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Biomedical subjects

B Dugue

Publications and source records attributed to B Dugue.

6 recordsLinked to original sources

Interval training program on a wheelchair ergometer for paraplegic subjects.

BACKGROUND: Various combinations of training intensity, duration and frequency are often proposed to people with spinal cord injuries in order to improve their fitness. However, no consensus about a specific training program has been reached for such a population. OBJECTIVE: This study investigated the effects of a short interval training program specifically designed for patients with spinal cord injuries. METHODS: Paraplegic men performed 30-min wheelchair ergometry three times per week, for 4 weeks. Maximal dynamic performance and endurance capacity were studied before and after the training program with an incremental test (10 W/2 min) until volitional fatigue and a constant work rate test, respectively. Cardiorespiratory responses were continuously studied during each of these tests. RESULTS: Training induced significant improvement in maximal tolerated power (+27.9%), and in peak oxygen consumption ([VO2, +18.5%). After training the subjects were able to maintain the load applied during the constant test (total mechanical work +210.7%), for a significantly longer time. The heart rate, [VO2 and ventilation values observed when the volunteers ended their first constant load test were significantly higher (+10%, +10%, +40% respectively) than those obtained after a similar time period during the second constant load test which was performed after the training program. CONCLUSION: After this short training period, with an appropriate combination of different types of training, duration, intensity and frequency exercises, we observed a significant improvement in the fitness level and endurance capacity of paraplegic subjects.

Adult↗

Intrinsic factor covalently bound to Sepharose as affinity medium for the purification of a soluble intrinsic factor receptor from human urine.

We have identified a soluble receptor for intrinsic factor (IF) in human urine. The purification of this protein by affinity chromatography required a preliminary purification of IF from hog pyloric mucosal extract. This was achieved by thermolabile cobalamin-ethanol-aminohexane Sepharose affinity chromatography with a 133-fold purification, a yield of 45% and a specific binding activity of 15720 pmol/mg protein. The purified Cbl-IF complex was coupled to epoxy-Sepharose with a yield of 23.8% and a specific activity of 1.2 nmol per mol of gel. The soluble IF receptor was purified form 200 ml of urine concentrate of pregnant women. Desorption was performed at pH 5.0 and in the presence of 5 mM EDTA. The soluble IF receptor was purified 17,200-fold with a yield of 52% and a IF binding capacity of 3260 pmol per mg of protein. A single protein with a Mr of 70,000 was found in silver-stained SDS-PAGE.

Animals↗

Covalent binding of elliptinium acetate (NSC 264137) to nucleic acids of L1210 cells in culture.

Elliptinium acetate (9-OH-NME; Celiptium) is an antineoplastic agent currently used in the treatment of metastatic breast cancer and is known to intercalate into DNA. Previous studies have demonstrated that this molecule can be oxidized, yielding a reactive electrophilic form, which is able to bind covalently to a nucleophilic biological molecule. In this work, we evidenced a covalent binding of this drug to nucleic acids of L1210 cells in culture. A high performance liquid chromatography technique allowed us to distinguish between reversible and nonreversible interaction and to determine the binding ratio (rb) of covalently bound elliptinium versus bases of nucleic acids extracted from cells. After an 8-h incubation of L1210 cells with 0.1 microM elliptinium (the dose corresponding to the 50% inhibitory dose), we obtained 2.4 X 10(-6) and 3.4 X 10(-6) as the rb for RNA and DNA, respectively. The kinetics of binding was also studied. The dose-response relationship obtained is linear in a concentration range of 0.025 to 0.5 microM 9-OH-NME. Furthermore, we demonstrated that the covalent binding of 9-OH-NME to DNA is not repaired during a period of 40 h (during this period, the cell population has undergone two doublings). The nonhydroxylated and non-antitumoral derivative of 9-OH-NME, N2-methylellipticinium, is 20 to 30 times less active in terms of covalent binding to nucleic acids, compared to the antitumor compound 9-OH-NME. The implication of the covalent binding of 9-OH-NME is discussed with respect to its mechanism of action.

Alkaloids↗

How can iron salts mediate the degradation of nucleos(t)ides by elliptinium acetate via free-radicals?

Elliptinium acetate (NSC 264137) is an antineoplastic agent currently used in anticancer chemotherapy. We report here the first evidence that this drug is able to modify DNA models via a redox process with iron salts. In presence of iron (III) salts, EDTA and H2O2, 9-OH-NME degrades deoxyguanosine. The two main products are guanine and 8-hydroxydeoxyguanosine which result from the formation of hydroxyl radicals. The biological implications of this phenomenon are briefly discussed.

Alkaloids↗

Covalent binding of the antitumor agent N2-methyl-9-hydroxy-ellipticinium acetate (NSC 264137) on RNA and poly A in vitro.

The antineoplastic compound N2-methyl-9-hydroxyellipticinium (9-OH-NME) is able to bind to different biological molecules after an oxidative activation by horseradish peroxidase and hydrogen peroxide. In this study, the efficient covalent binding in vitro of 9-OH-NME onto RNA and poly A is described. The phenomenon is analyzed by different HPLC methods and the yield of binding is determined using [3H]9-OH-NME. For an initial ratio drug per nucleotide of 0.07, the rb obtained (ratio of drug bound per nucleotide) of 0.026 for RNA and 0.044 for poly A, which represent respectively a yield of 40% and 60% for the drug fixation onto these macromolecules. These facts demonstrate the high electrophilicity of para-quinone-imine derivatives in ellipticinium series.

Alkaloids↗

Metabolism of the anti-tumour drugs N2-methyl-9-hydroxyellipticinium acetate (NSC 264137) and N2-methyl-9-hydroxyolivacinium acetate in the rat: preliminary identification of biliary 9-(O)-glucuronide and 10-(S)-glutathione conjugates.

The metabolites of the two anti-tumour drugs, N2-methyl-9-hydroxyellipticinium acetate (9-OH-NME, NSC 264137) and N2-methyl-9-hydroxyolivacinium acetate (9-OH-NMO), in bile of i.v.-treated rats have been studied. Three products have been identified in the bile: the unmetabolized drug (17% excreted products for ellipticinium, 3% for olivacinium derivative); a major metabolite, the corresponding 9-(O)-glucuronide (80 and 96%, respectively) and a minor metabolite, a possible 10-(S)-glutathione conjugate (3 and 1%). The elimination yield of these three products excreted over a period of 12 h represents 36% (ellipticinium) and 74% (olivacinium) of the administered dose. The detection of glucuronide and glutathione conjugates of these pyridinium derivatives was possible by direct injection of bile on to h.p.l.c. without prior extraction with organic solvents, in which these polar metabolites are poorly soluble. Metabolites were tentatively identified by the comparison of h.p.l.c. behaviour (retention times and u.v. absorption ratios) with those of reference samples. Reference conjugates have been prepared by chemical synthesis for the 9-(O)-glucuronides and by biosynthesis for the 10(S)-glutathione derivatives. The detection of the GSH conjugates in bile can be considered as the first experimental evidence of the involvement of oxidative activation in vivo of these ellipticine and olivacine derivatives.

Alkaloids↗