References of "Hanson, Julien"
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See detailThe use of an apoE–deficient (apoE-/-) mice model to characterize the therapeutic benefits of original thromboxane modulators
Cherdon, Céline ULg; Rolin, stephanie; Hanson, Julien ULg et al

Poster (2006, May 17)

The aim of our study was to use an apoE–deficient mouse model to test drugs acting as thromboxane A2 antagonist. Presented here is the “en face” method 6 which allows the evaluation of atherosclerosis ... [more ▼]

The aim of our study was to use an apoE–deficient mouse model to test drugs acting as thromboxane A2 antagonist. Presented here is the “en face” method 6 which allows the evaluation of atherosclerosis lesions development in wild type and APO E-/- mice. This method involves pinning out the aorta and quantifying lesion area as a percentage of total surface area. The use of this mice model offers a unique opportunity to characterize the therapeutic benefits of pharmacologicals agents designed in our laboratory of which antioxidants and thromboxane modulators. The pharmacological characterization of BM-573 as potential antiatherosclerotic agent will also be discussed [less ▲]

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See detailEvaluation of BM-573, a novel TXA(2) synthase inhibitor and receptor antagonist, in a porcine model of myocardial ischemia-reperfusion
Kolh, Philippe ULg; Rolin, S.; Tchana-Sato, Vincent ULg et al

in Prostaglandins & Other Lipid Mediators (2006), 79(1-2), 53-73

Aims: To investigate whether BM-573 (N-tert-butyl-N'-[2-(4'-methylphenylam\ino)-5-nitro-benzenesulfonyl]urea), an original combined thromboxane A(2) synthase inhibitor and receptor antagonist, prevents ... [more ▼]

Aims: To investigate whether BM-573 (N-tert-butyl-N'-[2-(4'-methylphenylam\ino)-5-nitro-benzenesulfonyl]urea), an original combined thromboxane A(2) synthase inhibitor and receptor antagonist, prevents reperfusion injury in acutely ischemic pigs. Methods: Twelve animals were randomly divided in two groups: a control group (n = 6) intravenously infused with vehicle, and a BM-573-treated group (n = 6) infused with BM-573 (10 mg kg(-1) h(-1)). In both groups, the left anterior descending (LAD) coronary artery was Occluded for 60 min and reperfused for 240 min. Either vehicle or BM-573 was infused 30 min before LAD occlusion and throughout the experiment. Platelet aggregation induced by arachidonic acid ex vivo measured was prevented by BM-573. Results: In both groups, LAD occlusion decreased cardiac output, ejection fraction, slope of stroke work-end-diastolic volume relationship, and induced end-systolic pressure-volume relationship (ESPVR) rightward shift, while left ventricular afterload increased. Ventriculo-arterial coupling and mechanical efficiency decreased. In both groups, reperfusion further decreased cardiac output and ejection fraction, while ESPVR displayed a further rightward shift. Ventriculo-arterial coupling and mechanical efficiency remained impaired. Area at risk, evidenced with Evans blue, was 33.2 +/- 3.4% of the LV mass (LVM) in both groups, and mean infarct size, revealed by triphenyltetrazolium chloride (TTC), was 27.3 +/- 2.6% of the LVM in the BM-573-treated group (NS). Histological examination and immunohistochemical identification of desmin revealed necrosis in the anteroseptal region similar in both groups, while myocardial ATP dosages and electron microscopy also showed that BM-573 had no cardioprotective effect. Conclusions: These data suggest that BM-573 failed to prevent reperfusion injury in acutely ischemic pigs. (C) 2005 Elsevier Inc. All rights reserved. [less ▲]

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See detailFrom the design to the clinical application of thromboxane modulators
Dogné, Jean-Michel ULg; Hanson, Julien ULg; de Leval, Xavier et al

in Current Pharmaceutical Design (2006), 12(8), 903-923

Arachidonic acid (AA) metabolites are key mediators involved in the pathogenesis of numerous cardiovascular, pulmonary, inflammatory, and thromboembolic diseases. One of these bioactive metabolites of ... [more ▼]

Arachidonic acid (AA) metabolites are key mediators involved in the pathogenesis of numerous cardiovascular, pulmonary, inflammatory, and thromboembolic diseases. One of these bioactive metabolites of particular importance is thromboxane A(2) (TXA(2)). It is produced by the action of thromboxane synthase on the prostaglandin endoperoxide H-2 (PGH(2)) which results from the enzymatic transformation of AA by the cyclooxygenases. It is a potent inducer of platelet aggregation, vasoconstriction and bronchoconstriction, and has been involved in a series of major pathophysiological conditions. Therefore, TXA(2) receptor antagonists, thromboxane synthase inhibitors and drugs combining both properties have been developed by different laboratories since the early 1980s. Several Compounds have been launched on the market and others are tinder clinical evaluation. In the first part of this review. we will describe the physiological properties of TXA(2), thromboxane synthase and thromboxane receptors. The second part is dedicated to a description of each class of thromboxane modulators with the advantages and disadvantages they offer. In the third part. we aim to describe recent studies performed with the most interesting thromboxane modulators in major pathologies: myocardial infarction and thrombosis, atherosclerosis, diabetes, pulmonary embolism, septic shock.. preeclampsia, and asthma. Each pathology will be systematically reviewed. Finally, in the last part we will highlight the latest perspectives in drug design of thromboxane modulators and in their future therapeutic applications such as cancer, metastasis and angiogenesis. [less ▲]

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See detailEffects of BM-573, a thromboxane A(2) modulator on systemic hemodynamics perturbations induced by U-46619 in the pig
Tchana-Sato, Vincent ULg; Dogné, Jean-Michel ULg; Lambermont, Bernard ULg et al

in Prostaglandins & Other Lipid Mediators (2005), 78(1-4), 82-95

The aim of our study was to evaluate the effects of thromboxane A(2) (TXA(2)) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA(2) receptor ... [more ▼]

The aim of our study was to evaluate the effects of thromboxane A(2) (TXA(2)) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA(2) receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group (n=6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group (n = 6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA(2) plays it main role in the increase of vascular resistance like in pathologies such as systemic hypertension. (c) 2005 Published by Elsevier Inc. [less ▲]

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See detailCharacterisation of an original model of myocardial infarction provoked by coronary artery thrombosis induced by ferric chloride in pig
Dogné, Jean-Michel ULg; Rolin, S.; Tchana-Sato, Vincent ULg et al

in European Heart Journal (2005, September), 26(Suppl. 1), 455-456

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See detailEffects of dobutamine on left ventriculoarterial coupling and mechanical efficiency in acutely ischemic pigs
Kolh, Philippe ULg; Lambermont, Bernard ULg; Ghuysen, Alexandre ULg et al

in Journal of Cardiovascular Pharmacology (2005), 45(2), 144-152

This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular ... [more ▼]

This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular properties, including peripheral resistance (R-2), compliance (C), and arterial elastance (E-a), were estimated with a windkessel model, and left ventricular (LV) function by the slope (E-es) of the end-systolic pressure-volume relationship (ESPVR) and stroke work (SW). VA coupling was defined as E-es/E-a, and mechanical efficiency as SW/pressure-volume area (PVA). In all animals, the left anterior descending coronary artery was ligated after basal measures. The animals were then randomly divided into 2 groups: group CTRL (n = 6) was followed for 180 minutes without other intervention, whereas group DOBU (n = 6) was infused with dobutamine (5 mug(.)kg(-1.)min(-1)) starting after T60 measures. Coronary occlusion induced a rightward shift of ESPVR and a decrease in E-es from 3.67 +/- 0.33 to 1.92 +/- 0.20 mm Hg(.)mL(-1), while E-a changed from 3.33 +/- 0.56 to 4.65 +/- 0.29 mm Hg(.)mL(-1), R-2 from 1.72 +/- 0.30 to 2.38 +/- 0.16 mm Hg(.)s(.)mL(-1), and C from 0.78 +/- 0.16 to 0.46 +/- 0.08 mL(.)mm Hg-1. This altered VA coupling from 1.22 +/- 0.11 to 0.44 +/- 0.07. SW decreased from 4056 +/- 223 to 2372 +/- 122 mm Hg(.)mL, and PVA and SW/PVA decreased from 5575 +/- 514 to 4830 +/- 3.17 mm Hg(.)mL, and from 0.76 +/- 0.04 to 0.49 +/- 0.03, respectively. In group DOBU, dobutamine restored E-es and the position of ESPVR to baseline values, while E-a decreased to 3.39 +/- 0.34 mm Hg(.)mL(-1) because of an R-2 decrease to 1.60 +/- 0.24 mm Hg(.)s(.)mL(-1). VA coupling was restored. SW and PVA increased to 3833 +/- 180 mm Hg(.)mL and to 7498 +/- 442 mm Hg(.)mL, respectively, while SW/PVA was unchanged. In ischemic pigs, dobutamine restored VA coupling through an increase in LV contractility and decrease in arterial elastance as a result of peripheral vasodilatation. However, myocardial oxygen consumption was increased, and mechanical efficiency impaired. [less ▲]

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See detailEffects of reperfusion on left ventricular hemodynamics and ventriculo-arterial coupling in acutely ischemic pigs
Lanoye, Lieve; KOLH, Philippe ULg; Rolin, Stéphanie et al

in Computer Methods in Biomechanics & Biomedical Engineering (2005), 8(suppl. 1), 169-170

Rapid restoration of coronary blood flow following a period of myocardial ischemia (due to coronary occlusion) is mandatory to preserve the cardiac muscle. Reperfusion, however, not necessarily restores ... [more ▼]

Rapid restoration of coronary blood flow following a period of myocardial ischemia (due to coronary occlusion) is mandatory to preserve the cardiac muscle. Reperfusion, however, not necessarily restores cardiac function, and cellular damage of the cardiac muscle cells following reperfusion (reperfusion injury) is well documented. The aim of this study was to investigate the effects of reperfusion on left ventricular (LV) hemodynamics and on left ventriculo-arterial (VA) coupling in acutely ischemic pigs. [less ▲]

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See detailCharacterization of an original model of myocardial infarction provoked by coronary artery thrombosis induced by ferric chloride in pig
Dogné, Jean-Michel ULg; Rolin, Stéphanie; Petein, Michel et al

in Thrombosis Research (2005), 116(5), 431-442

Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely ... [more ▼]

Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely contributed to the discovery and to the validation of original treatments. The purpose of the present work was to develop and validate an original model of acute myocardial infarction provoked in pig by thrombosis of the left anterior descending (LAD) coronary artery induced by topical application of ferric chloride solution. Methods and results: Myocardial infarction, resulting from an occlusive and adherent mixed thrombus formed in the LAD coronary artery, was examined at macroscopic level using dual staining technique (Evans blue dye; triphenyltetrazolium chloride) and at microscopic level using conventional histological analyses and immunohistochemical detection of desmin. Biochemical markers (troponin T and ATP), platelet reactivity and standard hemodynamic parameters (such as stroke volume, ejection fraction, stroke work and cardiac output) have also been evaluated. From these analyses, it was demonstrated that each pig developed a transmural area of irreversible damage mainly located in the anteroseptal region of the left ventricle. The more progressive development of coronary artery occlusion, as compared to an abrupt Ligation, was accompanied by a correspondingly progressive impairment in hemodynamics. Conclusion: We conclude that this original porcine model of myocardial infarction is quite close to clinical pathophysiological conditions, such as thrombus formation occurring after atherosclerotic plaque rupture. This certainly constitutes a further argument in favour of this model to assess pharmaceutical or mechanical support of an acutely ischemic heart. (c) 2005 Elsevier Ltd. All rights reserved. [less ▲]

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See detailIn vitro and in vivo pharmacological characterization of BM-613 [N-n-pentyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea]
Hanson, Julien ULg; Rolin, Stéphanie; Reynaud, Denis et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2005), 313

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See detailPharmacological profile and therapeutic potential of BM-573, a combined thromboxane receptor antagonist and synthase inhibitor.
Ghuysen, Alexandre ULg; Dogné, Jean-Michel; Chiap, Patrice ULg et al

in Cardiovascular Drug Reviews (2005), 23(1), 1-14

BM-573 (N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and receptor antagonist. The pharmacological ... [more ▼]

BM-573 (N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and receptor antagonist. The pharmacological profile of the drug is characterized by a higher affinity for the thromboxane receptor than that of SQ-29548, one of the most powerful antagonists described to date, by a complete prevention of human platelet aggregation induced by arachidonic acid at a lower dose than either torsemide or sulotroban, and by a significantly prolonged closure time measured by the platelet function analyser (PFA-100). Moreover, at the concentrations of 1 and 10 microM, BM-573 completely prevented production of TXB2 by human platelets activated by 0.6 mM of arachidonic acid. BM-573 prevents rat fundus contraction induced by U-46619 but not by prostacyclin or other prostaglandins. Despite possessing a chemical structure very similar to that of a diuretic torsemide, BM-573 has no diuretic activity. BM-573 does not prolong bleeding time and, unlike some of the other sulfonylureas, has no effect on blood glucose levels. In vivo, BM-573 appears to have antiplatelet and antithrombotic activities since it reduced thrombus weight and prolonged the time to abdominal aorta occlusion induced by ferric chloride. BM-573 also relaxed rat aorta and guinea pig trachea precontracted with U-46619. In pigs, BM-573 completely antagonized pulmonary hypertensive effects of U-46619 and reduced the early phase of pulmonary hypertension in models of endotoxic shock and pulmonary embolism. Finally, BM-573 protected pigs from myocardial infarction induced by coronary thrombosis. These results suggest that BM-573 should be viewed as a promising therapeutic agent in the treatment of pulmonary hypertension and syndromes associated with platelet activation. [less ▲]

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See detailEffect of BM-573[N-terbutyl-N '-[2-(4 '-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism
Ghuysen, Alexandre ULg; Lambermont, Bernard ULg; Dogné, Jean-Michel ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2004), 310(3), 964-972

The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane A(2) synthase inhibitor and receptor antagonist, on ... [more ▼]

The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane A(2) synthase inhibitor and receptor antagonist, on the hemodynamic response to acute pulmonary embolism. Six anesthetized pigs were infused with placebo ( placebo group) and compared with six other pigs receiving a continuous infusion of BM-573 ( BM group). Pulmonary embolization with 0.3 g/kg autologous blood clots was carried out 30 min after the start of the infusion. Right ventricular pressure-volume loops were recorded using a conductance catheter, and end-systolic ventricular elastance was periodically assessed by varying right ventricular preload. Pulmonary vascular properties were studied by use of a four-element wind-kessel model. Hemodynamic data, including assessment of right ventricular-arterial coupling, were collected at baseline and every 30 min for 4 h. Blood samples were collected to assess gas exchange, thromboxane A(2), and prostacyclin plasma levels and to evaluate platelet aggregation. Mean pulmonary arterial pressure in the placebo group increased significantly more than in the BM group, mainly because of an additional increase in pulmonary vascular resistance. Arterial and end-systolic ventricular elastances increased also more in the placebo group, whereas right ventricular efficiency decreased. BM-573 prevented both platelet aggregation induced by U-46619 (9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F-2alpha) or by arachidonic acid, and thromboxane A(2) overproduction, whereas prostacyclin liberation was preserved. Oxygenation, however, was not significantly improved. We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level. [less ▲]

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See detailDevelopment of thromboxane A2 modulators as promising anti-metastatic and anti-angiogenic compounds
De Leval, X.; Dassesse, T.; Benoit, V. et al

Conference (2004, May)

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See detailNew developments on thromboxane modulators
Dogné, Jean-Michel ULg; Hanson, Julien ULg; De leval, X. et al

in Mini Reviews in Medicinal Chemistry (2004)

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See detailNew developments on thromboxane and prostacyclin modulators. Part II: prostacyclin modulators
De Leval, X.; Hanson, Julien ULg; David, Jean-Louis ULg et al

in Current Medicinal Chemistry (2004), 11

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See detailCharacterization of preferential activity on platelet thromboxane A2 receptors of BM-613, a new thromboxane A2 antagonist
Hanson, Julien ULg; Rolin, S.; De Leval, X. et al

in Fundamental & Clinical Pharmacology (2004)

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