Disease relevance of LMFA03030004

• Multivariate analysis showed that diabetes, hypercholesterolemia, and hypertension were independently related to 11-dehydro-TXB2 excretion [1].
• Concentrations of 11-dehydro-TXB2 were increased in patients who had recently suffered a pulmonary embolism to a greater extent than either the 11-dehydro-13,14-dihydro-15-keto-TXB2 or the 2,3-dinor-TXB2 metabolites in plasma [2].
• Increased 11-dehydro-TXB2 excretion was present in 59% of all patients, in 60% (P<0.001) of patients with TIA, in 56% (P<0.001) of patients with ischemic stroke, and in 73% (P<0.001) of patients with intracerebral hemorrhage [3].
• Atrial fibrillation, no aspirin use, and severity of symptoms at follow-up contributed independently to the level of 11-dehydro-TXB2 excretion in a multiple linear regression analysis [3].
• We investigated whether enhanced urinary excretion of 11-dehydro-TXB2, a noninvasive index of platelet activation, was present in the chronic phase after a transient ischemic attack (TIA) or stroke, including intracerebral hemorrhage [3].

High impact information on LMFA03030004

• The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity [4].
• Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays [5].
• We established that whole blood possesses a minor capacity to form 11-dehydro-TXB2, attributable to nonenzymatic formation in erythrocytes [2].
• RESULTS: SLE patients had significantly higher 11-dehydro-TXB2 excretion, plasma F1+2, vWF, and tPA levels than controls [6].
• RESULTS: Similar to aspirin alone, NCX-4016 effectively inhibited platelet aggregation induced by 0.6 mmol/ arachidonic acid, clot-stimulated thromboxane (TX) B2 generation in whole blood, and urinary excretion of 11-dehydro-TXB2 [7].

Chemical compound and disease context of LMFA03030004

• RESULTS: Urinary 11-dehydro-TXB2 averaged 294+/-139, 413+/-419, and 557+/-432 pmol/mmol creatinine for patients with TIA, ischemic stroke, and intracerebral hemorrhage, respectively; the values were higher in all subgroups (P<0.01) than that in control patients (119+/-66 pmol/mmol) [3].
• To investigate the dynamics of PGI2, TXA2 and F2-isoprostanes in patients with hypertension and hyperlipidemia (HH group), we measured the major urinary metabolites of PGI2: 6-keto PGF1alpha (Keto) and 2,3-dinor-6-keto PGF1alpha, (Dinor), those of TXA2:TXB2 and 11-dehydro TXB2 (Dehydro), and urinary 8-isoprostane (Iso) in 34 patients [8].
• The plasma level of 11-dehydro TXB2 increased significantly during thrombus formation, and CV-4151 (10 mg/kg) markedly inhibited this increase [9].
• METHODS AND RESULTS: Urinary LTE4 and 11-dehydro-TXB2 were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain [10].
• Consistently, improvement of insulin sensitivity achieved with pioglitazone significantly decreased urinary 11-dehydro-TXB2 excretion (-43%, p < 0.05) without changes in body weight [11].

Biological context of LMFA03030004

• In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age > 55 and platelet count < 1,000 x 10(9)/1 [12].
• [1,1-18O2]11-Dehydrothromboxane B2 (11-dehydro-TXB2) was prepared by repetitive base-catalyzed hydrolysis of the lactone ring of its [1,1,11-18O3]-analogue, and evaluated for its suitability as an internal standard in gas chromatography/selected ion monitoring (GC/SIM) of 11-dehydro-TXB2 [13].
• A significant inverse correlation (r = -0.821, P < 0.005) was found between urinary LTE4 levels and the forced expiratory volume in 1 s (FEV1) but no significant correlation was observed between urinary 11-dehydro-TXB2 levels and FEV1 [14].
• Logistic regression analysis showed that high urinary 8-iso-PGF2alpha, plasma fibrinogen, and homocysteine, as well as low plasma vitamin E, advanced retinopathy, elevated diastolic blood pressure, and the absence of antihypertensive treatment, were predictors of high urinary 11-dehydro-TXB2 [15].

Anatomical context of LMFA03030004

• TXB2 was not converted into 11-dehydro-TXB2 by blood cells or plasma [16].
• Patients with central retinal artery occlusion or branch retinal artery occlusion showed greatly high 11-dehydro-TXB2 levels and TX/PGI ratios, although the number of patients was limited in the current study [17].

Associations of LMFA03030004 with other chemical compounds

• The urinary excretion of 11-dehydro-TxB2 was significantly higher in patients with COPD than in control subjects: median (range), 753 (277-4,409) and 275 (129-612) pg/mg creatinine, respectively; p < 0.0001) [18].
• Before and immediately after exercise, platelet adhesiveness, adenosine diphosphate-induced platelet aggregation and intracellular calcium concentration elevation, platelet cAMP and cGMP contents, urinary 11-dehydro-TXB2 and 6-keto-prostaglandin F1 alpha levels, and plasma nitric oxide metabolite level were determined [19].
• Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not [20].
• Cotinine plasma levels were elevated only in persons classified as smokers and serum TXB2 determination confirmed the absence of cyclooxygenase inhibition throughout the study. u-TXB2 and 11-dehydro-TXB2 were higher in smokers than in non-smokers [21].
• The concentrations of 15-hydroxyeicosatetraenoic acid and 11-dehydro-TxB2 in bronchoalveolar lavage fluid were measured by radioimmunoassay [22].

Gene context of LMFA03030004

• Basal measurements of urinary 11-dehydro-TXB2 and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age- and sex-matched controls [23].
• Rofecoxib had no significant effect on urinary excretion of 11-dehydro TXB2, a COX-1-derived product [24].
• Fluvastatin also lowered urinary 11-dehydro-TXB2 (1396 +/- 536 vs 1009 +/- 378 pg/mg creatinine [-27%], P = 0.0015) and von Willebrand Factor levels (1456 +/- 716 vs 1203 +/- 527 U/L [-17.4%], P = 0.0275), and a direct correlation was observed between P-selectin and 11-dehydro-TXB2 levels (r = 0.588, P = 0.0033) [25].
• Soluble CD40L linearly correlated with 11-dehydro-TXB2 (rho = 0.67, p < 0.0001), and both were reduced after one week of aspirin (p < 0.0026), with slow recovery over 10 days after aspirin withdrawal [26].
• Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with increased S(I) (+92%) and decreased CD40L (-27%), CRP (-37%), and 11-dehydro-TXB2 (-53%) (p < 0.05) [11].

Analytical, diagnostic and therapeutic context of LMFA03030004

• Urinary 11-dehydro-TXB2 was extracted and measured by a previously validated radioimmunoassay as a reflection of in vivo TXA2 biosynthesis [27].
• To address this hypothesis, we developed a sensitive assay for both 11-dehydro-TXB2 and TXB2, using capillary gas chromatography/negative-ion chemical ionization mass spectrometry [2].
• By contrast, 11-dehydro-TXB2 did not change significantly in the sequential catheter samples or in the samples drawn by separate venipuncture [2].
• 11-dehydro-TXB2 increased significantly, by up to 15-fold, in the 2.5- to 5.0-h urine collection encompassing PTCA and decreased by greater than 50% during the following 2-h period [28].
• Urinary 2,3-dinor-TxB2 was slightly stimulated during allograft rejection, urinary 11-dehydro-TxB2 did not change significantly [29].

References