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C Doutremepuich

Publications and source records attributed to C Doutremepuich.

At least 37 records · Page 2Linked to original sources

Effect of monoclonal and polyclonal antibodies against conjugated neurotransmitter on experimental venous thrombosis.

Vasomotoricity in veins is largely controlled by the sympathetic nervous system. Norepinephrine and acetylcholine modulate the vasoconstrictor effect mediated by alpha-adrenergic receptors. Our objective was to study the role of local vasomotoricity in venous thrombosis, and particularly to determine some of the factors regulating it. Although no attempt has been described until now, polyclonal and monoclonal antibodies against L-dihydroxyphenylalanine, acetylcholine, and dopamine were administered in an experimental model of venous thrombosis. In view of the rather high specific antibody recognition for each compound, the presence of endogenous epitopes of L-dopa-like molecules and acetylcholine-like molecules in the circulation can be postulated. The results of this study may open an important new approach in the treatment of vascular diseases.

Acetylcholine↗

Effects of ultra-low-dose aspirin on embolization in a model of laser-induced thrombus formation.

A laser-induced rat mesenteric vessel thrombosis model was used to evaluate the effect of acetylsalicylic acid (ASA) at ultra-low doses. A partial occlusion was induced in small mesenteric vessels (diameter 40-50 microns) by an argon laser. The laser induced damage of endothelial cells. Thrombi formed within seconds after the laser lesion and grew rapidly. Embolization began during the minute following the laser injury. Compared to placebo, the administration of ASA at ultra-low doses (334 x 10(-11) mol/mL) by subcutaneous injection in the thorax region (0.2 mL) induced three different phenomena: (1) a decrease in the number of laser injuries required to induce thrombus formation, (2) an increase in number of emboli removed by the blood stream, and (3) an increase in the duration of embolization. The ultra-low doses of ASA showed a strong increase in the number of emboli and in the duration of embolization.

Animals↗

Experimental thrombosis model induced by free radicals. Application to aspirin and other different substances.

A large number of experimental studies suggests that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-reperfusion. The purpose of this study was to determine whether oxygen free radicals can induce thrombosis. In so doing we have developed a new experimental thrombosis model. Reproducible focal thrombosis has been achieved by irradiating mesenteric arterioles of rat for variable time with green filtered light issuing from a mercury lamp after systemic injection of different rose bengal doses. The number of emboli that remove in the blood (N), the duration of total occlusion (T) and the number of emboli per minute were then measured. As control, no rose bengal administration was done and the vessels were exposed to the filtered light. In comparison with this control, results clearly showed that free radicals always induced thrombosis and the induced thrombus was mainly composed of platelets. In this new thrombosis model induced by free radicals antithrombotic drugs (aspirin, 200 mg/Kg, heparin, 2 mg/Kg) and antioxidants (vitamin C, 10 and 20 mg/Kg, allopurinol, 200 and 300 mg/Kg, vitamin E, 500 and 1000 mg/Kg) have been tested. Results have shown that only heparin and vitamin E had an antithrombotic effect on thrombus formation induced by free radicals. This model should be useful in studying the effects of different drugs and could lead to new treatment modalities for ischemic accident and other cardiovascular diseases.

Allopurinol↗

Arterial antithrombotic effect of piyavit, the novel pharmacological preparation from the medicinal leech, and of its components, prostanoids and enzyme destabilase.

Piyavit, the novel pharmacological preparation from the medicinal leech (Hirudo medicinalis) contained the leech saliva, produces the potent arterial antithrombotic effect examined on experimental of Laser Induced Thrombus formation. Administrated orally into rats or injected subcutaneously as water extract, non-diluted or in 1600 times diluted, it inhibits statistically significant comparing with control platelet thrombus stimulated by laser beams. Its components, prostanoid fraction and purified enzyme destabilase, endo-epsilon-(gamma-Glu)-Lys-isopeptidase, also inhibit thrombus formation in statistically different manner, comparing with control. All the tested preparations inhibit platelet aggregation induced by ADP. The dependence of arterial antithrombotic effect on the leech prostanoid is discussed.

Administration, Oral↗

Effect of the low molecular weight heparin/non steroidal anti-inflammatory drugs association on an experimental thrombosis induced by laser.

LMWH (Fraxiparine), and NSAIDs (Aspirin, Feldene, Indocid and Profenid) injected together in doses, 1 mg/kg (Aspirin was used at 100 mg/kg), subcutaneously into rats 30 minutes before the thrombosis induction by LASER beams, increased the number of LASER beams required to induce platelet thrombus formation, decreased the number of emboli and reduced the duration of embolization, compared with control (p < or = 0.05). Of all the studied NSAIDs being injected either with LMWH or separately 30 minutes before the thrombosis stimulation by LASER only Aspirin appeared to potentiate the antithrombotic effect of Fraxiparine. Neither LMWH nor NSAIDs (except for Aspirin) at the dosages used modified aggregatory parameters compared with control. But it was observed the inhibition of platelet aggregation by the associations of Fraxiparine with Aspirin, Feldene or Profenid, tested in the whole blood 90 minutes after the drug injections.

Animals↗

Thrombogenicity of ionic and nonionic contrast media tested in a laser induced rat thrombosis model.

Contrast media are used as substances for visualization of vascular system. But, their administration is often associated with thromboembolic complications. The purpose of this study is to evaluate the thrombogenic action of ionic and non-ionic contrast media on thrombus formation. The experimental destruction of endothelial cells by Laser injury leads to thrombus and emboli formation. Two ionic and two non-ionic contrast media were injected intravenously via penis vein and tested at various dosages (1.0 and 2.5 ml/kg) 5, 30, 45 and 65 minutes after injection. The administration of these contrast media decreases the number of Laser injuries required to induce thrombus formation, increases the number of emboli which detached from thrombus and prolongs duration of embolization (p < or = 0.05). These experimental results suggest that ionic and non-ionic contrast media induce thrombogenic effects. This thrombogenicity was the greatest for non-ionic contrast media. It was observed the decrease of the white cells, red cells and platelets.

Animals↗

[Experimental models of arterial thrombosis].

Arterial thrombosis is clearly responsible for a very wide range of cardiovascular diseases, which is why many models of arterial thrombosis have been developed. These models are based on various techniques such as electrical, mechanical, biochemical, photochemical induction. They are an essential prerequisite to the understanding of molecular and cellular phenomena and are also essential to test the antithrombotic activity of new molecules before the first clinical trials in man. The large range of models means that the most appropriate model can be selected for the study of the test substance. However, the antithrombotic activity of a substance needs to be studied by several models. Most of these models induce total occlusion in which the number of parameters studied is limited. As a result of technological progress and the development of techniques such as laser and image analysers, new perspectives are now available for both basic and pharmacological research. Consequently, the already major value for these models should continue to grow over the years to come.

Animals↗

[Antithrombotic effect of piavit--a substance from the medicinal leech (Hirudo medicinalis), containing prostanoid and destabilase fractions].

The protective antithrombotic effects of piyavit, a novel pharmacological preparation from the medicinal leech, its water extract concentrated and diluted 1600-fold, the piyavit fraction containing leech prostanoids and highly purified destabilase, epsilon-(gamma-Glu)-Lys-isopeptidase isolated from the medicinal leech (Hirudo medicinalis), have been studied. All the preparations under study inhibited clot formation in rat mesanterium arterioles stimulated by laser energy, contained leech prostanoids immunoenzymatically identified as 6-keto-PgF1 alpha and inhibited platelet aggregation induced by ADP. The putative mechanism of their antithrombotic effect is discussed.

Animals↗

Effects of aspirin on embolization in an arterial model of laser-induced thrombus formation.

This model of arterial thrombosis induced by laser was used to evaluate the effect of aspirin (Aspegic) on embolization. A partial occlusion was induced in small mesenteric arterioles (diameter 35-40 microns) with an Argon Laser. The laser induced the formation of a vessel wall lesion with damage of endothelial cells. Thrombus formed within seconds after the laser lesion and grew rapidly. Embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenomena. The duration of embolization was 6.50 +/- 0.84 min in the control group. Then the thrombus became stable and partially obstructed the vessel lumen. The administration of aspirin at three doses (50, 100, 200 mg/kg) by intramuscular injection, 15 min before the laser injury, induced three different phenomena: (1) an increase of the number of laser injuries required for the thrombus formation; (2) a dose-dependent decrease in the duration of embolization, and (3) a dose-dependent decrease in the number of emboli. The highest dose injected induced the strongest reduction in the duration of embolization and the number of emboli.

Animals↗

Effects of aprotinin on heparin activities and heparin neutralization with protamine.

In order to investigate the new situation in which aprotinin is proposed as a novel approach to reducing post operative bleeding, specially in cardiopulmonary bypass (CPB) surgery during which heparin and protamine are commonly used, preliminary in vitro and in vivo studies have been performed. Aprotinin increases the anticoagulant heparin effects in vitro, and the hemorrhage time in vivo. But in addition to protamine, there are no statistically significant differences with heparin-protamine situation, indicating aprotinin does not disturb the neutralizing activities of protamine on heparin.

Animals↗

Could non steroidal anti-inflammatory drugs be used to potentiate L.M.W.H. activity in thrombosis? (Part II).

Thromboembolic diseases are one of the main cause of mortality. Heparin fractions obtained by chemical or enzymatical depolymerization of unfractionated heparin are now widely used in the prevention of those illness. However, curative dosages have bad side effects which could be avoid by the potentiation of the antithrombotic efficacy of non-active dosages. A previous study (4) has shown that a non-steroidal anti-inflammatory (NSAI) drug like Phenylbutazone could favour the antithrombotic efficacy of Fraxiparine at a very low dose. The aim of this study was then to determine if other NSAI elements could present the same or better proactive effects.

Animals↗