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.

Role of dietary polyphenols in the platelet aggregation network - a review of the in vitro studies

"Several epidemiological studies have reported a negative association between the intake of dietary polyphenols and the risk for cardiovascular disease (CVD).  Conversely, a certain number of studies have reported no association."

"The activity of dietary polyphenols on CVD has been attributed to both their antioxidant activity in preventing LDL oxidation, and to their effect on the pathogenesis of thrombosis by interfering with platelet activation and function.  In fact, platelets play an important role not only in the formation of actute thrombus and vessel occulsion, but also in the development of athersclerosis and CVD."

“The anti-aggregating effect depends in part on the specific structure of the phenol, even though great differences in anti-aggregating activity have been observed within each class.”

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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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Efficiency of pharmacologically-active antioxidant phytomedicine radical fruits in treatment hypercholestermia at men

"Urinary 8-epi-PGF2 alpha level decreased from 450 +/- 170 to 330 +/- 159 Pg/mg creatinine, urinary 11-dehydro-TxB2 level decreased from 1,200 +/- 420 to 790 +/- 320 pg/mg creatinine with no changes in the placebo group."

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The effects of diet on inflammation: emphasis on the metabolic syndrome

"Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids and poor in natural antioxidants and fiber from fruits, vegetables, and whole grains may cause an activation of the innate immune system, most likely by an excessive reduction of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. This imbalance may favor the generation of a proinflammatory milieu, which in turn produces endothelial dysfunction at the vascular level and ultimately predisposes susceptible people to increased incidence of the metabolic syndrome and CHD."

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Molecular targets of dietary polyphenols with anti-inflammatory properties

"Inflammation is the immunological defense mechanism by which the body fights infection or injury from bacteria, viruses and other pathogens.  The defining clinical features of inflammation are known in Latin as rubor (redness), calor (warmth), tumor (swelling) and dolor (pain)."

"In the early 1970's, aspirin and other non-steroidal anti-inflammatory drugs were found to inhibit cyclooxygenase (COX), which produces prostaglandins (PG's), a class of physiological and pathophysiological inflammatory mediators.  Since then, the biosynthetic cascade of arachadonic acid (AA) has been the subject of intense research.  This is because AA, having been previously liberated from phospholipids using various stimuli, can be metabolized by the COX pathway into PG's and thromboxane A2, or by the lipoxygenase pathways to hydroperoxyeicosateraenoic acids, (HpETEs), hydroxyeicosateraenoic acids (HETEs), and leukotrienes (LTs).  These proteins play a vital role in inflammation by controlling the intensitry and duration of pain, as well as the occurrence of fever, swelling and heat of an affected area."

“Given that certain polyphenols are known to affect more than one protein, it is necessary consider the possibility that any single com- pound may affect multiple mechanisms.”

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Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease; effects of aspirin treatment

"Smoking is associated with endothelial dysfunction.  Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets.  We investigated whether (a) cigarette smoking is linked to increased cytokine production, which may mediate platelet activation and thrombin generation in chronic coronary artery disease (CAD), and (b) aspirin treatment inhibits smoking-related changes on cytokines, platelets, and thrombin."

"After aspirin treatment, M-CSF, CRP, 11-dehydro-TXB2, and prothrombin fragments 1 + 2 remained higher in smokers compared with non smokers despite a significant reduction of these markers by aspirin."

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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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Opposite effects of nicotinic acid and pyridoxine on systemic prostacyclin, thromboxane and leukotriene production in man

"The results of this study suggest that nicotinic acid increases thromboxane and leukotriene synthesis which may not be beneficial for patients with cardiovascular diseases or asthma.  In contrast, the increase of prostacyclin production and the inhibition in thromboxane and leukotriene synthesis by pyriodoxine might be beneficial in disorders where the production of prostacyclin is decreased and the formation of thromboxane and cysteinyl leukotrienes is enhanced.

"The treatment with nicotinic acid increased 11-DHTXB2 excretion to 2.6 fold and leukotriene E4 excretion to twice the basal values."

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Platelet activation in obese Women. Role of inflammation and oxidant stress.

“Women with android obesity had higher levels of 8-iso PGF2alpha and 11-dehydro-TxB2 than nonobese women.” 

“Both 8-iso PGF2alpha and 11-dehydroTxB2 were higher in women with android obesity than women with gynoid obesity” 

“Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change 23%  p<.05), 8-iso PGF2alpha (median change 32%  p=.04) and 11-dehydro-TXB2 (median change 54% p=.005)." 

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Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stoke, or cardiovascular death in patients at high risk for cardiovascular events

"Among aspirin-treated patients at high risk of cardiovascular events, persistent thromboxane generation predicts the risk of the composite outcome of myocardial infarction, stroke, or cardiovascular death, independent of other cardiovascular risk factors."

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