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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.

Role of Cox-2/PGE2 Mediated inflammation in Oral Squamous Cell Carcinoma

"Oral cancer include malignancy of the oral cavity and oropharynx, 90% of which are squamous cell carcinoma.  Oral and oropharyngeal squamous cell carcinoma (OSCCP) is a very aggressive neoplasm and is often diagnosed late in the disease.  Extensive research has demonstrated a relationship between chronic inflammation and a variety of cancer types, including OSCC."

"A significant amount of research indicates that the cyclooxygenase/prostaglandin E2 (PGE2) pathway of inflammation contributes to the development and progression of a variety of cancers, including squamous cell carcinoma of the oral cacity and oropharynx (OSCC). Although there have been promising results from studies examining the utility of anti-inflammatory drugs in the treatment of toxicities, this strategy has been met with only variable success and may make them inappropriate for some OSCC patients.  Improved inflammation-targeting therapies require continued study of the mechanisms linking inflammation and progression of OSCC.  In this review, a synopsis of OSCC biology will be provided, and recent insights into inflammation related mechanisms of OSCC pathobiology will be discussed  The roles of prostaglandin E2 and cluster of differentiation factor 147 (CD147) will be presented, and evidence for their interactions in OSCC will be explored.  Through continued investigation into the protumourigenic pathways of OSCC, more treatment modalities targeting inflammation-related pathways can be designed with the hope of slowing tumour progression and improving patient prognosis in patients with this aggressive form of cancer."

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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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Impact of commonly prescribed exercise interventions on platelet activation in physically inactive and overweight men

"The exercise paradox infers that, despite the well-established cardioprotective effects of repeated episodic exercise (training), the risk of acute atherothrombotic events may  be transiently increased during and soon after an exercise bout.  However, the acute impact of different exercise modalities on platelet function has not previously been addressed.  We hypothesized that distinct modalities of exercise would have differing effects on in vivo platelet activation and reactivity to agonists which induce monocyte-platelet aggregate (MPA) formation."

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Effects of pomegranate juice and extract polyphenols on platelet function

"Several clinical and In Vitro studies showed that polyphenols are able to inhibit platelet activation, preventing cerebro- and cardiovascular disease.  The Mediterranean diet includes fruit and vegetables rich in polyphenols known as effective protective agents.  Fruits and vegetables contain polyphenols such as tannins found in red wine and phenolic acid, flavonones, anthoscyanin, flavonols, stilbenes, and lignans found in pomegranates as protective agents from the hot Meditarranean sunshine."

“We have shown that pomegranate juice reduces every step of platelet activation, such as platelet aggregation, calcium mobilization, hydrogen peroxide formation, and TxA2 production induced by collagen and arachidonic acid.”

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Pentraxin 3 and platelet activation in obese patients after gastric banding

"High-sensitivity CRP decreased by 24 & 29.7% (P<0.0001), whereas CD40L decreased by 64.3 and 58.6% (P=0.002), respectively.  Urinary 11-dehydro-TxB2 decreased from 1,433 to 715 and 564 pg/mg creatinine, respectively, 6 months and 12 months after LAGB (P<0.0001). PTX3 was inversely related to platelet activation markers, 11-dehydro-TxB2 and CD40L.  Moreover, multiple regression analysis on pooled data showed that plasma PTX3 was an independent predictor of urinaty 11-dehydro-TxB2."

“There is an association between inflammation, platelet activation and metabolic dysfunction in obesity, and PTX3 is a key player within these circuits.”

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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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Nutraceuticals in diabetes and metabolic syndrome

"Metabolic syndrome represents a clustering of risk factors related to an elevated risk of cardiovascular disease and type 2 diabetes.  Occurrence of both metabolic syndrome and diabetes and their vascular complications share several pathogenetic features including subclinical, low-grade inflammation, alterred oxidative/antioxidant status, and persistent platelet activation."

"We examined the effects of short-term vitamin E supplementation (600 mg daily for 2 week) on the urinary excretion of 8-iso-PGF2alpha and 11-dehydro-TXB2. Vitamin E supplementation was associated with detectable changes in plasma vitamin E levels and caused virtually complete normalization of 8-iso-PGF2alpha excretion. Moreover, changes in F2-isoprostane formation were accompanied by similar reductions in thromboxane metabolite excretion."

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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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Case-Control study of aspirin use and risk of pancreatic cancer

"Pancreas-cancer prognosis is dismal, with 5-year survival less than 5%.  significant relationships between aspirin use and decreased pancreas-cancer incidence and mortality have been shown in four of 13 studies."

"Few Options besides the avoidance of smoking and obesity are available to prevent pancreatic cancer  The association between aspirin use and risk of pancreatic has been inconsistent across studies."

"We observed a significant inverse relationship between aspirin use and risk of pancreatic cancer."

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Urinary 11-dehydro-thromboxane B2 and coagulation activation markers measured within 24 h of human acute ischemic stroke

"The aim of this study was to determine the extent of change in platelet and coagulation markers in the acute phas of ischemic stroke and to assess the utility of marker mesurement in stroke subtype classification.  Urinary 11-dehydro-thromboxane B2 (11-deTXB2), a marker of in vivo platelet activation, and markers of coagulation activation, including prothrombin fragment 1 +2 (F1 + 2), thrombin-antithrombin complex (TAT) and fibrongen, were measured in 25 patients with ischemic stoke within 24 h of onset symptoms. Eight patients taking aspirin at the time of the stroke had signficantly lower 11-dTXB2 values than patients not taking aspirin (964 vs. 4,314 pg/mg of creatning P=0.0007).  Stroke patients not taking aspirin had significantly higher 11-dTXB2 concentration than age-matched controls (4,314 vs. 1,788 pg/mg of creatinine; P= 0.0006)."

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