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P Lechat

Publications and source records attributed to P Lechat.

At least 163 records · Page 9Linked to original sources
PubMed1984

[Modification of the growth of chondrocytes by the action of concanavalin A].

The effects of Concanavalin A have been assessed on the growth of articular cultured chondrocytes. A differential action in relation with cellular density has been observed. Concanavalin A (0.02, 0.2 and 2 micrograms/ml) exerted a stimulating effect on low density cultures, whereas it depressed the cell growth curve with high cell density cultures, especially at the concentration of 2 micrograms/ml. Such a discrepancy in the behaviour of cells related to the density does not seem to have been previously observed with chondrocytes. It could be explained by a modification of the accessibility of Concanavalin A receptors.

Animals↗
PubMed1984

[Endocavitary electric shock. Problems related to equipment].

Endocavitary catheter ablation is a new method of treating cardiac arrhythmias. It may be used indirectly, interrupting conduction through the His bundle in supraventricular arrhythmias, or directly by altering the arrhythmogenic substrate to prevent ventricular tachycardia or fibrillation. We have observed, together with other workers, that changes in the electrical properties of the catheters used to deliver the endocavitary electrical discharge. This was unexpected as the shock was delivered through a unipolar electrode with the indifferent electrode placed on the patient's back. An analysis of the morphology of the discharge impulse in intensity and voltage at increasing energy values showed that the unconnected electrodes of the multi-electrode catheter were raised to approximately the same voltage as the indifferent electrode. The change in electrical properties of some catheters was therefore the result of an insulation defect between the conducting wires leading to the electrodes. A study of the rupturing voltage of 32 USCI endocavitary catheters showed that 5 were able to sustain repeated shocks of 2 Kv and that 3 were able to sustain 3.5 Kv. The insulation of Cordis catheters was good but problems were encountered due to the resistance of the wires leading to the electrodes which dissipated an abnormally high amount of energy, so reducing the energy actually reaching the myocardium. These observations may explain the inconsistency of results obtained by different groups performing endocavitary catheter ablation with material not designed specifically for this purpose.

Arrhythmias, Cardiac↗
PubMed1984

Effect of indomethacin on collagen biosynthesis by rabbit articular chondrocytes in monolayer cultures.

The influence of indomethacin on collagen biosynthesis in rabbit articular chondrocyte monolayer cultures was studied. Two applications within the space of three days of therapeutic doses (10(-5) or 10(-6)M), as well as repeated applications four days running of lower doses (10(-8) or 10(-10)M), increased the biosynthesis of both collagen and non-collagen proteins. Two applications of higher doses (10(-3) or 10(-4M) decreased DNA synthesis and inhibited both collagen and non-collagen protein biosynthesis. These results might well be considered in connection with the adverse reactions observed in some patients with long-term use of indomethacin.

Animals↗
PubMed1984

[Hemodynamic effects of ARL 115 in left ventricular insufficiency].

ARL 115 has vasodilator and positive inotropic properties which justify its use in heart failure. The effects of this drug were studied in 8 patients with advanced myocardial failure (7 cases of primary cardiomyopathy and 1 case of ischaemic cardiomyopathy) undergoing diagnostic cardiac catheterization, 15 minutes after angiocardiography. The cardiac output pressures were measured and the M mode electrocardiogram was recorded under basal conditions and following an infusion of 1 mg/kg of ARL 115 over 10 minutes. An improvement was observed in 7 cases, with an increase in the cardiac output and a decrease in the left ventricular diastolic pressure (p less than 0.05). There was no significant modification in the heart rate and there were no side effects. In one case, an abrupt fall in the diastolic pressure led to a decrease in the cardiac output. The arterial and venous vasodilator properties were demonstrated in every case, but a positive inotropic action (increase in the dp/dtmax and modification of the end-diastolic pressure: dimension ratio) was demonstrated in only two cases. The absence of positive inotropic action in the 6 other cases could be due to the advanced myocardial deterioration in these patients or to a delay in the positive inotropic effect in relation to the vasodilator effect.

Adult↗
PubMed1984

Reversal of lethal digoxin toxicity in guinea pigs using monoclonal antibodies and Fab fragments.

To extend the potential application of digoxin-specific immunoglobulin (Ig) (Fab) fragments for the reversal of advanced digitalis intoxication, monoclonal digoxin-specific antibodies were obtained by fusion of myeloma cell lines with spleen cells from mice immunized with a digoxin-serum albumin conjugate. The monoclonal antibody from the cell line designated Dig 26-10 had high affinity (KA = 5 X 10(9) M-1) and specificity for digoxin and was tested for its efficacy in the reversal of advanced, otherwise lethal digoxin toxicity in guinea pigs given a loading dose of 500 micrograms of digoxin per kg b.wt. i.v. followed by continuous infusion of digoxin at 10 (IgG-treated group) or 50 (Fab-treated group) microgram/kg/min. Control animals given nonspecific rabbit or mouse Igs after the onset of digoxin-toxic ventricular arrhythmias all died. Administration of monoclonal digoxin-specific antibody as intact IgG in doses stoichiometrically equivalent to the digoxin dose fully reversed digoxin toxicity in six of eight animals and prolonged survival somewhat in the remaining two animals. Fab fragments from the Dig 26-10 monoclonal antibody were even more effective, with rapid reversal (mean time 7 min) of all arrhythmias and survival of all animals so treated. We conclude that murine monoclonal antibodies and their Fab fragments are capable of reversing advanced and otherwise lethal digoxin-induced arrhythmias in a guinea-pig experimental model and offer potential advantages over polyclonal antibodies in the management of this clinically important problem.

Animals↗
PubMed1983

Depressed isoprenaline vascular response in endotoxic rats.

The injection of a sublethal dose of E. coli endotoxin (0127 B8) to intact rats (2 mg/kg i.v) or adrenalectomized rats (0.01 mg/kg i.v.) depressed hypotensive responses to isoprenaline (0.2, 0.4, 0.8 microgram/kg i.v.) for at least 4 h following endotoxin injection. These findings evidence an early (under 1 h after administration) and long-lasting (over 4 h) depression of the vascular response to isoprenaline in endotoxic rats. This depression was not related to catecholamine adrenal discharge or to the hypotensive and lethal effects of endotoxin.

Adrenalectomy↗
PubMed1983

DNA flow cytometric analysis of monogranulocytic colony forming cells from mouse bone marrow in vitro.

An adaptation of a previously reported flow cytometric technique is described. This technique was applied to study the DNA distribution of mouse granulocyte-macrophage colony forming cells (GM-CFc) grown in a methyl cellulose culture system. This method involved the collection of cell clusters and colonies from the methyl cellulose culture medium for the subsequent determination of DNA content. The DNA content of the homogeneous GM-CFc suspensions was determined by applying a modification of the propidium iodide staining procedure described by Crissman et al. The relative percentage of cells in G0 + G1, S, and G2 + M stages of the cell cycle was calculated by applying mathematical analysis to the resulting DNA histograms. This method could be useful in studying the effects of drugs on GM-CFc kinetics.

Animals↗
PubMed1983

Effects of donor's age on growth kinetics of rabbit articular chondrocytes in culture.

The in vitro proliferative capacity of articular chondrocytes derived from young and old rabbits was investigated to examine if the modifications incurred can be related to the in vivo aging. Determinations were made of the cartilage cell density, cell volume, cell number at confluency, plating efficiency, growth curve and DNA content distributions. The old donor cells were characterized by a decline in all the parameters of cartilage growth studied: cell number at confluency, cell replication rate (from 20 h to 45 h) as well as an increase in cell volume. The mean cycle time in vitro increased from 17.5 h compared to 27 h during in vivo aging, essentially because of an elongation of the G1 phase. Chondrocytes derived from young and old donors may be an appropriate model system for studying the in vitro effects of drugs on rheumatoid diseases as a function of in vivo aging.

Aging↗
PubMed1983

Comparison of the chronotropic effect and the cyclic AMP accumulation induced by beta 2-agonists in rat heart cell culture.

1 The chronotropic response and the variation in cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation induced by isoprenaline and six beta 2-selective agonists (fenoterol, salmefamol, soterenol, zinterol, salbutamol and formoterol) were analyzed on cultured heart cells of the rat. 2 The compounds elicited an enhancement of the frequency, but the time course of the variation of the beating rate was not identical for all of them. A rapid onset was observed for isoprenaline, zinterol and formoterol while it was slower for fenoterol, salmefamol and salbutamol. 3 In contrast with isoprenaline, the beta 2-selective agonists gave concentration-beating frequency curves which were not sigmoidal. Their effects extended up to a concentration of 5 to 6 orders of magnitude. Nevertheless, the concentration at which the maximal effect occurred and the intrinsic activities of the various compounds agrees better with the responses observed on guinea-pig atria than with those on trachea. 4 All the beta 2-selective agonists increased the accumulation of cyclic AMP in rat heart cells with a maximal effect at 10(-5)M or less. The effects of beta 2-agonists on cyclic AMP production showed some analogies with those on beating frequency of the heart cells. The increase in cyclic AMP accumulation induced by beta 2-agonists also corresponded to their chronotropic effects on guinea-pig atria. Thus, the correlation coefficient between the inverse of the log of the concentration producing the half maximal cyclic AMP accumulation in cultured heart cells and the pD2 values on guinea-pig atria was 0.93. 5 It is concluded that, in contrast to what was observed in other models, the beta 2-selective agonists induce an increase in the production of cyclic AMP in rat heart cells. Furthermore, the effects of the beta 2-agonists on cyclic AMP accumulation and on beating rate in the heart cells may correspond with their beta 1-adrenoceptor potencies.

Adrenergic beta-Agonists↗
PubMed1983

Active transport and inotropic state in guinea pig left atrium.

Although the positive inotropic effect of cardiac glycosides correlates well with inhibition of Na+ pump activity in many preparations, digitalis at low concentrations (10(-9) to 10(-8) M) may produce an apparent stimulation of monovalent cation transport in isolated intact myocardium or produce an inotropic effect that does not correlate with pump inhibition. Digitalis is known to modify tissue metabolism of endogenous neurotransmitters that may affect inotropic state, Na,K-ATPase activity, and K+ permeability. We examined the interactions of low concentrations of ouabain with adrenergic and cholinergic influences in isolated guinea pig left atria stimulated at 3.3 Hz in which inotropic state and monovalent cation transport (measured as 86Rb+ uptake) were assessed simultaneously. Ouabain (10(-9) M) stimulated Rb+ transport (+25%) without an inotropic response; the stimulatory effect on transport was abolished by propranolol or atropine pretreatment. In atria pretreated with atropine, 10(-8) M ouabain produced a small positive inotropic effect (+10%) without measurable associated Na+-K+ pump inhibition. This inotropic response was abolished in catecholamine-depleted atria. Ouabain (10(-7) M) always produced a positive inotropic response (about +25%) independent of catecholamine depletion, beta-adrenergic blockade, or muscarinic blockade, but Rb+ uptake inhibition was observed only in beta-adrenergically-blocked atria. In all preparations, ouabain concentrations greater than 10(-7) M caused an inotropic response associated with pump inhibition. At concentrations 3 X 10(-7) M and higher, mechanical toxicity was observed in all preparations except those pretreated with propranolol. Incubation with low concentrations of ouabain did not modify the inotropic response to isoproterenol. At concentrations of isoproterenol sufficient to stimulate Rb+ transport by 25%, there was a large (+80%) inotropic response. We conclude first, that, in guinea pig atria exposed to ouabain, the mechanism as well as the extent of inotropic response and of monovalent cation transport modification is concentration dependent, second, that at low concentrations (1-10 X 10(-9) M), in vitro inotropic and monovalent cation transport responses are in part mediated by an effect of ouabain on endogenous neurotransmitters; and third, that in this preparation at concentrations between 10(-9) and 10(-7) M ouabain, monovalent cation transport as measured by tissue 86Rb+ uptake does not correlate with inotropic response.

Animals↗
PubMed1983

[Direct cardiac mechanism of action of digitalis glycosides].

The direct cardiac mechanism of action of digitalis remains obscure. The inhibition of membrane ATP-ase seems to correlate with the increase in free intracellular calcium at the contractile sites during membrane depolarization. Two mechanisms may explain this phenomenon: increase in the sodium-calcium exchange or labilisation of the calcium pool bound to the internal wall of the sarcoplasmic reticulum. Digitalis toxicity occurs when the sodium pump is inhibited to such an extent that cellular homeostasis cannot be maintained. The intracellular calcium overload is responsible for the increased automaticity of the automatic fibres by oscillations of the membrane potential, added to the spontaneous slope of diastolic depolarisation.

Animals↗
PubMed1983

In vivo effects of indomethacin and cyclophosphamide on CFU-GM proliferation and cyclic nucleotide levels in bone marrow of mice.

The effects of indomethacin (6 mg/kg daily, orally, for 4 days) or cyclophosphamide (150 mg/kg, a single dose, intraperitoneally) on myelopoiesis were studied in mice. A hyperplasia of the committed stem cell compartment (rise in the recognizable myeloid precursors, increase of both colony forming capacity and number of CFU-GM in S-phase) associated to an increase of cyclic AMP and GMP amounts in bone marrow cells of treated mice were observed. These results suggest a possible relationship between the in vitro enhancement of proliferative activity of CFU-GM and the in vivo increase of both cyclic nucleotide levels in medullary environment.

Animals↗
PubMed1983

Proliferation kinetics of rabbit articular chondrocytes in primary culture and at the first passage.

The in-vitro proliferation kinetics of young rabbit articular chondrocytes were compared in primary culture and at the first passage. The growth curves labelling and mitotic indices, percentage labelled mitosis (PLM) curves and DNA content distributions by flow-microfluorometric analysis during a 7-day growth period were determined in both cases. The length of the cell cycle and the doubling time calculated from the exponential part of the growth curve were quite similar: Tc = 19 hr and Td = 20 hr for the primary culture, Tc = 17 X 3 hr and Td = 20 hr for the first passage. However, the growth curve and the DNA distribution during the 7-day period showed some differences. The duration of the lag period studied by the growth curve was longer in the primary culture than at the first passage. This phenomenon was also observed using the FCM analysis. The growth fraction determination on the second day of culture was in accordance with the lower proliferation capacity of the cells in primary culture. These data suggest that it would be better to study growth kinetics and drug modifications in articular chondrocytes at the first passage than in primary culture.

Animals↗