0000000000173833
AUTHOR
Carlo Patrono
ABNORMALLY HIGH THROMBOXANE BIOSYNTHESIS IN HOMOZYGOUS HOMOCYSTINURIA. EVIDENCE FOR PLATELET INVOLVEMENT AND PROBUCOL-SENSITIVE MECHANISM.
Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, …
POSTPRANDIAL HYPERGLYCEMIA IS A DETERMINANT OF PLATELET ACTIVATION IN EARLY 2 DIABETES MELLITUS
BACKGROUND: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. OBJECTIVES: To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. METHODS: Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandi…
Enhanced Lipid Peroxidation and Platelet Activation in the Early Phase of Type 1 Diabetes Mellitus
Background— To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A 2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F 2 -isoprostane formation in this setting. Methods and Results— A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM (≤6 weeks, group A), matched for age and gender with 23 patients with s…
Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia
Abstract Thromboxane A 2 (TXA 2 ) biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia. Because simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) was previously shown to reduce platelet aggregation and TXB 2 production ex vivo, we investigated TXA 2 biosynthesis and platelet function in 24 patients with type IIa hypercholesterolemia randomized to receive in a double-blind fashion simvastatin (20 mg/d) or placebo for 3 months. The urinary excretion of 11-dehydro-TXB 2 , largely a reflection of platelet TXA 2 production in vivo, was measured by a previously validated radioimmunoassay technique. Blood lipid levels and urinary 11-dehyd…