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Chronic Diseases

The thromboxane A2 pathway through its end product thromboxane A2 is implicated in the development and progression of many chronic diseases. There is clear clinical and/or experimental evidence platelet thromboxane A2 release is greatly enhanced in a number of chronic diseases. Frequently in these diseases, the balance between thromboxane A2 and prostacyclin is significantly altered, resulting in excessive vasoconstriction and disorders of hemostasis. Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway resulting in thromboxane A2 generation.

Molecular targets of tea polyphenols in the cardiovascular system

"Tea-derived polyphenols have attracted considerable attention in the prevention of cancer and cardiovascular diseases.  In comparison to tumour cells, the elucidation of their molecular targets in cardiovascular relevant cells is still at the beginning.  Although promising, experimental and clinical data demonstrate protective effects for the cardiovasclar system, little information is actually available on how these beneficial effects of tea polyphenols are mediated at the cellular level.  By affecting the activity of receptor and signal transduction kinases, both catechins and theaflavins - the major ingredients of green and black tea, respectively - exert a variety of cardiovascular beneficial effects."

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The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients

Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients.  Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients."

“Diabetic patients with CAD treated with 81 mg aspirin exhibit a higher prevalence of aspirin resistance and have significantly higher ADP- and collagen-induced platelet aggregation, 11-DHXTB2 levels, and aspirin reaction units measured by Verify Now than nondiabetic patients.”

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Inflammation and platelet activation in peripheral arterial occlusive disease.

"Epidemiological evidence indicates that inflammation accompanies the progression of atherosclerosis.  The aim of the present cross-sectional study was to define relationships between platelet activation and inflammation in patients with mild to severe (stages II to IV) peripheral arterial occlusive disease (PAOD) and matched controls.  The effect of chronic administration of low-dose acetylsalicylic acid was investigated."

“A positive correlation between 11-DHTXB2 and CRP was found in the study population.”

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Olive oil and hemostasis: a review on its healthy effects

"Interest in the Mediterranean diet (MD) has grown worldwide in the course of the past decade, even among nutritionists outside of the Mediterranean area.  This is largely due to the fact that the consumption of the MD has been linked to greater longevity, improved quality of life and lower incidences of cardiovascular disease, cancer and age cognitive decline, in spite of being a dietary model with a high fat content, unlike the diets recommended for several decades by many experts in nutrition in other geographical areas."  

“A diet enriched in virgin olive oil can reduce the sensitivity of platelets to aggregation, decreasing von Willebrand and thromboxane B2 plasma levels."

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Activation of the Thromboxane A2 Pathway in Human Prostate Cancer Correlates with Tumor Gleason Score and Pathologic Stage

"We investigated the potential involvement of the thromboxane A2 (TXA2) pathway in human prostate cancer (PCa). Expression of cyclooxygenase-2 (COX-2), TXA2 synthase (TXS), and TXA2 receptors (TPRs), the main actors of the TXA2 pathway, was analyzed on serial tissue sections from 46 human PCa specimens.

"The expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells.  Increased immunoreactivity for these antigens was also observed in high-grade prostate intraepithelial neoplasia (HGPIN) glands.  COX-2, TXS, and TPR proteins usually displayed a coordinated overexpression pattern in PCa lesions, as assessed in serial tissue sections.  Increased levels of these proteins in the tumors were all significantly associated with higher Gleason scores and pathologic stages"

"Proteins specifically involved in the TXA2 pathway are upregulated in human PCa and their level of expression is associated with tumor extraprostatic extension and loss of differentiation.  Our study is the first to examine simultaneously all key proteins involved in the pathway including TXA2 receptors and results suggest that the TXA2 pathway may be a potential target for PCa prevention/therapy."

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Thromboxane-dependent CD40 ligand release in type II diabetes mellitus

"The goals of this study were to characterize the platelet contribution to soluble CD-40 ligand (sCD40L), to correlate its formation with the extent of oxidative stress and platelet activation, and to investigate the effects of improved metabolic control and low-dose aspirin on these processes."

“This study provides several lines of evidence for the dependence of sCD40L release on TXA2-dependent platelet activation in T2DM and provides novel mechanistic insight into the amplification loops of persistent platelet activation in this setting.”

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Relation between atherosclerosis risk factors and aspirin resistance in a primary prevention population.

"Resistance to inhibition of platelet function by aspirin may contribute to future myocardial infarction and stroke.  Adverse cardiovascular outcomes have been associated with aspirin resistance on several different platelet function assays, including the level of urinary 11-dehydro thromboxane B2 (Tx-M), platelet aggregation to arachidonic acid and adenosine diphosphate, and closure time on the platelet function analyzer-100.  We examined the concordance of these aspirin-resistance assays and their relation to cardiovascular risk factors in a primary prevention population."

“Aspirin resistance by platelet function analyzer-100 was associated only with increased von Willebrand factor levels and not with atherosclerotic risk profile.”

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Determinants of platelet activation in Alzheimer’s disease

"This study is to investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease.

“Urinary 11-dehydroTXB2 and 8-iso-PGF2a were significantly higher in Alzheimer patients than in controls”

“No difference was found in CRP, TNF-a and IL-6 levels between the two groups.”

“Platelet activation is persistently enhanced in Alzheimer’s disease.”

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Platelet activation in patients with colorectal cancer

“Enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low dose aspirin might restore anti tumor reactivity.”

"Thus we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2), occurs in patients with colorectal cancer.  In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors"

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Reduced Blood Platelet Sensitivity to Aspirin in Coronary Artery Disease: Are Dyslipidaemia and Inflammatory States Possible factors Predisposing to Sub-optimal Platelet Response to Aspirin?

"Both environmental and genetic factors, including aspirin pharmacokinetics, inflammation, platelet COX-2, use of non-steroid anti-ainflammatory drugs and dyslipidaemia may determine variable platelet response to acetylsalicylic acid.”’ 

"However, CRP level was significantly associated with the extent of platelet refractoriness to acetylsalicylic acid in these patients, which points out that even subclinical inflammatory states may be considered possible candidates for suboptimal acetylsalicylic acid response."

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