Biomedical subjects

R Roguet

Publications and source records attributed to R Roguet.

25 records · Page 2Linked to original sources

PubMed1985

The measurement of the stratum corneum reservoir. A predictive method for in vivo percutaneous absorption studies: influence of application time.

The relation existing in vivo between the reservoir function of the stratum corneum following a 30-min application time and the total percutaneous absorption of molecules applied for a longer time was studied on hairless rats. One thousand nanomoles of 4 radiolabeled molecules (theophylline, nicotinic acid, acetyl salicylic acid, benzoic acid) were applied on 1 cm2 of back skin for 0.5, 2, 4, and 6 h. The total recovery in excreta and the whole animal body were measured 4 days later in order to determine the level of absorption. A direct proportionality (r = 0.99) between the total percutaneous absorption of these compounds and the duration of their application was observed. This suggests that a constant flux of penetration does exist in vivo. The reservoir function of the stratum corneum was measured by successive stripping of the treated area. Following a 30-min application, a strict correlation (r = 0.99) between the total amounts of molecules penetrated in 4 days and the amounts found in the reservoir of the horny layer was demonstrated. All together these findings show that the simple knowledge of the reservoir effect of the stratum corneum for a molecule applied for 30 min allows the predictive assessment of its total penetration resulting from various times of application.

Animals↗

PubMed1984

In vivo relationship between horny layer reservoir effect and percutaneous absorption in human and rat.

The in vivo relationship between the reservoir effect of the stratum corneum and the percutaneous absorption was established in both human volunteers and hairless rats. Four doses of [ring-14C]benzoic acid, 125, 250, 500, and 1000 nmol, were applied on 1 cm2 either on the external side of the human arm or on the back of the rat, for 30 min. In both human and rat, the data on percutaneous absorption after 4 days is directly related to the dose administered. In rat, the permeability to benzoic acid is twice that of the human skin and the reservoir effect of the stratum corneum, measured at the end of application (30 min), is also doubled for this molecule in rat. Taking into account these findings and the observed histologic differences between the treated areas of these two species, the molecular reservoir of the horny layer may well be situated within the interlayer spaces. For both species, a linear relationship exists between (x), the amount of substance present in the stratum corneum at the end of application (30 min), and (y), the total amount penetrated in 4 days. The relationship, similar to that obtained in an earlier study on rat with 10 molecules, may be written as follows: y = 1.83 x - 0.52 (r = 0.998, p less than 0.001). Thus the amount of substance liable to penetrate through human skin within 4 days can be predicted by measuring the amount present in the stratum corneum 30 min after application of the drug.

Administration, Topical↗

PubMed1983

In vivo correlation between stratum corneum reservoir function and percutaneous absorption.

A relationship between stratum corneum reservoir function and percutaneous absorption has been established in the hairless rat. Two hundred nanomoles of 10 substances that have a wide range of chemical structures were topically applied for 30 min and the total body distribution was measured after 96 h. The quantity of substance present in the stratum corneum reservoir after 30-min application was measured by liquid scintillation counting after tape-stripping the treated area. A linear relationship exists between the quantity of substance in this reservoir x(nmol X cm-2) and the total amount of radioactivity distributed in the body and excreta y(nmol X cm-2) after 96 h. The relationship is given by: y = 1.644 X x - 0.536 (r = 0.998, p less than 0.001). Apart from the steroids, 80-95% of the compounds were excreted in the urine; and with the exception of thiourea, this elimination was rapid, especially for mannitol and benzoic acid. We confirmed that in terms of penetration there is a factor of 50 between benzoic acid (best) and dexamethasone (worst). Thus the quantity of substance penetrating through intact rat skin can be predicted by measuring the horny layer concentration. The animal data reported here should be verified in humans.

Animals↗

PubMed1978

Specific modifications of hepatoma cell-surface glycoproteins with enzymes. Effects on in vitro growth as investigated by the use of lectins.

The effects of enzymic treatment on the interactions between Zajdela's tumor cells and various lectins. Concanavalin A (ConA); Wheat Germ Agglutinin (WGA); Robinia lectin; have been studied. (1) The number of lectin-binding sites and the affinity constants were investigated. (2) The effects of the lectins on cell growth and [3H]thymidine incorporation were studied on untreated and enzyme-treated cells. It was observed that treatment of tumor cells with neuraminidase resulted in a change in the binding characteristics of each lectin. However, additional treatment of the cells with galactose oxidase had no further effect on lectin binding. ConA and Robinia lectin induced a decrease of the untreated tumor cell growth and a stimulation of the [3H]thymidine incorporation. This paradoxal result may be explained as a consequence of the stimulation of the [3H]thymidine uptake observed in the presence of lectins. The enzymatic treatments themselves did not change the cell growth although they did induce a change in the effect of ConA and Robinia lectin on cell growth and [3H]thymidine incorporation. As a result of neuraminidase treatment, the effects of ConA were totally suppressed but those of Robinia lectin only partially. Although WGA interacted with untreated and enzyme-treated cell surfaces, it had no effect on tumor cell growth nor [3H]thymidine incorporation. The results are discussed in terms of lectin transport.

Animals↗

PubMed1976

Embryo cell surfaces--lectin binding and cell proliferation.

The interaction between chick embryo fibroblasts and various lectins has been studied at different stages of embryo development. There is evidence that Robinia lectin, Dolichos lectin, and Concanavalin A decrease cell number and proportion of cells incorporating [3H] thymidine in case of 8- and 10-day-old chick embryo fibroblasts, whereas they stimulated the proliferation of 16-day-old embryo cells. No effect was noticed in 12-day cells. These results suggest that some cell surface changes occur during embryo development. The site number of Dolichos lectin remains the same during embryo development, and the affinity constant decreases. The site number of Robinia lectin and Concanavalin A decreases from the 8th to the 12th day of development, and slowly increases on the 16-day cells, the affinity constant remaining rather constant. The results indicate that the age-dependent effect of lectin on embryo cells could not be directly related to the number of lectin-binding sites. Competitive binding experiments revealed that Dolichos receptor sites were distincts from binding sites of Robinia lectin and Concanavalin A, and Robina receptor sites distinct from those of concanavalin A. Lectin effects on embryo fibroblasts were very specific as determined by inhibitory assays.

Animals↗

PubMed1975

Interaction between Dolichos biflorus lectin and chick embryonic fibroblasts at different stages of development.

The interaction between chick embryo fibroblasts and A1-specific blood group Dolichos biflorus lectin has been studied at various stages of embryo development. The site number ((0.26 plus or minus 0.03)-10-6 sites/cell) remains the same during development whereas the affinity constant apparently decreases from 8-day cells onwards. The effects of cell number, temperature and time course on the Dolichos binding to fibroblasts were not age dependent. Competitive binding experiments revealed that Dolichos receptor sites were distinct from binding sites fo Robina pseudoacacia lectin and concanavalin A, but partially related to binding sites of Ricinus lectin. Thymidine incorporation by fibroblasts in the presence of Dolichos lectin was age dependent. It was inhibited in 6-day cells and weakly stimulated in 16-day cells, but not modified in 12-day cells. Dolichos lectin effects on embryo fibroblasts were very specific because both binding to cells and effect on thymidine incorporation were blocked by N-acetylgalactosamine, the determinant of Dolichos lectin, as well as by Dolichos antiserum.

Animals↗

PubMed1975

Changes in lectin-induced deoxyribonucleic acid synthesis in cultures of chick-embryo fibroblasts at various stages of development.

Concanavalin A and Robinia pseudoacacia lectin decreased [(3)H]thymidine incorporation into acid-insoluble material of fibroblasts cultured from 6-10-day chick embryos. In contrast, these lectins stimulated [(3)H]thymidine incorporation in cells from 16-day embryos. These effects are due to neither [(3)H]thymidine permeability modification nor toxicity of the lectins. The specificity of lectin action was proved by blocking experiments with alpha-methyl mannopyranoside and with anti-(Robinia lectin) serum.

Animals↗