dinoprost and acetylsalicylic-acid-lysinate

Prostaglandin (PG)D2 is a major product of arachidonic acid metabolism in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD2, 9 alpha, 11 beta-PGF2, could serve as a marker of mast cell activation in the lungs. A commercially available enzyme immunoassay was validated and found to be specific and sensitive when applied to unpurified urine. There was no diurnal variation in the levels of 9 alpha, 11 beta-PGF2 in healthy volunteers. Morning baseline values of urinary 9 alpha, 11 beta-PGF2 were measured in three groups--healthy volunteers (n = 9), patients with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)--and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary excretion of 9 alpha, 11 beta-PGF2 was increased threefold immediately after allergen-induced bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced bronchoconstriction without extrapulmonary symptoms and was also followed by a significant increase in the urinary excretion of 9 alpha, 11 beta-PGF2. In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9 alpha, 11 beta-PGF2, supporting dose-dependent release of PGD2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge levels of urinary 9 alpha, 11 beta-PGF2 were not increased when bronchoconstriction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in allergen-induced bronchoconstriction and provides novel data, which strongly support the hypothesis that pulmonary mast cells are activated during aspirin-induced airway obstruction. It is finally suggested that measurement of urinary 9 alpha, 11 beta-PGF2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor mast cell activation in vivo.

Topics: Adult; Airway Obstruction; Allergens; Aspirin; Asthma; Bronchial Provocation Tests; Chromatography, High Pressure Liquid; Cross-Over Studies; Dinoprost; Double-Blind Method; Histamine; Humans; Immunoenzyme Techniques; Lysine; Mast Cells; Middle Aged; Prostaglandin D2

Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dinoprost; Female; Labor, Obstetric; Lysine; Male; Placenta; Pregnancy; Sheep; Time Factors

The influence of sympathetic stimulation (SS) (achieved by 2 min cold application) on the plasma concentration of PGE2, PGF2 alpha (radioimmunoassay), noradrenaline (NA) and adrenaline (A) (radioenzymatic assay) and on forearm vascular resistance (indirect measurement, FVR) was studied in 16 healthy volunteers before and after cyclooxygenase inhibition by indomethacin (200 mg per day orally for 3 days) and lysine acetylsalicylate (corresponding to 10 mg X kg-1 of acetylsalicylic acid -ASA- iv). SS induced a sharp increase in PGE2 (from 8.1 +/- 4.3 pg X ml-1 before SS to 23.9 +/- 6.5, P less than 0.001 2 min after the beginning of SS and then to 18.9 +/- 10.2, P less than 0.001 to 8.4 +/- 3.9, NS, 4 and 12 min respectively after the beginning of SS). Plasma levels of PGF2 alpha remained undetectable both before and after SS. The increase in PGE2 was associated with a simultaneous increase in NA (from 13.4 +/- 24.2 to 204.1 +/- 67.2 pg X ml-1, P less than 0.001 during SS and 140.6 +/- 39.5, NS at the end of the experiment), whereas A did not vary significantly. FVR increased significantly only during SS. ASA did not affect PGE2 and NA plasma levels at rest or after SS. No PGE2 was detected during IND administration either before or after SS. IND significantly increased NA plasma concentration at the observation made 12 min after the beginning of SS (185.2 +/- 64.3 pg X ml-1 vs basal values of 135.9 +/- 46.2 pg X ml-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aspirin; Cold Temperature; Dinoprost; Dinoprostone; Epinephrine; Female; Humans; Indomethacin; Lysine; Male; Norepinephrine; Prostaglandins E; Prostaglandins F; Sympathetic Nervous System; Vascular Resistance