Platelet aggregation Research Papers - Academia.edu (original) (raw)

This study is a significant milestone in the development of drug-eluting polyester vascular prosthesis using a polymer of cyclodextrins. It addresses experimentally the safety and the efficacy of these prostheses before this innovative... more

This study is a significant milestone in the development of drug-eluting polyester vascular prosthesis using a polymer of cyclodextrins. It addresses experimentally the safety and the efficacy of these prostheses before this innovative concept could be applied in clinical medicine. For that reason, this study is unique. The influence of this concept could be tremendous in the near future since one might be able to load specific bioactive molecules, especially antibiotics, onto a graft or stent graft according to therapeutic goals.

Introduction: Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible... more

Introduction: Depressive disorders have been identified as independent risk factors for coronary heart disease. The present study (i) compared platelet function of depressed patients with that of healthy controls, (ii) analysed possible aggregability changes during 3 months of treatment with antidepressants, and (iii) sought to assess different effects of escitalopram and nortriptyline on platelet aggregation. Methods: Blood samples of 91 major depressed patients and 91 healthy controls were analysed with whole blood aggregometry in a case-control setting. Depressed patients were randomized to two groups treated either with escitalopram (n = 47) or nortriptyline (n = 44). Platelet aggregation was studied on days 0, 1, 3, 7, 14, 21, 84 of continuing medication and was determined in response to adenosine diphosphate (ADP) and collagen. Results: Platelet aggregation induced by ADP was increased among depressive patients compared with that of healthy controls (26%, p = 0.006). With antidepressant treatment, changes in platelet aggregation remained comparable in both groups at early time points (d1 to 21). In contrast, at day 84, patients with antidepressive response revealed significant differences in both medication groups: Patients receiving escitalopram showed a 23% decrease of ADP induced aggregation (p = 0.03) and a 15% decrease of collagen induced aggregation (p = 0.03). With nortriptyline the increase in impedance was reduced by 29% after ADP induction (p = 0.046). Conclusion: Depressed patients have higher ex vivo platelet aggregation that may contribute to increased cardiovascular morbidity. After three months of antidepressant treatment with either escitalopram or nortriptyline, platelet aggregation was significantly reduced in antidepressant responders, irrespective of the antidepressant medication type.

In 2 siblings with recurring attacks of thrombotic thrombocytopenic purpura, platelet aggregation was found to be decreased during attacks. In contrast with reported observations in other patients, aggregation was found decreased also in... more

In 2 siblings with recurring attacks of thrombotic thrombocytopenic purpura, platelet aggregation was found to be decreased during attacks. In contrast with reported observations in other patients, aggregation was found decreased also in symptom-free periods. ATP/ADP ratio in platelet rich plasma was normal. The cause of decreased aggregation was not uraemia, alcohol or drugs. In a healthy sister, platelet aggregation induced by A D P was subnormal. The attacks in 1 of the patients responded to infusion of fresh frozen plasma.

To cite this article: Ulrichts H, Harsfalvi J, Bene L, Matko J, Vermylen J, Ajzenberg N, Baruch D, Deckmyn H, Tornai I. A monoclonal antibody directed against human von Willebrand factor induces type 2B-like alterations. J Thromb Haemost... more

To cite this article: Ulrichts H, Harsfalvi J, Bene L, Matko J, Vermylen J, Ajzenberg N, Baruch D, Deckmyn H, Tornai I. A monoclonal antibody directed against human von Willebrand factor induces type 2B-like alterations. J Thromb Haemost 2004; 2: 1622-28.

Background: Quercetin, a flavonoid present in the human diet, which is found in high levels in onions, apples, tea and wine, has been shown previously to inhibit platelet aggregation and signaling in vitro. Consequently, it has been... more

Background: Quercetin, a flavonoid present in the human diet, which is found in high levels in onions, apples, tea and wine, has been shown previously to inhibit platelet aggregation and signaling in vitro. Consequently, it has been proposed that quercetin may contribute to the protective effects against cardiovascular disease of a diet rich in fruit and vegetables. Objectives: A pilot human dietary intervention study was designed to investigate the relationship between the ingestion of dietary quercetin and platelet function. Methods: Human subjects ingested either 150 mg or 300 mg quercetin-4¢-O-b-D-glucoside supplement to determine the systemic availability of quercetin. Platelets were isolated from subjects to analyse collagen-stimulated cell signaling and aggregation. Results: Plasma quercetin concentrations peaked at 4.66 lM (± 0.77) and 9.72 lM (± 1.38) 30 min after ingestion of 150-mg and 300-mg doses of quercetin-4¢-O-b-Dglucoside, respectively, demonstrating that quercetin was bioavailable, with plasma concentrations attained in the range known to affect platelet function in vitro. Platelet aggregation was inhibited 30 and 120 min after ingestion of both doses of quercetin-4¢-O-b-D-glucoside. Correspondingly, collagen-stimulated tyrosine phosphorylation of total platelet proteins was inhibited. This was accompanied by reduced tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase Cc2, components of the platelet glycoprotein VI collagen receptor signaling pathway. Conclusions: This study provides new evidence of the relatively high systemic availability of quercetin in the form of quercetin-4¢-O-b-D-glucoside by supplementation, and implicates quercetin as a dietary inhibitor of platelet cell signaling and thrombus formation.

Aspirin (Asp), acetyl salicylic acid, is a drug widely used as an analgesic, an antipyretic and, in particular, as an inhibitor of platelet aggregation. Recently, a lipid perturbation mechanism for drug action has been given much priority... more

Aspirin (Asp), acetyl salicylic acid, is a drug widely used as an analgesic, an antipyretic and, in particular, as an inhibitor of platelet aggregation. Recently, a lipid perturbation mechanism for drug action has been given much priority as it is critically important for the rearrangements of membrane surface proteins, receptors, etc. In the present paper we have reported the lipid-ordering effect of Asp in the liposomal membrane of dipalmitoyl phosphatidyl choline from a fluorescence anisotropy study of a membrane-embedded fluorescent probe, 1,6-diphenyl-l,3,5-hexatriene. The result of our study indicates that the drug Asp disorders the liposomal membrane. This probably arises because of the structure (fiat ring) of Asp, and the fact that its lipophilicity is greater than its hydrophilicity (solution spectrum); it also accounts for the analgesic as well as inhibitory effects of Asp on platelet aggregation.

The mouse antithrombotic assay represents a model of fatal pulmonary thromboembolism induced by intravenous injection of collagen and epinephrine. Mice were protected by low doses of two disintegrins, albolabrin (10 l.@/mouse) and... more

The mouse antithrombotic assay represents a model of fatal pulmonary thromboembolism induced by intravenous injection of collagen and epinephrine. Mice were protected by low doses of two disintegrins, albolabrin (10 l.@/mouse) and eristostatin (0.6 pg/mouse), whereas high doses of a thrombin inhibitor and an inhibitor of von Willebrand Factor binding to glycoprotein Ib were not effective. Injection of collagen and epinephrine resulted in the drop of platelet count and accumulation of platelet aggregates in 'the lung that appears to be the immediate cause of death. Albolabrin or eristostatin administration did not prevent the decrease of platelet count. Injection of albolabrin resulted in the formation of smaller and reversible platelet aggregates in the lungs and decreased accumulation of SlCr-labeled platelets in the lung suggesting that this disintegrin decreases formation of platelet aggregates in viva We compared the effects of allbolabrin and eristostatin on platelet aggregation, tail bleeding time, and survival of challenged animals. Eristostatin was about 5 times more potent in inhibiting platelet aggregation in vitro than albolabrin and 38 times more potent than albolabrin in protecting animals from sudden death. Both disintegrins, at the same doses (0.6-5 ltglmouse), caused similar dose-dependent prolongation of the bleeding time; however, only eristostatin exerted a protective effect. In conclusion, a) the mouse antithrombotic assay is a suitable model to screen and to evaluate the potency of platelet fibrinogen receptor antagonists in vivo; b) the results of the antithrombotic assay correlate better with the inhibition of platelet aggregation in vitro than with the prolongation of bleeding time.

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet... more

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/- 3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/- 6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral supplementation, both plasma and platelet taurine concentrations increased significantly in the diabetic patients, reaching the mean values of healthy control subjects. The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 ...

We have previously shown that adhesion of human platelets to immobilized collagen is extremely rapid, with initial rates approaching 3% of single particles adhering per 10 ms. Here, we have investigated adhesion efficiency to collagen as... more

We have previously shown that adhesion of human platelets to immobilized collagen is extremely rapid, with initial rates approaching 3% of single particles adhering per 10 ms. Here, we have investigated adhesion efficiency to collagen as a function of platelet density. Platelet subpopulations: low-density (1.040<d < 1.065 g/ml), intermediatedensity (1.065 < d < 1.070 g/ml) and high-density (1.070<d< 1.080 g/ml) were separated by Percoll density gradient centrifugation. They constituted 24%, 47% and 29% of the total platelet population and had mean volumes of 6.01, 7.37 and 8.21 fl, respectively. Using a continuousflow, micro-affinity column, we found that the most dense (large) platelets exhibited initial rate of adhesion 4 times greater than the least dense (small) platelets. They were also less sensitive to inhibition by prostacyclin (PGIJ. In contrast, there was no significant difference in aggregation induced by high doses of ADP and collagen, indicating that the most dense platelets were not preferentially involved in aggregation induced by high doses of agonists. These results suggest that normal circulating platelets can be distinctly heterogeneous in their ability to adhere to collagen under arterial-flow conditions. The greater efficiency of high-density platelets may be related to increased content of the glycoprotein Ia/IIa (GPIa/IIa) complex.

We describe a patient with Klinefelter's syndrome complicated by recalcitrant leg ulcers, in whom marked platelet hyperaggregahility was demonstrated and venous disease excluded. Androgen replacement therapy appeared to bring about... more

We describe a patient with Klinefelter's syndrome complicated by recalcitrant leg ulcers, in whom marked platelet hyperaggregahility was demonstrated and venous disease excluded. Androgen replacement therapy appeared to bring about healing of the patient's ulcers and was associated with reversal of the platelet abnormality. The possible role of androgen deficiency in the pathogenesis of leg ulceration is discussed.

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Platelet aggregation may be an important factor in the feasibility of transcatheter laser angioplasty. The in vitro effects of increasing doses of CO, laser irradiation on platelet number, function, and surface ultrastructure were... more

Platelet aggregation may be an important factor in the feasibility of transcatheter laser angioplasty. The in vitro effects of increasing doses of CO, laser irradiation on platelet number, function, and surface ultrastructure were examined. Results indicated a progressive doseresponse reduction of both platelet number and function following laser irradiation. By scanning electron microscopy the irradiated platelets showed dose-related changes in pseudopods as well as progressive damage of the cell membrane.

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow... more

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worstcase biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.

Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role... more

Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50-100 AM) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O 2-were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O 2-were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O 2-(À70%, P b 0.001) and CD40L (À68%, P b 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression.

a b s t r a c t Introduction: Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific... more

a b s t r a c t Introduction: Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific mechanism by which this action occurs has not been established. The aim of this study was to investigate the inhibitory effect of soy-isoflavones and the metabolite of daidzein, equol, on agonist-induced platelet responses dependent on thromboxane A 2 (TxA 2 ) receptor. Material and methods: Competitive radioligand binding assay was used to screen for affinity of these compounds to the TxA 2 receptor. The effect of equol on platelet activation, evaluate through of release of the ATP, by analogs of TxA 2 was analyzed. The effect of equol on platelet aggregation was investigated with ADP, U46619 (a TxA 2 mimic) and the calcium ionophore A23187. Results: The data showed that aglycone isoflavones and equol bind to TxA 2 receptor in the µmol/L range, whereas their glucoside derivates had very low binding activity for this receptor. Under equilibrium conditions, the following order of the relative affinity in inhibiting [ 3 H]-SQ29585 binding was: equol N genistein N daidzein N glycitein ≫ genistin, daidzin, glycitin. Equol interaction was reversible and competitive for labeled-SQ29548 with not apparent decrease in the number of TxA 2 binding sites. In addition, from platelet activation studies, equol effectively inhibited ATP secretion elicited by the TxA 2 analog U46619. On the other hand, equol inhibited the platelet aggregation induced by U46619 and A23187, while it failed to inhibit that induced by ADP. Conclusions: The aglycone isoflavones from soy, and particularly equol, have been found to have biological effects attributable to thromboxane A 2 receptor antagonism. These findings may help elucidate how dietary isoflavone modulate platelet function and explain why soy-rich foods are claimed to have beneficial effects in the prevention of thrombotic events.

Updated guidelines on percutaneous coronary intervention recommend increasing the dose of clopidogrel to 150 mg in high-risk patients if <50% platelet inhibition is demonstrated. However, to date, the functional impact of this... more

Updated guidelines on percutaneous coronary intervention recommend increasing the dose of clopidogrel to 150 mg in high-risk patients if <50% platelet inhibition is demonstrated. However, to date, the functional impact of this recommendation has been poorly explored. The aim of this study was to assess the functional implications associated with the use of clopidogrel 150 mg/day in patients with inadequate platelet inhibition while receiving standard 75 mg/day maintenance treatment. Patients with diabetes mellitus have a higher prevalence of inadequate clopidogrel-induced antiplatelet effects and stent thrombosis compared with those without diabetes and were selected for this analysis. Platelet inhibition was assessed using the VerifyNow P2Y 12 assay in patients with type 2 diabetes receiving dual-antiplatelet therapy. Patients (n ‫؍‬ 17) with <50% platelet inhibition were treated with clopidogrel 150 mg/day for 1 month. Adenosine diphosphate-induced aggregation and the P2Y 12 reactivity ratio were also assessed. Platelet function profiles were compared with that of a control group (n ‫؍‬ 17) with >50% inhibition. Platelet inhibition increased from 27.1 ؎ 12% to 40.6 ؎ 18% in patients treated with clopidogrel 150 mg/day (p ‫؍‬ 0.009; primary end point). All other functional measures also showed enhanced clopidogrelinduced antiplatelet effects. The degree of platelet inhibition achieved after treatment with clopidogrel 150 mg/day varied broadly, and only 35% of patients yielded a degree of platelet inhibition >50%. Increasing the dose in patients with inadequate response to clopidogrel did not reach the same degree of antiplatelet effects as those achieved in patients with adequate response while receiving 75 mg/day. In conclusion, the use of a 150 mg maintenance dose of clopidogrel in patients with type 2 diabetes with <50% platelet inhibition is associated with enhanced antiplatelet effects. However, the antiplatelet effects achieved are nonuniform, and a considerable number of patients persist with inadequate platelet inhibition.

The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have highest antimicrobial activity. It is used as antidote... more

The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have highest antimicrobial activity. It is used as antidote against certain venom, due to its platelet inhibitory effect and also reported to have hypocholesterolemic effect. However its anticoagulant and thrombolytic effect were not been investigated, hence a prospective in-vitro/in-vivo study was designed to determine the effect of Citrus limon on blood parameters, coagulation and anticoagulation factors. In-vitro tests revealed highly significant increase in thrombin time and activated partial thromboplastin time by Citrus limon, whereas fibrinogen concentration was significantly reduced in comparison to control, however prothrombin time was not affected significantly. In-vivo testing of Citrus limon was done at three different doses i.e. 0.2ml/kg, 0.4ml/kg and 0.6ml/kg in healthy rabbits. Significant cha...

The effects of laminin isoforms on platelet aggregation were compared and characterized in platelet rich plasma (PRP) obtained from 26 healthy human volunteers. In approximately 38% of the individuals tested, human laminin produced a... more

The effects of laminin isoforms on platelet aggregation were compared and characterized in platelet rich plasma (PRP) obtained from 26 healthy human volunteers. In approximately 38% of the individuals tested, human laminin produced a biphasic platelet aggregation response. Human laminin produced only a primary phase in the remaining "non-responsive" individuals. Mouse laminin, rat laminin and human merosin did not cause platelet aggregation in any of the volunteers. The biphasic platelet aggregation response caused by human laminin was concentration-dependent (0.3-30 nM) and was consistently observed upon repeated testing of "responsive" individuals. The secondary phase of aggregation produced by human laminin in "responsive" individuals was abolished by aspirin, SQ 29,548, a selective thromboxane antagonist, and SK&F 106760, an RGD-derived platelet fibrinogen receptor (GPIIb/IIIa) antagonist. Also, the secondary phase of aggregation was not observed in...

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and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.

Calreticulin Transacetylase (CRTAase) catalyzes the transfer of acetyl group(s) from polyphenolic acetates (PAs) to functional proteins, such as Glutathione S-transferase (GST), NADPH Cytochrome c reductase and Nitric Oxide Synthase (NOS)... more

Calreticulin Transacetylase (CRTAase) catalyzes the transfer of acetyl group(s) from polyphenolic acetates (PAs) to functional proteins, such as Glutathione S-transferase (GST), NADPH Cytochrome c reductase and Nitric Oxide Synthase (NOS) resulting in the modulation of biological activities. A comparison of the specificities of the acetoxy derivatives of coumarins, biscoumarins, chromones, flavones, isoflavones and xanthones has been carried out earlier by us with an aim to study the effect of nature and position of the acetoxy groups on the benzenoid ring and the position of the carbonyl group with respect to oxygen/ nitrogen heteroatom for the catalytic activity of CRTAase. In this communication for the first time, we have studied the influence of differently substituted benzofurans on the CRTAase activity to study the effect of the replacement of pyran ring of coumarin with furan ring, presence of carbonyl at C-3, substitution of C-3 carbonyl group with acetoxy group and presence of various substituents (OAc/OH/Cl) on the benzenoid ring. It was observed that acetoxy derivatives of benzofurans lead to inhibition of ADP induced platelet aggregation by the activation of platelet Nitric Oxide Synthase catalyzed by CRTAase. Accordingly, the formation of NO in platelets by 3-oxo-2,3-dihydrobenzofuran-6,7-diyl diacetate (3a) was found to be comparable with that of model polyphenolic acetate (PA), 7,8-diacetoxy-4-methylcoumarin (DAMC).

Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that activates and directs the migration of leukocytes that have CXCR4, which is the unique receptor for SDF-1. Although SDF-1/CXCR4 interaction has been implicated in various... more

Stromal cell-derived factor-1 (SDF-1) is a CXC chemokine that activates and directs the migration of leukocytes that have CXCR4, which is the unique receptor for SDF-1. Although SDF-1/CXCR4 interaction has been implicated in various inflammatory conditions, its role in modulating ...

High-throughput screening of the GSK compound collection against the P2Y 1 receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity.... more

High-throughput screening of the GSK compound collection against the P2Y 1 receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity. An exemplar analog from this series was shown to inhibit platelet aggregation.

An acidic polysaccharide with anticoagulant activity was isolated from the edible mushroom Auricularia auricula using water, alkali or acid extracts. The alkali extract showed the highest anticoagulant activity and was thereby further... more

An acidic polysaccharide with anticoagulant activity was isolated from the edible mushroom Auricularia auricula using water, alkali or acid extracts. The alkali extract showed the highest anticoagulant activity and was thereby further purified using gel filtration chromatography. Specific anticoagulant activity of the purified polysaccharide was 2 IU/mg and its average mass was ∼160 kDa. The polysaccharide from this species of mushroom contains mainly mannose, glucose, glucuronic acid and xylose but no sulfate esters. Its anticoagulant activity was due to catalysis of thrombin inhibition by antithrombin but not by heparin cofactor II. Inhibition of Factor Xa by antithrombin was not catalyzed by the polysaccharide. The glucuronic acid residues were essential for the anticoagulant action of the mushroom polysaccharide since the activity disappeared after reduction of its carboxyl groups. In ex vivo tests using rats orally fed with the polysaccharide, we observed an inhibitory effect on platelet aggregation as observed with aspirin, a well-known antiplatelet agent. The polysaccharides from these mushrooms may constitute a new source of compounds with action on coagulation, platelet aggregation and, perhaps, on thrombosis.

The mechanism by which nonsteroidal antlinflammatory drugs interfere with the action of loop diuretics is not clear. We studied the renal response to an acute challenge of piretanide superimposed on pretreatment with either placebo,... more

The mechanism by which nonsteroidal antlinflammatory drugs interfere with the action of loop diuretics is not clear. We studied the renal response to an acute challenge of piretanide superimposed on pretreatment with either placebo, probenecid, indomethacin, or piroxicam in seven maximally hydrated subjects. No change was seen in glomerular filtration rate, as measured by creatinine clearance, throughout the experiments. When compared with responses to piretanide challenge after placebo pretreatment, probenecid reduced by 65% the peak fractional excretion of sodium (FENa), with a corresponding reduction in diuretic excretion. Pretreatment with indomethacin reduced peak FENa by 35%, but urinary delivery of piretanide was not altered. In contrast, piroxicam did not influence FENa but significantly reduced the delivery of both sodium and piretanide into urine. We conclude that the activity of nonsteroidal antiinflammatory drugs within the renal tubule varies among individual drugs and cannot be explained solely by their common mechanism of antiinflammatory action.

Introduction: Clopidogrel inhibits platelet P2Y12 ADP receptors, while ADP, as an inductor of aggregation, stimulates both P2Y12 and P2Y1 platelet receptors. Despite a clinical loading dose routine with clopidogrel, some patients still... more

Introduction: Clopidogrel inhibits platelet P2Y12 ADP receptors, while ADP, as an inductor of aggregation, stimulates both P2Y12 and P2Y1 platelet receptors. Despite a clinical loading dose routine with clopidogrel, some patients still experience coronary stent thrombosis suggesting persistent platelet activation. The VerifyNow-P2Y12 is a rapid assay that test platelet activity over 3 min and uses of the combination of ADP and prostaglandin E1 (PGE1) to directly measure the effects of clopidogrel on the P2Y12 receptor. ADP is used to maximally activate the platelets by binding to the P2Y1 and P2Y12 platelet receptors, while PGE1 is used to suppress the ADP-induced P2Y1-mediated increase in intracellular calcium levels. Objective: The VERIfy Thrombosis risk ASsessment (VERITAS) was a prospective study designed to measure platelet response to clopidogrel therapy in subjects with multiple risk factors or history of vascular disease using this novel point-of-care assay. Methods: 166 participants were enrolled in 4 participating sites. Data from 147 participants were analyzed after exclusion of 19 patients due to protocol violations. Platelets were assessed twice at baseline (before clopidogrel) and at 24 h postloading 450 mg (110 participants) or 7 days after chronic clopidogrel treatment 0049-3848/$ -see front matter D

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In a study of 20 patients with hypercholesterolemia (type IIa) the effects of lovastatin (20-80 mg/ day) on various clotting and thrombosis parameters were monitored for 12 months. On 11 occasions various cholesterol fractions and... more

In a study of 20 patients with hypercholesterolemia (type IIa) the effects of lovastatin (20-80 mg/ day) on various clotting and thrombosis parameters were monitored for 12 months. On 11 occasions various cholesterol fractions and clotting parameters were determined in each patient. In additon, the clotting inhibitors AT III, protein C, protein S, and C 1-esterase inhibitor and the fibrinolysis parameters plasminogen and a2-antiplasmin were examined. Platelet function was monitored on the basis of spontaneous and induced (collagen, ADP, epinephrine, ristocetin) aggregation. Lovastatin in the above dosage brought about a 66 mg/dl (from 320 ___ 12.6 to 254 _+ 12.0 mg/dl) reduction in the total cholesterol level and a 56 mg/dl (from 244 + 11.4 to 188 _+ 12.1 mg/dl) reduction in LDL cholesterol at the end of the study. Fibrinogen showed a significance decrease during the study period, whereas PT and aPTT remained unaffected. The initial slopes of the ADP-induced platelet aggregation revealed a significant decrease. C-reactive protein and platelet count remained within the normal range, indicating no significant change. Thrombin clotting time, AT III, Cl-esterase inhibitor, plasminogen, and ~t2-antiplasmin were not modified. Protein C and S behaved in a contradictory way, but remained within the normal range. Long-term treatment with lovastatin was associated with a significant reduction of fibrinogen levels and platelet aggregation induced by ADP in type-II a hypercholesterolemic patients. These alterations, as well as their role in cardiovascular disease, should be the subject of further investigations.

Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and... more

Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and antiatherosclerotic drug, was investigated for its suggested influence on the biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in isolated human polymorphnuclear leukocytes (PMNL) no influence on the biosynthesis was found, it could be shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner (IC50 ~ 5 μM). These results indicate that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata.

Chronic renal failure (CRF) is frequently associated with increased plasma levels of homocysteine (Hcy), an amino acid that can be considered a new uremic toxin according to recent evidence. Studies on Hcy described first homocystinuria,... more

Chronic renal failure (CRF) is frequently associated with increased plasma levels of homocysteine (Hcy), an amino acid that can be considered a new uremic toxin according to recent evidence. Studies on Hcy described first homocystinuria, an inherited disease characterized by high plasma Hcy levels and premature cardiovascular disease, resulting in high mortality rates. Hyperhomocysteinemia was then shown to be associated with cardiovascular events both in the general population and in CRF patients.

The present study established the pattern of isoprostanes (IsoPs) and prostaglandins metabolites (PGMs) in urine after triathlon training. Fifteen Caucasian triathletes -5 women and 10 men -performed 793 and 1603 Objective Load Scales,... more

The present study established the pattern of isoprostanes (IsoPs) and prostaglandins metabolites (PGMs) in urine after triathlon training. Fifteen Caucasian triathletes -5 women and 10 men -performed 793 and 1603 Objective Load Scales, respectively. The optimization of urine hydrolysis conditions, concerning to the type of buffer, the units of hydrolytic enzyme added, and the pH, allowed precise quantification of these metabolites by UPLC-MS/MS, avoiding the under-estimation of their concentrations that occurred in previous studies. Their rate of conjugation ranged between 36% and 100%. This implies significant importance since it supposes non-detection of some IsoPs and PGMs totally conjugated with glucuronic acid developed by other previous methodologies. Among the 13 compounds analyzed, this assay detected and characterized 4 IsoPs and 3 PGMs in the triathletes' urine. The PGMs tetranor-PGEM and 11␤-PGF 2␣ and the IsoP 8-iso-PGF 2␣ , showed lower concentrations after the training program, whereas the PGMs 6-keto-PGF 1␣ increased (vascular PGI 2 metabolite). In fact, their pattern in the triathletes' urine indicated that their variation may have been related with the physical activity. Due to its high variation, 6-keto PGF 1␣ stood out as a useful marker of the vasodilation and inhibition of the platelet aggregation of the PGI 2 linked to the physical exercise. The data obtained provided a global picture of changes in lipid peroxidation and vascular events as a consequence of chronic exercise.

The underlying mechanisms leading to recurrent ischaemic events or mortality after red blood cell (RBC) transfusion in anaemic acute coronary syndrome patients are poorly understood. The aim of this paper is to determine whether RBC... more

The underlying mechanisms leading to recurrent ischaemic events or mortality after red blood cell (RBC) transfusion in anaemic acute coronary syndrome patients are poorly understood. The aim of this paper is to determine whether RBC transfusion increases platelet activation and aggregation.

L'endothélium vasculaire joue un rôle primordial notamment dans la régulation du tonus vasculaire, en réponse à différents stimuli tels que la prostacycline, l'endothéline et surtout le monoxyde d'azote (NO • ). Le stress oxydant,... more

L'endothélium vasculaire joue un rôle primordial notamment dans la régulation du tonus vasculaire, en réponse à différents stimuli tels que la prostacycline, l'endothéline et surtout le monoxyde d'azote (NO • ). Le stress oxydant, caractérisé par une augmentation relative des espèces réactives de l'oxygène (ERO), peut diminuer la biodisponibilité du NO • , ce qui conduit à un dysfonctionnement vasculaire. En outre, les ERO (produites notamment par la NADPH oxydase) participent soit directement, soit par le biais des lipoprotéines de basse densité oxydées, à la transduction du signal dans les cellules vasculaires. Elles sont ainsi impliquées dans les phénomènes d'apoptose, la prolifération des cellules musculaires lisses, l'adhésion des monocytes aux cellules endothéliales et l'agrégation plaquettaire. Des perspectives thérapeutiques visant par exemple à moduler la production radicalaire au niveau des cellules endothéliales pourraient être envisagées pour restaurer la fonction endothéliale. © 2002 É ditions scientifiques et médicales Elsevier SAS. Tous droits réservés.

In a previous screening work, Foeniculum vulgare essential oil emerged from a pool of 24 essential oils for its antiplatelet properties and its ability to destabilize the retraction of the coagulum. In the present work the main component... more

In a previous screening work, Foeniculum vulgare essential oil emerged from a pool of 24 essential oils for its antiplatelet properties and its ability to destabilize the retraction of the coagulum. In the present work the main component of the oil, anethole, tested in guinea pig plasma was as potent as fennel oil in inhibiting arachidonic acid-, collagen-, ADP-and U46619-induced aggregation (IC 50 from 4 to 147 g ml −1 ). It also prevented thrombin-induced clot retraction at concentrations similar to fennel oil. The essential oil and anethole, tested in rat aorta with or without endothelium, displayed comparable NO-independent vasorelaxant activity at antiplatelet concentrations which have been proved to be free from cytotoxic effects in vitro. In vivo, both F. vulgare essential oil and anethole orally administered in a subacute treatment to mice (30 mg kg −1 day −1 for 5 days) showed significant antithrombotic activity preventing the paralysis induced by collagen-epinephrine intravenous injection (70% and 83% protection, respectively). At the antithrombotic dosage they were free from prohemorrhagic side effect at variance with acetylsalicylic acid used as reference drug. Furthermore, both F. vulgare essential oil and anethole (100 mg kg −1 oral administration) provided significant protection toward ethanol induced gastric lesions in rats. In conclusion, these results demonstrate for F. vulgare essential oil, and its main component anethole, a safe antithrombotic activity that seems due to their broad spectrum antiplatelet activity, clot destabilizing effect and vasorelaxant action.

AbstractÐThe continuing investigation of the root of Rhinacanthus nasutus aorded a 1,4-naphthoquinone ester, rhinacanthin-Q, accompanied by twenty-four known compounds. The structure was elucidated on the basis of spectroscopic analyses.... more

AbstractÐThe continuing investigation of the root of Rhinacanthus nasutus aorded a 1,4-naphthoquinone ester, rhinacanthin-Q, accompanied by twenty-four known compounds. The structure was elucidated on the basis of spectroscopic analyses. The cytotoxicity and antiplatelet eect of this compound was also discussed. #

Yucca schidigera (Agavaceae) is one of the major commercial source of steroidal saponins. Two products of yucca are available on the market. These include dried and finely powdered logs (yucca powder) or mechanically pressed and thermally... more

Yucca schidigera (Agavaceae) is one of the major commercial source of steroidal saponins. Two products of yucca are available on the market. These include dried and finely powdered logs (yucca powder) or mechanically pressed and thermally condensed juice (yucca extract). These products possess the GRAS label which allows their use as foaming agent in soft drink (root beer), pharmaceutical, cosmetic,

biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and... more

biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply

The aim of this study was to investigate whether etamsylate produces equine platelet activation. In vitro and in vivo studies were designed in which seven and eight adult healthy horses were included, respectively. In the in vitro study,... more

The aim of this study was to investigate whether etamsylate produces equine platelet activation. In vitro and in vivo studies were designed in which seven and eight adult healthy horses were included, respectively. In the in vitro study, citrated blood was incubated with different concentrations of etamsylate, and P-selectin expression and annexin V binding were determined by flow cytometry. In the in vivo study, blood was collected before and 1 and 2 h after IV administration of etamsylate, and P-selectin expression was evaluated.

Smectite suspensions, at low solids contents, are known to be naturally high in volume with diverse structural properties. The changing structural properties of smectite aqueous suspensions in the absence and presence of calcium ions were... more

Smectite suspensions, at low solids contents, are known to be naturally high in volume with diverse structural properties. The changing structural properties of smectite aqueous suspensions in the absence and presence of calcium ions were investigated using an acoustosizer and an advanced cryo-SEM technique to further understand and thereby control their environmental impact. In the absence of Ca(II) ions, smectite particles are present as a colloidally stable sol due to electrical double layer repulsion of the negatively charged platelets. The smectite network is observed to be extended throughout the suspension via clay platelets networking with an edge-edge (EE) orientation due to high basal surface repulsion. After the initial addition of Ca(II) ions, the smectite negative zeta potential reduces and the smectite platelets coagulate forming 2 µm aggregates. The platelets are randomly orientated, lettucelike, coagulated aggregates with a high presence of both edge-edge (EE) and edge-face (EF) orientations. After equilibration, the smectite platelets forming an orientated honeycomb cellular structure comprised of face-face (FF) multiply sheet aggregates. The voids in the cellular structure are larger than prior to Ca(II) addition, measured at 2-8 µm. The changing structural properties of a smectite suspension in the absence and presence of Ca(II) greatly influence smectite stability and in turn, mineral processing and/or environmental management. Adequate time is required to allow suppression of the initial swelling of the smectite, full Ca(II) exchange and platelet aggregation.

Studies in athletes have shown that carnitine supplementation may foster exercise performance. As reported in the majority of studies, an increase in maximal oxygen consumption and a lowering of the respiratory quotient indicate that... more

Studies in athletes have shown that carnitine supplementation may foster exercise performance. As reported in the majority of studies, an increase in maximal oxygen consumption and a lowering of the respiratory quotient indicate that dietary carnitine has the potential to stimulate lipid metabolism. Treatment with L-carnitine also has been shown to induce a significant postexercise decrease in plasma lactate, which is formed and used continuously under fully aerobic conditions. Data from preliminary studies have indicated that L-carnitine supplementation can attenuate the deleterious effects of hypoxic training and speed up recovery from exercise stress. Recent data have indicated that L-carnitine plays a decisive role in the prevention of cellular damage and favorably affects recovery from exercise stress. Uptake of L-carnitine by blood cells may induce at least three mechanisms: 1) stimulation of hematopoiesis, 2) a dose-dependent inhibition of collagen-induced platelet aggregatio...

Cocoa is an important source of polyphenols, which comprise 12-18% of its total dry weight. The major phenolic compounds in cocoa and cocoa products are mainly flavonoids such as epicatechin, catechin, and proanthocyanidins. These... more

Cocoa is an important source of polyphenols, which comprise 12-18% of its total dry weight. The major phenolic compounds in cocoa and cocoa products are mainly flavonoids such as epicatechin, catechin, and proanthocyanidins. These products contain higher amounts of flavonoids than other polyphenol-rich foods. However, the bioavailability of these compounds depends on other food constituents and their interactions with the food matrix. Many epidemiological and clinical intervention trials have concluded that the ingestion of flavonoids reduces the risk factors of developing cardiovascular disease. This review summarizes the new findings regarding the effects of cocoa and chocolate consumption on cardiovascular risk factors. The mechanisms involved in the cardioprotective effects of cocoa flavonoids include reduction of oxidative stress, inhibition of low-density lipoproteins oxidation and platelet aggregation, vasodilatation of blood vessels, inhibition of the adherence of monocytes to vascular endothelium, promotion of fibrinolysis, and immunomodulatory and anti-inflammatory activity. Scientific evidence supports a cause and effect relationship between consumption of cocoa flavonoids and the maintenance of normal endothelium-dependent vasodilation, which contributes to normal blood flow. However, larger randomized trials are required to definitively establish the impact of cocoa and cocoa products consumption on hard cardiovascular outcomes.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF... more

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial. The reasoning is structured around 4 fundamental events of cicatrization, namely,

There is evidence that equine platelet reactivity is altered by strenuous exercise. Changes in platelet reactivity could impact haemostasis following exercise-induced injury and may play a role in the pathophysiology of exercise-induced... more

There is evidence that equine platelet reactivity is altered by strenuous exercise. Changes in platelet reactivity could impact haemostasis following exercise-induced injury and may play a role in the pathophysiology of exercise-induced pulmonary haemorrhage. Interpretation of results of previous studies is hindered by potential in vitro-induced changes in platelet activity through the choice of anticoagulant and the use of platelet inhibitors. The present study was undertaken to re-evaluate the effect of exercise on equine platelets using methodologies that minimise in vitro-induced changes in platelet activation.