Disease relevance of LMFA03030003

• To evaluate the significance of vasoactive prostanoids in habitual abortion, we measured urinary excretion of prostacyclin metabolites (6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha) and of thromboxane A2 metabolites (TxB2 and 2,3-dinor-TxB2) during 25 pregnancies in 22 women with recurrent spontaneous abortion (RSA) [1].
• There is increased 2,3-dinor-TXB2 excretion in children with congenital heart disease and a high pulmonary blood flow that may reflect an imbalance in biosynthesis of TXA2 and PGI2 in the pulmonary vascular bed [2].
• Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2, the major systemic metabolites of TXA2, were significantly higher in patients with cirrhosis (1807 +/- 518 vs 341 +/- 121 ng/pg creatinine and 693 +/- 512 vs 205 (93 ng/pg creatinine, respectively, p < 0.001) [3].
• Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2,3-dinor-TXB2 [4].
• Using a specific quantitative method based on gas chromatography-mass spectrometry the urinary excretion of 2,3-dinor-TxB2 was measured in five patients with acute myocardial infarction shortly after the onset of symptoms [5].

High impact information on LMFA03030003

• Urinary 2,3-dinor TXB2, an index of in vivo TXA2 formation, decreased by 68 +/- 7% and recovered slowly, consistent with inhibition of platelet cyclooxygenase in vivo [6].
• Replacement of dietary saturated by unsaturated fatty acids: effects of platelet protein kinase C activity, urinary content of 2,3-dinor-TXB2 and in vitro platelet aggregation in healthy man [7].
• We, also, find a significant correlation between urinary excretion of 2,3-dinor-TXB2 and plasma F1+2, suggesting that clotting activation could partly account for in vivo platelet activation [8].
• METHODS: The urinary excretion rates of 2,3-dinor-6-keto-PGF1 alpha (major urinary metabolite of PGI2) and 2,3-dinor-TXB2 (major urinary metabolite of thromboxane A2) were used as indicators of platelet-endothelial cell interactions in vivo [9].
• Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2 were assayed by radioimmunoassay following chromatographic separation [3].

Chemical compound and disease context of LMFA03030003

• The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E2, TXB2 and 2,3-dinor-TXB2, a major urinary metabolite of TXA2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM) [4].
• There was a significant correlation between the number of central apneas and the 2,3-dinor-6-keto-PGF1alpha/2,3-dinor-TxB2-ratio in all infants combined (r = -0.72, p < 0.0001) as well as in the two subject groups [10].

Biological context of LMFA03030003

• Women whose pregnancies ended in abortion had higher (p less than 0.05) output of 2,3-dinor-TxB2 between weeks 4 and 7 of gestation and lower (p less than 0.01) excretion of 2,3-dinor-6-keto-PGF1 alpha between weeks 8 and 11 compared with women whose pregnancies proceeded to term [1].
• It is suggested that the cause of the increased urinary excretion of 2,3-dinor-TxB2 is the consequence of intrarenal platelet and macrophage activation, probably triggered by the endothelial damage [11].
• Co-administration of ASA significantly inhibits 2,3-dinor-TXB2 excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects [12].
• No significant increase in 11-dh-TXB2 was observed after TXB2 injection (10 micrograms/kg) in dogs, but the 2,3-dinor-TXB2 level rose significantly, its AUC ratio to TXB2 being 0.29, comparable with that in rabbits [13].

Anatomical context of LMFA03030003

• All three melanoma cell lines completely lacked formation of 6-keto-PGF1 alpha, TXB2, and 2,3-dinor-TXB2 [14].
• Following CPB, excretion rates of 2,3-dinor-TXB2 and TXB2 displayed parallel changes, suggesting that in these patients most urinary TXB2 derives from blood platelets rather than the kidney [15].

Associations of LMFA03030003 with other chemical compounds

• However, the combination of Ro 44-9883 and Ro 46-6240 reduced the time to reperfusion (40 +/- 8 vs. 68 +/- 15 min; n = 7, P < .05), prevented reocclusion and abolished the rise in urinary 2,3-dinor-TXB2 (5 +/- 1 ng/mg creatinine, n = 4) [16].
• The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in untrained and trained subjects before and after low-dose aspirin administration (50 mg/day, 7 days) [17].
• L-ARG infusion also inhibited platelet TXB2 formation and slightly, but not significantly decreased the urinary excretion rate of 2,3-dinor-TXB2; cGMP concentrations in PRP were significantly elevated during L-arginine infusion [18].
• The cyclooxygenase inhibitor indomethacin given by infusion in anaesthetized dogs (2.5, 8 and 25 micrograms/kg/min) dose-dependently inhibited 2,3-dinor TXB2 excretion measured by IA/GC-MS, with maximal inhibition (83.0 +/- 4.2%) being achieved after 6h (25 micrograms/kg/min) [19].
• The beneficial effects of indomethacin may be due to its ability to prevent the elevation of platelet aggregation, TXA2 (measured as urinary 2,3-dinor-TXB2 excretion) and 8-iso-PGF2alpha formation and to retard the decrease in endogenous nitric oxide synthesis (assessed as urinary excretion of nitrate) [20].

Gene context of LMFA03030003

• Selective inhibition of COX-1 reduced 2,3-dinor-TXB2 generation and lesion formation [21].
• Parameters investigated: CIn, CPAH, TxB2 in plasma, serum and urine; 6-oxo-PGF1 alpha in plasma and urine, urinary 2,3-dinor-TxB2 excretion [22].
• Despite marked changes in urine flow, GFR, urinary pH, osmolality, sodium and potassium excretion, only a insignificant or transient rise in the enzymatic prostanoid metabolites (2,3-dinor-6-keto-PGF1 alpha, PGE-M, 2,3-dinor-TxB2 and 11-dehydro-TxB2) was observed [23].
• A method for measurement of PGF2 alpha, PGE1, PGE2, 6-keto-PGF1 alpha, TXB2, 2,3-dinor-TXB2 as well as 5-, 8-, 9-, 11-, 12-, 15-HETE and HHT, utilizing negative ion chemical ionization GC/MS is presented [24].

Analytical, diagnostic and therapeutic context of LMFA03030003

• Urinary excretion rates of TXB2 and 2,3-dinor TXB2 were similar after treatment with GR32191B or placebo [25].
• In women who did not conceive, levels of 2,3-dinor-TXB2 were higher before embryo transfer than after transfer (p = 0.04) and than levels in women who did conceive (p = 0.01) [26].
• The synthesis of the prostanoids was assessed by measuring the urinary excretion of the metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using stable isotope dilution assays based on gas chromatography - mass spectrometry [27].
• The possible cross-reactivity of 2,3-dinor-TXB1 in immunoassays of urinary 2,3-dinor-TXB2 or even TXB2 in rats should be considered in future studies [28].
• In addition, we have demonstrated feasibility for a chemiluminescent assay to measure urinary 2,3-dinor TXB2 [29].

References