6-ketoprostaglandin-f1-alpha and Diarrhea

The role of prostacyclin (PGI2) in the pathogenesis of haemolytic uraemic syndrome (HUS) is controversial. In part, confusion has been caused by failure to distinguish between two main sub-types of the syndrome: extrinsic, diarrhoea-associated HUS (D+ HUS), usually caused by infection with verocytotoxin-producing Escherichia coli or Shigella dysenteriae, and the heterogeneous group of non-prodromal forms where intrinsic factors predominate (D- HUS). This paper critically reviews data confined to D+ HUS. Two methods have been used to assess PGI2 synthesis; the generation of PGI2 from endothelium in the presence of HUS plasma in vitro and the measurement of stable metabolites in body fluids. No concensus could be reached with regard to the former. The reported increase of PGI2 stable metabolites in plasma may represent reduced clearance or increased carriage by plasma lipids. Apparent differences between studies of urinary excretion of PGI2 metabolites may reflect the way excretion was expressed. If the metabolite concentration is factored for urinary creatinine, it appears that renal excretion and thus renal synthesis of PGI2 is reduced. However, these are insufficient data on which to attribute the pathogenesis of D+ HUS to disordered PGI2 metabolism.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Diarrhea; Endothelium, Vascular; Epoprostenol; Gas Chromatography-Mass Spectrometry; Hemolytic-Uremic Syndrome; Humans; Radioimmunoassay; Rats

This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment. Etoricoxib and celecoxib had no effect on the urinary thromboxane metabolite, 11-dehydrothromboxane B(2), while significantly decreasing the urinary prostacyclin metabolite, 2,3-dinor-6-keto PGF(1alpha). Decreases were greater for both metabolites following naproxen. Ambulatory systolic blood pressures were significantly higher than placebo for all treatments, with moderately greater increases for etoricoxib relative to other active treatments on day 14. Ambulatory diastolic blood pressures were significantly higher than placebo for etoricoxib and naproxen but not for celecoxib.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Celecoxib; Constipation; Creatinine; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Electrolytes; Etoricoxib; Female; Headache; Humans; Male; Middle Aged; Naproxen; Potassium; Prostaglandins; Pyrazoles; Pyridines; Sodium; Sulfonamides; Sulfones; Thromboxane B2