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G Thiroux

Publications and source records attributed to G Thiroux.

12 recordsLinked to original sources
PubMed1994

Lack of alteration in cardiac beta-adrenoceptor site concentration in rats treated with an adenylate cyclase-stimulating dose of endotoxin.

In previous experiments on male rats we showed that 2 mg kg-1, intravenously, lipopolysaccharide from Escherichia coli, a sublethal nonhypotensive dose, induced circulating cardiodepressant activity, maximal alterations in steroid hormonal response, and myocardial adenylate cyclase hyperactivity 4 h later. The purpose of the present study was to investigate a possible relation between this adenylate cyclase hyperactivity and alterations in total ventricular beta-adrenoceptors. To this end, ventricular beta-adrenoceptor concentration and affinity were measured under the same conditions. Binding assays were performed using [3H]dihydroalprenolol. No significant change was observed in both parameters.

Adenylyl Cyclases↗
PubMed1994

Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults.

1. Caffeine metabolism was studied in human liver microsomes from foetuses (n = 10), neonates (n = 10), infants (n = 9) and adults (n = 5). Caffeine and its metabolites, 1-3-7-trimethyluric acid, paraxanthine, theophylline and theobromine, were assayed by h.p.l.c. Methoxyresorufin-O-demethylase activity (MEROD) was determined and immunoquantifiable levels of CYP1A2 were measured. 2. The formation of the dimethylxanthines by N-3, N-7 or N-1-demethylation was significantly less in foetuses, neonates and infants than in adults, as shown previously in vivo. The formation of 1-3-7-trimethyluric acid (C-8-hydroxylation) was not significantly different between age groups. The production of total dimethylxanthines, paraxanthine and theophylline increased significantly with age within the neonate-infant group over at least the 0-300 day range (rs = 0.739, 0.667, 0.682, respectively). These data differ from those reported in vivo which suggested that N-3 and N-7-demethylations matured at about 120 days. The difference in maturational profiles of each metabolic pathway suggests that the reactions depend on different isoenzymes. The delay in the maturation of N-1 compared with N-3 and N-7-demethylation is in agreement with previous in vivo data. 3. In the neonate-infant group, only N-3-demethylation correlated with both MEROD activity (rs = 0.681; P < 0.05) and CYP1A2 microsomal concentration (rs = 0.454; P approximately 0.05), suggesting that, as in adults, this reaction depends on CYP1A2. 4. In the foetal samples, the production of total dimethylxanthines, paraxanthine and theobromine decreased significantly (rs = -0.879, -0.767, -0.708, respectively) with increasing gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Could saliva stand for plasma in theophylline monitoring in asthmatic children? Still a controversial problem.

Theophylline determination in saliva was proposed several years ago as a convenient and non-invasive alternative to monitoring plasma in children and adults. Published data demonstrated that theophylline saliva concentration linearly correlates plasma concentration. However, the variability found in interindividual serum/saliva ratios and the wide scattering among the data points precluded the clinical use of saliva for theophylline monitoring. The purpose of this study was to compare different standardized methods for obtaining stimulated saliva intending to reduce the variability in plasma/saliva ratios and to determine the most reliable one. A group of 150 ambulatory chronic asthmatic 4.5 to 20.83 (10 +/- 3.7; M +/- SD) year-old patients receiving theophylline 6.85 +/- 1.88 mg/kg every 12 h as slow release preparations for 4 to 100 days was studied. One ml venous blood and salivary specimens were simultaneously collected 5.15 +/- 0.36 h after the morning maintenance dose. In a subgroup of 75 patients, saliva was collected using first a new device called salivette, immediately followed by the collection of an expectorated sample 30 s after citric acid crystals stimulation. In the other patients saliva was collected using citric acid containing salivette. Theophylline concentration was determined using HPLC. For all types of saliva collection, salivary and plasma theophylline concentrations correlated significantly. However whichever method was used, based on the -2 to +2 SD interval, a large range of plasma theophylline was predicted from a single salivary theophylline concentration. Despite a further standardization of the sampling of saliva, saliva theophylline could not accurately predict plasma concentration.

Adult↗
PubMed1990

Unexpected hyperactivity of myocardial adenylate cyclase system in endotoxic male rats.

Ventricle beta-adrenoceptors have been investigated and serum steroid levels determined in male rats injected intravenously with lipopolysaccharide from E. coli (LPS) under light anesthesia. Two series of doses were successively studied: 1) 2 and 3 mg.kg-1 and 2) 1 and 4 mg.kg-1, each including controls. The second series was carried out owing to the unexpected results of the first one. Homogeneity of the two series was tested. Experiments were performed at hr 4 after injection, a time previously tested to induce hormonal variations and release of a cardiodepressant factor (CDF) in serum. The results indicate that 2 mg.kg-1 LPS induced an increased activity of adenylate cyclase. The unexpectedly high response was dose-dependent since it was not found with the lowest or highest doses. The determination of serum steroid levels (progesterone, 17 alpha-hydroxyprogesterone, corticosterone, delta 4-androstenedione, testosterone, estrone, and estradiol) was used as a kind of marker of endotoxin activity. The results point out that the light anesthesia used for LPS injection delayed the hormonal response, when compared with results previously obtained with the same LPS dose (2 mg.kg-1) in unanesthetized rats. It can be inferred that the present data should usually appear at an earlier stage. It is suggested that an endotoxin-induced protein kinase C activation could be involved in the observed hyperactivity of adenylate cyclase and the hyperdynamic phase of septic shock.

17-alpha-Hydroxyprogesterone↗
PubMed1986

Effect of propranolol on alpha-amino-isobutyric acid and water kinetics in the materno-fetal unit of the rat.

Pregnant Sherman rats were given propranolol (a) per os (50 mg X kg-1, twice a day) on days 17-19 of gestation, (b) by constant rate infusion: osmotic minipumps (6 mg X kg-1 X day-1) from day 13 of gestation. On day 20 (a-treated) or 21 (b-treated), [14C]-AIB + [3H]-H2O were injected intravenously; plasma and tissue samples were collected at different times up to 4 h (a-treated) or at 2 h (b-treated) for radioactivity measurements. Whatever the treatment, no difference was found between control and treated animals for all parameters studied (number of fetuses; weight, protein; DNA; [14C]-AIB or [3H]-H2O tissue levels) except in propranolol-treated mothers where maternal heart [14C]-AIB uptake was decreased and where fetal plasma and tissue [3H]-H2O levels where higher than control at 5 min. Another set of experiments were performed in a-treated rats. On day 20, each mother was anesthetized with ether and injected as above; maternal plasma sample and one feto-placental unit were collected at different times within 15 min after injection. For this period, [14C]-AIB uptake and mainly [3H]-H2O diffusion were increased in placentae and fetuses of propranolol-treated dams. Arterial blood pressure did not change throughout the experiment in propranolol-treated animals, but decreased in controls. Heart rate was slowed down in the former compared to controls. Thus, in our experimental conditions, propranolol treatment: does not modify fetal weight; has no effect on AIB placental transfer and tissue uptake, and could protect towards the stress of anesthesia and surgical injuries, since H2O transfer was impaired in control but not in treated animals.

Aminoisobutyric Acids↗
PubMed1985

Studies on methyl-xanthines in intact and hypophysectomised rats: differences in pharmacokinetics and adrenocortical response.

The effects of caffeine (Cf), theophylline (Tph) and theobromine (Tb) on the adrenal cortex were studied. No direct effect (hypophysectomized: hypo(-) rats) was observed with any of the three methyl-xanthines (MX) after chronic oral administration (5 days). An indirect effect (via the hypothalamo-hypophyseal-adrenal axis) was found for theophylline: plasma and adrenal corticosterone levels were increased in intact rats, after acute or chronic treatment. The high toxicity of MX (mainly Tph) observed in hypo(-) rats prompted the study of pharmacokinetic parameters: the clearance was decreased and the half-life was increased by a factor 3 for Cf and 1.6 for Tph. Thus, the elimination of Cf and Tph was slowed down in hypo(-) rats.

Adrenal Cortex↗
PubMed1982

[3H]-Salbutamol placental transfer in pregnant rats on the 19th day of gestation.

[3H]-salbutamol added in tracer doses (approximately equal to 250 nmol per animal) to the carrier solution (20 mg/kg) was injected intraperitoneally to pregnant rats on the 19th day of gestation. Some experiments were performed with intravenous administration (approximately equal to 2.5 microCi in 300 microliters 9 g/l NaCl). Drug distribution was studied in the maternal and fetal plasma, lung and liver, and in the placenta and amniotic fluid. 10% of the maternal salbutamol plasma radioactivity was recovered in the fetal plasma, in accordance with earlier findings reported from our laboratory using human placental lobules in vitro.

Albuterol↗
PubMedDate not supplied

Effect of pregnandiol on caffeine metabolism in female rats.

Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg/kg, respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines). Unlike in human in vitro or in vivo, 1,3,7-DAU (6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil) was an important metabolite (9.7% of total caffeine metabolites). Pregnandiol inhibited N-1, N-3 and N-7 demethylation in vitro (-33%, -33% and -28%, respectively, at 5 mg/kg/day), but it had no effect on N-1 demethylation at 1.25 or 2.50 mg/kg/day. Pregnandiol at all doses had no effect on 1,3,7-trimethyluric acid and 1,3,7-DAU formation. These results are consistent with the hypothesis that C-8 hydroxylation and demethylation of caffeine are mediated by different isoenzymes. They indicate that pregnandiol is a potent inhibitor of microsomal drug metabolism, specifically of cytochrome P450 IA, which could explain the immaturity of some metabolic pathways of caffeine in neonates.

Animals↗
PubMedDate not supplied

Caffeine metabolism in liver slices during postnatal development in rats.

The metabolism of caffeine was investigated in liver slices from newborn, preweanling, postweanling, and adult rats. All metabolites were identified and quantified by HPLC without using radioactive compound. Caffeine metabolism underwent dramatic changes during maturation in rats. The specific activity of the enzyme system was extremely low when liver slices from 1-day and 7-day-old rats were used. This capacity increased gradually with increasing age and reached a peak following weaning at 21 days of age. In rat liver slices, N-1 demethylation to theobromine was the main pathway of in vitro caffeine metabolism at all ages. Theobromine represented 25% of total caffeine metabolites at day 1 and about 40% at all others ages. 1,3,7-6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil is a minor metabolite in newborn (1-day-old), preweanling (7-day-old), and adult rats (120-day-old), but an important metabolite in postweanling rats. Conversely, 1,3,7-trimethyluric acid is a major metabolite in newborn and adult rats and a minor one in preweanling and postweanling rats. This liver slices model could be used as a simple and versatile model to study metabolism during maturation.

Animals↗