[Effects of radiation on man].

Living on Earth, man is subjected to a shower of radiation, of cosmic, telluric and internal origin. Variations in the level of radiation over time have left biological imprints; Man first learned about artificial radiation, then learned how to produce it, revolutionizing medical diagnosis and treatment, and producing huge quantities of energy, particularly electric energy. In les than a century, knowledge or radiobiology brought man to a good mastery of the use or radiation within precise norms.

[Involvement of PAF (Platelet-Activating Factor) in chloroquine-induced retinopathy].

Chloroquine retinopathy is a severe toxic retinal impairment which may result in loss of vision by alterations of the pigmentary epithelium and photoreceptors. Currently, there is no specific treatment for this retinopathy. In order to test the possible involvement of Platelet-Activating Factor (PAF) in chloroquine-induced retinopathy and the use of PAF antagonists for prevention of this condition, we have examined the effect of these substances on the electroretinogram (ERG) of isolated rat retina.

Phase I trial of cystemustine, a new cysteamine (2-chloroethyl) nitrosourea: an intrapatient escalation scheme.

A trial of cystemustine, a cysteamine nitrosourea, was carried out on 34 patients with advanced malignancies at increasing dosage of the drug over a period of up to 190 days in seven or eight cycles. A partial response to treatment was obtained in three patients. A degree of haematological toxicity developed in a number of the patients.

Excision of imidazole ring-opened N7-hydroxyethylguanine from chloroethylnitrosourea-treated DNA by Escherichia coli formamidopyrimidine-DNA glycosylase.

Alkylkation of the N7 of guanine residues in DNA favours the opening of the imidazole ring, yielding a formamidopyrimidine (Fapy). This Fapy residue blocks DNA replication and is actively excised by a DNA glycosylase. We have cloned and sequenced the Escherichia coli gene responsible for synthesis of the enzyme, which has also been purified to homogeneity.

[Perspectives of scintigraphic diagnosis of malignant lymphoma using a new radiopharmaceutical].

In the sequence of our studies on radiopharmaceuticals for malignant melanoma detection the results were most promising for the possible use of 125I or 123I-N-(2-diethyl amino ethyl)4-iodobenzamide. The biodistribution in mice bearing melanoma either human or animal from 4 to 24 hrs. post i.

Metabolism of a new radioprotector; S-acetyl-N-glycyl cysteamine. II. Main tissue metabolites in mice bearing EMT6 tumours.

1. The major tissue metabolites of the radioprotector S-acetyl-N-glycl cysteamine (I) labelled with 14C on the cysteamine group, were quantified and identified in normal tissues and EMT6 tumours implanted in mice, by chromatographic comparison with authentic reference compounds. 2.

Presence of specific platelet-activating factor binding sites in the rat retina.

The specificity of the effects of platelet-activating factor (PAF) on the electrophysiology of the retina suggests the existence of specific sites for PAF in this tissue. In this study, we report the presence of tritiated PAF ([3H]PAF) specific binding sites in membrane preparations of the retina of albino rats. The binding of [3H]PAF was saturable, specific, time-dependent and reversible.

[Inhibition of transducin by lithium: electrophysiological demonstration using the isolated retina].

Recently Avissar et al. have established that Li+ can inhibit G proteins implicated in brain function. In order to investigate the effect of Li+ on transducin, the evolution of the electroretinogram (ERG) recorded on isolated rat retina has been studied in presence of lithium.

Effects of platelet-activating factor on electrophysiology of isolated retinas and their inhibition by BN 52021, a specific PAF-acether receptor antagonist.

The effects of (R)PAF-acether have been tested on the isolated rat retina model. Results indicate that (R)PAF-acether inhibits the electrophysiological response (electroretinogram) elicited on isolated retina by a brief light flash. Immediately after the administration of (R)PAF-acether, an irreversible decrease of the electroretinogram b-wave amplitude is observed.

Disposition of new sulphur-containing 2-(chloroethyl)nitrosoureas in rats.

N'-(2-Chloroethyl)-N-[2-(methylsulphinyl) ethyl] and N'-(2-chloroethyl)-N-[2-(methylsulphonyl) ethyl]-N and N'-nitrosoureas (CMSOEN1, CMSO2EN1, CMSOEN2 and CMSO2EN2) are new nitrosoureas derived from cysteamine. Two of them (CMSOEN2 and CMSO2EN2) have shown excellent efficacy against several murine tumours. The inactive agents (CMSOEN1 and CMSO2EN1) display low alkylating activity but high carbamoylating activity.

Effects of PAF-acether on electrophysiological response of isolated retina.

Results of experiments performed on rat isolated retina indicate that platelet-activating factor (PAF) is able to inhibit the functional response of the retina electroretinogram (ERG) recorded in response to a brief light flash. In the presence of PAF, the ERG b-wave amplitude decreases according to a dose-dependent (2.10(-11) M; 2.

Cytostatic action of two nitrosoureas derived from cysteamine.

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.

Brain uptake of labelled adiphenine in rats.

This study describes the behaviour of a dual labelled drug, adiphenine, in the rat brain. Macroautoradiographies show images of the brain at different times after injection. Some of the tissue metabolites are identified at the brain level and the passage of the blood brain barrier is compared with tritiated water.

Metabolism of 2-chloroethyl nitrosocarbamoylcystamine by rat liver subcellular fractions.

Previously we have shown that a new nitrosourea, 2-chloroethyl nitrosocarbamoylcystamine (CNCC), undergoes an extensive metabolism in the rat. Two pairs of plasma metabolites have been identified. This suggested our hypothesis that the metabolic pathway involves the reduction of the disulfur bridge followed by the methylation and the oxidation of the thiol groups.

Adiphenine plasma levels and blood-brain barrier crossing in the rat.

Adiphenine was administered in 3H-labelled form in doses of 15 mumole/kg intravenously to male Wistar rats. Plasma and brain levels of the unchanged drug were measured. The elimination of the 3H-labelled compound from the plasma was monophasic with a half-life of 13 minutes.

New cysteamine (2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results.

Three chemical pathways were used for the synthesis of four new N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]- and N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N- or N'-nitrosoureas. These compounds are plasma metabolites of CNCC, a promising antineoplastic (2-chloroethyl)nitrosourea. Preliminary antitumor evaluation was performed against L1210 leukemia implanted intraperitoneally in mice.

IgG purification to measure the level of an iodinated thyroglobulin peptide, the 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine in human serum.

Antibodies reacting with 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.

Metabolic disposition of 2-chloroethyl nitrosocarbamoylcystamine in rats.

The disposition and the metabolism of 2-chloroethyl nitrosocarbamoylcystamine (CNCC), a new antitumor agent, has been studied in rats. For this purpose, three separate labeled species of CNCC have been used. The tissue distribution and the elimination of the radioactivity were determined in animals after gavage with a single dose of each labeled species of CNCC (35 mumol/kg).

Disposition in rats and mice of 7-methoxy-2-nitronaphtho[2,1-b]furan.

The disposition of 7-methoxy-2-nitronaphtho[2,1-b]furan (MNNF), labelled with 14C in the furan ring (label 1) and in the methoxy group (label 2) has been studied in rats and mice. After i.p.

Effects of leukotrienes on the electroretinographic profile of the isolated rat retina.

The isolated retina represents an excellent membrane model since it provides a specific electrophysiological response that is easy to quantify. Therefore the authors have tested the effects of B4, C4 and D4 leukotrienes on this model. In the presence of leukotrienes, electrical response generally decreases and survival duration of the isolated retina is generally shortened.

[Early diagnosis of postinfarction ventricular aneurysm. Value of contrast scintigraphy].

Early diagnosis of a ventricular aneurysm after myocardial infarction may provide a valuable means of preventing certain complications. We studied 55 patients with acute myocardial infarction on the 8th day by Technetium 99 angioscintigraphy with study of wall motion and ejection fraction at equilibrium. The results were compared with left ventriculography performed three months after infarction.

Effects of lipid peroxidation on the isolated rat retina.

The effects of membrane lipid peroxidation are determined in isolated albino rat retina. Lipoperoxidation induced by addition of Fe2+ + ascorbate to the perfusion liquid leads to an irreversible decrease of amplitude in the electroretinogram. The experimental model proposed here provides the possibility to monitor the survival of the retina and demonstrates that ocular lipid peroxidation very notably shortens the survival time.

Study of cell changes induced by radiolabelling of human lymphocytes with 99m-technetium.

With the aim of evaluating cell changes possibly induced by labelling lymphocytes with 99m-technetium (99mTc), several rosette tests and stimulation assays with mitogens have been carried out before and after radiolabelling. The results presented here show that (i) as the rosette tests are not modified statistically, the original labelling method does not seem to induce short term membrane structure modification and (ii) as stimulation by mitogens decreases after labelling with 99mTc, medium term radiation damage, linked to autoirradiation of the cells, can be evoked. This study indicates that there is reason to limit the time taken to perform scintigraphic explorations with labelled lymphocytes in man.