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Therapy

The thromboxane A2 pathway plays a major role in governing the reactions involved in both the inflammatory and hemostatic biological mechanisms. Cyclooxygenases 1 & 2 act to convert arachidonic acid to thromboxane A2. Scientific studies report cyclooxygenase-2 is up-regulated in many different chronic disease states as well as in chronic inflammation. This explains one major causes of residual thromboxane risk, “aspirin resistance.” Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway that result n thromboxane A2 generation. The assay is normalized to the patient’s urine creatinine concentration and is non-invasive and normalized utilizing standard controls.

Relation of fish oil supplementation to markers of atherothrombotic risk in patients with cardiovascular disease not receiving lipid-lowering therapy.

"Fish oil supplementation (FOS) is known to have cardiovascular benefits.  However, the effects of FOS on thrombosis are incompletely understood.  We sought to determine if the use of FOS is associated with lower indices of atherothrombotic risk in patients with suspected coronary artery disease."

"Fish oil supplementation (FOS) is known to have cardiovascular benefits. Patients on FOS had lower urinary 11-dehydrothromboxane B2 levels regardless of lipid-lowering therapy."

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The Current and Future Landscape of Urinary Thromboxane Testing to Evaluate Atherothrombotic Risk


"Biomarker testing for efficacy of therapy is an accepted way for clinicians to individualize dosing to genetic and/or environmental factors that may be influencing a treatment regimen.  Aspirin is used by nearly 43 million Americans on a regular basis to reduce risks associated with various artherothrombotic diseases.  Despite its widespread use, many clinicians are unaware of the link between suboptimal response to aspirin therapy and increased risk for inferior clinical outcomes in several disease states, and biomarker testing for efficacy of aspirin therapy is not performed as routinely as efficacy testing in other therapeutic areas.  This article reviews the clinical and laboratory aspects of determining whole-body thromboxane production, particularly as it pertains to efficacy assessment of aspirin responsiveness."

"Aspirin use has been shown to cause a dose-dependent reduction in urinary levels of 11-dehydroTxB2."

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Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example

"The connection between diet and cancer has been well established, as affirmed by the considerable international consistency among dietary and lifestyle recommendations for reducing risk of cancer and other chronic diseases. The World Cancer Research Fund, American Institute for Cancer Research, and the American Cancer Society guidance each emphasize a plant-based diet, a physically active lifestyle, limited alcohol, and maintaining a healthy weight."

“Both the walnut and fish diets inhibited prostaglandin E metabolite (PGEM) and 11-dehydro thromboxane B2, but had no effect on IL-1β, IL-6, TNF-α, CRP, or the number of circulating lymphocyte subsets.”

“A plant-based diet is associated with decreased risk for cancer and other chronic diseases, due in part to reduced chronic inflammation.”

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Synthetic analogues of flavonoids with improved activity against platelet activation and aggregation as novel prototypes of food supplements

"We investigated the ability of quercetin and apigenin to modulate platelet activation and aggregation, and compared the observed efficacy with that displayed by their synthetic analogues (2-phenyl-4Hpyrido, etc.) Platelet aggregation was explored through a spectorphotometric assay on platelet-rich-plasma treated with the thromboxane A2 mimetic, collagen and thrombin in presence/absence of various bioisosteres of flavanoids."

"The inhibitory effect of these compounds might rely on TXA2 antagonism."

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Flavonoids-clinical effects and applications in dentistry: a review

"Flavonoids include a huge group of naturally occurring organic compounds.  It is found in a large variety of plants including fruits, seeds, grains, tea vegetables, nuts and wine.  Many studies have shown that there is a strong association between flavonoid intake and the long-term effects on mortality.  It is widely used in dentistry and it has many clinical effects.  This article summarizes the effects of flavonoids to humankind and its clinical applications in dentistry."

"It is recognized that arachidonic acid, which is released during the inflammatory conditions, is metabolized by platelets to form endoperoxides, prostaglandin, and thromboxane A2 which leads primarily to platelet activation and aggregation."

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Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin

"Elevated 11-DHTXB2 was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-DHTXB2 may be a useful method to optimize statin dosing in order to reduce thrombotic risk."

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Effect of the Mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome

"Inflammation is now undisputedly recognized as being a key etiological factor in the pathogenesis of atherosclerosis and cardiovascular disease."

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Endogenous secretory RAGE in obese women: association with platelet activation and oxidative stress

"Excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease."

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Cyclooxgenase-1 mediated platelet reactivity in young male smokers

"Collagen-induced platelet aggregation and plasma/urinary thromboxane B2 (TXB2) and 11-dehydroxythromboxane B2 levels were higher in cigarette smokers compared to nonsmokers."

"The levels of plasma/urinary TXB2 were significantly increased an hour after cigarette smoking."

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The influence of aspirin dose and glycemic control on platelet inhibition in patients with type 2 diabetes mellitus

"Our baseline results are in line with earlier studies, which have shown an association between glycemic control and urinary 11-DHTXB2 excretion. In addition, improving glycemic control has been shown to lead to a decreased 11-DHTXB2 excretion."

"In the present study, the difference in urinary 11-DHTXB2 excretion was also influenced by C-reactive protein levels, which were different between the study groups and may reflect the influence of the inflammatory state found in diabetes on thromboxane formation."

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