Unlike other classic NSAIDs, some fenamates given at therapeutic concentrations, have been shown to inhibit, both in vitro and in vivo, the 5-lipoxygenase pathway of arachidonic acid cascade as well as the synthesis of cyclooxygenase products. This dual inhibitory property might represent an improvement in anti-inflammatory therapy. The aim of this work was to characterize the effect of morniflumate, administered at therapeutic dosages to normal human volunteers, on leukotriene B4 (LTB4) and thromboxane (TXB2) synthesis, both in purified PMNs and in whole blood. PMNs, isolated two hours after a single oral administration of morniflumate and at steady-state condition, fully retain their capacity to release LTB4 and TXB2. Since intracellular concentrations of the drug were undetectable, in spite of its elevated concentrations in platelet poor plasma, the results obtained using PMNs suggest a drug loss during the cells purification procedure. In whole blood experiments, morniflumate reduced blood LTB4 synthesis induced by Ca-ionophore A23187 Bx approximately 50%, both after single dose and at steady state; the degree of inhibition showed a pattern similar to the plasma levels of the bioactive metabolite of morniflumate (M1). The inhibition of serum TXB2 levels was higher than 85%. Hence, morniflumate is capable of reducing arachidonic acid metabolism acting both on cyclooxygenase and 5-lipoxygenase. This characteristic might provide a better approach in anti-inflammatory therapy.

No abstract

Abstractacterised by heightened immune processes at Background -Mediators released by al-the site of disease activity. 1 In particular, an veolar macrophages, as well as by T cells, enhanced recruitment and activation of implay an important part in modulating local munocompetent cells (alveolar macrophages immune processes in sarcoidosis. Among and T cells) occurs within the alveolar strucalveolar macrophage secretory products, tures. Once activated, these cells have a wide arachidonic acid metabolites are known to spectrum of effector functions including seregulate inflammatory and immune re-cretion of various mediators that play an imactions. It has been suggested that cyclo-portant part in the evolution and modulation oxygenase and lipoxygenase pathway of local immune processes in sarcoidosis.1-3 metabolites of arachidonic acid modulate Among the alveolar macrophage secretory the evolution of the granulomatous in-products, arachidonic acid metabolites are flammatory response in the lung differ-known to regulate inflammatory and immune ently.reactions. [3][4][5] Although there has been increasing Methods -Alveolar macrophages re-interest in the potential immunomodulatory covered from the bronchoalveolar lavage role of these metabolites, few studies have in-(BAL) fluid of 32 patients with sarcoidosis vestigated the characteristics of arachidonic in different states of disease activity and acid metabolism in relation to specific lung 10 normal subjects were evaluated for their diseases. 6-12 Department of ability to release prostaglandin E 2 (PGE 2 )Arachidonic acid is one of the most rep-

No abstract

Rabbits were immunized versus either an acetylcholinesterase- or a cholinergic receptor-rich fraction isolated from the electric organ of Torpedo marmorata. In both groups of animals we obtained a production of specific antibodies detected by immunodiffusion without cross reaction for the two antigens. Only rabbits immunized with the receptor-rich fraction developed a progressive flaccid paralysis, which affected first the leg muscles, progressively the neck muscles and eventually the respiratory muscles. The paralysis lasted in several animals up to 20 days. Eserine reversed the paralysis only in the first days but was ineffective in the "chronic" stage of the disease. In these animals high frequency stimulation of sciatic nerve induced a rapid failure of the responses of the anterior tibialis muscle while the muscle responded normally to a direct stimulation. A period of rest allowed a complete recovery of the muscle from fatigue. Tetani did not evoke the post-tetanic potentiation. Abnormalities, such as lymphocytic infiltration, fibers atrophy and necrosis, smearing and widening of Z line were sometimes present in muscles of Cho-R-immunized rabbits. In ACh-E immunized animals the neuromuscular transmission and the muscle morphology were similar to that of normal animals. Glycogen, ATP, cytochrome C oxidase, phosphorylases and acetylcholinesterase did not change significantly in the muscles of the immunized animals, while a large increase of cholineacetyltransferase activity was present. Red blood cell acetylcholinesterase showed a particularly high activity in ACh-E-immunized animals. The autoimmune paralysis induced in Cho-R-immunized rabbits may be a useful experimental model for further studies on human myasthenia gravis.