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Articles de revues sur le sujet "Low on-treatment platelet reactivity"

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Massimi, Isabella, Lavinia Lotti, Flavia Temperilli, Massimo Mancone, Gennaro Sardella, Simone Calcagno, Ombretta Turriziani, Luigi Frati et Fabio M. Pulcinelli. « Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment ». Thrombosis and Haemostasis 116, no 12 (novembre 2016) : 1100–1110. http://dx.doi.org/10.1160/th16-04-0316.

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SummaryPlatelet multidrug resistance protein4 (MRP4)-overexpression has a role in reducing aspirin action. Aspirin in vivo treatment enhances platelet MRP4 expression and MRP4 mediated transport inhibition reduces platelet function and delays thrombus formation. The aim of our work was to verify whether MRP4 expression is enhanced in platelets obtained from patients under chronic aspirin treatment and whether it correlates with residual platelet reactivity. We evaluated changes on mRNA and protein-MRP4 expression and platelet aggregation in four populations: healthy volunteers (HV), aspirin-free control population (CTR), patients who started the treatment less than one month ago (ASA<1 month patients) and aspirinated patients who started the treatment more than two months ago (ASA>2 months patients). In platelets obtained from ASA>2 months patients, it was found a statistically significant MRP4 enhancement of both mRNA and protein expression compared to HV, CTR and ASA<1 month patients. Platelets obtained from ASA>2 months patients that present high levels of platelet MRP4, have higher serum TxB2 levels and collagen-induced platelet aggregation compared to patient with low levels of MRP4 in platelets. In addition collagen induced platelet aggregation is higher in in vitro aspirinated platelets obtained from patients with high levels of MRP4 patients compared to those obtained from patients with low MRP4 levels. We can assert that, in patients under chronic aspirin treatment, platelets that present high MRP4 levels have an increase of residual platelet reactivity, which is due in part to incomplete COX-1 inhibition, and in part to COX-1–independent mechanism.
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Cardona, Francesco, Jens Schwindt, Angelika Berger, Stefan Kuhle, Monika Homoncik, Petra Jilma-Stohlawetz, Arnold Pollak, Bernd Jilma et Nadja Haiden. « Changes in thrombopoiesis and platelet reactivity in extremely low birth weight infants undergoing erythropoietin therapy for treatment of anaemia of prematurity ». Thrombosis and Haemostasis 93, no 01 (2005) : 118–23. http://dx.doi.org/10.1160/th04-02-0093.

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SummaryErythropoietin (Epo) is frequently administered to premature infants to stimulate erythropoiesis. There is evidence from studies in animals and healthy adults that Epo also interacts with thrombopoiesis and platelet function.This study investigates the effect of Epo therapy on platelet reactivity, peripheral platelet counts and thiazole orange-positive (TO+) platelets in extremely low birth weight (ELBW) infants. In a randomised-controlled trial, ELBW infants with a birth weight ≤ 800g and a gestational age ≤ 32 weeks were either randomised to a group receiving Epo during the first weeks of life or to a control group. Our results show that thrombin receptor-activating peptide (TRAP-6) -induced expression of P-selectin increased significantly during the first two weeks of Epo treatment.With the exception of week five, the number of TO+ platelets was significantly higher during the first eight weeks in Epo-treated infants compared to controls. The increase of TO+ platelets was not paralleled by an increase in total platelet count.We can conclude that Epo therapy has a short-lasting effect on platelet reactivity toTRAP-6 in ELBW infants during the first two weeks of life.Furthermore, Epo therapy is associated with an increase in the number of TO+ platelets compared to controls.
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Tscharre, Maximilian, Silvia Lee, Christoph W. Kopp, Simon Panzer et Thomas Gremmel. « Mean Corpuscular Volume Predicts Adverse Outcomes Following Peripheral Angioplasty With Stenting and Is Associated With On-Treatment Platelet Reactivity ». Angiology 72, no 1 (24 juillet 2020) : 16–23. http://dx.doi.org/10.1177/0003319720943816.

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Structural aspects of red blood cells have been associated with cardiovascular disease. No data linking mean corpuscular volume (MCV) to clinical outcomes and on-treatment platelet reactivity in patients with peripheral artery disease (PAD) are available. We investigated a composite of atherothrombotic events and target vessel restenosis or reocclusion following infrainguinal stenting for stable PAD. Residual platelet reactivity was measured by light transmission aggregometry (LTA) and the VerifyNow assays. We included 104 patients receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. In receiver-operating characteristic analysis, MCV effectively discriminated between patients with and without adverse outcomes and identified a MCV ≤90.8 fL as optimal cutoff. Adverse outcomes occurred significantly more often in patients with low MCV (log-rank P = .002). In univariable Cox regression analysis, low MCV was associated with an increased risk of future adverse outcomes (hazard ratio [HR]: 2.662 [95%CI: 1.304-5.434]; P = .007) and remained significantly associated after adjustment (HR: 2.591 [95%CI: 1.242-5.403]; P = .011). Mean corpuscular volume was inversely correlated with arachidonic acid (AA)- and adenosine diphosphate (ADP)-inducible platelet reactivity by LTA and with the VerifyNow aspirin assay. Low MCV is associated with adverse outcomes over 2 years following infrainguinal stenting. Mean corpuscular volume correlates inversely with AA- and ADP-inducible platelet reactivity during DAPT.
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Pedersen, Oliver Buchhave, Leonardo Pasalic, Erik Lerkevang Grove, Steen Dalby Kristensen, Anne-Mette Hvas et Peter H. Nissen. « Advanced Flow Cytometry Using the SYTO-13 Dye for the Assessment of Platelet Reactivity and Maturity in Whole Blood ». Methods and Protocols 6, no 1 (13 janvier 2023) : 8. http://dx.doi.org/10.3390/mps6010008.

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Newly produced immature platelets are larger, contain higher amounts of residual RNA, and are more reactive than mature platelets. Flow cytometry using the SYTO-13 dye is a method for the subdivision of immature platelets from mature platelets based on the labelling of intracellular platelet RNA, enabling the simultaneous investigation of the reactivity of each platelet population. This method provides detailed information on several aspects of platelet physiology using a combination of platelet surface markers and agonists. Currently, no standardized protocol exists across laboratories. Here, we describe a flow cytometry protocol in detail to investigate platelet reactivity and its relation to platelet maturity. We analyzed 20 healthy individuals with the protocol and compared the platelet subpopulation with the highest SYTO-13 labelling (in the first quintile, “SYTO-high”) corresponding to the most immature platelets (highest RNA content) with the platelet subpopulation with the lowest SYTO-13 labelling (in the fifth quintile, “SYTO-low”) corresponding to the mature platelets with the lowest RNA content. SYTO-high platelets had overall significantly increased platelet reactivity compared with that of SYTO-low platelets. The presented method may be a valuable research tool for the analysis of platelet reactivity and its relation to platelet maturity.
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Berger, Martin, Alexander Dressel, Marcus E. Kleber, Winfried März, Peter Hellstern, Nikolaus Marx et Katharina Schütt. « Platelet Reactivity and Cardiovascular Mortality Risk in the LURIC Study ». Journal of Clinical Medicine 12, no 5 (28 février 2023) : 1913. http://dx.doi.org/10.3390/jcm12051913.

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Background: The clinical and prognostic implications of platelet reactivity (PR) testing in a P2Y12-inhibitor naïve population are poorly understood. Objectives: This explorative study aims to assess the role of PR and explore factors that may modify elevated mortality risk in patients with altered PR. Methods: Platelet ADP-induced CD62P and CD63 expression were measured by flow-cytometry in 1520 patients who were referred for coronary angiography in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). Results: High- and Low-platelet reactivity to ADP were strong predictors of cardiovascular and all-cause mortality and risk equivalent to the presence of coronary artery disease. (High platelet reactivity 1.4 [95% CI 1.1–1.9]; Low platelet reactivity: 1.4 [95% CI 1.0–2.0]). Relative weight analysis indicated glucose control (HbA1c), renal function ([eGFR]), inflammation (high-sensitive C-reactive protein [hsCRP]) and antiplatelet therapy by Aspirin as consistent mortality risk modifiers in patients with Low- and High-platelet reactivity. Pre-specified stratification of patients by risk modifiers HbA1c (<7.0%), eGFR (>60 mL/min/1.73 m2) and CRP (<3 mg/L) was associated with a lower mortality risk, however irrespective of platelet reactivity. Aspirin treatment was associated with reduced mortality in patients with high platelet reactivity only (p for interaction: 0.02 for CV-death [<0.01 for all-cause mortality]. Conclusions: Cardiovascular mortality risk in patients with High- and Low platelet reactivity is equivalent to the presence of coronary artery disease. Targeted glucose control, improved kidney function and lower inflammation are associated with reduced mortality risk, however independent of platelet reactivity. In contrast, only in patients with High-platelet reactivity was Aspirin treatment associated with lower mortality.
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Psaila, Bethan, James B. Bussel, Matthew D. Linden, Bracken Babula, Youfu Li, Marc R. Barnard, Chinara Tate, Kanika Mathur, Andrew L. Frelinger et Alan D. Michelson. « In vivo effects of eltrombopag on platelet function in immune thrombocytopenia : no evidence of platelet activation ». Blood 119, no 17 (26 avril 2012) : 4066–72. http://dx.doi.org/10.1182/blood-2011-11-393900.

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Abstract The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased.
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JEONG, Y. H., K. P. BLIDEN, U. S. TANTRY et P. A. GURBEL. « High on-treatment platelet reactivity assessed by various platelet function tests : is the consensus-defined cut-off of VASP-P platelet reactivity index too low ? » Journal of Thrombosis and Haemostasis 10, no 3 (29 février 2012) : 487–89. http://dx.doi.org/10.1111/j.1538-7836.2011.04604.x.

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Dhillon, Ashwat S., Jorge Caro, Han Tun, David G. Armstrong, Vincent Rowe, David M. Shavelle et Leonardo C. Clavijo. « Therapeutic Window of Clopidogrel and Ticagrelor in Patients With Critical Limb-Threatening Ischemia ». Journal of Cardiovascular Pharmacology and Therapeutics 25, no 2 (24 septembre 2019) : 158–63. http://dx.doi.org/10.1177/1074248419877411.

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Background: Critical limb-threatening ischemia (CLTI) is associated with an increased risk of major adverse limb events and mortality. High on-treatment platelet reactivity (HPR) is associated with an increased risk of ischemic events, while low on-treatment platelet reactivity (LPR) is associated with an increased risk of bleeding. This study investigates the frequency with which patients with CLTI on clopidogrel or ticagrelor achieve a “therapeutic window” (TW) of platelet inhibition. Methods: Data from the “Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study” were assessed retrospectively to determine the incidence of TW of on-treatment platelet reactivity in 50 consecutive patients with CLTI (mean age: 65.2 ± 10.5 years, 54% male). The data included 4 measurements of patients’ platelet reactivity using the VerifyNow P2Y12 Assay: baseline and steady state platelet reactivity on clopidogrel 75 mg daily and on ticagrelor 90 mg twice daily. Results: At baseline, 46% of patients on clopidogrel were within TW of on-treatment platelet reactivity compared to 10% of patients on ticagrelor ( P < .0001). At steady state, 42% of patients on clopidogrel were within the TW compared to 10% of patients on ticagrelor ( P < .0001). Patients on ticagrelor exhibited higher rates of LPR compared to those on clopidogrel at baseline as well as at steady state (baseline 88% vs 18%, steady state 88% vs 28%; P < .0001). Conclusion: Although ticagrelor has been proposed as an alternative for patients with HPR on clopidogrel, the current study observes an excess of platelet inhibition with ticagrelor in most patients with CLTI at a dose of 90 mg twice daily.
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Liu, Ru, Tianyu Li, Deshan Yuan, Yan Chen, Xiaofang Tang, Lijian Gao, Ce Zhang et al. « Long-term effects of baseline on-treatment platelet reactivity in patients with acute coronary syndrome and thrombocytopenia undergoing percutaneous coronary intervention ». Journal of International Medical Research 50, no 4 (avril 2022) : 030006052210817. http://dx.doi.org/10.1177/03000605221081725.

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Objective To analyse the association between on-treatment platelet reactivity (TPR) and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. Methods This prospective observational study enrolled patients with coronary artery disease (CAD) that underwent percutaneous coronary intervention (PCI). Patients with ACS and TP under dual antiplatelet therapy were selected for analysis. The 2- and 5-year clinical outcomes were evaluated among patients with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), as tested by thromboelastogram at baseline. Results A total of 10 724 patients with CAD that underwent PCI were identified. Of these, 474 patients with ACS and TP met the inclusion criteria: 124 (26.2%) with HTPR, 163 (34.4%) with LTPR and 187 (39.5%) with NTPR. The 5-year rates of all-cause death, major adverse cardiovascular and cerebrovascular events, cardiac death, myocardial infarction, revascularization, stroke and bleeding were not significantly different among the three groups. Multivariate Cox regression analysis demonstrated that patients with HTPR were not independently associated with any of the 5-year endpoints compared with patients with NTPR. Conclusions TPR at baseline was not independently associated with long-term outcomes in patients with ACS and TP that underwent PCI.
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Settergren, Magnus, Felix Böhm, John Pernow, Paul Hjemdahl et Rickard Malmström. « No effect of lipid lowering on platelet activity in patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance ». Thrombosis and Haemostasis 101, no 01 (2009) : 157–64. http://dx.doi.org/10.1160/th08-06-0385.

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SummaryIn addition to lowering cholesterol, statins may reduce platelet activity and exert beneficial non-lipid (pleiotropic) effects. We evaluated the effects of two different simvastatin based treatment regimens on platelet reactivity in patients with dysglycemia and coronary artery disease (CAD). Thirty-two patients with type 2 diabetes or impaired glucose tolerance and stable CAD received six weeks of double-blind treatment with simvastatin 80 mg daily (S80; n=16) or ezetimibe 10 mg and simvastatin 10 mg daily (E10/S10; n=16). Total and low-density lipoprotein (LDL) cholesterol, and high sensitivity C-reactive protein (CRP) decreased similarly in the two groups. LDL (mM) decreased from 3.2 ± 0.6 to 1.7 ± 0.7 with E10/S10 and from 3.0 ± 1.0 to 1.4 ± 0.5 with S80 treatment. Platelet function was evaluated by whole blood flow cytometry and turbidimetric aggregometry with agonist stimulation ex vivo before and after treatment. Neither treatment affected basal or adenosine diphosphate (ADP)- or thrombin-induced platelet P-selectin expression, or fibrinogen binding, or platelet-leukocyte aggregation. Similarly, neither treatment affected ADP-induced platelet aggregation. In conclusion, lipid lowering treatment with high dose simvastatin or low dose simvastatin plus ezetimibe did not exert any substantial inhibitory effects on the basal or agonist-stimulated activity of circulating platelets in patients with stable CAD and type 2 diabetes or impaired glucose tolerance.
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Thèses sur le sujet "Low on-treatment platelet reactivity"

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Al-Mamary, Ahmed Hussien Hussien. « On-Treatment Platelet Reactivity in Peripheral and Coronary Arterial Blood in Patients Undergoing Primary PCI for ST-Segment Elevation Myocardial Infarction (STEMI) ». Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3424826.

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BACKGROUND Dual antiplatelet therapy is recommended in patients undergoing primary percutaneous coronary intervention (p-PCI) for ST-segment elevation myocardial infarction (STEMI). In the past few decades, oral antiplatelet agents have proved to significantly reduce the incidence of ischemic events in patients with atherothrombotic diseases. Nevertheless, recurrent ischemic events often occur in patients undergoing stent implantation. High platelets reactivity has been associated with a higher risk for major cardiovascular events in patients with acute coronary syndromes (ACS). Several pre-analytical variables may influence platelet function analysis. The aim of our study was to assess the on-treatment platelet reactivity in peripheral and coronary blood, in a group of patients receiving dual antiplatelet therapy undergoing primary percutaneous coronary intervention (p-PCI) for STEMI. METHODS Eligible patients for the study were considered as consecutively admitted patients to the emergency department of University-Hospital of Padua with a diagnosis of ACS with ST-segment elevation scheduled for an urgent procedure of coronary angioplasty. One hundred nine patients who consecutively underwent p-PCI (males: 72%, females: 28%; mean age: 64±13 years) were enrolled. Before the coronary angioplasty intervention, the patients were treated with dual antiplatelet therapy (aspirin 250mg I.V in association with one another oral thienopyridines; Clopidogrel 300/600mg, Prasugrel 60 mg or Ticagrelor 180 mg) and with anticoagulant therapy (unfractionated heparin 70U/Kg I.V). During the coronary angioplasty intervention two different samples were obtained, one from peripheral artery and the other from coronary blood. The platelet aggregation was studied using the impedance aggregometry Multiplate®, according to manufacturer’s indications. For each patient the values of “Area Under the Curve” (AUC) in ADP-test and ASPI-test were considered, both in the peripheral and in coronary blood. “Low responders of antiplatelet therapy” were considered when an AUC value of ASPI-test or ADP-test greater than or equal to a pre-established cut-off. RESULTS The Multiplate® analysis of ADP-test revealed that mean values were slightly higher in peripheral blood compared to coronary blood (peripheral blood: 41±28 U; coronary blood: 39±28 U), However these values with no statistically significant difference (p=0.68). Likewise, for the ASPI-test; no statistically significant difference between the mean values in the peripheral blood compared to the coronary blood (peripheral blood: 23±4 U; coronary blood: 17±2 U; p=0.06). The percentage of low-responders to ADP-receptor inhibitors was significantly greater than the percentage of low-responders to acetylsalicylic acid at time of primary PCI both in the peripheral and in the coronary blood samples (peripheral ADP-test: 38%; peripheral ASPI-test: 14%; p<0.01, Coronary ADP-test: 36%; coronary ASPI-test: 11%; p<0.01). In peripheral blood, the prevalence of “low Clopidogrel responders” was higher (45%) than that observed for Prasugrel (36%) and Ticagrelor (33%). Similar results were observed in coronary blood, the prevalence of “low Clopidogrel responders” was higher (40%) than that observed for Prasugrel (36%) and Ticagrelor (29%) however these results were with no significant statistical difference (p >0.05). Finally, a positive and statistically significant linear correlation was observed for both ASPI-test and ADP-test in peripheral and coronary blood (r2 0.23, p <0.001 and r2 0.12, p <0.001; respectively). That means; those who are resistant to acetylsalicylic acid tend to be resistant to ADP receptor inhibitors, and vice versa; those who are sensitive to acetylsalicylic acid therapy tend to be sensitive to ADP inhibitor therapy also. Our observed data did not show a correlation between platelet function and clinical outcome both for in-hospital and 1-year clinical outcomes. CONCLUSIONS In this study we observed that the overall platelet reactivity in coronary blood is lower than in peripheral blood, though not statistically significant. This more likely appears to be due to high antiplatelet drugs effect at plaque ulceration/thrombus site, where the hemostatic process is highly active at onset of STEMI. Larger studies are needed for better evaluation of these mechanisms in term of pharmacodynamic, pharmacokinetic and receptor kinetic properties of antiplatelet agents. The other interesting result emerging from data processing is the high incidence (about 30%) of low response to thienopyridine type antiplatelet drugs at the time of primary angioplasty. This result, moreover known for Clopidogrel in addition our results include patients treated with Prasugrel and Ticagrelor also. An explanation of this phenomenon which also involves potent recent drugs, requires careful analysis and further studies. The significant direct correlation between platelet reactivity in peripheral and in coronary blood is still a matter of debate. Larger studies are needed for in-depth assessment of any correlation between on–treatment platelet reactivity measured in coronary blood and clinical outcome.
INTRODUZIONE La doppia terapia antiaggregante (DAPT) è raccomandata in pazienti sottoposti ad intervento di angioplastica coronarica primaria (p-PCI) per infarto miocardico acuto con sopraslivellamento del tratto ST (STEMI). Infatti, il trattamento con farmaci antipiastrinici orali ha dimostrato di ridurre significativamente l'incidenza di eventi ischemici nei pazienti con malattie aterotrombotiche sia in fase acuta che in fase cronica. Tuttavia, spesso si verificano eventi ischemici ricorrenti nei pazienti sottoposti ad angioplastica ed impianto di stent. È stato dimostrato che una delle cause di recidiva ischemica sia l’elevata reattività delle piastrine. Pertanto, lo studio della funzione piastrinica diventa un elemento sempre più importante per valutare questo tipo di pazienti. Diverse variabili pre-analitiche possono influenzare l'analisi della funzione piastrinica. Lo scopo del nostro studio è stato quello di valutare la reattività piastrinica del sangue periferico e coronarico in un gruppo di pazienti trattati con DAPT e sottoposti p-PCI per STEMI. METODI Abbiamo considerato eleggibili allo studio tutti i pazienti consecutivamente giunti in urgenza al Pronto Soccorso dell’Azienda Ospedaliera di Padova con diagnosi di sindrome coronarica acuta con sopraslivellamento del tratto ST per i quali fosse indicata l’esecuzione in urgenza di una procedura di angioplastica coronarica. Sono stati arruolati 109 pazienti (maschi: 72%, femmine: 28%; età media: 64±13 anni). I pazienti arruolati nello studio sono stati trattati, prima di essere sottoposti alla procedura di angioplastica primaria, con doppia terapia antiaggregante (aspirina 250 mg e.v in associazione con uno dei seguenti tre farmaci: Clopidogrel 300/600 mg per os, Prasugrel 60 mg per os o Ticagrelor 180 mg per os) e con terapia anticoagulante (eparina non frazionata 70 U/Kg e.v). Durante la procedura di angioplastica primaria sono stati eseguiti due tipi di prelievo, uno dal sangue arterioso periferico ed uno dal sangue arterioso coronarico. L’aggregazione piastrinica è stata studiata con l’aggregometro Multiplate® secondo le indicazioni fornite dal costruttore. Per ogni paziente sono stati valutati i valori di “Area Under the Curve” (AUC) nell’ADP-test e nell’ASPI-test, ottenuti sul sangue periferico e sul sangue coronarico. “Low responders alla terapia antiaggregante” sono stati definiti quei pazienti con valori di “Area Under Curve” (AUC) all’ASPI test o all’ADP test sono maggiore o uguale a un range prestabilito. RISULTATI Non abbiamo osservato differenza statisticamente significativa tra i valori medi di ADP-test calcolati su sangue periferico e su sangue coronarico. I valori medi delle AUC sono risultati lievemente superiori nel sangue periferico che nel sangue coronarico (sangue periferico: 41±28 U; sangue coronarico: 39±28 U; p=0.68). Allo steso modo, non è stata riscontrata differenza statisticamente significativa tra i valori medi di ASPI-test calcolati su sangue periferico e su sangue coronarico. Anche in questo caso abbiamo osservato valori medi di AUC lievemente superiori nel sangue periferico che nel sangue coronarico (sangue periferico: 23±4 U; sangue coronarico: 17±2 U; p=0.06). Sia nel sangue periferico che nel sangue coronarico la percentuale di pazienti “low responders” al trattamento con inibitori del recettore per l’ADP è risultata essere statisticamente superiore alla percentuale di pazienti “low responders” alla terapia con acido acetilsalicilico al momento dell’angioplastica primaria (ADP-test periferico: 38%; ASPI-test periferico: 14%; p<0.01. ADP-test coronarico: 38%; ASPI-test coronarico: 11%; p<0.01). Nel sangue periferico la prevalenza di "low responders” al Clopidogrel era superiore (45%) a quella osservata rispettivamente per Prasugrel (36%) e Ticagrelor (33%). Risultati simili sono stati osservati nel sangue coronarico. In particolare, la prevalenza di "low responders” al Clopidogrel è stata superiore (40%) rispetto a quella osservata per Prasugrel (36%) e Ticagrelor (29%). Non è stata osservata alcuna differenza significativa (p> 0,05) nella prevalenza dei pazienti con valori di ADP-test superiori al cut-off prestabilito, considerando separatamente le tre diverse tienopiridine. Infine è stata individuata una correlazione lineare statisticamente significativa tra “low responders” all’acido acetilsalicilico e “low responders” agli inibitori del recettore dell’ADP. Questa osservazione indica come i pazienti resistenti al trattamento con acido acetilsalicilico tendono ad essere resistenti anche al trattamento con inibitori del recettore per l’ADP e, viceversa, pazienti “sensibili” alla terapia con acido acetilsalicilico tendono ad essere “sensibili” anche al trattamento con inibitori del recettore per l’ADP. Questi resultati sono stati osservati sia su sangue periferico (r2 0.23, p<0.001) che su sangue coronarico (r2 0.12, p<0.001). I dati che abbiamo osservato non mostrano un’associazione tra funzione piastrinica e outcome clinico nè per quanto riguarda gli “in-hospital outcome” né per quanto riguarda gli outcome a distanza di 1 anno. CONCLUSIONI I dati analizzati ci hanno permesso di dimostrare che la reattività piastrinica nel sangue coronarico era inferiore rispetto a quella osservata nel sangue periferico. Sembrerebbe quindi che, la risposta alla terapia farmacologica con doppia antiaggregante prima della procedura sia maggiore proprio laddove il processo emostatico è più attivo, ossia a livello della placca aterosclerotica sede della formazione del trombo responsabile dell’insorgenza della STEMI. Questo meccanismo necessità di conferma in termini di farmacodinamica, farmacocinetica e di cinetica recettoriale. L’altro dato estremamente interessante emerso dall’elaborazione dei dati è l’elevata incidenza (circa 30%) dei pazienti “low responders” al trattamento con farmaci antiaggreganti di tipo tienopiridinico al momento della angioplastica primaria. Questo risultato, peraltro noto per il Clopidogrel, comprende anche pazienti trattati con Prasugrel e Ticagrelor. Una possibile spiegazione di questo fenomeno, che coinvolge anche i farmaci di “seconda generazione”, necessita di un’attenta analisi. Abbiamo infine osservato una significativa correlazione tra reattività piastrinica nel sangue periferico e nel coronario. I nostri risultati, che alla luce dei limiti del nostro lavoro devono considerarsi come preliminari, necessitano di essere confermati su casistiche più numerose soprattutto per quanto riguarda la correlazione tra “on-treatment platelet reactivity” misurata nel sangue coronarico e outcomes clinici.
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Moreira, Ana Sofia Pereira. « Study of modifications induced by thermal and oxidative treatment in oligo and polysaccharides of coffee by mass spectrometry ». Doctoral thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/17074.

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Doutoramento em Bioquímica
Os polissacarídeos são os componentes maioritários dos grãos de café verde e torrado e da bebida de café. Os mais abundantes são as galactomananas, seguindo-se as arabinogalactanas. Durante o processo de torra, as galactomananas e arabinogalactanas sofrem modificações estruturais, as quais estão longe de estar completamente elucidadas devido à sua diversidade e à complexidade estrutural dos compostos formados. Durante o processo de torra, as galactomananas e arabinogalactanas reagem com proteínas, ácidos clorogénicos e sacarose, originando compostos castanhos de alto peso molecular contendo nitrogénio, designados de melanoidinas. As melanoidinas do café apresentam diversas atividades biológicas e efeitos benéficos para a saúde. No entanto, a sua estrutura exata e os mecanismos envolvidos na sua formação permanecem desconhecidos, bem como a relação estrutura-atividade biológica. A utilização de sistemas modelo e a análise por espectrometria de massa permitem obter uma visão global e, simultaneamente, detalhada das modificações estruturais nos polissacarídeos do café promovidas pela torra, contribuindo para a elucidação das estruturas e mecanismos de formação das melanoidinas. Com base nesta tese, oligossacarídeos estruturalmente relacionados com a cadeia principal das galactomananas, (β1→4)-Dmanotriose (Man3), e as cadeias laterais das arabinogalactanas, (α1→5)-Larabinotriose (Ara3), isoladamente ou em misturas com ácido 5-Ocafeoilquínico (5-CQA), o ácido clorogénico mais abundante nos grãos de café verde, e péptidos compostos por tirosina e leucina, usados como modelos das proteínas, foram sujeitos a tratamento térmico a seco, mimetizando o processo de torra. A oxidação induzida por radicais hidroxilo (HO•) foi também estudada, uma vez que estes radicais parecem estar envolvidos na modificação dos polissacarídeos durante a torra. A identificação das modificações estruturais induzidas por tratamento térmico e oxidativo dos compostos modelo foi feita por estratégias analíticas baseadas principalmente em espectrometria de massa, mas também em cromatografia líquida. A cromatografia de gás foi usada na análise de açúcares neutros e ligações glicosídicas. Para validar as conclusões obtidas com os compostos modelo, foram também analisadas amostras de polissacarídeos do café obtidas a partir de resíduo de café e café instantâneo. Os resultados obtidos a partir dos oligossacarídeos modelo quando submetidos a tratamento térmico (seco), assim como à oxidação induzida por HO• (em solução), indicam a ocorrência de despolimerização, o que está de acordo com estudos anteriores que reportam a despolimerização das galactomananas e arabinogalactanas do café durante a torra. Foram ainda identificados outros compostos resultantes da quebra do anel de açúcares formados durante o tratamento térmico e oxidativo da Ara3. Por outro lado, o tratamento térmico a seco dos oligossacarídeos modelo (individualmente ou quando misturados) promoveu a formação de oligossacarídeos com um maior grau de polimerização, e também polissacarídeos com novos tipos de ligações glicosídicas, evidenciando a ocorrência de polimerização através reações de transglicosilação não enzimática induzidas por tratamento térmico a seco. As reações de transglicosilação induzidas por tratamento térmico a seco podem ocorrer entre resíduos de açúcares provenientes da mesma origem, mas também de origens diferentes com formação de estruturas híbridas, contendo arabinose e manose como observado nos casos dos compostos modelo usados. Os resultados obtidos a partir de amostras do resíduo de café e de café instantâneo sugerem a presença de polissacarídeos híbridos nestas amostras de café processado, corroborando a ocorrência de transglicosilação durante o processo de torra. Além disso, o estudo de misturas contendo diferentes proporções de cada oligossacarídeo modelo, mimetizando regiões do grão de café com composição distinta em polissacarídeos, sujeitos a diferentes períodos de tratamento térmico, permitiu inferir que diferentes estruturas híbridas e não híbridas podem ser formadas a partir das arabinogalactanas e galactomananas, dependendo da sua distribuição nas paredes celulares do grão e das condições de torra. Estes resultados podem explicar a heterogeneidade de estruturas de melanoidinas formadas durante a torra do café. Os resultados obtidos a partir de misturas modelo contendo um oligossacarídeo (Ara3 ou Man3) e 5-CQA sujeitas a tratamento térmico a seco, assim como de amostras provenientes do resíduo de café, mostraram a formação de compostos híbridos compostos por moléculas de CQA ligadas covalentemente a um número variável de resíduos de açúcar. Além disso, os resultados obtidos a partir da mistura contendo Man3 e 5-CQA mostraram que o CQA atua como catalisador das reações de transglicosilação. Por outro lado, nas misturas modelo contendo um péptido, mesmo contendo também 5-CQA e sujeitas ao mesmo tratamento, observou-se uma diminuição na extensão das reações transglicosilação. Este resultado pode explicar a baixa extensão das reações de transglicosilação não enzimáticas durante a torra nas regiões do grão de café mais ricas em proteínas, apesar dos polissacarídeos serem os componentes maioritários dos grãos de café. A diminuição das reações de transglicosilação na presença de péptidos/proteínas pode dever-se ao facto de os resíduos de açúcares redutores reagirem preferencialmente com os grupos amina de péptidos/proteínas por reação de Maillard, diminuindo o número de resíduos de açúcares redutores disponíveis para as reações de transglicosilação. Além dos compostos já descritos, uma diversidade de outros compostos foram formados a partir dos sistemas modelo, nomeadamente derivados de desidratação formados durante o tratamento térmico a seco. Em conclusão, a tipificação das modificações estruturais promovidas pela torra nos polissacarídeos do café abre o caminho para a compreensão dos mecanismos de formação das melanoidinas e da relação estrutura-atividade destes compostos.
Polysaccharides are the major components of green and roasted coffee beans, and coffee brew. The most abundant ones are galactomannans, followed by arabinogalactans. During the roasting process, galactomannans and arabinogalactans undergo structural modifications that are far to be completely elucidated due to their diversity and complexity of the compounds formed. During the roasting process, galactomannans and arabinogalactans react with proteins, chlorogenic acids, and sucrose, originating high molecular weight brown compounds containing nitrogen, known as melanoidins. Several biological activities and beneficial health effects have been attributed to coffee melanoidins. However, their exact structures and the mechanisms involved in their formation remain unknown, as well as the structure-biological activity relationship. The use of model systems and mass spectrometry analysis allow to obtain an overall view and, simultaneously, detailed, of the structural modifications in coffee polysaccharides promoted by roasting, contributing to the elucidation of the structures and formation mechanisms of melanoidins. Based on this thesis, oligosaccharides structurally related to the backbone of galactomannans, (β1→4)-D-mannotriose, and the side chains of arabinogalactans, (α1→5)-Larabinotriose, alone or in mixtures with 5-O-caffeoylquinic acid, the most abundant chlorogenic acid in green coffee beans, and dipeptides composed by tyrosine and leucine, used as models of proteins, were submitted to dry thermal treatments, mimicking the coffee roasting process. The oxidation induced by hydroxyl radicals (HO•) was also studied, since these radicals seem to be involved in the modification of the polysaccharides during roasting. The identification of the structural modifications induced by thermal and oxidative treatment of the model compounds was performed mostly by mass spectrometry-based analytical strategies, but also using liquid chromatography. Gas chromatography was used in the analysis of neutral sugars and glycosidic linkages. To validate the conclusions achieved with the model compounds, coffee polysaccharide samples obtained from spent coffee grounds and instant coffee were also analysed. The results obtained from the model oligosaccharides when submitted to thermal treatment (dry) or oxidation induced by HO• (in solution) indicate the occurrence of depolymerization, which is in line with previous studies reporting the depolymerization of coffee galactomannans and arabinogalactans during roasting. Compounds resulting from sugar ring cleavage were also formed during thermal treatment and oxidative treatment of Ara3. On the other hand, the dry thermal treatment of the model oligosaccharides (alone or when mixed) promoted the formation of oligosaccharides with a higher degree of polymerization, and also polysaccharides with new type of glycosidic linkages, evidencing the occurrence of polymerization via non-enzymatic transglycosylation reactions induced by dry thermal treatment. The transglycosylation reactions induced by dry thermal treatment can occur between sugar residues from the same origin, but also of different origins, with formation of hybrid structures, containing arabinose and mannose in the case of the model compounds used. The results obtained from spent coffee grounds and instant coffee samples suggest the presence of hybrid polysaccharides in these processed coffee samples, corroborating the occurrence of transglycosylation during the roasting process. Furthermore, the study of mixtures containing different proportions of each model oligosaccharide, mimicking coffee bean regions with distinct polysaccharide composition, subjected to different periods of thermal treatment, allowed to infer that different hybrid and non-hybrid structures may be formed from arabinogalactans and galactomannans, depending on their distribution in the bean cell walls and on roasting conditions. These results may explain the heterogeneity of melanoidins structures formed during coffee roasting. The results obtained from model mixtures containing an oligosaccharide (Ara3 or Man3) and 5-CQA and subjected to dry thermal treatment, as well as samples derived from spent coffee grounds, showed the formation of hybrid compounds composed by CQA molecules covalently linked to a variable number of sugar residues. Moreover, the results obtained from the mixture containing Man3 and 5-CQA showed that CQA acts as catalyst of transglycosylation reactions. On the other hand, in the model mixtures containing a peptide, even if containing 5-CQA and subjected to the same treatment, it was observed a decrease in the extent of transglycosylation reactions. This outcome can explain the low extent of non-enzymatic transglycosylation reactions during roasting in coffee bean regions enriched in proteins, although polysaccharides are the major components of the coffee beans. The decrease of transglycosylation reactions in the presence of peptides/proteins can be related with the preferential reactivity of reducing residues with the amino groups of peptides/proteins by Maillard reaction, decreasing the number of reducing residues available to be directly involved in the transglycosylation reactions. In addition to the compounds already described, a diversity of other compounds were formed from model systems, namely dehydrated derivatives formed during dry thermal treatment. In conclusion, the identification of the structural modifications in coffee polysaccharides promoted by roasting pave the way to the understanding of the mechanisms of formation of melanoidins and structure-activity relationship of these compounds.
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Grifoni, Elisa. « Funzione piastrinica e rischio di eventi avversi in pazienti con arteriopatia periferica sottoposti a rivascolarizzazione percutanea (Platelet function and risk of adverse events in peripheral artery disease patients undergoing percutaneous revascularization) ». Doctoral thesis, 2018. http://hdl.handle.net/2158/1125789.

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Background and Aim: Lots of studies demonstrated that a different entity of on-treatment platelet function inhibition is associated with different clinical outcomes in patients with acute coronary syndromes. In particular, high on-treatment platelet reactivity (HPR) has been associated with an increased risk of ischemic complications (especially stent thrombosis), and there is a growing body of evidence that, on the contrary, low on-treatment platelet reactivity (LPR) could be associated with bleeding risk. Few data are available in the literature on the association between a different entity of platelet inhibition on-antiplatelet treatment and clinical outcomes in patients with peripheral artery disease (PAD). Aim of this study was to evaluate, in patients with PAD undergoing percutaneous revascularization, the degree of on-treatment platelet reactivity, and its association with ischemic and hemorrhagic adverse events at follow-up. Methods: In this observational, prospective, single center study, consecutive patients with PAD undergoing percutaneous transluminal angioplasty (PTA) with or without stenting, were enrolled. All patients were treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor. Platelet function was assessed by Light Transmission Aggregometry (LTA) using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists of platelet aggregation, on blood samples obtained within 24 hours from PTA. HPR was defined by LTA ≥20% if induced by AA, and LTA ≥70% if induced by ADP. Follow-up was performed in order to record the occurrence of ischemic and bleeding events. Results: The study enrolled 177 patients [118 males, median age 75 (IQR 68-81) years]. HPR by AA was found in 52% of patients, and showed a non significant association with older age and a higher prevalence of renal failure, whereas HPR by ADP was found in 32% of patients, and was significantly associated with older age. During follow-up [median duration 23 (IQR 13-27) months] 23 deaths (13%) were recorded; 27 patients (17.5%) underwent target limb revascularization, 2 (1.3%) amputation, and 6 (3.9%) myocardial revascularization. Twenty-four patients (15.6%) experienced a minor bleeding complication. At multivariate analysis HPR by AA and HPR by ADP were independent predictors of death [HR 3.75 (1.20-11.66), P=0.023 and HR 4.78 (1.57-14.52), P=0.006, respectively]. Moreover, patients with dual HPR both by AA and by ADP showed a significantly higher risk of death than those without (P<0.001). The median value of LTA by ADP was significantly lower in patients with bleeding complications than in those without [26.5 (22-39.2)% vs 62 (44.5-74)%, P<0.001). At ROC curve analysis the cut-off of platelet aggregation induced by ADP with the best sensitivity and specificity for increased risk of bleeding was 41%. LTA by ADP lower than 41% was independently associated with bleeding [HR 14.59 (2.55-24.01), P=0.001] at multivariate analysis. Conclusions: In PAD patients undergoing PTA, HPR by ADP and AA were predictors of death, whereas LPR by ADP was predictor of bleeding complications. These results suggest the potential utility of assessing platelet function, even in the setting of PAD, in order to ensure the patient the best tailored antiplatelet therapy.
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Livres sur le sujet "Low on-treatment platelet reactivity"

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Chistyakova, Guzel, Lyudmila Ustyantseva, Irina Remizova, Vladislav Ryumin et Svetlana Bychkova. CHILDREN WITH EXTREMELY LOW BODY WEIGHT : CLINICAL CHARACTERISTICS, FUNCTIONAL STATE OF THE IMMUNE SYSTEM, PATHOGENETIC MECHANISMS OF THE FORMATION OF NEONATAL PATHOLOGY. au : AUS PUBLISHERS, 2022. http://dx.doi.org/10.26526/monography_62061e70cc4ed1.46611016.

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The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
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Macdougall, Iain C. Clinical aspects and overview of renal anaemia. Sous la direction de David J. Goldsmith. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0123.

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Anaemia is an almost ubiquitous complication of chronic kidney disease, which has a number of implications for the patient. It is associated with adverse outcomes, an increased rate of red cell transfusions, poor quality of life, and reduced physical capacity. Severe anaemia also impacts on cardiac function, as well as on platelet function, the latter contributing to the bleeding diathesis of uraemia. Renal anaemia occurs mainly in the later stages of chronic kidney disease (stages 3B, 4, and 5), and up to 95% of patients on dialysis suffer from this condition. It is caused largely by inappropriately low erythropoietin levels, but other factors such as a shortened red cell survival also play a part. The anaemia is usually normochromic and normocytic, unless concomitant iron deficiency is present. The latter is also common in renal failure, partly due to low dietary iron intake and absorption, and partly due to increased iron losses. Prior to the 1990s, treatment options were limited, and many patients (particularly those on haemodialysis) required regular blood transfusions, resulting in iron overload and human leucocyte antigen sensitization. Correction of anaemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow. Ever since the introduction of recombinant human erythropoietin, it has been possible to boost erythropoietic activity, and both oral and intravenous iron products are available to provide supplemental iron. In dialysis patients, oral iron is usually poorly absorbed due to upregulation of hepcidin activity, and intravenous iron is often required. The physiological processes relevant to red cell production are described, as well as the prevalence, characteristics, pathogenesis, and physiological consequences of renal anaemia.
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Chapitres de livres sur le sujet "Low on-treatment platelet reactivity"

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Chistyakova, Guzel, Lyudmila Ustyantseva, Irina Remizova, Vladislav Ryumin et Svetlana Bychkova. « CHARACTERISTICS OF CONNECTED AND ADAPTIVE IMMUNITY OF CHILDREN WITH EXTREMELY LOW BODY WEIGHT OF DIFFERENT GESTIONAL AGE ». Dans CHILDREN WITH EXTREMELY LOW BODY WEIGHT : CLINICAL CHARACTERISTICS, FUNCTIONAL STATE OF THE IMMUNE SYSTEM, PATHOGENETIC MECHANISMS OF THE FORMATION OF NEONATAL PATHOLOGY, 47–77. au : AUS PUBLISHERS, 2022. http://dx.doi.org/10.26526/chapter_62061e70deca75.92242970.

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The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
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Chistyakova, Guzel, Lyudmila Ustyantseva, Irina Remizova, Vladislav Ryumin et Svetlana Bychkova. « FUNCTIONAL STATE OF THE IMMUNE SYSTEM OF CHILDREN WITH RETINOPATHY OF PREMATURE IN THE DYNAMICS OF THE POSTNATAL PERIOD ». Dans CHILDREN WITH EXTREMELY LOW BODY WEIGHT : CLINICAL CHARACTERISTICS, FUNCTIONAL STATE OF THE IMMUNE SYSTEM, PATHOGENETIC MECHANISMS OF THE FORMATION OF NEONATAL PATHOLOGY, 105–28. au : AUS PUBLISHERS, 2022. http://dx.doi.org/10.26526/chapter_62061e70e0ba78.92986346.

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The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
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Chistyakova, Guzel, Lyudmila Ustyantseva, Irina Remizova, Vladislav Ryumin et Svetlana Bychkova. « FEATURES OF THE FUNCTIONAL STATE OF THE IMMUNE SYSTEM OF NEWBORNS WITH BRONCHOPULMONARY DYSPLASIA ». Dans CHILDREN WITH EXTREMELY LOW BODY WEIGHT : CLINICAL CHARACTERISTICS, FUNCTIONAL STATE OF THE IMMUNE SYSTEM, PATHOGENETIC MECHANISMS OF THE FORMATION OF NEONATAL PATHOLOGY, 78–104. au : AUS PUBLISHERS, 2022. http://dx.doi.org/10.26526/chapter_62061e70dfbae2.28992721.

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The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
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Chistyakova, Guzel, Lyudmila Ustyantseva, Irina Remizova, Vladislav Ryumin et Svetlana Bychkova. « FEATURES OF THE POSTNATAL PERIOD OF PREMATURE INFANTS ». Dans CHILDREN WITH EXTREMELY LOW BODY WEIGHT : CLINICAL CHARACTERISTICS, FUNCTIONAL STATE OF THE IMMUNE SYSTEM, PATHOGENETIC MECHANISMS OF THE FORMATION OF NEONATAL PATHOLOGY, 25–46. au : AUS PUBLISHERS, 2022. http://dx.doi.org/10.26526/chapter_62061e70ddd515.23232017.

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The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
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Chistyakova, Guzel, Lyudmila Ustyantseva, Irina Remizova, Vladislav Ryumin et Svetlana Bychkova. « RISK FACTORS OF BIRTH OF PREMATURE CHILDREN ». Dans CHILDREN WITH EXTREMELY LOW BODY WEIGHT : CLINICAL CHARACTERISTICS, FUNCTIONAL STATE OF THE IMMUNE SYSTEM, PATHOGENETIC MECHANISMS OF THE FORMATION OF NEONATAL PATHOLOGY, 11–24. au : AUS PUBLISHERS, 2022. http://dx.doi.org/10.26526/chapter_62061e70dcd948.10387409.

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The purpose of the monograph, which contains a modern view of the problem of adaptation of children with extremely low body weight, is to provide a wide range of doctors with basic information about the clinical picture, functional activity of innate and adaptive immunity, prognostic criteria of postnatal pathology, based on their own research. The specific features of the immunological reactivity of premature infants of various gestational ages who have developed bronchopulmonary dysplasia (BPD) and retinopathy of newborns (RN) from the moment of birth and after reaching postconceptional age (37-40 weeks) are described separately. The mechanisms of their implementation with the participation of factors of innate and adaptive immunity are considered in detail. Methods for early prediction of BPD and RN with the determination of an integral indicator and an algorithm for the management of premature infants with a high risk of postnatal complications at the stage of early rehabilitation are proposed. The information provided makes it possible to personify the treatment, preventive and rehabilitation measures in premature babies. The monograph is intended for obstetricians-gynecologists, neonatologists, pediatricians, allergists-immunologists, doctors of other specialties, residents, students of the system of continuing medical education. This work was done with financial support from the Ministry of Education and Science, grant of the President of the Russian Federation No. MK-1140.2020.7.
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Noman, Durr-e.-Shahwar, et Gary Owens. « Wastewater Treatment and Role of Green Synthesized Metal Oxide Nanocomposites ». Dans Research Anthology on Synthesis, Characterization, and Applications of Nanomaterials, 1743–83. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-7998-8591-7.ch073.

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Water pollution by metalloids is a global environmental concern. Owing to their propensity for bioaccumulation, water solubility, and interaction with environment, they are threatening both human and ecosystem health. Inherent limitations like low efficiency, sensitive operating conditions, and high capital and operating costs are associated with conventional removal methods which restricts adoption of these technologies on large scale. While adsorption is commonly recognized as both an effective and affordable remediation technology, many common adsorbents often have inherited limitations including non-renewability and high operating costs. Thus, limitations in conventional remediation technologies have headed to the rapid progression of new avenues for advanced treatment technologies for metalloid pollutant removal such as green nanotechnology. In contrast to many of the currently available adsorbents, nanoparticles often have unique properties such as tiny size, more active sites and big surface area, easy separation, and high reactivity that enhance removal efficiencies.
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Noman, Durr-e.-Shahwar, et Gary Owens. « Wastewater Treatment and Role of Green Synthesized Metal Oxide Nanocomposites ». Dans Nanotechnology Applications in Environmental Engineering, 268–307. IGI Global, 2019. http://dx.doi.org/10.4018/978-1-5225-5745-6.ch012.

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Water pollution by metalloids is a global environmental concern. Owing to their propensity for bioaccumulation, water solubility, and interaction with environment, they are threatening both human and ecosystem health. Inherent limitations like low efficiency, sensitive operating conditions, and high capital and operating costs are associated with conventional removal methods which restricts adoption of these technologies on large scale. While adsorption is commonly recognized as both an effective and affordable remediation technology, many common adsorbents often have inherited limitations including non-renewability and high operating costs. Thus, limitations in conventional remediation technologies have headed to the rapid progression of new avenues for advanced treatment technologies for metalloid pollutant removal such as green nanotechnology. In contrast to many of the currently available adsorbents, nanoparticles often have unique properties such as tiny size, more active sites and big surface area, easy separation, and high reactivity that enhance removal efficiencies.
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Becker, Richard C., et Frederick A. Spencer. « Fibrinolytic Agents ». Dans Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0041.

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The generation of plasmin from plasminogen by plasminogen activators (fibrinolytic agents) induces a variety of effects in addition to dissolving fibrin strands, degrading fibrinogen, and inhibiting tissue factor pathway and factor VIII. It also, in high concentrations, causes platelet activation. Thus, fibrinolytic agents have both prothrombotic and antihemostatic properties—the latter of which is often augmented by the concomitant use of anticoagulants and platelet antagonists (see Chapter 12). Bleeding is the most common complication of fibrinolytic (and adjunctive antithrombotic) therapy. The most important predictors of nonintracranial hemorrhage are older age, invasive procedures, low body weight, and female sex (de Jaegre et al, 1992; GISSI 2 Investigators, 1990; GUSTO-III Investigators, 1997; INJECT Investigators, 1995). Predictors of intracranial hemorrhage include age (>65 years), low body weight (<70 kg), hypertension on admission, and alteplase (vs. streptokinase) (GUSTO-III Investigators, 1997). The approach to patient management in cases of fibrinolytic-induced bleeding is summarized in Figure 30.1. It is important to consider antithrombotic agents that may concomitantly increase hemorrhagic potential. Factor VIIa (recombinant; NovoSeven) represents a treatment alternative for life-threatening hemorrhagic complications.
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Aruch, Daniel, et Ronald Hoffman. « Thrombocytosis and essential thrombocythaemia ». Dans Oxford Textbook of Medicine, sous la direction de Chris Hatton et Deborah Hay, 5239–47. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0518.

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The term thrombocytosis refers to a platelet count elevated above 450 × 109/litre, which can be (1) primary—including essential thrombocythaemia, chronic myeloid leukaemia, polycythaemia vera, and myelodysplastic syndromes; or (2) secondary—including iron deficiency, infection, blood loss, and malignancy. Essential thrombocythaemia: aetiology—the JAK2 V617F missense mutation typical of polycythaemia vera is found in about 50% of cases. In addition, 10% of patients have a mutation in the thrombopoietin receptor gene, MPL, and 30% have a mutation in calreticulin (CALR). Approximately 10% of patients have none of these mutations and are referred to as ‘triple negative’ essential thrombocythaemia. Diagnosis requires all of the following four major criteria: (1) platelet count greater than 450 × 109/litre; (2) bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei without a significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibres; (3) failure to meet the criteria for other myeloproliferative neoplasms; and (4) presence of JAK2, CALR, or MPL mutations. Alternatively, diagnosis can be met when the first three major criteria are present and the one minor criterion, namely the presence of another clonal marker or absence of evidence for reactive thrombocytosis. Treatment requires risk stratification based on the age of the patient and any prior history of thrombosis, with treatment being reserved for those at a high risk of developing complications and not introduced simply on the basis of platelet counts alone unless there is extreme thrombocytosis (>1500 × 109/litre). Therapies include low-dose aspirin and cytoreduction.
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Bao, Xiaodong. « Obstetric : Preeclampsia ». Dans Anesthesiology Applied Exam Board Review, sous la direction de Ruchir Gupta et Minh Chau Joe Tran, 219–26. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190852474.003.0032.

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In this chapter the essential aspects of anesthesia for preeclampsia are discussed. Subtopics include HELLP syndrome, a life-threatening liver disorder comprising hemolysis, elevated liver enzymes, and low platelet count. Other subtopics addressed are eclampsia, disseminated intravascular coagulation, magnesium therapy, and hydralazine. The chapter is divided into preoperative, intraoperative, and postoperative sections with important subtopics related to the main topic in each section. Preoperative topics include potential effects of drug use on the mother and fetus, and identifying preeclampsia. Issues discussed related to intraoperative management include magnesium therapy, thrombocytopenia, and fetal heat rate deceleration. Postoperative concerns discussed are assessment and treatment of postpartum hemorrhage, seizure, and hypotension.
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Actes de conférences sur le sujet "Low on-treatment platelet reactivity"

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Chong, B. H., F. Ismail, J. Cade, A. S. Gallus, S. Gordon et C. N. Chesterman. « HEPARIN-INDUCED THROMBOCYTOPENIA : IN VITRO STUDIES WITH LOW MOLECULAR WEIGHT HEPARINOID, ORG 10172 ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643926.

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Heparin-induced thrombocytopenia (HIT), an adverse effect of heparin therapy, may be associated with serious thrombosis resulting in severe disability or death. An IgG heparin-dependent antibody may be demonstrated in HIT by platelet aggregation studies with patient serum/plasma and standard (s) heparin. A recent study showed high cross-reactivity of the antibody with low molecular weight (LMW) heparins as most of the 22 patient sera tested gave a positive reaction with various LMW heparins including CY222, CY216, PK10169 and Kabi 2165 (Messmore HL et al, Blood 64(5), 1984 suppl). However, cross-reactivity rate with Org 10172, a LMW heparinoid which has strong anti-Xa but negligible antithrombin activity, is unknown. We tested the plasma of 17 patients with HIT for cross-reactivity with Org 10172. Although all 17 patient plasmas reacted positively with s.heparin (0.2 1.0 IU/ml), only 3 patient plasmas gave a positive but weaker reaction with Org 10172 (0.2-1.0 IU/ml).Further studies were performed to investigate the effect of adding Org 10172 (0.2 to 2.0 anti-Xa U/ml) to a reaction mixture of normal platelet-rich plasma, patient plasma and s.heparin (0.2 IU/ml). With 7 patient plasmas which showed no cross-reactivity with Org 10172, the antibody-induced platelet aggregation was inhibited when the concentration of Org 10172 exceeded 0.5 to 1.0 anti-Xa U/ml. When the study was repeated with other s.heparin concentrations (0.05, 0.1, 0.4 IU/ml), this inhibitory effect was again present provided the ratio of Org 10172 concentration (anti-Xa U/ml) to heparin concentration (IU/ml) exceeds 2.5 to 5. However, this inhibitory effect was not observed with the 3 patient plasmas which showed cross-reactivity with the heparinoid whqp. the same concentrations of Org 10172 were added. This inhibitory effect appeared to be specific for platelet aggregation induced by the heparin-dependent antibody as Org 10172 (<10 anti-Xa U/ml) did not affect platelet aggregation induced by collagen (2 ug/ml) and ADP (2.5 uM). These findings together with our experience of 3 cases of HIT successfully treated with Org 10172 suggest that this LMW heparinoid may be a useful drug for the treatment of HIT.
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David, J. L., V. Legrand et H. E. Kulbertus. « RELEVANCE OF FREE PLATELET COUNT RATIO (PCR) TO CIRCULATING PLATELET AGGREGATES (CPA) AND TO THE RELEASE OF B-THROMBOGLOBULIN(β-tg) INDUCED BY EXERCICE IN PATIENTS WITH CORONARY HEART DISEASE (CHD). EFFECTS OF TICLOPIDINE (T) TREATMENT ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643026.

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CPA are considered as a possible cause of blood flow impairment and as a risk factor of sudden death in patients with CHD. The relevance of a low PCR to the presence of CPA is still debated. Indeed in a critical and well designed evaluation of this index, Sanibaldi et al.(1986) have shown that PCR obtained by counting free platelets in diluted whole blood was not lowered in patients with “thrombotic tendency”. They suggested that low CPA reported in other clinical studies may result from an artifact of blood sampling or from ex-vivo procedures.In order to reevalute the meaning of a low PCR, selected patients with CHD have been submitted to an exercice resulting in platelet stimulation. Free platelets were counted, whole blood and plasma β-tg were simultaneously determined by RIA after careful blood sampling performed before the exercice, at its end and 30 min later. Patients were previously treated by Placebo (P)or by T 500 mg per day given in a cross-over double blind manner.It was shown that : 1) after P treatment, PCR was lowered and β-tg was increased, both significantly, at the end of exercice; 30 min later, PCR was normalized whereas β-tg remained high presumably because β-tg is not cleared from plasma within 30 min. 2) T treatment significantly inhibited both platelet responses.In conclusion, when platelets are submitted to systemic and sustained stimuli occurring during exercice stress, lowered PCR reflects the presence of circulating platelet aggregates which can be dispersed ex-vivo by EDTA. In these conditions, the meaning of this index is strongly confirmed by the simultaneous release of βtg. T treatment significantly reduces platelet reactivity to exer cice stress and may reduce the effects of platelet aggregation and release on compromised microcirculation.
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Kos, M., F. X. Hainz, I. Assmann, M. Kundi, I. Pabinger, S. Panzer, Ch Korninger, Ch Kunz et K. Lechner. « RISK FACTORS FOR AIDS AND ARC IN MULTITRANSHJSED HAEMOPHILIACS : ASSOCIATION OF A WEAK GAG P 18 IN WESTERN BLOT (WB) AND IMMUNE THROMBOCYTOPENIA ? » Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644680.

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Lymphocyte subsets, platelet counts, immune globulin levels and antibody to HIV (Elisa, WB) were determined in 87 multitransfused asymptomatic haemophiliacs in 1982/83. Between 1982 and 1987 6 patients developed AIDS and 5 ARC (3 immune thrombocytopenia and 2 lymphadenopathy). AIDS or ARC developed in seropositive patients only (11/49). Patients who subsequently developed AIDS or ARC showed significantly lower numbers of T helper lymphocytes (378/mm3 versus 605/mm3; p 0.01), lower platelet counts (157x109 versus 194x109; p 0.05) and higher levels of IgG (2528 mg/dl versus 1992 mg/dl; p 0.01). AIDS or ARC occured in 4 of 7 patients(57.1%) with a low HIV antibody level ( 2000), but only in 7 of 42 (16.6%) with a high level of antibody to HIV ( 2000). A weak gag p 24 in WB was found in 4 of 11 patients (36.3%) who subsequently acquired AIDS or ARC , while none of the patients whq remained asymptomatic displayed this reactivity pattern in WB. 9 patients showed a weak gag p 18 in WB. 8 of them (88.8%) have platelet counts below 120x109 /1, 3 developed imiruine thrombocytopenia with platelet counts of less than 50xl09. Oily 6 of 40 patients (15%) without this reactivity pattern in WB have platelet counts lower than 120x109 and none below 50xl09.We conclude that a weak gag p 24 in WB has a strong positive predictive power for the development of AIDS or ARC in seropositive haemophiliacs. A weak gag p 18 in WB could possibly be associated with the occurence of immune thrombocytopenia in these patients.
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Cohen, H., I. J. Mackie, R. Patel, G. H. Neild et S. J. Machin. « THE EFFECTS OF CYCLOSPORIN A (CyA) ON PLATELET FUNCTION IN HUMAN RENAL ALLOGRAFT RECIPIENTS AND NZW RABBITS ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644125.

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CyA therapy is associated with microvascular thrombotic complications both in human allograft recipients and experimental animals. We have assessed evidence for increased platelet reactivity, i.e. presence of spontaneous aggregation, responses in platelet rich plasma (PRP) to ADP, total platelet nucleotide content and release to 20μg/ml collagen, and sensitivity to ZK 36,374, a prostacyclin analogue, serially in 21 human renal allograft recipients for 1 year post-transplantation and in 15 O NZW rabbits which received CyA 25mg/kg (n=5), or 'placebo' (the carrier for CyA) (n=5), or N saline (n=5) i.v. for 10 consecutive days. In the humans, spontaneous aggregation was observed on 10 occasions in 5 patients and responses to low doses of ADP, 0.5 and 1.0 μM, were significantly increased compared to normal controls up to 1 year (p<0.002) post transplantation. Total platelet nucleotide (ATP + ADP) content was significantly decreased (p<0.002) up to 3 months post-transplantation, indicative of in vivo activation, as was nucleotide release. Platelet sensitivity to ZK 36,374 decreased after 2 months (p<0.01) and this persisted at 1 year (p<0.02) compared to sensitivity at 1 week post transplantation (paired t tests). In the animal model, CyA or 'placebo' administration were unassociated with spontaneous aggregation, responses to ADP 0.5-5.0 μM and collagen 2.0-4.0 μg/ml remained unchanged as did sensitivity to ZK 36,374. In conclusion, CyA-treated renal allograft recipients exhibit spontaneous platelet aggregation, hyperaggregability to low doses of ADP, in vivo activation and decreased sensitivity to ZK 36,374, with abnormalities persisting up to one year posttransplantation. These abnormalities are not reproducible in an animal model.
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Bult, H., F. Jordaens, A. G. Herman, C. Van Hove et T. J. Verbeuren. « RELEASE OF ENDOTHELIUM DERIVED RELAXING FACTOR (EDRF), PROSTACYCLIN (PGI2) AND ANTI-PLATELET ACTIVITY BY RABBIT AORTIC ENDOTHELIUM ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643797.

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Endothelium may release EDRF and PGI2; the former causes relaxation of arterial smooth muscle cells, whereas PGI2 suppresses phagocyte and platelet activation and may relax some arteries. The aim of the present experiments was to investigate whether EDRF from rabbit aorta affects platelet reactivity. To this end the isolated thoracic aorta was perfused with a Krebs' solution (3 ml/min), andthe perfusate was continuously super fused over a de-endothe-lialized ring of the abdominal aorta, contracted withnoradrenaline in the presence of atropine, to monitor EDRF. Aliquots (200 μl) ofeffluent were also added to 200 (il prewarmedautologous citrate platelet rich plasma, which was immediately stimulated with ADP or U46619, a thromboxane (TX) A2 mimetic. Both agonists induce aggregation independently of TXA2 formation. Finally, the PGI2 content of the effluent was assessed by specific radioimmunoassay of 6-oxo-PGF1alpha(ir-6oxo). Infusion of 0.3,1 and 3 μM acetylcholine (Ach) through the aorta for 7.5 min caused a dose-dependent relaxation of the abdominal ring (33 to 100 % at 3 (μM Ach), indicating intraluminal EDRF release. Maximum relaxation was reached in 3 min and maintained. Release of platelet inhibitory activity was variable. At 3 μM Ach, anti-platelet activity(more than 10 % suppression of aggregation)was present in the effluent of 5 (of 7) aorta's for ADP-, and in effluent of 6 (of 7) aorta's for U46617-induced aggregation. U46619 was more sensitive to the anti-platelet activity, a finding consistent withauthentic PGI2. When a clear anti-platelet activity was monitored, its release was abolished by indo-methacin, which affected neither EDRF release nor platelet aggregation. Baseline release of ir-6oxo was low and variable, but dose-dependently stimulated by Ach, reaching a maximum for each concentration in the 2nd to 3rd minute. In contrast to EDRF, ir-6oxo release was not maintained during the subsequent 4 min and tapered off. Formation of ir-6oxo and anti-aggregatingeffect were positively correlated, but therewas no association between EDRF and ir-6oxo or anti-platelet activity. In conclusion, rabbit aortic endothelium could release EDRF and PGI2, but the present set-up did not reveal an anti-platelet effect of EDRF.
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Laustiola, K., R. Lassila, P. Koskinen et V. Manninen. « GEMFIBROZIL HAS ANTI-PLATELET EFFECTS IN PATIENTS WITH HYPERCHOLESTEROLAEMIA DURING PHYSICAL STRESS ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643462.

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Earlier studies indicate an increased platelet reactivity in patients with hypercholesterolaemia. Physical and mental stress have also been reported to cause increased reactivity. The present study was undertaken to evaluate the effect of gemfibrozil (G) a new lipid lowering drug on platelet reactivity during physical stress. Ten otherwise healthy male subjects with serum cholesterol levels above 7 mmol/l were involved in a double-blind study. It consisted of two treatment periods of 8 weeks during which the patients were given either G (600 mg b.i.d.) or placebo (PI) and an 8 weeks wash-out period before the cross-over. At the end of the treatment periods an exercise test was carried out and platelet reactivity tested. Adrenaline, ADP and collagen were used to induce aggregation and 5-HT and T×B2 release measured. Plasma beta-TG and fibrinogen were also determined.The treshold concentration of adrenaline necessary to evoke secondary aggregation was increased in 8/10 patients during exercise after G treatment and in 2/10 after PI. When the lowest ADP concentration to cause secondary aggregation (2-4 uM) was used there was a significant decrease in the 5-HT (− 44%) and T×B2 (− 48%) secretion and a significant decrease in the area under the aggregation curve (− 28%). A decrease in 5-HT secretion was also seen after G treatment when a fixed ADP concentration of 10 uM was used. During collagen stimulation no changes were seen between the two groups. Beta-TG remained unchanged irrespective of treatment and fibrinogen showed a modest increase during exercise in both treatment groups. These results indicate a new anti-platelet effect of gemfibrozil which might be of importance in prevention of acute thrombotic events in hypercho1estero1aemic patients.
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Wallentin, Lars, Ingyar Nyman, ULF Berglund et Eva Swahn. « HEPARIN AND ACETYLSALICYLIC ACID (ASA) 75 MG/DAY IN UNSTABLE CORONARY ARTERY DISEASE - EFFECTS ON PLATELET REACTIVITY ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643009.

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In unstable coronary artery disease (UCAD), i.e. unstable angina pectoris (UAP) or non-Q-myocardial infarction (NMI), treatment with heparin or ASA have given encouraging results. The present study attempts to verify the effects of i.v. heparin (5 days) and to evaluate the utility of ASA 75 mg/day (one year). Patients, admitted because of chest pain, who either develops NMI or signs of ischemia in resting or exercise ECG.s are included. Within 72 hours patients are randomized to obtain Heparin+ASA, Heparin+Placebo, Placebo + ASA or Placebo+Placebo . Platelet reactivity is studied in vitro in platelet rich plasma (PRP) in a subgroup of patients.The aggregation response is studied after addition of collagen and ADP and after preincubation with prostacyclin before aggregation with ADP. The figures present results from 85 randomized patients tested before, 5 days, one month and one year after start of therapy.Conclusion: In patients with unstable CAD long term treatment with ASA 75 mg/day inhibits collagen induced platelet aggregation and hampers the ADP response. I.v. heparin tends to raise platelet reactivity and reduce the inhibitory effect of prostacyclin. Heparin induced platelet activation is reduced by simultaneous ASA therapy.
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Aznar-Salatti, J., G. Escolar, L. Almirall, A. Ordinas et E. Bastida. « DIPYRIDAMOLE INDUCES CHANGES IN THE THROMBOGENIC PROPIERTIES OF ENDOTHELIAL CELL EXTRACELLULAR MATRICES ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643422.

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Dipyridamole (DIP) is a pirydo-pirymidine drug widely used as an antiplatelet agent.DIP has also been demonstrated to have effects on various cultured cells. We studied platelet reactivity of extracellular matrices (ECMs) produced by untreated (ECM-c) and DIP-treated (ECM-DIP) endothelial cells (ECs).Confluent monolayers of EC were incubated in buffer containing 0 or 10 pM. DIP for 48 h. The ECMs were prepared by removing the EC with 2% EGTA (1 h at 37°C). Platelet deposition onto the ECMs was measured under flow conditions using a flat chamber perfusion model ECM-c and ECM-DIP were exposed for 5 min to whole blood at shear rates of 300 or 1300 sec~1.Then, the perfused ECMs were processed for cross sectional morphometric evaluation using a computer system. The platelet, deposition is expressed as total surface covered with platelets (mean±SEM ) and shown in the table.Platelet aggregate formation on ECM-DIP at 1300 sec-1 was also reduced(by 25%)as measured morphometrically. We conclude that DIP-treatment of EC results in ECM modifications,which in turn decrease ECM-platelet interactions.These data also suggest that pharmacological treatment of the endothelium influences basement membrane reactivity.
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Samaden, A., F. Piovella, M. Vigotti, C. Bendotti, V. Fregoni, M. M. Ricetti et G. P. Montecchio. « EFFECT OF DEXAMETHASONE ON ENDOTHELIAL EXTRACELLULAR MATRIX FORMATION AND ON ITS REACTIVITY TO PLATELETS IN A PERFUSION SYSTEM ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643560.

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We previously demonstrated that dexamethasone increases fibronectin (FN) expression by human umbilical vein endothelial cell (HUVEC) as well as its incorporation in the extracellular matrix (EM). FN is primarily involved in platelet/vessel wall interactions as well as in cell attachment to substrates. The in vivo anti-haemorragic effect of glucocorticoids could therefore be related either to a better spreading and attachment of endothelial monolayer to the basement membrane or to an increase of vessel wall reactivity to platelets. To further investigate this, we studied the effect of dexamethasone treatment on EM reactivity to platelets in an in vitro perfusion system. Second passage HUVEC were seeded on glass coverslips at a density of 105/cm2 and treated with dexamethasone 1.0 μM for 48 hours. EM were prepared by exposure to 0.1 M NH4OH for 30’. Coverslips carrying the EM were perfused with citrated whole blood in a flat perfusion chamber(*) at wall shear rates of 300 and 900 sec™1 for 5’. Platelet adhesion to EM was evaluated by a morphometric method. The number of platelet adhering to EM at both shear rates was significantly increased by dexamethasone treatment, (+51.9% at 300 sec™1 (p<0.001) and +24.3% at 900 sec™1 (p<0.01)). Our results demonstrate that dexamethasone increases endothelial EM reactivity to platelets possibly through an increase of FN deposition. This, together with FN effect on cell spreading and anchorage to EM, might be responsible for the antl-haemorrhagic action of glucocorticoids.(*) K. Sakanassen et al . , J . Lab. Cl in . Med. 102:522, 1983
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Schrör, K., P. Löbel et E. Steinhagen-Thiessen. « SYNVINOLIN (SYN) IN TYPE Ha HYPERLIPOPROTEINAEMIA : NORMALIZED PLATELET HYPERREACTIVITY ASSOCIATED WITH AN IMPROVED RESPONSIVENESS AGAINST PGI2 AND ENHANCED PGI2 RECEPTORS ». Dans XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643460.

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Patients with familial hyperlipoproteinaemia (HLP) are at high risk for the premature development of atherosclerosis. This study was designed to investigate the effect of long-term treatment (8 months) with the HMG-CoA-reductase inhibitor SYN (20-40 mg/day) on platelet reactivity and PGIo receptors in 12 HLP patients (B) as compared with 11 untreated HLP patients (A) and 11 healthy subjects (C). Treatment with SYN reduced the plasma cholesterol to 234 ± 12 mg/dl as compared to 307 ± 21 (A) and 195 ± 14 mg/dl (C), respectively. Collagen (0.6 pg/ml) induced platelet thromboxane (TXB2) formation was 50±6 ng/ml in group A and significantly reduced to 32 ± 3 (B) which was not different from the 28±3 ng/ml in group C. Similar results were obtained by measuring pTatelet ATP secretion and aggregation. SYN treatment significantly improved the reduced number of PGI2 receptors (determined according to Schillinger & Prior, 1980) and normalized the iloprost (ILO, 30 nM) induced cAMP stimulation in platelet-rich plasma while the kg remained unchanged:These data demonstrate that SYN-treatment of HLP patients at doses that reduce plasma cholesterol by about 25% results in sig-ficant improvement of platelet function. This includes both normalization of platelet hyperreactivity against proaggregatory agents as well as platelet hyporeactivity aganist PGI2. The last effect might involve an increase of the (reduced) number of PGI2 receptors in HLP type IIa.
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Rapports d'organisations sur le sujet "Low on-treatment platelet reactivity"

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Banin, Amos, Joseph Stucki et Joel Kostka. Redox Processes in Soils Irrigated with Reclaimed Sewage Effluents : Field Cycles and Basic Mechanism. United States Department of Agriculture, juillet 2004. http://dx.doi.org/10.32747/2004.7695870.bard.

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The overall objectives of the project were: (a) To measure and study in situ the effect of irrigation with reclaimed sewage effluents on redox processes and related chemical dynamics in soil profiles of agricultural fields. (b) To study under controlled conditions the kinetics and equilibrium states of selected processes that affect redox conditions in field soils or that are effected by them. Specifically, these include the effects on heavy metals sorption and desorption, and the effect on pesticide degradation. On the basis of the initial results from the field study, increased effort was devoted to clarifying and quantifying the effects of plants and water regime on the soil's redox potential while the study of heavy metals sorption was limited. The use of reclaimed sewage effluents as agricultural irrigation water is increasing at a significant rate. The relatively high levels of suspended and, especially, dissolved organic matter and nitrogen in effluents may affect the redox regime in field soils irrigated with them. In turn, the changes in redox regime may affect, among other parameters, the organic matter and nitrogen dynamics of the root zone and trace organic decomposition processes. Detailed data of the redox potential regime in field plots is lacking, and the detailed mechanisms of its control are obscure and not quantified. The study established the feasibility of long-term, non-disturbing monitoring of redox potential regime in field soils. This may enable to manage soil redox under conditions of continued inputs of wastewater. The importance of controlling the degree of wastewater treatment, particularly of adding ultrafiltration steps and/or tertiary treatment, may be assessed based on these and similar results. Low redox potential was measured in a field site (Site A, KibutzGivat Brenner), that has been irrigated with effluents for 30 years and was used for 15 years for continuous commercial sod production. A permanently reduced horizon (Time weighted averaged pe= 0.33±3.0) was found in this site at the 15 cm depth throughout the measurement period of 10 months. A drastic cultivation intervention, involving prolonged drying and deep plowing operations may be required to reclaim such soils. Site B, characterized by a loamy texture, irrigated with tap water for about 20 years was oxidized (Time weighted average pe=8.1±1.0) throughout the measurement period. Iron in the solid phases of the Givat Brenner soils is chemically-reduced by irrigation. Reduced Fe in these soils causes a change in reactivity toward the pesticide oxamyl, which has been determined to be both cytotoxic and genotoxic to mammalian cells. Reaction of oxamyl with reduced-Fe clay minerals dramatically decreases its cytotoxicity and genotoxicity to mammalian cells. Some other pesticides are affected in the same manner, whereas others are affected in the opposite direction (become more cyto- and genotoxic). Iron-reducing bacteria (FeRB) are abundant in the Givat Brenner soils. FeRB are capable of coupling the oxidation of small molecular weight carbon compounds (fermentation products) to the respiration of iron under anoxic conditions, such as those that occur under flooded soil conditions. FeRB from these soils utilize a variety of Fe forms, including Fe-containing clay minerals, as the sole electron acceptor. Daily cycles of the soil redox potential were discovered and documented in controlled-conditions lysimeter experiments. In the oxic range (pe=12-8) soil redox potential cycling is attributed to the effect of the daily temperature cycle on the equilibrium constant of the oxygenation reaction of H⁺ to form H₂O, and is observed under both effluent and freshwater irrigation. The presence of plants affects considerably the redox potential regime of soils. Redox potential cycling coupled to the irrigation cycles is observed when the soil becomes anoxic and the redox potential is controlled by the Fe(III)/Fe(II) redox couple. This is particularly seen when plants are grown. Re-oxidation of the soil after soil drying at the end of an irrigation cycle is affected to some degree by the water quality. Surprisingly, the results suggest that under certain conditions recovery is less pronounced in the freshwater irrigated soils.
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