1In 13 of 15 experiments, prostaglandin E2 (PGE2) and sulprostone (a prostanoid EPI/EP3-receptor agonist) contracted isolated rings of human pulmonary artery at low concentrations () 5 and > 0.5 nM respectively). Tissue was obtained from patients undergoing surgery mainly for carcinoma of the lung. Characterization of the receptors involved was complicated by loss of sensitivity to the contractile PGE action over the experimental period. In contrast, contractile responses to KCI, phenylephrine and the specific thromboxane (TP-) receptor agonist, U-46619, did not decrease with time. 2 The relative contractile potencies for seven PGE analogues, measured during the first few hours after setting up the preparations, were as follows: sulprostone > misoprostol = gemeprost > PGE2 > GR 63799X> 17-phenyl-w-trinor PGE2 1 1 1-deoxy PGE1. This ranking indicates that an EP3-receptor is involved. 3 The contractile action of sulprostone was not blocked by the TP-receptor antagonists, EP 169 and GR 32191, and the EPI-receptor antagonist, AH 6809.4 In two experiments, PGE2 (50 nM) reduced basal tone and sulprostone was a weak contractile agent.Phenylephrine-induced tone was also inhibited by PGE2 (EC50 = 5-20 nM), 1 1-deoxy PGEI and butaprost (a selective EP2-receptor agonist); the latter prostanoids were about 2 and 4 times less potent than PGE2 respectively. Interactions with phenylephrine were different in experiments where PGE2 alone was contractile: PGE2 induced contraction superimposed on the phenylephrine response and 11-deoxy PGE, induced either further contraction or had no effect. Butaprost produced relaxation at high concentrations; this may not be an EP2 action since preparations were highly sensitive to relaxant actions of prostacyclin (IP-) receptor agonists (cicaprost and TEI-9063). 5 The study has shown that in the majority of experiments on the human isolated pulmonary artery, the contractile EP3 system outweighed the relaxant EP2 system. However, in two experiments the reverse was true. It is not clear to what extent these differences are due to disease processes affecting the tissues. The findings are discussed in relation to the adverse cardiovascular responses occasionally encountered during treatment of postpartum haemorrhage with sulprostone, and more generally to the clinical use of EP-receptor agonists in man.
Large rotator cuff tears are extremely uncommon in young people and when they occur they may be associated with shoulder instability. This paper reports on a series of six elite rugby union and rugby league footballers who presented with shoulder instability and large rotator cuff tears. They were treated with a two stage procedure: an open rotator cuff repair followed by an open shoulder stabilisation some 10 weeks later. All had successful outcomes. The paper also highlights the risk of tearing the rotator cuff when a patient continues to play contact sport with an untreated unstable shoulder.
1 Contraction of guinea-pig isolated aorta induced by the prostaglandin E analogue sulprostone (1 ± 400 nM) has a lower maximum response (40%) than that of phenylephrine or U-46619 (TP-receptor agonist). A prostanoid EP 3 -receptor subtype is involved based on agonist potency ranking: equi-e ective molar ratios (EMR) are sulprostone (EC 50 *23 nM) 1.0, SC-46275 0.11, misoprostol 2.2, gemeprost 3.3, PGE 2 5.4, 17-phenyl PGE 2 6.0, GR-63799 8.9. GR-63799, which contains a bulky ester group, is relatively more potent on neuronal EP 3 preparations than on the aorta. 2 ONO-AP-324, a relative of the non-prostanoid prostacyclin mimetic series, behaves as an EP 3 partial agonist on the aorta, inhibiting sulprostone responses but acting synergistically (in a similar manner to sulprostone) with phenylephrine; it may be a useful pharmacological tool for studying EP 3 -receptors. 3 Sulprostone contractions are markedly suppressed in zero-Ca 2+ bathing¯uid containing either 2 mM EDTA or 50 mM EGTA, and by Cd 2+ (500 mM), but are usually una ected by nifedipine (0.3 mM) and verapamil (4.44 mM). In¯ux of Ca 2+ , but not through L-type Ca 2+ -channels, appears to be the major contractile mechanism.
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