Comparative Effects of Platelet Suppressant Drugs on Platelet Survival Time

1975 ◽  
Author(s):  
E. Genton ◽  
J. Ellis ◽  
P. Steele
Keyword(s):  
Heart Disease ◽  
Venous Thromboembolism ◽  
Valvular Heart Disease ◽  
Laboratory Tests ◽  
Drug Effect ◽  
Platelet Reactivity ◽  
In Vitro Tests ◽  
Platelet Survival

The important role of platelets in thrombosis makes inhibitors of their reactivity potentially useful therapeutically. A number of laboratory tests have been identified which measure platelet reactivity, but it is not clear which test and which drug effect will correlate with thrombosis and thrombosis prevention. Platelet survival (SURV) correlates with thromboembolism in patients with valvular heart disease and is shortened in several other diseases. Therefore, it is of interest to identify drugs which prolong shortened SURV. Patients with arterial and venous thromboembolism and shortened SURV (51Chromium) were treated with platelet suppressants and restudied after 12 weeks. Sulfinpyrazone prolonged SURV(2.4±.04 to 3.1 ±.06 days; p < 0.001; n = 94; average ± SEM; normal, 3.7±.04 days) and 68 (72%) had some prolongation and 39 (42%) had normalization (> 3.3 days). Dipyridamole (100 mg qd) combined with aspirin (1200 mg qd) prolonged SURV (2.6±.11 to 3.2±0.12 days; p < 0.001; n = 13) and 9 of 13 (69%) had prolongation and 6 (46%) had normalization. Clofibrate altered SURV (2.6±.09 to 3.4±.14days;p < 0.001; n = 12) and 10 of 12 (83% ) had prolongation and normalization occurred in 6 (50%). Aspirin (1200 mg qd), cyproheptadine (32 mg qd) and propranolol (160 mg qd) failed to alter SURV.Thus, of drugs which alter in vitro tests of platelet reactivity, only sulfinpyrazone, dipyridamole and clofibrate improve shortened SURV.

scholarly journals Polyphenols: From Theory to Practice

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2595
Author(s):  
Alberto Bertelli ◽  
Marco Biagi ◽  
Maddalena Corsini ◽  
Giulia Baini ◽  
Giorgio Cappellucci ◽  
...  
Keyword(s):  
Matrix Effect ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Biological Properties ◽  
Health Claims ◽  
In Vitro Tests ◽  
The Matrix ◽  
Gender Characteristics

Background: The importance of polyphenols in human health is well known; these compounds are common in foods, such as fruits, vegetables, spices, extra virgin olive oil and wine. On the other hand, the different factors that modulate the biological activity of these compounds are less well known. Conceptualization of the work: In this review we took into account about 200 relevant and recent papers on the following topics: “polyphenols bioavailability”, “polyphenols matrix effect”, “food matrix effect”, “polyphenols-cytochromes interaction”, after having reviewed and updated information on chemical classification and main biological properties of polyphenols, such as the antioxidant, anti-radical and anti-inflammatory activity, together with the tricky link between in vitro tests and clinical trials. Key findings: the issue of polyphenols bioavailability and matrix effect should be better taken into account when health claims are referred to polyphenols, thus considering the matrix effect, enzymatic interactions, reactions with other foods or genetic or gender characteristics that could interfere. We also discovered that in vitro studies often underrate the role of phytocomplexes and thus we provided practical hints to describe a clearer way to approach an investigation on polyphenols for a more resounding transfer to their use in medicine.

scholarly journals The Emerging Role of Exercise Testing and Stress Echocardiography in Valvular Heart Disease

2009 ◽  
Vol 54 (24) ◽  
pp. 2251-2260 ◽  
Author(s):  
Eugenio Picano ◽  
Philippe Pibarot ◽  
Patrizio Lancellotti ◽  
Jean Luc Monin ◽  
Robert O. Bonow
Keyword(s):  
Heart Disease ◽  
Exercise Testing ◽  
Valvular Heart Disease ◽  
Stress Echocardiography

scholarly journals Role of Serotoninergic Pathways in Drug-Induced Valvular Heart Disease and Diagnostic Features by Echocardiography

2009 ◽  
Vol 22 (8) ◽  
pp. 883-889 ◽  
Author(s):  
Sakima A. Smith ◽  
Alan D. Waggoner ◽  
Lisa de las Fuentes ◽  
Victor G. Davila-Roman
Keyword(s):  
Heart Disease ◽  
Valvular Heart Disease ◽  
Drug Induced ◽  
Diagnostic Features

scholarly journals Functional Genomics for the Identification of Modulators of Platelet-Dependent Thrombus Formation

TH Open ◽  
2018 ◽  
Vol 02 (03) ◽  
pp. e272-e279
Author(s):  
Elien Vermeersch ◽  
Benedicte Nuyttens ◽  
Claudia Tersteeg ◽  
Katleen Broos ◽  
Simon De Meyer ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Cell Types ◽  
Correlative Analysis ◽  
Genome Expression ◽  
Genome Wide ◽  
Whole Genome Expression

AbstractDespite the absence of the genome in platelets, transcription profiling provides important insights into platelet function and can help clarify abnormalities in platelet disorders. The Bloodomics Consortium performed whole-genome expression analysis comparing in vitro–differentiated megakaryocytes (MKs) with in vitro–differentiated erythroblasts and different blood cell types. This allowed the identification of genes with upregulated expression in MKs compared with all other cell lineages, among the receptors BAMBI, LRRC32, ESAM, and DCBLD2. In a later correlative analysis of genome-wide platelet RNA expression with interindividual human platelet reactivity, LLRFIP and COMMD7 were additionally identified. A functional genomics approach using morpholino-based silencing in zebrafish identified various roles for all of these selected genes in thrombus formation. In this review, we summarize the role of the six identified genes in zebrafish and discuss how they correlate with subsequently performed mouse experiments.

scholarly journals RGS10 and RGS18 differentially limit platelet activation, promote platelet production, and prolong platelet survival

Blood ◽  
2020 ◽  
Vol 136 (15) ◽  
pp. 1773-1782 ◽  
Author(s):  
Daniel DeHelian ◽  
Shuchi Gupta ◽  
Jie Wu ◽  
Chelsea Thorsheim ◽  
Brian Estevez ◽  
...  
Keyword(s):  
Platelet Count ◽  
G Protein ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Rgs Proteins ◽  
Platelet Recovery ◽  
Platelet Production ◽  
Platelet Survival

Abstract G protein–coupled receptors are critical mediators of platelet activation whose signaling can be modulated by members of the regulator of G protein signaling (RGS) family. The 2 most abundant RGS proteins in human and mouse platelets are RGS10 and RGS18. While each has been studied individually, critical questions remain about the overall impact of this mode of regulation in platelets. Here, we report that mice missing both proteins show reduced platelet survival and a 40% decrease in platelet count that can be partially reversed with aspirin and a P2Y12 antagonist. Their platelets have increased basal (TREM)-like transcript-1 expression, a leftward shift in the dose/response for a thrombin receptor–activating peptide, an increased maximum response to adenosine 5′-diphosphate and TxA2, and a greatly exaggerated response to penetrating injuries in vivo. Neither of the individual knockouts displays this constellation of findings. RGS10−/− platelets have an enhanced response to agonists in vitro, but platelet count and survival are normal. RGS18−/− mice have a 15% reduction in platelet count that is not affected by antiplatelet agents, nearly normal responses to platelet agonists, and normal platelet survival. Megakaryocyte number and ploidy are normal in all 3 mouse lines, but platelet recovery from severe acute thrombocytopenia is slower in RGS18−/− and RGS10−/−18−/− mice. Collectively, these results show that RGS10 and RGS18 have complementary roles in platelets. Removing both at the same time discloses the extent to which this regulatory mechanism normally controls platelet reactivity in vivo, modulates the hemostatic response to injury, promotes platelet production, and prolongs platelet survival.

scholarly journals Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Abhishek Sharma ◽  
Vaseem Ahmed ◽  
Aakash Garg ◽  
Chirag Aggarwal
Keyword(s):  
Heart Disease ◽  
Natriuretic Peptides ◽  
Valvular Heart Disease ◽  
Clinical Utility ◽  
Surgical Intervention ◽  
Clinical Applications ◽  
Asymptomatic Patients ◽  
Routine Surveillance ◽  
Valvular Lesions

Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD.

scholarly journals Cardiac syndrome X. the possible role of Na+-Li+-countertransport activity and other pathophysiological mechanisms in pathogenesis

2013 ◽  
Vol 94 (3) ◽  
pp. 355-361
Author(s):  
V N Oslopov ◽  
Y V Oslopova ◽  
D V Borisov
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Vascular Dysfunction ◽  
Syndrome X ◽  
Cardiac Syndrome X ◽  
Pathophysiological Mechanisms ◽  
Cardiac Syndrome ◽  
Number Of Patients

There are numerous pathophysiological mechanisms unequally responsible for the cardiac syndrome X development. The most important is endothelium and smooth muscle cells dysfunction that can intensify vasoconstriction and depress both endothelium-dependant and endothelium-independent vasodilatation, finally leading to coronary micro vascular dysfunction as the basis of the cardiac syndrome X pathogenesis. Together with other possible mechanisms of pathogenesis, studying the importance of increased cell membrane Na+-Li+-countertransport activity seems promising. If was found that a significant number of patients with cardiac syndrome X have increased Na+-Li+-countertransport activity, which is an in vitro marker of Na+-H+-antiporter. Therefore, it is important to measure Na+-Li+-countertransport speed in patients with coronary heart disease, because its high levels increases the chance for cardiac syndrome X, which is a coronary heart disease with no anatomic signs of coronary arteries involvement.

scholarly journals In Vitro Mutagenic and Genotoxic Assessment of a Mixture of the Cyanotoxins Microcystin-LR and Cylindrospermopsin

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 318 ◽  
Author(s):  
Leticia Díez-Quijada ◽  
Ana I. Prieto ◽  
María Puerto ◽  
Ángeles Jos ◽  
Ana M. Cameán
Keyword(s):  
Risk Evaluation ◽  
Evaluation Framework ◽  
Kinase Assay ◽  
In Vitro Tests ◽  
Food Contaminants ◽  
The Individual ◽  
Mutation Assay ◽  
Mouse Lymphoma

The co-occurrence of various cyanobacterial toxins can potentially induce toxic effects different than those observed for single cyanotoxins, as interaction phenomena cannot be discarded. Moreover, mixtures are a more probable exposure scenario. However, toxicological information on the topic is still scarce. Taking into account the important role of mutagenicity and genotoxicity in the risk evaluation framework, the objective of this study was to assess the mutagenic and genotoxic potential of mixtures of two of the most relevant cyanotoxins, Microcystin-LR (MC-LR) and Cylindrospermopsin (CYN), using the battery of in vitro tests recommended by the European Food Safety Authority (EFSA) for food contaminants. Mixtures of 1:10 CYN/MC-LR (CYN concentration in the range 0.04–2.5 µg/mL) were used to perform the bacterial reverse-mutation assay (Ames test) in Salmonella typhimurium, the mammalian cell micronucleus (MN) test and the mouse lymphoma thymidine-kinase assay (MLA) on L5178YTk± cells, while Caco-2 cells were used for the standard and enzyme-modified comet assays. The exposure periods ranged between 4 and 72 h depending on the assay. The genotoxicity of the mixture was observed only in the MN test with S9 metabolic fraction, similar to the results previously reported for CYN individually. These results indicate that cyanobacterial mixtures require a specific (geno)toxicity evaluation as their effects cannot be extrapolated from those of the individual cyanotoxins.

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