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Biomedical subjects

C Bonne

Publications and source records attributed to C Bonne.

At least 55 records · Page 3Linked to original sources
PubMed1989

[Experimental herpes simplex keratitis in rabbits. Evaluation of pro-infectious effects of topical non-steroidal anti-inflammatory agents].

We tested 3 non steroidal anti-inflammatory drugs in experimental herpes keratitis in order to determine possible pro-infectious consequences. The drugs were Indomethacine, Flurbiprofen and a new non steroidal anti-inflammatory, CBS 113 A, mixed inhibitor of cycloxygenase and lipoxygenase. We studied simultaneously the evolution of the keratitis and viral excretion. We considered that an anti-inflammatory agent had a pro-infectious effect if the keratitis was more serious and/or viral excretion longer in comparison with placebo. We have shown, for the 3 drugs, in comparison with dexamethasone activity, absence of a pro-infectious effect. We compared our results on Flurpiprofen with an other study which gave this anti-inflammatory drug pro-infectious capacities; the concentration used was higher. CBS 113 A, inhibiting the metabolism of arachidonic acid via lipoxygenase and cycloxygenase and thus preventing the formation of metabolitis involved in inflammation (prostaglandins, leukotrienes,...), should have a spectrum of activity wider than that of NSAID. Subject to further studies, these 3 nonsteroidal anti-inflammatory could be used in herpetic kerato-uveitis.

Administration, Topical↗
PubMed1988

Characterization of specific leukotriene C4 binding sites on cultured human keratinocytes.

Peptidoleukotriene C4 (LTC4) and leukotriene B4 (LTB4) are both suspected of being inflammatory mediators and epidermal mitogenic agents in cutaneous psoriatic lesions. In the present study an LTC4 specific binding site was characterized in membranes from cultured human keratinocytes (Kd, 8.7 nmol/l; Bmax, 1.2 pmol/mg protein). In contrast LTB4 did not show any high affinity binding which could account for its biological effects. These data suggest that LTC4, unlike LTB4, acts on epidermal cells through a receptor-mediated mechanism.

Binding Sites↗
PubMed1987

Differential effects of leukotrienes B4 and C4 on bovine aortic endothelial cell proliferation in vitro.

The effect of leukotrienes derivated from arachidonic acid was studied on vascular endothelium proliferation. The peptido-leukotriene LTC4 (0.1 nM - 0.1 microM) promoted a dose-dependent growth of bovine aortic endothelial cells in culture with a maximal effect at 10 nM. This proliferative activity could be receptor-mediated since LTC4 specifically bound to endothelial cell membranes with a Kd value of 50 nM. The leukotriene B4 did not induce any significant proliferation in the same range of concentrations. This result was consistent with the lack of LTB4 specific binding sites. This data suggests that LTC4 could be one of the factors implicated in angiogenesis during inflammatory processes.

Animals↗
PubMed1987

Specific binding of leukotriene C4 to endothelial cell membranes.

Vascular endothelium is a target for leukotriene C4 (LTC4) as demonstrated by previous in vivo and culture experiments. Binding assays were carried out at 0 degrees C on membrane fraction obtained from bovine aortic endothelial cells in culture. Specific binding sites (Kd = 49.9 +/- 6.3 nmol X 1(-1), N = 1.2 X 10(6) sites per cell) for LTC4 were demonstrated in this preparation. Competition studies showed that LTB4, LTD4 and LTE4 did not displace LTC4 from its binding sites. FPL 55712, a sulfidopeptide antagonist, was seen to be a weak competitor and reduced glutathione exhibited a significant affinity for the binding site. The possible receptor role of this site is discussed.

Animals↗
PubMed1986

High-affinity binding site for leukotriene C4 in human erythrocytes.

A specific, high-affinity binding site for leukotriene C4 was identified in human erythrocyte particulate fraction and in vesicle preparation. The binding was saturable, reversible and specific. Vesicle preparations showed that binding sites were localized on the outside of the plasma membrane. The dissociation constant and site density were found to be Kd = 15.9 +/- 3.2 nmol X 1(-1) and N = 152 +/- 35 sites per cell, respectively, as calculated from Scatchard analysis. The effect of leukotriene C4 did not modify the calcium influx and did not inhibit the ATPase-dependent calcium efflux. In this paper, the physiological significance of these sites is discussed.

Calcium↗
PubMed1986

Critical assessment of the platelet adenylate cyclase system as a potential model for testing alpha 2 adrenergic activity.

We have studied the effects of KUM 32 and CBS 1276, two clonidine-related drugs, upon the adenylate cyclase system of human platelets. Both drugs behaved as potent antagonists of epinephrine-induced platelet aggregation. [3H]Yohimbine binding studies revealed that the drugs bind to the alpha 2 adrenergic receptor of human platelets. KUM 32 and CBS 1276 also behaved as strong inhibitors of adenylate cyclase activity. This inhibition, which was not competitive with respect to ATP, is not an alpha 2 adrenergic phenomenon since it was not antagonized by yohimbine and was still observed in the absence of GTP. Moreover, pretreatment of platelet membranes with islet activating protein from Bordetella pertussis (IAP) had no effect on the inhibition by KUM 32, CBS 1276 and adenosine, although it completely reversed the effect of epinephrine and partially reversed the effect of clonidine. These results show that clonidine-like drugs may have different impacts on the adenylate cyclase system of human platelets. This system cannot be used as a pharmacological predictive test for alpha 2 adrenergic agonist activity, as various compounds, known to have central alpha 2 adrenergic agonist properties, do not behave as full agonists for the alpha 2 adrenergic receptor of human platelets.

Adenylate Cyclase Toxin↗
PubMed1986

Inhibition of platelet thromboxane synthetase by 1-(3-benzyloxy-1[E]octenyl)imidazole.

1-(3-Benzyloxy-1[E]octenyl)imidazole (CBS-645) is a specific inhibitor of thromboxane synthetase. It inhibits the platelet enzyme in human and rabbit at micromolar concentrations. At a dose of 12.5 mg kg-1 in rabbits, CBS-645 displays a prolonged inhibitory effect on the formation of thromboxane (Tx) B2 induced by blood coagulation in vitro. In human volunteers, an oral dose of 50 mg leads to an average 70% inhibition of TxB2 formation. CBS-645 administered at a dose of 25 mg kg-1 p.o. in the rat, significantly increases bleeding time. In another test in which platelet interaction with the vessel wall is involved, i.e. in vivo platelet deposition onto desendothelialized aorta in the rabbit, the drug shows antithrombotic activity after a single oral administration of 5 mg kg-1. CBS-645 could be of interest in the treatment of the various diseases in which the pathological role of thromboxane A2 is suspected.

Adult↗
PubMed1985

[Mechanisms of aspirin intolerance].

Aspirin intolerance brings on cutaneous and/or respiratory reactions. The mechanisms are to be elucidated precisely, but are not IgE-mediated. 193 patients with nasal polyps are studied. With systematic aspirin oral challenge, 27% belong to the classical triad: asthma, polyps and aspirin sensitivity. Other drugs or chemicals intolerance are associated in 42%: alcohol, metabisulfites, benzoates, tartrazine, codeine... A link with the non-allergic eosinophilic rhinitis is suggested. A short review of several pathogenic hypothesis is discussed. Among a comparative study, the authors showed that the aspirin-intolerant patients' platelets have a quite normal arachidonic acid metabolism. The clue is probably towards an abnormal instability of cells membranes and excessive receptors sensitivity to leukotrienes.

Arachidonic Acids↗
PubMed1985

Arachidonic acid metabolism and inhibition of cyclooxygenase in platelets from asthmatic subjects with aspirin intolerance.

Exaggerated inhibition of cyclooxygenase has been proposed as a mechanism of drug-induced bronchospasm in aspirin-intolerant patients. This study, using platelets, shows that inhibition of prostaglandin biosynthesis by aspirin is unmodified in patients when compared with healthy subjects. The ratio of cyclooxygenase:lipoxygenase products is similar in platelets from patients and control subjects. We conclude that the cyclooxygenase alteration observed in cells from the respiratory tract is not generalised to other cells such as platelets. We also propose that the major abnormality in NSAID-intolerant patients would affect receptivity to lipoxygenase products more than their biosynthesis.

Arachidonic Acid↗
PubMed1985

Anti-inflammatory activity of a dual inhibitor of cyclooxygenase and lipoxygenase pathways, CBS-1108 (2-acetylthiophene-2-thiazolylhydrazone).

Anti-inflammatory therapy is actually devolved to glucocorticoids which prevent the release of arachidonic acid from phospholipids and consequently its subsequent transformation into prostaglandins and leukotrienes. This activity explains in part why steroids are better anti-inflammatory agents than acetylsalicylic acid (ASA)-like drugs which only reduce prostaglandin production. Despite their superior therapeutic actions, there are many side effects associated with corticosteroids. Therefore in recent years, research of non-steroid dual inhibitors of prostaglandin and leukotriene production has been developed. The present paper investigates the pharmacological activity of such a new compound, CBS-1108 (2-acetylthiophene-2-thiazolylhydrazone), in comparison with dexamethasone, cyclooxygenase inhibitors (ASA and indomethacin) and reference dual inhibitors (nordihydroguaiaretic acid (NDGA) and 3-amino-1-(m-trifluoromethylphenyl)-2-pyrazoline (BW-755 C]. The two-pathway inhibitors and ASA-like drugs are similarly effective on paracentesis-induced disruption of the blood-aqueous barrier and on croton oil-induced ear edema. On the contrary in an animal model of leukocyte migration and on mast cell degranulation, NDGA and CBS-1108 are very active when the other tested compounds are inefficient.

Animals↗
PubMed1984

Dual inhibition of cyclooxygenase and lipoxygenase by 2-acetylthiophene 2-thiazolylhydrazone (CBS-1108) and effect on leukocyte migration in vivo.

CBS-1108, 2- acetylthiophene 2- thiazolyhydrazone , inhibits 5-lipoxygenase activity in polymorphonuclear leukocytes (PMNs) (IC50 = 2 X 10(-6) M), 12-lipoxygenase (IC50 = 9 X 10(-6) M) and cyclooxygenase (IC50 = 2 X 10(-6) M) in platelets. Inhibition of the two pathways of arachidonic acid cascade could lead to additional beneficial anti-inflammatory activity by comparison with classical aspirin-like drugs. In fact, only inhibitors of both cyclooxygenase and lipoxygenase such as NDGA and CBS-1108 inhibit leukocyte migration in an animal model of acute inflammatory response.

Animals↗
PubMed1984

The pure antiandrogen RU 23908 (Anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer: a review.

The nonsteroidal antiandrogen RU 23908 ( Anandron ) weakly interacts with the prostatic cytosolic androgen receptor and shows a fast dissociation rate. When administered to immature castrated rats up to the daily dose of 100 mg/kg, it is devoid of any androgenic activity but efficiently blocks the growth-promoting activity of androgens on ventral prostate and seminal vesicle weight, thus showing the characteristics of a pure antiandrogen. In intact animals, on the other hand, the antiandrogen administered alone exerts only a partial inhibition of prostate and seminal vesicle weight. This is due to the property of the pure antiandrogen to neutralize the inhibitory feedback effect of androgens at the pituitary level on the LH responsiveness to LHRH, as illustrated in vitro in rat anterior pituitary cells in culture as well as in vivo in intact and castrated animals. In intact animals, neutralization of the inhibitory feedback action of endogenous androgens leads to an increased LH and testosterone secretion, which partly overcomes the direct action of the antiandrogen at the level of the prostate and seminal vesicles. In fact, the plasma testosterone concentration is more than doubled 6 hr after the administration of 10 mg of RU 23908 while plasma LH and testosterone levels are increased by 7- and 17-fold, respectively, after 14 days of similar daily treatment. Efficient neutralization of the androgenic action at the prostatic level in intact animals thus requires prevention of this escape phenomenon through inhibition of LH secretion. Although inhibition of LH release can be achieved by estrogen and progestins, an optimal inhibitory effect on the prostate is obtained by the combined administration of the antiandrogen with an LHRH agonist that causes a specific blockage of testicular androgen biosynthesis as well as an inhibition of the LH responsiveness to LHRH.

Androgen Antagonists↗
PubMed1984

Inhibition of rat mast cell degranulation by verapamil.

Calcium antagonists, e.g. verapamil, prevent exercise-induced asthma. This protective effect may proceed from inhibition of contraction of bronchial smooth muscle, release of mediators by primary effector cells, e.g. mast cells, or both. Therefore, we studied the inhibitory effect of increasing concentrations of verapamil on both in vitro antigen-induced degranulation and ionophore A23187-induced release of labelled serotonin by rat peritoneal mast cells. There was a dose-dependent inhibition by verapamil of both ovalbumin-induced degranulation of mast cells passively sensitized by incubation with mice IgE-rich serum and ionophore-induced release of tritiated serotonin by mast cells previously incubated with (3H)-5HT; the 50% inhibiting concentration was 1.4 X 10(-4) mol I-1 and 5.2 X 10(-5) mol I-1, respectively. An attractive explanation of our results is that verapamil inhibits the antigen-induced release of mediators by mast cells through its calcium antagonist effect. Our results also suggest that the preventing effect of calcium antagonists on asthma may be multi-factorial since other authors have clearly shown that these drugs inhibit contraction of guinea-pig tracheal smooth muscle in vitro.

Animals↗
PubMed1984

Prostacyclin and thromboxanes in carrageenan-induced pleurisy in the rat.

The cellular origin and kinetics of TXB2 and 6-keto PGF1 alpha in carrageenan-induced pleurisy has been studied. Maximum levels of these prostanoids occurred 1 hour after induction of pleurisy. Mononuclear cells initially present in the pleural cavity synthesized TXB2 and 6-keto PGF1 alpha from (14C) arachidonic acid. By contrast, PMN cells harvested 6 hours after the induction of inflammation did not produce 6-keto-PGF1 alpha. Selective inhibition of thromboxane synthetase with drugs in vitro and in vivo increased the formation of 6-keto-PGF1 alpha, the stable breakdown product of PGI2. This metabolic effect was parallel to an increase in the volume of exudate and in PMN migration. These results suggest that TXA2 seems to be implicated not only as a chemotactic agent but also as an antagonist of PGI2 vasodilator effects.

6-Ketoprostaglandin F1 alpha↗