scholarly journals Role of sodium tungstate as a potential antiplatelet agent

2015 ◽  
pp. 2777 ◽  
Author(s):  
Rebeca Fernandez-Ruiz ◽  
Marc Pino ◽  
Begoña Hurtado ◽  
Pablo García de Frutos ◽  
Carolina Caballo ◽  
...  
Keyword(s):  
Sodium Tungstate ◽  
Antiplatelet Agent

scholarly journals The Rivaroxaban Program and the Management of Unmet Needs in Thromboembolic Disease

2018 ◽  
Vol 118 (S 01) ◽  
pp. S2-S11
Author(s):  
A. Camm
Keyword(s):  
Potential Role ◽  
Unmet Needs ◽  
Antiplatelet Agent ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Thromboembolic Disease ◽  
Coagulation Cascade ◽  
Vascular Protection ◽  
Randomized Controlled

AbstractRivaroxaban is a non-vitamin K antagonist oral anticoagulant that acts as a direct factor Xa inhibitor, and is widely used for the prevention and treatment of thromboembolic disorders. As further knowledge gaps are identified in thrombosis management, the rivaroxaban research program has expanded in an attempt to elucidate the wider benefits of rivaroxaban. An increased understanding of the interactions taking place within the coagulation cascade may support a broader role for rivaroxaban (2.5 mg twice daily [bid] or 5 mg bid) in the setting of vascular protection, either alone or in combination with an antiplatelet agent. The aim of this article is to describe the potential role of rivaroxaban in the context of vascular protection and provide an overview of recently completed and ongoing randomized controlled trials of rivaroxaban in the areas of stroke prevention, venous protection and vascular protection.

scholarly journals Role of CYP2C19 alleles in the management of recurrent ischemic stroke

2018 ◽  
Vol 9 (2) ◽  
pp. 140-144
Author(s):  
Michael J. Lyerly ◽  
Kelly Bartlett ◽  
Karen C. Albright
Keyword(s):  
Ischemic Stroke ◽  
Stroke Prevention ◽  
Drug Exposure ◽  
Antiplatelet Agent ◽  
Platelet Inhibition ◽  
Secondary Stroke Prevention ◽  
Nucleotide Polymorphisms ◽  
Loss Of Function ◽  
Single Nucleotide

Purpose of reviewCYP2C19 is the primary enzyme involved in the activation of clopidogrel, an antiplatelet agent used for secondary stroke prevention. An individual's CYP2C19 alleles are used to understand their CYP2C19-clopidogrel metabolizer phenotype. Single nucleotide polymorphisms of the CYP2C19 gene result in altered metabolism of this prodrug.Recent findingsThree ischemic stroke cases were treated with clopidogrel. Despite confirming adequate drug exposure, medication adherence, and ruling out drug-drug interactions, all had recurrent ischemic stroke. Each case had a CYP2C19 *2/*17 genotype, categorizing them as intermediate clopidogrel metabolizers. Even with the gain-of-function allele, the loss-of-function allele resulted in lack of prodrug activation, leading to decreased efficacy in platelet inhibition.SummaryThese cases illustrate the importance of a thoughtful approach to secondary stroke prevention and demonstrate the utility of pharmacogenomic testing in clopidogrel hyporesponders. Recognition of the importance of CYP2C19 genotyping has the potential to enable better selection of appropriate secondary prevention strategies.

An in vivo study of the role of cytochrome P450 and aldehyde oxidase on imidacloprid and cypermethrin metabolism and related oxidative stress and DNA damage

2018 ◽  
Author(s):  
Αλέξανδρος Βαρδαβάς
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cytochrome P450 ◽  
Sodium Tungstate ◽  
Aldehyde Oxidase ◽  
Piperonyl Butoxide ◽  
In Vivo Study

Στην παρούσα διδακτορική διατριβή διερευνήθηκε (μελετήθηκε/εκτιμήθηκε)η δράση από τοξικολογικής πλευράς δύο φυτοφαρμάκων, του cypermethrin(CY), ενός συνθετικού πυρεθροειδούς και του imidacloprid (IMI), ενός νεονικοτινοειδούς, των σχετικών λειτουργιών τους, των ανεπιθύμητων παρενεργειών καθώς και το επικρατέστερο μεταβολικό μονοπάτι κάθε φυτοφαρμάκου. Στο πλαίσιο της πραγματοποίησης in vivo μελετών, πολλά φυτοφάρμακα χρησιμοποιούνται σε συνδυασμό με το Piperonyl Butoxide (PBO) το οποίο αποτελεί έναν ισχυρό αναστολέα της οξειδωτικής δράσης του Κυτοχρώματος P450 (CYP450) και είναι επίσης γνωστό για τις συνεργιστική του δράση, σε αυτές τις περιπτώσεις. Το PBO αποτελεί ένα διαγνωστικό εργαλείο ως προς δύο σημαντικές τοξικολογικές δράσεις των εντομοκτόνων και συμβάλλει στον προσδιορισμό του αν ο in vivo μεταβολισμός ενός εντομοκτόνου είναι οξειδωτικός καθώς και αν η αντοχή στα εντομοκτόνα περιλαμβάνει οξειδωτικό μεταβολισμό από το CYP450. Οι μονο-οξυγενάσες του κυτοχρώματος P450 ανήκουν σε μια μεγάλη οικογένεια ενζύμων με πολλαπλή δράση που διεξάγουν την αρχική οξείδωση σε μια πληθώρα λιποφιλικών ενώσεων. Τα ένζυμα αυτάδιαδραματίζουν κυρίαρχο ρόλο στο μεταβολισμό ξενοβιοτικών ουσιών όπως τα φάρμακα, φυτοφάρμακα, καρκινογόνα και άλλα περιβαλλοντικά χημικά.Είναι επίσης γνωστό πως η τοξικολογική βλάβη που προκύπτει από τη χρήση των φυτοφαρμάκων οφείλεται στους μεταβολίτες που παράγονται από τη συμμετοχή του κυτοχρώματος CYP450. Επιπρόσθετα, τα νεονικοτινοειδή in vivo μεταβολίζονται συγχρόνως από την αλδεΰδική οξειδάση (AOX), λόγω αναγωγής της νιτρο-ιμινο ομάδας, όπως και από τις CYP450 οξειδωτικές αντιδράσεις. Η μειωμένη δραστικότητα της AOX συσχετίζεται στενά με μειωμένο μεταβολισμότου IMI στα δύο κύρια μεταβολικά προϊόντα (IMI-NNO και IMI-NH) τα οποία θεωρούνται εξίσου δραστικά με την μητρική ουσία. Η παρούσα διδακτορική διατριβή βασίστηκε σε μια πληθώρα μελετών καθεμία σχεδιασμένη για να διαλευκάνει διαφορετική πλευρά του θέματος. Σε προηγούμενες μελέτες, το CY δεν έχει εκτενώς μελετηθεί σε συνδυασμό με το PBO όπως επίσης δεν έχει μελετηθεί το PBO ως προς τις ανασταλτικές δυνατότητες και την ικανότητα του να μειώνει την τοξική δράση όταν χρησιμοποιείται μόνο του. Η σύγκριση της παρούσας διδακτορικής διατριβής με τις προηγούμενες έρευνες παρουσιάζονται στη πρώτη δημοσίευση, στην οποία το ενδιαφέρον μας επικεντρώνεται στη συστημική κατάσταση αρσενικών κουνελιών Νέας Ζηλανδίας μετά την μακροπρόθεσμη έκθεση τους σε CY και PBO και η εκτίμηση αυτής βασίζεται στα εργαστηριακά αποτελέσματα του οξειδωτικού στρες και της ενεργότητας της τελομεράσης. Στη δεύτερη δημοσίευση, διεξήχθη μια συνέχιση του πρώτου μέρους της μελέτης, ώστε επιπλέον να εξετασθεί η φλεγμονή στο ήπαρ και τους νεφρούς καθώς και η γενοτοξικότητα σε αρσενικά κουνέλια Νέας Ζηλανδίας μετά την μακροπρόθεσμη έκθεση τους σε CY και PBO. Στην τελευταία δημοσίευση, μελετήσαμε την ανασταλτική αποτελεσματικότητα του sodium tungstate dihydrate (ST), ενός ανασταλτικού παράγοντα της AOX, ώστε να διασαφηνιστεί η σχετική συνεισφορά των CYP 450 και AOX μεταβολικών μονοπατιών στο μεταβολισμό του ΙΜΙ για να μπορέσουμε τελικά να διευκρινίσουμε ποια μεταβολική οδός είναι περισσότερο επιζήμια για τα αρσενικά κουνέλια Νέας Ζηλανδίας.

scholarly journals Discovery of a Novel ERp57 Inhibitor as Antiplatelet Agent from Danshen (Salvia miltiorrhiza)

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jia Zou ◽  
Yang Chen ◽  
Maggie Pui Man Hoi ◽  
Jun Li ◽  
Tao Wang ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Rosmarinic Acid ◽  
Salvia Miltiorrhiza ◽  
Antiplatelet Agent ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Protein Disulfide ◽  
First Time

Danshen (Salvia miltiorrhiza) is a well-known herb in Traditional Chinese Medicine (TCM) for treating cardiovascular diseases, but the underlying mechanism remains to be fully elucidated. Here, we showed that Danshen and its active ingredient rosmarinic acid exhibited antiplatelet effects through the inhibition of ERp57, a member of protein disulfide isomerase (PDI) with potential roles in platelet aggregation. Danshen extract (DSE) exhibited potent inhibitory effects on the platelet aggregation induced by arachidonic acid- (AA-) induced platelet aggregation and the enzymatic activity of ERp57. Rosmarinic acid was identified by virtual screening and molecular docking as one of the hit compounds for ERp57. In line with this, rosmarinic acid displayed significant inhibitory effect on ERp57 activity and inhibited AA-induced platelet aggregation. Taken together, we demonstrated for the first time that DSE and rosmarinic acid displayed inhibitory effects on the catalytic activity of ERp57, providing evidence of the regulatory role of ERp57 underlying the antiplatelet effects of Danshen.

scholarly journals Role of Different Antithrombotic Regimens after Percutaneous Left Atrial Appendage Occlusion: A Large Single Center Experience

2021 ◽  
Vol 10 (9) ◽  
pp. 1959
Author(s):  
Patrizio Mazzone ◽  
Alessandra Laricchia ◽  
Giuseppe D’Angelo ◽  
Giulio Falasconi ◽  
Luigi Pannone ◽  
...  
Keyword(s):  
Adverse Events ◽  
Antithrombotic Therapy ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Therapy Group ◽  
Oral Anticoagulants ◽  
Antiplatelet Agent ◽  
Atrial Appendage ◽  
Similar Distribution

Background: Optimal antithrombotic therapy after left atrial appendage (LAA) occlusion is still not clear. The aim of this study was to investigate the role of different antithrombotic regimens after the procedure. Methods and Results: We retrospectively analyzed data of 260 patients who underwent LAA occlusion and divided them into four groups according to therapy at discharge: dual antiplatelet therapy (group A, 71.5%); oral anticoagulants (group B, 19%); “minimal” antithrombotic therapy (single antiplatelet agent or without any antithrombotic therapy; group C, 4.5%) and other therapeutic regimens (such as a combination of antiplatelets and anticoagulants; group D, 4.5%). We analyzed baseline characteristics, procedural data, and clinical and transesophageal follow-up for each group. The incidence of adverse events was low in the whole population and had a similar distribution among groups. The majority of bleeding events was registered during the first 3 months after the procedure (34 out of 46, 70%). Ischemic events (2%), as well as silent left atrial thrombosis, were rare and not significantly higher in the population discharged with “minimal” antithrombotic therapy. Conclusion: Our experience seems to suggest that LAA occlusion was associated with a low incidence of adverse events, regardless of antithrombotic therapy. A “minimal” drug regimen may be feasible without losing efficacy on embolic prevention for patients with high bleeding risk.

Role Of Platelet cAMP And Prostaglandin Synthesis In Platelet Aggregation Inhibition By Ticlopidine Hydrochloride

1981 ◽  
Author(s):  
J J Bruno ◽  
D Yang ◽  
L A Taylor ◽  
C Feamster
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Camp Phosphodiesterase ◽  
Pde Inhibitors ◽  
Aggregation Inhibition ◽  
Induced Aggregation

Ticlopidine hydrochloride (T), 5-[(2-chlorophenyl) methyl]-4,5,6,7-tetrahydrothieno [3,2-c] pyridine hydrochloride, is a potent antiplatelet agent of unknown mechanism of action. T does not inhibit human platelet low Km, cAMP phosphodiesterase (PDE) in vitro, (IC50>>10-3M), but does have some activity versus the low Km, cGMP-PDE (IC503-4×10-4). Equivalent values for theophylline, a weak PDE inhibitor, are 1.6×10-4M and 4.2×10-4M, respectively. T has no synergistic effect in vitro on platelet aggregation inhibited by PGE1. PDE inhibitors do show synergism with PGE1 and other antiaggregatory PGs. Ex vivo in humans and animals, T inhibits ADP-induced aggregation. This inhibition is not altered by addition of SQ-22536 (f.c.-10-4M), a purported inhibitor of adenylate cyclase activity, whereas drugs whose platelet inhibitory activity depend on elevation of platelet cAMP, e.g., PGE1, adenosine and dipyridamole, have this inhibition partially reversed by SQ-22536.PG synthesis is not required for the antiplatelet activity of T. Addition of aspirin (f.c.-5×10-4M) in vitro to PRP from humans treated with T (500 mg/day) did not modify the aggregation response to ADP. In addition, PGI2 is not essential for the antiaggregation effect of T.The inhibition of ADP-induced aggregation of PRP prepared from blood of T-treated humans just after collection and more than 30 minutes after, to allow for inactivation of PGI2 were identical.We conclude that neither elevated cAMP nor PG synthesis is essential for T activity.

Role of dactinomycin in the improved survival of children with Wilms' tumor

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  
Wilms Tumor

Role of the allergist in diagnosis and management of patients with uveitis

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre
Keyword(s):  
Diagnosis And Management

The power of norms to sway fused group members

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam
Keyword(s):  
Evolutionary Anthropology ◽  
Normative Systems ◽  
Violent Extremism ◽  
Identity Fusion ◽  
Group Members

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.

Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Cognitive Processes ◽  
Evolutionary History ◽  
Behavioral Responses ◽  
History Of ◽  
Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

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