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Biomedical subjects

J Robert

Publications and source records attributed to J Robert.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

[Erythrocyte phospholipids in Duchenne muscular dystrophy (author's transl)].

The different fractions of erythrocyte phospholipids determined in eleven patients suffering from Duchenne muscular dystrophy and in six possible or probable heterozygous carriers do not differ significantly from those observed in controls. Distribution of their fatty acids shows a reduced amount of palmitoleic acid (C16 : 1) in total fatty acids, in sphingomyelin and phosphatidylethanolamine. The same anomaly is observed, but less significant, in the heterozygous carriers. The C20 : 0 acid is increased in sphingomyelin. Some overlap occurs between results determined in hemizygous or in heterozygous carriers and in controls. These anomalies in fatty acid distribution, if confirmed, may help a better understanding of the pathogenesis of the disease and perhaps be useful to its detection.

Adolescent↗
PubMedDate not supplied

Proposals for concomitant use of several modulators of multidrug resistance in clinics.

Numerous modulators of multidrug resistance present a good in vitro activity which has not always been reproduced in vivo or in clinics. One reason is the fact that the plasma concentration required might exceed the maximum tolerated dose of modulator, due to its own toxicity. In addition, it has been suggested that the different modulators thus far identified might act on different sites of P-glycoprotein and eventually on different targets. It has been shown that the combination of verapamil and quinine, and of verapamil and cyclosporine A, behave synergistically in the circumvention of multidrug resistance. There is therefore a good rationale for the evaluation of protocols combining two different modulators to cytotoxic chemotherapy.

Cyclosporine↗
PubMedDate not supplied

Synthesis and evaluation of benzimidazole and imidazole compounds as potential aromatase inhibitors.

Several series of benzimidazole and imidazole derivatives have been synthesized and their biological activity evaluated. Their ability to inhibit human placental aromatase activity was tested in vitro. Ten of the tested compounds are more active towards aromatase than aminoglutethimide, the reference molecule. The most active compound XI is five times more potent in the same system. Compounds bearing an aryl group substituted by one or two halogen atom(s) (fluorine or chlorine) in position 4 or 2,4 respectively have also the most interesting activity.

Aromatase Inhibitors↗
PubMedDate not supplied

Left ventricular contractility after hypothermic preservation: predictive value of phosphorus 31-nuclear magnetic resonance spectroscopy.

Early graft failure accounts for a substantial portion of the mortality after heart transplantation. This factor underscores the need for the development of reliable methods for predicting graft performance and thus ensuring optimal clinical outcome. The aim of this study was to describe the link between myocardial metabolism evaluated throughout preservation with the use of phosphorus 31-nuclear magnetic resonance spectroscopy and ventricular contractility after reperfusion. Thirteen pig hearts were excised and preserved from 3 to 12 hours with clinical techniques. During preservation the hearts underwent phosphorus 31-nuclear magnetic resonance spectroscopy. After reperfusion, left ventricular contractility was evaluated with an isolated heart model undergoing isovolumetric contraction. Throughout storage, beta-adenosine triphosphate remained stable and intracellular pH and phosphocreatine decreased exponentially, whereas inorganic phosphate increased exponentially. Intracellular pH, phosphocreatine, inorganic phosphates measured at the onset of preservation, and intracellular pH and phosphocreatine measured at the end of preservation correlated significantly with the left ventricular contractility after reperfusion. We conclude that the metabolic state of myocardium at excision is especially important and that phosphorus 31-nuclear magnetic resonance evaluation of the heart during preservation appears to provide reliable indexes for predicting subsequent ventricular contractility after reperfusion.

Animals↗
PubMedDate not supplied

Relationships between DNA damage and growth inhibition induced by topoisomerase II-interfering drugs in doxorubicin-sensitive and -resistant rat glioblastoma cells.

We have evaluated the DNA breaks occurring after action of three topoisomerase II-interfering drugs (doxorubicin, etoposide and amsacrine) on a line of rat glioblastoma cells in culture and its doxorubicin-resistant variant. DNA breaks were quantified by alkaline unwinding in the presence of a dye exhibiting a quenching of fluorescence with single stranded DNA. The antiproliferative activity of the three drugs was compared to their ability to damage DNA. We have shown that at low exposure doses (up to the IC50 of the drugs), the same low level of DNA damage determined the same inhibition of cell growth in sensitive and resistant cells, but that at higher exposure doses the resistant cells developed special mechanisms allowing them to tolerate more DNA breaks than sensitive cells without lethal effects. The origin of this tolerance of resistant cells to DNA breaks might be due to special mechanisms of protection of genomic sites hypersensitive to topoisomerase II-mediated drug action, to alterations of topoisomerase II or to alterations of the molecular events leading to cell death after occurrence of DNA breaks.

Amsacrine↗
PubMedDate not supplied

Comparative evaluation of the intracellular accumulation and DNA binding of idarubicin and daunorubicin in sensitive and multidrug-resistant human leukaemia K562 cells.

BACKGROUND: Idarubicin is a new anthracycline, more potent in in vitro models than the common anthracyclines doxorubicin and daunorubicin. The intracellular accumulation and DNA binding of daunorubicin and idarubicin have been studied in human leukaemia K562 cells and their doxorubicin-resistant variant, which presents all features of multidrug resistance. METHODS: This was achieved by measuring the decrease of total drug fluorescence during short-term incubation of cell suspensions, directly in the cuvette of a spectrofluorometer; this quenching is due to intercalation of the drug into DNA and represents an evaluation of the active intracellular concentration of the drugs. RESULTS: Accumulation of both anthracyclines was reduced in resistant cells when compared to sensitive ones. Accumulation of idarubicin was significantly higher than that of daunorubicin in both cell types. The difference in anthracycline accumulation between sensitive and resistant cells was lower for idarubicin than for daunorubicin. Verapamil increased the accumulation of both anthracyclines in resistant cells, with a more pronounced effect for idarubicin. Preincubation of the cells with either drug did not influence the accumulation of the other one. CONCLUSION: It has been shown, with this very rapid technique, that the high potency of idarubicin could be explained, at least in part, by its high level of accumulation, both in sensitive and multidrug-resistant leukaemia cells. This is not due to a lack of activity of P-glycoprotein on idarubicin, but rather to an enhanced influx of this drug compared to daunorubicin.

Antibiotics, Antineoplastic↗