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Biomedical subjects

F Fleury

Publications and source records attributed to F Fleury.

45 records · Page 3Linked to original sources
PubMed1984

Three-day treatment with butoconazole nitrate for vulvovaginal candidiasis.

A multicenter clinical trial of 274 patients compared the efficacy and safety of a new vaginal antifungal compound, butoconazole nitrate cream 2% (butoconazole), to clotrimazole vaginal tablets 200 mg/day (clotrimazole). Both drugs were administered for three days. The patients were randomly assigned to one or the other treatment regimen. Eight days after treatment completion, Candida albicans was absent in vaginal cultures of 95% of patients receiving butoconazole and of 91% of patients receiving clotrimazole; 30 days after treatment completion, 80% of patients receiving butoconazole were free of the fungal infection; the corresponding number for clotrimazole was 74%. Complete absence of the entrance signs and symptoms of vulvovaginal candidiasis was noted in 82% of patients receiving butoconazole and 72% of patients receiving clotrimazole. The phamacokinetic parameters were studied in three women volunteers who received one dose of radiolabeled butoconazole nitrate vaginal cream 2%. Measurable levels of radioactivity were not detected until two to eight hours after vaginal administration of the compound. Maximum plasma levels of radioactivity were achieved 24 hours after dosing and ranged from 19 to 44 ng/mL and fell to background levels after 96 to 120 hours. Total radioactivity was excreted to an equal extent in urine (2.7%) and in feces (2.8%).

Adult↗
PubMed1981

[The value of the treatment of post-radiotherapy hyposialorrhoea by dihydroergotamine (author's transl)].

This study of the Rennes anti-cancer Center reports the results of a clinical and isotope scan study of Dihydroergotamine-Sandoz in the treatment of post-radiotherapy hyposialorrhoea. Dihydroergotamine was used at an initial dose of 100 drops 3 times per day for two weeks, then 60 drops 3 times per day. Treatment must be continued for several months. The results of such treatment given to 11 patients in comparison with a "control" group of 19 patients were evaluated objectively using isotope studies of salivary function. It was found, in addition, that the interruption of treatment might be associated with a relapse of symptoms, reversible when the drug was restarted. Finally, and in the light of the results of this study, it would appear to be logical to treat patients immediately following the end of radiotherapy without awaiting the first symptoms of hyposialorrhoea.

Dihydroergotamine↗
PubMedDate not supplied

Synthesis of 5'-thioalkyl, sulfoxide and sulfone pyrimidine nucleosides.

The preparation of 5'-thioalkyl, sulfoxide and sulfone pyrimidine nucleosides is [4-11] is described. The key steps of this synthesis are the nucleophilic displacements of a chlorine by a thioalkyl sodium salt or the direct introduction of the thioalkyl group under Mitsunobu conditions.

Animals↗
PubMedDate not supplied

Expression, purification and DNA-cleavage activity of recombinant 68-kDa human topoisomerase I-target for antitumor drugs.

The gene encoding human DNA topoisomerase (topo) I, the target of numerous anticancer drugs, has been subcloned into bacterial, yeast and baculovirus-based expression systems in attempts to overexpress the enzyme for extensive structural and functional characterisation. Expression in E.coli produced a protein which was not suitable for structural studies. Expression in the yeast system was more successful enabling the enzyme to be purified and characterised. However, the resulting yield was modest for our requirements and the full-length protein was found to be susceptible to proteolysis when expressed in this system. As it is known that topo I from human placental tissue contains significant quantities of a 68kDa proteolytic fragment which retains both DNA relaxation and cleavage activity, we have isolated this fragment and shown by N-terminal sequence analysis that it starts at Lysine-191. This information was used to construct vectors which direct the overexpression of this fragment in baculovirus infected insect cells. The recombinant protein has been purified to homogeneity in a yield of 5-10mg/l of cell culture. The fragment is stable and retains all of the DNA driving activities of the intact enzyme. We have characterised the interactions of the topo I fragment with synthetic DNA substrates and identified oligonucleotides and conditions that allow covalent complexes between 68kDa topo I and DNA to be formed with high efficiency and in large quantity. A flow linear dichroism technique has been further developed and applied for real-time monitoring of supercoiled (sc) DNA relaxation by the enzyme and for comparative analysis of inhibition of 68kDa topo I by camptothecin (CPT).

Animals↗
PubMedDate not supplied

Confocal spectral imaging analysis of intracellular interactions of mitoxantrone at different phases of the cell cycle.

It is suggested that the cytotoxicity of anticancer agent mitoxantrone (MITOX) is related to a complex combination of molecular interactions which lead to slowing of S phase traverse and arresting of cells in G2 phase of the cell cycle or even to an apoptosis at high concentration of MITOX. Here intracellular molecular interactions of MITOX were visualised and studied using the confocal spectral imaging technique in synchronised K562 cells. Localisation, quantitative distributions of MITOX in the polar environment, MITOX bound to hydrophobic cellular structures (MITOXphob), nucleic acid-related complexes of MITOX (MITOXNA) and relative distributions of naphthoquinoxaline (NQX) metabolite and intrinsic cellular fluorescence of porphyrins were measured within cytoplasmic and nuclear compartments (chromosomes) of the G2, S, and M cells treated with 10 or 2 microM of MITOX for 1 hour. Colocalisation of MITOX, NQX metabolite and sites of intrinsic cellular fluorescence indicates an accumulation of MITOX within or near mitochondria. One may suppose that due to high concentration MITOX can compete with natural substrates for binding to the enzymes thus affecting the normal functioning of a mitochondria. A remarkable redistribution of MITOX and its complexes occurs in the M cells. In particular, a prominent amount of MITOX is associated with the surface of chromatids but not with the cytoplasmic structures in M cells. At the present time the exact location of the sites of MITOX accumulation in the M cells is not known. It is thought to be some cytoskeleton/microtubule structures associated directly with the chromosomes. Selective labelling of particular cytoskeleton structures and/or proteins in MITOX treated cells is in the progress now and the question will be addressed using the CSI technique.

Antineoplastic Agents↗
PubMedDate not supplied

[Study of P-glycoprotein effect on the lipid monolayer properties by the Langmuir-Blodgett technique].

Expression of the P-glycoprotein (Pgp) is proved to be one of the main reasons for the development of the multidrug resistance (MDR) phenotype by cancer cells. The effect of Pgp on the properties of lipid monolayers was studied using membrane fractions of sensitive and Pgp over-expressing multidrug resistance cancer cells containing 11, 24 or 32% of Pgp relative to the total content of membrane proteins. The effect of the Pgp membrane concentration on the properties of monolayers prepared from the membrane fractions was analyzed by the Langmuir-Blodgett method. The subphase composition was found to play a critical role in the stability of monolayers at any Pgp concentration. The optimal subphase comprised 10 mM tris-HCl buffer, pH 6.5, which made it possible to create very stable monolayer films with the pressure of collapse of about 30-40 mN/m. Monolayers prepared from membrane fractions of sensitive cells and cells containing the maximum (32%) amount of Pgp were found to be much more stable compared with fractions comprising 11 or 24% of Pgp. The analysis of monolayer compression dynamics revealed three distinct stages: (1) the self-organization of lipid molecules, which is characterized by an abrupt change of surface potential; (2) the compression of Pgp molecules at the constant potential of monolayers; and (3) the compression of lipid molecules, which is characterized by a quasilinear increase of both pressure and surface potential. It was shown that the specific surface areas of monolayers formed from sensitive and Pgp-enriched membranes containing 11 or 24% of Pgp are very similar, whereas the surface area of the monolayer formed from membranes containing 32% of Pgp is nearly 1.5-fold greater. This fact may reflect the effect of the threshold rearrangement of the structure of lipid molecules or cooperative modifications of lipid-Pgp interactions induced by the increase in the Pgp content from 24 to 32%. The effect of verapamil, a well-known Pgp modulator, on the properties of monolayers was studied. It was show that verapamil is able to induce changes of the surface of Pgp-containing monolayers, and these modifications are maximal at the Pgp:verapamil 1:1 molar ratio. The data present the first experimental evidence for the possible intervention of Pgp modulator into the processes of lipid-lipid or lipid-Pgp cooperative interactions within Pgp-enriched membranes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗