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J Oustrin

Publications and source records attributed to J Oustrin.

At least 19 recordsLinked to original sources
PubMed1997

The dosing-time dependent influence of chronic cyclosporin A treatment on daily profiles of plasma glucose and insulin in the Wistar rat.

The dosing-time dependent effects of cyclosporin A (CsA) on glucose and insulin plasma levels were evaluated in the light of possible alterations of their biological rhythms. Male Wistar rats weighing 200-250 g were habituated to a 12:12 h light-dark cycle. At the beginning of the experiments, on day D0 (before any treatment), significant rhythms were obtained for plasma glucose and immunoreactive insulin (IRI). The plasma glucose showed a 12 h periodicity and the plasma IRI a more pronounced rhythm, with both 12 h and 24 h significant components. Plasma glucose and IRI were then determined in drug-treated (20 mg CsA/kg b.wt/day; dosing time point: T01, T07, T13, or T20) and control rats during and after a 21-day treatment period. The CsA-treated rats developed hyperglycemia and a marked enhancement of the amplitude of the daily glucose rhythm. The magnitude of these effects differed among the groups (p < 0.001). Most pronounced alterations were observed on day 21 (D21) in group T07: M = 22.5 +/- 4.0 mmol/l; A = 9.2 +/- 6.0 mmol/l. The mean plasma insulin showed little though significant (p < 0.01) decreases. For instance, on D21 in group T01, M = 28.5 +/- 3.6 microU/ml, and in group T07, M = 28.7 +/- 2.5 microU/ml. In parallel, plasma CsA levels increased during the 21-day period and differed among groups (p < 0.01). The highest levels (4-5 mg/l) were obtained in T07 and T19 on D21. After drug cessation, the levels of plasma glucose were reduced, but stayed higher than control values. Body weights were monitored; the rate of growth was lower (p < 0.01) in CsA-treated rats than in controls (2.93 +/- 0.11 versus 5.1 +/- 0.11 g/day, respectively).

Animals↗
PubMed1996

[Suppression of platelet activating factor effects (PAF) on the retina by G-proteins inhibitors].

The Platelet Activating Factor (PAF) have been shown to alter the transretinal potential recorded from light stimulated isolated retina. In the present study, we investigated the effect of cholera and pertussis toxins on PAF-induced electroretinogram (ERG) impairment. Administrated alone, 2.10(-7) M PAF induced a very marked and rapid drop in the b-wave amplitude of the ERG. When 75 micrograms/l of cholera toxin was coadministrated with PAF (2.10(-7) M) into the perfusion solution, the fall of the b-wave was not observed, suggesting that PAF effect on retinal function was mediated through GTP-binding protein (G-protein). Similarly, low-dose of pertussis toxin (5 micrograms/l) 1) were sufficient to antagonize PAF (2.10(-7) M) consequence on the ERG. Our results suggest that the irreversible and deleterious effect of PAF on ERG is mediated by a G-protein mechanism, located in the neural retina.

Animals↗
PubMed1994

Dosing time-dependent nephrotoxicity of cyclosporin A during 21-day administration to Wistar rats.

The incidence of cyclosporine A (CsA) nephrotoxicity with reference to the temporal stage of administration was studied during a chronic 21-day treatment in male Wistar rats. Oral administration (20 mg/kg/day) was given at four different times: 1, 7, 13, or 19 hours after light onset (HALO). Plasma creatinine and blood urea nitrogen (BUN) levels were determined at regular intervals over the 24 h: before treatment (day 0); 7, 14, and 21 days after the beginning of treatment (days 7, 14, and 21); and 7 and 14 days after CsA withdrawal (days 28 and 35). At the same times, creatinine clearance and g-glutamyl transferase urinary excretion were determined in the groups of animals treated at 7 and 19 HALO. Residual concentrations of CsA in the renal tissue were measured at the end of the treatment period (day 21) in all groups. Nephrotoxicity of CsA was dependent on the temporal stage of administration. The renal vasoconstriction showed by the increase in plasma creatinine and BUN levels and the decrease in creatinine clearance was maximal when the CsA was given at 7 and 19 HALO and was correlated to the tissue concentrations of CsA. Tubular injury seems to occur earlier and the return to normal function less rapidly in animals treated at 19 HALO compared with animals treated at 7 HALO.

Administration, Oral↗
PubMed1991

Chronopharmacokinetics of doxorubicin in patients with breast cancer.

The chronopharmacokinetics of doxorubicin (DOX) has been studied in 18 patients suffering from breast cancer. They received combined chemotherapy including DOX (50 mg/m2 as an iv bolus), given at two different times (09.00 h or 21.00 h). The two randomized courses of the protocol were given to each patient at a four week interval. The total body clearance (CL) of DOX was significantly decreased when the drug was administered at 21.00 h, resulting in a longer elimination half-life and an increase in AUC. The renal clearance of DOX did not differ at the different times of administration, and it appears that the decrease in CL was related to a change in hepatic blood flow. The volume of distribution of the drug was not changed.

Adult↗
PubMed1991

Cyclosporine A dosing-time-dependent effects on plasma creatinine and body weight in male Wistar rats treated for 3 weeks.

Cyclosporine A (CsA) nephrotoxicity was assessed in 120 male Wistar rats (350 +/- 50 g) entrained to a 12-h cycle (light-dark 12:12); plasma creatinine level and body weight were examined in controls and in rats that had been treated daily with oral CsA or vehicle alone (olive oil-ethanol 90:10) for 21 days; daily dosing (40 mg/kg) was at one of six equally spaced given times during the 24-h cycle. The variations observed in both indexes were shown to be circadian dosing stage dependent. Nephrotoxicity was present as early as the third day of treatment with CsA; plasma creatinine level was enhanced by about 50% in rats dosed around the time of the change from darkness to light: at 22 HALO, 146.7 +/- 4.5 mumol/L, against 92.0 +/- 2.8 mumol/L for controls (p less than 0.05); and at 2 HALO, 148.3 +/- 10.0 mumol/L, against 95.0 +/- 4.3 mumol/L for controls (p less than 0.05). Thereafter, a remission episode was observed between days D5-D9. The more drastic effects were seen on days D16 and D21, in animals dosed in the beginning of the dark span (14 HALO): 185 +/- 10 mumol/L for CsA and 98.0 +/- 5.3 mumol/L for controls (p less than 0.01) and, to a lesser extent, in rats treated at the early resting phase (2 HALO): 152.4 +/- 31 mumol/L for CsA and 95.0 +/- 4 mumol/L for controls (p less than 0.05). The normal increase in body weight during the 21-day period (about 14 +/- 8% in controls) was impeded in CsA-administered rats, especially those dosed at the beginning of the activity span (14 HALO) that even suffered weight reduction. Differences in percentages of survivors were noticed, depending on dosing stage. About 40% of the animals in every time CsA-treatment group died, except for those dosed at the end of the resting period (10 HALO), when all animals died. In surviving rats, the cessation of CsA dosing resulted in a reversible effect on the study variables.

Administration, Oral↗
PubMed1989

Rapid quantitative determination of doxorubicin and its metabolites in biological samples.

A rapid sensitive and selective method is developed for the plasma analysis of doxorubicin and its metabolites, doxorubicinol and doxorubicinone with daunorubicin as the internal standard, by using high performance liquid chromatography (HPLC) with fluorescence detection and a "zorbax ODS" column. An eluent containing tetrahydrofuran and trietylamine afforded improved efficiency and resolution and was used to resolve the four anthracycline derivatives in a sole isocratic run. An example of the plasma levels obtained in a cancerous patient after two different administrations is shown.

Chromatography, High Pressure Liquid↗
PubMed1988

Influence of cadmium on the chain dynamics of collagen in rat tail tendon.

The molecular mobility of the chain dynamics of collagen was investigated by the thermally stimulated creep method on rat tail tendon after oral administration of cadmium (8 mg.kg-1.day-1) for six weeks. The high resolving power of the technique shows two manifestations of the pseudolathyrogen effect of cadmium: the polar side-chains of collagen, mobile in the immature specimen, which are cross-linked and so immobile in the mature specimen, remain mobile in the cadmium-treated mature specimen. There is also a subsequent decrease in the number of water molecules linked by two hydrogen atoms bound to the tropocollagen molecules. Probably these molecular modifications inhibit mineralization of the organic matrix and so osteogenesis.

Animals↗
PubMed1986

Alkaline phosphatase and bone calcium parameters.

Effects of cadmium, an alkaline phosphatase inhibitor, on the calcium content of rat bone were investigated in vivo by a radioisotopic method. Disturbance of bone metabolism is observed in both the superficial (delta) and slow exchanges (Ve), which are also significantly decreased. The crystallized calcium bone compartment (E) is also strongly affected. It appears that changes in the superficial calcium exchanges cause the observed decrease in the crystallized calcium mass. The slowing of osteogenesis is confirmed by the decrease of serum alkaline phosphatase activity. A statistical examination of the correlation coefficient reveals a close link (P less than 0.01) between serum alkaline phosphatase activity and the influx of superficial calcium (Vo+) and, as a result, the crystallized bone calcium parameters. These results show that cadmium can be used to study the relationship between alkaline phosphatase and calcification. The present observations allow us to consider the possibility that alkaline phosphatase may play a role in determining the calcium content of the crystallized phases in deep bone through its action on the tissue surface.

Alkaline Phosphatase↗
PubMed1986

Intestinal calcium absorption in the rat after oral Tween 80 administration.

Calcium absorption into rat intestine was investigated in vitro and in vivo after oral administration of Tween 80 (Polyoxyethylene (20) sorbitan monooleate). The in vivo study showed a significant decrease in serum calcium and in the quantity of calcium excreted by the intestine. In vitro, measurement of calcium influx into slices of intestine taken from Tween 80 treated animals showed that passive calcium diffusion was unchanged and that a decrease in the active transport alone is responsible for reduction in total calcium influx. Lineweaver-Burk analysis of the saturable component of calcium flux showed that the main variation was not due to a change of affinity of the system for the calcium but a decrease of the maximal calcium influx. Thus there are some arguments in favor of non-specific modifications of intestinal medium affecting calcium bioavailability rather than a specific action on the carrier.

Animals↗
PubMed1985

Interaction of local anaesthetics with cytochrome oxidase studied with fluorescence quenching.

The interaction of a series of eight local anaesthetics with cytochrome oxidase chosen as a membrane model protein has been studied with fluorescence technique using quinacrine as a fluorescent probe. The existence of hydrophobic interactions with a non polar region of cytochrome oxidase complex has been shown. The ability of the drug molecules to displace quinacrine bound to cytochrome oxidase correlate as closely with their anaesthetic potency as with their octanol-water partition coefficient. Our results are in good agreement with a recent model of local anaesthetic action on nerve membranes presenting a site of anaesthesia including both lipid binding and protein binding environments.

Anesthetics, Local↗
PubMed1983

Inhibition of cytochrome oxidase activity by local anaesthetics.

Using a polarographic method, we studied the inhibition of mitochondrial electron transport at the cytochrome c oxidase site caused by eight local anaesthetics. The diversity of the types of inhibition observed indicate the importance of electrostatic interactions between the anaesthetic molecules and the membrane protein. A linear relationship was recognized between the anaesthetic activity of infiltration and the affinity for the enzyme. We also observed a significant relationship between this affinity and the octanol-water partition coefficient. This result suggests that lipophilic interactions are involved in cytochrome oxidase-anaesthetic binding. We tried to establish a parallel between this binding and the mechanism of anaesthesia involving the nerve membrane proteins.

Anesthetics, Local↗
PubMed1983

Circadian changes in the elimination of misonidazole in mouse.

Intraperitoneal doses of Misonidazole were administered at 15.00 hours and 03.00 hours to Balb c/cenlco mice standardized in controlled environmental cages for 3 weeks before the experiment. Non linear pharmacokinetic and temporal variations in the apparent half life were obtained at higher doses.

Animals↗