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Biomedical subjects

O N Ulutin

Publications and source records attributed to O N Ulutin.

At least 19 recordsLinked to original sources
PubMed1990

The pharmacology and clinical pharmacology of defibrotide: a new profibrinolytic, antithrombotic and anti-platelet substance.

Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human.

Animals↗
PubMed1988

Clinical pharmacology and mode of action of a new antithrombotic compound: Defibrotide.

Defibrotide is a derivative of polydeoxyribonucleotide extracted from bovine lung. Defibrotide has been found to modulate endothelial cell function causing increase in t-PA production and release with correction the defect in Cuff test in vascular disorders. Defibrotide causes a significant elevation in the PGI2 formation. In addition increase of platelet c-AMP levels with a decrease of MDA and TXA2 formation has been shown in human subjects. Defibrotide causes an inhibition of platelet activation were demonstrated with surface activation method as well ultrastructurally. Besides, an increase of protein C and FV were observed, a synergic action with heparin was observed. A strong antithrombotic effect has been shown in animal models and unlike most antithrombotic drugs defibrotide did not cause any effect of clotting tests in animals and human subjects. All findings support our earlier suggestion that defibrotide mainly acts via the modulation of endothelial cell function and acts as a novel fashion in contrast to the other drugs used in this area.

Adult↗
PubMed1986

Alteration of platelet glucose transport system in atherosclerosis.

Functional and biochemical alterations of platelets in patients suffering from atherosclerosis were studied in our laboratory. One of the most striking alterations observed is in the platelet active glucose transport system. The Na+/K+ gradient dependent active transport system of glucose is found to be absent in the platelets of atherosclerotics. The platelet glucose transport kinetics in these subjects give unsaturable and linear kinetics. Furthermore, the specific glucose binding protein activity detected in the incubation fluid after cold osmotic shock to the platelets of normal subjects is found to be absent in the platelets of atherosclerotics. The platelet active glucose transport system is normal in juvenile onset diabetics, whereas it is impaired in maturity onset diabetics with clinical manifest atherosclerosis. The release inducers like ADP, adrenalin and collagen exert no effect on the platelet active glucose transport system. The specific glucose-binding protein is an unreleasable protein in the platelets of normal subjects. Hence, the absence of active glucose transport system in atherosclerotics is not due to the activated platelets in circulation.

Arteriosclerosis↗
PubMed1986

Effect of defibrotide in electrically induced thrombosis in dogs.

Thrombi were electrically induced in dogs. The alterations of the vessel wall were studied in samples obtained on the 8th day from control and treated animals. Changes in coagulation parameters were monitored daily. Animals were treated with 600 mg defibrotide (Crinos) daily for a week, starting 24 h after the induction of thrombi. In the control dogs there was thickening of intima with endothelial hyperplasia and smooth muscle proliferation. The treated animals did not show any morphological or ultrastructural alterations (SEM). This observation encourages us to examine the role of fibrinolytic and endothelial supportive therapy for prevention of development of vascular changes.

Animals↗
PubMed1986

Effects of defibrotide on peripheral obliterative vascular diseases.

Twenty-nine patients with atherosclerotic obliterative vascular disorder and 9 cases of Buerger's disease were treated with 600 mg defibrotide daily for 10 days and then three times weekly for 3 months. The response to therapy was evaluated from hemostatic parameters, venostasis test (cuff test), treadmill testing, and radionuclide arteriography. We observed increased pain-free intervals in daily life and during treadmill testing. There was also a significantly higher response in the cuff test and improved perfusion as seen by radionuclide arteriography.

Adult↗
PubMed1985

Alteration of prostanoids in atherosclerosis.

We have briefly summarized only the data obtained in our own laboratory without including an extensive literature review. We have evaluated the changes in platelet membrane phospholipids and prostanoid formation in platelets. In atherosclerosis platelets show an activated prostanoid formation, whereas the plasma PGI2 levels are decreased.

6-Ketoprostaglandin F1 alpha↗
PubMed1977

Some properties of autoprothrombin II-A anticoagulant.

Autoprothrombin II-A anticoagulant was isolated from bovine prothrombin. Purified prothrombin was applied to DEAE-cellulose chromatography after incubation with thrombin. Four protein peaks were obtained where the third peak corresponded to the anti-coagulant effect. The fractions under the third peak were pooled together and the anticoagulant effect was evaluated with different methods. From 25,470 +/- 2,800 U of prothrombin, 5,800 +/- 1,400 U of inhibitor were obtained. The inhibitor was found to be most effective at pH 7.2--7.8. In vitro, the inhibitor inhibited the thrombin time and the plasma clotting time highly significantly but had no effect on euglobulin lysis time and fibrin plates. In vivo, when injected into rabbits, the inhibitor effect was also significant on the same tests. The autoprothombin II-A anticoagulant had a protective effect on DIC formation with rabbit brain thromboplastin administration. This protective effect was found to be statistically significant.

Animals↗
PubMed1977

Platelet phospholipids in liver cirrhosis.

In the present study we have investigated and also compared the biochemical nature of the platelet phospholipids in patients with portal liver cirrhosis and in normals. Normal platelets contained 10.88 +/- 0.83 microgram of phospholipid phosphorus per 10(9) platelets whereas the cirrhosis platelets contained 7.63 +/- 1.29 microgramP/10(9) platelets. In cirrhosis there was a 29.87% decrease of phospholipids compared to normal. However the percentage distribution of phospholipids in cirrhosis was similar to normal. But each phospholipid value in cirrhosis was found lower then normal. Estimated as microgram phosphorus per 10(9) platelets decreased amounts of phosphotidyl inositol (PI) (0.29 +/- 0.16), phosphotidyl serine (PS) (0.49 +/- 0.12), phosphotidyl ethanolamine (PE) (2.0 +/- 0.43) and spingomyelin (SPH) (1.42 +/- 0.31) and phosphotidyl choline (PC) (3.25 +/- 0.62) and total lipid phosphorus (7.63 +/- 1.29) were found in the patient group.

Blood Platelets↗