A Review on the Radioprotective Activity of organogermanium and Organosilicon Compounds.

The present review describes the work carried out during the last 20 years in the field of the radioprotective activity and toxicity of several classes of organosilicon and organogermanium compounds (i.e. metallathiazolidines, metalladithioacetals, metallatranes and germathianes).

Synthesis and radioprotective activity of new organosilicon and germanium compounds.

Silathiazolidine and metalladithioacetals (M = Si, Ge) have been prepared by the interaction of dialkyldichloro- or bis(diethylamino)dialkylsilanes and -germanes with 3-[N-(2- thioethyl)]amino-propanamide (WR-2529) and [1-thioethyl-2-(1-naphtylmethyl)]-2- imidazoline. The study of these compounds in the field of chemical radioprotection has shown a notable decrease in the toxicity and a rather large increase in the radioprotective activity of these new derivatives in comparison with the starting organic compounds.

Effect of neutron-gamma radiation on dopamine and serotonin metabolism in the rat brain: a regional analysis.

The concentrations of dopamine (DA) and its metabolites and the levels of 5-hydroxyindoleacetic acid (5-HIAA), the metabolite of serotonin, were determined in discrete cerebral areas of rats 3 hr after (neutron-gamma) irradiation at 4 and 7 Gy. After the 7 Gy irradiation, no significant effect was observed. After the 4 Gy exposure, the most marked difference between irradiated and control rats was in the levels of DA and its metabolites in the striatum.

Anti-emetic effect of ondansetron and granisetron after exposure to mixed neutron and gamma irradiation.

The anti-emetic efficiency of orally administered ondansetron and granisetron has been tested in macaques exposed to a mixed y and neutron radiation (6 Gy) with a high neutron/gamma-ray ratio. Our experiments reveal that a single delivery of ondansetron (1 or 2 mg kg(-1)) or of granisetron (0.25 mg kg(-1)) 45-90 min before irradiation or 35-45 min after irradiation was not totally effective.

Real-time spike detection in EEG signals using the wavelet transform and a dedicated digital signal processor card.

This paper describes a complete real-time system for EEG signal analysis. Specific software and hardware have been designed to provide biologists with an efficient tool, which allows a complete study of the different states of vigilance as well as the paroxysmal activities. The analysis method which is based on the wavelet transform is first presented and compared to the standard spectral approach.

Activation of large conductance Ca(2+)-activated K+ channels in N1E-115 neuroblastoma cells by platelet-activating factor.

Using patch-clamp single channel recording techniques, we reported a Platelet-Activating Factor "PAF"-induced activation of large conductance Ca(2+)-activated K+ "BK(Ca)" channels in N1E-115 cells. This activation was only observed in cell-attached configuration and was blocked by the PAF antagonist BN50739 or removal of calcium from the bath. Nanomolar concentration of PAF produced a transient hyperpolarization observed in whole-cell current clamp configuration which was blocked by the bath application of BN50739 or iberiotoxin.

High-performance liquid chromatography-electrochemical determination of salicylate hydroxylation products as an in vivo marker of oxidative stress.

The in vivo measurement of highly reactive free radicals, such as hydroxyl radical (.OH), in humans is very difficult if not impossible. Specific markers are currently under investigation (amino acid hydroxylatin, protein, DNA adducts, and aromatic probes).

Presence of specific platelet-activating factor binding-sites in neuroblastoma N1E-115 cells.

In this study we reported evidence for the existence of specific binding sites for platelet-activating factor (PAF) in neuroblastoma N1E-115 cells. The specific [3H]PAF binding reached a steady state level within 60 min at 25 degrees C. Scatchard analysis of the specific [3H]PAF binding revealed the presence of two apparent populations of binding sites.

[NMR study of membrane incorporation of cysteamine].

The incorporation of the cysteamine molecule in small unilamellar vesicles was studies using proton NMR technics. A linear inclusion of the radioprotective molecule was firstly observed by increasing the Cysteamine/phospholipid molar ratios, followed by a saturation for the highest ratios. Such results may be adapted to a new galenic form study.

[Management of accidental internal exposure].

Radionucleides can penetrate into the body via the lung, the digestive tract, wounds and sometimes through healthy skin. Once they have penetrated the body, they can either remain localized at the site of entry or be rapidly metabolized. The risk is late effects.

Effects of neutron-gamma irradiation on striatal D1 and D2 receptor distribution.

The early effects of neutron irradiation on the striatal D1 and D2 dopaminergic receptor distribution were investigated by quantitative receptor autoradiography. One hour after exposure at the dose of 8.4 Gy, an increase of D1 (+21%) and D2 (+25%) receptor density was observed in the striatum, located at the most anterior levels, containing the richest plexus of dopaminergic fibers afferent from the substantia nigra.

Stimulated release of acetylcholinesterase in rat striatum revealed by in vivo microspectrophotometry.

The microspectrophotometric technique allows a direct in vivo measurement of brain extracellular acetylcholinesterase. An optical probe associated with electrodes for stimulation was implanted in striatum of anaesthetized rats to determine the effects of neuronal excitation on the acetylcholinesterase activity. Electrical stimulations induced a reversible increase in acetylcholinesterase activity of about 30 to 50%, with a recovery to baseline occurring after 1 or 2 h.

Early and transient effects of neutron irradiation on dopamine receptors in the adult rat brain.

The early neurochemical effects of neutron-gamma radiation exposures were studied through ligand dopamine D1, D2 receptors binding experiments. The parameters of binding were investigated on crude preparations from striatum at different delays (from 2 to 72 hours) after irradiation. An early and transient increase in the total number of sites was seen after exposure, even at infra-lethal dose.

Influence of the radioprotective agent WR 2721 on the striatal acetylcholinesterase activity in the rat.

The radioprotective thiophosphate S-2(3 amino-propyl-amino) phosphorothioic acid (WR 2721) induced an early reduction of striatal acetylcholinesterase activity followed by an increase, when intraperitoneally injected to rats, although it does not cross the blood-brain barrier. These results were obtained using an original technique which allows the measurements in the same animal for several days. Transient general oxidative metabolism inhibition might affect the extra-cellular enzyme amount or its activity.

[Early effects of neutron-gamma or gamma irradiation on the group toxicity induced by (+) amphetamine in mice].

To better understand the mechanism of action of gamma and neutron radiation on the dopaminergic system, the influence of the two irradiation modalities on the group toxicity of (+) amphetamine was studied in mice. Neutron-gamma irradiation (3.6-4.

Some recent data on chemical protection against ionizing radiation.

Once introduced in the organism, the radioprotectors are fastly degraded and that increases their toxicity, shortens their duration of action and renders them inactive after oral delivery. So, it was tried to protect them by their incorporation in vectors. When a cysteamine-liposomal suspension was orally delivered, it showed a radioprotective activity for about 4 hours.

Rapid postmortem decrease in the ectocellular acetylcholinesterase activity in rat striatum as assessed by in vivo microspectrophotometry.

The acetylcholinesterase (AChE) activity in striatum rat was determined before and shortly after death using the in vivo microspectrophotometric method. This technique allowed us to monitor the Ellman colorimetric reaction directly inside the brain using an optical probe implanted in a live animal and to determine locally the AChE activity. Whatever the cause of the animals death, we observed a drastic postmortem decrease of the AChE activity of about 35-50%, 10 min after death.

[Effects of neutron-gamma or gamma irradiation on plasma coagulation factors. Effect of a substitution treatment].

Neutron-gamma irradiation of the baboon at lethal dose altered the plasma clotting factors and induced a fibrinoformation alteration which occurred shortly before death. These disturbances, which were not found after gamma irradiation, could explain the importance of the haemorrhagic syndrome. Treatment by P.

In vivo spectrophotometric determination of striatal acetylcholinesterase activity: the modulation induced by the antidepressant amitriptyline.

A new technology called in vivo spectrophotometry was applied to the quantitative determination of the variations in local acetylcholinesterase (AChE) activities. Repeated measurements of the enzyme activities in the same live animal allowed the study of the in vivo inhibition of AChE by amitriptyline. Interactions between AChE and this tricyclic antidepressant were investigated at the striatal level in anesthetized rats.

Synthesis and radioprotective activity of dipeptide cysteamine and cystamine derivatives.

Some N-(dipeptidyl)-S-acetylcysteamine and N,N'-(dipeptidyl)cystamine salt derivatives were synthesized and evaluated as candidate radioprotector agents. Toxicity and radioprotective activity as the dose reduction factor (DRF) were determined in vivo on mice and compared to N-glycyl-S-acetylcysteamine trifluoroacetate. One of the most interesting compounds of this series was N-glycylglycyl-S-acetylcysteamine trifluoroacetate (8).

A radioprotector: cysteamine, inhibits oxygen transport in lipidic membranes.

Spin labeling techniques make possible the observation of oxygen diffusion or concentrations in phospholipid membranes. In such a system, cysteamine, depending upon the molecular cysteamine/DPPC ratio and the pH conditions, inhibits oxygen transport, and this result provides an original explanation for cellular hypoxia after cysteamine administration.

Radioprotective activity of ethylcellulose microspheres containing WR 2721, after oral administration.

Ethylcellulose microspheres containing WR 2721 were prepared by the emulsion-solvent evaporation technique. No significant loss or degradation of this phosphorothioate was noted during preparation. Oral administration of these microspheres to mice gave an important lowering of WR 2721 toxicity and an enhancement of its radioprotective activity with a D.

Radioprotective effect of an acute non-specific inflammation in mice.

Protection against 8.7 Gy whole-body gamma-irradiation (lethal in 100 per cent of mice by 30 days) was observed in 90 per cent of mice bearing a one-day-old granuloma induced by polyacrylamide beads. When the inflammatory reaction was induced sooner or later a lower or null protection was obtained.