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Biomedical subjects

P Pellegrin

Publications and source records attributed to P Pellegrin.

At least 19 recordsLinked to original sources
PubMed1998

Aggregates of an amphiphilic synthetic peptide bind and deliver all-trans retinol and all-trans retinoic acid into fibroblast cells.

The structure and conformational behaviour of a vector peptide, designed by association of a fusion peptide and a nuclear localization sequence, are described. A beta-sheet domain is observed in which fluorescence measurements show that ten peptide molecules bind one all-trans retinol or all-trans retinoic acid molecule with a strong affinity (K'd = 40 nM). Stoichiometry and affinity of the binding can be compared with those of cellular retinoid binding proteins, the structure of which is an anti-parallel beta barrel. Analogy between the system under study and cellular retinoid-binding proteins is discussed. Peptide-helped internalization and subsequent perinuclear localization of retinol in human fibroblast cells confirm this analogy. Also, this last result shows that the peptide is an efficient carrier for insoluble substances like retinoids.

Amino Acid Sequence↗
PubMed1998

[Synthetic peptide as retinoid vector and antiproliferative agent].

First part: Structure, conformational behaviour and vectorization properties of a peptide (PFNLS) designed by association of a fusion peptide and a nuclear localization sequence is described. Tryptophan fluorescence quenching measurements show that ten peptide molecules bind one all trans retinol or all trans retinoic acid molecule with a strong affinity (Kd' = 40 nM). And is able to help the internalization of all-trans retinol in human fibroblasts. Stoichiometry, structure and affinity of the binding can be compared with those of cellular retinoid binding proteins (CRBP), the structure of which is an antiparallel beta barrel. Second part: Cytotoxic properties of the amphiphilic synthetic peptide are presented. Comparative analysis of proliferating, differentiated and confluent H9C2 adherent cells shows a correlation between toxicity and cell cycle stage (proliferating cells). Electrophysiological measurements on Xenopus laevi oocytes bathed in the peptide also demonstrate the induction of cationic currents, which are voltage dependent. These results allow us to hypothesize that the observed toxicity is related to membrane hyperpolarization of proliferating cells at the G1/S cell cycle phase transition. An important point is that in the case of the "peptide-retinoid" complex, no cytotoxicity is observed.

Amino Acid Sequence↗
PubMed1997

Cell cycle dependent toxicity of an amphiphilic synthetic peptide.

The cytotoxic properties of an amphiphilic synthetic peptide are presented. Comparative analysis of proliferating, differentiated and confluent H9C2 adherent cells and L1210 cells in suspension shows a correlation between toxicity and cell stage (proliferating cells). Electrophysiological measurements on Xenopus laevis oocytes bathed in the peptide also demonstrated the induction of cationic currents, which is voltage and phosphate dependent. These results allow us to hypothesize that the observed toxicity is related to membrane hyperpolarization of proliferating cells at the G1/S cell cycle phase transition.

Amino Acid Sequence↗
PubMed1986

Site of action of torasemide in man.

The effect of torasemide, a new orally and parenterally active diuretic agent, on the renal mechanisms of dilution and concentration was studied in 6 healthy volunteers. The experimental conditions included water and osmotic diuresis. Torasemide caused maximal chloruresis and natriuresis during the 20-40 min after administration. The effect was more pronounced under osmotic diuresis and persisted throughout the 100 min of those experiments. A distinct effect both on free water clearance (CLH2O) during water diuresis and tubular reabsorption of solute free water (TcH2O) during osmotic diuresis strongly suggests that the major site of action of torasemide is the ascending limb of the loop of Henle. Comparison with furosemide under osmotic diuresis indicates longer abolition of TcH2O/GFR by torasemide in keeping with the fact that its half-life is 2- to 3-times longer than that of furosemide.

Adult↗
PubMed1983

Hepatic clearance of gitoxin: pharmacokinetic study on rabbit isolated liver. Influence of protein binding and comparison with digoxin.

Hepatic clearance of gitoxin has been studied in the rabbit and compared with that of digoxin using an isolated perfused liver technique. During 1.5 hour perfusions with a modified Krebs-Henseleit solution, gitoxin perfusate levels decreased biexponentially; the distribution and elimination half-lives were estimated to be 0.14 and 1.25 hour, Vd area to be 95.5 ml.g-1 and intrinsic metabolic clearance to be 1.98 ml.min-1.g-1. During 1.5 hour perfusions with modified Krebs-Henseleit solution containing 2.7% bovine serum albumin, gitoxin perfusate levels decreased monoexponentially. This is probably due to protein binding which moderates hepatic uptake so that distribution is not yet complete after 1.5 hour and it is therefore impossible to discriminate the two phases. This was confirmed by 5 hour perfusion experiments with an emulsion of perfluorocarbon in the modified Krebs-Henseleit solution also containing 2.7% bovine serum albumin, during which gitoxin levels decreased biexponentially. Distribution and elimination half-lives have been estimated to be 0.31 and 5.54 hours, Vd area to be 139 ml.g-1 and intrinsic metabolic clearance to be 1.36 ml.min-1.g-1. Gitoxin has been compared in these experimental conditions with digoxin, one of the most often used cardiotonic's. Distribution and elimination half-lives of digoxin were estimated to be 0.34 and 4.52 hours, Vd area to be 46.5 ml.g-1 and intrinsic metabolic clearance to be 0.17 ml.min-1.g-1. Other pharmacokinetic parameters (alpha, beta, V1, V2...) also have been calculated for these three types of perfusion experiments.

Animals↗
PubMed1979

The binding of gitoxin to human plasma proteins.

The binding of gitoxin, digitoxin and digoxin to human plasma proteins was measured by ultracentrifugation and equilibrium dialysis. At concentrations in the range of therapeutic plasma levels, protein binding amounted, respectively, to 85, 92 and 20%, the last two values being consistent with data reported in the literature. The affinity of purified human albumin was not significantly different for the three cardiac glycosides tested. No other protein than albumin was found to bind gitoxin in human plasma.

Blood Proteins↗