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Examines the expression and functional aspects of the prostaglandin E synthase (PGES) enzyme, mPGES-2, in mammalian cells and tissues. Forms of PGES; Synthesis of mPGES-2 as a Golgi membrane-associated protein; Inducibility of mPGES-2 constitutively expressed in various cells and tissues.

Distinct functional coupling between cyclooxygenases (COXs) and specific terminal prostanoid synthases leads to phase-specific production of particular prostaglandins (PGs). In this study, we examined the coupling between COX isozymes and PGF synthase (PGFS). Co-transfection of COXs with PGFS-I belonging to the aldo-keto reductase family into HEK293 cells resulted in increased production of PGF2α only when a high concentration of exogenous arachidonic acid (AA) was supplied. However, this enzyme failed to produce PGF2α from endogenous AA, even though significant increase in PGF2α production occurred in cells transfected with COX-2 alone. This poor COX/PGFS-I coupling was likely to arise from their distinct subcellular localization. Measurement of PGF2α-synthetic enzyme activity in homogenates of several cells revealed another type of PGFS activity that was membrane-bound, glutathione (GSH)-activated, and stimulus-inducible. In vivo, membrane-bound PGFS activity was elevated in the lung of lipopolysaccharide-treated mice. Taken together, our results suggest the presence of a novel, membrane-associated form of PGFS that is stimulus-inducible and is likely to be preferentially coupled with COX-2. [Copyright &y& Elsevier]

Mast cells release a variety of mediators, including arachidonic acid (AA) metabolites, to regulate allergy, inflammation, and host defense, and their differentiation and maturation within extravascular microenvironments depend on the stromal cytokine stem cell factor. Mouse mast cells express two major intracellular phospholipases A2 (PLA2s), namely group IVA cytosolic PLA2 (cPLA2α) and group VIA Ca2+-independent PLA2 (iPLA2β), and the role of cPLA2α in eicosanoid synthesis by mast cells has been well documented. Lipidomic analyses of mouse bone marrow-derived mast cells (BMMCs) lacking cPLA2α (Pla2g4a-/-) or iPLA2β (Pla2g6-/-) revealed that phospholipids with AA were selectively hydrolyzed by cPLA2α, not by iPLA2β, during Fc€RI-mediated activation and even during fibroblast-dependent maturation. Neither Fc€RI-dependent effector functions nor maturation-driven phospholipid remodeling was impaired in Pla2g6-/- BMMCs. Although BMMCs did not produce prostaglandin E2 (PGE2), the AA released by cPLA2α from BMMCs during maturation was converted to PGE2 by microsomal PGE synthase-1 (mPGES-1) in cocultured fibroblasts, and accordingly, Pla2g4a-/- BMMCs promoted microenvironmental PGE2 synthesis less efficiently than wild-type BMMCs both in vitro and in vivo. Mice deficient in mPGES-1 (Ptges-/-) had an augmented local anaphylactic response. These results suggest that cPLA2α in mast cells is functionally coupled, through the AA transfer mechanism, with stromal mPGES-1 to provide anti-anaphylactic PGE2. Although iPLA2β is partially responsible for PGE2 production by macrophages and dendritic cells, it is dispensable for mast cell maturation and function. [ABSTRACT FROM AUTHOR]

Although the secreted phospholipase A2 (sPLA2) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA2 (sPLA2-X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA2-X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA2-X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA2-X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing. [ABSTRACT FROM AUTHOR]

We investigated the medical and nursing records of 19 patients with unresectable advanced recurrent colorectal cancers treated using oxaliplatin and capecitabine(CapeOX)with or without bevacizumab at the outpatient tumor center of Showa UniversityHospital between November 1, 2009 and November 30, 2011, to clarifydifferences in the incidence of injection site reactions according to the use or non-use of an intravenous infusion solution warming device. Vascular pain and other injection site reactions occurred in 13 patients(68.4%). Injection site reactions occurred in 33 of the total of 77 chemotherapytreatments (42.9%). No difference in incidence of injection site reactions was seen according to whether the intravenous infusion solution warmer was used. The most common time to onset of injection site reactions after commencing oxaliplatin administration was 60-90 min, and symptoms were seen to decrease when non-steroidal anti-inflammatorydrugs were coadministered. We intend to leverage these studyfindings to demonstrate the mechanism of onset for injection site reactions and to propose measures for handling adverse drug reactions.

The solvent effects on the crystallization of porous isotactic (it) poly(methyl methacrylate) (PMMA) thin films as well as the incorporation behavior of syndiotactic (st) poly(methacrylic acid) (PMAA) into the porous films were investigated. The porous it-PMMA thin films were prepared by the extraction of st-PMAA from a stepwise layer-by-layer (LbL) assembly composed of it-PMMA and st-PMAA. The X-ray diffraction pattern of the it-PMMA thin films after immersion in acetonitrile/water (4/6, v/v) showed two characteristic peaks of a crystalline it-PMMA double-stranded helix (2theta = 9 degrees and 14 degrees , d = 0.96 and 0.62 nm). This suggested that acetonitrile promoted the crystallization of the thin films, because water is a nonsolvent for PMMA. The surface structural change of the it-PMMA films was also analyzed by atomic force microscopy. The it-PMMA conformation was maintained after crystallization as observed by infrared spectroscopy. The incorporation percentages of st-PMAA into the porous it-PMMA thin films under various solvent conditions were estimated using a quartz crystal microbalance. The incorporation of st-PMAA decreased as the it-PMMA films crystallized or with growing thickness of the porous it-PMMA films. This suggested that the polymer-polymer interactions and the entanglement of the it-PMMA chains played an important role. The incorporation was promoted as the acetonitrile content in the st-PMAA solution increased, indicating that it was necessary for st-PMAA incorporation to solvate it-PMMA.