Prostaglandin E2 glycerol ester, an endogenous COX-2 metabolite of 2-arachidonoylglycerol, induces hyperalgesia and modulates NFkappaB activity.

BACKGROUND AND PURPOSE: Recombinant cyclooxygenase-2 (COX-2) oxygenates 2-arachidonoylglycerol (2-AG) in vitro. We examined whether prostaglandin E2 glycerol ester (PGE2-G), a COX-2 metabolite of 2-AG, occurs endogenously and affects nociception and immune responses. EXPERIMENTAL APPROACH: Using mass spectrometric techniques, we examined whether PGE2-G occurs in vivo and if its levels are altered by inhibition of COX-2, monoacylglycerol (MAG) lipase or inflammation induced by carrageenan. We also examined the effects of PGE2-G on nociception in rats and NFkappaB activity in RAW264.7 cells. KEY RESULTS: PGE2-G occurs endogenously in rat. Its levels were decreased by inhibition of COX-2 and MAG lipase but were unaffected by carrageenan. Intraplantar administration of PGE2-G induced mechanical allodynia and thermal hyperalgesia. In RAW264.7 cells, PGE2-G and PGE2 produced similar, dose-related changes in NFkappaB activity. PGE2-G was quickly metabolized into PGE2. While the effects of PGE2 on thermal hyperalgesia and NFkappaB activity were completely blocked by a cocktail of antagonists for prostanoid receptors, the same cocktail of antagonists only partially antagonized the actions of PGE2-G. CONCLUSIONS AND IMPLICATIONS: Thermal hyperalgesia and immunomodulation induced by PGE2-G were only partially mediated by PGE2, which is formed by metabolism of PGE2-G. PGE2-G may function through a unique receptor previously postulated to mediate its effects. Taken together, these findings demonstrate that 2-AG is oxygenated in vivo by COX-2 producing PGE2-G, which plays a role in pain and immunomodulation. COX-2 could act as an enzymatic switch by converting 2-AG from an antinociceptive mediator to a pro-nociceptive prostanoid.

Foetal intralobar lung sequestration: antenatal diagnosis and management.

OBJECTIVES: The objectives of this study are to discuss the use of ultrasonography for the diagnosis of foetal intralobar sequestration (FILS) antenatally and the management options available for these pregnancies. METHODS: This is a retrospective review of six cases of FILS diagnosed antenatally by two dimensional (2D) and colour Doppler ultrasonography out of a total of 31,508 deliveries over a two-year period at the KK Women's and Children's Hospital. RESULTS: The incidence of FILS in this hospital was 1 in 5,251 deliveries. 2D ultrasonography showed an echogenic lung in all cases. FILS was confirmed by the demonstration of a systemic vessel leading to the affected lung on colour Doppler examination. After counselling, four terminated their pregnancies during mid-trimester, while two continued their pregnancies to term. Confirmation of the terminated cases was by post-mortem. In the two pregnancies that continued, regular growth scans were done to monitor the progression of the condition. Computed tomography confirmed the diagnosis post-delivery. Both were well but one had a resection of the sequestrated lung although he was asymptomatic. Histology also confirmed the diagnosis. CONCLUSION: FILS is a rare anomaly. 2D and colour Doppler ultrasonography are used to diagnose the condition antenatally. Termination of the pregnancy is not always indicated, as there are favourable outcomes from FILS.