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Biomedical subjects

A Beretz

Publications and source records attributed to A Beretz.

At least 55 records · Page 3Linked to original sources
PubMed1986

Inhibition of human platelet cyclic AMP phosphodiesterase and of platelet aggregation by a hemisynthetic flavonoid, amentoflavone hexaacetate.

Amentoflavone hexaacetate (AmAc) was synthesized from natural amentoflavone (Am), a biflavonoid extracted from Viburnum lantana L. Am does not inhibit aggregation of intact platelets up to a concentration of 100 microM but inhibits human platelet cAMP phosphodiesterase (IC50 = 22.0 microM). AmAc is a potent inhibitor of the aggregation of washed human platelets induced by ADP (IC50 = 2.3 microM) or collagen (IC50 = 4.7 microM). AmAc inhibits crude (IC50 = 8.6 microM) or partially purified (IC50 = 42.2 microM) human platelet cAMP phosphodiesterase. In the presence of prostaglandin E1, AmAc (10 microM) induces a 3.7-fold increase in total platelet cAMP. The characteristics of this action suggest a role for cAMP in the mechanism of action of AmAc. The incubation of AmAc with intact platelets for 5 min is necessary for its activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Potentiation by adrenaline of human platelet activation and the inhibition by the alpha-adrenergic antagonist nicergoline of platelet adhesion, secretion and aggregation.

Adrenaline (1 to 10 microM) can induce the aggregation of human platelets suspended in citrated plasma but does not induce the aggregation of washed human platelets at doses as high as 1 mM, although these platelets respond normally to ADP, PAF-acether, collagen, arachidonic acid, thrombin, the endoperoxide analog U-46619 and the Ca2+ ionophore A23187. Adrenaline (0.5 microM) potentiates the aggregation and secretion induced by all the previous agonists in citrated platelet-rich plasma (cPRP) or in washed platelets. The activation by adrenaline of human platelets is mediated by alpha 2-adrenergic receptors, as demonstrated by inhibition with a series of adrenergic antagonists. The alpha-adrenergic antagonist nicergoline inhibits the activation of human platelets by adrenaline in the following situations: nicergoline inhibits the aggregation and secretion caused by adrenaline in cPRP (IC50 0.22 microM and 0.28 microM respectively); nicergoline inhibits the aggregation and secretion induced by the combination of adrenaline and each aggregating agent listed above in cPRP (IC50 ranging from 0.1 to 2.5 microM) or in washed platelets (IC50 ranging from 0.1 to 0.8 microM); nicergoline inhibits the binding of 3H-yohimbine to washed human platelets (IC50 0.26 microM); the intravenous administration of nicergoline (0.5 mg/kg per day) to patients inhibits significantly the ex vivo response of their platelets to adrenaline in cPRP. High concentrations of nicergoline also inhibit the aggregation and secretion induced by the aggregating agents listed above in cPRP (IC50 range 108 to 670 microM) and in washed platelets (IC50 range 27 to 140 microM) and the adhesion of platelets to collagen-coated surfaces. This latter effect is not mediated through blockade of alpha-adrenoceptors. A possible role of adrenaline in platelet activation in vivo could justify the use of nicergoline (Sermion), an alpha-adrenergic antagonist in combination therapy to prevent arterial thrombosis.

Blood Platelets↗
PubMed1986

[Methods of studying platelet function. Biological markers of the activation of human platelets in vivo and in vitro].

Platelets play a key role in hemostasis, thrombosis, atherosclerosis and their pathological consequences. It is possible to follow platelet activation in vivo by measuring bleeding time, platelet count, existence of circulating platelet aggregates or platelet survival and sequestration. In vitro tests include measurement of platelet adhesion, aggregation alpha, and dense granule secretion. It is also possible to follow biochemical events linked to platelet activation such as prostaglandin metabolism, Ca2+ levels or platelet membrane modifications (receptors, glycoproteins, coagulant activities, antigens). Some of these markers of platelet activation are modified in diseases (thrombotic events, hyperlipoproteinemia) and the use of artificial surfaces. It is not always possible to know if the modifications are the cause or the consequence of the pathological event. Unfortunately, some results are questionable because of methodological procedures. Some of these tests have been used to follow the involvement of platelets in a pathological event or to evaluate a prethrombotic state in a patient. It is not yet possible to identify directly, or by the mean of a marker of platelet activation, a patient who is likely to experience a thrombotic episode.

Blood Platelets↗
PubMed1985

Non-immune interaction of erythrophilic IgG fractions with human red blood cells.

Immunoglobulin G was separated on cellulose phosphate column to afford four distinct protein fractions (CP-I, II, III and IV). 125I-labeled fractions CP-III and CP-IV were found to be capable of binding specifically to normal human erythrocytes. The effect of the four fractions on osmotic resistance of red blood cells (RBC) was studied. RBC were obtained from eight patients with hereditary spherocytosis (HS), from a single parent of two non-related patients, and from five normal donors. RBC fragility of normal and one parent were unaffected by any of the immunoglobulin fractions. In contrast, a small but significant decrease in osmotic resistance was observed when RBC from HS patients and the second parent were incubated with protein fractions CP-III and CP-IV.

Adult↗
PubMed1983

Tissue and substrate specificity of inhibition by alkoxy-aryl-lactams of platelet and arterial smooth muscle cyclic nucleotide phosphodiesterases relationship to pharmacological activity.

Alkoxy-aryl-lactams (cilostamide, AAL 05, ZK 62 711, Ro 20-1724) inhibit differently cAMP or cGMP phosphodiesterases from blood platelets or vascular smooth muscle. Cilostamide (IC50 0.23 microM) and AAL 05 (IC50 0.15 microM) are 100 times more potent towards platelet cAMP phosphodiesterase whereas ZK 62 711 (IC50 2 microM) and Ro 20-1724 (IC50 33 microM) inhibit more selectively the enzyme from aorta. The substrate specificity of the inhibitors is different in the two tissues: ZK 62 711 and cilostamide are respectively 345 and 290 times more potent as inhibitor of cAMP than cGMP phosphodiesterase from vascular smooth muscle (ZK 62 711) or platelets (cilostamide). M + B 22,948 selectively inhibits cGMP phosphodiesterase with an IC50 of 9 or 24 microM on platelet or aorta enzyme, respectively. In general, the potencies of spasmolytic and platelet inhibitor effects vary from one drug to the other with the potency of inhibition of phosphodiesterase from the corresponding tissue. These data suggest that phosphodiesterases from platelets are different from those of arterial smooth muscle.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

[Platelet aggregation: a tool for clinical investigation and pharmacological study. Methodology].

Platelet aggregation can be measured quantitatively by continuous recording of the transmission of a beam of light across a suspension of platelets in constant agitation in an aggregometer. In routine clinical investigation, the study of platelet aggregation is performed on platelet-rich citrated plasma (PRPc). The blood sample has to be excellent to eliminate all traces of thrombin. The blood is collected in 3.8% sodium dihydrate citrate (1 volume for 9 volumes of blood). It is centrifuged at 190 g for 15 minutes at ambiant temperature. The PRPc obtained can be diluted with platelet-poor plasma (PPP) to adjust the concentration of platelets to 3 X 10(5)/microliters. The PRPc is stored at ambiant temperature in stoppered tubes under CO2 to avoid variations in pH. The maximal delay between the collection of the blood and the end of the study of aggregation is 3 hours. In certain cases, in order to define the platelet lesion and to eliminate the influence of plasma proteins, clotting factors and anti-coagulants, a suspension of washed platelets is used. The blood is collected on acid-citrate-dextrose (ACD) and centrifuged at + 37 degrees C to obtain the PRPc. The platelet deposit obtained by centrifugation of the PRPc is washed twice, according to Mustard's method, in Tyrode-albumin buffer at a concentration of 0.35% at + 37 degrees C. It is re-suspended in the same buffer solution at + 37 degrees C in the presence of apyrase and the platelet concentration is adjusted to 3 X 10(5)/microliters. The aggregation or agglutination of the platelets is induced by several agents: ADP, adrenalin, collagen, thrombin, arachidonic acid, ionophor A 23187, PAF-acether and ristocetin. The quantitative study of the aggregation curves of human platelets allows us to study the physiological and biochemical mechanisms control platelet aggregation, to recognize and classify the hereditary or acquired platelet abnormalities which lead to clinical haemorrhagic or thrombotic manifestations and to study the effect of drugs which inhibit platelet aggregation and to understand their mechanism of action.

Anticoagulants↗
PubMed1982

Role of cyclic AMP in the inhibition of human platelet aggregation by quercetin, a flavonoid that potentiates the effect of prostacyclin.

Quercetin (3.3',4',5,7-pentahydroxyflavone) has previously been shown to inhibit cyclic nucleotide phosphodiesterases prepared from various cell homogenates and the function of intact human platelets. We now report that (1) high concentrations of quercetin raise platelet cAMP levels; and (2) quercetin potentiates the inhibitory effect of prostacyclin (PGI2) on ADP-induced washed human platelet aggregation and the elevation of platelet cAMP levels elicited by PGI2. These results suggest a role for cAMP in the mechanism of action of quercetin on blood platelets.

Adenosine Diphosphate↗
PubMed1982

Inhibition of aggregation and secretion of human platelets by quercetin and other flavonoids: structure-activity relationships.

Quercetin and 12 other natural flavonoid aglycones inhibit washed human platelet aggregation and secretion of serotonin induced by ADP, collagen or thrombin. The inhibitory effect of flavonoids is of the same order of magnitude as IBMX and dipyridamole. The structural features required for a flavonoid to inhibit human platelet function are similar to those previously reported by us to inhibit cyclic nucleotide phosphodiesterase. The inhibitory effect of flavonoids on human platelet function was diminished by saturation of the C-2, C-3 double bond, lack of the C-4 carbonyl, glycosylation at C-3 and a high number of hydroxyl substituents.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Tuftsin analogs for probing its specific receptor site on phagocytic cells.

Six new analogs of the phagocytosis-stimulating peptide tuftsin were synthesized with the eventual aim of characterizing and isolating the tuftsin receptor. These analogs can be classified as follows: (a) photoaffinity labelling analogs for the specific covalent attachment to the tuftsin receptor: (b) fluorescent analogs containing either rhodamine or dansyl fluorescent probes for microscopic visualization of the tuftsin receptor; (c) biotin analog for separation and purification of the receptor by affinity methods. In this paper we describe the various synthetic pathways employed to introduce sensitive prosthetic groups into the tuftsin molecule while preserving its biological activity. Activities of the various analogs synthesized as compared to tuftsin in biological and receptor-binding assays are described. All analogs are able to stimulate phagocytosis of the macrophage cell as well as complete specifically for tuftsin binding sites on these cells.

Affinity Labels↗
PubMed1982

[Thrombogenic properties of the vessel and their inhibition].

Vascular thrombosis is the response to injury of blood and the vessel wall. Normal endothelium is a non thrombogenic surface and is transformed into a thrombogenic surface by endothelial injury, the first step in thrombosis and in the development of atherosclerosis and its thrombotic complications. Many agents may injure the endothelial cells leading to at least three types of lesions: endothelial desquamation, local increase in endothelial turnover without de-endothelialization, endothelial dysfunction. The study of the factors controlling the functions of normal endothelial cells, their proliferation and their pathological modifications is possible with the use of human endothelial cell culture. Local generation of thrombin increases the thrombogenicity of the subendothelium and the accumulation of platelets, an effect inhibited by heparin. Thrombin binds specifically to the endothelium, but in a conformation preventing platelet interaction. PGI2 production by the vessel wall is not the main factor preventing adhesion of platelets to the endothelium or the subendothelium. PGI2 limits thrombus formation at the injury site. In the event of stasis, the inhibition of PGI2 formation by aspirin increases the size of the thrombus containing platelets and fibrin. The thrombogenic response of the vessel wall varies according to the nature of endothelial injury: a lesion causing removal of the endothelium and followed by adhesion of a single layer of platelets; chronic or repeated injury giving rise to a platelet-fibrin thrombus. Initiation and development of the thrombogenic properties of the vessel wall can be inhibited by dietary manipulations or pharmacologic interventions acting at the level of the endothelium, the interactions of platelets and the vessel wall or the coagulation system.

Aspirin↗
PubMed1978

Flavonoid compounds are potent inhibitors of cyclic AMP phosphodiesterase.

The inhibitory activity of 19 flavonoid molecules on cyclic AMP breakdown by a commercial beef heart phosphodiesterase preparation is reported. 7 compounds are active in the micromolar range, 2 of which have a potency equivalent to that of papaverine. Some structure activity relationships are drawn.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

Sulfated polysaccharides modulate effects of acidic and basic fibroblast growth factors on repair of injured confluent human vascular endothelium.

Semi-automatic analysis of the repair process of a circular mechanical lesion of confluent human vascular endothelial cells in vitro was used to evaluate the contributions of cell migration and cell proliferation. Standard heparin added to culture medium that contained 30% human serum induced an inhibition of cell migration at the lesion margin during the first day after injury. Several sulfated polysaccharides were tested in the presence of 5% human serum. Standard heparin, low molecular weight heparin, or pentosan polysulfate markedly reduced the rate of lesion regeneration. Cell proliferation, measured by 3H-thymidine incorporation at the lesion margin, and cell migration were both decreased. In contrast, the combination of acidic fibroblast growth factor with a sulfated polysaccharide accelerated the repair process. Basic fibroblast growth factor combined with a sulfated polysaccharide gave a regeneration rate similar to that of the control; however, at 4 days after injury, the residual lesion was the same when basic fibroblast growth factor was used alone or when it was combined with sulfated polysaccharides. Acidic fibroblast growth factor totally reversed the effects of sulfated polysaccharides on the repair process by enhancing endothelial cell proliferation and allowing endothelial cell migration.

Autoradiography↗