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Biomedical subjects

K Brune

Publications and source records attributed to K Brune.

At least 235 records · Page 13Linked to original sources
PubMed1981

Dissociation of tumour-promoter-induced effects on prostaglandin release, polyamine synthesis and cell proliferation of 3T3 cells.

The phorbol ester 12-O-tetradecanoylphorbol 13-acetate induces tumour promotion, inflammation, cell proliferation and prostaglandin release. Recent reports suggest that the prostaglandins released by 12-O-tetradecanoylphorbol 13-acetate (TPA) initiate a cascade of events leading to polyamine synthesis and cell proliferation. In experiments designed to test this contention, it was found that addition of TPA (1 microM to 1 nM) to confluent mouse 3T3 fibroblasts successively caused the release of prostaglandins E2 and I2, induction of the enzyme ornithine decarboxylase (EC 4.1.1.17), stimulation of [3H]thymidine incorporation into DNA, and cell proliferation. Pretreatment of the cells with the anti-inflammatory steroid dexamethasone (1 microM) or the non-steroidal anti-inflammatory drug indomethacin (1 microM) inhibited TPA-induced prostaglandin release. However, dexamethasone enhanced the other effects of TPA, whereas indomethacin was ineffective. Addition of prostaglandin E2 to the cultures did not induce ornithine decarboxylase activity and cell proliferation. Pretreatment of the cells with 1,3-diaminopropane (1 mM) or alpha-methylornithine (5 mM), inhibitors of polyamine synthesis, decreased TPA-induced ornithine decarboxylase activity without affecting DNA synthesis. TPA stimulated [3H]thymidine incorporation into DNA, even when the ornithine decarboxylase activity was completely blocked. These data suggest that the proliferative effect of TPA on 3T3 cells is independent of prostaglandin release and polyamine synthesis.

Animals↗
PubMed1981

Inhibition of anti-inflammatory drugs of prostaglandin production in cultured macrophages.

1. A sensitive, simple, reproducible, and economical assay for structure-activity investigations of non-steroidal anti-inflammatory drugs (NSAID) is lacking. This has prompted us to investigate the advantages and limitations of defining for that purpose the potency of NSAID's as inhibitors of tumour promoter-induced prostaglandin (PG) release from mouse peritoneal macrophages in culture. 2. These cells release mainly PGE2 and PGI2 (measured as its stable hydrolysis product 6-keto-PGF1 alpha) upon stimulation with the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). 3. The PG release was dose-dependently inhibited by a variety of NSAID's. Their inhibitory potency was dependent on the culture conditions employed. The widely used acidic NSAID's were more potent when assayed under serum free culture conditions at low pH. 4. Dose response curves for acidic NSAID tested under serum free conditions allowed for the definition of IC50 values being reproducible within their 95% confidence limits. 5. The IC50 values obtained for different standard acidic NSAID's varied within 4 orders of magnitude. They corresponded favourably to their clinical potency and their potency in a variety of standard tests for anti-inflammatory drugs. 6. IC50 values of five congeners of indomethacin differed up to 2 orders of magnitude in agreement with in vivo observations indicating the applicability of this assay for structure-activity investigations.

Animals↗
PubMed1981

Autoradiographic and biochemical observations on the distribution of non-steroid anti-inflammatory drugs.

A comparison has been made of the distribution of some new radioactively-labelled non-steroid anti-inflammatory (NSAI) drugs or pro-drugs with their respective progenitors and/or standard acidic NSAI drugs (i.e. aspirin, indomethacin and phenylbutazone), using whole body autoradiography and scintillation counting. The object of this study was to establish if the distribution of these new NSAI drugs may contribute to changes in their side-, or therapeutic effects compared with the older drugs. All the NSAI drugs accumulated in those tissues wherein the principle therapeutic and side-effects are manifest. The accumulation in inflamed tissues occurs regardless of the structural type of NSAI drugs, i.e. with specific accumulation occurring in this tissue of the acidic drugs or their acidic metabolites. New aspects of the distribution of the acetyl moiety of aspirin are reported which may be significant in relation to the side-effects induced by this drug.

Animals↗
PubMed1980

Paracetamol does not potentiate the acetylsalicylate inhibition of prostaglandin release from macrophages.

Prostaglandin (PGE2 and PGI2) synthesis can be stimulated in macrophages by the tumour promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibited by acetylsalicyclic acid (IC50 = 8.2 x 10(-6) M) and paracetamol (IC50 = 1.9 x 10(-4) M). When mixture of both drugs were tested only an additive effect was observed. This result is in contrast to recent reports describing both potentiation of acetylsalicylate-induced PG synthesis inhibition and enhancement of PG production by paracetamol.

Acetaminophen↗
PubMed1980

Bio-distribution in rats of some salicylates with low gastric ulcerogenicity.

The distribution of three radioactively labelled salicylate derivatives with low ulcerogenic activity was compared with that of acetylsalicylic acid (ASA) and salicylic acid using whole body autoradiography and liquid scintillation counting techniques in rats. The methyl ester of ASA (AME) was distributed in vivo very similarly to that observed with ASA and salicylic acid. AME is rapidly demethylated following absorption from the stomach and is subsequently converted to ASA and salicylate. Salicylate is the main metabolite produced from both AME and ASA, which specifically accumulates in inflamed tissues. The 3-methyl- and 6-methyl-substituted salicylic acids are not as rapidly absorbed as either ASA or salicylic acid and do not pass readily into the brain or bone marrow. These results show that the methyl (ester) group of AME (which adequately protects the gastric mucosa from damage caused by ASA itself) does not impair the quantity of pharmacologically active form of drug (salicylate and ASA) generated in vivo. However, insertion of the methyl group at the 3- and 6-position of salicylic acid markedly affects both absorption, distribution and pharmaco-activity of these acids.

Animals↗
PubMed1980

HEPES buffered media may induce prostaglandin release from macrophages in tissue culture.

On investigating the release of PGE2 from mouse peritoneal macrophages in tissue culture it was found that the spontaneous release of PGE2 was dependent on the culture conditions employed. The type of buffering of the medium was especially important. Using CO2- sodium bicarbonate buffers we observed little, if any, spontaneous release of prostaglandins (PGs) from macrophages, whereas in the presence of N-2-hydroxyethylpiperazine-N-2-ethane-sulfonic acid (HEPES) buffer in some cases a dramatic increase in PG release was observed.

Buffers↗
PubMed1980

Biodistribution of mild analgesics.

1 Macro-autoradiographic methods were used to assess the biodistribution of [3H]-, or [14C]-acidic (aspirin, indomethacin, phenylbutazone) and non-acidic (antipyrine, aminopyrine, paracetamol) mild analgesics in rats with carrageenan-induced inflammation. 2 At anti-inflammatory doses all the acidic drugs (and/or their metabolites) were found to reach high concentrations in the stomach wall, liver, blood and bone marrow, kidney cortex and the inflamed tissue, that is, the tissues in which these drugs exert their therapeutic or side-effects. 3 In contrast, at analgesic doses, the non-acidic mild analgesics (and/or their metabolites) are equally distributed throughout the body with the exception of the gastro-intestinal lumen and the liver. This distribution pattern correlates well with the lack of acute side-effects and anti-inflammatory action of these drugs at therapeutic doses.

Analgesics↗
PubMed1979

Prostaglandin D2 is the prevailing prostaglandin in the acute inflammatory exudate of urate arthritis in the chicken.

An acute inflammation was elicited in intertarsal joints of chicken by injection of urate crystals. Inflammatory exudates recovered at different times were assayed for prostaglandin D2(PGD2)E2 and F2 alpha and thromboxane B2 content by specific radioimmunoassays. We found that PGD2 was the prevailing prostaglandin reaching concentrations up to 10 times in excess of PGE2. This finding was confirmed by gas chromatography-mass spectrometry. It is concluded that PGD2 should be considered as a possible mediator of acute inflammation.

Animals↗