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G Labrecque

Publications and source records attributed to G Labrecque.

48 records · Page 3Linked to original sources

Temporal variations in the elimination of antipyrine in normal and adrenalectomized rats.

An oral dose of antipyrine was administered at 08:00 and 20:00 hours to groups of sham operated and adrenalectomized rats standardized in an alternating 12-hour-light-dark cycle for 7 days prior the experiments. Temporal variations in the rate of elimination of antipyrine were obtained in both groups. Adrenalectomy decreased the serum elimination of antipyrine but had no effect on the temporal variations.

Adrenalectomy

Acetylcholine antirelease effect of morphine and its modification by calcium.

The effects of morphine (10 mg/kg) and calcium (10 mg/kg) were studied on the neocortical release of acetylcholine (ACh) in ketamine-anesthetized rats. Morphine decreased ACh release as measured by the dorsal leech muscle as well as by an enzymatic assay. Calcium was ineffective alone but antagonized the action of morphine. This study supports the hypothesis that the ACh antirelease action of narcotics is mediated through an interaction with calcium.

Acetylcholine

Temporal variations in chloroform-induced hepatotoxicity in rats.

There is increasing evidence to show that drug metabolism and effects are modulated by biological rhythms; therefore the possibility that chloroform (CHCl3) induced acute hepatotoxicity may also vary as function of time of administration was investigated in male Sprague--Dawley rats. The animals were given a single intraperitoneal dose of CHCl3 or saline, 0.5 ml/kg, at 09:00 h, 13:00 h, 17:00 h, 21:00 h or 03:00 h and killed 4 h after treatment. The hepatotoxicity induced by CHCl3 was determined by the serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and lactic dehydrogenase (LDH) activities and by the glucose-6-phosphatase (G6Pase) activity of the liver. The increases in SGPT, SGOT and LDH were minimal and maximal when the organic solvent was injected at 09:00 h and 21:00 h, respectively, whilst the activity of G6Pase was depressed significantly at 03:00 h and 13:00 h under similar conditions. Starving the rats for 16 h prior to the injection of CHCl3 at 09:00 h increased substantially the hepatotoxicity as measured by the above enzyme activities. These findings may be relevant in the toxicity of CHCl3 in industrial workers exposed to this solvent at various times of the day.

Animals

Temporal variations in the pharmacokinetics of isoniazid and N-acetylisoniazid in rats.

The temporal variation in the pharmacokinetics of a single dose administration of isoniazid (INH) and its major metabolite, N-acetylisoniazid (AINH), was investigated at 0900 and 2100 in rats synchronized to a 12-hr light-dark cycle. INH and AINH were administered by the intraarterial and ip routes at a dose of 20 mg/kg, in order to determine the hepatic extraction ratio of both compounds. The mean AUC values of INH obtained after the intraarterial and ip injections of the drug were 42.6 and 8.4 micrograms.hr/ml at 0900 and 30.7 and 12.8 micrograms.hr/ml at 2100, respectively. Consequently, there were temporal variations (mean values at 0900 and 2100) in the clearance (491.6 and 665.3 ml/hr/kg), bioavailability (0.20 and 0.42), hepatic extraction ratio of INH (0.80 and 0.58), and apparent hepatic blood flow (9.7 and 18.6 ml/min). Also, the AUC of AINH was higher at 2100 when INH was injected intraarterially. Likewise, AINH had a lower t 1/2 and AUC values and a higher clearance at 2100, but the hepatic extraction ratio of AINH was 0.26 at 2100 compared with the value of 0.07 at 0900. No diurnal variations were present in the apparent volume of distribution of INH and AINH. In vitro experiments showed that the mean activity of the hepatic N-acetyltransferase was 135.3 nmol/mg at 2100, compared with 59.0 nmol/mg at 0900.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases

Aspects of chronopharmacology and chronotherapy in children.

Pediatric studies involving chronopharmacology until now have been limited mainly to investigation of circadian patterns in children of 6 to 15 years. This means that: a. data on newborns and even on infants of one year or younger are not available, and b. other bioperiodicities, such as those of one year (infradian rhythms), have not yet been explored in older children. Biological time-related changes have been documented for phenytoin and theophylline with regard to their pharmacokinetics and for orciprenaline, ipratropium bromide, corticosteroids and anticancerous agents with regard to their effectiveness. Despite the small number of investigations performed to date, results indicate that: a. more comprehensive and precise characterization of pharmacokinetic and pharmacodynamic phenomena can be achieved by a chronopharmacological approach than the conventional one and, b. better therapeutics can be achieved using chronopharmacological facts since an appropriate timing of medicines with regard to biological rhythms is likely to enhance desired and/or reduce undesired effects.

Adrenal Cortex Hormones