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Biomedical subjects

K Brune

Publications and source records attributed to K Brune.

At least 253 records · Page 14Linked to original sources
PubMed1978

Effect of imidazole on prostaglandin and thromboxane accumulation in urate arthritis.

High concentrations of prostaglandins E2 and F2alpha and much lower concentrations of thromboxane B2 occurs in joint washes of chicken 1--3 h after intra-articular injection of urate crystals. Pretreatment with 200 mg/kg imidazole i.v. reduced the concentration of prostaglandins and of thromboxane B2 in the joint washes significantly. Simultaneously, leucocyte invasion was delayed and development of oedema was inhibited. The results suggest that in urate crystal arthritis the effect on prostaglandin and thromboxane accumulation at the site of inflammation contributes to the anti-inflammatory activity of imidazole.

Animals↗
PubMed1978

Selective cytotoxic actions of aspirin on parietal cells: a principal factor in the early stages of aspirin-induced gastric damage.

Electronmicroscopic observations are reported on the effects of orally administered aspirin on the rat gastric mucosa to establish the cytotoxic events that occur during the early stages of the development of gastric damage induced by this drug. The results show that aspirin, apart from damaging superficial mucous cells, causes selective damage to the acid-secreting parietal cells located deep in the fundic mucosa. It is suggested that the selective accumulation of salicylates in the parietal cells may account for the specific cytotoxic actions of aspirin on these cells.

Animals↗
PubMed1978

Inflammatory, tumor initiating and promoting activities of polycyclic aromatic hydrocarbons and diterpene esters in mouse skin as compared with their prostaglandin releasing potency in vitro.

Release of prostaglandin E2 (PGE2) in cultured peritoneal macrophages of NMRI mice by skin irritant tumor initiators and promoters was investigated. Initiators of the polycyclic aromatic hydrocarbon type, e.g., DMBA, caused slight irritation on the mouse ear but even relatively high doses did not stimulate PGE2-release to any measurable extent within 4 h after administration in vitro. Apparently there is no correlation between irritation and initiating activity in mouse skin and PGE2-release in macrophages. On the other hand, promoters of the diterpene ester type, e.g., TPA, were strong irritants on the mouse ear. Even low doses of these compounds stimulated PGE2-release from macrophages dramatically within 1 h after administration in vitro. Moreover, a good correlation was established between irritant and promoting activity in mouse skin and PGE2-release in macrophages of a series of tigliane, ingenane and daphnane type diterpene derivatives. These results suggest that also in mouse skin PGE2-release may occur following exposure of the target cells to promoters of the diterpene ester type resembling one of the most early molecular events of promotion. This event could initiate both skin irritation and cell proliferation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Biodistribution of salicylates: a clue to the understanding of some effects and side effects.

According to our concept that biodistribution of salicylates (SA) might be an important factor of their mode of action the distribution of sodiumsalicylate (NaSA) and acetylsalicylic acid (ASA) was investigated in vivo and in vitro. It was shown that particular high concentrations of both compounds were found in vivo in the glandular stomach region and the kidney tubules of rats as well as in inflamed tissue. Quantitative studies showed that in chicken, in inflamed joints, higher concentrations as in plasma and about three times higher concentrations as in control joints were observed. In vitro studies using human erythrocytes suspended in buffer of different pH showed that added NaSA accumulated in these cells when the environmental pH was lowered from 7.4 to 6.8. From these results it is speculated that SA being weak acids accumulate within cells which are surrounded or bordering acidic fluids. This is the case in the stomach, the kidney and the inflamed tissue. This is where SA exert their effects and side effects.

Animals↗
PubMed1977

Prostaglandin release from macrophages: an assay system for anti-inflammatory drugs in vitro.

It is the intention of this communication to present a simple and reliable in vitro system for the evaluation of anti-inflammatory drugs. The system described appears to combine the advantages of two established procedures, i.e. measurement of the inhibition of prostaglandin (PG) synthesis in vitro using microsomal enzyme preparations and the measurement of the inhibitory effects of drugs on PG synthesis in vivo avoiding major limitations. We propose to measure the effect of drugs on the PG release from mouse peritoneal macrophages in vitro. The influence of culture conditions, phagocytosis and drugs on the PG release from these cells is described. We found that antibody-coated erythrocytes are especially suitable triggers of PG release, and that the release can be inhibited by steroidal and non-steroidal anti-inflammatory drugs in concentrations resembling their effective doses in vivo.

Animals↗
PubMed1976

Role of the parietal cell in gastric damage induced by aspirin and related drugs: implications for safer therapy.

The proton-secreting parietal cell is shown, from recent evidence, to be the principal focus for the actions of aspirin (and related drugs) in damaging the gastric mucosa. It is suggested that the selective damage to the parietal cells is due to the ph gradient favouring a high rate of aspirin uptake and subsequent entrapment of drug anions inside these cells. This concept may serve as a useful basis for developing procedures to minimize the gastric damage by aspirin and related acidic drugs.

Animals↗
PubMed1976

Inhibition of prostaglandin synthesis in vivo by nonsteroid anti-inflammatory drugs: evidence for the importance of pharmacokinetics.

A variety of acidic and non-acidic compounds are potent inhibitors of prostaglandin (PG) synthesis in vitro. However, only a few, namely the acidic nonsteroid anti-inflammatory drugs (NSAID) are useful anti-inflammatory analgesics in the clinic. Since inhibition of PG-synthesis is believed to be the main target of NSAID in inflammation this superiority of acidic compounds remains unexplained. We have considered that one explanation could be that only acidic NSAID appear in high concentrations in inflamed tissue to inhibit PG-synthesis sufficiently. To test this hypothesis the following experiments were carried out: (A) PG-synthesis and its inhibition by acidic and non-acidic NSAID was measured in vivo at the site of inflammation. It was found that in therapeutic doses only acidic NSAID were capable to reduce PG-synthesis significantly. (B) Measurement of drug concentration in inflamed tissue showed that only acidic NSAID were found in significantly higher concentrations in inflamed than in control tissue. From these observations it is concluded that a specific pharmacokinetic behaviour of acidic NSAID leading to high concentrations in inflamed tissue is a decisive aspect of their anti-inflammatory action.

Animals↗