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Biomedical subjects

A Etienne

Publications and source records attributed to A Etienne.

At least 37 records · Page 2Linked to original sources
PubMed1989

Chemotactic effect of PAF-acether on peritoneal eosinophils from normal rats.

The chemotactic activity of PAF-acether was compared with that of tetrapeptide eosinophil chemotactic factors of anaphylaxis (ECF-A, Ala-Gly-Ser-Glu and Val-Gly-Ser-Glu) using eosinophils obtained from the peritoneal cavity of normal rats. Cells were isolated by separation over discontinuous metrizamide gradients which resulted in eosinophil suspensions of 80 to 90% purity. PAF-acether produced a dose-dependent effect which, at its maximum, was more than 30-fold greater than control and about 5- to 7-fold greater than the maximal activity obtained with the ECF-A-tetrapeptides. BN 52021 and WEB 2086 inhibited PAF-acether-induced eosinophil chemotaxis in a dose-dependent manner, suggesting that this phenomenon is mediated by specific PAF-acether receptors.

Animals↗
PubMed1989

Protective effect of the PAF-antagonist BN 52021 on several models of gastro-intestinal mucosal damage in rats.

Platelet-activating factor (PAF) has been shown to induce gastro-intestinal damage similar to that evoked by endotoxin, suggesting that this mediator may be involved in the formation of gastrointestinal lesions observed in various pathologies. Thus, the effects of BN 52021, a specific PAF antagonist, were investigated in several experimental models of gastro-intestinal damage in rats. BN 52021 markedly reduced the gastric alterations and almost totally abolished the intestinal lesions induced by PAF. Similarly, BN 52021 reduced gastro-intestinal damage induced by endotoxin, but it afforded less protection against endotoxin-induced changes than those caused by PAF. This difference is probably due to the multicomponent activating effect of endotoxin. In the cold restraint stress model, BN 52021 decreased both gastro-intestinal lesions and the change in plasma transaminase level. The results presented in this paper confirm the role of PAF in gastro-intestinal damage induced by endotoxin but also suggest the involvement of this mediator in stress-induced lesions. PAF-antagonists could thus be of therapeutic use in such pathologies.

Animals↗
PubMed1989

[A study by infrared spectroscopy of interactions between the time of disintegration of tablets and liberation of the active principal].

It was shown that the study of the infrared spectra of a drug and of the mixture drug + additives facilitates the preliminary studies for a tablet formulation. Thus, any interaction that may occur or affect the product stability can be detected and located. Furthermore, it was noticed that an interaction between an active ingredient and the various additives may modify the tablet desintegration time, but not necessarily the dissolution rate of this substance.

Solubility↗
PubMed1988

Effects of the specific platelet-activating factor antagonists, BN 52021 and BN 52063, on various experimental gastrointestinal ulcerations.

Platelet-activating factor (PAF) has been shown recently to induce gastrointestinal damage similar to that evoked by endotoxin, suggesting that the autacoid could be implicated in other types of gastrointestinal damage. Thus, the effects of BN 52021 and BN 52063, two specific PAF antagonists, were investigated in various experimental models of gastrointestinal damage in rats. BN 52021 and BN 52063, markedly reduced both the PAF- and endotoxin-induced alterations of the mucosa, suggesting a role for the autacoid in the latter process. BN 52021 and another unrelated PAF antagonist, triazolam, partially reduced the restraint-stress-induced gastric damage in young female, but not male, rats. Similar partial protection was obtained in rats with ethanol-induced gastric damage. In contrast with atropine and ranitidine, BN 52021 did not affect the gastric hypersecretion in pylorus-ligated rats nor the aspirin-induced gastric ulcerations. The present results indicate that PAF plays a major role in the gastric damage induced by endotoxin and may also partially contribute to the gastric lesions induced by ethanol and stress. The results suggest that there is a potential therapeutic use for PAF antagonists in certain types of gastrointestinal lesions in man.

Animals↗
PubMed1988

Role of neutrophils in gastric damage induced by platelet activating factor.

Platelet-activating factor (PAF) has recently been shown to be a potent ulcerogenic agent in the stomach and intestinal mucosa. Its extract mechanism of action is not yet known although histological studies suggest that vasocongestion is an important feature of PAF-induced damage. We have therefore studied the activity of various agents with different modes of action toward PAF-induced gastrointestinal lesions in the rat (PAF 2 micrograms/kg i.v.; macroscopic lesions of tissue scored 20 min later; arbitrary scale from 0 to 4). Drugs were administered either i.m., s.c. (5 min) or orally (30 min) before PAF injection. PAF-induced gastric lesions were strongly inhibited by the natural PAF-antagonist BN 52021 as well as by atropine sulphate and cimetidine which implicates cholinergic stimulation in the ulcerogenic activity of PAF. The somatostatin analog BIM 23014 was also very potent against PAF, perhaps by reducing the parasympathetic stimulation in the gastric wall as described for somatostatin. Allopurinol, which is a free radical scavenger also almost totally inhibited PAF-induced gastric damage, suggesting that neutrophils are involved in the mucosal lesions. The considerable inhibition of the gastric effects of PAF found in neutrophil-depleted animal supports this hypothesis. Theophylline and disodium cromoglycate, mast cell stabilizing drugs which were also active in our model, could act by protecting mast cell degranulation induced by free radicals released from activated neutrophils. A multifunctional process seems to determine the mucosal gastric damage induced by PAF, but parasympathetic stimulation and neutrophil activation play a major role in this pathology.

Animals↗
PubMed1988

Role of platelet-activating factor (PAF) in the ovoimplantation in the rat: effect of the specific PAF-acether antagonist, BN 52021.

The role of PAF (platelet-activating factor) in early pregnancy has been recently postulated. Indeed, platelet count is markedly reduced immediately prior to and returns to normal following ovoimplantation. Using a pharmacological approach, we therefore further investigated the possible involvement of PAF in ovoimplantation. BN 52021 (10 nmol), a PAF antagonist, was administered after fecondation in the lumen of the left uterine horn. A group of animals was injected with the vehicle alone. The animals were sacrificed 1 week latter and the number of implanted embryos in the treated horn and in the untreated contralateral one was assessed. When injected on day 4 of pregnancy, the PAF antagonist, BN 52021, inhibited in a dose-dependent fashion ovoimplantation suggesting a role for this lipid mediator in this process. Total inhibition of ovoimplantation was observed in the horns treated with indomethacin, NDGA or BW 755 C. In addition, a significant inhibition of ovoimplantation was also produced by the lipoxygenase inhibitor, EP 10045 (10nmol). Since both PAF and leukotrienes trigger the generation of prostaglandins in various tissues, our results indicate that these two lipid mediators may be implicated in early stages of the inflammatory reaction accompanying ovoimplantation and may contribute to the local generation of cyclooxygenase metabolites.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1988

General pharmacology of cicletanine.

Cicletanine is a new antihypertensive molecule which acts directly on vascular smooth muscle by increasing prostacyclin synthesis and interacting with various agents which mobilize intracellular Ca2+ ions. General pharmacological studies have shown that in the anaesthetized normotensive dog, cicletanine does not induce tachycardia (even at high doses) and does not modify aortic, femoral or coronary blood flow. Moreover, cicletanine shows a protective effect on vascular permeability and capillary hyperpermeability. This protective action on the vascular wall is of importance, since one of the direct vascular consequences of arterial hypertension is a fragilisation of vessel walls, tissue oedema and even vascular rupture. Cicletanine slows down the thrombogenic process initiated by electric arterial stimulation. Retardation of the thrombogenic process by the drug may be explained by the stimulation that cicletanine exerts on the synthesis and production of prostacyclin. Behavioural studies in mice, rats and primates have shown that cicletanine has no sedative effects, even at very high doses. General pharmacological studies have demonstrated that both cardiovascular function and the central nervous system are equally tolerant to cicletanine. Cicletanine is an antihypertensive agent which has no effect on cardiovascular haemodynamics and is able to prevent some rheological and vascular-linked cardiac risks of hypertension.

Animals↗
PubMed1987

[Evaluation of the control quality of arterial hypertension over a 10-year period at a hemodialysis center].

Using the "Diaphane" computed medical record system enables multicentric statistical studies to be conducted. With this system, the quality of arterial hypertension control (supine systolic and diastolic arterial pressure before and after dialysis) was evaluated over a 10-year period in chronic haemodialysis patients in comparison with a multicentric population. A continuous statistical study of the results showed a regular voluntary decrease in arterial pressure. The evaluation of the quality of medical care represented by this comparison contributes to a therapeutic improvement.

Adult↗
PubMed1987

Inhibition of rat endotoxin-induced lethality by BN 52021 and BN 52063, compounds with PAF-acether antagonistic effect and protease-inhibitory activity.

Since proteolytic enzymes play a key role in endotoxaemia and anaphylaxis, diseases in which PAF-acether may be involved, we have investigated the activity of BN 52021 and BN 52063, two potent and specific PAF-acether antagonists, on plasma protease activity in the rat. After oral administration, both drugs dose-dependently decreased plasma trypsin-like activity (PTLA) although they did not show any inhibitory effect in vitro. PAF-acether and endotoxin injected into rats increased PTLA, the increase with endotoxin appearing more slowly but to a higher extent than with PAF-acether. Inhibition of the endotoxin-induced increase in PTLA was obtained with BN 52021, BN 52063 and dexamethasone, whereas aprotinin was ineffective. Since BN 52021 and BN 52063 reduced also the endotoxin-induced lethality in the rat, their antiprotease activity may be a consequence of their PAF-antagonistic effect. Further studies will be required with other PAF antagonists to assess fully this assumption.

Animals↗
PubMed1986

[Mechanism of action of Ginkgo biloba extract in experimental cerebral edema].

Oedema is one of the major complication of cerebral ischaemia being at the same time a consequence and an aggravating factor. Its first phase is intracellular and cytotoxic, with breakdown of ionic pumps through loss of energy, resulting in a whole sequence of ionic perturbations characterized by loss of intracellular K+ and accumulation of water and Na+, Cl-, and Ca2+ ions in the cells of the ischaemic zone. The second phase, termed vasogenic, applies to the accumulation of lactates, inorganic phosphates and free polyunsaturated fatty acids and in particular, arachidonic acid. This last compound is responsible for the production of membrane "aggressors", amongst which free radicals play an important rôle. Ginkgo biloba extract limits the formation of cerebral oedema and suppresses its neurological consequences, whether the oedema is of cytotoxic (triethyltin) or vasogenic (unilateral traumatic oedema) origin. Several membrane mechanisms could be implicated in the protective action manifested by Ginkgo biloba extract against cerebral oedema.

Animals↗
PubMed1986

Interference of BN 52021 (ginkgolide B) with the bronchopulmonary effects of PAF-acether in the guinea-pig.

The interaction between the ginkgolide BN 52021 and the effects of PAF-acether on the bronchopulmonary system of the guinea-pig was studied. In pentobarbitone or ethyl carbamate-anaesthetized animals, BN 52021 (1 mg/kg i.v. or 10 mg/kg p.o.) inhibited bronchoconstriction, the hematocrit increase and the accompanying thrombopenia and leukopenia induced by PAF-acether (33-100 ng/kg) and failed to block the bronchoconstriction produced by collagen, arachidonic acid and the tripeptide formyl-Met-Leu-Phe (FMLP). BN 52021, 3 mg/kg, reduced the bronchoconstriction induced by aerosolized PAF-acether. BN 52021, 300 microM, also inhibited the superoxide production by PAF-acether-stimulated alveolar macrophages and failed to reduce the same effects when triggered by FMLP (0.01-1 microM). BN 52021 blocked the formation of thromboxane-triggered by PAF-acether (100 ng) injected into perfused lung, under conditions where the effects of arachidonic acid where not modified. Finally, pretreatment of parenchyma lung strips with BN 52021 (100 microM) partially inhibited the contraction induced by PAF-acether (0.1 microM) and suppressed the accompanying release of thromboxane. BN 52021 is a selective antagonist of the effects of PAF-acether on the bronchopulmonary system and on circulating blood cells of the guinea-pig.

Animals↗
PubMed1986

[Ranitidine therapy of duodenal ulcer: comparison of once-a-day and twice-a-day administration. A Swiss multicenter double-blind study].

In a Swiss multicenter double-blind trial ranitidine was given in doses of 300 mg nocte and 150 mg b.d. for the treatment of duodenal ulcer. Ninety-seven patients with endoscopically proven ulcer were treated for four, and in cases of non-healing for eight, weeks. Cumulative healing rates with 300 mg and 2 X 150 mg were 77% and 78% after four weeks and 90% and 94% after eight weeks respectively. 60 and 65% of the patients were asymptomatic after four weeks. Smoking did not adversely affect healing. Thus, ranitidine in a dose of 300 mg nocte is as effective as ranitidine in a dose of 150 mg b.d. in the treatment of duodenal ulcer.

Adolescent↗
PubMed1986

In vivo inhibition of plasma protein leakage and Salmonella enteritidis-induced mortality in the rat by a specific paf-acether antagonist: BN 52021.

The effects of BN 52021, a new specific paf-acether receptor antagonist and the total Ginkgo Biloba extract (GBE 761) from which this product was isolated, were studied in the rat on paf-acether-induced permeability and cell number changes and on endotoxin-induced lethality. Their activities were compared to those of cyclooxygenase, 5-lipoxygenase and phospholipase A2 inhibitors. BN 52021 given s.c. or orally exerted a dose-related inhibition of paf-acether deleterious effects as well as of endotoxin lethality whereas the other drugs tested were poorly effective. These results strongly suggest paf-acether involvement in endotoxic and septic shock.

Animals↗
PubMed1986

Inhibition of antigen-induced lung anaphylaxis in the guinea-pig by BN 52021 a new specific paf-acether receptor antagonist isolated from Ginkgo biloba.

Paf-acether appears to be a potent mediator released in response to allergen exposure in sensitized animals and it could contribute to clinical manifestations of allergic asthma. In order to ascertain this assumption the inhibition of antigen-induced lung anaphylaxis in guinea-pig by BN 52021, a new highly specific paf-acether antagonist, was studied. Ovalbumin injected into passively sensitized guinea-pig induced a large bronchoconstriction which was accompanied by thrombocytopenia and leukopenia. Treatment of animals with BN 52021 i.v., five minutes before challenge, strongly (at the doses of 1 and 2 mg/kg) or totally (at 0.1 mg/kg) inhibited the bronchoconstriction and partially reduced the thrombocytopenia and leukopenia the thrombocytopenia occurring after challenge. These results confirm that paf-acether and platelets might play a key role in asthma. BN 52021 and other paf-acether antagonist could provide a new group of potent prophylactic anti-asthma drugs.

Anaphylaxis↗
PubMed1986

The relative role of PAF-acether and icosanoids in septic shock.

Endotoxemia and gram negative sepsis remain a clinically important problem since mortality rate is still high in these diseases. Recently, the participation of some new potential mediators in this pathology is beginning to be demonstrated but the results obtained on animal models with specific inhibitors are contradictory. In order to clarify the pathological importance of icosanoids and PAF-acether in the septicemic process, we investigated the effects of indomethacin (IND) a cyclooxygenase inhibitor, NDGA and EP 10045 two lipoxygenase inhibitors, dexamethasone (DXM) a phospholipase A2 inhibitor and BN 52021 a PAF-acether receptor antagonist, on the Salmonella enteritidis-induced endotoxic shock (E.S.) in the rat. Injected subcutaneously 15 min before the test, NDGA, EP 10045 and IND were moderately effective when DXM completely prevented the endotoxin lethality. BN 52021 decreased the death rate in a dose-related manner and exerted at a non-active dose a synergistic effect on IND treatment. Furthermore, given orally 1 hour before endotoxin, it provided a potent protective effect. Our results seem to confirm that PAF-acether exerted alone, or in conjunction with products of the cyclooxygenase pathway, a key role in E.S. when LTs seem to play a role of minor importance.

Animals↗
PubMed1986

Comparative effects of drugs on leukotrienes-, PAF-acether- and histamine- induced contractions of guinea-pig lung parenchymal strips.

Dose-response curves to leukotrienes B4 (LTB4), D4 (LTD4), PAF-acether and histamine applied as single or cumulative doses are studied on guinea-pig lung parenchymal strips (GPLP). A mole to mole comparison shows that PAF-acether is the most potent agonist, when GPLP contracts maximally to histamine. GPLP possesses specific receptors to histamine, LTD4 and PAF-acether which can be blocked by selective receptors antagonists: mepyramine as antihistaminic, FPL 55712 as anti-SRS-A substance, BN 52021 and kadsurenone as anti-PAF-receptor antagonists; meanwhile, a part of their action is mediated through the release of arachidonate metabolites. Histamine, LTB4, LTD4 and PAF-acether-induced contractions are all dependent on cyclooxygenase. Thromboxane A2 (TXA2) could be one of the cyclooxygenase products involved. A part of contractile effects of LTB4 and LTD4, but not of histamine, is liked to the generation of lipoxygenase metabolites as their contractions are partially inhibited by NDGA and ETYA. Contraction-induced by PAF-acether is reduced in presence of NDGA but not by FPL 55712, which indicates that lipoxygenase products other than peptidoleukotrienes are involved in the PAF-response.

Animals↗