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Biomedical subjects

D Braguer

Publications and source records attributed to D Braguer.

At least 37 records · Page 2Linked to original sources
PubMed1996

A controlled one-year trial of dextromethorphan in amyotrophic lateral sclerosis.

In a one-year parallel group double-blind placebo-controlled study of dextromethorphan (1.5 mg/kg) in amyotrophic lateral sclerosis, no significant differences were observed in the rate of progression (Norris scale) in comparing 24 patients randomly assigned to the dextromethorphan group and 25 patients randomly assigned to the placebo group. Of the 24 patients in the dextromethorphan group, 17 had limb onset and 7 had bulbar onset disease; average duration of disease was 12.5 +/- 6 months and sex ratio (M:F) was 1.4:1. Of the 25 patients in the placebo group, 18 had limb onset and 7 had bulbar onset disease; average duration of disease was 9.9 +/- 6 months and sex ratio (M:F) was 1.55:1. Dextromethorphan is a weak noncompetitive N-methyl-D-aspartate (NMDA) antagonist and higher doses or other potent NMDA receptor antagonists should be tested.

Adult↗
PubMed1996

[Modification of the response to paclitaxel of human differentiated colon cancer line after long-term treatment at very low dose].

Taxoids (paclitaxel, Taxol and docetaxel, Taxotere), drugs which stabilize microtubules, demonstrate marked activity against ovarian, brain and lung cancer. We investigated, on the human colon adenocarcinoma HT29-D4 cell line, firstly the effects of taxoids in function of the differentiation state and secondly the effects of a low dose of paclitaxel on the differentiation process. The cellular parameters studied were microtubular network, cell cycle and cell tubulin content. Undifferentiated cells treated with paclitaxel or docetaxel (10-100 nM) classically induced bundles in interphasic cells and pseudoasters in mitotic cells, arrest in cell cycle in G2M and increase in tubulin content. Inversely, no modification was observed in differentiated cells after similar taxoid treatment. Long-term low-dose pretreatment of differentiated cells restitutes some sensitivity to taxoids since these cells become responsive to further taxoid treatment, as reflected by modifications of the microtubule network.

Adenocarcinoma↗
PubMed1995

Simultaneous combination of microtubule depolymerizing and stabilizing agents acts at low doses.

The combined activity of a stabilizing and a depolymerizing agent was studied on microtubule formation in vitro and on cellular parameters related to the cytoskeleton. New compounds in each class of microtubular drugs, docetaxel, as stabilizing agent, and CI 980, as colchicine analog, currently in clinical trials, were tested at high and low concentrations. Simultaneous combination of docetaxel and CI 980, both in vitro and in cell lines, induced microtubule structures resulting from the association of the effects of the two drugs: short and numerous microtubules in vitro, abnormal asters or short bundles in cells depolymerized in their periphery. Moreover, combining the two drugs at low concentrations inducing neither modification of the microtubular network nor variation in cell polymerized tubulin content showed synergistic effects in mitotic cell block and, at lower concentrations, in inhibition of proliferation in the KB 3-1 cell line. Similar qualitative results were obtained with paclitaxel and colcemid, used in the place of docetaxel and CI 980, respectively. At low doses, the taxoid/colchine analog combination seems to induce some degree of mitotic inhibition, resulting from a subtle effect on the inhibition of microtubule dynamics.

Antineoplastic Agents↗
PubMed1994

Comparative effects of taxol and Taxotere on two different human carcinoma cell lines.

The effects of taxoids (taxol and Taxotere) were followed on two human cancerous cell lines (bladder carcinoma J82 cells and epidermoid carcinoma KB 3-1 cells). Three cellular parameters were studied, viz., the qualitative effect on cellular microtubules, the quantitation of tubulin, and the antimitotic action, using two-parametric flow-cytometric analyses in treated cells. In both of the cell lines the tubulin content increased after taxoid treatment before the accumulation of cells in the G2/M phase. The effects of taxoids on tubulin appeared at about a 10-fold lower concentration on KB cells than on J82 cells. After drug exposure, the microtubule network showed a striking difference between the two cell lines: microtubule bundles were predominant in the J82 cell line, whereas multiple asters were prevalent in the KB cell line. The formation of these structures was dose- and time-dependent. Asters were observed in mitotic cells and bundles were seen in interphase cells. The reversibility of these structures in both cell lines varied with the duration of exposure to drug. Some differences were shown between taxol and Taxotere: the effects of Taxotere as compared with taxol appeared at a 2-fold lower concentration and their reversibility was slower.

Antineoplastic Agents, Phytogenic↗
PubMed1994

Characterisation of a navelbine-resistant bladder carcinoma cell line cross-resistant to taxoids.

A bladder carcinoma cell line (J82) was selected for resistance to the new vinca alkaloid navelbine. The resistance factor of the resistant subline (J82-NVB) to navelbine was 17. P-glycoprotein was not detected in the membrane of J82-NVB cells. The lack of cross-resistance to multidrug-resistant (MDR) drugs such as doxorubicin, epipodophyllotoxins and colchicine, the absence of increase in navelbine efflux and the fact that a reduced accumulation of the drug cannot account for the resistance level confirmed that the phenotype of resistance of J82-NVB cells is not a classical MDR phenotype. Moreover, verapamil did not reverse the resistance of J82-NVB cells. The cells were cross-resistant to vinca alkaloids and taxoids which share the same target protein: tubulin. Analysis of microtubules using immunofluorescence showed that disassembly of the microtubular network occurred for the same concentration of navelbine in sensitive and resistant cells. However, after treatment with a concentration of navelbine inducing depolymerisation in both sensitive and resistant cells, reassembly of the microtubular network was observed only in resistant cells. This study suggests that the mechanism of resistance of J82-NVB cells involves recovery from the inhibition of microtubule dynamics induced by drug treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Qualitative study of the interaction mechanism of estrogenic drugs with tubulin.

Synthetic estrogenic drugs (E-diethylstilbestrol, erythro-hexestrol and E,E-dienestrol) inhibit tubulin assembly and erythro-hexestrol and E,E-dienestrol lead to the formation of twisted ribbon structures. For the inhibitory effect on tubulin assembly, estrogenic drugs seem to interact directly with tubulin 6S on site(s) analogous to the colchicine-site, but independent of the GTP- and vinblastine-sites. This binding does not involve tubulin tryptophanyl residues or sulfhydryl groups. The influence of temperature, calcium and magnesium on the formation of twisted ribbon structures induced by the binding of estrogenic drugs to microtubular protein and tubulin has also been studied. This formation is strongly magnesium-dependent whereas preformed twisted ribbon structures are calcium- and chilling-insensitive.

Binding Sites↗
PubMed1991

Restoration by biotin of the in vitro microtubule formation inhibited by uremic toxins.

Tubulin is an intracellular protein whose in vivo polymerization leads to the formation of microtubules (MT). MT are essential component of axons of nerve cells. This reaction is the limiting factor in the growth of axons. Uremic neuropathy is characterized in part by an axonal degeneration. A chromatographic fraction from uremic plasma (2-5 fraction) inhibits in vitro the tubulin polymerization and thus MT formation and therefore may be implicated in the occurrence of uremic neuropathy. In vitro, biotin counteracts the inhibitory effect of 2-5 fraction on MT formation. This effect could be a partial explanation of the possible clinical improvement brought on by biotin in uremic neuropathy.

Biopolymers↗
PubMed1989

Intraerythrocytic water relaxation rates in amyotrophic lateral sclerosis. An NMR investigation.

Water relaxation rates 1/T2 in erythrocytes from amyotrophic lateral sclerosis (ALS) patients were studied by NMR. The spin-spin relaxation time of water protons in erythrocyte suspension was measured in the presence of a paramagnetic reagent which did not enter the cell. Our results show that red blood cell membranes exhibit a diminished water permeability in some ALS patients. Moreover, the activation energy value of water is lower in ALS patients than in healthy controls.

Adult↗
PubMed1987

Interaction of some estrogenic drugs with tubulin. Formation of twisted ribbon structures.

We studied the action of E-diethylstilbestrol (E-DES), erythro-hexestrol (erythro-HES), and E,E-dienestrol (E,E-DIES) on microtubule formation. The three drugs inhibit this formation from microtubular protein; the percentages of inhibition were, respectively, 15% and 45% for 1.25 X 10-s M E-DES and E,E-DIES. With purified tubulin 6S, 7.5 X 10(-6) M E,E-DIES and erythro-HES induced a 20% inhibition. In the case of E-DES, our results are in good agreement with previous ones. These drugs partially disrupt preformed microtubules. Moreover, when E,E-DIES (5 X 10(-5) M) is added to tubulin, loosely organized aggregates composed of twisted ribbon structure are formed. In the case of erythro-HES, similar structures were observed but at higher concentrations. With E-DES, no organized structures are present.

Animals↗
PubMed1987

31P nuclear magnetic resonance study of variations in intra-erythrocytic ATP concentration and pH induced by surgical trauma.

Variations in intracellular pH and ATP concentrations in erythrocytes were studied in patients undergoing a mild surgical intervention. Intra-erythrocytic pH was decreased at the end of the operation; ATP concentrations concomitantly increased, but not highly significantly. These variables returned to their initial values by 20 h after the end of surgery.

Adenosine Triphosphate↗
PubMed1986

Inhibition of microtubule formation by uremic toxins: action mechanism and hypothesis about the active component.

We show in vitro inhibitory effect of a mixture of uremic toxins on tubulin 6S polymerization. It proves the existence of a direct interaction protein-toxin where micro-tubule associated proteins are not involved. A similar phenomenom could occur in uremic neuropathy. The action mechanism of this interaction is quite different from that of classical tubulin inhibitors: Vinca alcaloïdes and colchicine. Finally we hypothesize about the active molecule.

Animals↗
PubMed1986

In vitro inhibition of microtubule assembly by disulfiram.

Disulfiram (Tetraethylthiuram disulfide, DSF) inhibits in vitro tubulin polymerization in a dose-dependent manner after a preliminary incubation time. Electron micrographs show that microtubules are shorter and less numerous. This inhibition may be correlated to blockade of protein SH groups. The linkage of DSF-tubulin hinders the vinca alkaloids-tubulin binding as shown using radioactive assay and microcalorimetric measurements. These results could be responsible for the occurrence of some side effects observed during the therapeutic use of this drug.

Animals↗
PubMed1984

The in vitro effect of some nitroimidazoles on microtubule formation.

The in vitro effects of some nitroimidazoles (metronidazole, ornidazole) and their metabolites on microtubule formation have been tested. Cyclic metabolites are without effect. Metabolites proceeding from cleavage of the imidazole ring inhibit microtubule formation and reduce the polymerization rate of tubulin. This inhibitory effect might be correlated to some of the side-effects of these drugs. Isaxonine phosphate corrects this effect.

Animals↗