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Platelet Activating Factor (platelet + activating_factor)
Selected AbstractsChemInform Abstract: Syntheses and Bioactivities of Novel Carbamates Combining Platelet Activating Factor (PAF) Receptor Antagonist with Thromboxane Synthase Inhibitor (TxSI).CHEMINFORM, Issue 37 2002Masakazu Fujita Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Platelet activating factor (PAF) increases plasma protein extravasation and induces lowering of interstitial fluid pressure (Pif) in rat skinACTA PHYSIOLOGICA, Issue 1 2005V. V. Iversen Abstract Aim:, To investigate the ability of the microdialysis technique to measure capillary selectivity of different sized plasma proteins induced by local administration of platelet activating factor (PAF). Methods:, We used hollow plasmapheresis fibres with 3 cm membrane (cut off 3000 kDa) placed on the back of anaesthetized rats. Results:, Platelet activating factor (50 ,g mL,1) administered locally via the fibre, increased extravasation of radiolabelled 125I-HSA from plasma to the microdialysis fibre by approximately 900% compared both to baseline and the control fibre within 70 min (n = 6, P < 0.05). The extravasation in the control fibre did not change over time. HPLC measurement of plasma proteins in the microdialysis perfusate also demonstrated decreased capillary selectivity for proteins in the diameter range of 73 Å, 56 Å and 39 Å after local administration of PAF (n = 6, P < 0.05). PAF also significantly lowered interstitial fluid (Pif) pressure after subcutaneous administration (50 ,g mL,1). Mean arterial pressure (MAP) after intravenous injection of PAF (0.4 ,g kg,1) fell instantly by about 50 mmHg, and stabilized at 50 mmHg after 15 min (n = 6). MAP was unaltered when PAF was given through the microdialysis fibre (n = 4). Both total tissue water (TTW) and extravasation of albumin, measured as the plasma-to-tissue clearance (E-alb) showed a significant increase after PAF (n = 7, P < 0.05). Conclusions:, The present study demonstrates that PAF induces plasma protein extravasation and decrease capillary selectivity of different sized plasma proteins. It also increases transcapillary fluid flux, and lowers Pif, indicating a role for PAF in the interstitium for generation of transcapillary transport of water and large molecules followed by formation of oedema. [source] Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestationsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2000Tektonidou Background We assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases. Materials and methods Anti-PAF, anticardiolipin (aCL), anti,2 glycoprotein I (anti,2GPI) and antiphosphatidylcholine (anti-PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme-linked immunosorbent assay (ELISA) was developed for determining anti-PAF antibodies in a bovine serum-free fashion. Results The ELISA showed high specificity. Homologous inhibition experiments showed 60,70% inhibition. Anti-PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL, patients and 3/30 scleroderma patients. Anti-PAF antibodies were significantly associated with anti-PC antibodies (odds ratio [OR] 12.7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or anti,2GPI. Three SLE/aCL+ patients and five SLE/aCL, patients had clinical manifestations characteristic of APS. All these patients had anti-PAF antibodies, while none had high titres of aCL or anti,2GPI antibodies and only one had anti-PC antibodies. Among the combined APS and SLE groups, the presence of anti-PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and anti,2GPI antibodies. Conclusions Anti-PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti-PAF antibodies without other antiphospholipid specificities. [source] Differential effects of arachidonoyl trifluoromethyl ketone on arachidonic acid release and lipid mediator biosynthesis by human neutrophilsFEBS JOURNAL, Issue 15 2002Evidence for different arachidonate pools The goal of this study was to determine the effects of a putative specific cytosolic phospholipase A2 inhibitor, arachidonyl trifluoromethyl ketone (AACOCF3), on arachidonic acid (AA) release and lipid mediator biosynthesis by ionophore-stimulated human neutrophils. Initial studies indicated that AACOCF3 at concentrations 0,10 µm did not affect AA release from neutrophils. In contrast, AACOCF3 potently inhibited leukotriene B4 formation by ionophore-stimulated neutrophils (IC50 , 2.5 µm). Likewise, AACOCF3 significantly inhibited the biosynthesis of platelet activating factor. In cell-free assay systems, 10 µm AACOCF3 inhibited 5-lipoxygenase and CoA-independent transacylase activities. [3H]AA labeling studies indicated thatthe specific activities of cell-associated AA mimicked that of leukotriene B4 and PtdCho/PtdIns, while the specific activities of AA released into the supernatant fluid closely mimicked that of PtdEtn. Taken together, these data argue for the existence of segregated pools of arachidonate in human neutrophils. One pool of AA is linked to lipid mediator biosynthesis while another pool provides free AA that is released from cells. Additionally, the data suggest that AACOCF3 is also an inhibitor of CoA-independent transacylase and 5-lipoxygenase. Thus, caution should be exercised in using AACOCF3 as an inhibitor of cytosolic phospholipase A2 in whole cell assays because of the complexity of AA metabolism. [source] Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2006Manuel J. Barbanoj Abstract Introduction The Central Nervous System (CNS) impairment induced by moderate alcohol (ALC) ingestion may be enhanced if other drugs are taken simultaneously. Rupatadine (RUP) is a new H1 -antihistamine which also inhibits platelet activating factor (PAF) release in inflammatory reactions. Objective The main aim of the study was to assess the effects of ALC 0.8,g/Kg on RUP (10,mg and 20,mg) CNS effects. An evaluation of alcohol and RUP pharmacokinetics was also attained. Methods Eighteen healthy young volunteers of both sexes participated in a phase I, randomised, crossover, double-blind, placebo-controlled study. At 2-week intervals they received six treatments: (a) placebo (PLA), (b) ALC alone and ALC in combination with: (c) hydroxyzine 25,mg (HYD), (d) cetirizine 10,mg (CET), (e) RUP 10,mg or (f) RUP 20,mg. At baseline and several times thereafter, seven psychomotor performance tests (finger tapping, fine motoric skills, nystagmus, temporal estimation, critical-flicker-fusion frequency, ,d2' cancellation, simple reaction) and eleven subjective self-reports (drunkenness, sleepiness, alertness, clumsiness, anger, inattentiveness, efficiency, happiness, hostility, interest and extraversion) were carried out. Two-way (treatment, time) ANOVAs for repeated measures to each variable together with a multivariate non-parametric approach were applied. Plasma concentrations of alcohol, and of RUP and its metabolites, were quantified by validated immunofluorescence and LC/MS/MS methods, respectively. Plasma-time curves for all compounds were analysed by means of model-independent methods. Results The combination of alcohol with HYD, CET and RUP 20,mg produced more cognitive and psychomotor impairment as compared to alcohol alone, being the combination of alcohol and HYD the one which induced the greatest deterioration. The combination of alcohol and RUP 10,mg could not be differentiated from ALC alone. Subjective self-reports reflect effects on metacognition after the combination of alcohol with HYD and CET i.e. the increased objective impairment observed was not subjectively perceived by the subjects. No significant differences were obtained when comparing alcohol plasma concentrations assessed after the treatments evaluated. RUP showed a lineal kinetic relationship after 10 and 20,mg with a higher exposition to both metabolites assayed. Conclusions Present results showed that single oral doses of rupatadine 10,mg in combination with alcohol do not produce more cognitive and psychomotor impairment than alcohol alone. Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses. Copyright © 2006 John Wiley & Sons, Ltd. [source] Regulation of platelet activating factor-induced equine platelet activation by intracellular kinasesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009A. C. BROOKS Lipopolysaccharide (LPS) can activate equine platelets directly or indirectly, via leukocyte-derived platelet activating factor (PAF). Thromboxane (Tx) production by LPS-stimulated equine platelets requires p38 MAPK and this kinase has been suggested as a therapeutic target in endotoxaemia. The present study has utilised selective inhibitors to investigate the role of p38 MAPK and two other kinases, phosphatidylinositol-3 kinase (PI3K) and protein kinase C (PKC), in regulating PAF-induced Tx production, aggregation and 5-HT release in equine platelets, and the modification of these responses by LPS. LPS enhanced PAF-induced 5-HT release, an effect that was reduced by the p38 MAPK inhibitor, SB203580 (60 ± 8% reduction; n = 6). SB203580 did not affect responses to PAF alone; whereas inhibition of PKC reduced PAF-induced 5-HT release, Tx production and aggregation (maximal inhibition by the PKC, inhibitor, rottlerin: 69 ± 13%, 63 ± 14% and 97 ± 1%, respectively; n = 6). Wortmannin and LY249002, which inhibit PI3K, also caused significant inhibition of PAF-induced aggregation (maximal inhibition 78 ± 3% and 88 ± 2%, respectively; n = 6). These data suggest that inhibition of platelet p38 MAPK may be of benefit in equine endotoxaemia by counteracting some of the effects of LPS. However, detrimental effects of platelet activation mediated by PAF and not enhanced by LPS are unlikely to be markedly affected. [source] Identification of lysophosphatidylcholine (LPC) and platelet activating factor (PAF) from PC12 cells and mouse cortex using liquid chromatography/multi-stage mass spectrometry (LC/MS3)RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2008Jeffrey C. Smith Lipids play essential roles in cellular structural support, energy storage and signal transduction. Recently, mass spectrometry (MS) has been used to produce three-dimensional maps that elucidate the lipid composition of complex cellular lysates. The identification of individual lipids within these maps is slow and requires the synthesis and spiking of each candidate lipid. We present a novel MS-based technique that rapidly elucidates the atomic connectivity of the fatty acid/alcohol substituent on the sn -1 position of several different families of glycerophosphocholine-containing lipids within the confines of a chromatographic separation. Sodiated lipid species were fragmented to produce radical cations which lost successive methylene groups upon further collisional activation to reveal the identity of the parent molecule. This approach was demonstrated to be effective on isobaric members of the lysophosphatidylcholine (LPC) and platelet activating factor (PAF) families of glycerophospholipids. We demonstrate the application of this technique to unambiguously identify these species within complex cellular lysates and tissue extracts. Copyright © 2008 John Wiley & Sons, Ltd. [source] Modulation of the pathology of late xenograft rejection by PAF-antagonist UR-12670 in the hamster-to-rat liver xenotransplant model,APMIS, Issue 3 2003PAF antagonist alleviates xenogeneic rejection PAF antagonists have been used in xenotransplantation to alleviate the pathogenesis of hyperacute rejection. This study evaluated the ability of the PAF antagonist UR-12670 to improve graft function in late xenograft rejection (LXR) in an orthotopic liver xenotransplantation model, and the involvement of PAF (platelet activating factor) in this type of rejection. The recipients of a hamster xenograft received standard immunosuppression (tacrolimus 0.2 mg/kg/30 days, MMF 25 mg/kg/8 days). Study groups: group A, without UR-12670, group B, UR-12670 (20 mg/kg/8 d) and group C, continuous administration of UR-12670 (20 mg/kg/d). Serum levels of xenoantibodies were evaluated by flow cytometry and tissue deposits by immunofluorescence. Immunoblot and indirect immunofluorescence assessed specificity of xenoantibodies. Conventional histology was performed. Continuous administration of UR-12670 improved the histological pattern of liver xenografts, especially necrosis, loss of hepatocytes, hemorrhage, sinusoidal congestion and lymphocyte infiltration. There was not a shift in specificity of xenoantibodies at different times posttransplantation, as demonstrated by immunoblotting and indirect immunofluorescence. UR-12670 administration had a beneficial effect on graft function and considerably improved the histopathological pattern, but it failed to induce tolerance after withdrawal of immunosuppression. UR-12670 had an immunomodulatory effect on cellular response but not on antibody production. There was not a change in the specificity of xenoantibodies produced at LXR compared with pretransplant antibodies. [source] Synthesis, Antiplatelet and Vasorelaxing Activities of Xanthone DerivativesARCHIV DER PHARMAZIE, Issue 1 2009Kai-Wei Lin Abstract A series of ,-aminoalkoxylxanthones was synthesized and tested in vitro for their ability to inhibit platelet aggregation and cause vasorelaxing action. Compounds 4, 5, 12, 17, and 18 showed significant antiplatelet effects on thrombin-, arachidonic acid (AA)-, collagen-, and platelet activating factor (PAF)-induced washed rabbit platelet aggregation and exhibited inhibition of primary and secondary aggregation induced by adenosine-5'-diphosphate (ADP) in human platelet-rich-plasma (PRP). Compounds 4, 17, and 18 revealed vasorelaxing activities in rat thoracic aorta. We concluded that these compounds may be developed as new antithrombotic agents. [source] New 1H -Pyrazole-4-Carboxamides with Antiplatelet ActivityARCHIV DER PHARMAZIE, Issue 1 2009Klaus Rehse Abstract Nine title compounds were synthesized and investigated in the Born test for their antiplatelet activities against collagen, ADP, adrenaline, and platelet activating factor (PAF) as inducers of the aggregation. Using collagen three compounds with IC50 values below 100 ,M were found (3b, 3e, 3i). Activities in nanomolar concentrations were observed against ADP (3b, IC50 = 9.4 nM), adrenaline (3i, IC50 = 5.8 nM), and platelet activating factor (3e, IC50 = 0.45 nM). [source] Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2000Yoshio Tanaka In anaesthetized rats, platelet activating factor (PAF; 1 ,g kg,1) decreased mean arterial blood pressure by around 60 mmHg (n=18). This depressor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg,1), indicating the role of PAF-specific receptor in the response. NG -nitro- L -arginine methyl ester (L -NAME; 50 mg kg,1), an NO synthase inhibitor, profoundly elevated systemic blood pressure (n=19), indicating an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 ,g kg,1) normalized against that to sodium nitroprusside (SNP) (10 ,g kg,1) was not substantially different between rats treated without and with L -NAME (n=4). In contrast, the depressor effect of acetylcholine (0.03,1.0 ,g kg,1) normalized against that of SNP (10 ,g kg,1) was significantly attenuated by L -NAME (n=5). Charybdotoxin (0.4 mg kg,1) plus apamin (0.2 mg kg,1) significantly attenuated the depressor response to PAF (1 ,g kg,1) (n=5) without affecting the blood pressure change due to SNP (1 mg kg,1) (n=3). Charybdotoxin (0.4 mg kg,1) (n=4) or apamin (0.2 mg kg,1) (n=4) alone did not affect the PAF-induced depressor response. These findings suggest that EDHF may make a significant contribution to the depressor response to PAF in rats. Although NO plays the determinant role in the basal blood pressure regulation, its contribution to PAF-produced depressor response seems to be less as compared with that to the depressor response to acetylcholine. British Journal of Pharmacology (2000) 131, 1113,1120; doi:10.1038/sj.bjp.0703681 [source] | |||||||||||||