Local anti-inflammatory activities of tixocortol 21-pivalate, inhibition of prostaglandins and leukotrienes synthesis, in carrageenin-induced pleurisy. Reversion of effects by RU 486.

Since a direct effect of tixocortol pivalate (TP) has been described on cyclooxygenase pathway, local anti-inflammatory activities of some 21 thiol derivatives of steroids were investigated on the carrageenin-induced pleurisy model in comparison with dexamethasone (Dex) or other anti-inflammatory drugs. LTC4/D4 contents in pleural fluid were assayed by RIA as well as PGE2 levels to characterize the effects on arachidonate pathways. After oral administration, TP was inactive up to 1 g/kg on exudate volume and leukocyte migration as expected for this strict local anti-inflammatory steroid contrary to Dex (ID50 = 0.

Direct inhibition of cyclooxygenase pathway in platelets by tixocortol 21-pivalate: comparison with related structures, steroidal and non steroidal anti-inflammatory drugs.

Direct activity of the local anti-inflammatory steroid, tixocortol 21-pivalate (21 thioester derivative of cortisol) on metabolism of exogenous arachidonate by rabbit platelets was investigated in vitro. Tixocortol 21-pivalate inhibited generation of prostanoids from cyclooxygenase with an IC50 value of 19.6 microM without affecting the 12-lipoxygenase pathway.

The presence of lipocortin in human embryonic skin fibroblasts and its regulation by anti-inflammatory steroids.

Human embryonic skin fibroblasts in culture produce pro-inflammatory lipid mediators and all types of prostanoids. When these cells were treated with the anti-inflammatory steroid, dexamethasone, prostaglandin production was inhibited. This phenomenon required glucocorticoid receptor occupancy and mRNA and protein synthesis.

Inflammatory response linked to oxazolone-indued cutaneous basophil hypersensitivity: effect of different immunomodulator and anti-inflammatory drugs.

The potency of cytostatic and anti-inflammatory drugs was tested on the oxazolone-induced cutaneous basophil hypersensitivity (CBH) in mice. The challenge reaction was performed early after sensitization in order to minimize B-cell expression; exudative and cellular infiltration was estimated 6 h, 24 h and 48 h after challenge. The potency of drugs was tested at three different periods of immunization: 2 days before or after sensitization or before challenge.

The effect of high glucose concentration on the proliferation and the synthesis of lipids in endothelial cells in culture.

Influence of glucose concentration on growth and lipid synthesis was investigated in human endothelial cells in culture. The biosynthesis of lipids from acetate and glucose was present in endothelial cells, but a high glucose level in the culture medium failed to modify lipid synthesis. Neosynthesis in the lipidic fraction in the medium is higher when precursor is acetate compared to glucose.