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.

Targeting arachidonic pathway by natural products for cancer prevention and therapy

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogensis.  Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2S), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer."

"Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2."

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Aspirin and Cancer

"The place of aspirin in primary prevention remains controversial, with North American and European organizations issuing contradictory treatment guidelines.  More recently, the U.S. Preventive Services Task Force recommended "initiating low-dose aspirin use for the primary prevention of cardiovascular disease and colorectal cancer in adults aged 50-59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years."  This recommendation reflects increasing evidence for a chemopreventive effect of low-dose aspirin against colorectal (and other) cancer.  The intent of this paper is to review the evidence supporting a chemopreventive effect of aspirin, discuss its potential mechanism (s) of action, and provide a conceptual framework for assessing current guidelines in the light of ongoing studies."

"The protective effects of low-dose aspirin against cancer appear to reflect the prevention of early neoplastic transformation throughout the alimentary tract, as well as an antimetastatic action. Both effects may be explained by the antiplatelet effect of low-dose aspirin."

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The improvement of walking abilities and endothelial function after the supervised training treadmill program

"In this prospective study we evaluated the relationship between thromboxane B2 (TXB2), prostacyclin (PGI2) and lactate concentrations, and the improvement of walking abilities and endothelial function in patients with peripheral artery disease (PAD) undergoing a supervised treadmill training program (STTP)."

The Maximal Walking Time (MWT) improved significantly after STTP by 91% (p<0.0001) and PFWT by 97% (P<0.0001).  Also ankle/brachial index (ABI) values improved significantly after STTP in all patient groups and was more pronounced in those with longer MWT at baseline.  FMD values increased by 45% (p<0.0001) after STTP.  Urinary 11-dehydro-thromboxane B2 and 2, 3-dinor-6-keto-PGF1a concentration tend to decrease after STTP and their ratio remained unchanged.  Lactate levels did not change after the treadmill training program.  Hs-CRP and fibrinogen concentration decreased signficantly after STTP only in patients with longer MWT at baseline - fourth quartile".

"STTP in patients with PAD showed signficantly improved walking abilities and endothelialial function."

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Oxidative stress reflected by increased F2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane B2 levels in patients with coronary artery disease.2016

"Oxidative stress is a potential mechanism of incomplete inhibition of COX-1.

"8-isoPGF2a was found to be independently and positively associated with 11 dhTxB2."

"Elevated 11dhTxB2 was found to increase the risk of adverse events in patients with stable CAD [12] and myocardial infarction."

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11-Dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease during a one year follow-up period.

"Overall the mean TXB2 values immediately after PTA were significantly higher than either before the procedure (1524.4 pg/mg ± 1411.1 vs. 2098.1 pg/mg creatinine ± 1661.8; P=0.00002), the day after PTA, or at any other point during the study.”

"Moreover, preoperative TXB2 levels correlated well with the composite endpoints of death, myocardial infarction and stroke during the follow-up period"

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Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation

"Cardiovascular events (CVEs) represent the main cause of morbidity and mortality in the elderly population.  Several mechanisms have been proposed so far to explain the age-related incidence of CVs.  Thus, the prevalence of cardiovascular risk factors, such as smoking, hypertension and diabetes increases in elderly people.  Of note is that despite increasingly effective cardiovascular preventive strategies a portion of patients still experience cardiovascular complications."

"Urinary excretion of 11-dehydro-txb2 increases by advancing age, peaking after 70 years."

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Risk factors for nonplatelet thromboxane generation after coronary artery bypass graft surgery.

"A significant finding of our analysis was that U8-iso-PGF2a correlated directly with the incidence of early vein graft thrombosis. This suggests that therapies aimed at reducing oxidative stress might be a viable strategy to reduce nonplatelet TXA2 generation and improve outcomes after cardiac surgery."

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Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease: Effects of anti-TNFα treatment

"Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease dispite having a lower burden of traditional risk factors. IBD patients had significantly higher urinary 8-iso-PGF and 11-dehydro-TXB2."

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Obstructive Sleep Apnea Syndrome (OSA) and Cancer: Current Insights

"The obstructive sleep apnea syndrome (OSA) is an independent risk factor for atherosclerosis.  Chronic intermittent hypoxia (CHI) causes atherosclerosis in the occurrence of a pre-existing hyperlipidemia.  A new pathway, in animal models has been demonstrated that CIH significantly increased atherosclerotic lesion sizes, mRNA levels of Cox-1 and thromboxane synthase (TXBS).  Lesion size is correlated to COX-1 and TXBS mRNA levels.  COX-1 inhibition reduced lesion progression in intermittent hypoxia mice.  This study demonstrated for the first time, that the activation of the COX pathway exposed to CIH is associated with increased atherosclerotic lesions in mice, highlighting early atherosclerosis markers in OSA patients."

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Cyclooxygenase Pathway Activation in Sleep Apnea Syndrome

"Patients with obstructive sleep apnea syndrome (OSA) exhibit an early vascular remodelling and alterations of acid arachidonic pathway 2.  Thromboxane A2 (TXA2) is a cycloxygenase (COX)-derived metabolite of AA involved in vascular remodelling."

"Atherosclerosis is a chronic inflammatory disease characterized by the activation of some components of the cyclooxygenase pathway.  OSA is associated with activation of the thromboxane A(TXA2)-pathway, in which obesity seems to be a major confounding factor." 

"Urinary excretion of 11-dTXB2 did not differ between OSA patients free of cardiovascular complications and healthy volunteers but increased in OSA patients with cormobidities compared to OSA patients without 694.0 (425.9-1235.6) versus 616.0 (354.3-838.2) pg/mg creatinine respectively; p=0.007). Finally, urinary 11-dTXB2 was increased by 30% in OSA Patients with cartoid hypertrophy (IMT>compared to OSA patients without carotid hypertrophy (783.0 (582.8-938.0) versus 592.9 (278.9-782.5) pg/mg creatinine, respect p=0.02)."

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