bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable Platelet Response to Low-dose ASA and the Risk of Limb Deterioration in Patients Submitted to Peripheral Arterial Angioplasty
Authors: Mueller Michael Rolf , Salat Andreas , Stangl Petra , Murabito Marco , Pulaki Sad , Boehm Dagmar , Koppensteiner Renate , Ergun Erdem , Mittlboeck Martina , Schreiner Wolfgang , Losert Udo , Wolner Ernst 
Published: July 2018

SummaryA group of 100 patients with intermittent claudication (70 male, 30 female), treated with 100 mg ASA per day, were followed over 18 months after elective percutaneous balloon angioplasty. Platelet function was monitored over a period of 12 months by corrected whole blood aggregometry (CWBA). Upon stimulation by arachidonic acid (AA), adenosine diphosphate (ADP) and collagen, CWBA-results were obtained by an electronic acquisition and evaluation system correcting for hematocrit and platelet count of the blood sample.All patients showed a completely inhibited platelet response to AA stimulation. Comparison of the CWB A-results with clinical parameters revealed that reocclusions at the site of angioplasty occurred exclusively in male patients for which CWBA failed to prove an inhibition of aggregation upon both agonists, ADP and collagen, and for these patients the risk of complication is at least 87% higher (p = 0.0093).Only 40% of male patients show the expected effect of ASA on in vitro platelet aggregation at any given point in time and CWBA is capable of predicting those male patients which are at an elevated risk of reocclusion following peripheral angioplasty.
Aprotinin Reduces Blood Loss after Cardiopulmonary Bypass by Direct Inhibition of Plasmin
Authors: Ray Michael J , Marsh Neville A 
Published: July 2018

SummaryThe effectiveness and mechanism of aprotinin reduced bleeding after cardiopulmonary bypass surgery was studied in a double blind randomised study of 106 patients undergoing valve replacement surgery. Aprotinin therapy was associated with significant reduction in perioperative bleeding and postoperative blood transfusion requirements. Although initially tissue plasminogen activator (t-PA) activity was lower in the aprotinin than placebo group, as surgery proceeded this difference was reversed due to less plasminogen activator inhibitor-1 release in the aprotinin group. This indicates that aprotinin-mediated suppression of fibrinolysis as demonstrated by reduced D-dimer concentration was not related to t-PA. Furthermore, similar perioperative reduction of plasminogen levels in aprotinin and placebo groups indicated a similar degree of conversion of plasminogen to plasmin. However, less plasmin bound with alpha 2-antiplasmin in the plasma in the aprotinin group as it was already complexed with aprotinin where it remained protected from the natural inhibitor on the intact fibrin surface. The reduced fibrinolytic activity of the aprotinin group was thus brought about by the complexing of aprotinin with the plasmin which was bound to the fibrin surface.
Ultrasound Reversibly Disaggregates Fibrin Fibers
Authors: Braaten Julie V , Goss Rachel A , Francis Charles W 
Published: July 2018

SummaryUltrasound accelerates fibrinolysis in vitro and in vivo, primarily through non-thermal mechanisms including cavitation. We have previously observed that ultrasound reversibly increases flow through fibrin gels, a property primarily determined by the structure of the fibrin matrix. Therefore, the effect of ultrasound on the ultrastructure of fibrin gels was examined using scanning electron microscopy. Non-cross- linked fibrin gels were fixed and prepared for microscopy before, during and after exposure to 1 MHz ultrasound, and quantitative analysis of fiber population density and diameter was performed. Gels exposed and fixed in the presence of ultrasound exhibited an increase in density of 65 ± 26% (mean ± SD) at 4 W/cm2 (p <0.000001) accompanied by a decrease in fiber diameter of 27 ± 9% (p <0.000001). Gels fixed 15 min following ultrasound exposure showed no significant change in either density or diameter compared to unexposed gels, indicating that the ultrasound-induced change in fiber structure was reversible. Factor XIII-crosslinked fibrin gels exhibited no change in population density or diameter when exposed to ultrasound. These results indicate that ultrasound exposure causes reversible disaggregation of uncrosslinked fibrin fibers into smaller fibers, an effect that may alter flow resistance and create additional binding sites for fibrinolytic components, improving fibrinolytic efficacy.
Antithrombin Acts as a Negative Acute Phase Protein as Established with Studies on HepG2 Cells and in Baboons
Authors: Niessen R W  L M , Lamping R J , Jansen P M , Prins M H , Peters M , Taylor F B , de Vijlder J J  M , ten Cate J W , Hack C E , Sturk A 
Published: July 2018

SummaryPatients with sepsis or after major surgery have decreased plasma levels of the anticoagulant protein antithrombin. In such patients elevated levels of interleukin-6 (IL-6) are present and this interleukin is known to induce positive and negative acute phase responses. To investigate the possibility that antithrombin acts as a negative acute phase response-protein we performed studies on the human hepatoma cell line HepG2 in vitro and baboons in vivo. HepG2 cells were treated with recombinant human IL-6, ILß3, or combinations of the latter two, and tested for production of antithrombin, fibrinogen and prealbumin (transthyretin). This treatment resulted in a dose dependent increase in fibrinogen concentration (with a maximum effect of 2.8-2.9-fold) and a dose dependent decrease in prealbumin (with a maximum effect of 0.6-0.7-fold) and antithrombin concentrations (with a maximum effect of 0.6-0.8-fold). Simultaneous treatment of the HepG2 cells with IL-6 (1,000 pg/ml or 2,500 pg/ml) and IL-1β (25 pg/ml), provided more extensively decreased prealbumin (0.8 and 0.6-fold, respectively) and antithrombin concentration (0.7 and 0.6-fold, respectively) compared to the single interleukin treatment at these concentrations. Baboons treated with 2 µg IL-6 · kg body-weight-1 · day1 showed increased plasma CRP levels (59-fold, p <0.05) and decreased prealbumin (0.9-fold, p <0.05) and antithrombin (0.8-fold, p <0.05) plasma levels, without evidence for coagulation activation. Our results indicate that antithrombin acts as a negative acute phase protein, which may contribute to the decreased antithrombin plasma levels observed after major surgery or in sepsis.
Administration of Antioxidant Vitamins Does Not Alter Plasma Fibrinolytic Activity in Subjects with Central Obesity
Authors: Rifici Vincent A , Schneider Stephen H , Chen Yaoju , Khachadurian Avedis K 
Published: July 2018

SummaryIn vitro studies suggest that oxidized low density lipoprotein inhibits fibrinolysis by stimulating the production of plasminogen activator inhibitor -1 (PAI). We assessed the effects of dietary antioxidant vitamins for four weeks on three indices of copper mediated oxidation of very low and low density lipoproteins (VLDL+LDL) and plasma fibrinolytic activities in 15 male subjects with central obesity, a condition associated with increased PAI activity. Vitamin administration resulted in a decrease in production of thiobarbituric acid reactive substances from 29.3 ± 3.9 to 13.6 ± 3.5 nmoles/mg VLDL + LDL protein (mean ± SE, p <0.003), an increase in the lag phase of conjugated diene formation from 94.8 ± 5.5 to 225.0 ±31.9 min (p <0.001) and an increase in reactivity of lysine residues from 73.6% ± 4.8% to 86.8% ± 3.6% (p <0.034) demonstrating a reduction in the susceptibility of the lipoproteins to oxidation. However, antioxidant vitamins had no effect on plasma PAI activity, PAI antigen, tissue-type plasminogen activator activity and antigen, fibrinogen and fibrin degradation products. These results do not support the hypothesis that lipoprotein oxidation is a significant cause of impaired fibrinolysis in men with central obesity.
Inhibition of Thrombin Generation in Plasma by Inhibitors of Factor Xa
Authors: Prasa D , Svendsen L , Stürzebecher J 
Published: July 2018

SummaryA series of inhibitors of factor Xa (FXa) were investigated using the thrombin generation assay to evaluate the potency and specificity needed to efficiently block thrombin generation in activated human plasma. By inhibiting FXa the generation of thrombin in plasma is delayed and decreased. Inhibitor concentrations which cause 50 percent inhibition of thrombin generation (IC50) correlate in principle with the Ki values for inhibition of free FXa. Recombinant tick anticoagulant peptide (r-TAP) is able to inhibit thrombin generation with considerably low IC50 values of 49 nM and 37 nM for extrinsic and intrinsic activation, respectively. However, the potent synthetic, low molecular weight inhibitors of FXa (Ki values of about 20 nM) are less effective in inhibiting the generation of thrombin with IC50 values at micromolar concentrations.The overall effect of inhibitors of FXa in the thrombin generation assay was compared to that of thrombin inhibitors. On the basis of similar Ki values for the inhibition of the respective enzyme, synthetic FXa inhibitors are less effective than thrombin inhibitors. In contrast, the highly potent FXa inhibitor r-TAP causes a stronger reduction of the thrombin activity in plasma than the most potent thrombin inhibitor hirudin.
Akute Autoimmunthrombozytopenie bei Sarkoidose
Authors: Berger H. H. , Busse Petra , Loreth R. M. 
Published: July 2018

ZusammenfassungBei einem 35jährigen Patienten mit Sarkoidose im Stadium I trat nach einer Analfistelresektion ein kontinuierlicher Abfall der Thrombozyten bis 4 T/μl mit entsprechender klinischer Manifestation der dadurch bedingten hämorrhagischen Diathese auf. Nach Ausschluß einer heparinassoziierten Thrombozytopenie (HAT) und einer malignen hämatologischen Systemerkrankung wurde unter der Ausschlußdiagnose Autoimmunthrombozytopenie eine Hochdosis-Immuntherapie mit einem hochkonzentrierten Immunglobulinpräparat durchgeführt. Dies führte zu einem raschen Anstieg der Thrombozytenzahl, welcher auch nach Beendigung der Immunglobulingabe anhielt. Aufgrund des klinischen Verlaufes konnte die Diagnose einer Autoimmunthrombozytopenie bestätigt werden. Die vorangegangene Inhalationsnarkose muß als mögliches Triggerereignis angesehen werden.
Repeated Exercise Induces Release of Soluble P-Selectin in Patients with Intermittent Claudication
Authors: Kirkpatrick U J , Mossa M , Blann A D , McCollum C N 
Published: July 2018

SummaryControversy exists as to whether exercise in patients with intermittent claudication causes a harmful biochemical effect associated with an ischaemia-reperfusion injury of skeletal muscle. We report on exercise-induced changes in neutrophil activation, soluble P-selectin and von Willebrand factor in 34 patients with intermittent claudication and 12 matched controls.Von Willebrand factor (vWF) showed a cyclical pattern of response to exercise in control subjects (rising from 103 ± 8 to 119 ± 7 U/dl); claudicants did not show this pattern but had higher levels of vWF throughout (p <0.03). There was no consistent pattern of response in neutrophil hydrogen peroxide production to exercise in either claudicants or control subjects. Soluble P-selectin levels increased after exercise, but this only reached statistical significance after repeated exercise in claudicants (rising from 320 ± 28 to 357 ± 28 ng/ml). This rise in soluble P-selectin after exercise may indicate progressive platelet activation which may contribute to the excess cardiovascular mortality that claudicants are prone to.
Mechanism of Inhibitory Action on Platelet Activation of a Phospholipase A2 Isolated from Lachesis muta (Bushmaster) Snake Venom
Authors: Fuly André L , Machado Olga L T , Alves Elias W , Carlinis Célia R 
Published: July 2018

SummaryCrude venom from Lachesis muta exhibited procoagulant, proteolytic and phospholipase A2 activities. A phospholipase A2, denoted LM-PLA2 was purified from L. muta venom to homogeneity, through a combination of chromatographic steps involving gel-filtration on Sephacryl S-200 HR and reverse phase chromatography on a C2/C18 column. LM-PLA2 presented a single polypeptide chain with an isoelectric point at pH 4.7 and apparent molecular weight of 17 kDa. Partial aminoacid sequence indicated a high degree of homology for LM-PLA2 with other PLA2 from different sources.LM-PLA2 displayed a potent enzymatic activity as measured by indirect hemolysis of red blood cells but it was neither lethal when injected i.p. into mice nor did it present anticoagulant activity. Furthermore, LM-PLA2 displayed a moderate inhibitory activity on the aggregation of rabbit platelets induced by low levels of ADP, thrombin and arachidonate. In contrast, platelet aggregation induced by high doses of collagen was strongly inhibited by LM-PLA2 as well as ATP-release. Treatment of the protein with p-bromophenacyl bromide or 2-mercapto-ethanol, as well as thermal inactivation studies, suggested that the platelet inhibitory effect of LM-PLA2 is dependent on its enzymatic activity. Thus, the platelet inhibitory activity of LM-PLA2 was shown to be dependent on the hydrolysis of plasma phospholipids and/or lipoproteins, most probably those rich in phosphatidylcholine. Surprisingly, lyso-phosphatidylcholine released by LM-PLA2 from plasma was shown to preferentially inhibited collagen-induced platelet aggregation, in contrast to other PLA2s, whose plasma hydrolytic products indistinctly affect platelet’s response to several agonists.
Naturally Produced Extracellular Matrix Is an Excellent Substrate for Canine Endothelial Cell Proliferation and Resistance to Shear Stress on PTFE Vascular Grafts
Authors: Schneider A , Chandra M , Lazarovici G , Vlodavsky I , Merin G , Uretzky G , Borman J B , Schwalb H 
Published: July 2018

SummaryPurpose: Successful development of a vascular prosthesis lined with endothelial cells (EC) may depend on the ability of the attached cells to resist shear forces after implantation. The present study was designed to investigate EC detachment from extracellular matrix (ECM) precoated vascular prostheses, caused by shear stress in vitro and to test the performance of these grafts in vivo. Methods: Bovine aortic endothelial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE) vascular graft (10 X 0.6 cm), PTFE graft precoated with fibronectin (FN), or PTFE precoated with FN and a naturally produced ECM (106 cells/graft). Sixteen hours after seeding the medium was replaced and unattached cells counted. The strength of endothelial cell attachment was evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm2 for 1 h. The detached cells were collected and quantitated. PTFE or EC preseeded ECM coated grafts were implanted in the common carotid arteries of dogs. Results: While little or no differences were found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated PTFE, or FN+ECM precoated PTFE, respectively), the number of cells retained after a shear stress was significanly increased on ECM coated PTFE (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, respectively, p <0.01). Implantation experiments in dogs revealed a significant increase in EC coverage and a reduced incidence of thrombus formation on ECM coated grafts that were seeded with autologous saphenous vein endothelial cells prior to implantation. Conclusion: ECM coating significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adhesive macromolecules and potent endothelial cell growth promoting factors may render the ECM a promising substrate for vascular prostheses.
Trypsin- and SLIGRL-induced Vascular Relaxation and the Inhibition by Benzamidine Derivatives
Authors: Glusa Erika , Saft Andrea , Prasa Dagmar , Stürzebecher Jörg 
Published: July 2018

SummarySerine proteinases are involved in several physiological processes and elicit profound cellular effects in a variety of tissues. Besides the thrombin receptor a second receptor, activated by trypsin, the proteinase-activated receptor 2 (PAR-2), was cloned and characterized. Both enzymes generate a new extracellular N-terminus by limited proteolytic cleavage which functions as tethered ligand to activate the receptor. Synthetic peptides corresponding to the sequences of the newly generated N-terminus are able to mimic the effects of the enzymes.In porcine pulmonary arteries trypsin and the receptor-derived peptide SLIGRL elicited an endothelium-dependent transient relaxation of PGF2α-precontracted vessels. The EC50 values for trypsin and SLIGRL amounted to 1.1 ± 0.2 nM and 5.4 ± 0.6¼M, respectively. Trypsin and SLIGRL caused a homologous desensitization but thrombin and the thrombin receptor-activating peptide SFLLRN were still able to elicit pronounced relaxant effects. The trypsin- and SLIGRL-induced relaxant responses were markedly diminished after blockade of the nitric oxide synthesis by NG-nitro-L-arginine methyl ester (200 ¼M) and were absent in endothelium-denuded vessels. Indomethacin and hirudin did not influence the relaxant effects. The effect of trypsin but not that of SLIGRL was blocked by the proteinase inhibitor aprotinin suggesting that only proteolytically active trypsin activates the receptor. Benzamidine derivatives of the 3-amidinophenylalanine type with different affinity for trypsin and thrombin inhibited the vascular effects of trypsin (IC50 0.007-0.7 ¼M) correlating with its antitrypsin activity.The data suggest that the vascular effects of trypsin and SLIGRL are mediated through activation of PAR-2 which differs from the thrombin receptor.
Antithrombotic Effect of Two Low Molecular Weight Thrombin Inhibitors and a Low-Molecular Weight Heparin in a Caval Vein Thrombosis Model in the Rat
Authors: Eriksson B I , Carlsson S , Halvarsson M , Risberg B , Mattsson C 
Published: July 2018

SummaryA sensitive thrombosis model with a high reproducibility was developed in the rat, utilizing stasis of the caval vein and a standardized surgical trauma as the only thrombogenic stimuli. Since no procoagulant substances were used, the results of the present study might be relevant in a clinical situation. The antithrombotic effect of two recently synthesized low-molecular-weight thrombin inhibitors have been compared to dalteparin, (Fragmin) a low-molecular-weight heparin fragment. Each compound was studied at 8 different doses with 10 rats in each group. On a gravimetric basis, the thrombin inhibitor melagatran was twice as potent as dalteparin (ED50 16 and 33 µ/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 µLg/kg per h. No differences in antithrombotic effect were, however, found when the compounds were compared at anticoagulant equivalent doses (same APTT prolongation). A 50% reduction in the mean thrombus weight was obtained when APTT was prolonged to 1.2 to 1.3 times the pretreatment value.
Thrombotic Events during Oral Anticoagulant Treatment: Results of the Inception-cohort, Prospective, Collaborative ISCOAT Study
Authors: Palareti Gualtiero , Manotti Cesare , D’Angelo Armando , Pengo Vittorio , Erba Nicoletta , Moia Marco , Ciavarella Nicola , Devoto Gianluigi , Berrettini Mauro , Leali Nicoietta , Poggi Mario , Legnani Cristina , Musolesi Serena , Coccheri Sergio ,   ISCOAT Study Group (Italian Study on Complications of Oral Anticoagulant Therapy)
Published: July 2018

SummaryThe paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.5 per 100 patient years) were recorded in 67 patients: 20 fatal (1%), 39 major (1.9%) and 11 minor (0.6%). 34/70 events occurred within the first 90 days of treatment (relative risk - at multivariate analysis - of <90 days vs. >90 = 20.6, C.I. 12.7-33.5; p <0.0001). The risk was higher in patients aged >70 y (1.62, C.I. 1.0-2.61; p <0.05), and when indication for anticoagulant treatment was peripheral/cerebral arterial disease (1.84, C.I. 1.01-3.36; p <0.05). The frequency of thrombotic events was 17.5% when international normalised ratio (INR) levels were <1.5, decreasing to 2.3% for INRs within the 2-2.99 category (relative risk of INRs <2.0 vs. >2 = 1.88, C.1.1.16-3.07; p <0.05).The recorded rate of thrombotic events was lower than that reported in the few available studies. A greater risk should be expected during the first 90 days of treatment, when anticoagulation levels are <2.0 INR, in patients > 70 years and in those with cerebrovascular/peripheral arterial disease.
Activation of Coagulation and Fibrinolysis in Childhood Diarrhoea-associated Haemolytic Uraemic Syndrome
Authors: Nevard Corinne H F , Jurd Karen M , Lane David A , Philippou Helen , Haycock George B , Hunt Beverley J 
Published: July 2018

SummaryDiarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin producing Eschericia coli. We hypothesized that verotoxin binding to glomerular endothelial cells causes localised endothelial cell activation and thus activation of coagulation and reduction of fibrinolytic potential. We also proposed that treatment with fresh frozen plasma or dialysis would not affect these changes. Markers of activation of coagulation and fibrinolysis were measured in 30 children with acute D+ HUS serially, in healthy children and in children on dialysis.In acute D+ HUS, levels of thrombin-antithrombin III complex and prothrombin fragment 1+2 were significantly increased (p <0.001). The source of thrombin generation was unclear. Factor Xlla levels were increased in patients and controls with renal failure. Factor VIIa levels were not significantly raised in children with acute D+ HUS. D-dimers were increased, but fibrinolytic potential as measured by fibrin plate was reduced. Levels of plasminogen activator inhibitor antigen and activity and tissue plasminogen activator antigen were increased.Neither peritoneal dialysis nor administration of blood products, the most common treatments, altered parameters of coagulation or fibrinolysis.
Presence of P2X1 Purinoceptors in Human Platelets and Megakaryoblastic Cell Lines
Authors: Vial Catherine , Hechier Béatrice , Léon Catherine , Cazenave Jean-Pierre , Gachet Christian 
Published: July 2018

SummaryHuman platelets are thought to possess at least two subtypes of purinoceptor, one of which, coupled to G-proteins, could be the P2Y1 receptor (Léon et al. 1997). However, it has been suggested that the unique rapid calcium influx induced by ADP in platelets could involve P2X1 ionotropic receptors (MacKenzie et al. 1996) and the aim of this study was thus to investigate the presence of P2X purinoceptors in platelets and megakaryoblastic cells. Using PCR experiments, we found P2X1 mRNA to be present in human platelets and megakaryoblastic cell lines. In platelets, the selective P2X1 agonist αβMeATP induced a rise in intracellular calcium only in the presence of external calcium and this effect was antagonized by suramin and PPADS. Repeated addition of a�MeATP desensitized the P2X1 purinoceptor but only slightly affected the ADP response, while no calcium response to αβMeATP was observed in megakaryoblastic cells. These results support the existence of functional P2X1 purinoceptors on human platelets and the presence of P2X1 transcripts in megakaryoblastic cell lines.