Accumulation of cyclosporine in the conceptus during the first trimester of pregnancy after liver transplantation.
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Adult↗
Biomedical subjects
C Delouis
Publications and source records attributed to C Delouis.
Pharmacokinetics of tobramycin in pregnant women. Safety and efficacy of a once-daily dose regimen.
The pharmacokinetics of tobramycin, an aminoglycoside antibiotic, was investigated after a short intravenous infusion and once-daily dose regimen in two groups of nine pregnant women during the second (Group 1) and the third (Group 2) trimester of pregnancy. During these periods, the risk of infectious diseases is increased. Plasma concentrations of tobramycin were measured by fluorescence polarization immunoassay. The decrease in clearance (21%), at 28 weeks and more of gestation leads to an increase in half-life and the mean residence time (MRT) in the second group (33 and 29% respectively). The volume of distribution was unchanged in the two groups. No accumulation of the drug was observed in pregnant women. Pharmacokinetic disorders are correlated with the term and moreover with the weight deviation of women, i.e. the growth of the fetus. These findings suggest accumulation of the aminoglycoside antibiotic in the fetus. Moreover, the efficacy and the safety of this therapeutic regimen were excellent. To limit the potential nephrotoxicity and ototoxicity of tobramycin for the mother and the fetus, a once-daily dose regimen seems to be acceptable for the treatment of non-neutropenic pregnant women.
Adult↗
[Determination of the ratio of serum concentrations of tobramycin between fetus and mother at birth. A model of small scale pharmacokinetics].
Thirty women at term presenting with fever greater than or equal to 38 degrees C during labour were given a synergic combination of tobramycin-amoxicillin. Gestational ages ranged from 37 6/7 to 41 2/7 weeks. A single dose of 3 mg/kg of tobramycin was given every day intravenously. Feto-maternal tobramycin concentrations (F/M ratios) were systematically determined at birth and allowed to make a small scale pharmacokinetic study. Two curves were plotted from the pharmacokinetic analysis of maternal and fetal measurements, showing an intravenous and an intramuscular profile respectively. A high positive linear correlation (R = 0.82) was found between the F/M ratios and the time (delta T, -hours-) measured from the last administration to the mother to the time of delivery. Elimination of the aminoglycoside was slowed down in newborns (t1/2 lambda z = 5.1 hours). In newborns tobramycin levels were always less than or equal to 6 mg/l and still greater than or equal to 1 mg/l 6 hours after the last maternal injections. Measurement of F/M ratios allowed to study and compare the fetal and maternal pharmacokinetics facilitating (when necessary) the initial posologic adjustment in newborns. Such small scale pharmacokinetics could be extended, for a given gestational age, to other drugs with narrow therapeutic ranges. However, the size and the homogeneity of the population seem to be most important.
Amoxicillin↗
Transplacental passage of vancomycin during the second trimester of pregnancy.
Pharmacokinetics and drug monitoring of vancomycin were studied at mid-pregnancy in a patient with chorioamnionitis due to Streptococcus agalactiae. The terminal half-life remained in the normal range (4-6 hours) because of an equivalent increase in both volume of distribution and total plasma clearance. Transplacental passage of the drug was observed. Monitoring is mandatory for prolonged vancomycin therapy, and the results should be available within 24 hours. The therapeutic regimen of 15-20 mg/kg every 12 hours was sufficient for this patient's chorioamnionitis. Serum drug levels and renal function should be measured before increasing the vancomycin dosage.
Adult↗
[The administration of tobramycin in the 2nd and 3rd trimester of pregnancy: contribution to a pharmacokinetic study for the adaptation of posology].
Aminoglycosides are currently used during pregnancy for the treatment of Staphylococcus, Enterobacteriaceae, Listeria monocytogenes, and Pseudomonas aeruginosa infections. The pharmacokinetics of tobramycin, an aminoglycoside antibiotic, was investigated after a 2.5 mg/kg short intravenous infusion and a once-daily dose regime in 18 pregnant women divided into 2 groups of 9 during the second (Group I: from 20 to 28 weeks of amenorrhoea) and the third (Group II: greater than or equal to 28 weeks of amenorrhoea) trimesters of pregnancy (during these period, risks of infectious diseases are increased). Plasma concentrations of tobramycin were measured by fluorescence polarization immunoassay (FPIA). The decrease of clearance (decrement of 27.6%), at 28 weeks and more gestation leads to an increase in the half-life and the MRT observed in the second group (increment of 49% and 41% respectively), whereas the volume of distribution remained unchanged in the two groups. No accumulation of the drug was observed in pregnant women. Pharmacokinetic disorders are correlated with the duration and moreover with the weight deviation of the women i.e., the growth of the conceptus. In 10 cases, a feto-maternal concentration ratio was calculated at delivery using an umbilical cord blood sample. This findings suggest a phenomenon of accumulation in the conceptus. To limit the potential nephrotoxicity and ototoxicity of tobramycin for the mother and the fetus, a once-daily dose regime seems to be an advanced solution for treatment of nonneutropenic pregnant women.
Absorption↗
Xenotropic and amphotropic pseudotyped recombinant retrovirus to transfer genes into cells from various species.
The ability to transfer genes into cells from different species with murine recombinant retroviruses was evaluated with the SVnls LacZ reporter gene. Mouse and cat packaging cell lines can be used to transfer amphotropic pseudotype, in human, mouse, cat, rabbit, sheep, horse and beef cells and with a very low efficiency in pig and avian cells. Xenotropic pseudotype recombinant retroviruses, produced in cat and rabbit packaging cell lines, transferred genes with the same efficiency as amphotropic retroviruses in human, cat, rabbit and sheep cells. In contrast to amphotropic retroviruses, xenotropic retroviruses infect beef, pig and horse cells with a high efficiency. These results emphasize the need to determine carefully the producer cell line (the type of helper virus and the species origin of the cell) for efficient transfer of genes in cells and embryos.
Animals↗
Fetal levels of tobramycin following maternal administration.
A single dose of tobramycin 2 mg/kg was given intravenously to a woman who presented a 22-week heterotopic pregnancy with both intrauterine and ovarian gestations and two living fetuses. After excision of the adnexum, tobramycin levels were measured in the maternal serum and in the fetal fluids and tissues. Antibiotic levels were especially high in the fetal spleen and kidney.
Adult↗
Mammary metabolism in the goat during normal or hormonally-induced lactation.
Mammary metabolism was studied in 4 normal lactating goats (group N) and in 4 non-pregnant goats induced to lactate by hormonal treatment (group 1). Tissue was sampled by biopsy after 3, 9 and 18 weeks of lactation. Although milk potential was the same in both groups, group 1 produced 45% less milk than group N. The RNA-DNA ratio, activities of lipoprotein lipase (LPL), glucose-6-phosphate dehydrogenase and acetyl-CoA carboxylase, and the beta-casein % of in vitro protein synthesis were not significantly lower in the 1 than in the N goat mammary tissue. This suggests that differences in mammary cell hyperplasia during hormonal treatment, and not potential metabolic activities, partially accounted for the difference in milk yield levels. Milk composition was comparable in the two groups. However, milk fat in group N had a higher long-chain fatty acid content (stearic and oleic acids) during the first month of lactation due to the higher mobilization of body lipids in high-yielding animals. Another qualitative difference was the delayed increase in milk LPL secretion during the first 3 months of lactation in induced goats.
Animals↗
Evolution of prolactin and placental lactogen receptors in ewes during pregnancy and lactation.
The present paper describes a method of membrane preparation from ewe mammary gland using a sucrose cushion (1.3 M) to select smooth membranes; this results in a membrane preparation richer in PRL receptors than the microsomal preparation classically used. This method was used for the characterization and measurement of PRL and ovine placental lactogen (oPL) receptors in three organs of the ewe (mammary gland, liver, and adipose tissue). PRL receptors were measured by competition of iodinated human GH ([125I]hGH) with ovine PRL (oPRL). This hormone, which has both growth and lactogenic activities, appears to interact with PRL receptors with a higher affinity than oPRL itself and is a good probe for the determination of PRL receptors in the ewe. oPL receptors were measured by the specific binding of [125I]oPL. This hormone appears to bind exclusively to a somatogenic site in the ewe, since various GHs compete efficiently for binding, whereas oPRL is without effect. The evolution of PRL and oPL receptors was determined during pregnancy and lactation and at different periods after an estradiol and progesterone treatment, which provokes growth of the mammary gland and milk secretion. During pregnancy, PRL receptors increased in the mammary gland up to day 100. During the last trimester, receptor content remained stable, and a second increase occurred during early lactation. No additional significant changes were observed either for PRL receptors in liver or adipose tissue or for oPL receptors in any of the organs studied (mammary gland, liver, adipose tissue). Injections of large doses of estradiol and progesterone to nonpregnant ewes were able to reproduce effectively the pattern of PRL receptors observed during pregnancy, but had no effect on oPL receptor levels. These studies demonstrate the independence of PRL and PL receptor sites in the ewe and suggest a different hormonal regulation for each type of receptor.
Adipose Tissue↗
Comparative measurement of the lactogenic activity of ovine placental lactogen in rabbit and ewe mammary gland.
Ovine placental lactogen is known to bind to prolactin receptors and to initiate milk synthesis in the rabbit mammary gland. However, this hormone exhibited a very low capacity of competing with 125I-labeled human growth hormone for the binding to membranes extracted from ewe mammary gland. Ovine placental lactogen was very efficient in provoking the accumulation of beta-casein mRNA in rabbit mammary explants but was much less active on ewe mammary explants. These data indicate that the placental hormone is not a potent lactogen in the homologous species and that its role in the control of mammary gland development and activity may have been previously overestimated.
Animals↗
Lactogenesis induced by ovariectomy in pregnant rats and its regulation by oestrogen and progesterone.
Ovariectomy on day 19 of pregnancy augmented galactosyl transferase activity 24 h after surgery preceding by 6 h the significant alpha-lactalbumin accumulation. Progesterone, injected immediately after ovariectomy showed a clear inhibitory effect on both galactosyl transferase and alpha-lactalbumin concentration, measured 30 h after ovariectomy. However, once the synthesis of lactose has been induced, progesterone is no longer inhibitory. Oestrogen induced a significant increase in lactose synthetase activity but no effect was obtained on galactosyl transferase activity. Progesterone, in a time and dose dependent relationship, was capable of preventing the effect of estrogen on lactogenesis. The lactogenic action of oestrogen in ovariectomized pregnant rats might be due to a direct effect at the mammary gland level facilitating the action of prolactin or through an indirect effect mediated via an increase on prolactin release.
Animals↗
Induction of beta-casein mRNA accumulation by the putative prolactin second messenger added to the culture medium of cultured mammary epithelial cells.
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Animals↗
Prolactin receptor turnover in explants of pseudopregnant rabbit mammary gland.
Pseudopregnant rabbit mammary glands in organ culture were used to investigate prolactin (PRL) receptor turnover. Chloroquine (100 microM) results in an increase in prolactin receptor levels (15.7 +/- 1.2% to 35.9 +/- 3.5% specific binding), whereas cycloheximide (1 microgram/ml) induces a rapid decline (to 6.4 +/- 1.2%) suggesting a rapid synthesis and degradation of the receptor molecule. Inhibitors of cellular transcription have little effect on receptor levels. Neither actinomycin D nor dichlororibofuranosylbenzimidazole (DRB) diminish PRL receptor levels whereas total protein synthesis is almost completely inhibited, and chloroquine increases the binding even in the presence of transcriptional inhibitors. These results imply that receptor synthesis continues and that the mRNA for the receptor protein is particularly stable. Ouabain (3 micrometers), which blocks the ATP-dependent Na+/K+ pump, provokes a greater than 60% reduction in PRL receptor levels without modifying total protein synthesis. Dinitrophenol (DNP, 1 mM), an oxidative uncoupler, has little effect on receptor levels, possibly due to a blockage of both synthesis and degradation. Prolactin is capable of inducing a 60% down-regulation of its own receptor, and this phenomenon appears to be energy-dependent because it is partially inhibited by DNP. This process seems to involve an increased rate of receptor degradation. These studies suggest that, at any one time, the level of PRL receptors in a target cell is the result of a dynamic equilibrium between receptor synthesis and degradation and that the most frequent modulations occur at the level of translation and lysosomal degradation. In conclusion, in mammary glands of the pseudopregnant rabbit, the prolactin receptor molecule appears to have a short half-life; the mRNA for this protein, however, is relatively stable.
2,4-Dinitrophenol↗
Evidence that the activation of casein gene expression in the rabbit mammary gland can be elicited by a low amount of prolactin firmly retained on its receptors.
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Animals↗
Effects of insulin, cortisol and prolactin on lipid, protein and casein syntheses in goat mammary tissue in organ culture.
The actions of insulin, prolactin and cortisol on protein, lipid and casein syntheses were examined in goat mammary explants in culture. The synthesis of the three products was stimulated by insulin and prolactin associated or not with cortisol. Casein synthesis was stimulated only when prolactin was present in the culture medium. Prolactin alone was able to significantly support the induction of casein synthesis. After preculture in the presence of insulin alone, the tissue lost part of its capacity to respond to the prolactin stimulus but, when precultured in the presence of insulin + cortisol, it retained its total sensitivity. These data suggest that insulin, prolactin and cortisol are involved in the maintenance of goat mammary tissue in culture but that prolactin essentially stimulates milk synthesis.
Adipose Tissue↗
Hormone levels in plasma of ewes induced into lactation.
A short-term treatment with estradiol-17 beta and progesterone induced mammary gland growth and lactogenesis in non-pregnant ewes. These events normally occur during the second half of pregnancy. In order to compare the hormonal environment during the treatment to that during pregnancy, the concentrations of total estrogens (TE), progesterone (P4), glucocorticoids (G) and prolactin (Prl) in the plasma were characterized in non-pregnant, intact ewes induced into lactation with subcutaneous injections of estradiol-17 beta (E2-beta) and P4 for 7 consecutive days (days 1 to 7). Eight non-pregnant, intact, multiparous ewes were divided into two groups (groups I and II, 4 ewes each), according to their milk yields recorded during the previous lactation. All the ewes received the short-term treatment with E2-beta and P4; the ewes of group II were also injected with hydrocortisone acetate (H) and growth hormone (GH) twice daily on days 18 to 20. Blood was collected twice daily for 21 days and milking was initiated 19 days after the first injection of E2-beta and P4. Concentrations of TE, P4, G and Prl were measured in the plasma of ewes in group I but only G and Prl were measured in the plasma of the ewes in group II. Two ewes of group I and one of group II failed to lactate. Mean milk yields (2.5 +/- 0.4 and 6.3 +/- 0.9 kg/34 days) were highest when injections of H and GH were included. Average pretreatment concentrations of plasma TE and P4 were 3.1 +/- 0.8 and 2.1 +/- 0.4 ng/ml, respectively; these increased to 10.2 +/- 1.3 and 5.6 +/- 0.6 ng/ml during the week of the E2-beta and P4 injections. Peak concentrations occurred on days 7 and 6, respectively, and the plasma levels had returned to pretreatment values by days 18 to 20. Concentrations of G in plasma were higher (13.0 +/- 1.0 ng/ml) during E2-beta and P4 injections than during pre- or post-injection (7.4 +/- 1.4 and 8.2 +/- 0.7 ng/ml, respectively). Plasma Prl showed biphasic two to six-fold increases on days 4 and 7 during E2-beta and P4 injections and thereafter declined to lower average daily concentrations on days 10 to 13. Plasma Prl began to increase, and its average concentration was 579 +/- 56 ng/ml by days 18 to 20. These results suggest that the amount of the P4 injections should be increased and that the treatment with E2-beta and P4 should last long enough to insure the induction of an endocrine balance which would correspond more accurately to the hormonal events occurring during the second half of pregnancy in the ewe.
Animals↗
Hormonal control of casein synthesis in mammary explants from pregnant goats.
The effects of insulin, cortisol, prolactin, 3,3',5-triiodo-L-thyronine (L-T3) and progesterone on the synthesis of total protein and casein in mammary explants from pregnant goats were studied. In the absence of hormones and in the presence of insulin plus cortisol the rate of incorporation of 14C-leucine into proteins that were precipitated with the anti-casein antibody decreased during culture. The addition of prolactin to hormonal combination of insulin and cortisol caused large stimulation of rates of casein synthesis. Maximum incorporation of leucine was attained between 3 and 5 days of culture in the presence of 0.5 microgram ml-1 of prolactin. Prolactin stimulated-casein and total protein synthesis were not consistently affected by the addition of L-T3 or progesterone. The inhibition of DNA synthesis by hydroxyurea or cytosine-arabinofuranoside had no effect on casein synthesis in mammary explants from pregnant goats.
Animals↗
Effect of bovine growth hormone on development of goat mammary tissue in organ culture.
The effect of bovine growth hormone (bGH) on DNA, protein and casein synthesis in goat mammary explants was studied. Growth hormone was unable to stimulate DNA synthesis or potentiate insulin-stimulated DNA synthesis either in high or low oxygen concentrations. In the presence of insulin and cortisol bGH had no effect on the synthesis of explant cytosol proteins. Two preparations of bGH were tested for their effect on casein synthesis. The preparation NIH-GH-B17 at concentration 50 micrograms ml-1 increased casein synthesis similarly as about 0.5 micrograms ml-1 of prolactin. Our preparation, prepared by the method of Prusík and Braun [1967], at concentration 50 micrograms ml-1 had effect lower than 0.05 micrograms ml-1 of prolactin. The lactogenic activity of NIH-GH-B17 was decreased by treatment with specific antisera to bovine prolactin. When submaximum concentration of prolactin (0.05 microgram ml-1) was added, bGH at concentration as low as 0.5 microgram ml-1 had synergistic effect on prolactin stimulated casein synthesis.
Animals↗