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M J Parnham

Publications and source records attributed to M J Parnham.

103 records · Page 6Linked to original sources
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↗
PubMed1976

The effect of metyrapone on uterine prostaglandin output and smooth muscle activity.

Metyrapone, at low doses (0.5-1.0 mM), stimulated the output of both PGE and PGF from the isolated uterus of the pregnant rat determined following extraction of bath fluid, chromatographic separation and bioassay of the prostaglandin. At higher doses (2-4 mM), metyrapone inhibited PGF output, but had no effect on PGE output. Uterine activity was rapidly inhibited by metyrapone in a dose-related manner. This inhibition was not related to PG output as, at 1 mM metyrapone, activity was inhibited and PG output stimulated. Both metyrapone and papaverine produced dose-dependent inhibition of the activity of the isolated rabbit ileum, papaverine being 10 times more potent than metyrapone. Propranolol antagonised the response of the ileum to isoprenaline, but had no effect on the response to metyrapone. These observations confirm earlier data, suggsting that metyrapone exerts a differential effect on uterine PGE and PGF production and indicate that metyrapone has a direct inhibitory effect on smooth muscle activity.

Animals↗
PubMed1975

The influence of metyrapone on the synthesis and release of prostaglandins from the pregnant rat uterus in vitro.

1 Metyrapone (150 mg/kg, s.c. or i.p.) an inhibitor of corticosteroid biosynthesis, significantly reduced the release of prostaglandins of the F-type from isolated preparations of pregnant rat uteri in vitro, on day 22 - the expected day of delivery. 2 Metyrapone and indomethacin administered in vitro both inhibited the conversion of 14C-arachidonic acid to prostaglandin E2 by homogenates of day 22 pregnant rat uteri. Metyrapone was approximately 150 times less potent than indomethacin. Although indomethacin also inhibited prostaglandin F2alpha production, metyrapone stimulated synthesis of this prostaglandin. The differential inhibition of prostaglandin synthesis by metyrapone may reflect sensitivity of the inhibitor to changes in experimental conditions. 3 Inhibition of prostaglandin synthesis may explain the effects of metyrapone on parturition in the rat.

Animals↗
PubMed1975

Evidence for a possible foetal control of prostaglandin release from the pregnant rat uterus in vitro.

The release of prostaglandin-like material and these spontaneous contractions of individual horns from the pregnant rat uterus in vitro have been studied on day 22 of pregnancy - the expected day of delivery. Removal of foetuses (retaining placentae in utero) from one or both uterine horns on day 16 or 17 significantly reduced prostaglandin F release and spontaneous activity. Rats which had been made unilaterally pregnant after ligation of one uterine horn, exhibited a decrease in prostaglandin F output from both horns. Uterine activity and prostaglandin release were increased in quiescent uteri by the addition of arachidonic acid (5 mug/ml) or phospholipase A (160 mu./ml); the effects were abolished by indomethacin (20 mug/ml). However, the stimulation of uterine activity by PGF2alpha (30-60 ng/ml) was not affected by indomethacin. It is concluded that the release of prostaglandins from the pregnant rat uterus in vitro at term is related to the presence of viable foetuses.

Animals↗
PubMedDate not supplied

Experimental conditions determine effects of ascorbic acid on reperfusion injury: comparison of tissue damage with hemodynamic parameters in rat isolated hearts.

Restoration of coronary blood flow after myocardial ischemia is always a matter of urgency, but the resulting surgical or drug-induced reperfusion of ischemic tissue is often associated with myocardial functional disturbances and tissue injury. The present study was carried out to select experimental conditions under which optimal effects of antioxidants can be observed on the adverse effects of reperfusion of ischemic myocardium. The release of lactate dehydrogenase (LDH) and changes in hemodynamic parameters were compared in two models of cardiac reperfusion injury in rat isolated hearts. LDH release from electrically-stimulated hearts perfused under constant flow and with initial (5 min) reperfusion in calcium-free buffer was greater than that from hearts perfused under constant pressure in which ischemia was induced by reduced flow. Combined SOD+catalase was a weak inhibitor of LDH release in both models, ascorbic acid being more potent under constant pressure than under constant flow conditions. A longer ischemic period enhanced the inhibitory effect of ascorbate. Contractility and ventricular end-diastolic pressure recovered slowly during perfusion under constant flow and brief calcium removal, but remained unphysiological under constant pressure. SOD+catalase had no effect on hemodynamic parameters. Ascorbic acid exacerbated ischemia+reperfusion-induced changes in contractility, ventricular pressure, heart rate and coronary flow under constant pressure, but facilitated recovery of contractility on reperfusion under constant flow and brief calcium removal. In studies on antioxidants, different experimental conditions appear to be necessary to observe beneficial effects on tissue damage on the one hand and on hemodynamics on the other. Mild to moderate ischemia, with sustained pacemaker activity, appears to be the condition under which antioxidants provide hemodynamic improvement. In isolated rat hearts, biochemical parameters of tissue damage may be misleading for the effects of antioxidants.

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