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A Lejeune

Publications and source records attributed to A Lejeune.

44 records · Page 3Linked to original sources

Stochastic models to study the impact of mixing on a fed-batch culture of Saccharomyces cerevisiae.

The mechanisms of interaction between microorganisms and their environment in a stirred bioreactor can be modeled by a stochastic approach. The procedure comprises two submodels: a classical stochastic model for the microbial cell circulation and a Markov chain model for the concentration gradient calculus. The advantage lies in the fact that the core of each submodel, i.e., the transition matrix (which contains the probabilities to shift from a perfectly mixed compartment to another in the bioreactor representation), is identical for the two cases. That means that both the particle circulation and fluid mixing process can be analyzed by use of the same modeling basis. This assumption has been validated by performing inert tracer (NaCl) and stained yeast cells dispersion experiments that have shown good agreement with simulation results. The stochastic model has been used to define a characteristic concentration profile experienced by the microorganisms during a fermentation test performed in a scale-down reactor. The concentration profiles obtained in this way can explain the scale-down effect in the case of a Saccharomyces cerevisiae fed-batch process. The simulation results are analyzed in order to give some explanations about the effect of the substrate fluctuation dynamics on S. cerevisiae.

Bioreactors↗

Effect of alpha-, beta- and gamma-cyclodextrins on oxygen evolution by the thylakoid membrane. influence of pH and temperature.

The present work investigates the effect of alpha-, beta- and gamma-cyclodextrins (CD), i.e., alpha-CD, beta-CD and gamma-CD, on the oxygen evolution activity, the protein content and the uv-vis spectroscopic characteristics of thylakoid membranes. To study the pH-dependence, the thylakoids were incubated with the cyclodextrins at 273 K for a period of 10 min in the pH range from 5.5 to 9.0. To study the temperature-dependence the membranes were incubated at 273 and 293 K at pH 6.5, that is, the pH which induces a maximal oxygen evolution in the thylakoid preparations. The major observations are: (i) a stimulation of oxygen evolution in thylakoids incubated with alpha- and beta-CD either in acidic or alkaline conditions, (ii) a low inhibitory effect induced by gamma-CD on oxygen evolution, (iii) a significant decrease of the stimulatory effect of alpha- and beta-CD on oxygen evolution as the incubation temperature is raised from 273 to 293 K, (iv) the apparent inability of the cyclodextrins to change the protein contents of the thylakoids, and (v) a significant CD-induced red-shift from 681 to 683 nm observed in the absorption and second derivative spectra of the thylakoid membranes treated with beta-CD. First, it was found that the temperature effect described here is in accord with the general trend of the chemical effect of various cyclodextrins, i.e., the increase of the CD efficiency with decreasing temperature. Secondly, the CD effect is related to the size of the inner cavity diameter of the cyclodextrin molecules. An important conclusion in this work is that the molecular targets of the cyclodextrins are not limited to the thylakoid lipids as was described previously [Rawyler A. and Siegenthaler PA. (1996) Biochim. Biophys. Acta 1278, 89-97], but are located as well in other molecular species exposed at the stromal side of the thylakoid membrane. In particular, the CD-induced red-shift from 681 to 683 nm in the absorption and second derivative spectra of the thylakoid membranes indicates that the cyclodextrins targets might be either the exposed heme macrocycle in cytochrome b559, or the chlorophylls and pheophytins in the pigment-proteins of the photosystems I and II.

Chloroplasts↗

Nanoerythrosomes, a new derivative of erythrocyte ghost: IV. Fate of reinjected nanoerythrosomes.

Recently, we have developed a promising new drug carrier named nanoerythrosome (nEryt). This transporter are small vesicles made with the red blood cell membrane. Anticancer drugs like daunorubicin, linked to these nEryt, have a higher antineoplastic activity than the free drug. In this paper, we first analyzed the biodistribution of 125I-nEryt purified by dialysis following intravenous (i.v.) or intraperitoneal (i.p.) injections in CD1 mice. After i.v. administration, nEryt, are rapidly removed from blood circulation (< 30 min). Mainly the liver and spleen take up the vesicles. I.p. injections of nEryt purified by dialysis, showed a marked activity in the inguinal lymph nodes 2 hours post-injection. nEryt purified by centrifugation have a different biodistribution. They accumulate also in the lungs. We demonstrated that accumulation in the lungs is due to particle aggregation during the preparation procedure. Comparative analysis of size distribution of each nEryt preparation revealed that nEtyt purified by centrifugation has a mean diameter of 1.5 microm which is 10 times higher than its dialyzed counterpart. Light microscopic autoradiographs of dialyzed nEryt, reinjected i.v., showed accumulation of nEryt in the sinusoidal lumen as well as in the parenchymal cells of the liver. Autoradiographs of the spleen revealed that nEryt are distributed specifically near the marginal zone and that some of them have escaped the meshes of the red pulp cords.

Animals↗

[Oligodendrogliomas. Clinical and therapeutic study (author's transl)].

Preliminary study concerning oligodendrogliomas : 21 cases treated only by neurosurgery ; 10 more recent cases by neurosurgery associated with chemotherapy. Discussion of the various factor : clinical symptomatology ; scintigraphic and tomodensitometric data ; time of evolution ; histological type. Favourable impression of chemotherapy effects. Necessity of a multicentric projective study on this subject.

Brain↗

Nanoerythrosome, a new derivative of erythrocyte ghost: preparation and antineoplastic potential as drug carrier for daunorubicin.

Liposomes and monoclonal antibodies are used as drug carriers for the optimal delivery of pharmacologic agents. However, they present disadvantages that led us to develop a new model of drug carriers: the nanoerythrosomes. Nanoerythrosomes are vesicles prepared by the extrusion of red blood cell ghosts, the average diameter of these vesicles is 0.1 micron. Daunorubicin was covalently linked to nanoerythrosomes and the cytotoxicity of daunorubicin conjugated to nanoerythrosomes was assessed on P388D1 cell line. The results indicated that the cytotoxicity of conjugated daunorubicin was as high as the free daunorubicin. Daunorubicin--nanoerythrosome conjugates had a higher antineoplastic activity than the free drug on CDF1 leukemia tumors. These results indicate that nonoerythrosomes could be potentially used as drug carriers.

Animals↗

Nanoerythrosomes, a new derivative of erythrocyte ghost II: identification of the mechanism of action.

We have recently developed a new drug which is a carrier from red blood cell membrane. This carrier, named nanoerythrosome (nEryt), is prepared by extrusion of erythrocyte ghosts to produce small vesicles having an average diameter of 100 nm. Daunorubicin (DNR) was covalently conjugated to the nEryt (nEryt-DNR) using glutaraldehyde as homobifunctional linking arm. This led to a complex that is more active than free DNR both in vitro and in vivo. In this study, we identified the mechanisms that make the complex nEryt-DNR more active than free DNR. Using fluorescence microscopy and cellular-uptake, we observed that the nEryt-DNR complex cannot diffuse through the cell membrane and do not enter the cell by endocytosis. Our results suggest that the nEryt-DNR is rapidly absorbed onto the cell membrane. Free DNR is then slowly released by hydrolysis of the glutaraldehyde linking arm, producing a high concentration of free DNR in the cell's vicinity over a long period of time.

Animals↗

Nanoerythrosomes, a new derivative of erythrocyte ghost: III. Is phagocytosis involved in the mechanism of action?

We have previously developed a new drug carrier, named nanoerythrosome which is prepared by extrusion of erythrocyte ghosts to produce small vesicles having an average diameter of 100 nm. Daunorubicin (DNR) conjugated to these nanoerythrosomes has a higher antineoplastic index than the free drug. Moreover, since nanoerythrosomes are particles, phagocytosis may be involved in their mechanism of potentiation. In the present study, we have compared the mechanism of penetration between free DNR and conjugate DNR linked to nanoerythrosomes, on cells presenting high phagocytic activity, macrophages, and cells lacking phagocytic activity, the P388 D1 cell line. Our results demonstrate that: 1) The nanoerythrosome-DNR complex is rapidly adsorbed and phagocytosed by the macrophages, but not by the P388 D1 cell line. 2) On the contrary, DNR enters both phagocytic and non phagocytic cells. Furthermore, the cellular distribution of DNR is the same in both cell lines, the nucleus being the target organelle. We conclude that phagocytosis of the nanoerythrosome-DNR complex is not involved in its mechanism of action.

Animals↗