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Biomedical subjects

C Dumont

Publications and source records attributed to C Dumont.

At least 73 records · Page 4Linked to original sources
PubMed1983

Comparative study of central dopaminergic properties of RU 29717 (N-propyl-9-oxaergoline) and pergolide.

RU 29717, a 9-oxaergoline derivative, has been compared with pergolide in a variety of biochemical and behavioural tests indicative of dopaminergic (DAergic) activity. RU 29717 and pergolide have a similar affinity for DA receptors labelled by [3H]spiroperidol or [3H]dihydroergocryptine ( [3H]DHEC) by using striatal or anterior pituitary membranes respectively. Both compounds stimulate the striatal DA-sensitive adenylate cyclase and inhibit the activity of this enzyme in dispersed cells from the neurointermediate lobe of the pituitary gland. In anterior pituitary cells in primary culture, they decrease prolactin release with the same efficacy. In vivo, they exert a long-lasting inhibition of the reserpine-induced hyperprolactinemia. They equally retard the alpha-MPT-induced disappearance of striatal DA and increase striatal acetylcholine levels. In behavioural models, the similarity between RU 29717 and pergolide is also evident: they induce contralateral circling in animals lesioned unilaterally with 6-OHDA, produce stereotyped behaviour and have emetic activity within the same dose range. Therefore, RU 29717, like pergolide, is a potent direct acting DAergic agonist. In experimental models used to investigate this activity at the striatal or the anterior pituitary levels the compounds present a similar profile of action.

Acetylcholine↗
PubMed1983

Synthesis and central dopaminergic activities of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-9-oxaergolines].

The synthesis and biological activities of a series of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-trans-9-oxaergolines] with central dopamine (DA) agonist properties are described. The compounds were prepared from [2aRS-(2a alpha,4 beta,5 alpha)]-4-amino-1,2,2a,3,4, 5-hexahydro-1-(phenylmethyl)benz[cd]indol-5-ol (6b) by alkaline cyclization of the corresponding N-chloracetamide 7b, followed by reduction of the amido group [5aRS-(5a alpha, 6a beta, 10a alpha)]-4,5,5a,6,6a,7,9, 10a-octahydro-4-(phenylmethyl)-7H-indolo[3,4-gh][1,4]benzoxazin-8-one (8b) with LiAlH4. After debenzylation of the resulting amine 9a, the indoline ring of [5aRS-(5a alpha, 6a beta, 10a alpha)]-4,5,5a,6,6a,8,9, 10a-octahydro-7H-indolo[3,4-gh][1,4 ]benzoxazine (10a) was dehydrogenated with MnO2 to give (+/-)-trans-9-oxaergoline (11a), which can be alkylated on the nitrogen (11b,c and 12) and brominated in position 2 (13a,b). The compounds were examined in vitro for their ability to bind to DA receptors and to inhibit prolactin (PRL) secretion in pituitary cells in culture, in vivo both for their DA stimulant effects at the striatal level (circling in 6-OHDA-lesioned animals, DA turnover, and stereotypy) and inhibitory effects on plasma PRL levels in rats, and for their emetic effects in dogs. Most of the tested compounds were active in these tests, and the potency of (+/-)-trans-6-n-propyl-9-oxaergoline (11c) was comparable to that of pergolide mesylate.

Animals↗
PubMed1983

[Diffusion of fosfomycin into bone tissue in man].

Fosfomycine diffusion into spongious and cortical bone was studied in 20 patients undergoing total replacement of the hip after an intravenous infusion of 4 g (1 g/h). The serum and bone samples were collected 1 h and 3 h after administration of the drug. Concentrations at 1 h were 105.0 +/- 12.4 micrograms/ml, 19.6 +/- 4.8 micrograms/g and 13.3 +/- 3.7 micrograms/g in serum, spongious bone and cortical bone respectively; at 3 h these concentrations had become respectively 67.8 +/- 15.9 micrograms/ml, 10.0 +/- 4.2 micrograms/g and 8.2 +/- 3.6 micrograms/g. Antibiotic levels in bone tissue decreased in direct ratio to corresponding serum values, the mean tissue/serum ratio remaining at 15 +/- 4%.

Adult↗
PubMed1982

[Penetration of cloxacillin into human bone tissue after oral administration (author's transl)].

Cloxacillin diffusion into spongious and cortical bone was studied in 20 patients undergoing total replacement of the hip, after an oral single-dose of 1 g (10 patients) or an oral dose of 1 g every 8 hours (10 patients). Serum and bone samples were collected 2 and 3 hours after the last dose and assayed for antibiotic concentration by a microbiological method. Bone levels were similar in any group of patients, but significantly higher in spongious bone than in cortical bone. The bone/serum concentration ratios were 0.15 for spongious bone and 0.10 for cortical bone. Calculations from these data showed that adequate local levels inhibitory to Staphylococcus aureus, would be achieved by cloxacillin administration of 1 g dose every 4 hours orally.

Administration, Oral↗
PubMed1980

Time course of apomorphine-induced circling behaviour after striatal dopamine receptor denervation.

The curve describing the time course of apomophine-induced circling behaviour in rats with a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine (DA) pathway was studied with a microcomputerized rotometer. Up to a 2-week interval after lesioning, the contralateral circling response was a single bell-shaped curve but this gradually became a double-peaked curve after 4-5 months. At this time the bell-shaped curve was, however, restored by haloperidol pretreatment. It is concluded that the response of striatal DA receptors was modified either by the lesion of another neuronal system and/or that the absence of DA nerve endings induced changes in the striatal DA receptor itself.

Animals↗
PubMed1980

[Psychopharmacological profile of a new dopaminergic agonist, RU 24213 (author's transl)].

The psychopharmacological properties of RU 24213 were compared to those of other dopaminergic agonists (apomorphine, dexamphetamine, bromocriptine and L-dopa) in various behavioural tests. In naive mice the drug reduced the locomotor hyperactivity in the primary exploratory phase and produced stimulation in the subsequent stabilized activity period. In rats it provoked dose-related stereotypies, specially gnawing and sniffing. It delayed the cataleptic state induced by prochlorperazine without affecting its intensity. In animals unilaterally lesioned with 6-OHDA in the nigro-striatal pathway, RU 24213 caused contralateral turning. It exhibited relatively weak emetic and anorexic effects in dogs. Core temperature recordings in rats revealed a biphasic hypo- and hyperthermic activity. In drug interaction studies it was obsers in rats with unilateral electrolytical striatal lesion. The results obtained suggest that RU 24213 stimulates dopamine receptors both directly and indirectly. In this respect it could be compared to bromocriptine but unlike this latter compound it has an immediate effect which is of shorter duration.

Animals↗
PubMed1980

Comparative ototoxic effects of RU 25434, amikacin and neomycin in guinea-pigs.

The ototoxic effects of RU 25434, a new semi-synthetic aminoglycoside antibiotic, were compared to those of amikacin and neomycin. Experiments were performed in adult and new-born guinea-pigs, ototoxicity being assessed by Preyer's reflex response and the measurement of the cochlear microphonic potentials at the end of treatment. The well known ototoxicity of neomycin was observed and RU 25434 appeared to be relatively less toxic than amikacin. The use of new-born guinea-pigs seem to be particularly suitable for this type of study because of their apparent sensitivity to ototoxicity.

Age Factors↗
PubMed1980

Mechanism of ozone-induced tachypneic response to hypoxia and hypercapnia in conscious dogs.

In seven studies on three dogs exercising on a treadmill (1.6 km/h), we studied the effect of ozone on ventilatory responses to hypercapnia and to hypoxia. After ozone exposure (0.67 +/- 0.02 ppm by vol; 2 h), the responses of minute volume of ventilation (VE) to progressive hypercapnia and hypoxia were not changed, but the breathing pattern in response to these stimuli changed. We analyzed the breathing pattern by plotting the relationship between VE and tidal volume (VT). During progressive hypercapnia, the slope of VE-VT relationship increased from a control value of 36.1 +/- 1.6 (mean +/- SE) to 93.5 +/- 8.9 min-1 after ozone (n = 7, P less than 0.005); during hypoxia, the slope increased from a control value of 46.1 +/- 8.6 to 142.7 +/- 18.3 min-1 after ozone (n = 6, P less than 0.005). The ozone-induced tachypneic responses to hypercapnia and hypoxia were not affected by inhalation of atropine sulfate or isoproterenol aerosols, but were completely abolished by bilateral vagal blockade. These findings indicate an effect of ozone on the vagal receptors located in the airways and lungs that causes reflex tachypnea during hypercapnia and hypoxia.

Animals↗
PubMed1979

Mechanism of rapid, shallow breathing after ozone exposure in conscious dogs.

In 10 experiments on 3 conscious dogs exercising on a treadmill, we studied the effect of ozone on base-line ventilation and on ventilatory responses to inhaled bronchoconstrictor drugs. Prior to ozone exposure, inhalation of histamine diphosphate aerosol (1%; 5 breaths) increased respiratory frequency (f) by 86 +/- 11% (mean +/- SE), and inhalation of prostaglandin F2 alpha (PGF2 alpha) aerosol (0.1%; 5 breaths) increased f by 74 +/- 16%. Immediately after ozone exposure %0.65 ppm; 2 h), steady-state base line f was increased by 120 +/- 18% and tidal volume (VT) was decreased by 43 +/- 5%. When conduction in the cervical vagus nerves (that were exteriorized permanently in skin loops) was blocked by cooling, these changes caused by ozone were abolished (P greater than 0.05). The increased responses to both histamine and PGF2 alpha aerosols after ozone were unaffected by pretreatment of isoproterenol aerosol (0.5%; 15 breaths), but were completely abolished by vagal cooling. Our studies indicate that ozone-induced rapid, shallow breathing and the increased ventilatory responses to inhaled histamine and PGF2 alpha aerosols are mediated through vagal afferent pathways.

Aerosols↗