misoprostol and Hypersensitivity

In the first 18 months since mifepristone was approved by the Food and Drug Administration (FDA) for use with misoprostol for early medical abortion, approximately 80,000 women have been treated. One-hundred thirty-nine adverse events were reported to Danco Laboratories LLC and subsequently reported to the FDA. Thirteen patients required blood transfusions, 10 patients were treated with antibiotics for infection and 6 had a generalized allergic reaction. Fifty patients had an ongoing pregnancy, with 48 having suction curettage, leaving 2 ongoing pregnancies. Thirty-nine patients had a suction curettage for heavy or prolonged vaginal bleeding. The overall national experience has been highly favorable.

Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Induced; Anti-Bacterial Agents; Blood Transfusion; Female; Gestational Age; Humans; Hypersensitivity; Infections; Mifepristone; Misoprostol; Pregnancy; United States; Uterine Hemorrhage; Vacuum Curettage

In noninfected rats, challenge with allergen following local IgE sensitization induced a pleurisy marked by intense protein exudation that plateaued from 30 min to 4 h after challenge, reducing thereafter. Infection of rats with Angiostrongylus costaricensis induced a 5-fold increase in blood eosinophil numbers by 25 days postinfection, whereas the numbers of eosinophils in the pleural cavity ranged from normal to a weak increase. In infected rats, identically sensitized, challenge with Ag induced a much shorter duration of pleural edema with complete resolution by 4 h, but no change in the early edema response. In parallel, infection increased the number of eosinophils recovered from the pleural cavity at 4 h, but not at 30 min, following allergen challenge. Pretreatment with IL-5 (100 IU/kg, i.v.) also increased eosinophil numbers in blood and, after allergen challenge, shortened the duration of the pleural edema and increased pleural eosinophil numbers. There were increases in the levels of both PGE2 and lipoxin A4 (LXA4) in pleural exudate. Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats. Pretreatment of noninfected animals with the PGE analogue, misoprostol, or two stable LXA4 analogues did not alter the magnitude of pleural exudation response, but clearly shortened its duration. These results indicate that the early resolution of allergic pleural edema observed during A. costaricensis infection coincided with a selective local eosinophilia and seemed to be mediated by COX-2-derived PGE2 and LXA4.

Topics: Administration, Oral; Angiostrongylus; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Helminth; Corticosterone; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Edema; Eosinophilia; Exudates and Transudates; Female; Hydroxyeicosatetraenoic Acids; Hypersensitivity; Injections, Intraperitoneal; Injections, Intravenous; Interleukin-5; Isoenzymes; Kinetics; Leukotriene C4; Lipoxins; Male; Misoprostol; Pleural Effusion; Pleurisy; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Strongylida Infections

Misoprostol (MSP), the synthetic prostaglandin E1 (PGE1) analog, possesses multifunctional features, including modulating some inflammatory aspects of immune and allergic disorders.. To investigate the effect of MSP on histamine release (HR) from basophils of whole blood using anti-IgE, specific allergens, and calcium ionophore.. The study was performed using the automated glass fiber-based whole blood leukocyte histamine release test (LHRT).. Very low concentrations of MSP produced a marked inhibition of HR induced with anti-IgE. Maximum inhibition was observed at 10-9 M. It was also shown that the levels of HR inhibition with MSP varied at different incubation times. The greatest inhibition of HR was noted at 1 to 2 hours of incubation at MSP concentrations of 10-8 and 10-9 M, respectively. Incubation of blood from allergic patients at the optimal MSP concentration and optimal elapsed time (2 hours) resulted in significant reductions of allergen-specific HR induced by both Timothy pollen grass allergen and D.pteronissinus. Incubation of blood with varying concentrations of MSP and subsequent stimulation with calcium ionophore A23187 also inhibited HR from basophils. In the latter case, the most effective concentrations of MSP ranged from 10-8 to 10-6 M.. This study demonstrated that MSP can inhibit basophil HR indicating a potentially beneficial role of PGE1 analogs as pharmacotherapy for allergic diseases.

Topics: Anti-Ulcer Agents; Antibodies, Anti-Idiotypic; Basophils; Binding Sites, Antibody; Calcimycin; Histamine Release; Humans; Hypersensitivity; Ionophores; Misoprostol; Oxytocics