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E Moilanen

Publications and source records attributed to E Moilanen.

13 recordsLinked to original sources
PubMed1991

Tolfenamic acid inhibits leukotriene B4-induced chemotaxis of polymorphonuclear leukocytes in vitro.

Inhibition of prostanoid synthesis is usually regarded as the mode of action of nonsteroidal antiinflammatory drugs (NSAIDs). In addition, some NSAIDs have been reported to have prostanoid-independent inhibitory effects on neutrophil functions. In the present study, we examined the effects of acetylsalicylic acid, diclofenac, indomethacin, ketoprofen, piroxicam and tolfenamic acid on leukotriene B4 (LTB4)-induced chemotaxis of human polymorphonuclear leukocytes (PMNs) in vitro. Tolfenamic acid inhibited LTB4-induced chemotaxis (IC50 59 microM), whereas the other compounds were ineffective. Tolfenamic acid inhibited also FMLP-induced chemotaxis at the same concentration range (IC50 46 microM). About 25% reduction in the chemotactic response was achieved with therapeutic concentrations of tolfenamic acid. We suggest that the inhibition of PMN chemotaxis is an additional mechanism in the antiinflammatory action of tolfenamic acid and that this action is not ligand specific.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Catecholamines inhibit leukotriene formation and decrease leukotriene/prostaglandin ratio.

Adrenaline, noradrenaline, isoprenaline, and to a lesser extent dopamine inhibit the release of leukotriene (LT) B2 from calcium ionophore-stimulated human polymorphonuclear leukocytes, while the release of prostaglandin (PG) E2 is proportionally elevated. The inactivity of salbutamol, a noncatechol adrenergic beta 2-receptor agonist, and the inability of propranolol to antagonize the effects of adrenaline, suggest the mediation through beta-receptor independent mechanisms. Neither are alpha-1-receptors involved, as prazosin, a specific antagonist, fails to inhibit the reaction. As the principles for biochemical regulation of LT- and PG-production are met by catecholamines in several tissues, the mechanism is considered to be of general physiological importance. Catecholamines may function as coenzymes/antioxidants which, by altering the redox state of the enzyme iron or heme, decrease the LT/PG ratio thus protecting the organism against tissue anaphylaxis and other LT-related pathophysiology.

Albuterol↗
PubMed1989

Effects of diclofenac, indomethacin, tolfenamic acid and hydrocortisone on prostanoid production in healthy and rheumatic synovial cells.

Prostanoids, found in enhanced concentrations in rheumatic synovial fluid, are involved in the joint destruction seen in rheumatoid arthritis. Adherent cells isolated from rheumatic synovia produce higher amounts of prostanoids in a primary cell culture than cells originating from non-inflamed synovia. In the present study, it was found that exogenous arachidonic acid diminished the differences in prostanoid production between healthy and rheumatic synovial cells. Non-steroidal anti-inflammatory analgesics in clinically relevant concentrations had similar inhibitory effects on arachidonic acid-stimulated prostanoid synthesis in both healthy and rheumatic cells. In the presence of exogenous arachidonic acid, hydrocortisone (0.3-5.0 microM) did not affect prostanoid production in healthy cells. In rheumatic synovial cells hydrocortisone reduced PGE2 and PGF2 alpha synthesis to about half of the control value and the effect was not reversed by adding excess exogenous arachidonic acid. Altered regulation of phospholipase A2 activity in rheumatic synovia could explain the observed differences between healthy and rheumatic synovial cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Eicosanoid production in rheumatoid synovitis.

Leukotriene B4 (LTB4) synthesis in rheumatoid synovitis was studied using peripheral and synovial fluid polymorphonuclear leukocytes (PMNs) and rheumatic synovial lining cells. No differences were found in LTB4 synthesis between peripheral PMNs from healthy volunteers and rheumatoid arthritis patients. When peripheral and synovial PMNs from the same RA patient were compared, arachidonic acid-induced LTB4 synthesis in synovial fluid PMNs was increased 1.7-7.2 fold, whereas the response to Ca ionophore A23187 stimulation was similar. This suggests 5-lipoxygenase stimulating factor(s) in inflamed joints. Rheumatic synovial lining cells in a primary cell culture produced small amounts of LTB4, the concentrations being less than 0.1 per cent of those of prostaglandin E2 (PGE2). PGE2 synthesis in synovial cells was increased when arachidonic acid or interleukin-1 was added to the culture, whereas LTB4 production remained unaltered. The present results suggest that in inflamed joints LTB4 originates mainly from PMNs whereas synovial lining cells are the source for PGE2.

Adult↗
PubMed1989

Orally administered tolfenamic acid inhibits leukotriene synthesis in isolated human peripheral polymorphonuclear leukocytes.

Special interest has been focused on the development of dual inhibitors of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism. In contrast to other classic NSAIDs, some fenamates in clinically achievable concentrations have been shown to inhibit synthesis of 5-lipoxygenase products in vitro. In the present work, we studied the effect of orally administered tolfenamic acid (600 mg) on Ca ionophore A 23187 -induced leukotriene synthesis in isolated human polymorphonuclear leukocytes. Leukotriene production was reduced in all 14 subjects studied, the mean inhibition of LTB4 synthesis being 16 +/- 3% and that of LTC4 33 +/ 7%. The inhibition correlated positively with serum acid concentrations. We suggest that inhibition of leukotriene synthesis is an additional mechanism of the anti-inflammatory, antimigraine and antidysmenorrhoeic effects of tolfenamic acid, and a possible explanation for its rare gastric and bronchoconstrictive side-effects.

Adult↗
PubMed1989

Cough induced by enalapril but not by captopril.

We report a 68 yr old woman with hypertension who developed a dry cough on enalapril but not on captopril therapy. Pulmonary function tests, methacholine inhalation challenges, total blood eosinophil counts, and changes in plasma concentrations of prostaglandin E2 and thromboxane B2 did not explain the difference in the adverse reaction between these two angiotensin converting enzyme inhibitors.

Aged↗
PubMed1988

Effects of antirheumatic drugs on leukotriene B4 and prostanoid synthesis in human polymorphonuclear leukocytes in vitro.

The effects of D-penicillamine, sodium aurothiomalate, indomethacin, timegadine and tolfenamic acid on the lipoxygenase and cyclo-oxygenase pathways of arachidonic acid metabolism were studied in human polymorphonuclear leukocytes (PMNs) in vitro. In short-term incubations, D-penicillamine and aurothiomalate did not affect leukotriene B4 (LTB4), prostaglandin E2 (PGE2) or thromboxane B2 (TXB2) production. Each of the three non-steroidal anti-inflammatory drugs (NSAIDs) used were potent inhibitors of prostanoid synthesis. In higher concentrations they also reduced LTB4 production; timegadine and tolfenamic acid were effective in concentrations comparable to those measured in plasma during drug therapy, whereas indomethacin was needed in ten times higher concentrations. The different effects of NSAIDs on 5-lipoxygenase activity may be of importance in their therapeutic actions as well as in the appearance of some side-effects, e.g. gastric irritation and "aspirin-induced" asthma.

Anti-Inflammatory Agents↗
PubMed1988

CP-66,248, a new anti-inflammatory agent, is a potent inhibitor of leukotriene B4 and prostanoid synthesis in human polymorphonuclear leucocytes in vitro.

The effects of (Z)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H- indole-1-carboxamide (CP-66,248), a new anti-inflammatory agent, were tested on the synthesis of the pro-inflammatory arachidonic acid metabolites, LTB4 and PGE2, in isolated human peripheral polymorphonuclear leucocytes. At clinically achievable (i.e. plasma) drug concentration, CP-66,248 reduced A 23187-stimulated LTB4 (IC50 18 +/- 1 microM) and PGE2 (IC50 32 +/- 8 nM) synthesis. The corresponding IC50 values for arachidonic acid-induced LTB4 and PGE2 production were 13 +/- 4 microM and 65 +/- 15 nM, respectively. The inhibitory action of CP-66,248 towards 5-lipoxygenase was comparable with that of timegadine and exceeded that of caffeic acid, and its action against the cyclo-oxygenase pathway was similar to that of other NSAIDs tested. The dual inhibition of cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism is likely to be involved in the anti-inflammatory, antipyretic and analgetic action of CP-66,248 detected in a variety of experimental models.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Differences in prostanoid production between healthy and rheumatic synovia in vitro.

To evaluate further the complex role of prostanoids in rheumatoid arthritis we compared the immunoreactive prostanoid production of healthy and rheumatic synovial cells in a primary cell culture. During the first days in culture the adherent cells from rheumatic synovia produced higher amounts of prostanoids, especially the proinflammatory and immunosuppressive prostaglandin E2 (PGE2), than cells originating from non-inflamed synovia. This difference disappeared within one week culture and was partly explained by altered substrate availability.

Adult↗
PubMed1987

D-penicillamine effects on prostanoid production in adherent rheumatic synovial cells in primary culture.

The effect of D-penicillamine (DPA) on immunoreactive prostanoid concentrations was studied in a primary culture of adherent synovial cells from patients suffering from rheumatoid arthritis (RA). DPA in clinically achievable concentrations increased the levels of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) and reduced those of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) synthetized from endogenous substrate. The capacity for PGE2 and 6-keto-PGF1 alpha production in the presence of exogenous arachidonic acid was decreased by DPA. These effects may be connected with the antirheumatic and immunosuppressive action of DPA.

6-Ketoprostaglandin F1 alpha↗