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Biomedical subjects

G Raynaud

Publications and source records attributed to G Raynaud.

18 recordsLinked to original sources

Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin4 receptor subtype.

The occurrence of serotonin in the human adrenal gland was demonstrated both by immuno-histochemical and biochemical approaches. Using specific polyclonal antibodies to serotonin, the presence of numerous immunoreactive cells was revealed by means of the peroxidase-antiperoxidase technique. These cells exhibited the morphological characteristics of mast cells. Combination of high performance liquid chromatography and electrochemical detection showed the presence of substantial amounts of both serotonin and its metabolite 5-hydroxyindolacetic acid in adrenocortical extracts. The role of serotonin in the regulation of steroidogenesis from human adrenocortical slices was studied in vitro using a perifusion system technique coupled to a specific radioimmunoassay for cortisol. Graded doses of serotonin (from 10(-8) M to 3 x 10(-7) M) increased cortisol production in a dose-dependent manner. Prolonged exposure of adrenal fragments to serotonin (10(-7) M) induced a biphasic response, i.e. a rapid and transient increase in cortisol secretion followed by a plateau phase, suggesting the existence of a desensitization phenomenon. The stimulatory effect of serotonin (10(-7) M) was not altered during infusion of the serotonin1 and/or serotonin2 receptor antagonists methysergide (10(-6) M) and ketanserin (10(-6) M), respectively. In contrast, ICS 205 930 (10(-6) M), a non-selective serotonin3/serotonin4 antagonist, totally abolished the response of adrenal slices to serotonin (10(-7) M). The benzamide derivative zacopride, considered as a serotonin4 agonist, induced a robust stimulation of cortisol secretion. In addition, the corticotropic effects of serotonin (10(-7) M) and zacopride (10(-6) M) were not additive. Incubation of adrenocortical fragments with zacopride (10(-6) M) or serotonin (10(-6) M) caused a significant increase in cAMP formation. Taken together, these data suggest that serotonin, locally released by intra-adrenal mast-like cells, may act as a paracrine factor to stimulate cortisol secretion in man. Our results also indicate that serotonin-induced corticosteroid production is mediated through activation of a serotonin4 receptor subtype positively coupled to adenylate cyclase.

Adrenal Cortex

Effects of multiple doses of isoprinosine on Echinococcus multilocularis metacestodes.

Isoprinosine was given at daily doses of 0.5, 1, 2, and 4 g kg-1 of body weight to jirds that were infected for 3 months with Echinococcus multilocularis metacestodes. The effects of the different drug doses on metacestodes were studied by transmission electron microscopy and biochemical methods. At lower doses, increases in uric acid and adenosine deaminase activity were noted. At 4 g kg-1 of body weight, marked ultrastructural damage with metabolic perturbations was observed.

Adenosine Deaminase

Treatment of experimental alveolar echinococcosis: comparative study of mebendazole, isoprinosine and a mebendazole isoprinosine association.

A comparative biochemical study of the effects of mebendazole and Isoprinosine used separately or associated was conducted in six-month old gerbils infected three months ago by Echinococcus multilocularis metacestodes. Mebendazole treatment induced a decrease of glucose (81%) whereas Isoprinosine increased the glucose uptake in the parasite. The combination of the two drugs led to a decrease of about 40% of the glucose concentration. The specific activities of alkaline and acid phosphatases were also modified. Isoprinosine seemed more effective when used alone than associated with mebendazole with the chosen procedure of treatment.

Acid Phosphatase

[Cesium].

Cesium is an alkaline metal close to Rubidium, which is studied in psychopharmacology in the prospect of a possible antidepressive effect. It has stimulating properties of the motor activity on the animal, antagonizes some sedative substances but does not modify either self-stimulation behaviour or induced agressivity. Given in large doses, Cesium presents hypertensive effects bound with a stimulation of the adrenal Epinephrine secretion. As for the synapses Cesium increases the neuro-transmitter release. However the Norepinephrine turn-over is not modified in the central nervous system while that of Serotonin is increased as well as the cerebral concentrations of Tryptophan, Serotonin and 5.HIAA. These very fragmentary data about the toxico-pharmacological properties of Cesium, as well as the very prolonged half-life of this ion (from 50 to 100 days), explain that contrary to Rubidium it has not still been used in man.

Animals

Hepato- and thyreotoxicity of tifemoxone.

The oral toxicity of Tifemoxone, phenoxymethyl-6 tetrahydroxazine-1, 3 thione-2, a new potential antidepressant was studied during 6 months in rats at 30, 85 and 230 mg/kg/d and in beagle dogs at 10, 55 and 300 mg/kg/d. Thyroid hyperplasia and hypoactivity were observed in the rats and dogs plasma triiodothyronine, determined in dogs, was modified. A dose dependent hepatotoxic effect was observed in the rats and dogs. In dogs at low dose, one animal died after B.S.P. test. Water consumption and urinary volume increased, weight loss and anemia appeared at high doses in both rats and dogs. Hair loss was observed in rats and convulsions in dogs. In conclusion, Tifemoxone like tetrahydroxazine thione and some derivatives caused thyreotoxicity, hairlessness and increased in water comsumption and diuresis and in addition it had strong hepatotoxic effect especially in the dog.

Animals

[Results of a double-blind medium-term study comparing effects of timolol maleate and epinephrine in 120 patients with chronic open-angle glaucoma].

A double-blind medium term study of the activity of timolol in chronic open-angle glaucoma was conducted in four French ophthalmological centers, using the same protocol. A total of 119 patients were treated: --60 with timolol; --59 with épinéphrine, for comparison. Results showed a significantly superior efficacy for timolol over épinéphrine, after in weeks of treatment. Good tonometric control was obtained in 81.6% of the patients treated with timolol, against 52.5% of those receiving épinéphrine. In 68% of the glaucomatons patients treated with timolol, good tonometric control was obtained with the lowest dose preparation containing 0.1%. No side-effects were noted during the study, either locally or generally (particularly blood pressure changes).

Chronic Disease

Effect of toloxatone on behaviour of primates.

1. The effects of (3-methyl)-3-phenyl-5-hydroxy-methyl-2-oxazolidinone (toloxatone) were studied on the behaviour of three species of primates: baboon, rhesus monkeys and chimpanzee. 2. The activity against reserpine-induced depression is observed in baboon as in rodents. 2. The administration of toloxatone induces three effects which probably have the same origin: suppression of feeding inhibition of the subordinate baboon, improvement of escape reaction in the conditioned chimpanzee, increase in general activity and the active component of social behaviour in grouped rhesus monkeys. These three effects can be interpreted as resulting from the stimulating effect of toloxatone, or more precisely from a disinhibiting effect. 4. Contrary to amphetamine, toloxatone does not induce, even at high or repeated doses, behavioural disturbances.

Administration, Oral

Use of Freund's adjuvant arthritis test in anti-flammatory drug screening in the rat: value of animal selection and preparation at the breeding center.

The Freund's adjuvant technic, using killed Mycobacterium butyricum suspended in mineral oil, is a refined tool for anti-inflammatory drug evaluation. Its use has long been reserved for testing and not for screening due to technical problems in the preparation of valid animal models. After reviewing the methodology, the authors demonstrated that the availability of arthritic rats from a modern breeding center (Charles River France, SA, Elbeuf, France) make the procedure applicable to drug screening. This has both practical and economic advantages. The animals can be used as test organisms for drug evaluation 14 da after treatment. Three criteria for measuring the effectiveness of anti-arthritic drugs have been established: an arithritic index determined by examination of the 4 paws; changes in the erythrocyte sedimentation rate; and changes in levels of plasma fibrinogen. The curative activity of test substances can be evaluated by a single series of measurements of these 3 criteria after 14 da of treatment. This test was compared with 2 others; edema of the paw induced by the subcutaneous injection of kaolin or carrageenan, and was found to be superior.

Animals

Pharmacological study of a new substance, mecinarone.

Mecinarone, a benzofuranic chalcone, shows considerable vasodilating activity on the peripheral and cerebral circulation. The intramuscular irrigation is thus improved and the cerebral blood supply increased. This vasodilating activity is accompanied by only a slight drop in the systemic arterial pressure and occurs without cardiac depression. Mecinarone has also antibradykinin, antiserotonin and antiaggregation properties which added to the vasodilating activity, greatly increase its pharmacological interest.

Administration, Oral