by okadaic acid in Vero cells in a concentration-dependent manner (IC50 = 5.3 x 10(8) M-1). DNA synthesis inhibition in Vero cells occurred only after 8 h or longer. RNA synthesis was inhibited with an IC50 of 8.2 x 10(8) M-1. The time lag before DNA and RNA synthesis inhibition occurred was longer than the time lag before protein synthesis inhibition occurred in the same cells (4 h), indicating that protein synthesis is probably the main target and the first of okadaic acid's cytotoxic effects. Moreover, the inhibition of DNA and RNA synthesis is probably a consequence of the inhibition of protein synthesis. Since okadaic acid does not impair the uptake of the precursor of protein synthesis, it is assumed that the inhibition is due to a direct effect on one of the components of the protein synthesis machinery. We then used a cell-free system of rabbit reticulocyte lysate in which specific mRNA is translated into globin to ensure that protein synthesis is a direct target of okadaic acid in vitro. In rabbit reticulocyte lysate, okadaic acid inhibited protein synthesis in a concentration-dependent manner (IC50 = 6.3 x 10(12) M-1) with a correlation coefficient for percent inhibition values of r = .918. The molecular target of okadaic acid inside the cell whereby protein synthesis is inhibited remains to be discovered.

Animals↗

Bioaccumulation of water soluble aluminium chloride in the hippocampus after transdermal uptake in mice.

Normally, only very small amounts of ingested aluminium are absorbed and accumulated. Despite the percutaneous absorption of many drugs and chemicals, the skin has not been considered as a possible site at which aluminium could enter the body. Application of low aqueous concentrations of aluminium chloride (A1C1(3), 6H20) (0.025-0.1 micrograms/cm2) to healthy shaved Swiss mouse skin for 130 days led to a significant increase in urine, serum and whole brain aluminium, especially in the hippocampus, compared to control animals. This percutaneous uptake and accumulation of aluminium in the brain was greater than that caused by dietary exposure to 2.3 micrograms per day in feed and water. In vitro studies demonstrated the passage of aluminium through viable mouse skin. This study shows for the first time that aluminium is absorbed through the skin of mice in vivo and this contributes to a greater body burden than does oral uptake.

Administration, Cutaneous↗

High performance liquid chromatography with ultraviolet detection used for laboratory routine determination of fluvoxamine in human plasma.

Fluvoxamine is an antidepressant drug introduced into the clinic in 1986. It acts by selectively inhibiting neuronal serotonin recapture. It can be quantified by several methods, including high performance liquid chromatography. The HPLC method used so far needs special equipment and has poor sensitivity. The technique is difficult and time consuming. An easier, quicker and more sensitive HPLC assay for the routine determination of fluvoxamine in human plasma has therefore been developed. After alkalinisation and direct extraction by a mixture of n-hexane-isoamylic alcohol 985: 15 (v/v) of plasma samples, the organic phases were further extracted by HCl 0.1 N. Thirty microL of the final extract (with loxapine as internal standard) were injected directly into a C-8 column with a mobile phase consisting of 370 mL acetonitrile, 0.4 mL diethylamine, 630 mL of distilled water, 25 mL pic B5. UV detection at 254 nm was used. The whole process was completed in 40 min. The detection limit was 10 ng mL-1. No interference was found either with several benzodiazepines or with antidepressant drugs commonly associated during treatments.

Antidepressive Agents↗

Saturnism caused by hand-made plates: partial diagnosis by a computer-aided program.

A man, aged 41 years, suffering from anaemia and abdominal pains was admitted to the Department of Medicine. Over the previous 2 years he had had several periods in hospital for these symptoms. There was, apparently, no occupational or accidental exposure to toxic substances and a correct diagnosis of the condition had not been possible. The computer-aided program AIDEDIAG II was therefore used to attempt a diagnosis. This approach indicated possible saturnism which was confirmed by metabolic and lead analyses. The lead source was identified as the hand-made food-plates used by the patient for his meals.

Adult↗

[Contribution to the determination of four antimalarial molecules (chloroquine, quinine, pyrimethamine, sulfadoxime) mixed in biological fluids. I. Spectrophotometry UV (author's transl)].

Antimalarial therapy is directed more and more towards the use of associated substances: Pyrimethamine, sulfadoxime, quinine et chloroquine. The authors propose a method of direct determination of these four molecules mixed in biological fluids. The recommended extraction process followed by a spectrophotometric UV determination is fast, reproductible and sufficiently sensitive to study the evolution of a therapy.

Antimalarials↗