Search PubMed⌕ Search

Biomedical subjects

G Renault

Publications and source records attributed to G Renault.

At least 37 records · Page 2Linked to original sources
PubMed1987

Sequence effect on alkali-sensitive sites in UV-irradiated SV40 DNA.

Ultraviolet light at 254 nm induces various kinds of DNA damage. We have located and quantified the pyrimidine (6-4) pyrimidone photoproducts along three hundred and forty two nucleotides of SV40 DNA. The level of photoproduct induction varies greatly according to the position on the DNA, but unlike what happens with pyrimidine dimers, the very adjacent nucleotides do not play a major role in the frequency of formation. A new alkali-sensitive site has been found on the ACA sequence after UV irradiation. This complex lesion is insensitive to the T4 endonuclease V and the E. coli photolyase, and may be involved with mutagenesis.

Bacterial Proteins↗
PubMed1987

In vivo exposure to four ellipticine derivatives with topoisomerase inhibitory activity results in chromosome clumping and sister chromatid exchange in murine bone marrow cells.

A single dose of 9-hydroxy-ellipticine, 2-N-methyl-9-hydroxy-ellipticine, 9-fluoro-ellipticine, and 9-amino-ellipticine (5 to 10 mg/kg body wt, ip) resulted in murine bone marrow toxicity as shown by chromosome clumping, chromatid aberrations, and micronuclei formation. An increase in sister chromatid exchanges (SCE) was also observed. These effects are most likely directly related to the topoisomerase inhibitory effect of these drugs since topoisomerase II is involved in the separation of intertwined chromosomal DNA molecules during mitosis as well as being a mediator of DNA exchanges. The two antitumor drugs 2-N-methyl-9-hydroxy-ellipticine and 9-hydroxy-ellipticine were most genotoxic with chromosome abnormalities occurring in 33-95% of the cells and SCE on the order of 12.3 to 19.2 events per cell. Both of these drugs show high topoisomerase II inhibitory activity in vitro. In contrast, 9-amino-ellipticine and 9-fluoro-ellipticine were less genotoxic with chromosomal abnormalities occurring in 14-17% of the cells and SCE on the order of 7.1 to 7.7 events per cell. These two derivatives are both inactive toward experimental tumors and show less topoisomerase II inhibitory activity in vitro. Our results suggest that the ellipticine drugs owe at least some of their cytotoxicity to their genotoxic effects, which seem to be mediated through interaction with topoisomerase II.

Alkaloids↗
PubMed1987

NADH in situ laser fluorimetry: effect of pentobarbital on continuously monitored myocardial redox state.

NADH laser fluorimetry was applied to in situ monitoring of pentobarbital overload effect on myocardial redox state in rats. Experiments were carried out on open-chest rats anesthetized with pentobarbital. Use of very thin optical probes allowed measurements of NADH fluorescence directly within the myocardial wall. Quantitative analysis of fluorescent and backscattered light signals was made possible on-line. In 8 animals, a slow IV infusion of 6% pentobarbital (2 mg.min-1 for 10 min) induced an average twofold increase in NADH fluorescence, with constant return to baseline level prior to injection after a maximum period of 50 min. Thus, pentobarbital overload strongly affects the myocardial energetic state, and this effect was precisely evaluated with NADH fluorescence monitoring. In situ-monitored myocardial redox state variations during pentobarbital infusion can constitute a reference for similar studies on pharmacological agents aimed at protecting tissues against ischemic biochemical damages.

Animals↗
PubMed1987

[Study of myocardial metabolism of NADH by laser fluorimetry during cardiac catheterization].

Laser fluorimetry of reduced nicotinamide-adenine-dinucleotide (NADH) p6 a new technique used for in situ and real-time study of myocardial metabolism. We have evaluated its applicability to clinical situations in 5 patients undergoing haemodynamic exploration. An optic fibre was inserted in a catheter the end of which was positioned in the postero-diaphragmatic part of the left ventricle. The optic fibre was connected to a Cilas-Alcatel fluorimeter. Variations in fluorescence were studied during variations in left ventricular end-diastolic pressure (LVEDP) and during coronary arteriography. An increase in LVEDP resulted in a slight increase in NADH, but when the LVEDP was reduced by a nitroglycerin infusion, NADH fell significantly below baseline values in patients with coronary disease. This effect was most probably due to redistribution of the coronary blood flow from healthy territories to ischaemic territories. In patients without significant coronary stenosis, NADH was not modified by an injection of 10 ml of contrast medium into the right coronary artery. In contrast, in patients with severe stenosis NADH fluorescence significantly increased during the injection, reflecting the ischaemia or myocardial anoxia induced by the contrast medium. NADH laser fluorimetry therefore seems to be promising as a means of exploring myocardial metabolism during cardiac catheterization.

Cardiac Catheterization↗
PubMed1987

[The use of laser fluorometry of NADH in cardiology].

In this paper the first results of experimental studies of myocardial energy metabolism conducted in situ by laser fluorimetry are described. With this method the myocardial oxygen uptake is determined by measuring the fluorescence of NADH (reduced nicotinamide adenine dinucleotide). The equipment required consists of pulsed laser beams in the ultraviolet (337 nm) and visible (586 nm) spectra, very thin catheters with a single optic fibre, and an original digital data processing technique. The first applications envisaged concern: 1. pharmacological studies, notably evaluation of the protective effect of drugs against ischaemia; 2. evaluation of revascularization procedures in emergency surgery, notably assessment of reversibility of the ischaemic lesions; 3. monitoring of myocardial protection during cardiac surgery.

Cardiovascular Agents↗
PubMed1986

[Diagnosis of cellular respiratory arrest by NADH laser fluorimetry. Applications in heart surgery and in experimental pharmacology].

The continuous measurement of intratissular NADH concentration allows early detection of cellular respiration arrest during clinical situations, i.e. allows a non-destructive, in situ, continuous measurement of ATP formation. This detection enables the physician or surgeon to intervene during a phase of cellular respiration arrest, before structural cellular alterations occur, thereby preventing potential tissular necrosis. The method has now been validated in experimental cardiac surgery for the monitoring of myocardial preservation techniques during cardiopulmonary by-pass, and in cardiac pharmacology, for analysis of drugs' effects on myocardial energetic metabolism. Its industrial development is currently under way. Preliminary investigation strongly suggests the vast potential of this diagnostic method in both clinical and experimental fields.

Adenosine Triphosphate↗
PubMed1985

In situ monitoring of myocardial metabolism by laser fluorimetry: relevance of a test of local ischemia.

We have developed a hypoxia test by local ischemia, to be performed with a special probe adapted to an in situ NADH laser fluorimeter. Local ischemia is produced by pressurization on the organ surface in an area of approximately 0.2 mm2. In order to assess the method on open-chest rat hearts (ten), we used the following protocol: local ischemia tests (three), global anoxia (100% N2 ventilation), superimposition of local ischemia to global anoxia, and local ischemia tests during the period just prior to death and immediately thereafter. Three different responses were observed: large amplitude of compensated fluorescence (Fo) increase, medium amplitude of Fo increase, and no Fo increase. These responses were related to the metabolic state prior to the test (States 3, 4, and 5 of Chance's nomenclature). We have thus demonstrated the possibility of very rapidly determining the in situ NADH degree of reduction, without a destructive assay. Such a parameter may be of great relevance in heart surgery, as it might allow detection of potentially harmful situations, thereby enabling early and appropriate treatment.

Animals↗
PubMed1984

[In situ evaluation of tissue metabolism by laser fluorimetry].

Laser fluorimetry is a new technique which provides continuous information on tissue metabolism in situ and without destruction. For the moment, it is mainly applied to the study of changes in redox gradients in various organs, including the heart, brain, liver, kidney and skeletal muscle, in cases with imbalance between oxygen supply and oxygen consumption. Other metabolisms, such as that of the crystalline lens with incipient cataract, can also be investigated by this technique.

Animals↗
PubMed1984

In situ double-beam NADH laser fluorimetry: choice of a reference wavelength.

A double-beam laser fluorimeter, using a single optical fiber to guide the lights, was constructed for in situ and on-line monitoring of NADH concentration [( NADH]) from normally blood-perfused living tissues. The device was tested on an isolated blood-perfused rat heart system to determine the most efficient reference wavelength for the compensation of the hemodynamic artifact induced by blood circulation in the tissues on the fluorescence measure; 586 nm was found to be an accurate reference wavelength, and a mathematical relationship was established that allowed the digital treatment of the measured fluorescence to give a signal (compensated fluorescence) that varied only with [NADH] in the volume of tissue investigated.

Animals↗
PubMed1984

Performance of hypothermic isolated rat heart at various levels of blood acid-base status.

The effects of respiratory-induced pH variation on mechanical function and myocardial oxygenation of isolated, blood-perfused working rat hearts were studied in hypothermia (26 degrees C) and compared with control values (37 degrees C). In these experiments, the change of plasma pH during hypothermia was parallel to the change in pH of neutral water. At 37 degrees C, pH was varied from 7.15 to 7.62; heart rate increased with pH, both cardiac output and external work remaining unaltered. An increase in pH induced a decrease in coronary flow and an increase in the O2 arteriovenous difference. In hypothermia, hemodynamic performance and myocardial O2 consumption decreased proportionately with no change in cardiac efficiency. At 26 degrees C, the cardiac capacity to react to acid-base variations (pH from 7.34 to 7.86) was preserved, i.e., heart rate increased with pH. As at 37 degrees C, regulation of both coronary flow and myocardial oxygenation was maintained. The present data suggest that the myocardial function of a working isolated rat heart undergoing hypothermia was also preserved. Moderate variations in extracellular acid-base status during hypothermia did not impair either myocardial function or the O2 supply-to-demand ratio.

Acid-Base Equilibrium↗
PubMed1982

Kinetics of induction of sister-chromatid exchanges by X-rays through two cell cycles.

V79 Chinese hamster cells were exposed to X-rays at various times through the two cell cycles required to obtain harlequin-stained chromosomes. A two-fold SCE enhancement was found between the first and the second G1 phase when BrdUrd was incorporated during the first S phase only. This BrdUrd effect was not found when MNNG was used. Furthermore, the kinetics of SCE and aberrations were different, suggesting two separate mechanisms for their formation: SCE activity takes place when DNA damage occurs before the DNA replication, and aberration activity when the DNA damage occurs chiefly after the DNA replication.

Animals↗