Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo production of thromboxane A2 and prostacyclin was assessed in 31 samples from 25 patients with lupus anticoagulant and in 32 controls. The urinary excretion of 11-dehydro-thromboxane B2 (a major thromboxane metabolite of platelet origin) was very significantly increased (p less than 0.0003) in the patients contrasting with a lesser increase of urinary 2,3-dinor-6-keto-prostaglandin F1 alpha reflecting the vascular production of prostacyclin (p less than 0.02). Our study shows that in patients with lupus anticoagulant, platelet activation may occur without a compensatory increment in the vascular biosynthesis of prostacyclin suggesting an increased risk for thrombosis.
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PMID:Increased production of platelet-derived thromboxane in patients with lupus anticoagulant. 163

The mechanism involved in the association between antiphospholipid antibodies and thrombosis or fetal loss remains unclear. We assessed the biosynthesis of thromboxane A2 and prostacyclin in 31 samples from 25 patients with lupus anticoagulant and in 32 controls. The urinary excretion of the major thromboxane metabolite of platelet origin (11-dehydrothromboxane B2) was very significantly increased (P less than .0003) in the patients. In contrast, the urinary metabolite reflecting the vascular production of prostacyclin (2,3-dinor-6-keto-prostaglandin F1 alpha) was much less increased (P less than .02). We found no correlation between the levels of anticardiolipin antibodies and the urinary excretion of 11-dehydro-thromboxane B2. Six patients with elevated urinary 11-dehydrothromboxane B2 were treated with low-dose aspirin (20 mg/d during 7 days). In these patients, there was a close relationship between the extent of inhibition of the thromboxane urinary metabolite (72%) and serum thromboxane B2 (79%). In contrast, the urinary excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha was nearly unchanged (13% reduction). In addition, the F(ab')2 fragments isolated from six patients presenting increased urinary 11-dehydro-thromboxane B2 enhanced the generation of thromboxane B2 (P = .04) and the release of 14C serotonin (P = .009) by normal washed platelets, as compared with F(ab')2 from controls. In summary, our study shows that in patients with lupus anticoagulant, platelet activation may occur without a compensatory increment in the vascular biosynthesis of prostacyclin. This observation may be crucial to cause or reflect an increased risk for thrombosis. In addition, our results may suggest a rationale for antiplatelet agents for the prophylaxis of thrombosis in many patients with the antiphospholipid syndrome.
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PMID:Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant. 195 77

Platelet activation may contribute to the increased risk of thrombotic complications in patients with antiphospholipid antibodies (aPL). The increased urinary excretion of 11-dehydro-thromboxane B2 (11-DH-TXB2) reported in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (aCL) reflects in vivo platelet activation. However the majority of autoimmune aPL are directed to beta2 glycoprotein I (beta2GPI) or prothrombin (II). We investigated the relationship of these antibodies with 11-DH-TXB2 urinary excretion in 34 patients with aPL. The urinary 11-DH-TXB2 was measured by EIA after extraction on octadecyl columns and purification on silica gel columns, which was validated by thin-layer chromatography/EIA procedure. A significantly increased excretion of 11-DH-TXB2 was found in aPL patients as compared to 18 normal controls (p <0.01). But no differences were seen in the excretion of 11-DH-TXB2 between patients with or without LA, or aCL. The number of patients with anti-II antibodies was too small to draw any conclusion. In contrast, patients with anti-beta2GPI antibodies IgG at moderate/high titre (group A, n = 14) had higher levels of urinary 11-DH-TXB2 than those at low titre or negative (group B, n = 20) (p = 0.01). The group A of patients presented an increase in 11-DH-TXB2 compared to controls (p <0.001), but no statistically significant difference was found between patients from the group B and normal controls. A correlation between levels of urinary 11-DH-TXB2 and titre of antibodies was only found for anti-beta2GPI-IgG (r(s) = 0.51, p <0.005). Our data show that the observed platelet activation in aPL patients is related to the presence of antibodies reacting with beta2GPI.
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PMID:Anti-beta2 glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: association with increased excretion of platelet-derived thromboxane urinary metabolites. 945 20

The thromboxane A2/prostacyclin (TX/PGI) ratios were measured in patients with renal diseases to elucidate the relationship between the ratios and the pathological changes of the diseases. Urinary stable metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1alpha, respectively, were converted to 1-methyl ester-propylamide-9,12,15-tris-dimethylisopropylsilyl ether derivative and 1-methyl ester-6-methoxime-9,12,15-tris-dimethylisopropylsilyl ether derivative, respectively, and applied to a gas chromatography/selected ion monitoring. The TX/PGI ratios of 10 outpatients and 6 inpatients with chronic glomerulonephritis were higher than those of 13 healthy volunteers. In an inpatient with systemic lupus erythematoides, the TX/PGI ratios were gradually lowered to the normal level with the therapies. Furthermore, the ratios seemed to change in advance of the changes of the levels of urinary protein and hematuria. These observations suggested that the TX/PGI ratio was a useful index to assess the pathological condition of renal diseases and the effects of treatment.
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PMID:Changes of the thromboxane A2/prostacyclin balance in the urine of patients with renal diseases analyzed by gas chromatography/selected ion monitoring. 1068 Jul 70

The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro-thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy.
Lupus 2000
PMID:Antioxidant susceptibility of pathogenic pathways in subjects with antiphospholipid antibodies: a pilot study. 1119 24