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Biomedical subjects

P Braquet

Publications and source records attributed to P Braquet.

At least 19 recordsLinked to original sources
PubMed1992

The vasoconstrictor action of big endothelin-1 is phosphoramidon-sensitive in rabbit saphenous artery, but not in saphenous vein.

The effects of big endothelin-1 and endothelin-1 on vascular reactivity were compared in isolated rabbit saphenous artery and vein. The contractile potency of endothelin-1 was three times higher in the vein than in the artery. In contrast, big endothelin-1 was two times more effective in the artery. Phosphoramidon (100 microM), a metalloproteinase inhibitor, antagonised the contractile action of big endothelin-1 in the artery but not in the vein. These data suggest that the biosynthetic pathway leading to the formation of endothelin differs in arterial and venous vessels.

Animals↗
PubMed1992

Ligation of CD23 triggers cAMP generation and release of inflammatory mediators in human monocytes.

Transduction through the CD23 molecule (Fc epsilon RII) was analyzed in normal human monocytes using monoclonal antibodies to CD23 (MHM6 and 135) and IgE/anti-IgE immune complexes. Monocytes expressing an increased amount of CD23 molecules were obtained by stimulation with IL-4 (30 U/ml). Anti-CD23 mAb as well as IgE/anti-IgE immune complexes were unable to induce any significant calcium mobilization [Ca2+]i in CD23-bearing monocytes whereas they elicited [Ca2+]i increase in B lymphocytes of the same donors. Despite their failure to induce calcium mobilization, the same CD23 ligands triggered a dose-dependent increase of intracellular cAMP, with a maximum 20 to 30 min after the onset of stimulation. This effect is mediated via CD23 inasmuch as: 1) F(ab)'2 fragments are as active as intact anti-CD23 mAb and 2) it is not observed in CD23- monocytes. The increase in cAMP was only partially altered in the presence of 1 microM indomethacin suggesting that it was not due to the release of PG. The possible role of CD23 in the activation of human monocytes was next documented by showing that anti-CD23 mAb and IgE/anti-IgE immune complexes induced the generation of IL-6 and of thromboxane B2 by CD23+ but not by CD23- monocytes. In addition, the IgE/anti-IgE-induced IL-6 production was potentiated in the presence of cAMP inducer such as the beta 2-adrenoceptor agonist salbutamol. These results indicate that ligation of CD23 induces cAMP generation in CD23+ human monocytes and that CD23 may regulate the IgE-dependent functions in normal human monocytes.

Acute-Phase Reaction↗
PubMed1992

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cytostatic activity of new synthetic anti-tumor aza-alkyllysophospholipids.

Alkyllysophospholipids are analogues of the naturally occurring 2-lysophosphatidylcholine which have been reported to have selective in vitro/in vivo anti-tumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of 2 newly synthetized aza-alkyllysophospholipids (AALPs), the BN52205 and the BN52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. We used 3 different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the antiproliferative activity of the 2 AALPs. By applying the biparametric analysis of 5'-bromo-2-deoxyuridine incorporation vs. DNA content we have been able to demonstrate that the 2 AALPs do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein vs. DNA content in isolated HT29 nuclei enabled us to exclude a block in the M phase of the cell cycle. Finally, stathmokinetic analysis enabled us to show that cytostatic activity of the 2 new AALPs is characterized by multiple "terminal points" as the drugs' action results in a G1 block, in a slow-down of the transition from late S to G2 followed by an accumulation of HT29 cells in the G2 phase of the cell cycle.

Adenocarcinoma↗
PubMed1992

Involvement of a phosphoramidon-sensitive endopeptidase in the processing of big endothelin-1 in the guinea-pig.

In anaesthetized and ventilated guinea-pigs, i.v. injection of 1 nmol/kg big endothelin-1 (big ET-1) did not evoke significant changes in pulmonary inflation pressure (PIP) and mean arterial blood pressure (MBP), whereas injection of the same dose of endothelin-1 (ET-1) induced marked and rapid bronchoconstrictor and pressor responses. Administered at the dose of 10 nmol/kg, big ET-1 provoked significant increases in PIP and MBP, which developed slowly and were long-lasting as compared to those evoked by ET-1. When big ET-1 was incubated for 45 min at 37 degrees C with alpha-chymotrypsin (2 mU/nmol) or pepsin (1 microgram/nmol) and then injected into guinea-pigs at the dose of 1 nmol/kg, marked bronchoconstrictor and pressor responses were observed, with kinetics similar to those noted after administration of the same dose of ET-1. The magnitude of the alpha-chymotrypsin- or pepsin-treated big ET-1 responses was similar to that induced by ET-1, incubated or not with the enzymes. Injected i.v. at the dose of 5 mg/kg, 5 min before the challenge, phosphoramidon almost totally inhibited the bronchoconstrictor and pressor responses induced by 10 nmol/kg big ET-1, whereas thiorphan (5 mg/kg) partially reduced the increase in PIP and exerted a minimal effect on the changes in MBP. Administered at the dose of 20 mg/kg per os, 1 h before i.v. administration of 10 nmol/kg big ET-1, enalapril maleate and captopril did not significantly alter the bronchoconstriction and the hypertensive response evoked by the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Tumor cell kinetics following antineoplastic ether phospholipid treatment.

Ether phospholipids are analogues of the naturally occurring 2-lyso-phosphatidylcholine that have been reported to have in vitro/in vivo antitumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of two ether phospholipids, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and 1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine, on a human tumor cell line derived from a colon adenocarcinoma, HT29. We have used three different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the antiproliferative activity of the two ether phospholipids. By applying the biparametric analysis, 5'-bromo-2-deoxyuridine incorporation versus DNA content, we have been able to demonstrate that ether phospholipids do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein versus DNA content in isolated HT29 nuclei has enabled us to exclude a block in the M phase of the cell cycle. Finally, the stathmokinetic analysis has allowed us to show that the cytostatic activity of the two ether phospholipids 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and 1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine is characterized by multiple "terminal points" as the drugs action results in a G1 block and in a slow-down of the transition from late S to G2, followed by an accumulation of HT29 cells in the G2 phase of the cell cycle.

Antineoplastic Agents↗
PubMed1992

Preparation of immunoaffinity mini-columns for the analysis of platelet activating factor (PAF) in biological samples.

Using an antibody to BN 52719, an analogue of platelet activating factor (PAF), immunoaffinity mini-columns for the separation of PAF from biological samples were prepared. Rabbits were immunized with BN 52719 and immunoglobulin G (IgG) from the antiserum was coupled with Sepharose 4B. The resulting suspension of the IgG-coated Sepharose 4B in 25 mM phosphate buffer (pH 6.9) was poured into a plastic mini-column (bed volume 2.0 x 0.8 cm). Stepwise elution of the column with methanol revealed that lyso-PAF is eluted with 20-30% methanol in water whereas PAF is eluted with 50-80% methanol. For the determination of PAF in biological samples, it is recommended that lipids are extracted from the samples and the extract, reconstituted in 20% methanol, is loaded on the column. The column is then washed with 50% methanol followed by elution of PAF with 80% methanol. A small amount of [3H]PAF is added to the samples for measurement of the recoveries of PAF during the procedures of extraction and elution. The PAF is then quantified by radioimmunoassay or bioassay. Employing the immunoaffinity mini-column and radioimmunoassay, the contents of PAF in macrophages and conditioned medium after stimulation with calcium ionophore A23187, or tumor promoters such as TPA and thapsigargin, were measured.

Animals↗
PubMed1992

Induction of nitric oxide synthase by lipoteichoic acid from Staphylococcus aureus in vascular smooth muscle cells.

Inducible vascular nitric oxide synthase accounts for the contractile impairment observed in endotoxemia. We provide evidence that lipoteichoic acid (LTA) from Staphylococcus aureus, a micro-organism without endotoxin, also induces nitric oxide synthase. Our study demonstrates that on endothelium-free rings of rat aorta. LTA-like lipopolysaccharide induces a loss of contractility restored by Methylene blue and NG-nitro-L-arginine-methyl ester (LNAME). Moreover in cultured vascular smooth muscle cells, LTA produces a dose-dependent increase in intracellular cyclic GMP which is antagonized by LNAME and prevented by dexamethasone.

Amino Acid Oxidoreductases↗
PubMed1992

PAF-acether induced arterial thrombosis and the effect of specific antagonists.

Platelet-vessel wall interactions and local thrombosis are investigated in vivo in a branch of the mesenteric artery of the guinea pig, using optoelectronic registration and ultrastructural control. Following an electrical challenge resulting in changes of cell membrane polarization, subsequent superfusion by PAF-acether or a stable analogue, (1-O-alkyl-2-N-methylcarbamyl-sn-glycero-3-phosphocholine, 10(-8) M focal concentration (f.c.)) for a restricted period results in endothelial cell retraction and bleb formation followed by platelet adhesion and the development of a thrombus which over time becomes invaded by leukocytes and eventually occludes the vascular lumen. It was demonstrated in a previous investigation that these phenomena are triggered by the generation of endogenous PAF-acether by the endothelial cells. Specific PAF-acether-antagonists, such as BN 52021 a ginkgolide, but also synthetic molecules, derivatives of the triazolo-pyridino-diazepine group (BN 50727, BN 50755 and BN 50789), significantly inhibit platelet-vessel wall interactions and thrombosis, but not the formation of blebs in the endothelial cells. Hydrogen peroxide (10(-5)M f.c.) not only primes the effect of PAF-acether, but is by itself capable of inducing thrombosis through a PAF-acether-mediated mechanism. Inhibition of acetyl hydrolase by PMSF (phenyl-methyl-sulfonyl-fluoride, 10(-5)M f.c.) invariably results in a significant enhancement of thrombosis, while conversely, inhibition of acetyl transferase by 27584 RP (4-(naphtylvinyl)pyridine hydrochloride, 10(-6)M f.c.) inhibits thromboformation indicating that the remodeling pathway is involved.

Acetyltransferases↗
PubMed1992

Oxidative stress in diabetic retina.

The authors describe the alterations usually associated with diabetic retinopathy. They concern the classical thickening of the basal membrane of retinal capillaries and the associated modification of retinal vessel permeability. These alterations correspond to the blood-retinal barrier disruption. The authors then discuss the participation of oxygenated free radicals in the pathogenesis of diabetic retinopathy. They report several experimental studies establishing such a participation and finally describe their own results obtained on a model of retinas isolated from alloxan-induced diabetic rats. After one month of evolution, the electroretinograms (ERG) recorded on isolated retinas from diabetic rats had an amplitude about 20% lower than the controls, whereas after two months of diabetes, this decrease was about 60%. Under these conditions, the authors tested the protective properties of Ginkgo biloba extract (EGb 761) on their model. They observed that in EGb-treated animals (100 mg/kg/day), the ERG had a significantly (p less than 0.001) greater amplitude than untreated animals after two months of diabetes evolution. In conclusion, the authors discuss the possible utilization of a free radical scavenger, such as EGb 761, in the prevention of the retinal impairment in diabetes.

Animals↗
PubMed1992

Cicletanine sulfate: inhibition of anion transport systems and natriuretic activity.

In contrast with cicletanine, its urinary sulfoconjugate metabolite (cicletanine sulfate) was active on membrane ion transport in human red blood cells. Cicletanine sulfate was a more potent inhibitor of the Na+ dependent [Cl-/HCO3-] exchanger (IC50 = 9 +/- 3 x 10(-5) mol/l; mean +/- SD of 4 experiments) than cicletanine (IC50 = 10(-3) mol/l). This inhibitory potency was intermediate between that of xipamide (IC50 = 2 x 10(-5) mol/l) and that of furosemide (IC50 = 2 x 10(-4) mol/l). Moreover, cicletanine sulfate exhibited modest inhibitory potency against the [Na+,K+,Cl-]-cotransport system (IC50 = 1 +/- 0.3 x 10(-3) mol/l; mean +/- SD of 4 experiments) and poor inhibitory activity against the [K+,Cl-]-cotransport system. Cicletanine sulfate was unable to modify the activity of Cl(-)-independent membrane carriers (Na+:H+ exchanger, Ca2+ pump, Na+:Li+ countertransport system and Na+,K+ pump). Following renal intraarterial administration in rats, cicletanine sulfate and not cicletanine, exhibited salidiuretic activity. In conclusion, the urinary sulfo-conjugate of cicletanine is an active anion transport inhibitor and natriuretic metabolite. In fact, this metabolite may be responsible for the salidiuretic action of cicletanine.

Animals↗
PubMed1992

Separate induction of human blood platelet aggregation or cytotoxicity by different concentrations of PAF-acether and thrombin.

Using decreasing concentrations of PAF-acether or thrombin, it was possible to observe on human platelets, first, aggregation, classically associated to activation, then , below a threshold, cytotoxicity towards Schistosoma mansoni larvae, proposed here as stimulation. These two activities appeared as distinct and antithetic. However, their induction might be the consequence of triggering of the same receptors with different intensity, since PAF-induced, but not thrombin-induced, cytotoxicity could be inhibited with specific PAF-antagonists BN 52021 and BN 52024 also known to inhibit PAF-induced aggregation. These results give credit to the hypothesis that haemostatic and cytotoxic properties of platelets are two distinct functions of these blood elements.

Animals↗
PubMed1992

Reversible or irreversible modification of [3H]PAF binding on rabbit platelet membranes differentiates various PAF receptor antagonists.

[3H]Platelet-activating factor (PAF) binding to rabbit platelet membranes was examined before and after 20 min preincubation at 25 degrees C in the presence of PAF, lysoPAF, or of five different PAF receptor antagonists (L 652731, BN 52021, WEB 2086, BN 52111 and BN 52115). When platelet membranes were not washed after preincubation with PAF or PAF antagonists, no significant specific binding of [3H]PAF was observed, which suggests full occupancy of the binding sites. When membranes were extensively washed, full recovery of specific [3H]PAF binding was attained with L 652731 and partial recoveries (60%, 55% and 30%) were reached with BN 52021, WEB 2086 and PAF, respectively; no recovery was seen with the dioxolanes BN 52111 and BN 52115. Scatchard analysis of the binding data indicated that no significant change in the dissociation constant (Kd) and maximum number of binding sites (Bmax) occurred after preincubation of platelet membrane with L 652731, whereas a reduction of Bmax was observed when PAF and BN 52021 were measured. When platelet membranes were preincubated with WEB 2086, Bmax and Kd significantly increased. The data suggest differing binding properties for PAF and the PAF antagonists. Some of the PAF antagonists may tightly bind to the PAF receptor site(s) and/or irreversibly modify or downregulate PAF recognition sites. Our results also suggest that the interaction of PAF receptor antagonists with PAF receptor can be divided into at least two components, namely a reversible component and an irreversible one.

Animals↗
PubMed1992

Ischaemia- and reperfusion-induced Na+, K+, Ca2+ and Mg2+ shifts in rat retina: effects of two free radical scavengers, SOD and EGB 761.

Using Sprague-Dawley rats with transient (90-min) regional ischaemia induced by retinal artery occlusion in the eye, we have shown that superoxide dismutase (SOD) and EGB 761 (IPSEN, France), two free radical scavengers, can dramatically reduce the reperfusion-induced sodium and calcium gains, and potassium loss in retinal tissue. Investigating whether this was a 'direct' protective effect, operating during reperfusion, or an 'indirect' effect arising from the action of SOD or EBG 761 on the tissue during ischaemia. SOD (15,000 U kg-1) and EGB 761 (100 mg kg-1) were added to the rats at the moment of reperfusion (after an ischaemic insult). Eyes were subjected to 90 min ischaemia followed by 4 and 24 hr of reperfusion, respectively. In the drug-free control group, 90 min of ischaemia resulted in an accumulation of retinal sodium (2-fold) and calcium (3-fold), and a loss of cell potassium (by 40%) and magnesium (by 40%). During the first 4 hr of reperfusion the ionic imbalance was unchanged, while after 24 hrs of reperfusion a normalization was observed and the ion content of the retina almost returned to their preischaemic values. SOD and EGB 761 treatment significantly reduced the reperfusion-induced ionic imbalance (magnesium was an exception) and improved the recovery of retinal ion contents. Our results indicate that the elimination of oxygen radicals by free radical scavengers may reduce the reperfusion-induced ionic imbalance and improve the ionic homeostasis in the injured retinal cells.

Animals↗
PubMed1992

Role of platelet-activating factor in hemodynamic derangements in an acute rodent pancreatic model.

Systemic hemodynamics were assessed in a model of experimental pancreatitis induced in rats by the retrograde injection of sodium deoxycholate, 40%, 1 mL/kg, in the pancreatic duct, using the radioactive microsphere technique before and 25 minutes after pancreatitis induction while blood pressure was stable (n = 10). A 55% decrease in cardiac out-put, a 14% decrease in heart rate, and a 3.3-fold increase in total peripheral resistances, without significant changes in blood pressure, were observed. Renal blood flow decreased by 68%. When rats were given BN-52021, a blocker of platelet-activating factor receptors (5 mg/h, IV; n = 13) coinciding with pancreatitis induction, no significant hemodynamic changes were observed. Animals treated with BN-52021 survived 89 +/- 10 minutes, whereas death occurred 67 +/- 5 minutes after pancreatitis induction in untreated rats (P less than 0.001). A different group of rats with pancreatitis showed higher blood levels of platelet-activating factor (0.28 +/- 0.06 ng/mL; n = 11) than control rats (0.16 +/- 0.03; n = 15; P less than 0.05). Very high levels of platelet-activating factor were found in peritoneal exudate from rats with pancreatitis. These data show an effective protective effect of BN-52021 on the hemodynamic impairment that follows pancreatitis induction, as well as a role of platelet-activating factor in these alterations.

Acute Disease↗
PubMed1992

Effect of cicletanine on reperfusion-induced arrhythmias and myocardial ion contents: a comparison with furosemide.

We studied the effects of cicletanine, a furopyridine antihypertensive drug, and furosemide, a loop diuretic, on ventricular arrhythmias, such as sustained ventricular fibrillation (VF) and ventricular tachycardia (VT), and myocardial ion content in Langendorff rat hearts subjected to 30 min global ischaemia then 10 min reperfusion. Myocardial Na+, K+, Ca2+ and Mg2+ concentrations were measured by washout technique and atomic absorption spectrophotometry before and after ischaemia and reperfusion. Drugs were either perfused (acute treatment) or orally gavaged daily to the rats for 14 days before isolation of their hearts (chronic treatment). Under in vitro conditions 10(-5), 3 x 10(-5), 10(-4) or 3 x 10(-4) M of cicletanine reduced the incidence of sustained VF and VT from the control values of 91% and 100% to 83% and 100%, 50% (P less than 0.05) and 67%, 33% (P less than 0.01) and 50% (P less than 0.05), 25% (P less than 0.01) and 41% (P less than 0.05), respectively. Chronic treatment with 3, 10, 30 or 100 mg.kg-1.day-1 of cicletanine also resulted in a dose-dependent anti-arrhythmic effect. Neither acute (10(-5), 3 x 10(-5) and 10(-4) M) nor chronic furosemide treatment (3, 10 and 30 mg.kg-1.day-1) influenced the incidence of arrhythmias. Acute treatment with cicletanine or furosemide did not change myocardial ion concentrations, in non-ischaemic hearts, while chronic treatment with 30 mg.kg-1.day-1 furosemide significantly reduced myocardial Na+, K+ and Mg2+ content and increased Ca2+ concentration. Both acute and chronic cicletanine treatments attenuated ischaemia/reperfusion-induced myocardial Na+ and Ca2+ gains and K+ loss, while furosemide did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗