Disease relevance of thromboxane B2

• In 8 patients dying with septic shock the concentration of plasma TXB2 (912 +/- 250 pg/ml) was ten times higher than that in 4 survivors of septic shock (92 +/- 25 pg/ml) and 6 controls (91 +/- 18 pg/ml) [1].
• These data indicate that leukocyte filters inhibit the myocardial ischemia and release of TxB2 induced by C5a via mechanisms not related to PMN depletion.(ABSTRACT TRUNCATED AT 400 WORDS)[2]
• TxB2 was isolated from protein-free culture medium of cell lines Calu-3, Calu-6, A549, and A549/Asc-1, derived from human lung adenocarcinomas [3].
• Thromboxane B2 (TxB2) release during IgE anaphylaxis in the rabbit [4].
• CONCLUSIONS: Interleukin-1 may be a necessary mediator of increased circulating PGI, TxB2, LTC4D4E4, TNF, and IL-6 levels in patients with severe sepsis [5].

High impact information on thromboxane B2

• We show here that prostaglandins of the E series (PGE) are potent inhibitors of the expression of Ia-antigens on macrophages and that thromboxane B2 (TXB2) antagonizes the effect of PGE [6].
• These results suggest that ex vivo platelet activation and/or analytical problems confound estimates of endogenous thromboxane release based on plasma TxB2 and provide a rationale for seeking longer-lived enzymatic metabolites of TxB2 in plasma [7].
• Indeed after an oral or intraduodenal dose of 5 mg/kg aspirin, generation of portal vein 6-keto-PGF1 alpha was inhibited to much the same extent as platelet TxB2, while inferior vena cava 6-keto-PGF1 alpha formation was spared [8].
• Infusion of the thromboxane synthetase inhibitor UK-37248-01 into the renal artery of 3-d allografts significantly decreased urinary TXB2 excretion and significantly increased renal blood flow (RBF) and glomerular filtration rate (GFR) [9].
• We evaluated several well-characterized indexes of platelet activation: platelet count, platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), and thromboxane B2 (TXB2) [10].

Chemical compound and disease context of thromboxane B2

• Exposure of isolated bovine neutrophils to partially purified Pasteurella haemolytica leukotoxin caused increased synthesis of leukotriene B4 (LTB4) but not thromboxane B2 (TXB2) from endogenous arachidonic acid [11].
• The mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1a (6-keto PGF1a) [12].
• The calcium entry blockers (CEBS), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TXB2 levels [12].
• Decreased production of interleukin-1-beta, prostaglandin-E2 and thromboxane-B2, and elevated levels of interleukin-6 and -10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame seed oil supplemented with Quil-A saponin [13].
• We have studied prospectively the clinical course and serum concentrations of thromboxane B2 (TxB2) and leukotriene B4 (LTB4) in patients developing adult respiratory distress syndrome (ARDS) after oesophagectomy [14].

Biological context of thromboxane B2

• We studied platelet aggregation and secretion with a lumiaggregometer and thromboxane-B2 formation by radioimmunoassay [15].
• Thromboxane B2 (TxB2) is the stable nonenzymatic hydrolysis product of thromboxane A2, a substance implicated in the initiation of the facilitative role of thrombocytes in the metastatic process [3].
• This study examined the effect of the consumption of moderate amounts of three species of fish on platelet fatty acid profile (PFA), bleeding time (BT), platelet aggregation, and ex vivo production of thromboxane B2 (TXB2) [16].
• After acebutolol, the cold treatment led to a lower increase of blood pressure with a reduction of the heart rate, as well as to a diminished release of BTG, PF4 and TXB2 no changes in the reduced platelet sensitivity to prostacyclin were noticed [17].
• After re-calculating TxB2 production as a function of platelet count and haematocrit all but one of the patients fell in the range of values obtained for controls [18].

Anatomical context of thromboxane B2

• The addition of 10(-5) M exogenous arachidonic acid to the cultured cells resulted in a 2- to 3-fold increase in TxB2 and bisenoic prostanoid production with no significant alterations in the proportion of TxB2 production [3].
• In contrast, the neutrophils from women demonstrated relatively higher O-2 production with a cyclic pattern of both TxB2 and O-2 which correlated with their menstrual cycle [19].
• In this study, we determined whether production levels of the eicosanoids prostaglandin E2 (PGE2) and thromboxane B2 (TxB2), both potent modifiers of lymphocyte function, were altered in lymphoid organs concomitant with a breakdown of tolerance in these mice [20].
• The release of thromboxane B2 (TXB2) from freshly isolated monocytes stimulated by opsonized zymosan (OPZ) was inhibited by 39.3 +/- 5.5% in the presence of isoprenaline (10(-7) M) [21].
• Upon calcium ionophore stimulation guinea pig eosinophils released thromboxane B2 (TXB2) and leukotriene B4 (LTB4) while monkey and human cells produced LTC4, LTB4, and 5-HETE [22].

Associations of thromboxane B2 with other chemical compounds

• Mean eicosanoid lavage fluid concentrations in control patients were 14.1 pg/ml for LTB4, 5.6 pg/ml for PGE2, and 397 pg/ml for TXB2 [23].
• Inhibition of human platelet aggregation and thromboxane-B2 production by melatonin: evidence for a diurnal variation [24].
• Furthermore, in 3 independent studies with different numbers of human male volunteers, a Harpagophytum extract was administered orally and tested in whole blood samples for Cys-LT and thromboxane B2 (TXB2) biosynthesis and for the determination of pharmacokinetic parameters of harpagoside [25].
• Hypercholesterolemic pigs fed the TRF supplement showed a 44% decrease in total serum cholesterol, a 60% decrease in low-density-lipoprotein (LDL)-cholesterol, and significant decreases in levels of apolipoprotein B (26%), thromboxane-B2 (41%), and platelet factor 4 (PF4; 29%) [26].
• Post-reperfusion TXB2 levels tended to be lower in the nonischemic control group and in the indomethacin-flush groups [27].

Gene context of thromboxane B2

• Serum was assayed for ex-vivo concentrations of thromboxane B2 (TxB2) to determine cyclooxygenase-1 (COX-1) inhibitory activity [28].
• ET-3 (2.5 nM) is also a potent releaser of PGI2 and TxB2 from the guinea-pig lungs (maximal release: PGI2: 2.4 +/- 1.0 ng ml-1; TxB2: 3.8 +/- 0.6 ng ml-1) [29].
• Collectively, the proinflammatory cytokines could enhance COX-1 but not COX-2 expression in GMC leading to increased PGE2 and TXB2 production [30].
• Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), beta-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels [31].
• After cold stimulation, a significant increase of NEFA, BTG, and plasma TXB2 was observed, which was still discernible 15 min after the application of cold [17].

Analytical, diagnostic and therapeutic context of thromboxane B2

• As renal function deteriorated, thromboxane B2 (TXB2) production by ex vivo perfused renal allografts increased progressively from 2 to 6 d after transplantation [9].
• In the immediate postoperative period, however, there was significant release of PF4 and beta-TG and generation of TXB2 [10].
• The response to C5a during coronary perfusion with arterial blood depleted of PMNs with Sepacell or Pall filters (less than 0.1 x 10(3) cells/microliters) was greatly blunted, with flow and contractile function falling by less than 14 and 8%, respectively, from baseline, and release of TxB2 was greatly attenuated [2].
• Prostaglandin E(2) (PGE(2)) and thromboxane B2 (TxB2) production was assayed by enzyme immunoassay [32].
• Addition of salbutamol, inactive alone, potentiated the generation of superoxide anion and of nitric oxide generation, as well as the production of IL-6 and TxB2 triggered by CD23 ligation [33].

References