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M J Adolfs

Publications and source records attributed to M J Adolfs.

46 records · Page 3Linked to original sources
PubMed1979

Effects of 2-aminomethyl-4-t-butyl-6-iodophenol (MK-447) on granulomatous inflammation: lack of correlation with changes in levels of prostaglandin-like material.

MK-447, administered locally to carrageenan-soaked sponges implanted in the backs of rats, either on the day of implantation (day 1) or on days 4-7, exhibited a weak, dose-related inhibition of subsequent granuloma formation. With the later treatment period, prostaglandin (PG)-like material in day 8 exudates was increased at all doses, but with MK-447 treatment on day 1, levels of PG-like material after 24 h were unaffected. Thus, inhibition of granuloma formation was unrelated to local levels of PG-like material. Following treatment with low doses of MK-447 on implantation, mononuclear cell counts in 24 h exudates were reduced. Similar results were obtained with PGE1. Higher doses of MK-447 did not alter monuclear cell counts, but both high and low doses of MK-447 markedly increased polymorphonuclear cell counts in 24-h exudates. The results do not permit the conclusion that the anti-granuloma action of MK-447 is necessarily related to alteration of stable PG level at the inflamed site. Therefore, MK-447 cannot be used unequivocably as a tool to investigate the role of endogenous stable PGs during granulomatous inflammation.

Animals↗
PubMed1979

Modulation of granulomatous inflammation by prostaglandin E. Involvement of mononuclear cells.

The effects of exogenous PGE, administered locally to carrageenan sponge-induced granulomata in rats, have been studied in relation to changes in PGE-like material (PGL) and cell counts in exudates. Levels of PGL achieved a peak within 24h, declining thereafter. Administration of PGE during the acute phase led to irregular slight enhancement of subsequent granuloma formation. In contrast, administration of exogenous PGE to pre-formed granuloma, inhibited its formation. The early administration of PGE1, on day 1, inhibited mononuclear cell counts in 24h exudates. This inhibition was still present in 8 day exudates, together with reduced PGL levels. A significant correlation was also observed between phagocytosing macrophages and PGL levels in 8 day exudates after exogenous PGE1 treatment of pre-formed granuloma, suggesting that the exogenous PGE was inhibiting macrophage function, including PGL production. Further studies are necessary to establish whether the observed pharmacological effects indicate that PGE, released during granulomatous inflammation, modulates the process through actions on infiltrating leucocytes.

Animals↗
PubMed1979

Mimickry of anti-granuloma effect of prostaglandin E by dibutyryl cyclic-AMP and some phosphodiesterase inhibitors.

Local administration of PGE1 to pre-formed inflammatory granulomata of rats results in a decrease of granulomatous tissue and reduction of prostaglandin concentrations in granulomatous exudates. Under the same experimental conditions, a similar correlation between these two effects is observed with dibutyryl cyclic-AMP. An anti-granuloma effect is also achieved with the phosphodiesterase inhibitors, IBMX and RA-233, but not with theophylline, a rather feeble inhibitor of this enzyme. The present findings provide further support for the concept that elevation of cyclic-AMP in cell population(s) within granuloma is a promising line for pharmacological suppression of inflammatory tissue proliferation.

1-Methyl-3-isobutylxanthine↗
PubMed1978

Cyclic AMP and prostaglandin E in perfusates of rat hind paws during the development of adjuvant arthritis.

The contralateral uninjected hind paws of rats which had been injected with Freund's complete (FCA) or incomplete (FIA) adjuvant 10,14, 18, or 22 days previously were perfused under urethane anaesthesia using a stainless steel coaxial catheter. In one series of experiments cyclic AMP (cAMP) levels were determined after a 2-hour perfusion. cAMP levels were also determined in rats treated on days 16-22 with either prostaglandin E(1) (PGE(1)) (500 mug/kg per day subcutaneously) or saline. When compared with control rats injected with FIA, after 22 days, cAMP levels in FCA-injected rats fell between days 10 and 18 and then rose between days 18 and 22. After PGE(1) treatment, paw volume on day 22 increased in rats injected with FCA, but cAMP levels were not significantly altered when compared with day 22 FCA-injected controls treated with saline. In a second series of experiments, using a slightly modified perfusion method, PG levels in extracts of 30-minute perfusates were determined after chromatography and bioassay. Protein levels and paw volume were also measured. No PGF was detectable in any perfusate. Changes in PGE levels in FCA-injected animals paralleled changes in paw volume, increasing from day 14 and reaching a maximum on day 22. Both parameters remained unchanged in FIA-injected rats. Protein levels in perfusates from FCA-injected animals were significantly greater than FIA-injected controls only on day 22. We suggest that the early changes in cAMP reflect the infiltration of activated leucocytes into the inflamed joint and that the increase in PGE is attributable to lysosomal enzyme activity. Later increases in cAMP are attributable both to the increasing PGE levels and to other changes in cellular activation. We suggest that high levels of PGE contribute to tissue damage which is reflected in raised protein levels.

Animals↗
PubMed1977

A polyether sponge constituent which is antioxidant, anti-inflammatory and increases prostaglandin concentrations at the inflamed site.

Granuloma formation was studied in rats following s.c. implantation of polyether sponges soaked in carrageenin. Sponges, which had been boiled in ethanol, produced larger granulomata and more exudate than unboiled sponges, but prostaglandin (PG) concentrations were lower in exudates from boiled sponges. Sub-cutaneous injection of the ethanolic sponge extract inhibited the delayed phase of carrageenin-induced rat hind paw oedema. A counter irritant action was ruled out by the demonstration that local administration of the extract also inhibited hind paw oedema. Ultra-violet spectrophotometry of the anti-inflammatory extract indicated that the main constituent was probably a phenolic material, commonly used as an antioxidant in the manufacture of polymers. The antioxidant nature of the extract was confirmed by its inhibition of the autoxidation of adrenaline. The results are discussed in the light of recent reports on the anti-inflammatory properties of phenolic antioxidants and their effects on the PG biosynthetic pathway.

Animals↗
PubMed1977

Reduced exudation and increased tissue proliferation during chronic inflammation in rats deprived of endogenous prostaglandin precursors.

Two models of chronic inflammation were studied in rats deprived of endogenous precursors of prostaglandins by feeding the animals on essential fatty acid deficient (EFAD) food. During kaolin-induced pouch-granuloma, exudate production was markedly reduced in EFAD rats, when compared with normal animals. The exudates from normal rats contained large amounts of PGE, but in the exudates from EFAD rats the amount of PGE was very markedly reduced. Similarly, with carrageenan-impregnated polyether sponges, the exudative component of inflammation was reduced in EFAD rats. However, the proliferative component was significantly increased, particularly in relation to the stunted growth of EFAD rats. Sponge exudates from EFAD rats contained fewer leucocytes than those from normal animals but the fall in leucocyte count was much smaller than the very marked reduction in PGE activity. EFAD rats also exhibited a significant increase in adrenal weights. The results are discussed in the light of the ambivalent (pro- or anti-inflammatory) role of endogenous PGS. It appears that, in the proliferative phase of inflammation, the anti-inflammatory role of PGs is more dominant.

Animals↗
PubMed1977

The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats.

Treatment of normal rats with metyrapone (20 mg kg-1 day-1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids.

Animals↗