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Biomedical subjects

C Pasquier

Publications and source records attributed to C Pasquier.

At least 73 records · Page 4Linked to original sources
PubMed1994

Modulation of the expression of the granulocyte adhesion molecule, CR3, by percutaneous transluminal coronary angioplasty and contrast media.

RATIONALE AND OBJECTIVES: The effects of percutaneous transluminal coronary angioplasty (PTCA) and iodinated contrast media on the functional state of polymorphonuclear leukocytes (PMN) were determined; the expression of the PMN adhesion molecule, CR3, was assessed. METHODS: CR3 expression was measured by flow cytometry in whole blood samples in vivo, before and after PTCA (n = 17) or coronary angiography (n = 16); and in vitro, before and after incubation of PMNs with iodinated contrast media (n = 5). RESULTS: CR3 expression (mean +/- standard error of the mean, arbitrary units) decreased significantly after PTCA (221 +/- 25 to 168 +/- 21, P < .005) and coronary angiography (297 +/- 43 to 218 +/- 25, P < .05). In vitro, there was a dose-dependent decrease of CR3 expression and a significant and strong inverse correlation between CR3 expression and the contrast agent concentrations regardless of the type of contrast agent used. CONCLUSIONS: These data suggest that PTCA does not activate circulating PMNs, and that contrast media decrease CR3 expression. Whether this is related to the systemic adverse effects of contrast media remains to be clarified.

Angioplasty, Balloon, Coronary↗
PubMed1993

Oxidative damage to lysozyme by the hydroxyl radical: comparative effects of scavengers.

The hydroxyl radical (OH.) is a highly-damaging reactive oxygen species, given its high reactivity and the consequent generation of secondary free radicals. This study was aimed at determining the qualitative and quantitative aspects of OH. scavenging by pentoxifylline (Ptx, a methylxanthine), uric acid and thymine on the OH.-induced alterations of a protein, lysozyme. Lysozyme was inactivated by OH. with a yield of 6.5 mol OH./mol lysozyme; moreover, SDS-PAGE showed a loss of native lysozyme (14.4 kDa), the presence of dimer and trimer aggregates and characteristic fragmentation. Tryptophan fluorescence was lost before aggregation became detectable in terms of bityrosine formation. Increasing concentrations of OH. scavengers gave increasing protection of lysozyme activity. Although all three compounds scavenge OH. with high rate constants, their effects were different: uric acid and Ptx prevented aggregation and preserved enzyme activity, whereas thymine preserved activity but did not prevent aggregation. These differences appear to be related to the formation of reducing secondary radicals, underlining the importance of this mechanism in the effects of scavengers.

Free Radical Scavengers↗
PubMed1993

Expression of human cytomegalovirus immediate early protein IE1 in insect cells: splicing of RNA and recognition by CD4+ T-cell clones.

Recombinant baculoviruses containing the unspliced gene (Bac-IE1) and a truncated cDNA (Bac-EX4) of the immediate early protein 1 (IE1) of human cytomegalovirus (HCMV) were constructed. The recombinant proteins IE1 and EX4 were expressed in Sf 9 insect cells. Immunoblot analyses using a specific monoclonal antibody or human sera from HCMV seropositive subjects revealed that the IE1 protein had an apparent molecular mass of 71 kDa which was similar to that observed in both HCMV infected human fibroblasts and infected or transfected human astrocytoma cells. Furthermore, HCMV-specific CD4+ T cell clones proliferated in the presence of IE1 or of EX4 used as a control, and appropriate antigen presenting cells. Our data on the IE1 gene provide evidence that two introns can be properly spliced out in baculovirus infected insect cells. The expressed proteins should be useful in further studies on the immune response to the virus.

Animals↗
PubMed1993

Evidence for priming and activation of neutrophils early after coronary angioplasty.

OBJECTIVES: Percutaneous transluminal coronary angioplasty (PTCA) induces deep arterial wall injury and transient ischaemia. The aim of this study was to demonstrate that PTCA could result in priming or activation of the neutrophils and the complement system. METHODS: Blood was drawn from the coronary sinus before and immediately after PTCA in 7 patients and before and immediately after coronary angiography in 7 patients (to ensure that the changes observed after PTCA were not solely related to the angiographic procedure). Neutrophil priming was assessed ex vivo by whole blood chemiluminescence stimulated in vitro by formyl-methionyl-leucyl-phenylalanine, phorbol myristate and opsonized zymosan. Neutrophil activation was assessed by measurement of plasma lactoferrin. RESULTS: Whole blood chemiluminescence increased after PTCA, regardless of the stimulus used, while it did not after arteriography. After PTCA, lactoferrin increased 2-fold (p < 0.02) whereas after arteriography a non-significant increase was observed. Neutrophil count and adherence properties were not modified by either PTCA or arteriography. Total haemolytic complement (CH50), C3, C4 and B factor decreased slightly (7 to 16%) after both PTCA and arteriography. CONCLUSIONS: Early after PTCA, the neutrophil oxidative response, assessed by stimulated whole blood chemiluminescence, increased, suggesting a "priming" effect of PTCA on neutrophils. In addition, plasma lactoferrin levels increased, indicating neutrophil activation. Finally, there was a mild global activation of the complement system, most likely related to the contrast agent, and which may play a role in the "priming" process. Neutrophil priming and activation may participate in several phenomena occurring after angioplasty such as enhanced vasoconstriction and post-ischaemic myocardial dysfunction. In addition, it may participate in triggering local inflammatory processes.

Angioplasty, Balloon, Coronary↗
PubMed1992

Mechanism of lysozyme inactivation and degradation by iron.

The site-specific lysozyme damage by iron and by iron-catalysed oxygen radicals was investigated. A solution of purified lysozyme was inactivated by Fe(II) at pH 7.4 in phosphate buffer, as tested on cleavage of Micrococcus lysodeikticus cells; this inactivation was time- and iron concentration-dependent and was associated with a loss of tryptophan fluorescence. In addition, it was reversible at pH 4, as demonstrated by lysozyme reactivation and by the intensity of the 14.4-kD-band on SDS-PAGE. Desferal (1 mM) and Detapac (1 mM) added before iron, prevented lysozyme inactivation, while catalase (100 micrograms/ml), superoxide dismutase (100 micrograms/ml) and bovine serum albumin (100 micrograms/ml) gave about 30 to 40% protection by competing with lysozyme for iron binding. The denaturing effect of iron on lysozyme was studied in the presence of H2O2 (1 mM) and ascorbate (1 mM); under these conditions the enzyme underwent partly irreversible inactivation and degradation different to that produced by gamma radiolysis-generated .OH. Catalase almost fully protected lysozyme; in contrast, mannitol (10 mM), benzoate (10 mM), and formate (10 mM) provided no protection because of their inability to access the site at which damaging species are generated. In this system, radical species were formed in a site-specific manner, and they reacted essentially with lysozyme at the site of their formation, causing inactivation and degradation differently than the hydroxyl radical.

Catalase↗
PubMed1992

K562 cells produce an anti-inflammatory factor that inhibits neutrophil functions in vivo.

We have previously reported that K562, a chronic myelogenous leukemia cell line, releases a low molecular weight factor (6 to 8 Kd) that inhibits human polymorphonuclear neutrophil (PMN) adherence and adherence-related functions tested in vitro. We now report that this factor, which we have named K562 inhibitory factor (K562-IF), has potent anti-inflammatory activity in mice, associated with an inhibition of PMN functions. Its in vitro actions were less marked with mouse PMN than with human PMN. They included (1) an inhibition of both nonstimulated locomotion and locomotion induced by FMLP or serum; (2) an inhibition of the chemiluminescence induced by opsonized zymosan, but not that induced by phorbol myristate acetate or FMLP; (3) an inhibition of the degranulation stimulated by opsonized zymosan, as reflected by lactoferrin and lysozyme release; and (4) a decrease in arachidonic acid release and leukotriene B4 production by A23187-stimulated PMN. The in vivo actions of K562-IF after intraperitoneal injection included (1) an inhibition of subcutaneous PMN accumulation at the site of injection of opsonized zymosan (PMN accumulated neither outside the vessels nor intravascularly, as shown by means of histochemistry); (2) an inhibition of neutrophil accumulation in the peritoneum of mice having received sodium caseinate or opsonized zymosan intraperitoneally; and (3) lysozyme concentration in neutrophils having reached the peritoneum after opsonized zymosan treatment equal to that in blood, suggesting diminished release. PMN influx and degranulation in the peritoneum were reduced by 50% after 3 hours of treatment with 1 microgram of K562-IF (equivalent to the effect of 120 micrograms of prednisolone). Taken together, these results show that K562-IF is a potent anti-inflammatory agent that acts by inhibiting PMN functions.

Animals↗
PubMed1992

Effects of N-acetylcysteine on diaphragmatic function and malondialdehyde content in Escherichia coli endotoxemic rats.

We evaluated the effects of sublethal Escherichia coli endotoxemia with or without concomitant administration of N-acetylcysteine, an antioxidant agent, on diaphragmatic strength, endurance, and malondialdehyde (MDA) content in rats. One hundred ninety rats were inoculated subcutaneously on 2 successive days with 0.6 and 1.2 mg/100 g body weight of E. coli lipopolysaccharide respectively (E animals, n = 100) or saline (C group, n = 90). E and C animals were divided into two groups based on administration of endotoxin or saline alone (E group, n = 55; C group, n = 47, respectively) or endotoxin or saline plus N-acetylcysteine (1 g/kg body weight/day intraperitoneally) (E-NAC group, n = 45; C-NAC group, n = 43, respectively). Diaphragmatic strength was assessed in vivo 48 h after the first endotoxin or saline administration by measuring the transdiaphragmatic pressure (Pdl) generated during electrical stimulation of the phrenic nerves at 0.5, 10, 20, 30, 50, and 100 Hz. Endurance index was calculated as the percent ratio of Pdl generated after 30 s of phrenic stimulation at 10 Hz divided by the initial force. Diaphragmatic MDA (fluorometric technique) was measured 0, 6, 18, 30, 42, and 48 h after the first dose of endotoxin or saline. Pdl for 50 and 100 Hz was significantly reduced in Group E as compared with group C. This phenomenon was associated with a reduced endurance performance as assessed by a lower diaphragmatic endurance index in E as compared with C animals (90.9 +/- 4.2 versus 114.3 +/- 4.1 respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1991

Gamma and pulse radiolysis study of pentoxifylline, a methylxanthine.

Pentoxifylline (Ptx) is a tri-substituted purine with anti-inflammatory properties which are thought to be due, in part, to oxygen radical scavenging. This paper reports an investigation of the reaction of Ptx with the hydroxyl radical [OH.], superoxide anion, azide radical and hydrogen peroxide generated by pulse and gamma-radiolysis, which was carried out to determine the scavenging properties of Ptx towards oxygen radicals. The superoxide anion, azide radical and hydrogen peroxide did not react with Ptx, whereas OH. reacted rapidly. In gamma-radiolysis, the action of OH. on Ptx at pH 7.4 gave rise to an end-product separated by high-performance liquid chromatography and identified by nuclear magnetic resonance and mass spectrometry as C-8-OH-Ptx (yield 0.12 x 10(-6) mol J-1). The reaction of Ptx with OH. after pulse radiolysis at pH 7-7.4 occurred with a rate constant of (7.7 +/- 1.0) x 10(9) mol-1 s-1, forming time-dependent transient radicals. The initial spectrum (2 microseconds after the pulse) showed three maxima (310, 338 and 500 nm). A decrease in the absorbance around 500 nm and an increase around 310 nm reflected a first-order reaction, suggesting a unimolecular rearrangement. It was shown by redox titration that at least two OH-adducts were formed, one with reducing and the other with oxidizing properties. These results suggest that the reducing radical may be (C-8-OH-Ptx)(.).

Cobalt Radioisotopes↗
PubMed1991

The effect of cilazapril, a new angiotensin converting enzyme inhibitor, on peak and trough blood pressure measurements in hypertensive patients.

Cilazapril (CLZ) is a new, long-acting nonsulfhydril converting enzyme inhibitor (ACE-I). Its effect on peak and trough sitting diastolic blood pressure (SDBP) was studied in a total of 85 patients with uncomplicated, essential hypertension at three centers. After 4 weeks of a single-blind placebo (PLA) run-in period, patients whose SDBP was between 100 and 115 mm Hg, were randomized into active treatment with either PLA (n = 27), CLZ 2.5 mg (n = 29), or CLZ 5 mg (n = 29) once daily in a double-blind fashion for another 8 weeks. At the end of the PLA run-in and after 4 and 8 weeks active therapy, an hourly blood pressure (BP) profile during 1-10 and 21-24 h postdose was performed. The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinically significant for both CLZ doses in comparison with the PLA group. The peak/trough ratio after subtraction of the PLA effect was 62% for CLZ 2.5 mg and 59% for CLZ 5 mg. These results indicate that the dose regimen of CLZ 2.5-5 mg once daily is adequate and effective for 24 h.

Adult↗
PubMed1991

Quinine uptake by human polymorphonuclear neutrophils.

The antimalarial drug quinine has been shown to impair human polymorphonuclear leukocyte (PMN) functions. To gain insight into the mechanism of this phenomenon, we investigated quinine uptake by PMN with a fluorometric assay based on the fluorescence properties of this drug. After 30 min of incubation at 37 degrees C in the presence of 1 and 10 micrograms of quinine per ml, PMN-associated quinine reached 90 +/- 6 and 780 +/- 150 ng/2.5 x 10(6) PMN, respectively, giving a cellular-to-extracellular concentration ratio of 140 to 150. A steady state was reached within 5 min. Uptake was partially dependent on temperature, cell viability, and extracellular pH. Fractionation studies showed that 30 to 40% of the PMN-associated quinine was located in the particulate fraction. The efflux of PMN-associated quinine was rapid and complete when the incubation mixture was replaced by drug-free medium. These data suggest that several mechanisms are involved in the uptake of quinine by PMN, including a viability- and energy-independent process possibly related to reversible association of quinine to cell structures (particularly the membrane). Other mechanisms could involve trapping by protonation and/or active PMN transport systems. Thus, most of the quinine taken up by resting PMN is found in the soluble fraction of disrupted cells. This may partly explain the depressive properties of quinine.

Antimetabolites↗
PubMed1991

Phase II trial of copper zinc superoxide dismutase (CuZn SOD) in the treatment of Crohn's disease.

Bovine Cu Zn SOD was used during an 8 year period as an antiinflammatory drug in 26 patients with severe Crohn's disease (CDAI 300) usually after failure of corticotherapy or when this drug was discontinued because of side effects or infection. This was a phase II trial during which doses routes of administration and concomitant therapies were progressively modified. We obtained 73% good short term responses (judged upon CDAI and anatomic healing) and 82% positive results on long term evolution (the criteria were: i CDAI lower than 100 in between relapses, ii complete healing or notable improvement of lesions, iii no surgery needed, iv return to work. The acceptability was excellent with the free enzyme. Since the above described experience, published in Free Radical Biology and Medicine (1989, 7: 145-151), we used always the same treatment schedule (SOD 8 mg/day associated with Desferroxamine--500 mg subcutaneous every 2 days). The follow-up during the 87-89 period showed that 12 are in good health without any relapse, 9 experienced one or more relapses, and showed good responses upon resumption of treatment, 5 failed to respond to treatment, all part of the initial group on which SOD treatment had already failed, and among whom 3 were lost for follow-up before 1987, and two others took up another SOD treatment which also failed. 3 new patients (2 females, 1 male) were treated since then, and all 3 had positive results (one with disappearance of ileocoecal mass). The efficacy of SOD as an antiinflammatory drug in Crohn's disease needs to be confirmed by controlled trials.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

[Short- and long-term outcome of 250 patients admitted in surgical intensive care units after multiple injuries].

Two hundred and fifty polytrauma patients (mean age: 30 years) had been hospitalizated in the same trauma center, along a period of two years. Hospital mortality rate was 33% (11% in the first day). The mean I.S.S. of alive patients was 25, and 35 for dead patients. Long term survey was analysed by three questionnaires (before one year, between one and two years and after two years). Answer rate was about 80%. Sixty hundred p. cent of patients worked less than one year after multiple trauma, and 80% between one and two years; 75% noted that their family life was normal less than one year after injury; 80% presented sequelae two years after; they were subjective in 60% of cases. These sequelae did not interfere with family life or work. There was no parallelism between objective sequelae and duration of work stop in one side and gravity of lesions (I.S.S.) in other side.

Adult↗
PubMed1989

Metabolic action of N-methyl-D-aspartate in newborn rat brain ex vivo: 31p magnetic resonance spectroscopy.

N-methyl-D-aspartate (NMDA) is an agonist used to identify neuronal receptive sites for dicarboxylic amino acid neurotransmitters; NMDA receptors are implicated in neuronal damage of ischemic or hypoglycemic origin in newborns although involved mechanisms remain to be identified. In the present study, 31P magnetic resonance spectroscopy with fast (6/min) data acquisition was used in newborn rat brain slices to measure changes of intracellular phosphocreatine and nucleotide triphosphate levels following extracellular NMDA applications. The rapid exhaustion of phosphocreatine stores in 50% of the total population of brain cells was induced in all cases by application of NMDA (30-45 s, 25-100 mM). It was not reproduced by other excitatory agents: potassium ions (24.6 mM, 4 min), isobutylxanthine (1mM), muscarine (10 mM), serotonin (0.1 mM) or substance P (10 microM). Such an effect of NMDA was not modified after tetrodotoxin (1 microM) and was reduced by extracellular 2-amino-5-phosphonovalerate (50 microM) or magnesium ions (2.2 mM). However it did develop during NMDA-induce neuronal excitations and was reversible within 10-30 min. This action of NMDA was followed by an irreversible decrease of phosphorus metabolites if mitochondrial creatine kinase and adenosine triphosphatase were decoupled by atractyloside (50 microM). Experiments revealed a link between selective NMDA action at neuronal plasma membranes, neurotoxicity and energy production by mitochondria.

Animals↗
PubMed1989

Study of a delta-hydroxy ketone-hemiketal equilibrium by 2D-NMR exchange spectroscopy for the antibiotic grisorixin: involvement in cationic transport through membranes.

Study of a delta-hydroxyketone-hemiketal equilibrium in the polyether antibiotic grisorixin was performed with 2D-NMR spectroscopy. The efficiency of 13C chemical exchange spectroscopy for the assignment of 1H and 13C resonances, in the 2 forms, was shown, making possible a conformational investigation of both forms. This equilibrium was observed for grisorixin in solvents of varying polarity, such as CD2Cl2, CDCl3, CD3CN, or CD3OD, but not in C6D12 or C6D6. Other related antibiotics with the same terminal heterocycle were described only in the closed hemiacetalic structure. The low ionic fluxes measured in a bulk chloroformic membrane for grisorixin were explained by this equilibrium, which competed unfavorably with the cation capture process at the water-chloroform interface. This equilibrium would not be present in a phospholipidic bilayer membrane containing the ionophore, published experimental results are taken into account. The peculiar tautomeric equilibrium observed for grisorixin could be linked to the specific axial stereochemistry of the C7-C8 bond, which creates tension in the globular conformation.

Anti-Bacterial Agents↗
PubMed1989

[Brain stem auditory evoked potentials in children with partial seizures].

BAEP were recorded in 34 children with partial seizures. Epilepsy with rolandic spikes and occipital paroxysms were excluded. Results were then compared with data from subjects without neurological diseases. Twelve children presented abnormal responses. There were no relationship between results of BAEP and either number of seizures, duration of epilepsy or therapy. Eight of 13 children with complex partial seizures showed abnormal BAEP. Prognostic value of results is discussed. This study shows that Brain stem may be involved in the neuronal dysfunction observed during partial epilepsy.

Acoustic Stimulation↗
PubMed1988

Metabolic acidosis induced by N-methyl-D-aspartate in brain slices of the neonatal rat: 31P- and 1H-magnetic resonance spectroscopy.

1H- and 31P-magnetic resonance spectroscopy was used to monitor intracellular lactate, phosphorus metabolites and pH in superfused brain slices from 2- to 9-day-old rats. N-Methyl-D-aspartate (NMDA) (100 microM, 0.5-3 min) was applied in the extracellular magnesium-free perfusion medium. NMDA induced intracellular metabolic acidosis, i.e., an increase of freely mobile lactate levels and an 0.3 pH unit acidification. This was abolished when the extracellular glucose supply was reduced. Experiments also indicate that acidosis is not responsible for the cell damage resulting from activation of NMDA receptors in hypoglycemic conditions.

Acidosis, Lactic↗